Journal articles on the topic 'CC mice'
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Pangestuti, Dewi. "PENGARUH PEMBERIAN AIR PERASAN JERUK NIPIS (CITRUS AURANTIFOLIA SWINGLE) TERHADAP KADAR KOLESTEROL PADA MENCIT HIPERKOLESTEROLEMIA." Jurnal Riset Hesti Medan Akper Kesdam I/BB Medan 4, no. 1 (June 1, 2019): 42. http://dx.doi.org/10.34008/jurhesti.v4i1.88.
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Lime (Citrus Aurantifolia) contains of main flavonoid in limes, that is herperidin. Hesperidin can help reducing total Cholesterol level and has the property of hypercholesterolemic. Hypercholesterolemia is the main factor independent risk factor of coronary heart disease (CHD). This study intend to determine whether or not the effect od water lime extract orally with cholesterol level in the hypercholesterolemia mice. This isi an experimental study designed following randomize control design and post test only control group design by using 24 mice (Mus musculus) adult male strain DD Webster divided into 4 groups: control group (P0) that Given adlibitum, (P1) that given hypercholesterolemia 0,2 cc, (P3) that given hypercholesterolemia 0,2 cc and water lime extract 0,3 cc by gastric sonde once a day for 15 days. In the day46 mice are done neck dislocation. Data result was analyzed by One Way- Anova test and continuous and continued with post-hoc test. Result of this study showed that giving of water lime extract 0,3 cc orally per mice could reduced cholesterol level of mice hypercholesterolemia than giving water lime extract 0,1 cc orraly per mice.
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Anhê, Fernando F., Renato T. Nachbar, Thibault V. Varin, Jocelyn Trottier, Stéphanie Dudonné, Mélanie Le Barz, Perrine Feutry, et al. "Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice." Gut 68, no. 3 (July 31, 2018): 453–64. http://dx.doi.org/10.1136/gutjnl-2017-315565.
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ObjectiveThe consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique phytochemical profile, strong antioxidant potential and purported anti-inflammatory potential.DesignBy using metabolic tests coupled with 16S rRNA gene-based taxonomic profiling and faecal microbial transplantation (FMT), we have assessed the effect of a crude extract of camu camu (CC) on obesity and associated immunometabolic disorders in high fat/high sucrose (HFHS)-fed mice.ResultsTreatment of HFHS-fed mice with CC prevented weight gain, lowered fat accumulation and blunted metabolic inflammation and endotoxaemia. CC-treated mice displayed improved glucose tolerance and insulin sensitivity and were also fully protected against hepatic steatosis. These effects were linked to increased energy expenditure and upregulation of uncoupling protein 1 mRNA expression in the brown adipose tissue (BAT) of CC-treated mice, which strongly correlated with the mRNA expression of the membrane bile acid (BA) receptor TGR5. Moreover, CC-treated mice showed altered plasma BA pool size and composition and drastic changes in the GM (eg, bloom of Akkermansia muciniphila and a strong reduction of Lactobacillus). Germ-free (GF) mice reconstituted with the GM of CC-treated mice gained less weight and displayed higher energy expenditure than GF-mice colonised with the FM of HFHS controls.ConclusionOur results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.
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Detombe, Sarah A., Fu-Li Xiang, Joy Dunmore-Buyze, James A. White, Qingping Feng, and Maria Drangova. "Rapid microcomputed tomography suggests cardiac enlargement occurs during conductance catheter measurements in mice." Journal of Applied Physiology 113, no. 1 (July 1, 2012): 142–48. http://dx.doi.org/10.1152/japplphysiol.00831.2011.
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Conductance catheters (CC) represent an established method of determining cardiac function in mice; however, the potentially detrimental effects a catheter may have on the mouse heart have never been evaluated. The present study takes advantage of rapid three-dimensional (3D) microcomputed tomography (CT) to compare simultaneously acquired micro-CT and CC measurements of left ventricular (LV) volumes in healthy and infarcted mice and to determine changes in LV volume and function associated with CC insertion. LV volumes were measured in C57BL/6 mice (10 healthy, 10 infarcted, 2% isoflurane anesthesia) using a 1.4-Fr Millar CC. 3D micro-CT images of each mouse were acquired before CC insertion as well as during catheterization. Each CT scan produced high-resolution images throughout the entire cardiac cycle in <1 min, enabling accurate volume measurements as well as direct visualization of the CC within the LV. Bland-Altman analysis demonstrated that CC measurements underestimate volume compared with CT measurements in both healthy [bias of −18.4 and −28.9 μl for end-systolic (ESV) and end-diastolic volume (EDV), respectively] and infarcted mice (ESV = −51.6 μl and EDV = −71.7 μl); underestimation was attributed to the off-center placement of the catheter. Individual evaluation of each heart revealed LV dilation following CC insertion in 40% of mice in each group. No change in ejection fraction was observed, suggesting the enlargement was caused by volume overload associated with disruption of the papillary muscles or chords. The enlargement witnessed was not significant; however, the results suggest the potential for CC insertion to detrimentally affect mouse myocardium, necessitating further investigation.
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Yuan, Zihao, Peipei Chen, Tingting Zhang, Bin Shen, and Ling Chen. "Agenesis and Hypomyelination of Corpus Callosum in Mice Lacking Nsun5, an RNA Methyltransferase." Cells 8, no. 6 (June 6, 2019): 552. http://dx.doi.org/10.3390/cells8060552.
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Williams-Beuren syndrome (WBS) is caused by microdeletions of 28 genes and is characterized by cognitive disorder and hypotrophic corpus callosum (CC). Nsun5 gene, which encodes cytosine-5 RNA methyltransferase, is located in the deletion loci of WBS. We have reported that single-gene knockout of Nsun5 (Nsun5-KO) in mice impairs spatial cognition. Herein, we report that postnatal day (PND) 60 Nsun5-KO mice showed the volumetric reduction of CC with a decline in the number of myelinated axons and loose myelin sheath. Nsun5 was highly expressed in callosal oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) from PND7 to PND28. The numbers of OPCs and OLs in CC of PND7-28 Nsun5-KO mice were significantly reduced compared to wild-type littermates. Immunohistochemistry and Western blot analyses of myelin basic protein (MBP) showed the hypomyelination in the CC of PND28 Nsun5-KO mice. The Nsun5 deletion suppressed the proliferation of OPCs but did not affect transition of radial glial cells into OPCs or cell cycle exit of OPCs. The protein levels, rather than transcriptional levels, of CDK1, CDK2 and Cdc42 in the CC of PND7 and PND14 Nsun5-KO mice were reduced. These findings point to the involvement of Nsun5 deletion in agenesis of CC observed in WBS.
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Nagasawa, Hiroshi, Erika Yada, Yoko Udagawa, and Hideo Inatomi. "Effects of Coffee Cherry, the Residue Left after Removal of the Beans from the Coffeee Fruit, on Mammary Glands, Automatic Behavior and Related Parameters in Mice." American Journal of Chinese Medicine 29, no. 01 (January 2001): 119–27. http://dx.doi.org/10.1142/s0192415x01000137.
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To clarify the mechanisms of the anti-mammary tumor activity of coffee cherry (CC), the residue left after the removal of beans from the fruit, the effects in SHN mice of CC on plasma and urine component levels, mammary gland growth, spontaneous motor activity and several related parameters were examined. Hot water extract of CC was given to 2-month-old mice in drinking water (0.5%) for 60 days. The treatment prevented the elevation of plasma and urine levels of alanin aminotransferase and asparate aminotransferase, indicating that CC can protect against metabolic abnormality, which is a cause of the high mammary tumor susceptibility of SHN mice. It also resulted in an inhibition of the formation of precancerous mammary hyperplastic alveolar nodules. Neither food and water intake nor spontaneous motor activity was affected by CC. The findings provide novel information on the mechanism of the protective effect of CC on mammary tumorigenesis and confirm the usefulness of CC as a safe chemopreventive agent of mammary and other types of tumors.
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Shen, Weixing, Faiyaz Ahmad, Steven Hockman, John Ma, Hitoshi Omi, Nalini Raghavachari, and Vincent Manganiello. "Female infertility in PDE3A-/-mice." Cell Cycle 9, no. 23 (December 2010): 4720–34. http://dx.doi.org/10.4161/cc.9.23.14090.
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Spong, Adam, and Andrzej Bartke. "Rapamycin slows aging in mice." Cell Cycle 11, no. 5 (March 2012): 845. http://dx.doi.org/10.4161/cc.11.5.19607.
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Wysoczynski, Marcin, HakMo Lee, Rui Liu, Wan Wu, Janina Ratajczak,, and Mariusz Z. Ratajczak. "Mobilization Studies in Complement-Deficient Mice Reveal That AMD3100 Mobilization Depends On Complement Cascade Activation and Suggest Involvement of “Membrane Attack Complex - MAC” in Egress of Hematopoietic Stem/Progenitor Cells." Blood 114, no. 22 (November 20, 2009): 367. http://dx.doi.org/10.1182/blood.v114.22.367.367.
