Protective effect of Hypericum perforatum Linn (St. John's wort) against hydrogen peroxide-induced apoptosis on human neuroblastoma cells

The medicinal plant Hypericum perforatum Linn, commonly known as St. John's wort, has been used as an antidepressant. To investigate whether St. John's wort possesses a protective effect against hydrogen peroxide (H(2)O(2))-induced cytotoxicity in neuronal cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, flow cytometry analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with H(2)O(2) exhibited several apoptotic features, while those pre-treated with St. John's wort prior to H(2)O(2) exposure showed a decreased occurrence of apoptotic features. In addition, pre-treatment with St. John's wort inhibited H(2)O(2)-induced increase in caspase-3 enzyme activity. These results suggest that St. John's wort may exert a protective effect against H(2)O(2)-induced apoptosis in human neuroblastoma cells.     

Cooperative transformation of murine fibroblast NIH3T3 cells by hepatitis C virus core protein and hepatitis B virus X protein

Co-infection with hepatitis B virus (HBV) and hepatitis C Virus (HCV) is associated with increased frequency in the development of hepatocellular carcinoma (HCC). Here, we demonstrated that HBV X protein (HBx) and HCV core cooperate to transform mouse fibroblast NIH3T3 cells. They additively stimulated cell growth, especially in the absence of serum growth factors. In addition, co-expression of HBx and HCV core had additive effects on the induction of anchorage-independent cell growth as well as on the secretion of matrix metalloproteases, which may contribute to increased metastatic potential. Furthermore, the cells expressing both viral proteins exhibited higher tumorigenicity, as demonstrated in athymic nude mice.     

Vimentin expression of newly formed rat bile duct epithelial cells in secondary biliary fibrosis

Summary The intermediate filament profile and the growth fraction of hepatocytes and bile duct epithelial cells were studied in a rat model of biliary fibrosis secondary to common bile duct ligation and scission. Strong vimentin expression was observed in epithelial cells of newly formed bile ductules, while normal liver contained only few weakly positive bile duct epithelial cells. All epithelial cells reacted with a pan-cytokeratin antibody. A monoclonal antibody specific for human cytokeratin 7 selectively reacted with both normal and newly formed bile duct epithelial cells. The intermediate filament profile of hepatocytes was constant, showing no changes during proliferation or in periportal areas adjacent to excessive bile duct formations. The proliferation-associated antigen detected by the antibody Ki-67 was present in many hepatocytes, homogeneously distributed in the lobules, but was seen only in a small proportion of the epithelial cells of the newly formed bile ducts. We conclude that vimentin may serve as an indicator for cellular reorganization in the bile duct system, and that the epithelial cells of newly formed bile ductules in this particular model of secondary biliary fibrosis were most likely to be derived from an outgrowth of the biliary duct system and recruitment of preductular epithelial cells. No morphological or immunohistological evidence suggesting a derivation from hepatocytes by ductular metaplasia or from oval cells was obtained.     

Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor induce adhesion and chemotaxis of human eosinophils via p38 mitogen-activated protein kinase and nuclear factor kappaB

Hematopoietic cytokines such as interleukin (IL)-3, IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF) play a fundamental role in eosinophil functions in allergic asthma. The intracellular signal transduction mechanisms of these cytokines regulating the activation of eosinophils have been potential therapeutic targets. We investigated the roles of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-kappaB) in IL-3, IL-5, and GM-CSF-induced adhesion, morphological changes, and subsequence transmigration of human eosinophils. IL-3, IL-5, and GM-CSF could augment the phosphorylation of p38 MAPK and nucleus translocation of NF-kappaB in eosinophils. cDNA expression arrays demonstrated that the gene expression levels of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), alpha6, beta2 integrin (CD18), and CD44 were upregulated by these cytokines. Results from functional assays showed that adhesion of eosinophils onto airway epithelial cells was enhanced after IL-3 and IL-5 but not GM-CSF stimulation. These cytokines could markedly induce shape change and augment the transmigration of eosinophils. Moreover, administration of either p38 MAPK inhibitor, SB 203580, or proteasome inhibitor, N-cbz-Leu-Leu-leucinal (MG-132), could inhibit the cytokine-induced adhesion, shape change, and transmigration of eosinophils. Together, our findings suggest that IL-3, IL-5, and GM-CSF regulated the adhesion and chemotaxis of human eosinophils through shared signaling pathways involving both p38 MAPK and NF-kappaB. Our results therefore shed light on the further development of more effective agents for allergic and inflammatory diseases.     

Liver profile in COVID-19: a meta-analysis

Journal of Public Health - Few studies have been performed to investigate multiorgan failure occurring with extrapulmonary symptoms like diarrhea, anorexia, and vomiting. There has been no attempt...     

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A,F, and S in 6-Year-old Children in Korea

ObjectivesBisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children.MethodsPrenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T₃, and free T₄) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations.ResultsThe associations between prenatal BPA and total T₃ levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T₄ levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only.ConclusionsOur findings identified significant associations between prenatal BPA exposure and total T₃ levels in all children and between BPF exposure and free T₄ levels in girls only.     

Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome

Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.     

Causal Effects of Homocysteine,Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study

Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change −0.95 (−1.21, −0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (−0.11 (−0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment.     

Efficacy of testosterone replacement therapy for treating metabolic disturbances in late-onset hypogonadism: a systematic review and meta-analysis

International Urology and Nephrology - Late onset hypogonadism (LOH) is an age-dependent reduction of testosterone associated with alterations of metabolic profile, including glucose control,...