Osteoporosis is prevalent in elderly women and it may cause dental implant failure. In particular, estrogen deficiency in postmenopausal women leads to higher rates of osteoporosis prevalence. Immune cell-mediated effects involving the development of osteoporosis have been studied previously; however, the role of IL-10-producing regulatory B (B10) cells in osteoporosis is largely unclear. Here, we examined the role of B10 cells in osteoporosis. C57BL/6 mice were subjected to ovariectomy (OVX). Fifteen weeks after OVX surgery, the first molar of the right maxillary was extracted, and twenty-four weeks after OVX surgery, serous progression of osteoporosis was observed in the alveolar bone. Moreover, the proportion of CD19+CD5+CD1dhigh regulatory B cells, B10, and CD4+CD25+FoxP3+ regulatory T cells from the spleen of OVX mice decreased during the progression of osteoporosis, compared to controls. In contrast to regulatory cells, IL-17-producing Th (Th17) cell levels were increased in OVX mice. Adoptive transfer of B10 cells to OVX mice led to a decrease in Th17 cell abundance and inhibited the development of osteoporosis in the alveolar bone from OVX mice. Thus, our results suggest that B10 cells may help suppress osteoporosis development.

Traditional Chinese medicine (TCM) syndrome is an important basis for TCM diagnosis and treatment. As Child-Pugh classification as well as compensation and decompensation phase in liver cirrhosis, it is also an underlying clinical classification. In this paper, we investigated the correlation between single nucleotide polymorphisms (SNPs) of Interleukin-10 (IL-10) and TCM syndromes in patients with hepatitis B cirrhosis (HBC). Samples were obtained from 343 HBC patients in China. Three SNPs of IL-10 (-592A/C, -819C/T, and -1082A/G) were detected with polymerase chain-reaction-ligase detection reaction (PCR-LDR). The result showed the SNP-819C/T was significantly correlated with Deficiency syndrome (P = 0.031), but none of the 3 loci showed correlation either with Child-Pugh classification and phase in HBC patients. The logistic regression analysis showed that the Excess syndrome was associated with dizzy and spider nevus, and the Deficiency syndrome was associated with dry eyes, aversion to cold, IL-10-819C/T loci, and IL-10-1082A/G loci. The odds ratio (OR) value at IL-10-819C/T was 4.022. The research results suggested that IL-10-819C/T locus (TC plus CC genotype) is probably a risk factor in the occurrence of Deficiency syndrome in HBC patients.

Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/D ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated. Results. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus C/D ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus C/D ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus C/D ratios difference of IL-10 polymorphisms was found in our data. Conclusions. IL-18 polymorphisms may influence tacrolimus elimination in lung transplantation patients.

Differentially methylated genes (DMGs) serve a crucial role in the pathogenesis of glioma via the regulation of the cell cycle, proliferation, apoptosis, migration, infiltration, DNA repair and signaling pathways. This study aimed to identify aberrant DMGs and pathways by comprehensive bioinformatics analysis. The gene expression profile of GSE28094 was downloaded from the Gene Expression Omnibus (GEO) database, and the GEO2R online tool was used to find DMGs. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DMGs were performed by using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed with Search Tool for the Retrieval of Interacting Genes. Analysis of modules in the PPI networks was performed by Molecular Complex Detection in Cytoscape software, and four modules were performed. The hub genes with a high degree of connectivity were verified by The Cancer Genome Atlas database. A total of 349 DMGs, including 167 hypermethylation genes, were enriched in biological processes of negative and positive regulation of cell proliferation and positive regulation of transcription from RNA polymerase II promoter. Pathway analysis enrichment revealed that cancer regulated the pluripotency of stem cells and the PI3K-AKT signaling pathway, whereas 182 hypomethylated genes were enriched in biological processes of immune response, cellular response to lipopolysaccharide and peptidyl-tyrosine phosphorylation. Pathway enrichment analysis revealed cytokine-cytokine receptor interaction, type I diabetes mellitus and TNF signaling pathway. A total of 20 hub genes were identified, of which eight genes were associated with survival, including notch receptor 1 (NOTCH1), SRC proto-oncogene (also known as non-receptor tyrosine kinase, SRC), interleukin 6 (IL6), matrix metallopeptidase 9 (MMP9), interleukin 10 (IL10), caspase 3 (CASP3), erb-b2 receptor tyrosine kinase 2 (ERBB2) and epidermal growth factor (EGF). Therefore, bioinformatics analysis identified a series of core DMGs and pathways in glioma. The results of the present study may facilitate the assessment of the tumorigenicity and progression of glioma. Furthermore, the significant DMGs may provide potential methylation-based biomarkers for the precise diagnosis and targeted treatment of glioma.

The study aimed to elucidate abscopal effects of thoracic X-ray irradiation on spermatogenesis in mice. Male C57BL/6 mice were randomly divided into sham group and radiation group, and subjected to thorax fractionated X-ray irradiation or sham irradiation with the total dose of 5 Gy/day for each animal for four consecutive days. After irradiation, sperm morphology was observed, and sperm number was counted under microscope, and sperm apoptosis was detected by flow cytometry. Meanwhile, testis index was calculated, testicular morphology was observed using haematoxylin-eosin (HE) staining, and testicular ultrastructure was observed under transmission electron microscopy. The permeability of blood-testis barrier (BTB) was detected by Evans Blue fluorescence colorimetry. The protein levels of Bcl-2 associated X protein (Bax), B-cell leukemia-lymphoma-2 (Bcl-2) and Cleaved caspase 3, promyelocytic leukaemia zinc finger (PLZF) and c-kit proto-oncogene (c-kit) in testes were determined by western blotting (WB). The location of apoptotic cells was confirmed by terminal deoxynucleotidyl transferase (TdT) enzymaticated dUTP nick end labelling (TUNEL) assay. The levels of tumor necrosis factor alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by the biochemical assay kit. Compared with sham group, the sperm quality of mice in radiation group showed decreased number and survival rate, along with increased abnormality and total apoptosis rate. The testis index of irradiated mice was lower, the testicular apoptosis was increased, and their testicular histology and ultrastructure was severely damaged. The permeability of BTB was increased, the level of PLZF in testis was decreased, and the level of c-kit was increased by irradiation. After irradiation, the levels of TNF-α, TGF-β1, IL-10, T-SOD and MDA in testes were significantly changed. Taken together, abscopal effects of thoracic X-ray irradiation on spermatogenesis were obvious, which could decrease sperm quality and damage testicular morphology and increase the permeability of BTB, and a series of inflammation and oxidative stress factors were involved in the process. These findings provide novel insights into prevention and treatment for male reproductive damage induced by clinical thoracic irradiation.

Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis. Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death. Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P < 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury. Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.