Integrative proteomics and metabolomics explore the effect and mechanism of Qiyin granules on improving nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a prominent global health concern, representing a substantial burden within the spectrum of chronic liver diseases. Despite its escalating prevalence, a definitive therapeutic strategy or efficacious pharmacological intervention for NAFLD has yet to receive official approval to date. While Fu Fang Qiyin granules have exhibited efficacy in addressing NAFLD, the intricacies of their underlying mechanism of action remain inadequately elucidated. In this study, we substantiated the ameliorative impact of Qiyin on highfat diet (HFD)induced NAFLD in rat models. The results of metabonomics showed that 108 potential biomarkers in serum and urine related to amino acid metabolism, energy metabolism, and pyrimidine metabolism, have returned to normal levels compared to the model group. Hepatic transcriptomics further indicated that Qiyin potentially confers protective effects against NAFLD by mediating liver inflammation and fibrosis through lumican (LUM) and decorin (DCN). In summation, our investigation provides compelling evidence affirming the therapeutic promise of Qiyin for NAFLD. It elucidates the underlying mechanistic pathways, furnishing a compelling rationale for its prospective clinical application.

A study on the association between gut microbiota, inflammation, and type 2 diabetes.

Type 2 diabetes mellitus (T2DM) was reported to be associated with impaired immune response and alterations in microbial composition and function. However, the underlying mechanism remains elusive. To investigate the association among retinoic acid-inducible gene-I-like receptors (RLRs) signaling pathway, intestinal bacterial microbiome, microbial tryptophan metabolites, inflammation, and a longer course of T2DM, 14 patients with T2DM and 7 healthy controls were enrolled. 16S rRNA amplicon sequencing and untargeted metabolomics were utilized to analyze the stool samples. RNA sequencing (RNA-seq) was carried out on the peripheral blood samples. Additionally, C57BL/6J specific pathogen-free (SPF) mice were used. It was found that the longer course of T2DM could lead to a decrease in the abundance of probiotics in the intestinal microbiome. In addition, the production of microbial tryptophan derivative skatole declined as a consequence of the reduced abundance of related intestinal microbes. Furthermore, low abundances of probiotics, such as Bacteroides and Faecalibacterium, could trigger the inflammatory response by activating the RLRs signaling pathway. The increased level of the member of TNF receptor-associated factors (TRAF) family, nuclear factor kappa-B (NF-κB) activator (TANK), in the animal colon activated nuclear factor kappa B subunit 2 (NFκB2), resulting in inflammatory damage. In summary, it was revealed that the low abundances of probiotics could activate the RLR signaling pathway, which could in turn activate its downstream signaling pathway, NF-κB, highlighting a relationship among gut microbes, inflammation, and a longer course of T2DM. KEY POINTS: Hyperglycemia may suppress tryptophanase activity. The low abundance of Bacteroides combined with the decrease of Dopa decarboxylase (DDC) activity may lead to the decrease of the production of tryptophan microbial derivative skatole, and the low abundance of Bacteroides or reduced skatole may further lead to the increase of blood glucose by downregulating the expression of glucagon-like peptide-1 (GLP1). A low abundance of anti-inflammatory bacteria may induce an inflammatory response by triggering the RLR signaling pathway and then activating its downstream NF-κB signaling pathway in prolonged T2DM.

Genome-wide analysis of transcription factors in hippocampal tissue of cerebral palsy rats after acupuncture treatment.

BACKGROUND: Acupuncture has been shown to be effective in treating cerebral palsy (CP), reducing muscle tension, and improving motor function. However, macro-screening of key gene sets and gene-causal interaction networks for their therapeutic mechanisms have not been studied. METHODS: Applying high-throughput sequencing technology, this research discussed differentially expressed mRNAs and differential alternative splicing pre-mRNAs at the transcriptome level in rats with CP treated with acupuncture and moxibustion, and analyzed the regulatory mechanisms of these differentially expressed genes (DEGs) in CP. Changes in the levels of transcripts and alternative splicing in the hippocampi of CP rats after acupuncture treatment were analyzed. Global genes that were differentially expressed and alternative splicing events (ASEs) and regulated ASEs (RASEs) in acupuncture treatment of CP rats were analyzed. RESULTS: The RNA-seq data of acupuncture-treated rat hippocampi revealed 198 DEGs, 125 of which were related to CP, and the transcriptional regulation of RNA polymerase II was up-regulated; moreover, there were 1168 significantly different ASEs associated with CP and transcriptional regulation. There were 14 overlapping gene expression changes in transcription factors (TFs) and DEGs. CONCLUSIONS: This study found that 14 TFs were differentially expressed and a large number of TFs underwent differential alternative splicing. It is speculated that these TFs and the translated proteins of the two different transcripts produced by the differential alternative splicing of these TFs may play corresponding functions in acupuncture treatment of young rats with CP by modulating the differential expression of their target mRNAs.

