MicroRNA-181a regulates Treg functions via TGF-β1/Smad axis in the spleen of mice with acute gouty arthritis induced by MSU crystals

Regulatory T cells (Tregs) play critical roles in restricting inflammatory pathogenesis and limiting undesirable Th2 response to environmental allergens. However, the role of miR-181a in regulating acute gouty arthritis (AGA) and Treg function remains unclear. This study aimed to investigate the potential roles of miR-181a in Treg immunity and the associated signaling pathway in the AGA mouse model. A solution with monosodium urate (MSU) crystals was injected into the joint tissue of mice to induce AGA. ELISA was used to examine inflammatory factors in blood samples, and flow cytometry was used to analyze Treg profile in mice with MSU-induced AGA. Cell proliferation and viability were assessed by CCK-8 assay. TGF-β1/Smad signaling activation was detected by western blot. We found that miR-181a expression showed a positive correlation with the changes of splenic Tregs percentage in AGA mice. miR-181a regulated the TGF-β1/Smad axis, since the transfection of miR-181a mimic increased the level of TGF-β1 and the phosphorylation of Smad2/3 in Tregs in AGA mice. Additionally, miR-181a mimic also promoted responses of Tregs via TGF-β1 in vitro and in vivo. Our work uncovered a vital role of miR-181a in the immune function of Treg cells by mediating the activity of the TGF-β1/Smad pathway in the AGA mouse model induced by MSU.

Spatial-temporal clustering analysis of soil-transmitted helminth transmission risk in Jiangxi, 2016-2019 / 中国热带医学

@#Abstract: Objective　To analyze the epidemic characteristics of soil-transmitted helminth (STH) by the spatial epidemiological method in Jiangxi Province. Methods　Surveillance data of STH in Jiangxi Province from 2016 to 2019 were collected for descriptive epidemiological analysis. The space-time permutation distribution of STH infection areas was analyzed with spatial autocorrelation, hotspot analysis methods and retrospective space-time permutation scan statistics. Results　The infection rates of STH were 1.32% (947/71 766), 1.14% (803/70 547), 0.87% (604/69 507) and 0.90% (628/69 620), respectively, and the differences were statistically significant in different years (P<0.01). The rates of hookworm infection were 0.65% (466/71 766), 0.64% (450/70 547), 0.48% (336/69 507) and 0.52% (362/69 620), respectively, and the differences were statistically significant (P<0.01). The infection rates of Ascaris lumbricoides were 0.55% (393/71 766), 0.41% (287/70 547), 0.32% (221/69 507) and 0.32% (225/69 620), respectively, and the differences were statistically significant in different years (P<0.01). The infection rates of Trichuris trichiura were 0.17% (125/71 766), 0.10% (74/70 547), 0.08% (57/69 507) and 0.07% (49/69 620), respectively, and the differences were statistically significant among different years (P<0.01). The results of global spatial autocorrelation analysis showed that there was a spatial autocorrelation index Moran's I value of hookworm infection rate in 2016, Trichuris trichiura infection rate in 2016, 2018 and 2019, with statistical significance (P<0.05). The results of hotspot analysis, SaTScan and FleXScan spatial and temporal scanning analysis showed that there were high-value aggregation regions for each species in each year. Conclusion　The infection rates of STH, hookworm, Ascaris lumbricoides and Trichuris trichiura showed a decreasing trend and space-time clustering from 2016 to 2019. It should be taken into account in the formulation of control strategies.

Source, metabolism and function of dopamine in digestive tract / 生理学报

Dopamine (DA), as a catecholamine neurotransmitter widely distributed in the central nervous system and the peripheral tissues, has attracted a lot of attention. Especially in recent years, DA has been found to regulate the function of the immune system, and the involvement of DA in the intestinal mucosal inflammation-related diseases has become a hot research topic. The digestive tract is an important source of peripheral DA, and DA is not only produced in the enteric nervous system and gastrointestinal epithelium, but also produced by intestinal microorganisms. In addition to the synthetases of DA, the DA contents in body tissues are also affected by the two kinds of metabolic enzymes, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). This article reviewed the sources, metabolism, and functions of DA in digestive tract, especially focusing on the distribution and function of MAO and COMT, the enzymes degrading DA.

SULF2 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells through the ERK/AKT signaling pathway

The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.

