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61.
Mohamed El-Sherbiny Mohamed Ahmed Eladl Anu Vinod Ranade Maha Guimei Hala Gabr 《Singapore medical journal》2020,61(1):39
INTRODUCTIONThis study aimed to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (UCBMSCs) among albino rats with streptozotocin (STZ)-induced diabetes mellitus.METHODSControl group (GI; n = 25) rats were fed with standard rat diet. Rats with STZ-induced diabetes mellitus without (GII; n = 25) and with (GIII; n = 25) differentiated human UCBMSCs implantation were the test groups. Rats were sacrificed in Week 11 following implantation. Liver biopsies were sectioned and stained in order to highlight both the presence and function of impregnated cells in the liver tissue.RESULTSHaematoxylin and eosin-stained sections in GI and GII rats showed normal liver architecture while GIII rats showed presence of cell clusters inside the liver tissue and around the central veins. Cell clusters with blue cytoplasm were present in sections in GIII rats but absent in GI and GII rats, indicating the presence of injected differentiated human UCBMSCs. The anti-human insulin immunostaining of GIII rats showed clusters of cells within the liver parenchyma and around central veins, indicating that these cells were active and secreting insulin.CONCLUSIONUCBMSCs are proficient in differentiating into insulin-producing cells in vivo under specific conditions and, when transplanted into the liver of albino rats with STZ-induced diabetes mellitus, were able to secrete insulin and partially control the status of diabetes mellitus in rats. 相似文献
62.
Ahmed Elhassanny Rene Escobedo Daniel Ladin Colin Burns Rukiyah Van Dross 《Oncotarget》2020,11(52):4788
Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15dPMJ2). As such, the current study investigates whether 15dPMJ2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ2-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ2-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ2 and the ER stress pathway. These results demonstrate that 15dPMJ2 is a tumor-selective inducer of DAMP signaling in melanoma. 相似文献
63.
64.
Xiaoxuan Liu Ameenat L. Solebo Livia Faes Sophie Beese Tasanee Braithwaite Matthew E. Round 《Ocular immunology and inflammation》2020,28(6):898-907
ABSTRACT
Purpose
New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. 相似文献65.
Regina K. Rowe David M. Pyle J. David Farrar Michelle A. Gill 《European journal of immunology》2020,50(10):1550-1559
Rhinovirus (RV) infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate DC antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 development. In this study, we investigate the effects of IgE-mediated stimulation on monocyte-driven, RV-induced T cell development utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 differentiation. This increase in RV-induced Th2 development was regulated by IgE-mediated inhibition of virus-induced type I IFN and induction of IL-10. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations—IgE-mediated stimulation and rhinovirus infection—may synergistically promote Th2 differentiation and allergic inflammation. 相似文献
66.
《Molecular immunology》2015,63(2):296-304
Regulatory B cells (Bregs) are defined by their ability to restrain inflammatory responses both in vivo and in vitro. Interleukin 10 (IL-10) production by Bregs is thought to be central to their ability to regulate inflammation, largely due to IL-10s’ ability to suppress pro-inflammatory cytokine production by effector lymphocytes and to maintain the differentiation of regulatory T cells (Tregs). However, with an increase in available published data, it has become evident that Bregs utilize a number of suppressive mechanisms in order to alter the activation of a variety of different lymphocytes. Here, we summarize the multiplicity of cellular targets of Breg-mediated suppression and describe the mechanisms employed by Bregs to suppress chronic inflammatory responses. 相似文献
67.
ObjectiveProgrammed death ligand 1 (PD-L1) has been reported to be connected to prognosis in individuals with malignant pleural mesothelioma (MPM), although there is no consensus based on data from previous studies. Accordingly, this quantitative meta-analysis investigated prognostic and clinicopathological utility of PD-L1 in patients with MPM.MethodsA comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases for articles published up to October 4, 2019 was performed. Studies using immunohistochemical techniques to detect/quantify the expression of PD-L1 in MPM tissue were enrolled in the analysis. The combined hazard ratio (HR) and corresponding 95% confidence interval (CI) was applied to assess the association between PD-L1 expression and overall survival (OS).ResultsA total of 11 studies comprising 1606 patients was included in the present meta-analysis. For OS, pooled data revealed an HR of 1.50 (95% CI 1.32–1.70; p < 0.001), suggesting that patients with PD-L1 overexpression experience inferior OS. Subgroup analysis revealed that elevated PD-L1 remained a significant prognostic indicator for worse OS, irrespective of sample size, cut-off value, ethnicity, and Newcastle-Ottawa Scale score. Moreover, PD-L1 overexpression was associated with non-epithelioid histology (odds ratio 4.30 [95% CI 1.89–9.74]; p < 0.001).ConclusionsResults of this meta-analysis show that elevated expression of PD-L1 could be a factor predicting poorer survival in patients with MPM. 相似文献
68.
AbstractThe autoimmune condition Hashimoto’s thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. In this study, we utilize female SD rats induced HT to evaluated the ability of transplanted MSCs to regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. The results showed that Rats in the HT model group exhibited increased thyroid autoantibody levels consistent with successful model development, whereas these levels were lower in rats treated with MSCs. There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells – an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto’s thyroiditis. 相似文献
69.
Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs
Mariam Naveed Amjad Ali Nadeem Sheikh Shazia Rafique Muhammad Idrees 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2020,128(4):326-334
Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective. 相似文献
70.
目的 研究养精胶囊促进小鼠精原干细胞(SSCs)增殖的分子机制。方法 将不同浓度的养精胶囊提取物加入SSCs中培养48 h,CCK-8检测细胞的增殖活性,流式细胞仪检测细胞周期,荧光素酶报告基因检测Cyclin D1启动子的活性,qRT-PCR以及免疫荧光检测Cyclin D1的表达。之后进行阻断实验,在加入养精胶囊前预先加入siRNA-Cyclin D1,同样的方法检测细胞的增殖活性、细胞周期、Cyclin D1启动子的活性以及Cyclin D1的表达情况。结果 低、中、高浓度的养精胶囊可以促进SSCs的增殖,提高S期细胞的比例,增强Cyclin D1启动子的活性,促进Cyclin D1的表达。阻断Cyclin D1后,SSCs的增殖活性降低,S期细胞比例减少,Cyclin D1启动子的活性降低,Cyclin D1的表达减少。结论 养精胶囊通过增强Cyclin D1启动子的活性提高Cyclin D1的转录和翻译水平,进而促进SSCs增殖。 相似文献