• Anker Thomson posted an update 6 months, 2 weeks ago

    Background Human bone marrow mesenchymal stem cell-derived hepatocyte-like cells (hBMSC-HLCs) are a promising alternative for primary human hepatocytes (HHs) for treating liver disease. However, the molecular characteristics of HLCs remain unclear. Here, we aimed to clarify the transcriptome characteristics of hBMSC-HLCs for future clinical application. Materials and Methods hBMSCs were isolated from the bone marrow of healthy volunteers and differentiated into hepatocytes. mRNA sequencing was used in the transcriptome profiling of hBMSC-HLCs, with hBMSCs and HHs as controls. Results hBMSC-HLCs exhibited a polygonal morphology, glycogen accumulation and albumin expression. A total of 630 upregulated and 1082 downregulated genes were observed in hBMSC-HLCs and HHs compared with undifferentiated hBMSCs. The upregulated genes were mainly involved in hepatic metabolism and inflammatory and immune responses. The downregulated genes were mainly associated with stem cell characteristics (multipotent differentiation, cell cycle regulation, etc.). Confirmatory qRT-PCR of 9 upregulated and 9 downregulated genes with log2 fold changes > 5 showed similar results. In vivo transdifferentiation of hBMSCs in pigs with fulminant hepatic failure confirmed the similarly upregulated expression of 5 hepatogenic genes (TDO2, HP, SERPINA3, LBP and SAA1), showing a 150-fold change in liver tissues at 7 days after hBMSC transplantation. These 5 genes mainly contributed to liver metabolism and inflammation. Conclusion hBMSC-HLCs possess a hepatic transcriptome profile and express hepatic-specific genes in vitro and in vivo, which might be useful for future clinical applications. The five upregulated genes identified herein could be potential biomarkers for the characterization of hBMSC-HLCs. © The author(s).Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1β, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. Fumarate hydratase-IN-1 compound library inhibitor We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia. © The author(s).Objectives The study was aimed to assess γ‑glutamyltransferase (GGT) activity and concentration as a marker of oxidative stress induced by exposure to tobacco smoke in acute pancreatitis (AP) course. Examination of the relationship between GGT activity/concentration and single-nucleotide polymorphism (SNP rs5751901 and rs2236626) in GGT1 gene was performed. Subjects and methods We examined SNPs in 38 AP patients and 51 healthy subjects by PCR-RFLP methods. GGT concentration in blood was measured with the use of the ELISA method; GGT activity and GSH concentration were measured by the Szasz and Patterson methods, respectively. Results In the non-AP smokers group with TC genotype for SNPrs5751901 an increased blood GGT activity compared to smokers with CC genotypes was shown. In the course of AP was observed an elevated GGT activity and the value of GGT activity/GGT concentration ratio in smokers compared to non-smokers, in AP patients with TC genotypes and CC genotypes, respectively, for both SNP rs5751901 and rs2236626. In the group of smoking AP patients with the CC and TC genotypes in rs5751901 locus and CC and TT genotypes in rs2236626 locus a decreases in GSH concentration during hospitalization were noted. Conclusions SNP rs5751901 and rs2236626 cause changes in GGT activity. Smoking in the AP course contributes to increased GGT activity and excessive GSH use up in patients with TC and CC genotypes for both SNPs. Exposure to smoke xenobiotics enhances (3-fold) the risk of AP occurrence in individuals with TC genotypes for SNP rs5751901. © The author(s).Chronic inflammatory demyelinating polyneuropathy (CIDP) is a kind of autoimmune-mediated inflammation and demyelinating disease. The etiology is mainly related to autoimmune dysfunction. The conventional treatments of CIDP have relied on immunomodulation and inhibition therapies such as adrenal cortex hormone, intravenous immunoglobulin (IVIg) and plasma exchange. Hematopoietic stem cell transplantation (HSCT) is known as a novel therapy for autoimmune disorders, which provides the chance to cure CIDP. More than 70 patients with refractory CIDP have received HSCT. The clinical symptoms and electrophysiological examination results of most patients have been improved. However, the treatment still has risks. This review describes the pathogenesis of CIDP and the current conventional treatments, and highlights the application of HSCT in CIDP, including its efficacy and safety. © The author (s).Background Adenomyosis is a quite common gynecological disorder and above 30% of patients have typical secondary and progressive dysmenorrhea. Current treatments still have many disadvantages and thereby the novel treatment aiming to relieve dysmenorrhea still needs to be further investigated. Mifepristone is a wonderful drug because it is effective, safe and cheap in many diseases including adenomyosis. In this study, we aim to investigate if mifepristone could be used in the treatment of adenomyosis-associated dysmenorrhea. Methods Human primary endometrial epithelial and stromal cells from adenomyosis patients were isolated and treated with mifepristone. RNA-sequencing was then performed to detect the gene changes of pain-related inflammatory mediators. Meanwhile, the effect of mifepristone on the infiltration and degranulation of mast cells were investigated in adenomyosis lesions. Additionally, the role of mifepristone on the density of nerve fibers was also studied in the ectopic endometrium. At last, to evaluate the therapeutic efficacy of mifepristone on dysmenorrhea of adenomyosis, twenty participants were included and the visual analog scale (VAS) score was assessed and compared before and after treatment with mifepristone.

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