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1
Ji, Xiao-Wei, Jie Lin, Yan-Ting Wang, Jing-Jing Ruan, Jing-Hong Xu, Kai Song, and Jian-Shan Mao. "Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study." World Journal of Gastrointestinal Oncology 16, no. 8 (August 15, 2024): 3529–38. http://dx.doi.org/10.4251/wjgo.v16.i8.3529.
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BACKGROUND Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM To explore endoscopic detection and diagnostic strategies for MGCs. METHODS This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.
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Iberri, David, and Michaela Liedtke. "MGCS: where do we stand today?" Hematology 2024, no. 1 (November 25, 2024): 482–88. https://doi.org/10.1182/hematology.2024000572.
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Abstract Monoclonal gammopathies of clinical significance (MGCS) are a heterogeneous group of disorders characterized by the presence of an indolent B-cell or plasma-cell clone producing a toxic monoclonal immunoglobulin resulting in end-organ dysfunction. MGCS is a clinicopathologic diagnosis that requires the demonstration of a monoclonal immunoglobulin in the correct clinical setting. The most common MGCS syndromes are renal, neurologic, and cutaneous, although hematologic and multi-organ MGCS syndromes are also increasingly recognized. Therapy most commonly targets the underlying clonal population; immunoglobulin-targeting therapies as well as complement and cytokine antagonists have emerged for selected MGCS syndromes and may be temporizing in a subset of patients. Other chapters review renal and neurologic MGCS; this chapter focuses on hematologic and multi-organ MGCS syndromes.
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Joseph, Jayanthi J., Amy Leestemaker-Palmer, Soheila Kazemi, Lia Danelishvili, and Luiz E. Bermudez. "Mycobacterium avium Infection of Multinucleated Giant Cells Reveals Association of Bacterial Survival to Autophagy and Cholesterol Utilization." Cellular Microbiology 2023 (February 11, 2023): 1–14. http://dx.doi.org/10.1155/2023/5064371.
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Mycobacterium avium subsp. hominissuis (M. avium) is an opportunistic environmental pathogen that typically infects patients with existing lung conditions such as cystic fibrosis or COPD. Pulmonary M. avium infection generates peribronchial granulomas that contain infected macrophages and multinucleated giant cells (MGCs). While granuloma formation with MGCs is a common feature of mycobacterial infection, the role of MGCs within the granulomas as well as in the host-pathogen interaction is poorly understood. To shed light on the role of MGCs, we established a novel in vitro model utilizing THP-1 cells stimulated with a combination of IFN-γ and TNF-α. In this study, we show that MGCs can take up M. avium, which replicates intracellularly before leaving the cell. Bacteria that escape the MGC exhibit a highly invasive phenotype, which warrants further evaluation. Characterization of MGCs with transmission electron microscopy revealed an accumulation of cytoplasmic lipid droplets, autophagic activity, and multiple nuclei. Autophagy markers are upregulated in both uninfected and infected MGCs early in infection, measured by RT-qPCR analysis of Beclin-1 and LC3. Inhibition of autophagy with siRNA significantly reduced M. avium survival significantly in THP-1 macrophages. Depletion of host cholesterol and sphingomyelin in MGCs also resulted in decreased survival of M. avium. These processes potentially contribute to the formation of a supportive intracellular environment for the pathogen. Collectively, our results suggest that M. avium is adapted to replicate in MGCs and utilize them as a springboard for local spread.
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Gulubova, Maya Vladova, and Koni Vancho Ivanova. "The Expression of Tumor-Associated Macrophages and Multinucleated Giant Cells in Papillary Thyroid Carcinoma." Open Access Macedonian Journal of Medical Sciences 7, no. 23 (December 10, 2019): 3944–49. http://dx.doi.org/10.3889/oamjms.2019.715.
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BACKGROUND: Inflammation that occurred in the tumor microenvironment was characterized by abundant macrophage infiltration, playing role in innate immunity. Multinucleate giant cells (MGCs) occur in a variety of inflammatory, hyperplastic, and neoplastic thyroid disorders. They also have been recognized as a feature of papillary thyroid carcinoma (PTC).
AIM: The aim of this study was to evaluate cases of PTC for the presence of macrophages, and estimate CD68+ TAMs density in tumor stroma, margin and the surrounding tissue. We assessed also MGCs.
METHODS: Macrophages and MGCs densities were correlated with clinicopathologic parameters to assess the possible prognostic significance. We investigated 56 patients immunohistochemically and immunofluorescence with antibodies against CD68 and IL-17.
RESULTS: A statistically significant correlation was established between PTC patients in III stage, containing many MGCs, and PTC in I and II stage, with many MGCs. Eighty Percent of patients in III stage showed many MGCs in comparison with patients in I and II stage, where many MGCs were found only in 21,1% (χ2 = 6.189, p = 0.013).
CONCLUSION: Our study demonstrates that the increased density of MGCs is associated with advanced stage of PTC, and therefore with tumor progression and that cases of PTC should be carefully screened for their presence.
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Sun, Lei, Pengju Zhang, and Wenfa Lu. "lncRNA MALAT1 Regulates Mouse Granulosa Cell Apoptosis and 17β-Estradiol Synthesis via Regulating miR-205/CREB1 Axis." BioMed Research International 2021 (February 17, 2021): 1–9. http://dx.doi.org/10.1155/2021/6671814.
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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a known long noncoding RNA, was reported to play a crucial role in follicular growth and ovarian disease. However, the physiological function of MALAT1 in mouse granulosa cells (mGCs) remains largely unclear. The aims of this study were to determine the biological function and molecular mechanism of MALAT1 in mGCs. We knocked down MALAT1 in mGCs by using siRNA against MALAT1. We found that knockdown of MALAT1 promoted apoptosis and caspase-3/9 activities in mGCs. Enzyme-linked immunosorbent assay demonstrated that knockdown of MALAT1 significantly decreased the production of estradiol (E2) and progesterone (P4) in mGCs. Mechanistically, MALAT1 serves as a competing endogenous RNA (ceRNA) to sponge microRNA-205 (miR-205), thereby facilitating its downstream target of cyclic AMP response element- (CRE-) binding protein 1 (CREB1). Furthermore, CREB1 overexpression or miR-205 downregulation partially recovered the effect of MALAT1 depletion in mGCs. In summary, these findings suggested that MALAT1 regulated apoptosis and estradiol synthesis of mGCs through the miR-205/CREB1 axis.
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Li, Fan, Yan Huang, Kai Huang, Jing Lin, and Peng Huang. "Functional Magnetic Graphene Composites for Biosensing." International Journal of Molecular Sciences 21, no. 2 (January 8, 2020): 390. http://dx.doi.org/10.3390/ijms21020390.
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Magnetic graphene composites (MGCs), which are composed of magnetic nanoparticles with graphene or its derivatives, played an important role in sensors development. Due to the enhanced electronic properties and the synergistic effect of magnetic nanomaterials and graphene, MGCs could be used to realize more efficient sensors such as chemical, biological, and electronic sensors, compared to their single component alone. In this review, we first reviewed the various routes for MGCs preparation. Then, sensors based on MGCs were discussed in different groups, including optical sensors, electrochemical sensors, and others. At the end of the paper, the challenges and opportunities for MGCs in sensors implementation are also discussed.
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Tian, Xue-Fei, Tie-Jun Li, and Shi-Feng Yu. "Giant Cell Granuloma of the Temporal Bone: A Case Report With Immunohistochemical, Enzyme Histochemical, and In Vitro Studies." Archives of Pathology & Laboratory Medicine 127, no. 9 (September 1, 2003): 1217–20. http://dx.doi.org/10.5858/2003-127-1217-gcgott.
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Abstract A case of giant cell granuloma (GCG) that occurred in the right temporal bone is reported. The lesion showed histologic features identical to GCG. The multinuclear giant cells (MGCs) in the lesion showed strong reactivity with CD68, but patchy staining for myeloid/histiocyte antigen, α-1-antitrypsin, α-1-antichymotrypsine, and lysozyme. Activity of tartrate-resistant acid phosphatase was also consistently detected in the MGCs. Some of the mononuclear cells of the lesion exhibited similar immunocytochemical and histochemical reactivity as the MGCs. Ki-67 staining, however, was only detected in the mononuclear cells. The MGCs isolated from the lesion presented characteristic morphology of osteoclasts and possessed the ability to excavate bone in vitro. Thus, the MGCs in GCG appeared to express both macrophage- and osteoclast-associated phenotypes. The mononuclear cells were the major proliferative elements in the lesion and a subpopulation of these cells may represent precursors of the MGCs.
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Sanchez, María C., and Gustavo A. Chiabrando. "Multitarget Activities of Müller Glial Cells and Low-Density Lipoprotein Receptor-Related Protein 1 in Proliferative Retinopathies." ASN Neuro 14 (January 2022): 175909142211363. http://dx.doi.org/10.1177/17590914221136365.
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Müller glial cells (MGCs), the main glial component of the retina, play an active role in retinal homeostasis during development and pathological processes. They strongly monitor retinal environment and, in response to retinal imbalance, activate neuroprotective mechanisms mainly characterized by the increase of glial fibrillary acidic protein (GFAP). Under these circumstances, if homeostasis is not reestablished, the retina can be severely injured and GFAP contributes to neuronal degeneration, as they occur in several proliferative retinopathies such as diabetic retinopathy, sickle cell retinopathy and retinopathy of prematurity. In addition, MGCs have an active participation in inflammatory responses releasing proinflammatory mediators and metalloproteinases to the extracellular space and vitreous cavity. MGCs are also involved in the retinal neovascularization and matrix extracellular remodeling during the proliferative stage of retinopathies. Interestingly, low-density lipoprotein receptor-related protein 1 (LRP1) and its ligand α2-macroglobulin (α2M) are highly expressed in MGCs and they have been established to participate in multiple cellular and molecular activities with relevance in retinopathies. However, the exact mechanism of regulation of retinal LRP1 in MGCs is still unclear. Thus, the active participation of MGCs and LRP1 in these diseases, strongly supports the potential interest of them for the design of novel therapeutic approaches. In this review, we discuss the role of LRP1 in the multiple MGCs activities involved in the development and progression of proliferative retinopathies, identifying opportunities in the field that beg further research in this topic area. Summary Statement MGCs and LRP1 are active players in injured retinas, participating in key features such as gliosis and neurotoxicity, neovascularization, inflammation, and glucose control homeostasis during the progression of ischemic diseases, such as proliferative retinopathies.