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Abstract Abstract 367 We reported that complement cascade (CC) becomes activated in bone marrow (BM) during mobilization of hematopoietic stem/progenitor cells (HSPCs) by immunoglobulin (Ig)-dependent pathway and/or by alternative Ig-independent pathway as seen during G-CSF- or Zymosan mobilization, respectively. As a result, several potent bioactive CC anaphylatoxins (C3 and C5 cleavage fragments) are released that regulate egress of HSPCs (Blood 2003;101,3784; Blood 2004;103,2071; Blood 2005;105,40, Leukemia 2009; in press.). This explains why: i) NOD/SCID and RAG-/- animals that do not activate the Ig-dependent CC classical pathway; ii) C2fB-/- and C3-/- mice that do not activate the classical and alternative CC pathways; and iii) C5-/- mice that do not activate the distal pathway of CC are all poor G-CSF- and/or Zymosan mobilizers. In this study, we evaluated the role of CC in mobilization induced by CXCR4 antagonist AMD3100. We noticed that all CC activation-deficient mice mentioned above, except C5-/- mice, mobilize normally in response to AMD3100 administration. Accordingly, the number of mobilized CD34- SKL cells, leucocytes, and CFU-GM clonogeneic progenitors in mutant mice was similar to wt littermates. More important we observed that AMD3100 mobilization of HSPCs was preceded by a massive egress of leucocytes from BM and that AMD3100 was able to stimulate in these cells i) phosphorylation of MAPKp42/44 and ii) secretion of MMP-9. At the same time, ELISA data to detect CC activation revealed that serum levels of CC cleavage fragments, which were low in the initial phase of AMD3100 mobilization during granulocyte egress, become elevated later during HSPC egress. Thus, our data show that despite a fact that G-CSF and AMD3100 mobilize HSPCs by involving different mechanisms, activation of CC is a common phenomenon occurring during mobilization induced by both compounds. This further supports a pivotal role of CC activation in the egress of HSPCs from BM; however, both compounds activate CC differently. While G-CSF administration initiates CC activation at its proximal C1q-C3 level, AMD3100 induces CC activation at the distal C5 level, pointing to a crucial role of C5 cleavage in executing mobilization. To support this, all mice employed in our studies that display defects in activation of proximal stages of CC (NOD/SCID, RAG, C2fB-/-, and C3-/-) are normal AMD3100 mobilizers. However, C5 is cleavage required for mobilization occurs in the plasma of these animals latter on - directly by proteases released from AMD3100-stimulated granulocytes that egress from the BM as a first wave of mobilized cells. This compensatory mechanism cannot occur from obvious reasons in C5-/- mice. We conclude that AMD3100-directed mobilization similarly as G-CSF-induced one depends on activation of CC; however, AMD3100 in contrast to G-CSF activates CC at distal stages – directly by proteases released from mobilized/activated granulocytes. Cleavage of C5 and release of C5a and desArgC5a create a sinusoid-permissive environment in BM for HSPCs egress. This suggests involvement of both C5 cleavage fragments as well as a potential role of downstream elements of CC activation - membrane attack complex - MAC (C5b-C9) in stem cell mobilization. Therefore, some poor AMD3100 patient responders could possess a defect in activation of the distal steps of CC. Disclosures: No relevant conflicts of interest to declare.
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Mishra, Mudit, Ilayaraja Muthuramu, Joseph Aboumsallem, Herman Kempen, and Bart De Geest. "Reconstituted HDL (Milano) Treatment Efficaciously Reverses Heart Failure with Preserved Ejection Fraction in Mice." International Journal of Molecular Sciences 19, no. 11 (October 30, 2018): 3399. http://dx.doi.org/10.3390/ijms19113399.
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Heart failure with preserved ejection fraction (HFpEF) represents a major unmet therapeutic need. This study investigated whether feeding coconut oil (CC diet) for 26 weeks in female C57BL/6N mice induces HFpEF and evaluated the effect of reconstituted high-density lipoprotein (HDL)Milano (MDCO-216) administration on established HFpEF. Eight intraperitoneal injections of MDCO-216 (100 mg/kg protein concentration) or of an equivalent volume of control buffer were executed with a 48-h interval starting at 26 weeks after the initiation of the diet. Feeding the CC diet for 26 weeks induced pathological left ventricular hypertrophy characterized by a 17.1% (p < 0.0001) lower myocardial capillary density and markedly (p < 0.0001) increased interstitial fibrosis compared to standard chow (SC) diet mice. Parameters of systolic and diastolic function were significantly impaired in CC diet mice resulting in a reduced stroke volume, decreased cardiac output, and impaired ventriculo-arterial coupling. However, ejection fraction was preserved. Administration of MDCO-216 in CC diet mice reduced cardiac hypertrophy, increased capillary density (p < 0.01), and reduced interstitial fibrosis (p < 0.01). MDCO-216 treatment completely normalized cardiac function, lowered myocardial acetyl-coenzyme A carboxylase levels, and decreased myocardial transforming growth factor-β1 in CC diet mice. In conclusion, the CC diet induced HFpEF. Reconstituted HDLMilano reversed pathological remodeling and functional cardiac abnormalities.
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Wysoczynski, Marcin, Ryan Reca, Wu Wan, Magda Kucia, Marina Botto, Janina Ratajczak, and Mariusz Z. Ratajczak. "The Studies in Various Murine Strains with Defects in Activation of Complement Cascade (CC) Reveal Both Pivotal and Pleiotropic Role of CC in Mobilization of Hematopoietic Stem/Progenitor Cells." Blood 110, no. 11 (November 16, 2007): 774. http://dx.doi.org/10.1182/blood.v110.11.774.774.
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Abstract We reported that complement cascade (CC) becomes activated in bone marrow (BM) during mobilization of hematopoietic stem/progenitor cells (HSPC) by i) immunoglobulin (Ig)-dependent pathway and/or by ii) alternative Ig-independent pathway and, as result of this, iii) several potent bioactive CC anaphylatoxins (C3a, desArgC3a, C5a and desArgC5a) are released (Blood2003;101,3784; Blood2004;103,2071; Blood2005;105,40). To learn more on the role of CC and innate immunity in this process, we compared mobilization in mice that possess defects in CC activation by i) classical pathway (C1q−/−, Ig-deficient), ii) both classical and alternative pathway (C2fB−/−) and in animals iii) that do not generate CC-derived anaphylatoxins (C3−/−, C5−/−). For mobilization, we employed G-CSF and zymosan that activate classical and alternative pathways of CC, respectively. First, we found by ELISA that CC activation in fact correlates with the level of HSPC mobilization. Next, studies in mice deficient in CC activation revealed that CC plays both pivotal and pleiotropic roles in this process. Accordingly, while C1q−/− and C3−/− mice turned out to be easy mobilizers, mobilization was very poor in Ig-deficient, C2fB−/− and C5−/− mice that demonstrate that C3 and C5 cleavage fragments differently control the mobilization of HSPC. To explain this at molecular level, we found that C3 cleavage fragments (C3a, desArgC3a) directly interact with HSPC and increase their responsiveness to SDF-1 gradient and thus prevent uncontrolled egress of HSPC from BM. It explains why C1q−/− and C3−/− mice that do not generate C3 cleavage fragments in BM release easily HSPC into circulation. In contrast, C5 cleavage fragments (C5a, desArgC5a) increase permeability of BM-endothelium and thus are crucial for the egress of HSPC from BM to occur. This explains why mice that do not activate efficient CC such as Ig-deficient, C2fB−/− and C5−/− animals are poor mobilizers. We conclude that the mobilization of HSPC is i) dependent on C activation by the classical or alternative pathway and balanced differently by C3 and C5 cleavage fragments that enhance retention or promote egress of HSPC respectively. Thus, modulation of C activation in BM may help to develop new more efficient strategies for both HSPC mobilization and their homing/engraftment.
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Janowska-Wieczorek, Anna, Leah A. Marquez-Curtis, Danila Leontyev, Donald R. Branch, Janina Ratajczak, and Mariusz Z. Ratajczak. "Studies in C4b-Deficient Mice Provide Further Evidence That Complement Cascade Orchestrates the Mobilization of Hematopoietic Stem/Progenitor Cells." Blood 120, no. 21 (November 16, 2012): 2316. http://dx.doi.org/10.1182/blood.v120.21.2316.2316.
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Abstract Abstract 2316 Introduction: Complement cascade (CC) and innate immunity have emerged as important modulators of hematopoietic stem/progenitor cell (HSPC) trafficking. We reported that the CC becomes activated in bone marrow (BM) during HSPC mobilization induced by G-CSF or AMD3100 and proposed that the generation of C5a and C5b-C9 (membrane attack complex; MAC) is required for optimal mobilization (Stem Cells 2007; 25:3093; Leukemia 2010; 24:976). While C5a induces a proteolytic microenvironment in BM that attenuates SDF-1-CXCR4 retention signals for HSPC and promotes egress of leucocytes, C5b-C9 (MAC) induces the release of a crucial chemoattractant, sphingosine-1 phosphate (S1P), from red blood cells and augments mobilization of HSPC from BM. On the other hand, C3 cleavage fragments attenuate mobilization by enhancing responsiveness of HSPC to SDF-1 retention signals thus promoting HSPC retention in BM. Thus our findings suggest that mobilization is differently regulated by the proximal and distal parts of CC (upstream and downstream of C3, respectively). We also demonstrated that C3-deficient mice (lacking C3 cleavage fragments) are easy mobilizers whereas C5-deficient mice (lacking C5 cleavage fragments and not generating MAC) mobilize HSPC very poorly (Leukemia 2009; 23:2052). C4 is part of the classical pathway of CC whose activation/cleavage is initiated by C1 and C2, releasing smaller (C4a and C2b) and larger (C4b and C2a) fragments. C2a binds with C4b to form an enzymatic complex termed C3 convertase that cleaves C3 into C3a anaphylatoxin and C3b. Aim of Study: In the present study we investigated the role of C4 in HSPC mobilization and hypothesized that C4-deficient mice are easy mobilizers, supporting the notion that the proximal part of CC is crucial for retention of HSPC in the BM microenvironment. Experimental Approach: We employed 6–8 week old C4b-deficient mice (strain B6.129S-C4btm1Crr/J from Jackson Laboratory, Bar Harbour, ME) and wild type (WT) littermates. Mice were injected subcutaneously with 250 μg/kg of human recombinant G-CSF (Amgen, Thousand Oaks, CA) or saline (control) daily for 3 days. At 6 h after the last G-CSF injection, the mice were sacrificed and blood was collected from the vena cavae. Mobilization was evaluated by determining the number of leukocytes (WBC) and colony-forming unit granulocyte-macrophages (CFU-GM) circulating in the peripheral blood (PB). We also measured the level of mouse terminal complement complex C5b-C9 (MAC) in plasma using ELISA (Kamiya) in G-CSF-mobilized and non-mobilized C4b-deficient and WT mice. Results: We found that C4b-deficient mice treated with saline have slightly higher WBC counts than WT mice and that G-CSF induced a greater increase in WBC counts in these mice than in WT mice. Based on CFU-GM counts after G-CSF mobilization, C4b-deficient mice mobilized significantly more HSPCs into PB than WT mice (p < 0.0065). These observations were consistent in all four experiments performed involving 18–20 mice per experiment. The G-CSF mobilization responses correlated with a greater increase in activation of the distal part of CC in C4b-deficient mice compared to WT mice, as evidenced by C5b-C9 levels evaluated by ELISA. Conclusions: Our data indicate that C4-deficient mice are easy mobilizers, thus supporting a role for the proximal part of CC in retention of HSPC in BM. Furthermore, mobilization of HSPC in C4b-deficient mice correlated with activation of the distal part of CC and generation of C5b-C9 (MAC) suggesting that activation of the distal part of CC is crucial for egress of HSPCs into PB. Moreover, activation of the distal part of CC in C4-deficient mice that have defective activation of the proximal part of CC indicates that C5 may be cleaved in a C3-independent manner by other proteolytic enzymes present in blood plasma. Finally, our data further support that mobilization is part of a more general immune response in which all complement components, including C4, play a significant role. Disclosures: No relevant conflicts of interest to declare.
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Zhu, Mengjing, Ling Zhou, Jian Fu, Yijin Wang, Xiaofeng Xu, Jun Wu, Xiangyi Kong, Jian Li, Zhe Zhou, and Huaijun Zhou. "Artemin Promotes the Migration and Invasion of Cervical Cancer Cells through AKT/mTORC1 Signaling." Journal of Oncology 2022 (November 26, 2022): 1–13. http://dx.doi.org/10.1155/2022/3332485.
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Background. The neurotrophic factor Artemin (ARTN) is involved in tumor proliferation and metastasis. Nonetheless, ARTN’s significance in cervical cancer (CC) has not been studied. In our study, we propose to investigate the biological function of ARTN in CC as well as its particular regulatory mechanism. Methods. Immunohistochemistry (IHC) was used to examine the degree of ARTN protein expression in CC patient tissue. Real-time PCR and Western blotting were performed to reveal related genes’ levels in CC cells. The CCK-8 test, the colony formation assay, the wound-healing assay, and the transwell assay were utilized to determine the proliferation, migration, and invasion capabilities, respectively. To generate lung metastasis models, stable ARTN-expressing SiHa cells were injected into the caudal tail vein of mice. IHC was used to examine the protein levels in CC mice model tissues. Results. ARTN was overexpressed in CC tissues relative to normal cervical tissues and linked positively with lymph node metastases ( P = 0.012 ) and recurrence ( P = 0.015 ) in CC patients. In vitro, ARTN overexpression promoted the proliferation, invasion, and migration of CC cells. In contrast, the consequences of depleting endogenous ARTN were the opposite. Moreover, overexpression of ARTN increased lung metastasis of CC cells in vivo and shortened the lifespan of mice models. In addition, ARTN overexpression significantly enhanced AKT phosphorylation on Ser473 and mTOR phosphorylation on Ser2448 and promoted the epithelial-mesenchymal transition (EMT) cascade. In addition, rapamycin, a selective inhibitor of mTORC1, might rescue the EMT phenotype caused by ARTN. Conclusion. Our findings suggested that ARTN may enhance CC metastasis through the AKT/mTORC1 pathway. ARTN is anticipated to be a novel potential therapeutic target for the treatment of CC metastases.
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Zhou, Yayan, Minjie Fang, Dong Yang, Maosheng Yan, Long Gong, Zhanhong Tan, Jingwen Liu, and Xianming Li. "Expression Mechanism of miR-10b in Cervical Cancer Under Treatment of Methoxy-Polyethylene Glycol-Polylactic Drug-Loaded Nanoparticles." Science of Advanced Materials 13, no. 8 (August 1, 2021): 1557–64. http://dx.doi.org/10.1166/sam.2021.4050.
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This work aimed to analyze expression mechanism of micro ribonucleic acid (RNA)-10b (miR-10b) in cervical cancer (CC) based on Curcumin-monomethoxy polyethylene glycol-polylactic acid-drug-loaded nanoparticles (CUR-MPEG-PLA DLNPs). 36 Kunming mice were selected and randomly rolled into group A and group B, and 18 nude mice were deemed as controls. CUR-MPEG-PLA DLNPs were prepared for the treatment of 18 Kunming mice in group A. The CC tumor tissues of 36 Kunming mice were harvested, the miR-10b of CC cells was extracted, and the expression level of CC cells was detected by fluorescence quantitative polymerase chain reaction (qPCR). The results showed that the average particle size of CUR-MPEG-PLA DLNPs was 362.52±6.34 nm. The tumor inhibition rate of Kunming mice in group A against CC tumor strains 63.35±3.62% was considerably superior to those in group B (26.31 ±2.54%) (P < 0.05). In group A, expression rate of miR-10b (77.78%) was remarkably superior to controls (55.55%) (x2 = 2.364, P < 0.05). In 20 cases of CC tissues with positive expression of latent membrane protein 1 (LMP-1), expression of miR-10b in metastasis group was obviously higher relative to non-metastasis group (Z = −3.214, P < 0.05). In 16 cases of CC tissues with negative expression of LMP-1, expression of miR-10b in metastasis group was also considerably higher versus non-metastasis group (Z = −2.245, P < 0.05). In conclusion, the average particle size of CUR-MPEG-PLA DLNPs was 362.52 ±6.34 nm, the electromotive force was −9.23 mV, the dispersion coefficient was 0.064, the drug loading rate of nanoparticles was 8.54%, and the encapsulation rate was 72.36%. miR-10b has certain correlation with the metastasis of cervical cancer. LMP-1 gene has the function of promoting the metastasis of cervical cancer tumor cells, which may be dependent on miR-10b. CUR-MPEG-PLA DLNPs loading system can inhibit tumor growth obviously, and has excellent therapeutic effect in CC disease.
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Arthur, L. Matthew, Renee M. Demarest, Lise Clark, Dmitri Gourevitch, Kamila Bedelbaeva, Rhonda Anderson, Andrew R. Snyder, et al. "Epimorphic regeneration in mice is p53-independent." Cell Cycle 9, no. 18 (September 15, 2010): 3691–97. http://dx.doi.org/10.4161/cc.9.18.13119.
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Pallas, Brooke D., Dawn M. Keys, Michael P. Bradley, Elizabeth J. Vernasco-Price, Joe D. Sanders, Portia S. Allen, and Zachary T. Freeman. "Compressed Paper as an Alternative to Corn Cob Bedding in Mouse (Mus musculus) Cages." Journal of the American Association for Laboratory Animal Science 59, no. 5 (September 1, 2020): 496–502. http://dx.doi.org/10.30802/aalas-jaalas-19-000151.
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Bedding material is a critical component of the mouse environment and affects animal wellbeing and research integrity. Corn cob (CC) bedding has been a common bedding choice in research despite several potential negative aspects of its use. We investigated the use of compressed paper (CP) bedding as a refinement to CC bedding. CP bedding demonstrated greater total and immediate absorption, compared with CC bedding. CP-bedded cages had a reduced frequency of early cage changing prior to the Guide-recommended 2-wk interval for IVC; this reduction was proportional to room census. Intracage ammonia levels were lower in CP-bedded IVC compared with CC-bedded IVC, independent of the age, sex, and number of mice per cage. By contrast, ammonia levels were similar between CP-bedded and CC-bedded static cages. Collectively, these data support the use of CP bedding as a refinement for CC in ventilated mouse cages, in light of increased husbandry efficiency and its positive effect on the welfare of mice.
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Silva, Fábio Henrique, Mário Angelo Claudino, Carla Fernanda Franco-Penteado, Edson Antunes, and Fernando Ferreira Costa. "Townes Transgenic Sickle Cell Mouse Model Displays Erectile Dysfunction." Blood 124, no. 21 (December 6, 2014): 1376. http://dx.doi.org/10.1182/blood.v124.21.1376.1376.
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Abstract Introduction: Erectile function alterations result from an imbalance of nitric oxide (NO)-mediated relaxations and sympathetic-mediated vasoconstriction in the erectile tissue. The degree of contraction of corpus cavernosum (CC) smooth muscle determines the functional state of penile flaccidity, tumescence, erection, or detumescence. Patients with sickle-cell disease (SCD) display alterations in erectile function. Priapism is most frequently reported and untreated acute ischaemic priapism results in erectile dysfunction (ED). Previous studies have shown that patients with ED exhibit priapic activity, however, ED unassociated with priapism is still poorly investigated. Transgenic sickle cell mice have been employed to better understand the complex pathophysiology of SCD. The Berkeley murine model displays features of priapism and is associated with an upregulation of the NO-cGMP signaling pathway in the cavernosal tissue, reflecting in an uncontrolled erectile response. Townes mice express human sickle hemoglobin and exhibit the major features found in humans with SCD. However, no detailed study has investigated the pathophysiological alterations of corpus cavernosum (CC) in Townes SCD mice. Thus, the aim of this study was to characterize the erectile function in these animals, focusing on the role of the NO signaling pathway and contractile machinery. Methods: Townes transgenic sickle cell mice and C57BL/6 mice (control) aged 3 to 4 months-old were used (Wu et al Blood 2006). The intracavernous pressure (ICP) was assessed following electrical stimulation of cavernous nerve in anaesthetized mice. In separate protocols, strips of CC were mounted in isolated organ baths, and the relaxing responses to acetylcholine (ACh; endothelium-dependent responses) and sodium nitroprusside (SNP; endothelium-independent responses), as well as electrical-field stimulation (EFS; nitrergic relaxations) were obtained in cavernosal strips precontracted with the α1-adrenergic receptor agonist phenylephrine (3-10 µM). Contracting responses to phenylephrine and EFS were also obtained in both control and SCD mice. Results: The cavernous nervous stimulation caused frequency-dependent increases of ICP in control and SCD groups. However, ICP was 37% lower in SCD mice compared to the control group (P < 0.05). Phenylephrine (0.01 – 100 µM) induced concentration-dependent CC contractions in both control and SCD mice, but maximal contractile responses were significantly greater (P < 0.05) in SCD compared to control mice (1.32 ± 0.11 and 0.80 ± 0.04 mN, respectively). Likewise, EFS-induced neurogenic CC contractions in SCD mice were 50% higher (P < 0.05) compared to the control. The cumulative addition of ACh (0.001 – 10 µM) produced concentration-dependent CC relaxations in both groups, but maximal relaxations were significantly higher in SCD (78 ± 6%; P < 0.05) compared to control mice (50 ± 4%). Similarly, SNP (0.01 – 10 µM) produced concentration-dependent CC relaxations, but, again, the maximal relaxations elicited by this agent were significantly higher in SCD (96 ± 3; P < 0.05) compared to control mice (77 ± 5 %; n=9). The nitrergic relaxations induced by EFS were also significantly higher (P < 0.001) in SCD mice compared to control mice (8 Hz: 90 ± 6 and 65 ± 4 %, respectively; n=5). Conclusion: Our study shows that this type of SCD mouse exhibits enhanced α1-adrenoceptor-mediated vasoconstriction and erectile dysfunction. Interestingly, however, NO-mediated CC relaxations are greater in the SCD mice. It is likely, therefore, that CC vasoconstriction in SCD overcomes the NO-dependent erectile stimulus, making penile tumescence more difficult to occur. These results are in contrast with the data from the Berkeley SCD mice, which indicate exaggerated in vivo erectile responses. The reason to this difference among the two SCD models is not clear. Taken together our results indicate that ED, unassociated with priapism, as seen in the Townes mouse, should be investigated in SCD patients. Financial Support: FAPESP/CNPq. Disclosures No relevant conflicts of interest to declare.
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Lim, Seongkyun, J. William Deaver, Megan E. Rosa-Caldwell, Wesley S. Haynie, Francielly Morena da Silva, Ana Regina Cabrera, Eleanor R. Schrems, et al. "Development of metabolic and contractile alterations in development of cancer cachexia in female tumor-bearing mice." Journal of Applied Physiology 132, no. 1 (January 1, 2022): 58–72. http://dx.doi.org/10.1152/japplphysiol.00660.2021.
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Our study demonstrates divergent tumor development and tissue wasting within 3- and 4-wk mice, where approximately half the mice developed large tumors and subsequent cachexia. Unlike previous male studies, where metabolic perturbations precede the onset of cachexia, females appear to exhibit protections from the metabolic perturbations and cachexia development. Our data provide novel evidence for divergent cachectic development in tumor-bearing female mice compared with previous male CC studies, suggesting different mechanisms of CC between sexes.
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Di Liberto, Diana, Massimo Locati, Nadia Caccamo, Annunciata Vecchi, Serena Meraviglia, Alfredo Salerno, Guido Sireci, et al. "Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection." Journal of Experimental Medicine 205, no. 9 (August 11, 2008): 2075–84. http://dx.doi.org/10.1084/jem.20070608.
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D6 is a decoy and scavenger receptor for inflammatory CC chemokines. D6-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis. The death of D6−/− mice was associated with a dramatic local and systemic inflammatory response with levels of M. tuberculosis colony-forming units similar to control D6-proficient mice. D6-deficient mice showed an increased numbers of mononuclear cells (macrophages, dendritic cells, and CD4 and CD8 T lymphocytes) infiltrating inflamed tissues and lymph nodes, as well as abnormal increased concentrations of CC chemokines (CCL2, CCL3, CCL4, and CCL5) and proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) in bronchoalveolar lavage and serum. High levels of inflammatory cytokines in D6−/− infected mice were associated with liver and kidney damage, resulting in both liver and renal failure. Blocking inflammatory CC chemokines with a cocktail of antibodies reversed the inflammatory phenotype of D6−/− mice but led to less controlled growth of M. tuberculosis. Thus, the D6 decoy receptor plays a key role in setting the balance between antimicrobial resistance, immune activation, and inflammation in M. tuberculosis infection.
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Tanaka, Tomohito, Ruri Nishie, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Hiromi Konishi, Shinichi Terada, et al. "Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review." International Journal of Molecular Sciences 22, no. 17 (August 29, 2021): 9369. http://dx.doi.org/10.3390/ijms22179369.
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Background: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. Methods: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. Results: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. Conclusion: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.
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Song, Mi Young, Seok Yong Kang, Anna Kang, Ji Hye Hwang, Yong-Ki Park, and Hyo Won Jung. "Cinnamomum cassiaPrevents High-Fat Diet-Induced Obesity in Mice through the Increase of Muscle Energy." American Journal of Chinese Medicine 45, no. 05 (January 2017): 1017–31. http://dx.doi.org/10.1142/s0192415x17500549.
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The cortex of Cinnamomum cassia Presl (Cinnamomi Cortex: CC) has commonly been used for weight control in traditional medicines, but without a scientific basis. Therefore, this study was undertaken to investigate the anti-obesity effect of CC extract in a high-fat diet (HFD)-induced obese mouse model and in C2C12 mouse skeletal muscle cells. Male C57BL/6 mice were fed a normal diet or a HFD for 16 consecutive weeks, and orally administered CC extract (100 or 300[Formula: see text]mg/kg) or metformin (250[Formula: see text]mg/kg; positive control) daily for 16 weeks. CC extract administration significantly decreased body weights, food intakes, and serum levels of glucose, insulin, total cholesterol and ALT levels, prevented oral glucose tolerance and insulin resistance, inhibited the protein expressions of MyHC and PGC1[Formula: see text] and the phosphorylation of AMPK, suppressed lipid accumulation in liver, decreased adipocyte size and increased muscle mass in obese mice. For this in vitro study, C2C12 myoblasts were differentiated into the myotubes for five days, and then treated with CC extract (0.1 or 0.2[Formula: see text]mg/ml) for 24[Formula: see text]h. CC extract significantly increased ATP levels by increasing the mRNA expressions of mitochondrial biogenesis-related factors, such as, PGC1[Formula: see text], NRF-1, and Tfam, and the phosphorylations of AMPK and ACC. Our results suggest CC extract controls weight gain in obese mice by inhibiting lipid accumulation and increasing energy expenditure, and that its action mechanism involves the up-regulation of mitochondrial biogenesis in skeletal muscle cells.
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D’Arcangelo, Gabriella. "Rapamycin treatment suppresses epileptogenic activity in conditionalPtenknockout mice." Cell Cycle 9, no. 13 (July 2010): 2487–88. http://dx.doi.org/10.4161/cc.9.13.12272.
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Marches, R., R. Scheuermann, and J. Uhr. "Cancer Dormancy from Mice to Man: A Review." Cell Cycle 5, no. 16 (August 2, 2006): 1772–78. http://dx.doi.org/10.4161/cc.5.16.2995.
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Blackwell, Thomas A., Igor Cervenka, Bhuwan Khatri, Jacob L. Brown, Megan E. Rosa-Caldwell, David E. Lee, Richard A. Perry, et al. "Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice." Physiological Genomics 50, no. 12 (December 1, 2018): 1071–82. http://dx.doi.org/10.1152/physiolgenomics.00061.2018.
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Cancer-cachexia (CC) is a wasting condition directly responsible for 20–40% of cancer-related deaths. The mechanisms controlling development of CC-induced muscle wasting are not fully elucidated. Most investigations focus on the postcachectic state and do not examine progression of the condition. We recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations before wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Lewis lung carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wk of age with tumor allowed to develop for 1, 2, 3, or 4 wk and compared with PBS-injected control. Muscle wasting was evident at 4 wk LLC. RNA sequencing of gastrocnemius muscle samples showed widespread alterations in LLC compared with PBS animals with largest differences seen in 4 wk LLC, suggesting extensive transcriptomic alterations concurrent to muscle wasting. Commonly altered pathways included: mitochondrial dysfunction and protein ubiquitination, along with other less studied processes in this condition regulating transcription/translation and cytoskeletal structure. Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.
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Umukoro, Solomon, Somtochukwu Ogboh, Osarume Omorogbe, Abdul-lateef Adekeye, and Matthew Olatunde. "Evidence for the Involvement of Monoaminergic Pathways in the Antidepressant-Like Activity of Cymbopogon citratus in Mice." Drug Research 67, no. 07 (May 12, 2017): 419–24. http://dx.doi.org/10.1055/s-0043-106586.
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Abstract Objectives Depression is a complex neuropsychiatric disorder, which affects the quality of life of the sufferers and treatment approach is associated with serious adverse effects and sometimes therapeutic failures. Cymbopogon citratus leaf (CC) has been reported to exert anti-depressant effect but its mechanism of action is yet to be elucidated hence, the need for this study. Methods The anti-depressant-like effect of Cymbopogon citratus aqueous leaf was evaluated using forced swim test (FST), tail suspension test (TST) and yohimbine-induced lethality test (YLT) in aggregated mice. Interaction studies involving p-chlorophenylalanine (pCPA), an inhibitor of serotonin biosynthesis and yohimbine, α2-adrenergic receptor antagonist were carried out to evaluate the role of monoaminergic system in the anti-depressant-like effect of CC. The effect of CC on spontaneous motor activity (SMA) was also assessed using activity cage. Results Cymbopogon citratus (25 and 50 mg/kg, p.o.) demonstrated antidepressant-like activity devoid of significant stimulation of the SMA in mice. However, the antidepressant-like property of CC was significantly (p<0.05) attenuated by pretreatment with yohimbine suggesting involvement of noradrenergic pathway in the action of the extract. Also, pCPA reversed the anti-immobility effect of CC, indicating the role of serotonergic system in the mediation of its antidepressant activity. Moreover, CC (25 and 50 mg/kg) potentiated the lethal effect of yohimbine in aggregated mice, which further suggest the involvement of monoaminergic systems in its action. Conclusions The results of the study showed that C. citratus might be interacting with serotonergic and noradrenergic pathways to mediate its anti-depressant-like effect in mice.
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Martin, Matthew D., Ramakrishna Sompallae, Christina Winborn, John T. Harty, and Vladimir P. Badovinac. "Diverse CD8 T cell responses to infection revealed by the collaborative cross." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 95.16. http://dx.doi.org/10.4049/jimmunol.204.supp.95.16.
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Abstract Enhanced host protection against re-infection requires generation of memory T cells of sufficient quantity and functional quality. Unlike well-studied inbred mice, T cell responses of diverse size and quality are generated following infection of humans and outbred mice. Thus, additional models are needed that more accurately reflect variation in immune outcomes in genetically diverse populations and to uncover underlying genetic causes. The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in this pursuit due to the high degree of genetic variation present and because it allows for assessment of genetic factors underlying unique phenotypes. The objectives of this study were to determine if the CC models diversity of immune outcomes seen in the human population, and if it could be used to identify genetic factors contributing to the generation of qualitatively and quantitatively distinct memory CD8 T cells. To this end, we analyzed the T cell response following acute LCMV Armstrong infection in 47 strains of CC mice. We found variability in resting immune cell composition and adaptive immune responses generated among CC strains in response to infection and reveal quantitative trait loci and candidate genes responsible for generation of CD62L+ memory CD8 T cells. Our results support the use of the CC to model diversity in immune responses observed in genetically diverse organisms and to uncover regulatory networks and host genetic factors underlying diverse immune outcomes following infection. This study and future studies utilizing the CC have the potential to improve translational efforts for the generation of protective immune responses against cancer and infections of global importance.
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Nansen, Anneline, Jan Pravsgaard Christensen, Susanne Ørding Andreasen, Christina Bartholdy, Jeanette Erbo Christensen, and Allan Randrup Thomsen. "The role of CC chemokine receptor 5 in antiviral immunity." Blood 99, no. 4 (February 15, 2002): 1237–45. http://dx.doi.org/10.1182/blood.v99.4.1237.
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The CC chemokine receptor CCR5 is an important coreceptor for human immunodeficiency virus (HIV), and there is a major thrust to develop anti-CCR5–based therapies for HIV-1. However, it is not known whether CCR5 is critical for a normal antiviral T-cell response. This study investigated the immune response to lymphocytic choriomeningitis virus in mice lacking CCR5 (CCR5−/− mice). This infection is a classical model for studying antiviral immunity, and influx of CCR5-expressing CD8+ T cells and macrophages is essential for both virus control and associated immunopathology. Results showed that the virus-induced clonal expansion of antigen-specific T cells was augmented in CCR5−/− mice especially with regard to the CD4+ subset. Despite absence of CCR5, intracerebral infection invariably resulted in lethal T cell-mediated meningitis, and quantitative and qualitative analysis of the inflammatory exudate cells did not reveal any significant differences between gene-targeted mice and wild-type controls. CCR5 was also found to be redundant regarding the ability to eliminate virus from internal organs. Using delayed-type hypersensitivity to evaluate CD8+ T cell-mediated inflammation, no significant influence of CCR5 was found, not even when viral peptide was used as local trigger instead of live virus. Finally, long-term CD8+ T cell-mediated immune surveillance was efficiently sustained in CCR5−/− mice. Taken together, these results indicate that expression of CCR5 is not critical for T cell-mediated antiviral immunity, and this molecule may therefore constitute a logic and safe target for anti-HIV therapies.
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Mehrabi, Syrina F., Souvik Ghatak, Lubna M. Mehdawi, Geriolda Topi, Shakti Ranjan Satapathy, and Anita Sjölander. "Brain-Derived Neurotrophic Factor, Neutrophils and Cysteinyl Leukotriene Receptor 1 as Potential Prognostic Biomarkers for Patients with Colon Cancer." Cancers 13, no. 21 (November 3, 2021): 5520. http://dx.doi.org/10.3390/cancers13215520.
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The tumor microenvironment has been recognized as a complex network in which immune cells play an important role in cancer progression. We found significantly higher CD66b neutrophil expression in tumor tissue than in matched normal mucosa in the Malmö colon cancer (CC) cohort and poorer survival of stage I-III patients with high CD66b expression. Additionally, mice lacking CysLT1R expression (cysltr1−/−) produce less brain-derived neurotrophic factor (BDNF) compared to WT mice and Montelukast (a CysLT1R antagonist)-treated mice also reduced BDNF expression in a mouse xenograft model with human SW480 CC cells. CD66b and BDNF expression was significantly higher in patient tumor tissues than in the matched normal mucosa. The univariate Cox PH analysis yielded CD66b and BDNF as an independent predictor of overall survival, which was also found in the public TCGA-COAD dataset. We also discovered a strong positive correlation between CD66b, BDNF and CysLT1R expression in the Malmö CC cohort and in the TCGA-COAD dataset. Our data suggest that CD66b/BDNF/CysLT1R expression as a prognostic combined biomarker signature for CC patients.
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Warren, Gordon L., Laura O'Farrell, Mukesh Summan, Tracy Hulderman, Dawn Mishra, Michael I. Luster, William A. Kuziel, and Petia P. Simeonova. "Role of CC chemokines in skeletal muscle functional restoration after injury." American Journal of Physiology-Cell Physiology 286, no. 5 (May 2004): C1031—C1036. http://dx.doi.org/10.1152/ajpcell.00467.2003.
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The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1α, MIP-1β, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradually returned to control (uninjured) levels by 14 days. Muscle function and histological characteristics were monitored in injured mice that were genetically deficient for the CCR5 receptor (a major receptor for MIP-1α and MIP-1β) and also rendered MCP-1 deficient with neutralizing antibodies. To dissect the role of these chemokines, additional studies were conducted in CCR5- and CCR2-deficient mice. CCR5-/- mice injected with MCP-1 antiserum for the first 3 days after injury exhibited a twofold greater maximal isometric tetanic torque deficit at 14 days after injury than did controls (i.e., 33% vs. 17%; P = 0.002). The impaired functional recovery was accompanied with an increased fat infiltration within the regenerating muscle without a significant difference in the influx of inflammatory cells, including macrophages. Strength recovery was also impaired in mice deficient for the receptor of MCP-1, CCR2, but not in CCR5-/- mice that were not injected with MCP-1 antiserum. The data suggest that MCP-1/CCR2 plays a role in the regeneration and recovery of function after traumatic muscle injury.
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Bui, Khac Cuong, Mai Ly Thi Nguyen, Samarpita Barat, Xi Chen, Vikas Bhuria, Jun Xing, Linh Toan Nguyen, et al. "Effect of AdipoR agonist in cholangiocarcinoma." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 323. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.323.
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323 Background: Adiponectin is the key adipokine, which plays an important role in health and disease such as obesity, diabetes, and cancer. Adiponectin is reduced in different tumor types, especially in obesity-related cancer, and recent studies showed that Adiponectin had a potential anti-cancer effect. Obesity is a risk factor for various tumor diseases including cholangiocarcinoma (CC), the second most common primary hepatic cancer. The aim of this study is to investigate for the first time the anti-cancer effect of AdipoR agonist in CC cell lines and a CC engineered mouse model. Methods: Human CC cell lines (TFK-1 and SZ-1) and CC engineered mice (Alb-Cre/KRASG12D/p53L/L) were used to investigate the anti-cancer effects of an AdipoR agonist (2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide). Cell proliferation, migration, invasion, colony formation, apoptosis assay were applied to evaluate the effect of AdipoR agonist in vitro. In addition, important cancer signalling pathways and targets were analysed by Western Blot. Mice (n = 12) were treated with AdipoR or verhicle and tumor burden and survival were monitored. Results: AdipoR agonist suppressed proliferation, migration, invasion, colony formation and apoptosis in CC cells. AdipoR agonist regulated the expression of different proteins such as EMT markers, pAMPK, pSTAT3, and PARP, which have pivotal functions in cholangiocarcinogenesis. AdipoR agonist also prolonged survival time in a CC engineered mouse model. Conclusions: Our data revealed that AdipoR agonist inhibited successfully cell proliferation, migration, invasion, colony formation and apoptosis in vitro, and prolonged mice survival in vivo through regulation of crucial signaling pathways in cholangiocarcinogenesis. These results suggested that AdipoR agonist might become a new potential candidate for CC treatment in the future.
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Moreno, Christophe, Charles Nicaise, Thierry Gustot, Eric Quertinmont, Nathalie Nagy, Marc Parmentier, Hubert Louis, and Jacques Devière. "Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute pancreatitis in mice." American Journal of Physiology-Gastrointestinal and Liver Physiology 291, no. 6 (December 2006): G1089—G1099. http://dx.doi.org/10.1152/ajpgi.00571.2005.
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Acute pancreatitis (AP) is an inflammatory disease involving the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands [the CC chemokines CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/regulated upon activation, normal T cell expressed and secreted (RANTES)] regulate leukocyte chemotaxis and activation, we investigated the expression of CCR5 ligands and the role of CCR5 and its ligands in experimental AP in mice. AP was induced by hourly intraperitoneal injections of cerulein in CCR5-deficient (CCR5−/−) or wild-type (WT) mice. Induction of AP by cerulein resulted in an early increase of pancreatic CCL2, CCL3, and CCL4 mRNA expression, whereas CCL5 mRNA expression occurred later. CCR5−/− mice developed a more severe pancreatic injury than WT mice during cerulein-induced AP, as assessed by a more pronounced increase in serum amylase and lipase levels and by more severe pancreatic edema, inflammatory infiltrates (mainly neutrophils), and necrosis. CCR5−/− mice also exhibited increased production of CCL2/MCP-1, CCL3/MIP-1α, and CCL4/MIP-1β during the course of cerulein-induced AP. In vivo simultaneous neutralization of CC chemokines with monoclonal antibodies in CCR5−/− mice reduced the severity of cerulein-induced AP, indicating a role of CC chemokines in exacerbating the course of AP in the absence of CCR5. Moreover, simultaneous neutralization of CCR5 ligands in WT mice also reduced the severity of cerulein-induced AP. In conclusion, lack of the chemokine receptor CCR5 exacerbates experimental cerulein-induced AP and leads to increased levels of CC chemokines and a more pronounced pancreatic inflammatory infiltrate, suggesting that CCR5 expression can modulate severity of AP.
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Loegito, Mas, Paulus Liben, and Thin Soedarti. "PENGARUH PERASAN UMBI AKAR LOBAK (Rhapanus sativus L) TERHADAP PENINGKATAN KADAR PROLAKTIN DALAM DARAH MENCIT (Mus musculus) BETINA." Berkala Penelitian Hayati 11, no. 2 (June 30, 2006): 135–37. http://dx.doi.org/10.23869/bphjbr.11.2.20066.
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The objective of this research was to prove that the administration of radish tuber extract (Rhapanus sativus L) to female mice (Mus musculus) might increase blood prolactin level. This was an experimental research using complete randomized design by involving three treatment groups and three control group, each with five replications. Materials consisted of radish tuber extract and 30 female mice of 8 weeks old divided into 6 groups, i.e., control groups of C1, C2, and C3, and treatment groups of T1, T2, and T3. C1, C2, and C3 groups were given water of 1x 0.5 cc/day per oral, 2x0.5 cc/day, and 3x0.5 cc/day respectively. Treatment groups of T1, T2, and T3 were given radish tuber extract of respectively 1x0.5 cc/day per oral, 2x0.5 cc/day, and 1x0.5 cc/day. Treatment was carried out for 21 days. Blood was subsequently taken from those rats for blood prolactin level. Data were analyzed using Anove test. If the results indicated significant difference of 95 percent (p = 0.05), the analysis was continued with LSD. The conclusions of this experiment is the administration of radish tuber extract per oral may result in the increase of blood prolactin level.
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Murray, Stephen A., and Thomas Gridley. "Snail1 Gene Function During Early Embryo Patterning in Mice." Cell Cycle 5, no. 22 (November 2, 2006): 2566–70. http://dx.doi.org/10.4161/cc.5.22.3502.
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Lai, Edwin W., Olga C. Rodriguez, Maral Aventian, Caroline Cromelin, Stanley T. Fricke, Lucia Martiniova, Irina A. Lubensky, et al. "ErbB-2 Induces Bilateral Adrenal Pheochromocytoma Formation in Mice." Cell Cycle 6, no. 15 (August 2007): 1946–50. http://dx.doi.org/10.4161/cc.6.15.4521.
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Smibert, Peter, and Eric C. Lai. "Lessons from microRNA mutants in worms, flies and mice." Cell Cycle 7, no. 16 (August 15, 2008): 2500–2508. http://dx.doi.org/10.4161/cc.7.16.6454.
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de Almeida, Cecilia J., Agnieszka K. Witkiewicz, Jean-François Jasmin, Herbert B. Tanowitz, Federica Sotgia, Philippe G. Frank, and Michael P. Lisanti. "Caveolin-2-deficient mice show increased sensitivity to endotoxemia." Cell Cycle 10, no. 13 (July 2011): 2151–61. http://dx.doi.org/10.4161/cc.10.13.16234.
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Sugiyama, Daisuke, Hiroko Sugiyama, and Nancy A. Speck. "A Role for Twist in Thymocyte Development." Blood 106, no. 11 (November 16, 2005): 4252. http://dx.doi.org/10.1182/blood.v106.11.4252.4252.
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Abstract Twist-1 and Twist-2 are basic helix-loop-helix (bHLH)- containing transcription factors important for mesoderm and muscle formation, and for osteoblast differentiation. The Twist proteins were previously shown to interact both physically and genetically with Runx2, a member of the core binding factor family of transcription factors (Bialek et al. Dev. Cell6: 423, 2004). Twist-1 and Twist-2 transiently inhibit Runx2 function during bone formation by inhibiting DNA binding by the Runx2 Runt domain. Since the Runt domains of the core binding factors are highly conserved, this raised the possibility that the Twist proteins may also regulate Runx1 function in hematopoiesis. To address this hypothesis we used Charlie Chaplin (CC) mice, which contain a hypomorphic Twist-1 allele generated by N-ethyl-N-nitrosourea (ENU) mutagenesis (Justice, Nat. Rev. Genet.1: 109, 2000). The CC allele encodes a single amino acid substitution (Ser192Pro) in the Twist box of Twist-1, which normally interacts with the Runt domain. CC/CC mice die from an unknown cause shortly after birth, and have small thymuses. No other hematopoietic organs show significant differences in cellularity. The number of bone marrow hematopoietic progenitors is almost identical among CC/CC, CC/+, and +/+ littermates as assessed by flowcytometry and colony forming assays. The ratios of CD4/CD8 single positive cells, and DN1-4 thymocytes are unperturbed, suggesting that T cell maturation is normal in CC/CC fetuses. However, CC/CC thymuses are reconstituted by wild type bone marrow at a lower efficiency than are wild type thymuses in fetal thymus organ culture assays, suggesting that Twist-1 may have an important non-cell autonomous role in thymocyte development.
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Han, Booyeon Julia, Nathania Figueroa, Brian Belt, Michael O'Dell, Aram F. Hezel, and David Linehan. "Mice with targeted KrasG12D and loss of p53 in the liver: A robust model for studying immunologic interventions for treating cholangiocarcinoma." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 281. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.281.
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281 Background: Inflammation in the tumor microenvironment—chronically elevated cytokines, chemokines, and inflammatory cells—promotes tumorigenesis. Cholangiocarcinoma (CC) is the most common liver malignancy within the biliary tree with few treatment options and a poor 5-year survival. CC tumors are characterized with a dense tumor stroma and abundant inflammatory immune cell infiltrate, yet little is known about the immune dynamics underlying the disease. Here, we characterize immune signaling pathways in human CC and a spontaneous mouse model of the disease to identify potential targets susceptible to immune based therapies. Methods: Histology and immunohistochemistry (IHC) were performed on archived human specimens and tissue microarrays of 52 CC specimens constructed under an IRB approved protocol to identify the prognostic significance of cytokine and immune markers. Peripheral blood, bone marrow, and tissue from mice with targeted activation of KrasG12D and loss of p53 (Kras-p53-/-) in the liver that spontaneously developed CC tumors versus normal controls were collected and analyzed by histology, IHC, quantitative gene expression, and flow cytometry based studies. Results: High levels of inflammatory leukocytes in human CC were predominantly of monocytic and granulocytic origin including macrophages (TAM) and granulocytic-myeloid derived suppressor cells (G-MDSC) respectively. Malignant cells expressed high levels of CCL2 and TAM stained positive for its cognate receptor CCR2. In addition, CD8+ and CD4+ T cells expressing PD-1 were associated with PD-L1+ tumor cells. Kras-p53-/- mice developed CC tumors histologically similar to human disease: tumors had high levels of cytokines and induced myelopoiesis leading to significantly more monocytes and granulocytes in the bone marrow, blood, and spleen compared to normal liver controls. Tumors also expressed higher levels of CCL2 and PD-L1 with more CCR2+ TAMs and PD-1+ T cells compared to controls. Conclusions: Human CC utilizes immune signaling pathways and Kras-p53-/- mice recapitulate the immune dynamics of the disease representing a model to study immune based therapies for treating CC.
