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Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, diabetes belongs to the category of "emaciation-thirst disease" in traditional Chinese medicine (TCM). Bushen Huoxue Prescription (BHP) is composed of traditional Chinese materia medica, which has therapeutic effects on DR and early diabetic retinal edema (EDRE). However, the therapeutic mechanism is unclear. Exploring the mechanism of BHP against EDRE. Feeding Sprague Dawley (SD) rats a high-fat, high-sugar diet as well as providing intraperitoneal injections of streptozotocin (STZ) to promote inner blood-retinal barrier (iBRB) damage that can trigger EDRE, evaluating the therapeutic effect of BHP by the level of expressiveness of TJ proteins (ZO-1,Occludin) of the iBRB and the leakage of rhodamine B isothiocyanate (RITC) in the retina. The combination of network pharmacology and metabolomics was employed to study the mechanism of BHP in preventing of EDRE, then four proteins which were closely to the damage of iBRB were chosen for the validation by employing Western Blot (WB). Research of network pharmacology had shown that BHP had efficacy against EDRE by regulating targets such as AKT1, ALB, TNF, PPARG, etc, its potential pathways mainly involving signaling pathways such as HIF-1. In untargeted metabolomics analysis of serum, 15 differential metabolites were identified, with the metabolic pathways focusing on ketone body metabolism and synthesis, sphingolipid metabolism and phenylalanine metabolism. The conclusions of metabolomics and network pharmacology revealed that BHP can treat EDRE by alleviating hypoxia and oxidative stress and exerting protection of the iBRB. Finally, BHP's protection behavior of the iBRB was validated by WB experiments. Through integrating pharmacodynamics, network pharmacology and metabolomics, BHP was discovered to have a crucial function in EDRE therapy by preserving the integrity of iBRB. This comprehensive strategy also provided a reasonable way to reveal the multi-components, multi-targets, multi-pathways mechanism of TCM. [Display omitted] • Presentation of "early diabetic retinal edema" as a crucial therapeutic point. • Dyslipidemia is believed to play a significant influence in the progression of EDRE. • The mechanism of BHP anti-EDRE was studied. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) progresses rapidly with a high short-term death rate. Although JianPi LiShi YangGan formula (YGF) has been used to treat ACLF by managing inflammatory responses and reducing endotoxemia, hepatocyte injury, and mortality, the underlying mechanisms remain unclear. This study aims to investigate the potential mechanisms underlying the efficacy and protective benefits of YGF in mice with ACLF. YGF composition was determined using high-performance liquid chromatography coupled with mass spectrometry. We constructed a mouse model of ACLF using carbon tetrachloride, lipopolysaccharide (LPS), and D-galactosamine (D-Gal), as well as an in vitro model of D-Gal/LPS-induced hepatocyte injury. The therapeutic effects of YGF in ACLF mice were verified using hematoxylin-eosin, Sirius red, and Masson staining, and by measuring serum alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokine levels. Mitochondrial damage in hepatocytes was evaluated using electron microscopy, while superoxide anion levels in liver tissue were investigated using dihydroethidium. Transcriptome analysis, immunohistochemistry, western blotting, and immunofluorescence assays were performed to explore the mechanisms underlying the ameliorative effects of YGF against ACLF. In mice with ACLF, YGF therapy partially decreased serum inflammatory cytokine levels, as well as hepatocyte injury and liver fibrosis. The livers of ACLF mice treated with YGF exhibited decreased mitochondrial damage and reactive oxygen species generation, as well as a decreased number of M1 macrophages and increased number of M2 macrophages. Transcriptome analysis revealed that YGF may regulate biological processes such as autophagy, mitophagy, and PI3K/AKT signaling. In ACLF mice, YGF promoted mitophagy and inhibited PI3K/AKT/mTOR pathway activation in hepatocytes. Meanwhile, the autophagy inhibitor 3M-A reduced the capacity of YGF to induce autophagy and protect against hepatocyte injury in vitro. In contrast, the PI3K agonist 740 Y–P suppressed the ability of YGF to control PI3K/AKT/mTOR pathway activation and induce autophagy. Together, our findings suggest that YGF mediates autophagy, tight junctions, cytokine generation, and other biological processes. In addition, YGF inhibits hepatic inflammatory responses and ameliorates hepatocyte injury in mice with ACLF. Mechanistically, YGF can promote mitophagy to ameliorate acute-on-chronic liver failure by inhibiting the PI3K/AKT/mTOR pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway. [Display omitted] • XLP combined with 5-FU could alleviate the diarrhea and reduce the inflammation of gastrointestinal mucosa in GC mice model. • XLP combined with 5-FU could inhibit the growth of xenogaft and promote tumor cell apoptosis in GC mice model. • Those effects were related to the regulation of p38MAPK/NF-κB signaling pathway by XLP. [ABSTRACT FROM AUTHOR]

Fuzheng Kang-Ai (FZKA) decoction is mainly composed of 12 components with different types of herbs. In the last decade, FZKA has been used as an adjuvant treatment for lung cancer in clinical practice. Our previous studies have confirmed that FZKA shows a strong anti-cancer activity, significantly increases the clinical efficacy of gefitinib and reverses gefitinib resistance in non-small cell lung cancer (NSCLC). However, the molecular mechanism still needs to be further elucidated. The aim of this study was to investigate the role and mechanism by which FZKA inhibited the cell growth, proliferation and invasion of lung adenocarcinoma(LUAD) and reversed the acquired resistance of gefitinib for the therapy in LUAD. Cell viability assay and EDU assay were used for detecting of cell viability and cell proliferation. Transwell assay was performed to measure cell invasion. Western Blot and qRT-PCR were used for protein and gene expression test. The gene promoter activity was determined by dul-luciferase reporter assay. The in situ expression of protein was measured by cell immunofluorescence. Stabilized cell lines were established for stable overexpression of EZH2. Transient transfection assay was used for gene silence and overexpression. Xenograft tumors and bioluminescent imaging were used for in vivo experiments. FZKA significantly inhibited the cell viability, proliferation and cell invasion of LUAD, the combination of FZKA and gefitinib had a great synergy on the above processes. Moreover, FZKA significantly decreased EZH2 mRNA and protein expression, FZKA reversed the resistance of gefitinib by down-regulation of EZH2 protein. ERK1/2 kinase mediated the down-regulation of EZH2 reduced by FZKA. In addition, FZKA decreased the expression of Snail and EGFR by decreasing EZH2. Overexpression of Snail and EGFR significantly reversed the effect of FZKA-inhibited cell invasion and cell proliferation. More important, the combination of FZKA and gefitinib enhanced the inhibitory effect on EZH2, Snail and EGFR proteins. Furthermore, the growth inhibition and reversal of gefitinib resistance induced by FZKA were further validated in vivo. Finally, the expression and clinical correlation of EZH2,EGFR and Snail in cancer patients were further validated using bioinformatics analysis. FZKA significantly suppressed tumor progression and reversed gefitinib resistance by regulating the p-ERK1/2-EZH2-Snail/EGFR signaling pathway in LUAD. [Display omitted] • FZKA significantly inhibited the cell growth, proliferation and invasion of LUAD and reversed the resistance of gefitinib. • The pERK1/2-EZH2-Snail/EGFR pathway is the underlying mechanism by which FZKA reversed gefitinib resistance in LUAD. • Bioinformatics analysis further confirmed the clinical correlation of EZH2, EGFR and Snail in patients with human cancer. [ABSTRACT FROM AUTHOR]