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Kamkin, Andre G., Vadim M. Mitrokhin, Olga V. Kamkina, Viktor E. Kazansky, Anastasia S. Rodina, Alexandra D. Zolotareva, Valentin I. Zolotarev, et al. "SIMULATED MICROGRAVITY CHANGES THE NUMBER OF MECHANICALLY GATED AND MECHANOSENSITIVE ION CHANNELS GENES TRANSCRIPTS IN RAT VENTRICULAR CARDIOMYOCYTES." Доклады Российской академии наук. Науки о жизни 512, no. 1 (September 1, 2023): 428–32. http://dx.doi.org/10.31857/s2686738923600383.
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The mechanoelectrical feedback in the heart is based on the work of mechanically gated (MGCs) and mechanosensitive (MSCs) channels. Since microgravity alters the heart’s morphological and physiological properties, we hypothesized that the expression of both MGCs and MSCs would be affected. We employed RNA transcriptome sequencing to investigate changes in the gene transcript levels of MGCs and MSCs in isolated rat ventricular cardiomyocytes under control conditions and in a simulated microgravity environment. For the first time, our findings demonstrated that simulated microgravity induces alterations in the gene transcript levels of specific MGCs, such as TRPM7, TRPV2, TRPP1, TRPP2, Piezo1, TMEM63A, TMEM36B, and known MSCs, including K2P2.1, K2P3.1, Kir6.1, Kir6.2, NaV1.5, CaV1.2, KV7.1. However, other voltage-gated channels and channels lacking a voltage sensor remained unaffected. These findings suggest that the altered expression of MGCs and MSCs could lead to changes in the net currents across the membrane, ultimately impacting the heart’s function.
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Hua, Qi, Hao Cheng, Yong-Qing Yang, Jin-Song An, Min Zhang, Shuai Gong, Ming-Jiu Luo, and Jing-He Tan. "Role of tPA in Corticosterone-Induced Apoptosis of Mouse Mural Granulosa and Oviductal Epithelial Cells." Cells 12, no. 3 (January 31, 2023): 455. http://dx.doi.org/10.3390/cells12030455.
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Although studies indicate that female stress-increased secretion of glucocorticoids impairs oocyte competence and embryo development, by inducing apoptosis of ovarian and oviductal cells, respectively, the mechanisms by which glucocorticoids induce apoptosis of ovarian and oviductal cells are largely unclear. Tissue plasminogen activator (tPA) has been involved in apoptosis of different cell types. However, while some studies indicate that tPA is proapoptotic, others demonstrate its antiapoptotic effects. This study has explored the role and action mechanisms of tPA in corticosterone-induced apoptosis of mouse mural granulosa cells (MGCs) and oviductal epithelial cells (OECs). The results demonstrate that culture with corticosterone significantly increased apoptosis, while decreasing levels of tPA (Plat) mRNA and tPA protein in both MGCs and OECs. Culture with tPA ameliorated corticosterone-induced apoptosis of MGCs and OECs. Furthermore, while tPA protected MGCs from corticosterone-induced apoptosis by interacting with low-density lipoprotein receptor-related protein 1 (LRP1), it protected OECs from the apoptosis by acting on Annexin 2 (ANXA2). In conclusion, tPA is antiapoptotic in both MGCs and OECs, and it protects MGCs and OECs from corticosterone-induced apoptosis by interacting with LRP1 and ANXA2, respectively, suggesting that tPA may use different receptors to inhibit apoptosis in different cell types.
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El Sadaney, Ahmed O., Anika Dutta, Joselle Cook, and Francis I. Baffour. "Monoclonal Gammopathy of Clinical Significance (MGCS) and Related Disorders: A Review and the Role of Imaging." Diagnostics 14, no. 17 (August 29, 2024): 1907. http://dx.doi.org/10.3390/diagnostics14171907.
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The term monoclonal gammopathy of clinical significance (MGCS) refers to a group of symptomatic monoclonal gammopathies that do not meet the diagnostic criteria for malignant plasma cell disorders, such as multiple myeloma or Waldenström macroglobulinemia. These symptoms are attributable to the paraneoplastic effects of monoclonal immunoglobulins that occur through diverse mechanisms. The presence of symptoms distinguishes MGCS from monoclonal gammopathy of undetermined significance, which lacks significant symptomatic presentation. The presentations of MGCS are manifold, adding to the diagnostic challenge. Clinical suspicion is key for accurate and timely diagnosis. Radiologic imaging can provide pivotal information to guide the diagnosis. In this review, we discuss MGCS from a radiology perspective and highlight pertinent imaging features associated with the disorders.
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Dispenzieri, Angela. "Monoclonal gammopathies of clinical significance." Hematology 2020, no. 1 (December 4, 2020): 380–88. http://dx.doi.org/10.1182/hematology.2020000122.
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Abstract “Monoclonal gammopathy of clinical significance” (MGCS) is the term used to describe nonmalignant monoclonal gammopathies causing important disease. MGCS is the differential diagnosis for any patient presenting with what appears to be a monoclonal gammopathy of undetermined significance but is also experiencing other unexplained symptoms. Broadly, these conditions can be separated into symptoms and signs referable to the nerves, the kidneys, and the skin. The first step in making these diagnoses is to consider them. With a particular condition in mind, the next step is to order those tests that can help confirm or dismiss a particular diagnosis. Nearly all of the renal and dermatologic conditions are diagnosed by renal and skin biopsies, respectively. The importance of a highly competent renal pathologist and dermatopathologist cannot be underestimated. Biopsy is less specific for the neuropathic conditions. Because several of the MGCSs are syndromes, recognizing other manifestations is also key. Treatment recommendations for many of these conditions are anecdotal because of their rarity, but for several of the conditions, IV immunoglobulin, rituximab, and plasma cell–directed therapy are the best options.
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Jungenitz, Tassilo, Marcel Beining, Tijana Radic, Thomas Deller, Hermann Cuntz, Peter Jedlicka, and Stephan W. Schwarzacher. "Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells." Proceedings of the National Academy of Sciences 115, no. 20 (April 30, 2018): E4670—E4679. http://dx.doi.org/10.1073/pnas.1801889115.
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Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.
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Olsen, K. W., J. Castillo-Fernandez, A. Zedeler, N. C. Freiesleben, M. Bungum, A. C. Chan, A. Cardona, et al. "A distinctive epigenetic ageing profile in human granulosa cells." Human Reproduction 35, no. 6 (May 30, 2020): 1332–45. http://dx.doi.org/10.1093/humrep/deaa071.
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Abstract STUDY QUESTION Does women’s age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells? SUMMARY ANSWER Accumulation of epimutations by age and a higher number of age-related differentially methylated regions (DMR) in MGCs were found compared to leukocytes from the same woman, suggesting that the MGCs have a distinctive epigenetic profile. WHAT IS KNOWN ALREADY The mechanisms underlying the decline in women’s fertility from the mid-30s remain to be fully elucidated. The DNAm age of many healthy tissues changes predictably with and follows chronological age, but DNAm age in some reproductive tissues has been shown to depart from chronological age (older: endometrium; younger: cumulus cells, spermatozoa). STUDY DESIGN, SIZE, DURATION This study is a multicenter cohort study based on retrospective analysis of prospectively collected data and material derived from healthy women undergoing IVF or ICSI treatment following ovarian stimulation with antagonist protocol. One hundred and nineteen women were included from September 2016 to June 2018 from four clinics in Denmark and Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS Blood samples were obtained from 118 healthy women with varying ovarian reserve status. MGCs were collected from 63 of the 119 women by isolation from pooled follicles immediately after oocyte retrieval. DNA from leukocytes and MGCs was extracted and analysed with a genome-wide methylation array. Data from the methylation array were processed using the ENmix package. Subsequently, DNAm age was calculated using established and tailored age predictors and DMRs were analysed with the DMRcate package. MAIN RESULTS AND ROLE OF CHANCE Using established age predictors, DNAm age in MGCs was found to be considerable younger and constant (average: 2.7 years) compared to chronological age (average: 33.9 years). A Granulosa Cell clock able to predict the age of both MGCs (average: 32.4 years) and leukocytes (average: 38.8 years) was successfully developed. MGCs differed from leukocytes in having a higher number of epimutations (P = 0.003) but predicted telomere lengths unaffected by age (Pearson’s correlation coefficient = −0.1, P = 0.47). DMRs associated with age (age-DMRs) were identified in MGCs (n = 335) and in leukocytes (n = 1) with a significant enrichment in MGCs for genes involved in RNA processing (45 genes, P = 3.96 × 10−08) and gene expression (152 genes, P = 2.3 × 10−06). The top age-DMRs included the metastable epiallele VTRNA2-1, the DNAm regulator ZFP57 and the anti-Müllerian hormone (AMH) gene. The apparent discordance between different epigenetic measures of age in MGCs suggests that they reflect difference stages in the MGC life cycle. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION No gene expression data were available to associate with the epigenetic findings. The MGCs are collected during ovarian stimulation, which may influence DNAm; however, no correlation between FSH dose and number of epimutations was found. WIDER IMPLICATIONS OF THE FINDINGS Our findings underline that the somatic compartment of the follicle follows a different methylation trajectory with age than other somatic cells. The higher number of epimutations and age-DMRs in MGCs suggest that their function is affected by age. STUDY FUNDING/COMPETING INTEREST(S) This project is part of ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS, the Danish National Research Foundation and the European Research Council. The authors declare no conflict of interest.
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Waku, Yoshiharu. "High Temperature Characteristics of Melt Growth Composites and Their Application to Ultra High Efficiency Gas Turbine Components." Key Engineering Materials 317-318 (August 2006): 473–80. http://dx.doi.org/10.4028/www.scientific.net/kem.317-318.473.