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Ulfhake, B., H. Lerat, J. Honetschlager, K. Pernold, M. Rynekrová, K. Escot, C. Recordati, et al. "A multicentre study on spontaneous in-cage activity and micro-environmental conditions of IVC housed C57BL/6J mice during consecutive cycles of bi-weekly cage-change." PLOS ONE 17, no. 5 (May 25, 2022): e0267281. http://dx.doi.org/10.1371/journal.pone.0267281.
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Mice respond to a cage change (CC) with altered activity, disrupted sleep and increased anxiety. A bi-weekly cage change is, therefore, preferred over a shorter CC interval and is currently the prevailing routine for Individually ventilated cages (IVCs). However, the build-up of ammonia (NH3) during this period is a potential threat to the animal health and the literature holds conflicting reports leaving this issue unresolved. We have therefor examined longitudinally in-cage activity, animal health and the build-up of ammonia across the cage floor with female and male C57BL/6 mice housed four per IVC changed every other week. We used a multicentre design with a standardised husbandry enabling us to tease-out features that replicated across sites from those that were site-specific. CC induce a marked increase in activity, especially during daytime (~50%) when the animals rest. A reduction in density from four to two mice did not alter this response. This burst was followed by a gradual decrease till the next cage change. Female but not male mice preferred to have the latrine in the front of the cage. Male mice allocate more of the activity to the latrine free part of the cage floor already the day after a CC. A behaviour that progressed through the CC cycle but was not impacted by the type of bedding used. Reducing housing density to two mice abolished this behaviour. Female mice used the entire cage floor the first week while during the second week activity in the latrine area decreased. Measurement of NH3 ppm across the cage floor revealed x3 higher values for the latrine area compared with the opposite area. NH3 ppm increases from 0–1 ppm to reach ≤25 ppm in the latrine free area and 50–100 ppm in the latrine area at the end of a cycle. As expected in-cage bacterial load covaried with in-cage NH3 ppm. Histopathological analysis revealed no changes to the upper airways covarying with recorded NH3 ppm or bacterial load. We conclude that housing of four (or equivalent biomass) C57BL/6J mice for 10 weeks under the described conditions does not cause any overt discomfort to the animals.
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Jensen, Isaac J., Matthew D. Martin, Sandeep K. Tripathy, Vladimir P. Badovinac, and Donna L. Farber. "Novel mouse model of MCMV-induced adaptive NK cells." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 126.07. http://dx.doi.org/10.4049/jimmunol.208.supp.126.07.
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Abstract NK cells are important mediators of viral control with the capacity to form adaptive immune features following infection. However, studies of infection-induced adaptive NK cells require adoptive cell transfer to lower the precursor frequency of ‘antigen-specific’ NK cells, potentially limiting the diversity of the NK cell response. In seeking an unmanipulated model to probe the adaptive NK cells, we interrogated a wide range of Collaborative Cross (CC) inbred mice, inbred mouse strains which exhibit broad genetic diversity across strains. Our assessment identified and validated a putative ‘ideal’ CC strain, CC006, which does not require manipulation to generate and maintain adaptive NK cells. Critically, CC006 mice, in contrast to C57Bl/6 mice, are capable of developing enhanced NK cell-mediated protective responses to MCMV infection following m157-mediated vaccination. This work both furthers our understanding of adaptive NK cells and demonstrates the utility of CC mice in the development and interrogation of immunologic models. Supported by T32AI007511 (IJJ), T32AI007485 (IJJ), 5R01AI114543 (VPB), 1R35GM134880 (VPB), U01-AI150680 (DLF)
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Lang, Undine E., Teresa F. Ackermann, David Wolfer, Florian Schubert, Reinhard Sohr, Heide Hörtnagl, Florian Lang, and Juergen Gallinat. "Phosphoinositide-Dependent Protein Kinase 1 (PDK1)." Zeitschrift für Psychologie 223, no. 3 (July 2015): 165–72. http://dx.doi.org/10.1027/2151-2604/a000217.
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Abstract. Phosphatidylinositol-3-kinase (PI3K) signaling influences susceptibility to virus infections, anoxia, obstetric complications, and cancer; which are changed in patients with schizophrenia and their first degree relatives. Therefore PI3K signaling might have impact on the pathophysiology of schizophrenia. PI3K signaling crucially involves phosphoinositide-dependent protein kinase (PDK1). Increased anxiety behavior is observed in PDK1 hypomorphic mice. Here we show enhanced prevalence of schizophrenia in carriers of the PDK1 CC genotype in human beings. Moreover, decreased parietal P300 amplitude, which is a well-studied schizophrenic endophenotype, was observed in PDK1 CC carriers. Glutamate and glutamine concentrations are increased in the frontal lobe of PDK1 dysmorphic mice and human CC individuals. Our results demonstrate that the PDK1 CC genotype is associated with increased risk to develop schizophrenia, a typical endophenotype profile observed in the disease and modified neurotransmitter concentrations in brain regions associated with the disease.
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Prabowo, Nurhasan Agung, Zainal Arifin Adnan, Arief Nurudhin, Yulyani Werdiningsih, and Kukuh Prasetyo. "Mesenchymal Stem Cell Conditioned Medium as Good as Methyl Prednisolone in Decreasing Levels of Interleukin 10 and The Degree of Pulmonary Vasculitis in Lupus Mice." Bangladesh Journal of Medical Science 20, no. 2 (February 1, 2021): 426–30. http://dx.doi.org/10.3329/bjms.v20i2.51560.
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Background: Systemic lupus erythematosus is a chronic autoimmune disease that affects target organs. mesenchymal stem cell conditioned medium has immunosuppressive, anti-inflammatory, and immunoregulatory properties in lupus. Methyl prednisolone is a standard drug for lupus with immunosuppressive and anti-inflammatory properties. This study aims to compare the therapeutic effect of mesenchymal stem cell conditioned medium administration compared to methyl prednisolone on interleukin 10 levels and the degree of pulmonary vasculitis of lupus mice.
Methods: The subjects were 24 female mice of Mus musculus Balb/C strain, which were categorized into 4 groups of 8 mice, i.e. the control group receiving 0.5 cc of 0.9% NaCl injection and placebo, the lupus group receiving 0.5 cc of pristane injection and placebo, and the treatment mesenchymal stem cell conditioned medium group receiving 0.5 cc pristane injection and mesenchymal stem cell conditioned medium 0,5 cc, and methylprednisolone group receiving 0,5 cc pristiane injection and methylprednisolone p.o 1,5 mg/kgbodyweight. After 24 days the mice were terminated and kidney and blood samples were taken. Statistical analysis was performed using ANOVA test followed by independent T-test. The p value was considered significant when the p < 0.05.
Results: The study showed that there was no difference on the levels of interleukin level10 among mesenchymal stem cell conditioned medium goup and methyl prednisolone group (CM = 5,94 ± 2,49 pg/mL, mp = 5,86+1,73 pg/mL; p = 1) and the degree of pulmonary vasculitis (CM= 1,94 ± 0,25, MP=1,89+ 0,11 pg/ml; p = 0.667). Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice.
Conclusion: Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice
Bangladesh Journal of Medical Science Vol.20(2) 2021 p.426-430
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Henning, Golo, Lars Ohl, Tobias Junt, Phillip Reiterer, Volker Brinkmann, Hideki Nakano, Werner Hohenberger, Martin Lipp, and Reinhold Förster. "CC Chemokine Receptor 7–dependent and –independent Pathways for Lymphocyte Homing." Journal of Experimental Medicine 194, no. 12 (December 17, 2001): 1875–81. http://dx.doi.org/10.1084/jem.194.12.1875.
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Cognate interaction of chemokine receptor CCR7 on lymphocytes with its ligands CCL19 and CCL21 expressed on high endothelial venules (HEVs) is essential for effective migration of T and B cells across HEVs into secondary lymphoid organs. Plt mice, which lack expression of CCL19 and CCL21-ser, both ligands for CCR7 on HEVs, as well as CCR7-deficient mice, have a defective cell migration and reduced homing of lymphocytes. FTY720, a novel immunosuppressant, causes a reduction of lymphocytes in peripheral blood and tissues and their sequestration into lymphoid tissues. In this study we demonstrate that FTY720 rescues the homing defect in both CCR7−/− mice and plt mice. After FTY720 treatment, the number of CD4+ and CD8+ T cells as well as B cells in peripheral blood is reduced while pertussis toxin–sensitive homing into peripheral lymph nodes, mesenteric lymph node, and Peyer's patches is increased. Immunohistology demonstrates that FTY720 enables these cells to enter lymphoid tissue through HEVs. Thus, our data suggest an alternative G-αi-dependent, CCR7-CCL19/CCL21-independent mechanism for lymphocyte homing through HEVs which is strongly augmented in the presence of FTY720.
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Turner, Brie E., Melinda Christensen, Janusz Lange, Ann-Marie Burns, Derek N. J. Hart, Kerry Atkinson, David J. Munster, and Alison M. Rice. "Conditioning Intensity and Dendritic Cell (DC) Activation: Implications for GVHD Control Using DC Depleting Antibodies." Blood 106, no. 11 (November 16, 2005): 3112. http://dx.doi.org/10.1182/blood.v106.11.3112.3112.
