Latest Issue
Issue 10 ， 2019
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Regulation of bile acid metabolism-related signaling pathways by gut microbiota in diseases
Abstract：Over the past decade, there has been increasing attention on the interaction between microbiota and bile acid metabolism. Bile acids are not only involved in the metabolism of nutrients, but are also important in signal transduction for the regulation of host physiological activities. Microbial-regulated bile acid metabolism has been proven to affect many diseases, but there have not been many studies of disease regulation by microbial receptor signaling pathways. This review considers findings of recent research on the core roles of farnesoid X receptor (FXR), G protein-coupled bile acid receptor (TGR5), and vitamin D receptor (VDR) signaling pathways in microbial–host interactions in health and disease. Studying the relationship between these pathways can help us understand the pathogenesis of human diseases, and lead to new solutions for their treatments.Keywords：Gut microbiota;Bile acid;Farnesoid X receptor;Vitamin D receptor;Metabolism- 15
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Published：2022-01-05
Review
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Changes in peripheral blood inflammatory factors (TNF-α and IL-6) and intestinal flora in AIDS and HIV-positive individuals
Abstract：Objective:In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4+ T lymphocytes.Methods:Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4+ T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4+ T lymphocyte values were evaluated using the Spearman correlation coefficient.Results:The levels of TNF-α and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4+ T lymphocytes was lower. The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faecium were much higher. The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-α and IL-6 and the CD4+ T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium.Conclusions:The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4+ T lymphocytes and the levels of TNF-α and IL-6.Keywords：Acquired immune deficiency syndrome (AIDS);Tumor necrosis factor-α(TNF-α);Interleukin-6 (IL-6);Intestinal flora;CD4+ T lymphocytes- 20
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Published：2022-01-05 -
Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells#
Abstract：Activated nuclear factor-κB (NF-κB) plays an important role in the development of cardiovascular disease (CVD) through its regulated genes and microRNAs (miRNAs). However, the gene regulation profile remains unclear. In this study, primary mouse vascular endothelial cells (pMVECs) were employed to detect CVD-related NF-κB-regulated genes and miRNAs. Genechip assay identified 77 NF-κB-regulated genes, including 45 upregulated and 32 downregulated genes, in tumor necrosis factor α (TNFα)-treated pMVECs. Ten of these genes were also found to be regulated by NF-κB in TNFα-treated HeLa cells. Quantitative real-time PCR (qRT-PCR) assay confirmed the up-regulation of Egr1, Tnf, and Btg2 by NF-κB in the TNFα-treated pMVECs. The functional annotation revealed that many NF-κB-regulated genes identified in pMVECs were clustered into classical NF-κB-involved biological processes. Genechip assay also identified 26 NF-κB-regulated miRNAs, of which 21 were upregulated and 5 downregulated, in the TNFα-treated pMVECs. Further analysis showed that nine of the identified genes are regulated by seven of these miRNAs. Finally, among the identified NF-κB-regulated genes and miRNAs, 5 genes and 12 miRNAs were associated with CVD by miRWalk and genetic association database analysis. Taken together, these findings show an intricate gene regulation network raised by NF-κB in TNFα-treated pMVECs. The network provides new insights for understanding the molecular mechanism underlying the progression of CVD.Keywords：Cardiovascular disease;Nuclear factor-κB (NF-κB);MicroRNA;Endothelial cell- 18
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Published：2022-01-05 -
Catalpol ameliorates LPS-induced endometritis by inhibiting inflammation and TLR4/NF-κB signaling
Abstract：Catalpol is the main active ingredient of an extract from Radix rehmanniae, which in a previous study showed a protective effect against various types of tissue injury. However, a protective effect of catalpol on uterine inflammation has not been reported. In this study, to investigate the protective mechanism of catalpol on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and mouse endometritis, in vitro and in vivo inflammation models were established. The Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway and its downstream inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence techniques. The results from ELISA and qRT-PCR showed that catalpol dose-dependently reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, and chemokines such as C-X-C motif chemokine ligand 8 (CXCL8) and CXCL5, both in bEECs and in uterine tissue. From the experimental results of WB, qRT-PCR, and immunofluorescence, the expression of TLR4 and the phosphorylation of NF-κB p65 were markedly inhibited by catalpol compared with the LPS group. The inflammatory damage to the mouse uterus caused by LPS was greatly reduced and was accompanied by a decline in myeloperoxidase (MPO) activity. The results of this study suggest that catalpol can exert an anti-inflammatory impact on LPS-induced bEECs and mouse endometritis by inhibiting inflammation and activation of the TLR4/NF-κB signaling pathway.Keywords：Catalpol;Endometritis;Inflammation;Toll-like receptor 4 (TLR4);Nuclear factor-κB (NF-κB)- 124