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Much attention has been paid to unidirectionally solidified ceramic composites as a candidate for a high-temperature structural material. We have recently developed eutectic composites, which are named as Melt Growth Composites (MGCs). The binary MGCs (Al2O3/YAG and Al2O3/GAP binary systems) have a novel microstructure, in which continuous networks of single-crystal Al2O3 phases and single-crystal oxide compounds (YAG or GAP) interpenetrate without grain boundaries. Therefore, the MGCs have excellent high-temperature strength characteristics, creep resistance, superior oxidation resistance and thermal stability in an air atmosphere at very high temperatures. Manufacturing processes for the MGCs are being examined under a Japanese national project, scheduled from 2001 - 2005. To achieve higher thermal efficiency for gas turbine systems, a bowed stacking nozzle vane has been fabricated on an experimental basis.
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Liu, Yang, Zhiyu Ren, Yuanlong Wei, Baojiang Jiang, Shanshan Feng, Lingyi Zhang, Weibing Zhang, and Honggang Fu. "Synthesis and applications of graphite carbon sphere with uniformly distributed magnetic Fe3O4 nanoparticles (MGCSs) and MGCS@Ag, MGCS@TiO2." Journal of Materials Chemistry 20, no. 23 (2010): 4802. http://dx.doi.org/10.1039/b925706c.
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Dabrowski, S., R. R. Starzynski, P. Trzeciak, L. Rapala, A. Poniatowski, A. Piliszek, and A. M. Duszewska. "173 THE IMPACT OF ELEVATED TEMPERATURE ON HSP70 EXPRESSION IN CATTLE MURAL GRANULOSA CELLS." Reproduction, Fertility and Development 27, no. 1 (2015): 177. http://dx.doi.org/10.1071/rdv27n1ab173.
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Elevated temperature has an adverse impact on cattle fertility, causing disorders in ovarian functions and follicle development. Heat shock caused by elevated temperature leads to disruption in the cytoskeleton structure and the nuclear maturation of oocytes. Furthermore, it has an impact on mural granulosa cells (MGC), which are responsible for maintaining an appropriate microenvironment for oocyte development and signal transmission through the ovarian follicle. Heat-shock protein 70 is considered as a fundamental marker of cellular defence mechanisms related to heat shock. It protects other proteins from denaturation by forming complexes and stabilisation of their structure. HSP70 has also an ability to repair damaged proteins and allows them to return to their native structure. Furthermore, members of the HSP70 subfamily participate in the folding of newly synthesised proteins and their transport to different cell compartments. The aim of this study was to determine the impact of elevated temperature on HSP70 expression in mural granulosa cells. MGCs were obtained postmortem from mural layers of cattle ovarian follicles with diameters greater than 15 mm and randomly assigned to one of 5 variants: I (control) – MGCs after isolation; II – MGCs cultured in medium with LH at 38.5°C; III – MGCs cultured in medium with LH at elevated temperature, 41°C; IV – MGCs cultured in medium without LH at 38.5°C; and V – MGCs cultured in medium without LH at elevated temperature, 41°C. HSP70 expression was determined using real-time PCR method, and was normalised to s18/h2a expression. Statistical analysis was made in Statgraphics (Statpoint Technologies Inc., Warrenton, VA, USA; P = 0.01) using one-way ANOVA to compare expression of hsp70 between experimental variants and multifactor ANOVA to determine the influence of temperature and LH stimulation on hsp70 expression. Mean values of hsp70 expression in real-time PCR were compared using Tukey's test (a = 0.05). The significant increase of hsp70 expression was observed in MGCs cultured at 41°C (groups III and V) in comparison to MGCs cultured at 38.5°C (groups II and IV) and the control group. Simultaneously, there is no significant impact of LH stimulation on hsp70 expression. In conclusion, mural granulosa cells are susceptible to elevated temperature, which induces activation of cellular defence mechanisms performed by increased hsp70 expression. This may lead to disorders in the function of MGCs followed by changes in follicular fluid composition and signal transmission through the follicle. Research was supported by 505-10-023300-L00171-99.
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Qin, Mengqi, Zhi Xie, Ting Cao, Zhiruo Wang, Xiaoyu Zhang, Feifei Wang, Wei Wei, et al. "Autophagy in Rat Müller Glial Cells Is Modulated by the Sirtuin 4/AMPK/mTOR Pathway and Induces Apoptosis under Oxidative Stress." Cells 11, no. 17 (August 25, 2022): 2645. http://dx.doi.org/10.3390/cells11172645.
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Müller glial cells (MGCs) are a group of glial cells in the retina that provide essential support to retinal neurons; however, the understanding of MGC apoptosis and autophagy remains limited. This study was aimed at investigating the role of autophagy in MGCs under normal and oxidative conditions, and identifying the underlying mechanisms. In addition, the sirtuin 4 (SIRT4)-mediated signaling pathway was observed to regulate the autophagic process in MGCs. To assess the effect of autophagy on MGC mitochondrial function and survival, we treated rMC-1 cells—rat-derived Müller glial cells—with rapamycin and 3-methyladenine (3-MA), and found that MGC death was not induced by such treatment, while autophagic dysfunction could increase MGC apoptosis under oxidative stress, as reflected by the expression level of cleaved caspase 3 and PI staining. In addition, the downregulation of autophagy by 3-MA could influence the morphology of the mitochondrial network structure, the mitochondrial membrane potential, and generation of reactive oxygen species (ROS) under oxidative stress. Moreover, SIRT4 depletion enhanced autophagosome formation, as verified by an increase in the LC3 II/I ratio and a decrease in the expression of SQSTM1/p62, and vice versa. The inhibition of AMPK phosphorylation by compound C could reverse these changes in LC3 II/I and SQSTM1/p62 caused by SIRT4 knockdown. Our research concludes that MGCs can endure autophagic dysfunction in the absence of oxidative stress, while the downregulation of autophagy can cause MGCs to become more sensitized to oxidative stress. Simultaneous exposure to oxidative stress and autophagic dysfunction in MGCs can result in a pronounced impairment of cell survival. Mechanically, SIRT4 depletion can activate the autophagic process in MGCs by regulating the AMPK–mTOR signaling pathway.
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Dwyer, Terry M., and Jerry M. Farley. "Human neutrophil elastase releases two pools of mucinlike glycoconjugate from tracheal submucosal gland cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 278, no. 4 (April 1, 2000): L675—L682. http://dx.doi.org/10.1152/ajplung.2000.278.4.l675.
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Neutrophil elastase can contribute to the pathogenesis of increased airway reactivity and excess mucus secretion in many pulmonary diseases. Ten nanomolar human neutrophil elastase (HNE) effectively empties airway serous cells, raising the question of why HNE is not equally effective at emptying mucous cells of their stored mucin because total release of mucin granules is not seen in postmortem examination of even the most severe disease. To better resolve the mucus secretagogue action of HNE, we measured secretion of mucinlike glycoconjugates (MGCs) released from freshly isolated swine tracheal submucosal gland cells in fractions of the superfusate acquired every 2 min. Six to fifty nanomolar HNE released a fixed quantity of MGCs at an increasing rate with increasing concentrations of enzyme, an action consistent with the release of cell surface mucinlike molecules. The polycation poly-l-lysine (1 μg/ml) released a similar transient of MGCs. A steady-state doubling of MGC rate of release was seen as long as 100 nM HNE was present, but this stimulus represented less than a 1% release of stored MGCs/min and was consistent with release of mucin vesicles from cell stores. Both actions of HNE were inhibited by the specific inhibitors L-680833 and DMP-777 but not by 30 μM erythromycin. Therefore, HNE release of MGCs from tracheal submucosal glands is limited by both the fixed quantity of the MGCs in the transient pool and by the small steady-state response to the higher concentrations of enzyme.
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Waku, Yoshiharu, and Hideyuki Yasuda. "High Temperature Characteristics of Unidirectionally Solidified Eutectic Ceramic Composites and some Potential Applications." Materials Science Forum 638-642 (January 2010): 997–1002. http://dx.doi.org/10.4028/www.scientific.net/msf.638-642.997.
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We have recently developed ceramic eutectics, which are named Melt Growth Composites (MGCs). The binary MGCs (Al2O3/YAG and Al2O3/GAP binary systems) have a novel microstructure, in which continuous networks of single-crystal Al2O3 phases and single-crystal oxide compounds (YAG or GAP) interpenetrate without grain boundaries. To characterize the entangled structure of the typical MGCs, the X-ray computerized tomography (micro X-ray CT) was performed at a synchrotron radiation facility Spring8. The micro X-ray CT showed that the Al2O3 and the GAP are entangled with each other. Therefore, the MGCs have excellent high-temperature strength characteristics, creep resistance, superior oxidation resistance and thermal stability in the air atmosphere at very high temperatures. To achieve higher thermal efficiency for gas turbine systems, MGC bowed stacking nozzle vanes have been fabricated on an experimental basis.
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Lee, Holly, Lesley Street, Jason Tay, Jennifer Grossman, John F. Thaell, Dawn Goodyear, Sylvia McCulloch, Peter Duggan, Paola Neri, and Victor Jimenez-Zepeda. "Monoclonal Gammopathy of Clinical Significance - a Single Center Experience." Blood 132, Supplement 1 (November 29, 2018): 4495. http://dx.doi.org/10.1182/blood-2018-99-117819.
