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Inflammatory bowel disease (IBD) can be caused by a variety of factors, including hereditary and environmental influences, that lead to dysfunction of the intestinal immune system. Mesenchymal stem cells (MSCs) exhibit important regulatory roles in relieving inflammation and repairing damaged tissues. Although neutrophils are important participants in the development of inflammatory reactions, they are also essential for maintaining intestinal balance during the process of mitigation of IBD by MSCs. Here, we constructed a dextran sulfate sodium (DSS)-induced mouse IBD model and evaluated the effects of treatment with human umbilical cord MSCs. Mouse body weight, faecal traits, colon/spleen gross morphology, tissue histology and immunohistochemical staining, and inflammatory factors were analysed. Magnetic beads were used to sort infiltrating neutrophils from intestinal tissues, and their phenotypes were identified. The neutrophil inflammatory environment was also simulated in vitro, and signalling pathways involved in MSC regulation of neutrophil phenotype were analysed. Human umbilical cord MSCs effectively alleviated DSS-induced weight loss, colon shortening, and intestinal mucosal injury, and reduced clinical disease activity index. The number of neutrophils that infiltrated the intestines of mice treated with human umbilical cord MSCs were decreased and polarised toward the N2 phenotype; at the same time, ERK phosphorylation was inhibited. In vitro experiments showed that addition of the ERK phosphorylation inhibitor, PD98059, down-regulated the expression of N1 neutrophils, while up-regulating that of N2 neutrophils. The colon tissues from patients with IBD were infiltrated with neutrophils. Further, relative to healthy controls, the markers of N1 neutrophils (ICAM-1, FAS, and CCL3) were highly expressed in colon tissues from patients with IBD, whereas the markers of N2 neutrophils (VEGF, CCL2, and CXCR4) were almost undetectable. In conclusion, during alleviation of IBD, human umbilical cord MSCs polarise neutrophils toward the "N2" phenotype by inhibiting activation of ERK signalling.

Background Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. Methods In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. Results hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. Conclusion hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulatory abilities, making them potential treatment options for many diseases. Therefore, the therapeutic potential of MSCs in various diseases including autoimmune conditions has been explored. In addition to an imbalance of T cell subsets in most patients with autoimmune diseases, they also exhibit complex disease manifestations, overlapping symptoms among diseases, and difficult treatment. MSCs can regulate T cell subsets to restore their immune homeostasis toward disease resolution in autoimmune conditions. This review summarizes the role of MSCs in relieving autoimmune diseases via the regulation of T cell phenotypes.

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract with nonobvious early symptoms and late symptoms of anemia, weight loss, and other systemic symptoms. Its morbidity and fatality rate are next only to gastric cancer, esophageal cancer, and primary liver cancer among digestive malignancies. In addition to the conventional surgical intervention, other therapies such as radiotherapy and chemotherapy and new treatment methods such as biologics and microbiological products have been introduced. As a promising cell therapy, mesenchymal stem cell (MSC) has attracted extensive research attention. MSCs are early undifferentiated pluripotent stem cells, which have the common features of stem cells, including self-replication, self-division, self-renewal, and multidirectional differentiation. MSCs come from a wide range of sources and can be extracted from a variety of tissues such as the bone marrow, umbilical cord, and fat. Current studies have shown that MSCs have a variety of biological functions such as immune regulation, tissue damage repair, and therapeutic effects on tumors such as CRC. This review outlines the overview of MSCs and CRC and summarizes the role of MSC application in CRC.

Aims: miR-181a and miR-181b have been investigated as prognostic biomarkers of colorectal cancer (CRC). However, there is controversy about the role of miR-181a and miR-181b in predicting CRC prognosis. Therefore, we performed this meta-analysis to evaluate prognostic values of miR-181a and miR-181b in CRC patients. Materials & methods: Studies were systemically searched from publications and analyzed, and 999 CRC cases in nine studies were examined in this meta-analysis. Results: Hazard ratio for overall survival of high miR-181a and miR-181b expression in CRC was 1.65. More prominent predictive effects were observed in black people, miR-181b group and small-sample-size group. Conclusion: High levels of miR-181a and miR-181b predict poor overall survival in CRC patients. miR-181a and miR-181b are promising biomarkers for CRC prognosis.

