Herbal Compound “Jiedu Huayu” Reduces Liver Injury in Rats via Regulation of IL-2, TLR4, and PCNA Expression Levels

Aim of the Study. To investigate the preventative effects of Jiedu Huayu (JDHY) on D-galactosamine (D-GalN) and lipopolysaccharide-induced acute liver failure (ALF) and to evaluate the possible mechanisms of action. Materials and Methods. ALF was induced in Wistar rats by administrating D-GalN (900 mg/kg) and lipopolysaccharide (10 μg/kg). After treatment with JDHY granules, the levels of blood alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin time were determined. Proliferating cell nuclear antigen was detected by immunohistochemistry staining. The expression of interleukin-2 (IL-2) and toll-like receptor 4 (TLR4) was examined by fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results. JDHY treatment dramatically improved liver function and increased survival rates in an ALF model in rats. We observed a decrease in IL-2 and TLR4 expression following treatment with JDHY in liver cells from ALF rats using qRT-PCR and Western blot analysis. Conclusion. We hypothesize that the therapeutic potential of JDHY for treating ALF is due to its modulatory effect on the suppression of inflammation and by promoting hepatocyte regeneration. Our results contribute towards validation of the traditional use of JDHY in the treatment of liver disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Association of serum 25-hydroxyvitamin D concentrations with all-cause and cardiovascular mortality among US adults with prehypertension: a prospective cohort study

Abstract Background Prehypertension affects 25–50% of adults worldwide and no prior study has examined the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality risk in individuals with prehypertension. This study aims to investigate the association of serum 25(OH)D concentrations with all-cause and CVD mortality among prehypertensive adults by utilizing data from the US National Health and Nutrition Examination Survey (NHANES) 2007–2014 and linked 2019 mortality file. Methods We included 4345 prehypertensive adults who participated in the NHANES between 2007 and 2014 and were followed up until 31 December 2019. Weighted Cox proportional hazards models were used with adjustments for multiple covariates to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risks of dying from any cause and CVD. Results During a median follow-up of 8.8 years, 335 deaths from any causes were documented, of which 88 participants died from CVD. Compared with participants with sufficient 25(OH)D (≥ 75 nmol/L), the multivariate-adjusted HRs and 95% CIs for participants with severe deficiency (< 25 nmol/L), moderate deficiency (25–49.9 nmol/L), and insufficient concentrations (50–74.9 nmol/L) of serum 25(OH)D for all-cause death were 2.83 (1.46–5.52), 1.17 (0.74–1.86), and 1.36 (0.93–1.98), respectively. Similarly, the multivariable-adjusted HRs and 95%CIs for CVD death were 4.14 (1.10–15.51), 1.23 (0.46–3.28), and 1.73 (0.96–3.14), respectively. We found that there was a 9% reduction in the risk of death from all causes and a 14% reduction in the risk of death from CVD for every 10 nmol/L increase in serum 25(OH)D concentrations. Conclusion Severe serum 25(OH)D deficiency among prehypertensive adults was associated with increased risk of mortality from all causes as well as from CVD. Our work suggests that supplementing with vitamin D may prevent premature death in severely deficient individuals with prehypertension

Jie-Du-Hua-Yu Granules Promote Liver Regeneration in Rat Models of Acute Liver Failure: miRNA-mRNA Expression Analysis

Purpose. Jie-Du-Hua-Yu (JDHY) granules are a traditional Chinese medicine with known therapeutic effects for the treatment of acute liver failure (ALF). This study explored the potential molecular mechanism(s) of JDHY granules in promoting liver regeneration and preventing ALF. Methods. Rat models of ALF were constructed through administration of D-galactosamine (D-GalN) (600 mg/kg) and lipopolysaccharides (LPS) (20 μg/kg). Rats were gavaged with JDHY granules, and serum and liver samples were collected at 12 h post-D-GalN/LPS administration. The degree of liver injury was evaluated through hepatic pathology and alanine/aspartate aminotransferase (ALT/AST) activity. miRNA chips were used to detect the miRNA expression profiles of rat models. Bioinformatics analysis was used to identify the biological processes and cell signaling pathways mediating the therapeutic effects of JDHY. Real-time PCR (RT-PCR) and western blotting were used to validate the data. Results. JDHY granules could effectively decrease the levels of ALT and AST, relieve D-GalN/LPS-induced liver injury, and improve hepatic function. JDHY granules were found to regulate the expression of 20 miRNAs and 19 mRNAs, which influenced 21 biological processes and 9 signaling pathways. Upon analysis of the therapeutic mechanism(s) governing the effects of JDHY granules on liver regeneration, enhanced DNA replication and an improved cholesterol metabolic ratio were identified. JDHY granules were also found to increase the expression of MCM3, CDK4, and TC, confirming the involvement of these pathways. Moreover, JDHY granules were found to promote hepatocyte mitosis and inhibit the progression of ALF. Conclusion. JDHY granules protect against D-GalN/LPS-induced ALF in rats by promoting liver regeneration through enhanced DNA replication and an improved cholesterol metabolic ratio