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Abstract Introduction Monoclonal gammopathy of clinical significance (MGCS) is a newly described entity that defines clinical conditions and organ damage resulting from the effects of monoclonal proteins (Fermand et al., 2018). In MGCS, the underlying clone burden resembles an MGUS state, and does not meet criteria for multiple myeloma or lymphoma. A wide spectrum of conditions has been described in MGCS (Fermand et al., 2018). In this retrospective study, our purpose was to identify the incidences of patients with MGCS at our hematology clinics. Methods We collaborated with three clinicians who see the majority of MGUS patients at the University of Calgary Medical Group clinics (UCMG). Patients who were referred and diagnosed with MGUS at the hematology clinic at UCMG since 2014 were assessed. The diagnosis of MGUS and MGCS were made based on consensus criteria (Rajkumar et al., 2014) and the recent publication (Fermand et al., 2018). Retrospective chart reviews were performed and cases with MGCS were analyzed. MGUS risk stratification score was calculated per previous reports (Katzmann et al., 2013; Kyle et al., 2018). Hematological response was assessed using the International Myeloma Working Group criteria (Rajkumar et al., 2014), and renal response was measured using KDIGO guidelines (Radhakrishnan & Cattran, 2012). Results A total of 606 MGUS patients were seen at our clinic from February 2014 to June 2018. Patients who had MGUS and co-existing conditions which met MGCS criteria (Fermand et al., 2018) were evaluated. There were 25 MGCS patients identified. Median age at diagnosis was 60, and 28% were female. Clinical characteristics are outlined in Table 1. Three patients had light chain MGUS. Among the non-light chain MGUS patients, there were 11 high-intermediate risk (55%), 1 intermediate risk (5%), 5 low-intermediate risk (25%), and 3 low risk MGUS (15%). At the time of analysis all patients were alive, and 3 patients have progressed. Median follow up was 2 years (0-16 years). Renal involvement was the most common with 14 patients having biopsy proven renal pathologies that met criteria for monoclonal gammopathy of renal significance (MGRS) (Leung et al., 2012). Four patients had neuropathies, including Anti-MAG, chronic inflammatory demyelinating polyneuropathy (CIDP), distal acquired demyelinating symmetric neuropathy (DADS-M), and autonomic neuropathy. Three patients had skin manifestations (Schnitzler syndrome, necrobiotic xanthogranuloma, scleromyxedema), 1 patient had corneal involvement (crystalline keratopathy), 1 patient had gastrointestinal manifestation (mixed light chain deposition disease), 1 patient had acquired C1 esterase inhibitor deficiency with angioedema, and 1 patient was diagnosed with Sweet syndrome in 1993 which had led to her original monoclonal gammopathy workup. Five out of the 14 patients with MGRS received plasma cell directed chemotherapy, and 1 patient with crystalloid podocytopathy underwent auto-stem cell transplant. Of these 5 patients, 4 had renal response. Treatment for other MGCS cases are indicated in Table 1. Discussion and Conclusion Our series demonstrates that cases of MGCS represent a small minority within our larger MGUS cohort. The most common organ involvements seen in our MGCS patients were renal, nerve and skin. One of the major diagnostic challenges is confirming that the organ dysfunction and MGUS co-exist by true association, and not by coincidence. In our patient cohort, tissue biopsies were obtained when possible (all renal, skin, and GI cases), and others were diagnosed through review with local experts and relying on published literature. The distinction of MGCS from MGUS is important, as it may change treatment decisions. In renal diseases associated with monoclonal gammopathy, referred to as MGRS, renal prognosis is poor and clone directed treatment is associated with improved renal outcomes (Fermand et al., 2013). As prospective or randomized trials are unavailable for MGRS or MGCS, the treatments given at our center were determined on a case-by-case basis relying on expert opinions, local experiences, and a recent guideline (Fermand et al., 2013). Interdisciplinary care is required for both the diagnosis and management of MGCS. Further studies with long term follow-up are needed. Disclosures McCulloch: Takeda: Other: Travel expenses; Celgene: Honoraria. Neri:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.
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Andrei, Daniela, Roland A. Nagy, Aafke van Montfoort, Uwe Tietge, Martijn Terpstra, Klaas Kok, Anke van den Berg, Annemieke Hoek, Joost Kluiver, and Rogier Donker. "Differential miRNA Expression Profiles in Cumulus and Mural Granulosa Cells from Human Pre-ovulatory Follicles." MicroRNA 8, no. 1 (November 27, 2018): 61–67. http://dx.doi.org/10.2174/2211536607666180912152618.
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Background: Mural Granulosa Cells (MGCs) and Cumulus Cells (CCs) are two specialized cell types that differentiate from a common progenitor during folliculogenesis. Although these two cell types have specialized functions and gene expression profiles, little is known about their microRNA (miRNA) expression patterns. Objective: To describe the miRNA profile of mural and cumulus granulosa cells from human preovulatory follicles. </P><P> Methods: Using small RNA sequencing, we defined the miRNA expression profiles of human primary MGCs and CCs, isolated from healthy women undergoing ovum pick-up for in vitro Fertilization (IVF). Results: Small RNA sequencing revealed the expression of several hundreds of miRNAs in MGCs and CCs with 53 miRNAs being significantly differentially expressed between MGCs and CCs. We validated the differential expression of miR-146a-5p, miR-149-5p, miR-509-3p and miR-182-5p by RT-qPCR. Analysis of proven targets revealed 37 targets for miR-146a-5p, 43 for miR-182-5p, 2 for miR-509-3p and 9 for miR-149-5p. Gene Ontology (GO) analysis for these 4 target gene sets revealed enrichment of 12 GO terms for miR-146a-5p and 10 for miR-182-5p. The GO term ubiquitin-like protein conjugation was enriched within both miRNA target gene sets. We generated miRNA expression profiles for MGCs and CCs and identified several differentially expressed miRNAs.
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Vaglienti, María V., Paula V. Subirada, Mariana B. Joray, Gustavo Bonacci, and María C. Sánchez. "Protective Effect of NO2-OA on Oxidative Stress, Gliosis, and Pro-Angiogenic Response in Müller Glial Cells." Cells 12, no. 3 (February 2, 2023): 494. http://dx.doi.org/10.3390/cells12030494.
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Inflammation and oxidative and nitrosative stress are involved in the pathogenesis of proliferative retinopathies (PR). In PR, a loss of balance between pro-angiogenic and anti-angiogenic factors favors the secretion of vascular endothelial growth factor (VEGF). This vascular change results in alterations in the blood–retinal barrier, with extravasation of plasma proteins such as α2-macroglobulin (α2M) and gliosis in Müller glial cells (MGCs, such as MIO-M1). It is well known that MGCs play important roles in healthy and sick retinas, including in PR. Nitro-fatty acids are electrophilic lipid mediators with anti-inflammatory and cytoprotective properties. Our aim was to investigate whether nitro-oleic acid (NO2-OA) is beneficial against oxidative stress, gliosis, and the pro-angiogenic response in MGCs. Pure synthetic NO2-OA increased HO-1 expression in a time- and concentration-dependent manner, which was abrogated by the Nrf2 inhibitor trigonelline. In response to phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS), NO2-OA prevented the ROS increase and reduced the gliosis induced by α2M. Finally, when hypoxic MGCs were incubated with NO2-OA, the increase in VEGF mRNA expression was not affected, but under hypoxia and inflammation (IL-1β), NO2-OA significantly reduced VEGF mRNA levels. Furthermore, NO2-OA inhibited endothelial cell (BAEC) tubulogenesis. Our results highlight NO2-OA’s protective effect on oxidative damage, gliosis; and the exacerbated pro-angiogenic response in MGCs.
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da Costa, Cristiana E. T., Nicola E. Annels, Claudia M. J. M. Faaij, Ramses G. Forsyth, Pancras C. W. Hogendoorn, and R. Maarten Egeler. "Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis." Journal of Experimental Medicine 201, no. 5 (March 7, 2005): 687–93. http://dx.doi.org/10.1084/jem.20041785.
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Langerhans cell histiocytosis (LCH) is a disease that can involve one or multiple organ systems characterized by an accumulation of CD1a+ Langerhans-like cells as well as several other myeloid cell types. The precise origin and role of one of these populations, the multinucleated giant cell (MGC), in this disease remains unknown. This work shows that in three different lesional tissues, bone, skin, and lymph node, the MGCs expressed the characteristic osteoclast markers, tartrate-resistant acid phosphatase and vitronectin receptor, as well as the enzymes cathepsin K and matrix metalloproteinase-9. Although, in bone lesions, the osteoclast-like MGCs were only CD68+, in the nonostotic sites, they coexpressed CD1a. The presence of osteoclast-like MGCs may be explained by the production of osteoclast-inducing cytokines such as receptor activator of nuclear factor κB ligand and macrophage colony-stimulating factor by both the CD1a+ LCH cells and T cells in these lesions. As osteoclast-derived enzymes play a major role in tissue destruction, the osteoclast-like nature of MGCs in all LCH lesions makes them a potential target for the treatment of this disease.
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Wu, YiFei, Evgeniya Kushchaeva, and Tatiana Ugarova. "The Role of Integrins aMb2 (CD11b/CD18) and aDb2 (CD11d/CD18) in Macrophage Fusion." Blood 120, no. 21 (November 16, 2012): 2138. http://dx.doi.org/10.1182/blood.v120.21.2138.2138.
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Abstract Abstract 2138 Macrophage fusion leading to the formation of multinucleated giant cells (MGCs) is a hallmark of many chronic inflammatory reactions. MGCs are an invariable constituent of tuberculoid lesions and also found in a variety of conditions leading to granulomatous inflammation as well as the foreign body reaction. Despite the prominent phenotype, the molecular mechanisms underlying macrophage fusion are not well understood. MGCs originate from macrophages that are recruited to sites of chronic inflammation. The major myelo-monocytic integrin αMβ2 (CD11b/CD18, Mac-1), together with a related integrin αDβ2 (CD11d/CD18), mediate critical adhesive reactions of monocyte/macrophages. The function of β2 integrins in macrophage fusion remains controversial. Some studies using function blocking antibodies implicated αMβ2 in the cell/substrate adhesive interactions that are required for MGC formation, whereas one recent report indicated that this integrin plays a minor role. Moreover, the contribution of αDβ2, a receptor with recognition specificity overlapping that of αMβ2, to macrophage fusion is unknown. To evaluate the role of αMβ2 and αDβ2 in MGC formation, we examined fusion of inflammatory peritoneal macrophages isolated from wild-type mice and mice with deficiency of αM or αD integrin subunits. Macrophages were isolated at day 3 after thioglycollate injection and cultured for 24–72 hours in the presence of IL-4 to induce fusion. Percentage fusion was quantified as the number of giant cell nuclei (≥2 nuclei) to the number of total nuclei. The number of fused macrophages isolated from wild-type mice gradually increased and ∼40–50% macrophages formed MGCs after IL-4 stimulation by day 3. Analyses of fusion of αMβ2-deficient macrophages demonstrated that fusion was significantly reduced. By day 3, macrophage fusion of αMβ2-deficient macrophages was 23 ± 2% of wild-type macrophages. Fusion of αDβ2-deficient macrophages was also decreased and the change was statistically significant, albeit to a smaller degree (75 ± 4%). Using a mouse model of sterile peritonitis induced by thioglycollate injection, we also examined the formation of MGCs in vivo. In wild-type mice, the number of MGCs gradually increased from 2.5 ± 0.3% at day 0 (resident macrophages) to 17 ± 2% at day 18 (the resolution phase of inflammation). Moreover, expression of αMβ2 and αDβ2 on peritoneal macrophages increased by ∼2 and 1.6-fold, respectively, on 18th day after induction of inflammation. In αMβ2-deficient mice, the number of MGCs was reduced by 2.1-fold compared to wild-type mice. Furthermore, while the size of wild-type and αMβ2-deficient giant cells was the same, the number of cells with 3 and more nuclei in fused αMβ2-deficient MGCs was 4-fold less than in wild-type cells. The results indicate that both αMβ2 and αDβ2 integrins support macrophage fusion with αMβ2 playing a dominant role. Disclosures: No relevant conflicts of interest to declare.
