Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective: To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata (Willd.) Ohwi root (P. lobata, Ge Gen) and Hovenia dulcis Thunb. (H. dulcis, Zhi Ju Zi) against ethanol-induced liver damage in vitro, using a human hepatoma cell line G2 (HepG2) cell model. Methods: HepG2 cells were cultured in medium containing 4% ethanol to establish a model of alcoholic liver damage. The cells were then treated with the combined extract obtained via cryogenic extraction. Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers, antioxidant enzymes, and inflammatory cytokines. In addition, activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was examined to elucidate the mechanisms underlying the effects of the extract. Results: Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells; promoted the elevated expression of superoxide dismutase, catalase, and glutathione, indicating enhanced antioxidant defenses; and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals. In addition, by activating the PI3K/AKT pathway, treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets, subsequently inhibiting apoptosis. Moreover. inflammatory responses were mitigated, as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6, and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase, thereby indicating hepatoprotective effects. Conclusion The combined P. lobata root and H. dulcis extract was established to have notable antioxidative and anti-inflammatory properties, effectively alleviating ethanol-induced liver damage in vitro. These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.

Preeclampsia(PE)is a severe pregnancy complication that poses significant risks to maternal and fetal health,and its pathogenesis remains unclear.Recent studies have shown that lactate dehydrogenase(LDH),a key enzyme in glycolysis,plays a piv-otal role in the development and progression of PE.This article reviews the abnormal changes in the levels of LDH and its isozymes in serum and placental tissue and their impact on the pathogenesis of PE and analyzes the molecular mechanisms by which LDH subunits contribute to placental dysfunction through multiple pathways including hypoxia,inflammation,autophagy dysregulation,and cellular damage.In addition,this article discusses the role of lactate,a metabolic product of LDH activity,in the pathogenesis of PE.LDH can be used as a potential biomarker for PE,and the regulation of non-metabolic functions and metabolic reprogramming mediated by LDH provide new targets for the prevention and treatment of PE.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*

Catechins have been proven to exert antitumor effects in different kinds of cancers. However, the underlying mechanisms have not been completely clarified yet. This study aimed to assess the effects and mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) on human melanoma skin A375 cells. Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect. Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest. EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level, indicating the development of apoptosis. Furthermore, EGCG and ECG could decreased mitochondrial membrane potential of A375 cells. In addition, the expression of Beclin-1, LC3 and Sirt3 were downregulated at protein levels, which known to be associated with autophagy. After autophagy was increased by rapamycin, the apoptotic trend was not change, indicating that apoptosis and autophagy are independent. Mechanistically, EGCG and ECG treatments decreased phosphorylated-AMPK (p-AMPK) and increased the ratios of p-PI3K, p-AKT and p-mTOR in melanoma cells. Conclusively, EGCG and ECG induced apoptosis via mitochondrial signaling pathway, downregulated autophagy through modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathway. It indicated that EGCG and ECG may be utilized in human melanoma treatment.
AMP-Activated Protein Kinases/genetics* ; Apoptosis ; Autophagy ; Catechin/analogs & derivatives* ; Electrocardiography ; Humans ; Melanoma/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

Objective:To describe the clinical features and analyze the prognostic factors of blastemaltype Wilms tumor. To explore the clinical risk factors affecting the prognosis of blastoma.Methods:Clinical data of 75 patients admitted to the surgery department of Beijing Children's Hospital from January 2008 to June 2020 who were confirmed to be blastemal-type Wilms tumor by postoperative pathology without preoperative chemotherapy. The patients' general information, clinical characteristics, inspection data, surgical methods and follow-up results were collected. The related factors which influences its prognosis were analyzed. Among the 75 patients, 45 cases (60.0%) were male and 30 cases (40.0%) were female. The diagnosis age was 6-144 m, mean age was 39.1 m. Left side: 38 cases (50.7%), right side: 37 cases (49.3%). The clinical manifestations were abdominal mass in 35 cases (46.7%), hematuria in 24 cases (32.0%), abdominal pain in 7 cases (9.3%) and physical examination in 9 cases (12.0%). There were Stage Ⅰ 30 cases, Stage Ⅱ 28 cases, Stage Ⅲ 15 cases, Stage Ⅳ 2 cases. There were preoperative tumor rupture in 5 cases, intraoperative tumor rupture in 2 cases. Clinical stage Ⅰ and Ⅱ were classified as early, while stage Ⅲ, Ⅳ were classified as late. According to COG protocol, stage Ⅰ and Ⅱ patients received EE4A, stage Ⅲ and Ⅳ patients received DD4A protocol and radiotherapy. The number of lymph nodes sampled during operation was more than 7 in 10 patients.Results:7 cases were tested for 1p16q. One case(stage Ⅱ) was absent at 1p/16q LOH, and chemotherapy was upgraded from EE4A to DD4A. After the recurrence of 1 case in clinical stage Ⅰ, the 1p/16q heterozygotic deletion test was performed, which was changed to M regimen chemotherapy. Only 1p lost in one case, and 1p/16q was negative in 4 cases, so the original chemotherapy regimen was maintained. A total of 67 patients were recruited to the study. The median follow-up time was 57 months. The 5-year relapse-free survival(RFS) rate was74.7%, and the 5-year overall survival(OS) rate was 88.0%. Cox multivariate regression analysis showed that: advanced clinical stage ( HR=4.9, 95% CI 1.2-19.6, P=0.025), tumor volume ( HR=1.7, 95% CI 0.4-6.9, P=0.048), and tumor rupture ( HR=20.1, 95% CI 4.7-85.5, P<0.001) were independent risk factors for prognosis of blastoma. Gender, age, side profile, clinical manifestations, tumor embolism, and number of lymph nodes sampled had no significant influence on the survival rate of blastoma ( P>0.05). Conclusion:Advanced stage (Ⅲ-Ⅳ), tumor volume≥1 000 ml, tumor weight and tumor rupture were independent risk factors for relapse. Insufficient lymph node sampling and incomplete 1p16q, may be the reasons for the increased risk of local recurrence in low-stage patients due to the underestimated risk classification and insufficient treatment intensity.

Alpha-keto acid is a bifunctional organic compound containing both carboxyl and ketone groups, and widely applied in the industries of food, pharmaceutical and cosmetics. Based on the demand of eco-friendly process, safety and sustainable development, production of α-keto acids by enzymatic conversion technology has been paid more and more attention. In this article, we review the status of α-keto acids biosynthesis from three aspects: enzymatic screening, enzymatic modification and optimization of enzymatic conversion conditions. Meanwhile, we also indicate future research directions for further improving α-keto acids production.
Keto Acids ; metabolism

Since the Eighteenth National Congress of the Communist Party of China, China has constantly innovated and developed its diplomatic concept, and proposed the important idea of the Community of Shared Future for Mankind (CSFM), which contributes a discourse system with Chinese characteristics to the world. It is indicated that discourse builds its subject and governs the subject’s discourse practices, and the discourse subject strengthens and reiterates discourse rules in discourse practices. China aid project of schistosomiasis control in Zanzibar is a discourse subject of the CSFM discourse system. This paper analyzes the discourse status, discourse practices and the reiteration of discourse rules of China aid project of schistosomiasis control in Zanzibar.

The gene of beta-glucuronidase from Thermotoga maritima was cloned into the plasmid pHsh, and expressed in Escherichia coli JM109. The recombinant protein was purified to homogeneity by a simple step, heat treatment. The recombinant enzyme had a molecular mass of 65.9 kD. The optimal activity of beta-glucuronidase was found at pH 5.0 and 80 degrees C. The purified enzyme was stable over a pH range from 5.8 to 8.2 and had a half life of 2 h at 80 degrees C. The kinetic experiments at 80 degrees C with p-nitrophenyl-beta- glucuronide as substrate gave a K(m) and V(max) of 0.18 mmol/L and 312 u per mg of protein. The purified enzyme could transform glycyrrhizin to glycyrrhetinic acid.
Cloning, Molecular ; Enzyme Stability ; Escherichia coli ; enzymology ; genetics ; Glucuronidase ; biosynthesis ; genetics ; metabolism ; Glycyrrhetinic Acid ; metabolism ; Glycyrrhizic Acid ; metabolism ; Hot Temperature ; Kinetics ; Recombinant Proteins ; biosynthesis ; genetics ; metabolism ; Thermotoga maritima ; enzymology ; genetics