A Web-Based Pharmacological Approach to the Mechanism of Action of Rhizoma Phragmitis and Rhizoma Curcumae in the Treatment of Chronic Atrophic Gastritis.

Objective: To analyze and test the effect of Rhizoma phragmitis and Rhizoma curcumae on the network pharmacology of MAPK (mitogen-activated protein kinase) and TNF (tumor necrosis factor) signaling channels and inflammatory factor target gene regulation in successful modeling of chronic atrophic gastritis rats. Methods: Rats with chronic atrophic gastritis that were modeled successfully were randomly divided into control and study groups and were treated with conventional western medicine or Rhizoma phragmitis and Rhizoma curcumae, respectively. The pharmacological mechanism of action and efficacy were evaluated. Results: The treatment efficiency was 76.32% and 97.37% in the control and study group, respectively. After treatment, the serum tumor necrosis factor-α (TNF-α) and serum malondialdehyde (MDA) levels in the study group were lower than those in the control group and the serum epidermal growth factor (EGF) and superoxide dismutase (SOD) levels in the study group were higher than those in the control group (P < 0.05); the pain behavioral scores in the study group were lower than those in the control group, and the free acid quantity and total acid quantity in the study group were higher than those in the control group (P < 0.05); the serum MTL index in the study group was higher than that in the control group, and the serum gastrin (GAS) and pepsinogen I (PG I) indices in the study group were lower than those in the control group (P < 0.05); the number of 24-hour reflux in the study group was less than that in the control group (P < 0.05), and the longest reflux time in the study group was lower than that in the control group (P < 0.05). Conclusion: Based on the network pharmacological results, Rhizoma phragmitis and Rhizoma curcumae will modulate MAPK, TNF signaling circuits, and inflammatory factor target genes in the chronic atrophic gastritis rat model. This treatment protocol is efficient and beneficial to enhance the gastric function of the chronic atrophic gastritis rat model, while it can alleviate the inflammatory response and significantly reduce the number and duration of reflux, which is a safe and reliable treatment modality.

Protective Effects of Catalpol on Limb Motor Function and Ultrastructure of Hippocampal Neurons in Rats with Cerebral Ischemia.

This study aimed to examine the protective effects of catalpa on ultrastructure of hippocampal neuron and limb motor function in rats with cerebral ischemia. 90 healthy Sprague-Dawley male rats were randomly divided into control (n = 30) and model (n = 60) groups. Cerebral ischemia and hippocampal neurons were induced by occluding the internal carotid artery and injection of high blood glucose, respectively. Model rats were randomly divided into routine (n = 30) and observational (n = 30) groups. Animals in the routine group received edaravone injection (7 mg/kg/day) for 14 days, while rats in the observation group were treated with catalpol (30 mg/kg/day) for 14 days. Limb motor function score, fine motion execution capability, number of hippocampal neurons retained, and the ultrastructure of hippocampal nerve cells were considered at 3, 7, and 14 days after treatments. A significant difference was observed in the mean scores of limb motor function, fine motor execution ability, and the number of hippocampal neurons retained between groups (p < 0.001). Repetitive treatments with catalpol significantly improved the mean number of hippocampal neurons retained (p < 0.01), limb motor function (p < 0.001), and fine motor execution ability scores (p < 0.01) at 3, 7, and 14 days compared to edaravone. Catalpol treatments also improved the ultrastructure morphology of neuronal cells. Catalpa can effectively improve limb motor function and protect hippocampal neuron function in rats with cerebral ischemia.

Association between peroxisome proliferator-activated receptor γ gene polymorphism and susceptibility to northwest dryness syndrome.

OBJECTIVE: To investigate the relationship between gene polymorphism of peroxisome proliferator- activated receptor (PPAR) and susceptibility to northwest dryness syndrome (NDS). METHODS: The polymorphisms of 11 PPARγ gene loci rs10510418, rs12633551, rs1373640, rs17036188, rs2921190, rs4135247, rs4135275, rs4135283, rs6768587, rs709156, and rs7615916 were detected in 249 patients with NDS and 260 patients with non-NDS (control group) by using Snapshot single-nucleotide polymorphism typing technology. RESULTS: All locus detections were in accordance with Hardy-Weinberg equilibrium test. Compared with the control group, rs2921190 genotype frequency showed statistical difference in the NDS group (P < 0.05). Two-two comparison result showed that CC genotype frequency in the NDS group was higher than that in the control group. CT and TT genotype distribution frequencies showed differences between the two groups. The rare allele frequency in the NDS group was lower than that of the control group (P < 0.01). Multi-factor logistic regression analysis showed that the age and genotype entered the regression equation. The subjects in the age bracket 30-55 and 45-45 were 1.796 and 1.561 times likely, respectively, than those in other age brackets to contract NDS,. The patients with CC genotype was only 0.524 times likely than those with CT/TT genotype to suffer from NDS. CONCLUSION: PPARγ gene rs2921190 polymorphism was correlated with the susceptibility to NDS.