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Fu, Xiongjie, Ming Wang, Yingfeng Wan, Ya Hua, Richard F. Keep, and Guohua Xi. "Formation of Multinucleated Giant Cells after Experimental Intracerebral Hemorrhage: Characteristics and Role of Complement C3." Biomedicines 12, no. 6 (June 4, 2024): 1251. http://dx.doi.org/10.3390/biomedicines12061251.
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Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear. The current study investigated the following: (1) the characteristics of MGC formation after ICH, (2) whether it was impacted by complement C3 deficiency in mice and (3) whether it also influenced hematoma degradation (hemosiderin formation). Young and aged male mice, young female mice and C3-deficient and -sufficient mice received a 30 μL injection of autologous whole blood into the right basal ganglia. Brain histology and immunohistochemistry were used to examine MGC formation on days 3 and 7. Hemosiderin deposition was examined by autofluorescence on day 28. Following ICH, MGCs were predominantly located in the peri-hematoma region exhibiting multiple nuclei and containing red blood cells or their metabolites. Aging was associated with a decrease in MGC formation after ICH, while sex showed no discernible effect. C3 deficiency reduced MGC formation and reduced hemosiderin formation. Peri-hematomal MGCs may play an important role in hematoma resolution. Understanding how aging and complement C3 impact MGCs may provide important insights into how to regulate hematoma resolution.
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Wang, Yunduan, Qiao Li, Zifeng Ma, Hongmei Xu, Feiyu Peng, Bin Chen, Bo Ma, et al. "β-Nicotinamide Mononucleotide Alleviates Hydrogen Peroxide-Induced Cell Cycle Arrest and Death in Ovarian Granulosa Cells." International Journal of Molecular Sciences 24, no. 21 (October 27, 2023): 15666. http://dx.doi.org/10.3390/ijms242115666.
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Maintaining normal functions of ovarian granulosa cells (GCs) is essential for oocyte development and maturation. The dysfunction of GCs impairs nutrition supply and estrogen secretion by follicles, thus negatively affecting the breeding capacity of farm animals. Impaired GCs is generally associated with declines in Nicotinamide adenine dinucleotide (NAD+) levels, which triggers un-controlled oxidative stress, and the oxidative stress, thus, attack the subcellular structures and cause cell damage. β-nicotinamide mononucleotide (NMN), a NAD+ precursor, has demonstrated well-known antioxidant properties in several studies. In this study, using two types of ovarian GCs (mouse GCs (mGCs) and human granulosa cell line (KGN)) as cell models, we aimed to investigate the potential effects of NMN on gene expression patterns and antioxidant capacity of both mGCs and KGN that were exposed to hydrogen peroxide (H2O2). As shown in results of the study, mGCs that were exposed to H2O2 significantly altered the gene expression patterns, with 428 differentially expressed genes (DEGs) when compared with those of the control group. Furthermore, adding NMN to H2O2-cultured mGCs displayed 621 DEGs. The functional enrichment analysis revealed that DEGs were mainly enriched in key pathways like cell cycle, senescence, and cell death. Using RT-qPCR, CCK8, and β-galactosidase staining, we found that H2O2 exposure on mGCs obviously reduced cell activity/mRNA expressions of antioxidant genes, inhibited cell proliferation, and induced cellular senescence. Notably, NMN supplementation partially prevented these H2O2-induced abnormalities. Moreover, these similar beneficial effects of NMN on antioxidant capacity were confirmed in the KGN cell models that were exposed to H2O2. Taken together, the present results demonstrate that NMN supplementation protects against H2O2-induced impairments in gene expression pattern, cell cycle arrest, and cell death in ovarian GCs through boosting NAD+ levels and provide potential strategies to ameliorate uncontrolled oxidative stress in ovarian GCs.
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Dufrançais, Ophélie, Rémi Mascarau, Renaud Poincloux, Isabelle Maridonneau-Parini, Brigitte Raynaud-Messina, and Christel Vérollet. "Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune." Cellular and Molecular Life Sciences 78, no. 17-18 (July 23, 2021): 6087–104. http://dx.doi.org/10.1007/s00018-021-03875-x.
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AbstractDifferent types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in bone homeostasis. MGCs are formed by cell-to-cell fusion, and most types have been observed in pathological conditions, especially in infectious and non-infectious chronic inflammatory contexts. The precise role of the different MGCs and the mechanisms that govern their formation remain poorly understood, likely due to their heterogeneity. First, we will introduce the main populations of MGCs derived from the monocyte/macrophage lineage. We will then discuss the known molecular actors mediating the early stages of fusion, focusing on cell-surface receptors involved in the cell-to-cell adhesion steps that ultimately lead to multinucleation. Given that cell-to-cell fusion is a complex and well-coordinated process, we will also describe what is currently known about the evolution of F-actin-based structures involved in macrophage fusion, i.e., podosomes, zipper-like structures, and tunneling nanotubes (TNT). Finally, the localization and potential role of the key fusion mediators related to the formation of these F-actin structures will be discussed. This review intends to present the current status of knowledge of the molecular and cellular mechanisms supporting multinucleation of myeloid cells, highlighting the gaps still existing, and contributing to the proposition of potential disease-specific MGC markers and/or therapeutic targets.
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Rivera Umenza, Erick Lefred, Eduardo Marlés-Sáenz, and Eduardo Gómez-Luna. "Requerimientos y pruebas del sistema de control de la microrred, de acuerdo con los estándares IEEE Std 2030-7-2017 e IEEE Std 2030.8-2018." INGENIERÍA Y COMPETITIVIDAD 24, no. 02 (May 26, 2022): 21. http://dx.doi.org/10.25100/iyc.v0i00.11269.
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Este artículo presenta los requisitos y pruebas del sistema de control de la microrred MGCS establecidos en la IEEE Std 2030.7-2017 e IEEE Std 2030.8-2018respectivamente, y la recomendación para las comunicaciones por la IEEE Std 2030.9-2019.
La sección 2 abordará las funciones básicas del MGCS, que son envío y transición. También se presentarán una serie de tablas donde se describirán los requisitos de las funciones centrales, así como sus características y métricas. En la sección 3 se muestran las pruebas de las funciones centrales, se expone los escenarios donde se deben probar y las variables que se deben medir.
En el apartado 4 se expone la importancia de las comunicaciones dentro del MGCS, por ejemplo, que la sinergia de todos los activos, como protecciones, generación distribuida DG y cargas, depende de una excelente comunicación, por lo que se mencionará una variedad de tecnologías para lograr esta interacción entre todos estos elementos ya mencionados.
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Zeng, Shaohua, Mingxia Shen, Pengpeng Duan, Fengling Lu, Shangneng Chen, and Yijiao Xue. "Effect of ultrasonic-assisted impregnation parameters on the preparation and interfacial properties of MWCNT/glass-fiber reinforced composites." e-Polymers 18, no. 1 (January 26, 2018): 35–47. http://dx.doi.org/10.1515/epoly-2017-0112.
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AbstractIn this study, an ultrasonic-assisted impregnation method was employed to deposit carboxyl multiwalled carbon nanotubes (MWCNTs) onto the E-glass fiber fabric (GFf) for the preparation of the MWCNT-GFf reinforcer. The effects of ultrasonic power, duration and temperature on the dispersion of MWCNTs onto GFf were investigated, and the mechanical properties, interlaminar adhesion, and dynamic viscoelasticity of the resulting MWCNT-GFf-reinforced composites (MGCs) were evaluated. The results indicated that an effective dispersion of MWCNTs onto GFf without obvious breakage of the MWCNTs was achieved under an ultrasonic power of 600 W, duration of 6 min, and processing temperature of about 0°C. Compared with the GFf-reinforced composite, the tensile strength, flexural strength and interlaminar shear strength of the MGCs exhibited maximum increments of 38.4%, 34.6% and 47.1%, respectively. Moreover, the storage moduli and glass-transition temperatures of the MGCs were significantly enhanced. The ultrasonic parameters were of key importance for dispersing MWCNTs onto GFf and improving the interfacial properties of the composites.
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Kloc, Malgorzata, Arijita Subuddhi, Ahmed Uosef, Jacek Z. Kubiak, and Rafik M. Ghobrial. "Monocyte–Macrophage Lineage Cell Fusion." International Journal of Molecular Sciences 23, no. 12 (June 12, 2022): 6553. http://dx.doi.org/10.3390/ijms23126553.
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Cell fusion (fusogenesis) occurs in natural and pathological conditions in prokaryotes and eukaryotes. Cells of monocyte–macrophage lineage are highly fusogenic. They create syncytial multinucleated giant cells (MGCs) such as osteoclasts (OCs), MGCs associated with the areas of infection/inflammation, and foreign body-induced giant cells (FBGCs). The fusion of monocytes/macrophages with tumor cells may promote cancer metastasis. We describe types and examples of monocyte–macrophage lineage cell fusion and the role of actin-based structures in cell fusion.
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Nath, Madhu, Yang Shan, Angela M. Myers, and Patrice Elie Fort. "HspB4/αA-Crystallin Modulates Neuroinflammation in the Retina via the Stress-Specific Inflammatory Pathways." Journal of Clinical Medicine 10, no. 11 (May 28, 2021): 2384. http://dx.doi.org/10.3390/jcm10112384.
