Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

ObjectiveTo investigate the disruptive effects of perinatal exposure to the environmental endocrine disruptor bisphenol AF (BPAF) on hepatic lipid metabolism in prepubertal (postnatal day 21, PND21) male offspring rats, and to provide scientific evidence for assessing the obesogenic effect of BPAF. MethodsSprague-Dawley (SD) rats aged 8 weeks were used in this study. Pregnant rats were divided into BPAF dose groups (2, 10, 50 mg·kg⁻¹) and a vehicle control group (corn oil), with 6 confirmed pregnant females per group. Gavage administration started from gestational day 0 and continued until the end of lactation. At PND21, one male offspring per litter was randomly selected. Serum concentrations of glucose (GLU), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), leptin (LEP), free fatty acid (FFA), as well as oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA), were measured. Pathological changes in liver and adipose tissues were evaluated, and the expression levels of genes related to hepatic lipid metabolism were measured. ResultsCompared to the vehicle control group, the 50 mg·kg⁻¹ group showed significantly increased serum LEP and MDA levels in male offspring (P<0.05), and significant upregulation of hepatic lipoprotein lipase (Lpl), fatty acid synthetase (Fas), and peroxisome proliferator-activated receptor γ (Pparg) gene expression (P<0.05). The 2 mg·kg⁻¹ group exhibited a significant increase in adipocyte length (P<0.05), while the 50 mg·kg⁻¹ group showed significant increases in both adipocyte area and length (P<0.05). No significant abnormalities were observed in liver histopathological examination. ConclusionPerinatal exposure to 50 mg·kg⁻¹ BPAF induced adipocyte hypertrophy, elevated leptin levels, upregulation of lipid synthesis gene expression, and enhanced oxidative stress in prepubertal male offspring, suggesting that BPAF may exert environmental obesogenic effects by disrupting lipid metabolism pathways.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

This study investigated the mechanism of Chaishao Kaiyu Decoction in improving hippocampal neuroinflammation in depressed rats based on complement component 3(C3)/C3 receptor(C3aR). A total of 60 SD rats were randomly divided into a blank group, a model group, high, medium, and low dose groups of Chaishao Kaiyu Decoction, and a positive drug group, with 10 rats in each group. Except for the blank group, chronic unpredictable mild stress(CUMS) was used to construct depression models in other groups. Sucrose preference, open-field experiment, forced swimming, and water maze were used to detect the changes in depression-like behavior in each group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum inflammatory factor level in rats, and hematoxylin-eosin(HE) staining and Nissl staining were employed to observe the pathological damage of hippocampal neurons. Golgi-Cox staining was used to observe the dendritic spine damage of hippocampal neurons, and immunofluorescence and Western blot were utilized to detect the expression of microglial marker Iba-1 and C3/C3aR protein in the hippocampus of rats. The behavioral results showed that compared with the model group, Chaishao Kaiyu Decoction could significantly strengthen the sugar water preference, increase the distance and number of voluntary activities, shorten the immobility time in forced swimming and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant. ELISA results showed that the content of inflammatory factors in the hippocampus of depressed rats was significantly higher than that of the blank group, and the content of inflammatory factors decreased significantly after the intervention of Chaishao Kaiyu Decoction. In addition, Chaishao Kaiyu Decoction could relieve pathological damage such as cell swelling and loose arrangement of hippocampus tissue. In the Western blot experiment, the expression levels of C3 and C3aR proteins in the model group were higher than those in the blank group, while the expression of C3 and C3aR in Chaishao Kaiyu Decoction could be down-regulated. Immunofluorescence results showed that compared with the model group, the fluorescence intensity of microglia marker Iba-1 decreased significantly after the intervention of Chaishao Kaiyu Decoction and positive drugs. The antidepressant effect of Chaishao Kaiyu Decoction may be related to the down-regulation of C3/C3aR signaling pathway-related proteins, thus alleviating hippocampal inflammation.
Animals ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Male ; Depression/metabolism* ; Complement C3/metabolism* ; Receptors, Complement/metabolism* ; Humans ; Neuroinflammatory Diseases/genetics*

Coronary heart disease is a cardiovascular disease that affects coronary arteries. It presents high incidence and high mortality worldwide, bringing a serious threat to human health and quality of life. Salviae Miltiorrhizae Radix et Rhizoma derived from Salvia miltiorrhiza is widely used in the treatment of cardiovascular diseases, such as coronary heart disease. Salvianolic acid B is an active component in Salviae Miltiorrhizae Radix et Rhizoma extracts, and studies have shown that it has anti-inflammatory, antioxidant, apoptosis-and autophagy-regulating, anti-fibrosis, and metabolism-modulating effects. This article reviews the research progress regarding the therapeutic effect of salvianolic acid B on coronary heart disease in the recent decade. It elaborates on the role and mechanism of salvianolic acid B in treating coronary heart disease from multiple perspectives, such as the inhibition of thrombosis, improvement of blood circulation, reduction of myocardial cell injury, and inhibition of cardiac remodeling. This article provides a theoretical basis for the application of Chinese medicinal materials and TCM prescriptions containing salvianolic acid B in the treatment of coronary heart disease.
Humans ; Benzofurans/administration & dosage* ; Coronary Disease/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Salvia miltiorrhiza/chemistry* ; Animals ; Depsides

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts