Artykuły w czasopismach: „HYOU1”

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Rao, Shan, Linda Oyang, Jiaxin Liang, Pin Yi, Yaqian Han, Xia Luo, Longzheng Xia i in. "Biological Function of HYOU1 in Tumors and Other Diseases". OncoTargets and Therapy Volume 14 (marzec 2021): 1727–35. http://dx.doi.org/10.2147/ott.s297332.

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Hao, Aixin, Yu Wang, Xiao Zhang, Jialiang Li, Yingzhou Li, Dangdang Li, George Kulik i Guangchao Sui. "Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding hnRNPA1 to promote HYOU1 expression". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1868, nr 4 (kwiecień 2021): 118951. http://dx.doi.org/10.1016/j.bbamcr.2021.118951.

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Liu, Kaiqiang, Xiancai Hao, Qian Wang, Jilun Hou, Xiaofang Lai, Zhiguo Dong i Changwei Shao. "Genome-wide identification and characterization of heat shock protein family 70 provides insight into its divergent functions on immune response and development of Paralichthys olivaceus". PeerJ 7 (11.11.2019): e7781. http://dx.doi.org/10.7717/peerj.7781.

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Flatfish undergo extreme morphological development and settle to a benthic in the adult stage, and are likely to be more susceptible to environmental stress. Heat shock proteins 70 (hsp70) are involved in embryonic development and stress response in metazoan animals. However, the evolutionary history and functions of hsp70 in flatfish are poorly understood. Here, we identified 15 hsp70 genes in the genome of Japanese flounder (Paralichthys olivaceus), a flatfish endemic to northwestern Pacific Ocean. Gene structure and motifs of the Japanese flounder hsp70 were conserved, and there were few structure variants compared to other fish species. We constructed a maximum likelihood tree to understand the evolutionary relationship of the hsp70 genes among surveyed fish. Selection pressure analysis suggested that four genes, hspa4l, hspa9, hspa13, and hyou1, showed signs of positive selection. We then extracted transcriptome data on the Japanese flounder with Edwardsiella tarda to induce stress, and found that hspa9, hspa12b, hspa4l, hspa13, and hyou1 were highly expressed, likely to protect cells from stress. Interestingly, expression patterns of hsp70 genes were divergent in different developmental stages of the Japanese flounder. We found that at least one hsp70 gene was always highly expressed at various stages of embryonic development of the Japanese flounder, thereby indicating that hsp70 genes were constitutively expressed in the Japanese flounder. Our findings provide basic and useful resources to better understand hsp70 genes in flatfish.

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Sargiacomo, Camillo, i Aleksandr Klepinin. "Density Gradient Centrifugation is an Effective Tool to Isolate Cancer Stem-Like Cells from Hypoxic and Normoxia Triple-Negative Breast Cancer Models". International Journal of Molecular Sciences 25, nr 16 (17.08.2024): 8958. http://dx.doi.org/10.3390/ijms25168958.

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Accumulating evidence has indicated that stemness-related genes are associated with the aggressiveness of triple-negative breast cancer (TNBC). Because no universal markers for breast CSCs are available, we applied the density gradient centrifugation method to enrich breast CSCs. We demonstrated that the density centrifugation method allows for the isolation of cancer stem cells (CSCs) from adherent and non-adherent MCF7 (Luminal A), MDA-MB-231 (TNBC) and MDA-MB-468 (TNBC) breast cancer cells. The current study shows that the CSCs’ enriched fraction from Luminal A and TNBC cells have an increased capacity to grow anchorage-independently. CSCs from adherent TNBC are mainly characterized by metabolic plasticity, whereas CSCs from Luminal A have an increased mitochondrial capacity. Moreover, we found that non-adherent growth CSCs isolated from large mammospheres have a higher ability to grow anchorage-independently compared to CSCs isolated from small mammospheres. In CSCs, a metabolic shift towards glycolysis was observed due to the hypoxic environment of the large mammosphere. Using a bioinformatic analysis, we indicate that hypoxia HYOU1 gene overexpression is associated with the aggressiveness, metastasis and poor prognosis of TNBC. An in vitro study demonstrated that HYOU1 overexpression increases breast cancer cells’ stemness and hyperactivates their metabolic activity. In conclusion, we show that density gradient centrifugation is a non-marker-based approach to isolate metabolically flexible (normoxia) CSCs and glycolytic (hypoxic) CSCs from aggressive TNBC.

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Yuan, Tao, Hong Qian, Xin Yu, Jia Meng, Cheng-Teng Lai, Hui Jiang, Jian-Ning Zhao i Ni-Rong Bao. "Proteomic analysis reveals rotator cuff injury caused by oxidative stress". Therapeutic Advances in Chronic Disease 12 (styczeń 2021): 204062232098705. http://dx.doi.org/10.1177/2040622320987057.

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Background and aims: Rotator cuff tendinopathy is common and is related to pain and dysfunction. However, the pathological mechanism of rotator cuff injury and shoulder pain is unclear. Objective: to investigate the pathological mechanism of rotator cuff injury and shoulder pain, and screen out the marker proteins related to rotator cuff injury by proteomics. Methods: Subacromial synovium specimens were collected from patients undergoing shoulder arthroscopic surgery. The experimental group were patients with rotator cuff repair surgery, and the control group were patients with habitual dislocation of the shoulder joint. Pathological examination was performed, and then followed by non-labeled quantitative proteomic detection. Finally, from analysis of the biological information of the samples, specific proteins related to rotator cuff injury and shoulder pain were deduced by functional analysis of differential proteins. Results: All the patients in experimental groups were representative. A large number of adipocytes and inflammatory cells were found in the pathological sections of the experimental group; the proteomics analysis screen identified 80 proteins with significant differences, and the analysis of protein function revealed that S100A11 ( p = 0.011), PLIN4 ( p = 0.017), HYOU1 ( p = 0.002) and CLIC1 ( p = 0.007) were closely related to oxidative stress and chronic inflammation. Conclusion: Rotator cuff injury is closely related to oxidative stress and chronic inflammatory response, and the results suggest that the expression of S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury provides a new marker for the study of its pathological mechanism.

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Wu, Yujia, Zhenlin Wu, Qiying Jin, Jinyuan Liu i Peiping Xu. "Identification and Analysis of Biomarkers Associated with Lipophagy and Therapeutic Agents for COVID-19". Viruses 16, nr 6 (7.06.2024): 923. http://dx.doi.org/10.3390/v16060923.

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Background: Lipids, as a fundamental cell component, play an regulating role in controlling the different cellular biological processes involved in viral infections. A notable feature of coronavirus disease 2019 (COVID-19) is impaired lipid metabolism. The function of lipophagy-related genes in COVID-19 is unknown. The present study aimed to investigate biomarkers and drug targets associated with lipophagy and lipophagy-based therapeutic agents for COVID-19 through bioinformatics analysis. Methods: Lipophagy-related biomarkers for COVID-19 were identified using machine learning algorithms such as random forest, Support Vector Machine-Recursive Feature Elimination, Generalized Linear Model, and Extreme Gradient Boosting in three COVID-19-associated GEO datasets: scRNA-seq (GSE145926) and bulk RNA-seq (GSE183533 and GSE190496). The cMAP database was searched for potential COVID-19 medications. Results: The lipophagy pathway was downregulated, and the lipid droplet formation pathway was upregulated, resulting in impaired lipid metabolism. Seven lipophagy-related genes, including ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2, were used as biomarkers and drug targets for COVID-19. Moreover, lipophagy may play a role in COVID-19 pathogenesis. As prospective drugs for treating COVID-19, seven potential downregulators (phenoxybenzamine, helveticoside, lanatoside C, geldanamycin, loperamide, pioglitazone, and trichostatin A) were discovered. These medication candidates showed remarkable binding energies against the seven biomarkers. Conclusions: The lipophagy-related genes ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2 can be used as biomarkers and drug targets for COVID-19. Seven potential downregulators of these seven biomarkers may have therapeutic effects for treating COVID-19.

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Wang, Jia‐Mei, Jing‐Yi Jiang, Da‐Lin Zhang, Xin Du, Tong Wu i Zhen‐Xian Du. "HYOU1 facilitates proliferation, invasion and glycolysis of papillary thyroid cancer via stabilizing LDHB mRNA". Journal of Cellular and Molecular Medicine 25, nr 10 (31.03.2021): 4814–25. http://dx.doi.org/10.1111/jcmm.16453.

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Zhou, Yujuan, Qianjin Liao, Xiayu Li, Hui Wang, Fang Wei, Jie Chen, Jing Yang i in. "HYOU1, Regulated by LPLUNC1, Is Up-Regulated in Nasopharyngeal Carcinoma and Associated with Poor Prognosis". Journal of Cancer 7, nr 4 (2016): 367–76. http://dx.doi.org/10.7150/jca.13695.

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An, Meng, Xiaowen Zang, Jimin Wang, Jie Kang, Xiaoyu Tan i Bo Fu. "Comprehensive analysis of differentially expressed long noncoding RNAs, miRNAs and mRNAs in breast cancer brain metastasis". Epigenomics 13, nr 14 (lipiec 2021): 1113–28. http://dx.doi.org/10.2217/epi-2021-0152.

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Aim: To delineate the transcriptomic landscape and potential molecular mechanisms of breast cancer brain metastasis (BCBM). Materials & methods: Whole-transcriptome sequencing was performed to identify long noncoding RNA (lncRNA), miRNA and mRNA expression profiles associated with BCBM. Results: A total of 739 differentially expressed lncRNAs, 115 differentially expressed miRNAs and 5749 differentially expressed mRNAs were identified in 231-BR cells compared with MDA-MB-231 cells. Real-time quantitative PCR results revealed the expression levels of candidate molecules were consistent with their correspondence RNA-seq data. Protein–protein interaction analysis identified some hub genes associated with BCBM, such as PTBP1, NUP98 and HYOU1. LncRNA-miRNA-mRNA network highlighted a potential mechanism of BCBM in which lncRNA FIRRE and RP11-169F17.1 sponging hsa-miR-501-5p to regulate the expression of MMS19, PTBP1 and NUP98. Conclusion: This study provides a framework for better understanding molecular mechanisms of BCBM.

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Wang, Zhe, Chen Tan, Caihan Duan, Junhao Wu, Dan Zhou, Lingzhi Hou, Wei Qian, Chaoqun Han i Xiaohua Hou. "FUT2-dependent fucosylation of HYOU1 protects intestinal stem cells against inflammatory injury by regulating unfolded protein response". Redox Biology 60 (kwiecień 2023): 102618. http://dx.doi.org/10.1016/j.redox.2023.102618.

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Liang, Zheng, i July Liang Chen. "Identification of apoptosis as key biochemical mechanism in nonalcoholic fatty liver disease after hepatic steatosis through bioinformatics and functional analyses". International Journal of Public Health and Medical Research 1, nr 1 (25.03.2024): 53–59. http://dx.doi.org/10.62051/ijphmr.v1n1.07.

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Background: Non-alcoholic fatty liver disease (NAFLD) represents a growing global health crisis and is closely associated with increases in obesity and type 2 diabetes. Despite its ubiquity, its underlying biochemical mechanisms and effective therapeutic strategies remain poorly defined, hampering the development of targeted interventions. Methods: Candidate genes were obtained from the GEO database, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis and gene set enrichment analysis were used to identify pathways involved in NAFLD-related pathways. The top genes with higher degree in the protein-protein interaction network were crossed with the top genes enriched in key pathways, and then the correlation analysis between key genes and chemotherapy response was performed. Result: Apoptosis, oxidative stress, NF-kB pathway, etc. are key pathways related to NAFLD. Lcn2, Mt1, Egr1, Jun, Nqo1, Btg2, Foxq1 and Hyou1 were enriched in key pathways of apoptosis. Conclusion: Apoptosis, oxidative stress, NF-kB pathway are key pathways related to NAFLD.

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Martin, J., O. Maurhofer, A. Schaller i J. F. Dufour. "43 THE MITOCHONDRIAL HINT2 MODULATES THE EXPRESSION OF HYOU1 AND ACO2 PROTEINS UNDER FAS AND ETHANOL INDUCED APOPTOSIS". Journal of Hepatology 48 (styczeń 2008): S19. http://dx.doi.org/10.1016/s0168-8278(08)60045-8.

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Lee, Minji, Yeonhwa Song, Inhee Choi, Su-Yeon Lee, Sanghwa Kim, Se-Hyuk Kim, Jiho Kim i Haeng Ran Seo. "Expression of HYOU1 via Reciprocal Crosstalk between NSCLC Cells and HUVECs Control Cancer Progression and Chemoresistance in Tumor Spheroids". Molecules and Cells 44, nr 1 (31.01.2021): 50–62. http://dx.doi.org/10.14348/molcells.2020.0212.

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Ren, Chunhuan, Zhipeng Sun, Yale Chen, Jiahong Chen, Shijia Wang, Qingqing Liu, Penghui Wang, Xiao Cheng, Zijun Zhang i Qiangjun Wang. "Identification of Biomarkers Affecting Cryopreservation Recovery Ratio in Ram Spermatozoa Using Tandem Mass Tags (TMT)-Based Quantitative Proteomics Approach". Animals 13, nr 14 (20.07.2023): 2368. http://dx.doi.org/10.3390/ani13142368.

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Sperm proteins play vital roles in improving sperm freezing resilience in domestic animals. However, it remains poorly defined which proteins regulate the freezing resilience of spermatozoa in rams (Ovis aries). Here, we compared the proteome of ram sperm with a high cryopreservation recovery ratio (HCR) with that of ram sperm with a low cryopreservation recovery ratio (LCR) using a tandem mass tag-based quantitative proteomics approach. Bioinformatic analysis was performed to evaluate differentially expressed proteins (DEPs). A total of 2464 proteins were identified, and 184 DEPs were screened. Seventy-two proteins were higher in the LCR group. One hundred and twelve proteins were more abundant in the HCR group, and they were mainly involved in the regulation of oxidative phosphorylation and thermogenesis pathways. Proteins in high abundance in the HCR group included the S100A family, such as S100A8, S100A9, S100A14, and S100A16, effectively controlling for CA2+ and maintaining flagella structure; HYOU1 and PRDX1, which participate in antioxidant protection and anti-apoptosis to prevent cell death; and HSP90B1, which maintains cell activity and immune response. Our results could help illuminate the molecular mechanisms underlying cryopreservation of ram semen and expand the potential direction of cryopreservation of high-quality semen.

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Ham, Ju Ri, Ra-Yeong Choi, Yongjin Lee i Mi-Kyung Lee. "Effects of Edible Insect Tenebrio molitor Larva Fermentation Extract as a Substitute Protein on Hepatosteatogenesis and Proteomic Changes in Obese Mice Induced by High-Fat Diet". International Journal of Molecular Sciences 22, nr 7 (31.03.2021): 3615. http://dx.doi.org/10.3390/ijms22073615.

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Mealworms (Tenebrio molitor larva) are an edible insect and a protein-rich food; however, research on mealworms as a substitute protein is insufficient. In this study, mealworm fermentation extract (TMP) was assessed as a replacement for soy protein (SP) in a control diet (CON) or a high-fat diet (HFD) of mice for 12 weeks. TMP substitution reduced body weight, body weight gain, body fat mass (perirenal and mesenteric), fat size, glucose intolerance, and insulin resistance compared to the HFD-SP group. TMP alleviated hepatic steatosis (lipid contents and lipid droplets) in high-fat-fed mice and down-regulated the PPARγ, CD36, and DGAT2 gene levels. Proteomic analysis showed that a HFD for 12 weeks up-regulated 20 proteins and down-regulated 17 proteins in mice fed SP. On the other hand, TMP reversed the protein profiles. TMP significantly down-regulated KHK, GLO1, ATP5H, SOD, and DDAH1 and up-regulated DLD, Mup1, CPS1, Ces3b, PDI, and HYOU1 compared to the HFD-SP group. These proteins are involved in the glucose, lipid, and amino acid metabolism, as well as in oxidative stress and endoplasmic reticulum stress. Thus, substituting SP for TMP helped improve HFD-induced obesity, steatosis, and insulin resistance in mice. These results suggest that TMP is a potential substitute for commonly used protein sources.

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Lu, Wen-Li, Hong-Yan Ren, Cao Liang, Yuan-Yuan Zhang, Ji Xu, Zhi-Qiang Pan, Xiao-Mei Liu, Zhong-Hua Wu i Zhao-Qin Fang. "Akebia trifoliate (Thunb.) KoidzSeed Extract Inhibits the Proliferation of Human Hepatocellular Carcinoma Cell Lines via Inducing Endoplasmic Reticulum Stress". Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/192749.

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Akebia Fructus has long been used for hepatocellular carcinoma (HCC) in China, while the molecular mechanism remains obscure. Our recent work found thatAkebia trifoliate (Thunb.) Koidzseed extract (ATSE) suppressed proliferation and induced endoplasmic reticulum (ER) stress in SMMC-7721. The present study aimed to throw more light on the mechanism. ER stress occurred after ATSE treatment in HepG2, HuH7, and SMMC-7721 cells, manifested as ER expansion, and SMMC-7721 was the most sensitive kind in terms of morphology. Cell viability assay showed that ATSE significantly inhibited cells proliferation. Flow cytometry analysis indicated that ATSE leads to an upward tendency of G0/G1 phase and a reduced trend of the continuous peak after G2/M phase in HepG2; ATSE promoted apoptosis in HuH7 and a notable reduction in G0/G1 phase; ATSE does not quite influence cell cycles of SMMC-7721. Western blot analysis showed an increased trend of the chosen ER stress-related proteins after different treatments but nonsignificantly; only HYOU1 and GRP78 were decreased notably by ATSE in HuH7. Affymetrix array indicated that lots of ER stress-related genes’ expressions were significantly altered, and downward is the main trend. These results suggest that ATSE have anticancer potency in HCC cells via partly inducing ER stress.

