ABSTRACT
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD.
Subject(s)
Fatty Liver , Humans , Fatty Liver/epidemiology , Cost of Illness , Global Health , Prevalence , IncidenceABSTRACT
A novel facile method for on-site detection of antipertensive chemicals (e. g. nicardipine hydrochloride, doxazosin mesylate, propranolol hydrochloride, and hydrochlorothiazide) adulterated in traditional Chinese medicine for hypertension using thin layer chromatography (TLC) combined with surface enhanced Raman spectroscopy (SERS) was reported in the present paper. Analytes and pharmaceutical matrices was separated by TLC, then SERS method was used to complete qualitative identification of trace substances on TLC plate. By optimizing colloidal silver concentration and developing solvent, as well as exploring the optimal limits of detection (LOD), the initially established TLC-SERS method was used to detect real hypertension Chinese pharmaceuticals. The results showed that this method had good specificity for the four chemicals and high sensitivity with a limit of detection as lower as to 0.005 microg. Finally, two of the ten antipertensive drugs were detected to be adulterated with chemicals. This simple and fast method can realize rapid detection of chemicals illegally for doping in antipertensive Chinese pharmaceuticals, and would have good prospects in on-site detection of chemicals for doping in Chinese pharmaceuticals.
Subject(s)
Antihypertensive Agents/analysis , Chromatography, Thin Layer , Drug Contamination , Drugs, Chinese Herbal/analysis , Limit of Detection , Sensitivity and Specificity , Spectrum Analysis, RamanABSTRACT
The effects of Salvianolic acid A (Sal A) on the treatment of Alzheimer's disease (AD) were investigated. Sal A significantly inhibits amyloid beta [Formula: see text] self-aggregation and disaggregates pre-formed [Formula: see text] fibrils, reduces metal-induced [Formula: see text] aggregation through chelating metal ions, and blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells. Sal A protects cells against [Formula: see text]-induced toxicity. Furthermore, Sal A, possibly because of the effects of decreasing toxicity effects of [Formula: see text] species, alleviates [Formula: see text]-induced paralysis in transgenic Caenorhabditis elegans. Circular dichroism (CD) experiments and Molecular dynamic (MD) simulations demonstrate that Sal A inhibits [Formula: see text] self-aggregation through binding to the C-terminus of [Formula: see text], and therefore stabilizing the [Formula: see text]-helical conformations. Altogether, our data show that Sal A, as the multifunctional agent, is likely to be promising therapeutics for AD.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/drug effects , Caffeic Acids/pharmacology , Lactates/pharmacology , Plaque, Amyloid/drug therapy , Serum Amyloid A Protein/drug effects , Animals , Caenorhabditis elegans/drug effects , Cell Line, Tumor , Circular Dichroism , Copper/chemistry , Drug Evaluation, Preclinical , Humans , Iron/chemistry , Iron Chelating Agents , Molecular Dynamics Simulation , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Reactive Oxygen Species/antagonists & inhibitors , Salvia miltiorrhiza , Serum Amyloid A Protein/metabolism , Zinc/chemistryABSTRACT
Recent evidence has revealed the occurrence of an apoptotic phenotype in Candida albicans that is inducible with environmental stresses such as acetic acid, hydrogen peroxide, and amphotericin B. In the present study, we found that the Chinese herbal medicine Baicalein (BE), which was one of the skullcapflavones, can induce apoptosis in C. albicans. The apoptotic effects of BE were detected by flow cytometry using Annexin V-FITC and DAPI, and it was confirmed by transmission electron microscopy analysis. After exposure to 4 microg/ml BE for 12 h, about 10% of C. albicans cells were apoptotic. Both the increasing intracellular levels of reactive oxygen species (ROS) and upregulation of some redox-related genes (CAP1, SOD2, TRR1) were observed. Furthermore, we compared the survivals of CAP1 deleted, wild-type, and overexpressed strains and found that Cap1p attenuated BE-initiated cell death, which was coherent with a higher mRNA level of the CAP1 gene. In addition, the mitochondrial membrane potential of C. albicans cells changed significantly ( p<0.001) upon BE treatment compared with control. Taken together, our results indicate that BE treatment induces apoptosis in C.albicans cells, and the apoptosis was associated with the breakdown of mitochondrial membrane potential.