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Published：2022-01-05 -
Protective effects of methane-rich saline on mice with allergic asthma by inhibiting inflammatory response, oxidative stress and apoptosis
Abstract：Background:Asthma is a common cause of breathing difficulty in children and adults, and is characterized by chronic airway inflammation that is poorly controlled by available treatments. This results in severe disability and applies a huge burden to the public health system. Methane has been demonstrated to function as a therapeutic agent in many diseases. The aim of the present study was to explore the effect of methane-rich saline (MRS) on the pathophysiology of a mouse model of asthma and its underlying mechanism.Methods:A murine model of ovalbumin (OVA)-induced allergic asthma was applied in this study. Mice were divided into three groups: a control group, an OVA group, and OVA-induced asthmatic mice treated with MRS as the third group. Lung resistance index (RI) and dynamic compliance (Cdyn) were measured to determine airway hyper-responsiveness (AHR). Haematoxylin and eosin (H&E) staining was performed and scored to show histopathological changes. Cell counts of bronchoalveolar lavage fluid (BALF) were recorded. Cytokines interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor α (TNF-α), and C-X-C motif chemokine ligand 15 (CXCL15) from BALF and serum were measured by enzyme-linked immunosorbent assay (ELISA). The oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), and 8-hydroxydeoxyguanosine (8-OHdG), were determined using commercial kits. Apoptosis was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical examination. Results:MRS administration reversed the OVA-induced AHR, attenuated the pathological inflammatory infiltration, and decreased the cytokines IL-4, IL-5, IL-13, TNF-α, and CXCL15 in serum and BALF. Moreover, following MRS administration, the oxidative stress was alleviated as indicated by decreased MDA, MPO, and 8-OHdG, and elevated SOD and GSH. In addition, MRS exhibited an anti-apoptotic effect in this model, protecting epithelial cells from damage. Conclusions:Methane improves pulmonary function and decreases infiltrative inflammatory cells in the allergic asthmatic mouse model. This may be associated with its anti-inflammatory, antioxidative, and anti-apoptotic properties.Keywords：Asthma;Methane-rich saline;Antioxidation;Anti-inflammation;Anti-apoptotic- 30
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Published：2022-01-05 -
IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis
Abstract：Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.Keywords：Diabetic osteoporosis;Insulin-like growth factor-1 receptor (IGF-1R);Signaling axis;Pathogenesis- 83
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Published：2022-01-05 -
Potential value of autoantibodies as biomarkers of chronic graft-versus-host disease after allogeneic stem cell transplantation
Abstract：We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease (cGVHD) by analyzing the autoantibody profiles of 65 patients (34 cGVHD and 31 non-cGVHD) surviving longer than three months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Autoantibodies to at least one antigen were detected in 45 patients (70.8%), with multiple autoantibodies detected in 30 patients (46.2%). Antinuclear antibodies (ANAs) were the most frequently detected autoantibodies, with a significantly higher prevalence in non-cGVHD patients and cGVHD patients than that in healthy controls (HCs). ANA-nucleolar (ANA-N) was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and cGVHD groups. There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC. Liver cGVHD was significantly associated with anti-Ro52-positivity. However, cGVHD activity and severity were not associated with the presence of autoantibodies. Similarly, there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies. Our results suggest that autoantibodies have limited value in predicting cGVHD.Keywords：Autoantibody;Chronic graft-versus-host disease (cGVHD);Anti-Ro52- 32
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Published：2022-01-05
Article
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Endoscopic ultrasonography is useful in the diagnosis and treatment of rectal neuroendocrine neoplasms: a case series#
Abstract：Rectal neuroendocrine neoplasms (NENs) are low-grade malignancies, which are slow-growing and usually become symptomatic late in the course of the disease (Basuroy et al., 2016). In recent years, rectal NENs are increasingly frequently detected, with the widespread availability and accessibility of endoscopy and cross-sectional imaging modalities (Kos-Kudla et al., 2017). Multiple studies have shown that endoscopic ultrasound (EUS) is an advanced endoscopic technique and is currently used in the diagnosis and preoperative assessment of NENs (Kim, 2012; Liu et al., 2013; Zhang et al., 2017). However, EUS imaging of rectal NEN and differential diagnosis with other submucosal tumors (SMTs) has not been adequately reported. In this study, we reviewed and summarized the EUS imaging and pathological features of rectal NENs of 38 cases to improve preoperative diagnosis rate and reduce unreasonable treatment.Keywords：Rectal neuroendocrine neoplasm;Endoscopic ultrasonography;Diagnosis- 17
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Published：2022-01-05
Correspondence
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