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Liu, Jun, i Yingmei Wang. "Long non-coding RNA KCNQ1OT1 facilitates the progression of cervical cancer and tumor growth through modulating miR-296-5p/HYOU1 axis". Bioengineered 12, nr 1 (1.01.2021): 8753–67. http://dx.doi.org/10.1080/21655979.2021.1982230.

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Tseng, Chung-Chih, Chen-Han Tsou, Shi-Ying Huang, Chia-Wei Wu i Tsung-Hua Hsieh. "Using Next-Generation Sequencing and Bioinformatic Methods to Predict New Genes That May Be Regulated by CD47 in Oral Squamous Cell Carcinoma". Current Issues in Molecular Biology 44, nr 5 (17.05.2022): 2243–56. http://dx.doi.org/10.3390/cimb44050152.

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world, and the incidence and death rate of OSCC in men is twice that of women. CD47 is a ubiquitous cell surface transmembrane protein, also known as integrin-related protein (IAP). Previous studies have pointed out that CD47 can inhibit the growth of OSCC, but the detailed mechanism is not clear. This study aimed to explore the effect of CD47 gene expression profiles in OSCC. The OSCC cell lines, OECM-1 and OC-2, overexpressed CD47, and the expression profiles of mRNAs were analyzed through next-generation sequencing (NGS) with a bioinformatic approach. A total of 14 differentially expressed genes (DEGs) were listed. In addition, ingenuity pathway analysis (IPA) was used to analyze the molecular function (MF), biological process (BP), and cellular component (CC) network signaling. The human protein atlas (HPA) database was used to analyze gene expression and the survivability of human cancer. The results found that HSPA5, HYOU1, and PDIA4 were involved in the IPA network and when highly expressed, mediated the survivability of cancer. In addition, HSPA5 was positively and significantly correlated with CD47 expression (p < 0.0001) and induced by CD47-overexpression in the OECM-1 and OC-2 OSCC cancer cell lines. These findings provide important insights into possible new diagnostic strategies, including unfolded protein for OSCC-targeting CD47.

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Slaby, O., K. Sobkova, M. Svoboda, I. Garajova, P. Fabian, M. Sachlova, T. Smerdova, D. Knoflickova i R. Vyzula. "Altered expression of heat shock protein 110 (HSP110), hypoxia up- regulated 1 (HYOU1) and translationally controled tumor protein (TCTP) during colorectal cancer progression". European Journal of Cancer Supplements 6, nr 9 (lipiec 2008): 129. http://dx.doi.org/10.1016/s1359-6349(08)71668-9.

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Sharma, Kavita, Aastha Mishra, Himanshu N. Singh, Deepak Parashar, Perwez Alam, Tashi Thinlas, Ghulam Mohammad, Ritushree Kukreti, Mansoor Ali Syed i M. A. Qadar Pasha. "High-altitude pulmonary edema is aggravated by risk loci and associated transcription factors in HIF-prolyl hydroxylases". Human Molecular Genetics 30, nr 18 (18.05.2021): 1734–49. http://dx.doi.org/10.1093/hmg/ddab139.

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Abstract High-altitude (HA, >2500 m) hypoxic exposure evokes several physiological processes that may be abetted by differential genetic distribution in sojourners, who are susceptible to various HA disorders, such as high-altitude pulmonary edema (HAPE). The genetic variants in hypoxia-sensing genes influence the transcriptional output; however the functional role has not been investigated in HAPE. This study explored the two hypoxia-sensing genes, prolyl hydroxylase domain protein 2 (EGLN1) and factor inhibiting HIF-1α (HIF1AN) in HA adaptation and maladaptation in three well-characterized groups: highland natives, HAPE-free controls and HAPE-patients. The two genes were sequenced and subsequently validated through genotyping of significant single nucleotide polymorphisms (SNPs), haplotyping and multifactor dimensionality reduction. Three EGLN1 SNPs rs1538664, rs479200 and rs480902 and their haplotypes emerged significant in HAPE. Blood gene expression and protein levels also differed significantly (P < 0.05) and correlated with clinical parameters and respective alleles. The RegulomeDB annotation exercises of the loci corroborated regulatory role. Allele-specific differential expression was evidenced by luciferase assay followed by electrophoretic mobility shift assay, liquid chromatography with tandem mass spectrometry and supershift assays, which confirmed allele-specific transcription factor (TF) binding of FUS RNA-binding protein (FUS) with rs1538664A, Rho GDP dissociation inhibitor 1 (ARHDGIA) with rs479200T and hypoxia upregulated protein 1 (HYOU1) with rs480902C. Docking simulation studies were in sync for the DNA-TF structural variations. There was strong networking among the TFs that revealed physiological consequences through relevant pathways. The two hydroxylases appear crucial in the regulation of hypoxia-inducible responses.

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Cox, Lindsay, Dirk K. Vanderwall, Kate C. Parkinson, Alexis Sweat i S. Clay Isom. "Expression profiles of select genes in cumulus–oocyte complexes from young and aged mares". Reproduction, Fertility and Development 27, nr 6 (2015): 914. http://dx.doi.org/10.1071/rd14446.

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There is compelling evidence that oocytes from mares >18 years of age have a high incidence of inherent defects that result in early embryonic loss. In women, an age-related decrease in oocyte quality is associated with an increased incidence of aneuploidy and it has recently been determined that the gene expression profile of human oocytes is altered with advancing age. We hypothesised that similar age-related aberrations in gene expression occur in equine oocytes. Therefore, the aim of the present study was to compare gene expression profiles of individual oocytes and cumulus cells from young and aged mares, specifically evaluating genes that have been identified as being differentially expressed with advancing maternal age and/or aneuploidy in human oocytes. Expression of 48 genes was compared between 14 cumulus–oocyte complexes (COCs) from mares aged 3–12 years and 10 COCs from mares ≥18 years of age. Three genes (mitochondrial translational initiation factor 3 (IF3), heat shock transcription factor 5 (HSF5) and Y box binding protein 2 (YBX2)) were differentially expressed in oocytes, with all being more abundant in oocytes from young mares. Three genes (ADP-ribosylation factor-like 6 interacting protein 6 (ARL6IP6), BCL2-associated X protein (BAX) and hypoxia upregulated 1 (HYOU1)) were differentially expressed in cumulus cells, with all being more abundant in aged mares. The results of the present study confirm there are age-related differences in gene expression in equine COCs, which may be associated with the lower quality and decreased developmental competence of oocytes from aged mares.

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Pan, Po-Kai, Kuang-Teng Wang, Fan-Hua Nan, Tsung-Meng Wu i Yu-Sheng Wu. "Red Algae “Sarcodia suieae” Acetyl-Xylogalactan Downregulate Heat-Induced Macrophage Stress Factors Ddit3 and Hyou1 Compared to the Aquatic Animal Model of Nile Tilapia (Oreochromis niloticus) Brain Arachidonic Acid Expression". International Journal of Molecular Sciences 23, nr 23 (24.11.2022): 14662. http://dx.doi.org/10.3390/ijms232314662.

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Anthropogenic climate change is known to be an increased stress that affects aquatic animal behavior and physiological alternations, which can induce the animal’s death. In order to known whether the extracted acetyl-xylogalactan function on the regulation of the external high temperature induced death, we first selected the mammalian cell line “RAW 264.7” used in the previous experiment to evaluate the extracted acetyl-xylogalactan function. We aimed to evaluate the effects of the acetyl-xylogalactan on the RAW 264.7 macrophages and Nile Tilapia stress factor expression under the heat environment. In the in vitro cell observation, we assessed the cell survival, phagocytic activity, intracellular Ca2+ level, mitochondria potential exchange, apoptotic assay findings, galactosidase activity, RNA-seq by NGS and real-time polymerase chain reaction (QPCR) expression. In the in vivo Nile Tilapia observation aimed to evaluate the blood biochemical indicator, brain metabolites exchange and the liver morphology. In our evaluation of RAW 264.7 macrophages, the RNA sequencing and real-time polymerase chain reaction (PCR) was shown to upregulate the expression of the anti-apoptosis Cflar gene and downregulate the expression of the apoptosis factors Ddit3 and Hyou1 to protect macrophages under heat stress. We already knew the extracted acetyl-xylogalactan function on the mammalian “RAW 264.7” system. Following, we used the aquatic Nile Tilapia model as the anthropogenic climate change high temperature experiment. After feeding the Nile Tilapia with the acetyl-xylogalactan, it was found to reduce the brain arachidonic acid (AA) production, which is related to the NF-κB-induced apoptosis mechanism. Combined with the in vitro and in vivo findings, the acetyl-xylogalactan was able to reduce the heat induced cell or tissue stress.

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Bhatia, Sugandha, Tony Blick, Cletus Pinto, Mark Waltham, James Monkman, Ekaterina Ivanova, Pamela M. Pollock i in. "Identifying Therapies to Combat Epithelial Mesenchymal Plasticity-Associated Chemoresistance to Conventional Breast Cancer Therapies Using An shRNA Library Screen". Cancers 12, nr 5 (30.04.2020): 1123. http://dx.doi.org/10.3390/cancers12051123.

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Background: Breast cancer (BC) is a heterogeneous disease for which the commonly used chemotherapeutic agents primarily include the anthracyclines (doxorubicin, epirubicin), microtubule inhibitors (paclitaxel, docetaxel, eribulin), and alkylating agents (cyclophosphamide). While these drugs can be highly effective, metastatic tumours are frequently refractory to treatment or become resistant upon tumour relapse. Methods: We undertook a cell polarity/epithelial mesenchymal plasticity (EMP)-enriched short hairpin RNA (shRNA) screen in MDA-MB-468 breast cancer cells to identify factors underpinning heterogeneous responses to three chemotherapeutic agents used clinically in breast cancer: Doxorubicin, docetaxel, and eribulin. shRNA-transduced cells were treated for 6 weeks with the EC10 of each drug, and shRNA representation assessed by deep sequencing. We first identified candidate genes with depleted shRNA, implying that their silencing could promote a response. Using the Broad Institute’s Connectivity Map (CMap), we identified partner inhibitors targeting the identified gene families that may induce cell death in combination with doxorubicin, and tested them with all three drug treatments. Results: In total, 259 shRNAs were depleted with doxorubicin treatment (at p < 0.01), 66 with docetaxel, and 25 with eribulin. Twenty-four depleted hairpins overlapped between doxorubicin and docetaxel, and shRNAs for TGFB2, RUNX1, CCDC80, and HYOU1 were depleted across all the three drug treatments. Inhibitors of MDM/TP53, TGFBR, and FGFR were identified by CMap as the top pharmaceutical perturbagens and we validated the combinatorial benefits of the TGFBR inhibitor (SB525334) and MDM inhibitor (RITA) with doxorubicin treatment, and also observed synergy between the inhibitor SB525334 and eribulin in MDA-MB-468 cells. Conclusions: Taken together, a cell polarity/EMP-enriched shRNA library screen identified relevant gene products that could be targeted alongside current chemotherapeutic agents for the treatment of invasive BC.

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Vendrell, Joan, Elsa Maymó-Masip, Francisco Tinahones, Antonio García-España, Ana Megia, Enric Caubet, Eduardo García-Fuentes i Matilde R. Chacón. "Tumor Necrosis-Like Weak Inducer of Apoptosis as a Proinflammatory Cytokine in Human Adipocyte Cells: Up-Regulation in Severe Obesity Is Mediated by Inflammation But Not Hypoxia". Molecular Endocrinology 24, nr 5 (1.05.2010): 1107. http://dx.doi.org/10.1210/mend.24.5.9998.

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abstract Context: Adipose tissue hypoxia and endoplasmic reticulum (ER) stress may link the presence of chronic inflammation and macrophage infiltration in severely obese subjects. We previously reported the up-regulation of TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in adipose tissue of severely obese type 2 diabetic subjects. Objectives: The objective of the study was to examine TWEAK and Fn14 adipose tissue expression in obesity, severe obesity, and type 2 diabetes in relation to hypoxia and ER stress. Design: In the obesity study, 19 lean, 28 overweight, and 15 obese nondiabetic subjects were studied. In the severe obesity study, 23 severely obese and 35 control subjects were studied. In the type 2 diabetes study, 11 type 2 diabetic and 36 control subjects were studied. The expression levels of the following genes were analyzed in paired samples of sc and visceral adipose tissue: Fn14, TWEAK, VISFATIN, HYOU1, FIAF, HIF-1a, VEGF, GLUT-1, GRP78, and XBP-1. The effect of hypoxia, inflammation, and ER stress on the expression of TWEAK and Fn14 was examined in human adipocyte and macrophage cell lines. Results: Up-regulation of TWEAK/Fn14 and hypoxia and ER stress surrogate gene expression was observed in sc and visceral adipose tissue only in our severely obese cohort. Hypoxia modulates TWEAK or Fn14 expression in neither adipocytes nor macrophages. On the contrary, inflammation up-regulated TWEAK in macrophages and Fn14 expression in adipocytes. Moreover, TWEAK had a proinflammatory effect in adipocytes mediated by the nuclear factor-κB and ERK but not JNK signaling pathways. Conclusions: Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.

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Phillips, Ian R., Sunil Veeravalli, Sanjay Khadayate i Elizabeth A. Shephard. "Metabolomic and transcriptomic analyses of Fmo5-/- mice reveal roles for flavin-containing monooxygenase 5 (FMO5) in NRF2-mediated oxidative stress response, unfolded protein response, lipid homeostasis, and carbohydrate and one-carbon metabolism". PLOS ONE 18, nr 6 (2.06.2023): e0286692. http://dx.doi.org/10.1371/journal.pone.0286692.

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Flavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins, best known for their roles in the detoxification of foreign chemicals and, more recently, in endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is characterized by decreased fat deposition, lower plasma concentrations of glucose, insulin and cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced obesity. In the present study we report the use of metabolomic and transcriptomic analyses of livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of Fmo5-/- mice and gain insights into the function of FMO5. Metabolomics was performed by the Metabolon platform, utilising ultrahigh performance liquid chromatography-tandem mass spectroscopy. Transcriptomics was performed by RNA-Seq and results analysed by DESeq2. Disruption of the Fmo5 gene has wide-ranging effects on the abundance of metabolites and expression of genes in the liver. Metabolites whose concentration differed between Fmo5-/- and wild-type mice include several saturated and monounsaturated fatty acids, complex lipids, amino acids, one-carbon intermediates and ADP-ribose. Among the genes most significantly and/or highly differentially expressed are Apoa4, Cd36, Fitm1, Hspa5, Hyou1, Ide, Me1 and Mme. The results reveal that FMO5 is involved in upregulating the NRF2-mediated oxidative stress response, the unfolded protein response and response to hypoxia and cellular stress, indicating a role for the enzyme in adaptation to oxidative and metabolic stress. FMO5 also plays a role in stimulating a wide range of metabolic pathways and processes, particularly ones involved in lipid homeostasis, the uptake and metabolism of glucose, the generation of cytosolic NADPH, and in one-carbon metabolism. The results predict that FMO5 acts by stimulating the NRF2, XBP1, PPARA and PPARG regulatory pathways, while inhibiting STAT1 and IRF7 pathways.

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Park, Hyoun. "The Death of ‘Big Data’?" New Electronics 52, nr 14 (23.07.2019): 24–26. http://dx.doi.org/10.12968/s0047-9624(22)61578-5.

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MAKI, Hiroko, Munenori MINAGAWA, Tatsuyo ISHIGAMI i Yasuzou KURONO. "Relationship between Myakusasin and Gogyou-Shikitai-Hyou." Zen Nihon Shinkyu Gakkai zasshi (Journal of the Japan Society of Acupuncture and Moxibustion) 44, nr 4 (1994): 333–38. http://dx.doi.org/10.3777/jjsam.44.333.

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Lin, Cindy, Tiffany T. Khong, Sridurga Mithraprabhu i Andrew Spencer. "CD45-Ve but Not CD45+Ve U266 Myeloma Cells Demonstrate an Active Epithelial to Mesenchymal Transition (EMT) Transcriptional Programme". Blood 120, nr 21 (16.11.2012): 3988. http://dx.doi.org/10.1182/blood.v120.21.3988.3988.

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Abstract Abstract 3988 Multiple myeloma (MM) is an incurable plasma cell malignancy predominantly negative for the surface protein tyrosine phosphatase CD45. Published data show that an increased proportion of CD45-ve cells present at diagnosis correlates with poorer patient outcome and increased risk of extra-medullary disease. The aim of this study was to investigate whether the identification of biological differences associated with variable CD45 expression might explain this apparent adverse clinical impact. The U266 human myeloma cell line (HMCL) comprises both CD45+ve and CD45-ve populations and was used as an isogenic model to characterise the biology of each subset. Gene expression profiling (GEP) was performed on sorted cells (U266 CD45+ve vs U266 CD45-ve populations) using the Illumina HT12-V2 array. GeneGo analysis identified the hypoxia-induced epithelial-mesenchymal transition (EMT) pathway as being the most differentially active pathway between the CD45-ve (EMT on) and CD45+ve (EMT off) populations. EMT enables vital cellular changes during embryogenesis and wound healing and has been shown to be utilised by a range of carcinomas as a mechanism that promotes disease progression and metastasis. The GEP findings were validated with qRT-PCR that confirmed the increased expression of SNAI1 (SNAIL), CTGF and HES1 in the CD45-ve subset. There was, however, no difference in the level of expression of hypoxia-inducible genes including HIF1B, HIF2B, CREBBP, HYOU1 or VEGFA. NOTCH pathway activation was confirmed within the CD45-ve population by a high HES1:DTX1 transcriptional ratio and intra-cellular NICD protein, again consistent with high EMT activity. Interestingly the GEP data, again confirmed with qRT-PCR, also demonstrated increased expression of a range of tumour suppressor genes prone to promoter hypermethylation within the CD45+ve subset while the CD45-ve cells preferentially expressed a range of oncogenes known to be associated with a more aggressive clinical phenotype in solid tumours but not known to be associated with MM. Biological characterisation of the two populations demonstrated distinct cellular phenotypes. The CD45+ve and CD45-ve subsets expressed similar levels of IL-6R, IGF-1R, CD49d and CD95, however, the CD45+ve population expressed increased CXCR4 and ICAM-1 (both p<0.001) compared to the CD45-ve population with both enhanced migration toward (1.55-fold, p=0.0037) and adhesion to (1.39-fold, p<0.0001) HS5 stromal cells, consistent with CD45 negativity correlating with greater metastatic potential. This phenotypic variation was recapitulated in a patient presenting with plasma cell leukaemia whereby the bone marrow MM cells were CD45HI, CXCR4HI, whereas the peripheral blood MM cells were CD45LOW, CXCR4LOW. Finally, the CD45-ve U266 cells exhibited increased resistance to bortezomib induced cell death when compared to their CD45+ve counterparts. Utilising the U266 HMCL as a model of variable CD45 expression we have demonstrated that CD45 negativity was associated with an active EMT transcriptional programme and a range of adverse biological characteristics. Our data supports the hypothesis that in some instances MM disease progression may be driven by the irreversible activation of the EMT pathway leading to a more malignant and metastatic phenotype. Whether the loss of CD45 expression in vivo is likewise correlated with EMT-like characteristics or plays a causative role in their development remains to be determined. Disclosures: No relevant conflicts of interest to declare.

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AKSENOVA, KSENIYA A. "LEXICAL MEANS OF EXPRESSING THE CONCEPT OF “INDETERMINATE LARGE AMOUNT” IN THE ENGLISH AND GREEK LANGUAGES". Cherepovets State University Bulletin 4, nr 109 (2022): 7–16. http://dx.doi.org/10.23859/1994-0637-2022-4-109-1.

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The article examines the semantics of nouns that are sources (called “donor zones”) for English and Greek quantifiers. This term is taken from the article by E. V. Rakhilina, Lee Su Hyoun “Semantics of lexical plurality in Russian”. In the analysis, several groups are identified that may partially overlap each other. When considering this layer of vocabulary, a structural approach is put into practice, based on the comparative and typological method, as well as the analysis of dictionary definitions. The article focuses on the nouns that characterize indeterminate large amount in the English and Greek languages. All lexemes under consideration are analysed in a comparative manner.

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Azab, Abdel Kareem, Jinsong Hu, Phong Quang, Feda Azab, Costas Pitsillides, Brian Thompson, Patricia Maiso i in. "Hypoxia Promotes Dissemination of Multiple Myeloma Through Acquisition of Endothelial to Mesenchymal Transition (EMT) Features". Blood 118, nr 21 (18.11.2011): 471. http://dx.doi.org/10.1182/blood.v118.21.471.471.

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Abstract Abstract 471 Multiple myeloma (MM) is characterized by widespread dissemination of the MM cells at diagnosis associated with multiple focal bone lesions, implying (re)circulation of MM cells into the peripheral blood and (re)entrance or homing into new sites of the BM. However, the driving force for MM cells to leave the BM, egress, and home to new BM niches is still not well understood. Hypoxia (low oxygen) in solid tumors was shown to promote metastasis in solid tumors through activation of proteins involved in the endothelial to mesenchymal Transition (EMT). In this study, we hypothesized that MM tumor progression induces hypoxic conditions, which in turn activates EMT related proteins and promotes metastasis of MM cells. To test this hypothesis, we examined levels of hypoxia in MM cells at different stages of tumor progression in vivo in two animal models: the first by injecting MM1s cell to SCID mice, and the second by injecting 5T33MM cells to C57BL/KaLwRijHsd mice. Hypoxic markers were examined using flow cytometry and immunohistochemistry. We found that tumor progression induced hypoxia in both the MM cells and the tumor microenvironment. Similarly, hypoxia induced genes (HIF1a, HIF1b, HIF2b, CREBBP, HYOU1, VEGF1, HIF1a-inhibitory protein) were increased in MM patients (n=68) compared to plasma cells from healthy donors (n=14). Using flow cytometry we found that the number of circulating MM cells increased with the progression; however, the correlation was observed in late stages of the progression but not in the early stages. A better direct correlation was achieved with the hypoxic state of the MM cells in the BM. Circulating MM cells were more hypoxic that MM cells in the BM (especially at low tumor burden). Moreover, we found that the level of hypoxia in MM cells in the PB did not correlate with the hypoxia in the BM. Next, we tested the mechanism in which hypoxia induces cell egress. We found that MM cells isolated from MM patients have higher gene expression of EMT inducing proteins (E-cadherin, SNAIL, FOXC2, TGFb1) in parallel to a decrease of expression in E-cadherin, and we confirmed the downregulation of E-cadherin expression in correlation with the increase of hypoxia in MM cell and cells in the BM microenvironment in vivo. Culturing MM cells under hypoxic conditions increased the expression of HIF1a and HIF2a. In parallel, hypoxia induced acquisition of EMT related features including downregulation of E-cadherin, upregulation of SNAIL, and inhibition of GSK3b. In addition, hypoxia decreased the adhesion of MM cells to stromal cells. To complete the metastatic process after egress, MM cells need to home to new sites in the BM. Therefore we investigated the effect of hypoxia on expression of CXCR4, chemotaxis and homing of MM cells to the BM. Using flow cytometry we found a direct correlation between hypoxia and the expression of CXCR4 in MM cells in vivo using the SCID-MM1s model. These results were confirmed in vitro, where hypoxia increased the expression of CXCR4 at protein and mRNA levels in MM cells. Moreover, the expression of CXCR4 in MM cells isolated from the PB was higher than cells isolated from the BM especially at low tumor burden, correlating with higher hypoxic state of the circulating tumor cells. Functionally, hypoxia increased the chemotaxis of MM cells towards SDF1a in vitro and, using in vivo confocal microscopy, it was shown to accelerate the homing of MM cells to the BM in vivo. To demonstrate that the chemotaxis and homing were CXCR4 dependent, we treated the hypoxic MM cells with AMD3100 (a CXCR4 inhibitor) and showed that it inhibited chemotaxis in vitro and homing of MM to the BM in vivo. In conclusion, we demonstrate that tumor progression induces hypoxia in the MM cells and in the BM microenvironment. Hypoxia activates EMT-related machinery in MM cells, decreases expression of E-cadherin and consequently decreased the adhesion of MM cells to the BM, and enhance egress of MM cells to the circulation. In parallel, hypoxia increases the expression of CXCR4, and consequently increased the migration and homing of MM cells in from the peripheral blood to the BM. Further studies to manipulate hypoxia in order to regulate tumor dissemination as a therapeutic strategy are warranted. Disclosures: Roccaro: Roche: . Kung:Novartis Pharmaceuticals: Consultancy, Research Funding. Ghobrial:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Noxxon: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Navale, Sachin, Ali Mirzaei, Sanjit Manohar Majhi, Hyoun Woo Kim i Sang Sub Kim. "State-of-the-Art Research on Chemiresistive Gas Sensors in Korea: Emphasis on the Achievements of the Research Labs of Professors Hyoun Woo Kim and Sang Sub Kim". Sensors 22, nr 1 (23.12.2021): 61. http://dx.doi.org/10.3390/s22010061.

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This review presents the results of cutting-edge research on chemiresistive gas sensors in Korea with a focus on the research activities of the laboratories of Professors Sang Sub Kim and Hyoun Woo Kim. The advances in the synthesis techniques and various strategies to enhance the gas-sensing performances of metal-oxide-, sulfide-, and polymer-based nanomaterials are described. In particular, the gas-sensing characteristics of different types of sensors reported in recent years, including core–shell, self-heated, irradiated, flexible, Si-based, glass, and metal–organic framework sensors, have been reviewed. The most crucial achievements include the optimization of shell thickness in core–shell gas sensors, decrease in applied voltage in self-heated gas sensors to less than 5 V, optimization of irradiation dose to achieve the highest response to gases, and the design of selective and highly flexible gas sensors-based WS2 nanosheets. The underlying sensing mechanisms are discussed in detail. In summary, this review provides an overview of the chemiresistive gas-sensing research activities led by the corresponding authors of this manuscript.

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Choi, Sang-Ki. "Review and Prospects of an epitaph of Ko Jok-You(高足酉): Focusing on decipherment and discussion". Institute for Historical Studies at Chung-Ang University 59 (31.08.2023): 5–38. http://dx.doi.org/10.46823/cahs.2023.59.5.

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The epitaph of Ko Jok-You(高足酉) is noteworthy in that it tells the lives of Koguryo(高句麗) refugees that are not recorded in the literature. Analyzing the meaning of various expressions used in the epitaph and interpreting the characters and events in the epitaph while considering the historical context of Ko Jok-You's time can broaden the understanding of the lives of ancient refugees, which are still unknown. Ko Jok-You was born in 626 in the late Koguryo period, lived in the Luoyang(洛陽) area after moving to Tang(唐) Dynasty, and died in the Jingzhou(荊州) area at the age of 70 while returning from the war in the southwestern region in 695. In the epitaph, he was described as a person from Liaodong Pingrang(遼東平壤人), which can be said to be an expression that claims that he is from Koguryo and belongs to the Tang Dynasty. This would have reflected the situation in which Ko Jok-You served as a military officer of the Tang Dynasty. Although the epitaph did not reveal when he entered the Tang Dynasty, it is highly likely that he entered between 667 and 668, considering that he was related to Ko Hyoun(高玄) and Cheon Heon-Seong(泉獻誠). Since entering the Tang Dynasty, Ko Jok-You has made many achievements in the military field as a foreign military officer(蕃將). He served as a high-ranking military officer and served in the royal guard with Ko Hyoun, but also commanded the Tang army himself toachieve results in wars against various other ethnic groups, including Tufan(吐蕃) and Tujue(突厥) on the border. Based on these military achievements, Ko Jok-You seems to have risen to the position of representing the Koguryo refugee group in its late years. Ko Jok-You participated in the construction of the Column of Tianshu(天樞) built by Wu Zetian(武則天) to show off her virtue and received a reward that was sealed with a Chief of Koryo refugee group(高麗蕃長), and his name seems to have been engraved on the Column of Tianshu along with the chiefs of other ethnic groups. In particular, among Koguryo refugees, Cheon Heon-seong was originally involved in the production of the Column of Tianshu, which is believed to be because the Cheon clan was the most powerful force among Koguryo refugees. However, the fact that Ko Jok-You appeared after Cheon Heon-seong's death can be interpreted as meaning that he was a person with enough status to replace Cheon Heon-seong during Wu Zetian‘s reign.

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Hou, Danping, Yuan Wei, Kun Liu, Jinsong Tan, Qingyu Bi, Guolan Liu, Xinqiao Yu, Junguo Bi i Lijun Luo. "The Response of Grain Yield and Quality of Water-Saving and Drought-Resistant Rice to Irrigation Regimes". Agriculture 13, nr 2 (27.01.2023): 302. http://dx.doi.org/10.3390/agriculture13020302.

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Of all the crops, rice is the one that consumes the most water. Rice yields and quality are significantly influenced by irrigation. However, it is still unknown how different irrigation practices would affect the grain yield and quality of water-saving and drought-resistant rice. Hyou 518 (high-yielding rice variety) and Hanyou 73 (water-saving and drought-resistant rice variety) were employed as materials. Three irrigation regimes were set up in the field: conventional flooding irrigation (CF), alternate wetting and moderate soil drying irrigation (AWD), and dry cultivation (D). It was investigated how various irrigation regimes affected the two varieties’ yield and quality. The results revealed the following: 1. D considerably increased water-use efficiency while drastically reducing the yield, compared to CF and AWD. In comparison to other irrigation regimes, the grain yield and water use efficiency of Hanyou 73 enhanced synergistically under AWD treatment. 2. In contrast to CF treatment, AWD and D (especially) treatments decreased perfect rice kernel, total starch content, amylose content, amylopectin content, amylose/amylopectin, gel consistency, and breakdown, but increased green rice kernel, chalky kernel, protein content, and setback. 3. After heading, AWD and D lowered, and D treatment decreased more, the activities of ADP-glucose pyrophosphorylase (AGP), soluble starch synthase (SSS), and starch branching enzyme (SBE). AGP, SSS, and SBE were strongly inversely linked with perfect rice kernel, amylopectin content, gel consistency, and breakdown, but significantly negatively correlated with green rice kernel, chalky kernel, protein content, and setback. The results indicate that with AWD treatment, Hanyou 73 might provide a synergistic boost grain production, water-use efficiency, and quality. D treatment could significantly improve water-use efficiency. Compared with Hyou518, Hanyou 73 could maintain higher AGP, SSS, and SBE activities, head milled rice, perfect rice kernel, amylopectin content, and gel consistency under AWD and D treatment.

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Lim, Sunki, Yujeong Gho, Seoyoung Kim, Min Ki Kim, Jong Seob Park, Wang Jun Lee, Young-Kwan Lee i Hyoun Jong Moon. "Abstract 3200: Non-engineered T cells with specific anticancer effects in KRAS-mutated colorectal cancer". Cancer Research 83, nr 7_Supplement (4.04.2023): 3200. http://dx.doi.org/10.1158/1538-7445.am2023-3200.

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Abstract Cytokine-induced killer (CIK) cell therapy is known as a useful treatment for cancer immunotherapy due to its anticancer activity and safety. However, its clinical efficacy is limited due to its lack of antigen specificity and low in vivo persistence. KRAS mutations play an important role in promoting tumorigenesis in cancer. But, its clinical application as a biomarker for cancer treatment is still difficult. Non-engineered T cell therapy approaches could be a promising strategy for treating KRAS-mutated cancer. Herein we developed non-engineered T cells empowered with specific anticancer effects in KRAS-mutated colorectal cancer (CRC), and investigated its properties and anticancer effects compared to CIK cells. A recombinant overlapping peptide was designed to overlap the KRAS protein by 15 amino acids linked by a cathepsin S cleavage site (LRMK). It contained KRASG12D, KRASG12V, KRASG13D, and KRASWT epitope peptides and other KRAS protein regions. Peripheral blood mononuclear cells (PBMCs) from CRC patients with KRAS mutations were stimulated with the recombinant overlapping peptides in vitro for two days in the presence of interleukin (IL)-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β, and prostaglandin 2, and expanded using the 12-day CIK cell expansion method in the presence of IL-2 (200 IU/mL). To verify the enrichment of KRAS mutant-specific T cells, the expanded T cells were restimulated by pulsed monocyte-derived dendritic cells with KRAS mutant antigen for two days and the frequency of KRAS mutation-specific T cells was determined using the interferon (INF)-γ capture assay. Red fluorescent protein (RFP)-expressing HLA-matched cell lines and cell line-derived spheroids T3M10 (KRASG12D) and MCF-7 (KRASWT) were used for the Incucyte immune cell killing assay. T-cell phenotypes were determined by flow cytometry. The expanded non-engineered T cells stimulated with KRAS mutant antigen showed skewed CD4 T cell differentiation and increased central memory T cells compared to CIK cells, suggesting that they may have more long-term immunity and functionality than CIK cells. The KRASG12D-specific T cells were enriched 12-13% (9.4-fold) by in vitro stimulation compared to 1.3% in CIK cells. Anticancer activity in a 2D-culture model was significantly higher in KRASG12D-specific enriched T cells (82.5%) than in CIK cells (64.9%) co-cultured with T3M10 cells for 48 h. In a 3D spheroid-culture model, increased cytotoxicity was also detectable in the KRASG12D-specific enriched T cells (13.2% at 72 h and 14.1% at 142 h) compared to CIK cells. These results demonstrated that non-engineered T cells with KRAS mutated-specific anticancer activity are an ideal candidate for KRAS mutant cancer-targeted immunotherapy. Further studies are necessary to verify the anticancer effects in vivo. Citation Format: Sunki Lim, Yujeong Gho, Seoyoung Kim, Min Ki Kim, Jong Seob Park, Wang Jun Lee, Young-Kwan Lee, Hyoun Jong Moon, Excelsisbio.Inc, Goyang, Korea. Non-engineered T cells with specific anticancer effects in KRAS-mutated colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3200.

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Kim, Seoyoung, Young-Kwan Lee, Hyoun Jong Moon, Sunki Lim, Yujeong Gho, Wang Jun Lee i Sanghun Lee. "Abstract 4123: Rhus verniciflua Stokes (RVS) inhibits PD-1 expression and induces anticancer effects via enhancing T-cell function". Cancer Research 83, nr 7_Supplement (4.04.2023): 4123. http://dx.doi.org/10.1158/1538-7445.am2023-4123.

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Abstract Rhus verniciflua Stokes (RVS) has traditionally been used for centuries as a therapeutic herb and food supplement in East Asian countries. Over the last decade, the anticancer effects of RVS have been demonstrated in various preclinical and clinical studies. RVS contains major flavonoids such as fustin, fisetin, and sulfuretin, which were known to have apoptotic or anti-proliferative activities in various cancer cell lines. In clinical retrospective studies, RVS administration exclusively suggested more favorable outcomes with prolonged overall survival in solid cancer patients. However, the effect of RVS on immuno-oncology, especially the functional properties of T cells and their phenotypes remain unclear. Dried RVS grown in Wonju (Korea) was extracted with sterile distilled water after removing the allergen (urushiol). Peripheral blood mononuclear cells (PBMCs) from breast cancer patients with HLA-A*02:01 were isolated using a vacutainer tube and cultured for T cell expansion in the presence of interleukin (IL)-2 for 14 days. Cells were enriched above 90% CD3+ T cells after 14 days of expansion. Red fluorescent protein (RFP)-expressing HLA-A*02:01-matched breast cancer cell lines (MCF7 and MDA-MB-231), were used to determine the anticancer activity of T cells in the presence or absence of RVS. For in vitro killing assays, MCF7 and MDA-MB-231 cell lines expressing RFP were co-cultured with T cells with or without RVS treatment for 48 h, and cell viability was measured by the MTT assay. The phenotypic characteristics of the T cells were profiled by staining with various T cell surface markers, including CD3, CD4, CD8, PD-1, and CTLA4. RVS toxicity in the target cells (MCF7 and MDA-MB-231) was not observed at RVS concentrations up to 250 ug/mL. The anticancer activity of T cells against breast cancer cells was significantly increased by adding both 10 ug/mL and 100ug/mL of RVS. T cells co-cultured with MCF7 and MDA-MB-231 cells in the presence of 100 ug/mL of RVS showed 20.6% increases in cytotoxicity in MCF7 cells and 36.2% in MDA-MB-231 cells compared to no RVS treatment. Interestingly, relative reductions in programmed death-1 (PD-1) were found in T cells co-cultured with target cells by adding RVS, even though there was no significant difference in the other markers observed. Our findings showed that RVS could improve the function of T cells against cancer cells in the tumor microenvironment, as interpreted by reduced PD-1 expression in T cells after RVS treatment. Therefore, the components of RVS are candidates for restoring T cells exhausted against cancer. Active compounds should be identified for clinical efficacy, and further studies are necessary for combination strategies with conventional cancer treatments, such as chemotherapy and radiotherapy. Citation Format: Seoyoung Kim, Young-Kwan Lee, Hyoun Jong Moon, Sunki Lim, Yujeong Gho, Wang Jun Lee, Sanghun Lee, Excelsisbio Inc.. Rhus verniciflua Stokes (RVS) inhibits PD-1 expression and induces anticancer effects via enhancing T-cell function. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4123.