Subject(s)
Antioxidants/administration & dosage , Apoptosis/drug effects , Candida albicans/drug effects , Flavanones/administration & dosage , Basic-Leucine Zipper Transcription Factors , Candida albicans/physiology , Candida albicans/ultrastructure , Candidiasis/drug therapy , Candidiasis/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Genes, Fungal , Humans , Membrane Potential, Mitochondrial/drug effects , Microscopy, Electron, Transmission , RNA, Fungal/biosynthesis , RNA, Fungal/genetics , Reactive Oxygen Species/metabolism , Up-RegulationABSTRACT
1. The aim of the present study was to investigate the effects of ascorbic acid (AA) on the antifungal activity of fluconazole (FCZ) in a systemic murine candidiasis model as well as in vitro. 2. The murine model was established by infusion of Candida albicans via the tail vein. Control mice received no further treatment. Other groups of mice were injected with FCZ (0.5 mg/kg, i.p.) and then treated or not with 50 or 500 mg/kg AA intragastrically (i.g.) or i.p. In all groups, FCZ was administered i.p. 2 h after fungal inoculation, whereas AA was administered 6 h after fungal inoculation. Survival rate, kidney fungal burden and renal pathological changes were evaluated. 3. The in vitro effects of AA (5, 1 and 0.2 mmol/L) on the growth of various Candida strains in the presence of FCZ (0.125-64 microg/mL) were also investigated. The in vitro effects of two anti-oxidants, namely N-acetylcysteine (NAC; 5, 1 and 0.2 mmol/L) and reduced glutathione (GSH; 5, 1 and 0.2 mmol/L), on FCZ activity were evaluated to determine the mechanism of action of AA. 4. Intragastric administration of AA (50 or 500 mg/kg) significantly decreased the antifungal effect of 0.5 mg/kg FCZ. Although i.p. administration of AA (50 or 500 mg/kg) had no significant effect on the survival of mice, it dose-dependently inhibited the activity of FCZ, with significant inhibition observed with 500 mg/kg AA. 5. In vitro, AA decreased the activity of FCZ against various Candida strains. Both NAC and GSH dose-dependently decreased the activity of FCZ. 6. The results of the present study indicate that AA inhibits the antifungal activity of FCZ, suggesting that the two should not be used together clinically for the treatment of candidiasis.
Subject(s)
Antifungal Agents/therapeutic use , Ascorbic Acid/pharmacology , Candidiasis/drug therapy , Fluconazole/therapeutic use , Animals , Antifungal Agents/pharmacology , Antioxidants/pharmacology , Candida albicans/drug effects , Candidiasis/mortality , Disease Models, Animal , Drug Antagonism , Drug Evaluation, Preclinical , Drug Resistance, Fungal/drug effects , Fluconazole/pharmacology , Mice , Microbial Sensitivity TestsABSTRACT
The study was aimed to investigate the effects and mechanism of action of Changtai granule (CT), a traditional compound Chinese medicinal formula, in rodent 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Rats with TNBS/ethanol-induced colitis were used. The colonic wet weight, myeloperoxidase (MPO) activity, macroscopic and histological colon injury was observed. Inflammation cytokines were determined by ELISA methods and semi-quantitative RT-PCR. When dosed orally once daily, CT markedly attenuated TNBS-induced colitis. CT significantly attenuated colonic wet weight, macroscopic and histological colon injury. CT decreased mucosal mRNA levels for several inflammatory mediators: inducible nitric oxide synthase, cyclooxygenase 2, and macrophage inflammatory protein 2. CT also decreased mucosal mRNA and protein levels of T effectors cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Systemic levels of these cytokines were also dramatically attenuated. CD3/CD28-mediated costimulation of T helper 1 effector cytokines release in lamina propria mononuclear cells (LPMC) was markedly inhibited by CT ex vivo and in vitro. Also CT prevented cytokines production by nuclear factor-kappaB (NF-kappaB). The potential anti-inflammatory and immunomodulatory effect of CT in TNBS colitis suggests that CT may be an effective treatment approach for inflammatory bowel disease.
Subject(s)
Colitis/drug therapy , Inflammation/drug therapy , Plant Preparations/pharmacology , Animals , Colitis/chemically induced , Colitis/immunology , Enzyme-Linked Immunosorbent Assay , Euphorbia/chemistry , Haptens , Inflammation/etiology , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Male , Medicine, Chinese Traditional , Phellodendron/chemistry , Polygonum/chemistry , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Sanguisorba/chemistry , Trinitrobenzenesulfonic AcidABSTRACT
Candida albicans biofilms are structured microbial communities with high levels of drug resistance. Farnesol, a quorum-sensing molecule that inhibits hyphal formation in C. albicans, has been found to prevent biofilm formation by C. albicans. There is limited information, however, about the molecular mechanism of farnesol against biofilm formation. We used cDNA microarray analysis to identify the changes in the gene expression profile of a C. albicans biofilm inhibited by farnesol. Confocal scanning laser microscopy was used to visualize and confirm normal and farnesol-inhibited biofilms. A total of 274 genes were identified as responsive, with 104 genes up-regulated and 170 genes down-regulated. Independent reverse transcription-PCR analysis was used to confirm the important changes detected by microarray analysis. In addition to hyphal formation-associated genes (e.g., TUP1, CRK1, and PDE2), a number of other genes with roles related to drug resistance (e.g., FCR1 and PDR16), cell wall maintenance (e.g., CHT2 and CHT3), and iron transport (e.g., FTR2) were responsive, as were several genes encoding heat shock proteins (e.g., HSP70, HSP90, HSP104, CaMSI3, and SSA2). Further study of these differentially regulated genes is warranted to evaluate how they may be involved in C. albicans biofilm formation. Consistent with the down-regulation of the cell surface hydrophobicity-associated gene (CSH1), the water-hydrocarbon two-phase assay showed a decrease in cell surface hydrophobicity in the farnesol-treated group compared to that in the control group. Our data provide new insight into the molecular mechanism of farnesol against C. albicans biofilm formation.