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Purpose: We have previously demonstrated that HspB4/αA-crystallin, a molecular chaperone, plays an important intrinsic neuroprotective role during diabetes, by its phosphorylation on residue 148. We also reported that HspB4/αA-crystallin is highly expressed by glial cells. There is a growing interest in the potential causative role of low-grade inflammation in diabetic retinopathy pathophysiology and retinal Müller glial cells’ (MGCs’) participation in the inflammatory response. MGCs indeed play a central role in retinal homeostasis via secreting various cytokines and other mediators. Hence, this study was carried out to delineate and understand the regulatory function of HspB4/αA-crystallin in the inflammatory response associated with metabolic stresses. Methods: Primary MGCs were isolated from knockout HspB4/αA-crystallin mice. These primary cells were then transfected with plasmids encoding either wild-type (WT), phosphomimetic (T148D), or non-phosphorylatable mutants (T148A) of HspB4/αA-crystallin. The cells were exposed to multiple metabolic stresses including serum starvation (SS) or high glucose with TNF-alpha (HG + T) before being further evaluated for the expression of inflammatory markers by qPCR. The total protein expression along with subcellular localization of NF-kB and the NLRP3 component was assessed by Western blot. Results: Elevated levels of IL-6, IL-1β, MCP-1, and IL-18 in SS were significantly diminished in MGCs overexpressing WT and further in T148D as compared to EV. The HG + T-induced increase in these inflammatory markers was also dampened by WT and even more significantly by T148D overexpression, whereas T148A was ineffective in either stress. Further analysis revealed that overexpression of WT or the T148D, also led to a significant reduction of Nlrp3, Asc, and caspase-1 transcript expression in serum-deprived MGCs and nearly abolished the NF-kB induction in HG + T diabetes-like stress. This mechanistic effect was further evaluated at the protein level and confirmed the stress-dependent regulation of NLRP3 and NF-kB by αA-crystallin. Conclusions: The data gathered in this study demonstrate the central regulatory role of HspB4/αA-crystallin and its modulation by phosphorylation on T148 in retinal MGCs. For the first time, this study demonstrates that HspB4/αA-crystallin can dampen the stress-induced expression of pro-inflammatory cytokines through the modulation of multiple key inflammatory pathways, therefore, suggesting its potential as a therapeutic target for the modulation of chronic neuroinflammation.
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Chen, Chien-Hung, Yu-Wei Hsieh, Jen-Fu Huang, Chih-Po Hsu, Chia-Ying Chung, and Chih-Chi Chen. "Predictors of In-Hospital Mortality for Road Traffic Accident-Related Severe Traumatic Brain Injury." Journal of Personalized Medicine 11, no. 12 (December 9, 2021): 1339. http://dx.doi.org/10.3390/jpm11121339.
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(1) Background: Road traffic accidents (RTAs) are the leading cause of pediatric traumatic brain injury (TBI) and are associated with high mortality. Few studies have focused on RTA-related pediatric TBI. We conducted this study to analyze the clinical characteristics of RTA-related TBI in children and to identify early predictors of in-hospital mortality in children with severe TBI. (2) Methods: In this 15-year observational cohort study, a total of 618 children with RTA-related TBI were enrolled. We collected the patients’ clinical characteristics at the initial presentations in the emergency department (ED), including gender, age, types of road user, the motor components of the Glasgow Coma Scale (mGCS) score, body temperature, blood pressure, blood glucose level, initial prothrombin time, and the intracranial computed tomography (CT) Rotterdam score, as potential mortality predictors. (3) Results: Compared with children exhibiting mild/moderate RTA-related TBI, those with severe RTA-related TBI were older and had a higher mortality rate (p < 0.001). The in-hospital mortality rate for severe RTA-related TBI children was 15.6%. Compared to children who survived, those who died in hospital had a higher incidence of presenting with hypothermia (p = 0.011), a lower mGCS score (p < 0.001), a longer initial prothrombin time (p < 0.013), hyperglycemia (p = 0.017), and a higher Rotterdam CT score (p < 0.001). Multivariate analyses showed that the mGCS score (adjusted odds ratio (OR): 2.00, 95% CI: 1.28–3.14, p = 0.002) and the Rotterdam CT score (adjusted OR: 2.58, 95% CI: 1.31–5.06, p = 0.006) were independent predictors of in-hospital mortality. (4) Conclusions: Children with RTA-related severe TBI had a high mortality rate. Patients who initially presented with hypothermia, a lower mGCS score, a prolonged prothrombin time, hyperglycemia, and a higher Rotterdam CT score in brain CT analyses were associated with in-hospital mortality. The mGCS and the Rotterdam CT scores were predictive of in-hospital mortality independently.
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Lee, Eun-Jin, Mengmei Zheng, Cheryl Mae Craft, and Shinwu Jeong. "Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) are localized in the nucleus of retinal Müller glial cells and modulated by cytokines and oxidative stress." PLOS ONE 16, no. 7 (July 16, 2021): e0253915. http://dx.doi.org/10.1371/journal.pone.0253915.
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Matrix metalloproteinases (MMPs) are involved in the pathology of numerous inflammatory retinal degenerations, including retinitis pigmentosa (RP). Our previous work revealed that intravitreal injections with tissue inhibitor of metalloproteinases 1 (TIMP-1) reduce the progression of rod cell death and inhibit cone cell remodeling that involves reactive gliosis in retinal Müller glial cells (MGCs) in rodent models. The underlying cellular and molecular mechanisms of how TIMP-1 functions in the retina remain to be resolved; however, MGCs are involved in structural homeostasis, neuronal cell survival and death. In the present study, MMP-9 and TIMP-1 expression patterns were investigated in a human MGC line (MIO-M1) under inflammatory cytokine (IL-1β and TNF-α) and oxidative stress (H2O2) conditions. First, both IL-1β and TNF-α, but not H2O2, have a mild in vitro pro-survival effect on MIO-M1 cells. Treatment with either cytokine results in the imbalanced secretion of MMP-9 and TIMP-1. H2O2 treatment has little effect on their secretion. The investigation of their intracellular expression led to interesting observations. MMP-9 and TIMP-1 are both expressed, not only in the cytoplasm, but also inside the nucleus. None of the treatments alters the MMP-9 intracellular distribution pattern. In contrast to MMP-9, TIMP-1 is detected as speckles. Intracellular TIMP-1 aggregation forms in the cytoplasmic area with IL-1β treatment. With H2O2 treatments, the cell morphology changes from cobbles to spindle shapes and the nuclei become larger with increases in TIMP-1 speckles in an H2O2 dose-dependent manner. Two TIMP-1 cell surface receptors, low density lipoprotein receptor-related protein-1 (LRP-1) and cluster of differentiation 82 (CD82), are expressed within the nucleus of MIO-M1 cells. Overall, these observations suggest that intracellular TIMP-1 is a target of proinflammatory and oxidative insults in the MGCs. Given the importance of the roles for MGCs in the retina, the functional implication of nuclear TIMP-1 and MMP-9 in MGCs is discussed.
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Moghimi-Khorasgani, Ali, Farshad Homayouni Moghadam, and Mohammad Hossein Nasr-Esfahani. "Ferulic Acid reduces amyloid beta mediated neuroinflammation through modulation of Nurr1 expression in microglial cells." PLOS ONE 18, no. 8 (August 17, 2023): e0290249. http://dx.doi.org/10.1371/journal.pone.0290249.
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Microglial cells (MGCs) serve as the resident macrophages in the brain and spinal cord, acting as the first line of immune defense against pathological changes. With various phenotypes, they can shift from a homeostatic state to a reactive state or transit from a reactive to a non-inflammatory reactive state (alternative homeostatic). A well-timed transit is crucial in limiting excessive microglial reaction and promoting the healing process. Studies indicate that increased Nurr1 expression promotes anti-neuroinflammatory responses in the brain. In this study, we investigated the possible role of ferulic acid (FA) in facilitating microglia transition due to its anti-inflammatory and Nurr1-inducing effects. MGCs were extracted from the brains of male NMRI mice at postnatal day 2 (P2) and cultured with or without FA and beta-amyloid (Aβ). Real-time qRT-PCR was conducted to measure the expressions of Nurr1, IL-1β, and IL-10 genes. Immunostaining was performed to determine the number of NURR1-positive cells, and the ramification index (RI) of MGCs was calculated using Image J software. Treating MGCs with FA (50 μg/ml) induced Nurr1 and IL-10 expressions, while reducing the level of IL-1β in the absence of Aβ-stress. Further assessments on cells under Aβ-stress showed that FA treatment restored the IL-10 and Nurr1 levels, increased the RI of cells, and the number of NURR1-positive cells. Morphological assessments and measurements of the RI revealed that FA treatment reversed amoeboid and rod-like cells to a ramified state, which is specific morphology for non-inflammatory reactive microglia. To conclude, FA can provide potential alternative homeostatic transition in Aβ-reactive microglia by recruiting the NURR1 dependent anti-inflammatory responses. This makes it a promising therapeutic candidate for suppressing Aβ-induced neuroinflammatory responses in MGCs. Furthermore, given that FA has the ability to increase NURR1 levels in homeostatic microglia, it could be utilized as a preventative medication.
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Zhang, Qinli, Bingyi Zhang, and Daolin Wang. "Environmental Benefit Assessment of Blended Cement with Modified Granulated Copper Slag." Materials 15, no. 15 (August 3, 2022): 5359. http://dx.doi.org/10.3390/ma15155359.
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This study aimed to investigate the environmental impact of modified granulated copper slag (MGCS) utilization in blended cement production at a representative cement plant in China. Sensitivity analysis was performed on the substance inputs, and the life cycle impact assessment (LCIA) model was applied. A detailed comparative analysis was conducted of the environmental impact of cement production in other studies, and ordinary Portland cement production at the same cement plant. Results showed that calcination has the largest contribution impact of all the impact categories, especially in causing global warming (93.67%), which was the most prominent impact category. The life cycle assessment (LCA) result of blended cement was sensitive to the chosen LCIA model and the depletion of limestone and energy. In this study, producing blended cement with MGCS effectively mitigated the environmental impact for all the selected impact categories. Results also show a reduction in abiotic depletion (46.50%) and a slight growth (6.52%) in human toxicity. The adoption of MGCS in blended cement would therefore generally decrease the comprehensive environmental impact of cement, which contributes to the development of sustainable building materials.
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Emori, Chihiro, Haruka Ito, Wataru Fujii, Kunihiko Naito, and Koji Sugiura. "Oocytes suppress FOXL2 expression in cumulus cells in mice†." Biology of Reproduction 103, no. 1 (April 20, 2020): 85–93. http://dx.doi.org/10.1093/biolre/ioaa054.