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Mann, Melissa J., Chris Melendez-Suchi, Hannah E. Vorndran, Maria Sukhoplyasova, Ashley R. Flory, Mary Carson Irvine, Anuradha R. Iyer i in. "Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum function". Molecular Biology of the Cell, 6.03.2024. http://dx.doi.org/10.1091/mbc.e24-01-0012.

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GRP170 ( Hyou1) is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds non-native proteins and acts as nucleotide exchange factor for BiP, is poorly understood. Here, we report on the isolation of mouse embryonic fibroblasts obtained from mice in which LoxP sites were engineered in the Hyou1 loci ( Hyou1LoxP/LoxP). A doxycycline-regulated Cre recombinase was stably introduced into these cells. Induction of Cre resulted in depletion of Grp170 protein which culminated in cell death. As Grp170 levels fell we observed a portion of BiP fractionating with insoluble material, increased binding of BiP to a client with a concomitant reduction in its turnover, and reduced solubility of an aggregation-prone BiP substrate. Consistent with disrupted BiP functions, we observed reactivation of BiP and induction of the unfolded protein response (UPR) in futile attempts to provide compensatory increases in ER chaperones and folding enzymes. Together, these results provide insights into the cellular consequences of controlled Grp170 loss and provide hypotheses as to why mutations in the Hyou1 locus are linked to human disease.

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Qian, Z., C. Li, W. Zhao i B. Yao. "(088) The Essential Role of O-GlcNAcylation in the Testis Aging". Journal of Sexual Medicine 20, Supplement_1 (maj 2023). http://dx.doi.org/10.1093/jsxmed/qdad060.084.

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Abstract Introduction With the delay of reproductive age, reproductive disorders related to advanced age have gradually attracted widespread attention. Studies have shown that the decline in male fertility due to aging is manifested as a decrease in semen parameters and spermatogenetic cells histologically. O-GlcNAc (O-acetylglucosamine) glycosylation is a post-translational modification that exists widely in cells. The level of UDP-GlcNAc, which is the substrate of O-GlcNAcylation, changes rapidly with various nutrients and external factors. Therefore, O-GlcNAcylation can respond to glucose, amino acid, fatty acid, and nucleoside metabolism, and is considered to be an important sensor of cellular metabolism. The previous study of our project found that the level of O-GlcNAc modification in aged testis tissue was significantly increased, so this study aimed to explore the specific mechanism of O-GlcNAc modification involved in testicular aging. Objective 1.Explore the modification pattern of O-GlcNAcylation in testis 2.Mimic the high O-GlcNAcylation state of aging mice in young mice, to study the effect of elevated high O-GlcNAcylation level on testis. 3.Reveal the role of key proteins modified by O-GlcNAc in testicular aging Methods Mice were injected intraperitoneally with OGA inhibitor Thiamet-G for 35 days to increase the level of O-GlcNAc to simulate aging. CASA system was used to detect semen parameters, and chromosome spreading technology was used to study mouse testis meiosis. Using protein profiling technology, the differentially modified O-GlcNAc proteins in aged testis and young testis were screened, and point mutations were made at their O-GlcNAc sites to study the specific mechanism of key O-GlcNAc proteins involved in testis aging. Results The O-GlcNAc modification level in the testis of aged mice was significantly increased. After intraperitoneally injecting Thiamet-G into mice for 35 days, the level of O-GlcNAcylation in the testis tissue was significantly increased. High level of O-GlcNAcylation in testis damaged the sperm parameter, decreased the thickness of seminiferous epithelium and increased apoptosis in testis. Chromosome spreading experiments showed that, γH2Ax, which is the marker of DNA double strand breaks, stained unusually at autosomes in pachytene spermatocytes. The elevation of γH2Ax affected the transition of pachytene spermatocytes to diplotene. Importantly, we found that the O-GlcNAcylation of Hyou1 protein was significantly increased in the testis of aged mice. O-GlcNAcylation of Hyou1 promotes the degradation of Hyou1. An O-GlcNAc site of Hyou1 was identified at S634 and mutation of this site decreased the O-GlcNAcylation, increased the protein stability and exerts protective roles in aging testis. Conclusions In the testis of aged mice, the level of O-GlcNAcylation is increased, which leads to the arrest of spermatocyte meiosis by affecting the DNA damage repair pathway. Hyou1 is the key O-GlcNAc protein in testicular aging and mutation of this site exerts protective roles. This study revealed for the first time the specific mechanism of O-GlcNAc involved in testicular aging, and provided a new therapeutic target for clinically delaying testicular aging and treating male infertility. Disclosure No

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Hao, Aixin, Yu Wang, Xiao Zhang, Jialiang Li, Yingzhou Li, Dangdang Li, George Kulik i Guangchao Sui. "Long Non-coding Antisense RNA HYOU1-AS is Essential to Human Breast Cancer Development Through Competitive Binding hnRNPA1 to Promote HYOU1 Expression". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, styczeń 2021, 118951. http://dx.doi.org/10.1016/j.bbamcr.2021.118951.

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Papadopoulou, Dimitra, Vasiliki Mavrikaki, Filippos Charalampous, Christos Tzaferis, Martina Samiotaki, Konstantinos D. Papavasileiou, Antreas Afantitis i in. "Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation". Angewandte Chemie International Edition, 10.02.2024. http://dx.doi.org/10.1002/anie.202319157.

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Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to identify and optimize small molecule inhibitors of pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments and chemical absorption, distribution, metabolism, excretion and toxicity (ADMET)/Pharmacokinetic (PK)/in vivo evaluation. The parallel synthesis employed for the production of the new benzamide derivatives enabled us to a) pinpoint key structural elements of the scaffold that provide potent fibroblast‐deactivating effects in cells, b) discriminate atoms or groups that favor or disfavor a desirable ADMET profile, and c) identify metabolic “hot spots”. Furthermore, we report the discovery of the first‐in‐class inhibitor leads for Hypoxia up‐regulated protein 1 (HYOU1), a member of the heat shock protein 70 (HSP70) family often associated with cellular stress responses, particularly under hypoxic conditions. Targeting HYOU1 may therefore represent a potentially novel strategy to modulate fibroblast activation and treat chronic inflammatory and fibrotic disorders.

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Papadopoulou, Dimitra, Vasiliki Mavrikaki, Filippos Charalampous, Christos Tzaferis, Martina Samiotaki, Konstantinos D. Papavasileiou, Antreas Afantitis i in. "Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation". Angewandte Chemie, 10.02.2024. http://dx.doi.org/10.1002/ange.202319157.

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Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to identify and optimize small molecule inhibitors of pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments and chemical absorption, distribution, metabolism, excretion and toxicity (ADMET)/Pharmacokinetic (PK)/in vivo evaluation. The parallel synthesis employed for the production of the new benzamide derivatives enabled us to a) pinpoint key structural elements of the scaffold that provide potent fibroblast‐deactivating effects in cells, b) discriminate atoms or groups that favor or disfavor a desirable ADMET profile, and c) identify metabolic “hot spots”. Furthermore, we report the discovery of the first‐in‐class inhibitor leads for Hypoxia up‐regulated protein 1 (HYOU1), a member of the heat shock protein 70 (HSP70) family often associated with cellular stress responses, particularly under hypoxic conditions. Targeting HYOU1 may therefore represent a potentially novel strategy to modulate fibroblast activation and treat chronic inflammatory and fibrotic disorders.

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Journal of Japan Veterinary Cancer Society 1, nr 1 (2010): HYOU1. http://dx.doi.org/10.12951/jvcs.1.hyou1.

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Arab, Fatemeh, Nima Rezaei, Forough Taheri, Hamideh Kouhpeikar, Elham Rayzan, Mona Mirbeyk, Davood Zare‐Abdollahi i Mohsen Ghadami. "Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects". Iranian Journal of Allergy, Asthma and Immunology, 21.06.2022. http://dx.doi.org/10.18502/ijaai.v21i3.9808.

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Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.

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Zhou, Shaocheng, Lijuan Sheng, Lin Zhang, Jianan Zhang i Lei Wang. "METTL3/IGF2BP3-regulated m6A modification of HYOU1 confers doxorubicin resistance in breast cancer". Biochimica et Biophysica Acta (BBA) - General Subjects, grudzień 2023, 130542. http://dx.doi.org/10.1016/j.bbagen.2023.130542.

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Kademani, Sangeetha P., Prabhudas Nelaturi, Sathya Sagar Kalidas, Vishnu Bhat Ballambattu i Ravikumar Sambandam. "Mass Spectrometric Identification of Urinary Biomarkers of Chronic Kidney Disease: A Proteomic-related Preliminary Report". Indian Journal of Nephrology, 8.07.2024, 1–6. http://dx.doi.org/10.25259/ijn_255_23.

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Background Chronic kidney disease (CKD) is a gradual loss of kidney function and has an increased prevalence rate worldwide. Our study was intended to identify potential biomarkers of progression using urine proteomics. Materials and Methods This preliminary study consisted of 32 patients with stage V CKD. Urine samples were subjected to liquid chromatography–mass spectrometry (LCMS), and the network of protein interaction was analyzed using STRING. Results A total of 135 proteins were identified, of which 35 were listed as candidates based on their clinical significance. Protein– protein interaction study provides novel insights into the functional constitution of the proteome, selecting urine as a source of biomarkers. Conclusion The present study observed that the potential markers such as EndoG, HPX, APN, AnxA1, Mic60, LONP1, and HYOU1 correlate with renal damage and its progression to CKD stage V.

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Wang, Weiguo, Xinjie Jiang, Fei Xia, Xudong Chen, Guojun Li, Lizhuan Liu, Qiang Xu, Min Zhu i Cheng Chen. "HYOU1 promotes cell proliferation, migration, and invasion via the PI3K/AKT/FOXO1 feedback loop in bladder cancer". Molecular Biology Reports, 8.11.2022. http://dx.doi.org/10.1007/s11033-022-07978-x.

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Nguyen, Phuong-Nam. "Biomarker discovery with quantum neural networks: a case-study in CTLA4-activation pathways". BMC Bioinformatics 25, nr 1 (12.04.2024). http://dx.doi.org/10.1186/s12859-024-05755-0.

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Abstract Background Biomarker discovery is a challenging task due to the massive search space. Quantum computing and quantum Artificial Intelligence (quantum AI) can be used to address the computational problem of biomarker discovery from genetic data. Method We propose a Quantum Neural Networks architecture to discover genetic biomarkers for input activation pathways. The Maximum Relevance-Minimum Redundancy criteria score biomarker candidate sets. Our proposed model is economical since the neural solution can be delivered on constrained hardware. Results We demonstrate the proof of concept on four activation pathways associated with CTLA4, including (1) CTLA4-activation stand-alone, (2) CTLA4-CD8A-CD8B co-activation, (3) CTLA4-CD2 co-activation, and (4) CTLA4-CD2-CD48-CD53-CD58-CD84 co-activation. Conclusion The model indicates new genetic biomarkers associated with the mutational activation of CLTA4-associated pathways, including 20 genes: CLIC4, CPE, ETS2, FAM107A, GPR116, HYOU1, LCN2, MACF1, MT1G, NAPA, NDUFS5, PAK1, PFN1, PGAP3, PPM1G, PSMD8, RNF213, SLC25A3, UBA1, and WLS. We open source the implementation at: https://github.com/namnguyen0510/Biomarker-Discovery-with-Quantum-Neural-Networks.

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Wang, Weiguo, Xinjie Jiang, Fei Xia, Xudong Chen, Guojun Li, Lizhuan Liu, Qiang Xu, Min Zhu i Cheng Chen. "Correction to: HYOU1 promotes cell proliferation, migration, and invasion via the PI3K/AKT/FOXO1 feedback loop in bladder cancer". Molecular Biology Reports, 18.04.2023. http://dx.doi.org/10.1007/s11033-023-08325-4.

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Piórkowska, Katarzyna, Kacper Żukowski, Wojciech Witarski, Katarzyna Kowalska, Katarzyna Ropka-Molik i Mirosław Tyra. "Identification of genes related to fat deposition as candidates for er stress based on combined RNA-ATAC sequencing analysis". Annals of Animal Science, 24.01.2024. https://doi.org/10.2478/aoas-2025-0009.

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Abstract Endoplasmic reticulum (ER) stress is associated with obesity as this state challenges lipid and carbohydrate metabolisms, resulting in glucolipotoxicity and endoplasmic reticulum dysfunction. It can be induced by excessive ectopic fat accumulation, rising blood glucose levels or meta-inflammatory factors, which disturb the liver’s numerous pathways favoring hepatic lipogenesis. In the present study, It was attempted to identify liver molecular processes associated with fat deposition in pigs based on combined RNA-ATAC-seq analysis. The pig groups used in the present study were significantly different in terms of subcutaneous and visceral fat deposition; they belonged to a native Polish breed and were not under selection pressure. Based on RNAATAC-seq combined analysis, it was identified 45 significant differentially expressed genes (DEGs) in liver tissue dependent on fat deposition, for which open chromatin regions in transcription start sites were found. The functional analysis pinpointed that 5 of them are involved in the ER stress process (MANF, SELENOS, HYOU1, PIK3R1, and HSPA5). These five proposed genes expressed in the liver as candidates associated with fat deposition in pigs because ER stress plays a significant role in this organ in molecular process associated with the determination of fat level in the organism, which was previously broadly described in humans.

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Lv, Liangjie, Aiju Zhao, Yelun Zhang, Hui Li i Xiyong Chen. "Proteome and transcriptome analyses of wheat near isogenic lines identifies key proteins and genes of wheat bread quality". Scientific Reports 11, nr 1 (11.05.2021). http://dx.doi.org/10.1038/s41598-021-89140-4.

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AbstractThe regulation of wheat protein quality is a highly complex biological process involving multiple metabolic pathways. To reveal new insights into the regulatory pathways of wheat glutenin synthesis, we used the grain-filling period wheat grains of the near-isogenic lines NIL-723 and NIL-1010, which have large differences in quality, to perform a combined transcriptome and proteome analysis. Compared with NIL-1010, NIL-723 had 1287 transcripts and 355 proteins with significantly different abundances. Certain key significantly enriched pathway were identified, and wheat quality was associated with alanine, aspartate and glutamate metabolism, nitrogen metabolism and alpha-linolenic acid metabolism. Differentially expressed proteins (DEPs) or Differentially expressed genes (DEGs) in amino acid synthesis pathways were upregulated primarily in the glycine (Gly), methionine (Met), threonine (Thr), glutamic acid (Glu), proline (proC), cysteine (Cys), and arginine (Arg) synthesis and downregulated in the tryptophan (trpE), leucine (leuC), citrulline (argE), and ornithine (argE) synthesis. Furthermore, to elucidate changes in glutenin in the grain synthesis pathway, we plotted a regulatory pathway map and found that DEGs and DEPs in ribosomes (RPL5) and the ER (HSPA5, HYOU1, PDIA3, PDIA1, Sec24, and Sec31) may play key roles in regulating glutenin synthesis. The transcriptional validation of some of the differentially expressed proteins through real-time quantitative PCR analysis further validated the transcriptome and proteomic results.

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Liu, Yan, Da Huang, Zhile Li, LiuFang Zhou, Tuan Cen, Baomin Wei, Liuqing Wei i in. "A plasma proteomic approach in patients with heart failure after acute myocardial infarction: insights into the pathogenesis and progression of the disease". Frontiers in Cardiovascular Medicine 10 (17.05.2023). http://dx.doi.org/10.3389/fcvm.2023.1153625.

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AimsThe pathogenesis of disease progression targets for patients with heart failure after acute myocardial infarction was investigated by using plasma proteomics.MethodsThe plasma proteomes of acute myocardial infarction patients with (MI-HF) and without (MI-WHF) heart failure were compared. Each group consisted of 10 patients who were matched for age and sex. The peptides were analyzed by 2-dimensional liquid chromatography coupled to tandem mass spectrometry in a high definition mode. Parallel reaction monitoring (PRM) verified the selected target proteins.ResultsWe identified and quantified 2,589 and 2,222 proteins, respectively, and found 117 differentially expressed proteins (DEPs) (≥1.5-fold), when the MI-HF and MI-WHF groups were compared. Of these 51 and 66 were significantly up-regulated and down-regulated, respectively. The significant DEPs was subjected to protein–protein interaction network analysis which revealed a central role of the NF-κB signaling pathway in the MI-HF patients. PRM verified that MB, DIAPH1, VNN1, GOT2, SLC4A1, CRP, CKM, SOD3, F7, DLD, PGAM2, GOT1, UBA7 and HYOU1 were 14 proteins which were highly expressed in MI-HF patients.ConclusionsThese findings showed a group of proteins related to the NF-κB signaling pathway in the pathogenesis of patients with poor outcomes after experiencing MI-HF. These proteins may be useful candidate markers for the diagnosis of MI-HF as well as help to elucidate the pathophysiology of this major cause of mortality in older patients.

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