Clinical Application Analysis of Andrographolide Total Ester Sulfonate Injection, a Traditional Chinese Medicine Licensed in China / 华中科技大学学报（医学）（英德文版）

Andrographolide total ester sulfonate (ATES) injection is one of the products of traditional Chinese medicine (TCM) currently used against viral infection in China.ATES injection was approved for manufacturing and marketing in January 2002.It is indicated for acute respiratory infections,tonsillitis,chronic obstructive pulmonary disease,influenza,foot and mouth disease,bronchiolitis,herpangina,mumps,infectious mononucleosis and psychosis.However,its usage also carries risk.We investigated the use of ATES at the Wuhan Union Hospital from January 2014 to December 2014 and evaluated its real-word clinical application using the hospital centralized monitoring method.A total of 848 cases were enrolled in this study.In these cases,it was mainly used for postoperative anti-inflammation and treating upper respiratory infection,pneumonia and bronchitis.Among them,39.86％ were contraindicated.Irregular medication of adults and children accounted for 1.91％ and 23.38％,respectively.Improper choice of solvent accounted for 3.18％.The choice of intravenous drip versus aerosol inhalation was reasonable.A case of adverse events (AEs) was observed in the monitoring period,and the incidence of adverse drug reaction (ADR) of ATES injection was 0.12％.ATES injection in our hospital is relatively safe with a low incidence of adverse reactions.The study assesses the clinical usage and adverse reactions of ATES injection,and provides suggestions for rational use in clinical practice.

Corticotropin-releasing Factor Changes the Phenotype and Function of Dendritic Cells in Mouse Mesenteric Lymph Nodes

BACKGROUND/AIMS: Dendritic cells (DCs) are a significant contributor to the pathology of numerous chronic inflammatory autoimmune disorders; however, the effects of Corticotropin-releasing factor (CRF) on intestinal DCs are poorly understood. In this study, we investigated the role of CRF in alterations of intestinal dendritic cell phenotype and function. METHODS: Mouse mesenteric lymph node dendritic cells (MLNDCs) were obtained using magnetic bead sorting. Surface expression of CRF receptor type 1 (CRF-R1) and CRF-R2 was determined by double-labeling immunofluorescence and quantitative polymerase chain reaction (qPCR) and MLNDCs were subsequently exposed to CRF in the presence or absence of CRF-R1 and CRF-R2 antagonists. Expression of surface molecules (MHC-I and MHC-II) and co-stimulatory molecules (CD80 and CD86) was determined by flow cytometric and western blot analyses, and the T cell stimulatory capacity of MLNDCs was evaluated by mixed lymphocyte reaction. RESULTS: Immunofluorescent staining and quatitative polymerase chain reaction indicated that both the CRF receptors (CRF-R1 and CRF-2) are expressed on the surface of MLNDCs. Exposure to CRF increased the expression of MHC-II on MLNDCs as well as their capacity to stimulate T cell proliferation. MLNDCs treated with CRF-R1 antagonist exhibited a phenotype characterized by a less activated state and reduced surface expression of MHC-II, and consequently showed reduced capacity to stimulate T cells. In contrast, treatment of MLNDCs with CRF-R2 antagonist yielded an opposite result. CONCLUSIONS: CRF can alter the phenotype and function of intestinal DCs through direct action on CRF-R1 and CRF-R2, and activation of the CRF-R1 and CRF-R2 pathways yields opposing outcomes.

Association of PPARgama2 polymorphisms with carcass and meat quality traits in a Pietrain x Jinhua F2 population

The PPARγ2 gene is a key regulator of both proliferation and preadipocyte differentiation in mammals. Herein its genotype and allele frequencies were analyzed using PCR-SSCP in eight pig breeds (N = 416). Two kinds of polymorphisms of the PPARγ2 gene were detected, including a previously reported shift SNP A177G (Met59Val) in exon 1 and a novel silent mutation G876A in exon 5. The results revealed that European pig breeds carry a higher allele A frequency at the A177G locus and a fixed GG genotype at the G876A locus. Allele A at the G876A locus was only found in Jinhua pigs. The association between haplotype (A177G/G876A) and carcass and meat quality traits was analyzed in a Pietrain x Jinhua F2 population (N = 248). The PPARγ2 gene was found to be significantly associated with backfat thickness at the shoulder (p < 0.05), 6-7th ribs (p < 0.01), last rib (p < 0.01), gluteus medius (p <0.05) and ham weight (p < 0.01). Significant effects of different haplotypes on ham weight and backfat thickness at the 6-7th ribs, last rib, and gluteus medius were also observed.