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Abstract Graft versus Host Disease (GVHD) and treatment related mortality (TRM) are the major limitations to the widespread application of allogeneic haematopoietic stem cell transplantation (HSCT) for haematological and non-haematological malignancies. Dendritic cells (DC) as the key initiators and directors of the immune response are central to allogeneic transplant interactions. Preparative conventional conditioning (CC) regimens aim to control disease and ablate the host immune response to facilitate normal haematopoietic reconstitution. The conditioning also unleashes a cytokine storm that activates the residual host immune system, driving host DC and donor T cell interactions that result in GVHD. Reducing the intensity of conditioning (RIC) regimens maintains immune anti-leukaemic activity of T replete HSCT, reduces TRM and delays the onset of GVHD, but the overall incidence of GVHD is unchanged. We hypothesise that this is due to increased persistence of host DC. We propose that strategic administration of DC depleting antibodies could be an effective means to control GVHD. Whilst there is some information on the effects of CC on DC; we have shown that mature plasmacytoid (p) DC are increased in mouse spleen after conditioning by radiation, there is no information on the effects of RIC on DC. We have established murine models of conditioning (CC = Cyclophosphamide [CY] + 800cGy and RIC = Fludarabine [FLU] + CY + 200cGy). The effects on DC numbers, activation and subset composition (myeloid (m) DC and DC), cytokine and systemic endotoxin levels were studied on each day of the conditioning regimens in the absence of HSCT. Mice receiving CC have a significantly higher percentage of DC which are pDC compared to RIC (p<0.001) which results in a decrease in the overall percentage of mDC. However, mice that received RIC have significantly higher absolute numbers of host pDC than CC mice. Preliminary data shows no difference in endotoxin levels in mice receiving RIC or CC without HSCT. However, there may be a transient increase in endotoxin levels in mice after 2 FLU injections (p=0.12). No such increase was seen after CC. There were significantly higher levels of TNF-α (p=0.02) and IL1-β (p=0.03) in mice receiving RIC rather than CC without HSCT. The higher absolute numbers of DC, altered subset ratio and cytokine production appears to account for the delayed onset of GVHD in RIC transplant recipients. Intra-peritoneal (ip) injection of N418, a monoclonal antibody to mouse leukocyte integrin CD11c depleted murine DC in vivo. Preliminary experiments show elimination of 50% of DC after injection of N418 (500mg). Subsequent experiments show that 1mg of N418 is sufficient to significantly delay, but not prevent, GVHD in a full MHC mismatched model of HSCT (p=0.025). The action of N418 is specific, as DC depletion was not seen in mice treated with 1 mg hamster Ig. Together, these observations suggest that increasing antibody concentration and prolonged administration may be required to prevent GVHD. The successful application of DC depletion to control GVHD will improve the safety of HSCT for patients with leukaemia.
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Ireton, Renee C., Aimee McMillan, Sunil Thomas, Piper Treuting, Kathleen Voss, Duncan Hendrick, Courtney Wilkins, et al. "Pathobiology of West Nile Virus infection in the Collaborative Cross mouse model." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 217.37. http://dx.doi.org/10.4049/jimmunol.196.supp.217.37.
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Abstract West Nile Virus (WNV) is an emerging neuroinvasive flavivirus that causes serious encephalitis disease that is lethal in 6% of human cases. The immunopathology of WNV infection has been well-studied in C57BL/6J mice, but the model lacks the diversity in susceptibility and outcomes that are observed in humans, thus limiting its usefulness as a model to understand the host genetics and overall breadth of WNV infection outcomes and immune response. We are using the Collaborative Cross (CC) mouse model to evaluate the pathobiology and immune regulation that underlies WNV disease progression and neuroinvasion. Our studies reveal that the CC model captures the diversity in susceptibility and outcomes of WNV observed in humans. We generated a standardized histology scoring system to evaluate viral localization and immunopathology of WNV infection in tissue including brain isolates from CC lines. Our studies show a diverse array of histological phenotypes that link with the susceptibility and disease outcomes of the CC mice with WNV infection. Time course studies also showed variation in the temporal progression of viral induced-pathology and immunopathogenesis among different CC lines. Our findings show that the CC model of WNV is a relevant and powerful mouse model for mechanistic studies of WNV infection and neuropathology. Application of the CC model to genetic mapping of quantitative trait loci that impart immune regulation of WNV infection will be presented.
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Enriquez, Josue, Brianyell T. McDaniel, Kathryn Furr, and Matthew B. Grisham. "Susceptibility of genetically diverse outbred mice to acute graft vs. host disease (aGVHD)." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 87.31. http://dx.doi.org/10.4049/jimmunol.204.supp.87.31.
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Abstract Mice are the primary animal of choice for modeling aGVHD. One aspect of these mouse models that may limit translation of promising therapeutic strategies to patient treatment is the use inbred mice as surrogates for genetically diverse human populations. Objective Quantify and compare tissue inflammation and injury in inbred vs. genetically diverse outbred mice using a well-characterized model of aGVHD-mediated bone marrow (BM) failure and spleen hypoplasia. Methods C57Bl6 (Bl6) CD4+ T cells (20,000 T cells/g b.w.) were injected (i.p.) into sub-lethally irradiated Bl6-H2-Ab1bm12(BM12) recipients (Bl6→BM12) or into Collaborative Cross (CC) or CD1 outbred recipients. Results Adoptive transfer of allogeneic Bl6 T cells into BM12 recipients induced marked weight loss (25%) at 20 days post T cell transfer that was associated with dramatic reductions in hematocrit as well as large and significant decreases in circulating granulocytes, platelets and erythrocytes when compared to their syngeneic controls (BM12→BM12). Total cell numbers in BM and spleen were also found to be dramatically reduced in these mice. Histopathological inspection confirmed severe hypocellularity in BM and spleen whereas no aGVHD was present in the lungs, liver, skin and colon. In contrast, adoptive transfer of Bl6 T cells into sub-lethally irradiated CC or CD1 or CC mice induced little or no weight loss at 25–30 days post T cell transfer with no significant reductions in hematocrit, circulating leukocytes, erythrocytes or platelets. BM- and spleen-associated cell numbers were not reduced when compared their CC controls. Conclusions Genetically diverse outbred mice are resistant to aGVHD-mediated BM failure and spleen hypoplasia.
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Qin, Zhenxian, Wei Wang, Dengqun Liao, Xiaoying Wu, and Xian’en Li. "UPLC-Q/TOF-MS-Based Serum Metabolomics Reveals Hypoglycemic Effects of Rehmannia glutinosa, Coptis chinensis and Their Combination on High-Fat-Diet-Induced Diabetes in KK-Ay Mice." International Journal of Molecular Sciences 19, no. 12 (December 11, 2018): 3984. http://dx.doi.org/10.3390/ijms19123984.
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Diabetes is a worldwide severe health issue which causes various complications. This study aimed to evaluate the hypoglycemic effects of Rehmannia glutinosa (RG), Coptis chinensis (CC) alone and their combination on high-fat-diet-induced diabetes in mice via biochemical assays and UPLC-Q/TOF-MS-based serum metabolomic analysis. Diabetic KK-Ay mice were induced by high-fat diet and treated for eight weeks, separately with RG, CC and their combination and the positive control drug metformin. Administration of RG and CC alone, and their combination could decrease the fasting blood glucose level, ameliorate the tolerance of glucose, and recover the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in sera of diabetic mice. Orthogonal partial least squares discriminant analysis (OPLS-DA) on serum metabolomes revealed that 79 ESI+ and 76 ESI− metabolites were changed by diabetes mellitus (DM) compared to the normal control. Heatmaps on these diabetes-related metabolites showed that CC and RG/CC were clustered closer with the normal control, indicating that they had the better antidiabetic effects at the metabolite level. Fifteen of the differential metabolites in DM serum were annotated and their related metabolic pathways were lipid metabolism. These data suggested that RG and CC alone and in combination treatment had the antidiabetic activity in lowering glycemia and improving lipid metabolism. UPLC-Q/TOF-MS-based metabolomics shed light on the differential metabolite effects of RG and CC in DM treatment. However, it should be noted that some differential metabolites were possibly generated or not detected due to our groupwise run order, which possibly contributed to or covered the group difference in our experiment. They need to be further discriminated in the future work.
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Wang, Pin, Yunshan Wang, Sasha A. Langley, Yan-Xia Zhou, Kuang-Yu Jen, Qi Sun, Colin Brislawn, et al. "Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis." Gut 68, no. 11 (March 6, 2019): 1942–52. http://dx.doi.org/10.1136/gutjnl-2018-316691.
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ObjectiveThe Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum.DesignWe monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of ISG15 by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis.ResultsCC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified Nfκb1 as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS.ConclusionsCC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.
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Shomper, Maria, Christina Lappa, and Greg FitzHarris. "Kinetochore microtubule establishment is defective in oocytes from aged mice." Cell Cycle 13, no. 7 (February 11, 2014): 1171–79. http://dx.doi.org/10.4161/cc.28046.
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Kosmider, Olivier, and Françoise Moreau-Gachelin. "From Mice to Human: The “Two-Hit Model” of Leukemogenesis." Cell Cycle 5, no. 6 (February 7, 2006): 569–70. http://dx.doi.org/10.4161/cc.5.6.2577.
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Merlet, Jorge, Evelyne Moreau, René Habert, and Chrystèle Racine. "Development of Fetal Testicular Cells in Androgen Receptor Deficient Mice." Cell Cycle 6, no. 18 (September 15, 2007): 2258–62. http://dx.doi.org/10.4161/cc.6.18.4654.
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