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Abstract Cumulus cells and mural granulosa cells (MGCs) play distinct roles during follicular development, and normal development of these cell lineages is critical for the female fertility. Transcriptomic diversification between the two cell lineages is obviously a critical mechanism for their functional diversification; however, the transcriptional regulators responsible for this event have not been fully defined. In this study, we sought to identify key transcriptional regulators responsible for the differential gene expression between the two cell lineages. In silico analysis of transcriptomic comparison between cumulus cells and MGCs identified several candidate regulators responsible for the diversification of the two cell lineages. Among them, we herein focused on forkhead box L2 (FOXL2) and showed that expressions of FOXL2 as well as its target transcripts were differentially regulated between cumulus cells and MGCs. The lower expression of FOXL2 in cumulus cells seemed to be due to the suppression by oocyte-derived paracrine signals. These results suggest that FOXL2 is one of the critical transcription factors that determine cumulus cell and MGC lineages under the control of oocytes.
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Falzoni, Simonetta, Paola Chiozzi, Davide Ferrari, Gary Buell, and Francesco Di Virgilio. "P2X7Receptor and Polykarion Formation." Molecular Biology of the Cell 11, no. 9 (September 2000): 3169–76. http://dx.doi.org/10.1091/mbc.11.9.3169.
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Cell fusion is a central phenomenon during the immune response that leads to formation of large elements called multinucleated giant cells (MGCs) of common occurrence at sites of granulomatous inflammation. We have previously reported on the involvement in this event of a novel receptor expressed to high level by mononuclear phagocytes, the purinergic P2X7receptor. Herein, we show that blockade of this receptor by a specific monoclonal antibody prevents fusion in vitro. In contrast, cell fusion is stimulated by addition of enzymes that destroy extracellular ATP (i.e., apyrase or hexokinase). Experiments performed with phagocytes selected for high (P2X7hyper) or low (P2X7hypo) P2X7expression show that fusion only occurs between P2X7hyper/P2X7hyper and not between P2X7hyper/P2X7hypo or P2X7hypo/P2X7hypo. During MGCs formation we detected activation of caspase 3, an enzyme that is powerfully stimulated by P2X7. Finally, we observed that during MGCs formation, the P2X7receptor is preferentially localized at sites of cell-to-cell contact. These findings support the hypothesis originally put forward by our group that the P2X7receptor participates in multinucleated giant cell formation.
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D. Parga, Andres, Elizabeth George, and Donald Rudikoff. "Optimal Treatment Strategies for Chronic Cutaneous Vasculitis with Concurrent IGA Monoclonal Gammopathy: A Case Report." Journal of Clinical Rheumatology Research 4, no. 2 (September 16, 2024): 01–04. https://doi.org/10.33140/jcrr.04.02.01.
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This case report investigates the complex presentation and management of a 61-year-old female patient with bilateral leg ulcerations, ultimately diagnosed with cutaneous vasculitis and concurrent IgA monoclonal gammopathy, classified as monoclonal gammopathy of clinical significance (MGCS). MGCS refers to nonmalignant monoclonal gammopathies that cause significant disease, often manifesting with symptoms affecting the nerves, kidneys, and skin. Our patient exhibited chronic ulcerations and a challenging clinical course over four years, requiring extensive investigation and multiple therapeutic interventions. Initial treatments, including high-dose corticosteroids and rituximab, provided minimal to limited improvement. However, significant clinical response was observed following the administration of hydroxychloroquine and dapsone. This case underscores the importance of recognizing MGCS in patients presenting with monoclonal gammopathy and unexplained symptoms, the critical role of skin biopsies in diagnosis, and the necessity of a multidisciplinary approach in managing these rare and complex conditions. The report highlights the complexities of diagnosing and treating cutaneous vasculitis associated with IgA monoclonal gammopathy and discusses the potential benefits of targeted therapies such as hydroxychloroquine and dapsone in achieving optimal outcomes
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Bladé, Joan, and M. Teresa Cibeira. "M-protein–related disorders: MGCS." Blood 132, no. 14 (October 4, 2018): 1464–65. http://dx.doi.org/10.1182/blood-2018-07-865642.
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Adam, Zdeněk, David Zeman, Luděk Pour, Marta Krejčí, Soňa Štěpánková, Vladimír Vašků, Eva Vlčková, et al. "Monoclonal gammopathy of undetermined signifikace (MGUS and monoclonal gammopathy of clinical significance (MGCS)." Onkologie 16, Suppl. B (October 14, 2022): 33–56. http://dx.doi.org/10.36290/xon.2022.055.
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Lin, Huicong, Mingzhu Ye, Yanjuan Lin, Fuhong Chen, Sally Chan, Hongxia Cai, and Jiemin Zhu. "Mobile App for Gynecologic Cancer Support for Patients With Gynecologic Cancer Receiving Chemotherapy in China: Multicenter Randomized Controlled Trial." Journal of Medical Internet Research 25 (November 13, 2023): e49939. http://dx.doi.org/10.2196/49939.
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Background Patients with gynecologic cancer receiving chemotherapy often report unmet supportive care needs. Compared with traditional face-to-face clinical interventions, mobile health can increase access to supportive care and may address patients’ needs. Although app-based support programs have been developed to support patients with gynecologic cancer, their efficacy has not been adequately tested. Objective The aim of this study was to examine the efficacy of a mobile app for gynecologic cancer support (MGCS) for patients with gynecologic cancer receiving chemotherapy in China. Methods A multicenter randomized controlled trial was conducted in 2 university-affiliated hospitals in China. A total of 168 Chinese patients with gynecologic cancer were recruited and randomized to receive routine care or MGCS program plus routine care for 24 weeks. The Mishel uncertainty in illness theory guided the development of MGCS program, which has 4 modules: weekly topics, emotional care, discussion center, and health consultation. The primary outcome of this program was the assessment of the uncertainty in illness. The secondary outcomes were quality of life, symptom distress, and social support. All health outcomes were evaluated at baseline (T0), 12 weeks (T1), and 24 weeks (T2). Repeated measures analysis of covariance was used to assess the efficacy of the MGCS program. Results In this trial, 67 patients in the control group and 69 patients in the intervention group completed 2 follow-up assessments (response rate, 136/168, 81%). At 12 weeks, no significant differences were observed in any of the health outcomes between the 2 groups. At 24 weeks, compared to patients in the control group, those in the intervention group reported significant decreased uncertainty in illness (P<.001; d=–0.60; adjusted mean difference –7.69, 95% CI –11.31 to –4.07) and improved quality of life (P=.04; d=0.30; adjusted mean difference 4.77, 95% CI 0.12-9.41). Conclusions The MGCS program demonstrated efficacy in supporting patients with gynecologic cancer receiving chemotherapy. This trial illustrates that an app-based program can be incorporated into routine care to support patients with cancer and suggests that allocation of more resources (grants, manpower, etc) to mobile health in clinics is warranted. Trial Registration Chinese Clinical Trial Registry ChiCTR2000033678; https://www.chictr.org.cn/showproj.html?proj=54807
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Farjallah, Mohamed, Dibyendu Sardar, Bimalendu Deb, and Hamid Berriche. "Electronic Structure, Spectroscopy, Cold Ion–Atom Elastic Collision Properties, and Photoassociation Formation Prediction of the (MgCs)+ Molecular Ion." Atoms 11, no. 9 (September 15, 2023): 121. http://dx.doi.org/10.3390/atoms11090121.
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In this paper, we extensively study the electronic structure, interactions, and dynamics of the (MgCs)+ molecular ion. The exchanges between the alkaline atom and the low-energy cationic alkaline earths, which are important in the field of cold and ultracold quantum chemistry, are studied. We use an ab initio approach based on the formalism of non-empirical pseudo-potential for Mg2+ and Cs+ cores, large Gaussian basis sets, and full-valence configuration interaction. In this context, the (MgCs)+ cation is treated as an effective two-electron system. Adiabatic potential energy curves and their spectroscopic constants for the ground and the first 20 excited states of 1,3Σ+ symmetries are determined. Furthermore, we identify the avoided crossings between the electronic states of 1,3Σ+ symmetries. These crossings are related to the charge transfer process between the two ionic limits, Mg/Cs+ and Mg+/Cs. Therefore, vibrational-level spacings and the transition and permanent dipole moments are presented and analyzed. Using the produced potential energy data, the ground-state scattering wave functions and elastic cross-sections are calculated for a wide range of energies. In addition, we predict the formation of a translationally and rotationally cold molecular ion (MgCs)+ in the ground-state electronic potential energy through a stimulated Raman-type process aided by ion–atom cold collision. In the low-energy limit (<1 mK), elastic scattering cross-sections exhibit Wigner law threshold behavior, while in the high-energy limit, the cross-sections act as a function of energy E go as E−1/3. A qualitative discussion about the possibilities of forming cold (MgCs)+ molecular ions by photoassociative spectroscopy is presented.
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Cui, Kaixuan, Hongmiao Pan, Jianwei Chen, Jia Liu, Yicong Zhao, Si Chen, Wenyan Zhang, Tian Xiao, and Long-Fei Wu. "A Novel Isolate of Spherical Multicellular Magnetotactic Prokaryotes Has Two Magnetosome Gene Clusters and Synthesizes Both Magnetite and Greigite Crystals." Microorganisms 10, no. 5 (April 28, 2022): 925. http://dx.doi.org/10.3390/microorganisms10050925.
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Multicellular magnetotactic prokaryotes (MMPs) are a unique group of magnetotactic bacteria that are composed of 10–100 individual cells and show coordinated swimming along magnetic field lines. MMPs produce nanometer-sized magnetite (Fe3O4) and/or greigite (Fe3S4) crystals—termed magnetosomes. Two types of magnetosome gene cluster (MGC) that regulate biomineralization of magnetite and greigite have been found. Here, we describe a dominant spherical MMP (sMMP) species collected from the intertidal sediments of Jinsha Bay, in the South China Sea. The sMMPs were 4.78 ± 0.67 μm in diameter, comprised 14–40 cells helical symmetrically, and contained bullet-shaped magnetite and irregularly shaped greigite magnetosomes. Two sets of MGCs, one putatively related to magnetite biomineralization and the other to greigite biomineralization, were identified in the genome of the sMMP, and two sets of paralogous proteins (Mam and Mad) that may function separately and independently in magnetosome biomineralization were found. Phylogenetic analysis indicated that the sMMPs were affiliated with Deltaproteobacteria. This is the first direct report of two types of magnetosomes and two sets of MGCs being detected in the same sMMP. The study provides new insights into the mechanism of biomineralization of magnetosomes in MMPs, and the evolutionary origin of MGCs.