Sufentanil is a new kind of opioid analgesic and acts on μ opioid receptor. In this study, we aim to investigate the effects of sufentanil on gastric cancer cell line SGC-7901, after being exposed to different concentrations of sufentanil. Gastric cancer cells were exposed to sufentanil for a predetermined time at concentrations of 0, 0.5, 5, 50 and 500 nmol/l, respectively. Cell viability at different time points after exposure to sufentanil was tested by CCK-8 assay. FDA-PI staining was used to observe membrane integrity of gastric cancer SGC7901 cells. The apoptosis of gastric cancer cells was analyzed by Annexin V-FITC/PI Flow Cytometry and the changes of the cell cycle was determined by a detection kit. As a result, cell viability decreased in a dose- and time-dependent manner. Furthermore, with the concentration of sufentanil increased, the proportion of dead and apoptotic SGC-7901 cells increased, and more cells were arrested in G2/M phase. In a word, sufentanil can inhibit the cell viability and induce the apoptosis of gastric cancer SGC-7901 cells in vitro.

Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by several bloom-forming cyanobacteria, has strong reproductive toxicity. We examined whether MC-LR could enter spermatogonia and investigated the toxic effects of MC-LR on spermatogonia in vitro. Multispecific organic anion-transporting polypeptides (Oatps), which transported MCs, were screened as well. Spermatogonia were exposed to 0, 0.5, 5, 50, and 500 nmol/L (nM) MC-LR for 6 h. Cell viability and total antioxidant capacity significantly decreased, meanwhile, the ratio of apoptotic cells, reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), and intracellular free Ca2+ increased after exposure to 5 nM and higher concentrations of MC-LR. MC-LR can immigrate into spermatogonia. At least 5 Oatps (Oatp1a5, -3a1, -6b1, -6c1, and -6d1) were detected at the mRNA level in spermatogonia, and the expression of these Oatps was affected by MC-LR, especially Oatp3a1. This study demonstrated that MC-LR can be transported into spermatogonia and leads to cytotoxicity.

A new spectrophotometric titration method coupled with chemometrics for the simultaneous determination of mixtures of weak acids has been developed. In this method, the titrant is a mixture of sodium hydroxide and an acid-base indicator, and the indicator is used to monitor the titration process. In a process of titration, both the added volume of titrant and the solution acidity at each titration point can be obtained simultaneously from an absorption spectrum by least square algorithm, and then the concentration of each component in the mixture can be obtained from the titration curves by principal component regression. The method only needs the information of absorbance spectra to obtain the analytical results, and is free of volumetric measurements. The analyses are independent of titration end point and do not need the accurate values of dissociation constants of the indicator and the acids. The method has been applied to the simultaneous determination of the mixtures of benzoic acid and salicylic acid, and the mixtures of phenol, o-chlorophenol and p-chlorophenol with satisfactory results.

Ple iotropic proinflammatory cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-α (TNF-α), involved in the regulations of various immune responses, inflammatory processes and hematopoiesis. In the present study, the expression levels of IL-1 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). Following the cytokine blockade as a successful clinical therapy for autoimm une diseases such as rheumatoid arthritis, the patients are more susceptible to a variety of opportunistic infections. IL-1 and TNF-α may be useful predictive biomarkers of diseases and offer potential targets for therapeutic intervention of inflammatory diseases. However, our results showed that the plasma IL-1 level was significantly higher in women compared to men (69.5 ± 19.8 pg/ ml in men and 80.1 ± 19.5 pg/ml in women, respectively); the plasma levels of TNF-α were higher in men than women (20.8 ± 4.9 pg/ml and 18.7 ± 7.1 pg/ml, respectively). The significant gender difference of plasma interleukin-1 (IL-1) and TNF-α levels present in healthy adults in Jiangsu Province, China (P=0.002 and P=0.015, respectively), and may be as a hint for sex differences of susceptibility to many diseases and elementary immune response.

Background. Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. Objective. To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. Material and methods. The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. Results. There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051-2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. Conclusions. The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.

It was discovered that a second order spectra data matrix of Sudan I produced from the solvent components gradual change-visible absorption spectra can be expressed as the combination of two bilinear data matrices. Based on this discovery, a new method for the determination of Sudan I in gray systems using second order calibration algorithms has been developed. The second order calibration algorithms were based on the popular parallel factor analysis (PARAFAC) and rank annihilation factor analysis (RAFA), respectively. In the method described here, the components of the solvent were changed gradually by adding ethanol into cyclohexane, the absorption spectra of Sudan I and chilli samples in a series of cyclohexane-ethanol mixed solvents with various ethanol volume fractions were recorded, and then the second order data were obtained from the solvent components gradual change-visible absorption spectra. Thus, the concentration of Sudan I in a gray system could be determined from the spectra matrices using second order calibration algorithms. This method is simple, convenient and dependable. The method has been used to determine Sudan I in chilli powder with satisfactory results.