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Gülersoy, Erdem, and İsmail Günal. "Atypical Presentation of a Tick Paralysis in a Dog." Acta VETERINARIA Indonesiana 10, no. 1 (March 31, 2022): 23–30. http://dx.doi.org/10.29244/avi.10.1.23-30.
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An 11-month-old Guregh dog was admitted to the hospital with history of vomiting and regurgitation, gait disorder and unilateral thread-like hypersalivation for last a few days. Clinical and radiographic examinations revealed quadriplegia, facial paralysis, grave MGCS (5) and VAS (4) scores, severe megaesophagus and gas-filled distended intestines. In hematochemical analysis, leucocytosis due to granulocytosis with polycythemia, elevated BUN, creatinine, CPK and AST levels were determined. During careful clinical examination, engorged ticks were found in the head and neck region of the dog. After excluding diseases that may cause similar symptoms, diagnosis of atypical tick paralysis was made on the basis of clinical findings such as history of vomiting and regurgitation before the onset of gait abnormalities and the presence of megaoesophagus although the patient is less than 1 year old. The clinical appearance, MGCS and VAS scores improved after 5 days of hospitalization period. It was concluded that the presence of megaesophagus in young dogs with vomiting and/or regurgitation before the onset of neurological findings are observed in atypical tick paralysis and hospitalization of the patient, tick removal, supportive treatment administration and MGCS and VAS score assessments provide successful clinical results.
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Chiozzi, Paola, Juana M. Sanz, Davide Ferrari, Simonetta Falzoni, Arrigo Aleotti, Gary N. Buell, Ginetta Collo, and Francesco Di Virgilio. "Spontaneous Cell Fusion in Macrophage Cultures Expressing High Levels of the P2Z/P2X7 Receptor." Journal of Cell Biology 138, no. 3 (August 11, 1997): 697–706. http://dx.doi.org/10.1083/jcb.138.3.697.
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Mouse and human macrophages express a plasma membrane receptor for extracellular ATP named P2Z/P2X7. This molecule, recently cloned, is endowed with the intriguing property of forming an aqueous pore that allows transmembrane fluxes of hydrophylic molecules of molecular weight below 900. The physiological function of this receptor is unknown. In a previous study we reported experiments suggesting that the P2Z/P2X7 receptor is involved in the formation of macrophage-derived multinucleated giant cells (MGCs; Falzoni, S., M. Munerati, D. Ferrari, S. Spisani, S. Moretti, and F. Di Virgilio. 1995. J. Clin. Invest. 95:1207– 1216). We have selected several clones of mouse J774 macrophages that are characterized by either high or low expression of the P2Z/P2X7 receptor and named these clones P2Zhyper or P2Zhypo, respectively. P2Zhyper, but not P2Zhypo, cells grown to confluence in culture spontaneously fuse to form MGCs. As previously shown for human macrophages, fusion is inhibited by the P2Z/P2X7 blocker oxidized ATP. MGCs die shortly after fusion through a dramatic process of cytoplasmic sepimentation followed by fragmentation. These observations support our previous hypothesis that the P2Z/P2X7 receptor is involved in macrophage fusion.
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Ruvolo, Giovanni, Domenica Matranga, Maria Magdalena Barreca, and Liana Bosco. "AKT, p-AKT, ERK1/2 and p-ERK1/2 in Mural Granulosa Cells Are Not Correlated to Different Ovarian Stimulation Protocols in Patients Undergoing Assisted Reproductive Treatment." Life 14, no. 5 (April 25, 2024): 554. http://dx.doi.org/10.3390/life14050554.
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(1) Background: In this paper we aim to study the relationship between the expression levels of molecules involved in apoptotic/survival pathways, considered as molecular markers of oocyte competence (i.e., AKT, p-AKT, ERK1/2, and p-ERK1/2) in mural granulosa cells (MGCs) and the administration of r-FSH alone or combined with exogenous r-LH, in ovarian stimulation protocol. Moreover, we aim to evaluate oocyte competence by comparing normally cleaved embryos that were transferred in the uterus, with embryos that were arrested during in vitro culture. (2) Methods: The study included 34 normo-responder women undergoing ICSI procedures. All subjects were divided into two groups. Group A consisted of 18 women stimulated with r-FSH and used as a control group; Group B consisted of 14 women stimulated with r-FSH combined with r-LH. The MGCs were obtained from individual follicles. Immunoblot analyses were carried out to analyze the AKT, p-AKT, ERK1/2, and p-ERK1/2 levels in MGCs and to correlate them with the ovarian stimulation protocol. Furthermore, the oocyte competence was evaluated, for each follicle, according to the development of the embryo during in vitro culture and the pregnancy outcome. (3) Results: We found no significant difference in the levels of molecules in isolated MGCs between groups A and B. These results, in light of our previous research, suggest for the first time, to our knowledge, that cumulus cells and mural granulosa cells in the same follicle show different expression levels of molecules involved in the apoptotic mechanism. (4) Conclusions: Our results could clarify some controversial data in the literature where cumulative cell pools of cumulus and granulosa were analyzed, described as ovarian follicle cells, and used as markers of oocyte competence. In this paper, we found evidence that cumulus and granulosa cells need to be analyzed separately.
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Beck, Marianne, Erling A. Bringeland, Gunnar Qvigstad, and Reidar Fossmark. "Gastric Cancers Missed at Upper Endoscopy in Central Norway 2007 to 2016—A Population-Based Study." Cancers 13, no. 22 (November 10, 2021): 5628. http://dx.doi.org/10.3390/cancers13225628.
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Background: The rates of missed gastric cancers (MGC) at upper endoscopy (UE) has been reported at 5–10% in Western countries. We aimed to calculate the rate of MGC and identify factors associated with MGC. Methods: Retrospective population-based cohort study including 730 patients diagnosed with gastric adenocarcinoma in Central Norway 2007–2016. MGCs were incident gastric adenocarcinomas diagnosed 6–36 months after a previous UE. Factors associated with MGC were examined. Definitely missed (UE 6–12 months prior) and potentially missed (UE 12–36 months prior) MGCs were compared. Results: Sixty-seven (9.2%) of 730 gastric cancers were MGC. MGC were associated with localization (p = 0.009) and more frequent in the corpus, Lauren’s histological type (p = 0.028) and diffuse type more prevalent, and previous Billroth 2-operation (14.9% vs. 4.7%, p = 0.001). MGCs were diagnosed at earlier stages (p = 0.037). An ulceration was more common in patients with definitely missed than potentially MGC (40.9% vs. 17.8%, p = 0.041). Conclusions: MGC accounted for 9.2% of gastric cancers in Central Norway. MGC were associated with localization in the corpus, Lauren´s diffuse type and previous Billroth-2-operation. Intensified follow-up and adequate biopsy sampling of patients with gastric ulcerations could reduce the rate of missed gastric cancers.
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Pascal Andreu, Victòria, Jorge Roel-Touris, Dylan Dodd, Michael A. Fischbach, and Marnix H. Medema. "The gutSMASH web server: automated identification of primary metabolic gene clusters from the gut microbiota." Nucleic Acids Research 49, W1 (May 21, 2021): W263—W270. http://dx.doi.org/10.1093/nar/gkab353.
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Abstract Anaerobic bacteria from the human microbiome produce a wide array of molecules at high concentrations that can directly or indirectly affect the host. The production of these molecules, mostly derived from their primary metabolism, is frequently encoded in metabolic gene clusters (MGCs). However, despite the importance of microbiome-derived primary metabolites, no tool existed to predict the gene clusters responsible for their production. For this reason, we recently introduced gutSMASH. gutSMASH can predict 41 different known pathways, including MGCs involved in bioenergetics, but also putative ones that are candidates for novel pathway discovery. To make the tool more user-friendly and accessible, we here present the gutSMASH web server, hosted at https://gutsmash.bioinformatics.nl/. The user can either input the GenBank assembly accession or upload a genome file in FASTA or GenBank format. Optionally, the user can enable additional analyses to obtain further insights into the predicted MGCs. An interactive HTML output (viewable online or downloadable for offline use) provides a user-friendly way to browse functional gene annotations and sequence comparisons with reference gene clusters as well as gene clusters predicted in other genomes. Thus, this web server provides the community with a streamlined and user-friendly interface to analyze the metabolic potential of gut microbiomes.
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Yuan, Hong-Jie, Zhi-Bin Li, Xin-Yue Zhao, Guang-Yi Sun, Guo-Liang Wang, Ying-Qi Zhao, Min Zhang, and Jing-He Tan. "Glucocorticoids impair oocyte competence and trigger apoptosis of ovarian cells via activating the TNF-α system." Reproduction 160, no. 1 (July 2020): 129–40. http://dx.doi.org/10.1530/rep-20-0025.
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Mechanisms by which female stress and particularly glucocorticoids impair oocyte competence are largely unclear. Although one study demonstrated that glucocorticoids triggered apoptosis in ovarian cells and oocytes by activating the FasL/Fas system, other studies suggested that they might induce apoptosis through activating other signaling pathways as well. In this study, both in vivo and in vitro experiments were conducted to test the hypothesis that glucocorticoids might trigger apoptosis in oocytes and ovarian cells through activating the TNF-α system. The results showed that cortisol injection of female mice (1.) impaired oocyte developmental potential and mitochondrial membrane potential with increased oxidative stress; (2.) induced apoptosis in mural granulosa cells (MGCs) with increased oxidative stress in the ovary; and (3.) activated the TNF-α system in both ovaries and oocytes. Culture with corticosterone induced apoptosis and activated the TNF-α system in MGCs. Knockdown or knockout of TNF-α significantly ameliorated the pro-apoptotic effects of glucocorticoids on oocytes and MGCs. However, culture with corticosterone downregulated TNF-α expression significantly in oviductal epithelial cells. Together, the results demonstrated that glucocorticoids impaired oocyte competence and triggered apoptosis in ovarian cells through activating the TNF-α system and that the effect of glucocorticoids on TNF-α expression might vary between cell types.