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1.
SIRT3: A potential therapeutic target for liver fibrosis.
Ning, Y, Dou, X, Wang, Z, Shi, K, Wang, Z, Ding, C, Sang, X, Zhong, X, Shao, M, Han, X, et al
Pharmacology & therapeutics. 2024;:108639
Abstract
Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.
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Performance and mechanism of chromium reduction in denitrification biofilm system with different carbon sources.
Cao, G, Gao, J, Song, J, Jia, X, Liu, Y, Niu, J, Yuan, X, Zhao, Y
The Science of the total environment. 2024;:167191
Abstract
In the process of biological reduction of Cr(VI), the type of carbon sources affects the rate and effect of Cr(VI) reduction, but its specific performance and influencing mechanism have not yet been explored. In this study, four denitrification biofilm reactors were operated under four common carbon sources (C6H12O6, CH3COONa, CH3OH, CH3COONa:C6H12O6 1:1) to reveal the impact of carbon sources on Cr(VI) reduction. Through preliminary experimental concentration research, 75 mg/L Cr(VI) was selected as the dosing concentration. In long-term operation, the composite carbon sources of CH3COONa and C6H12O6 demonstrated excellent stability and achieved an impressive Cr(VI) removal efficiency of 99.5 %. The following sequence was C6H12O6, CH3COONa, and CH3OH. Among them, CH3OH was less competitive and the system was severely unbalanced with lowest Cr(VI) reduction efficiency. The toxicity reactions, changes in EPS and its functional groups, and electron transfer revealed the reduction and fixation mechanism of chromium on denitrification biofilm. The changes in microbial communities indicated that microbial communities in composite carbon sources can quickly adapt to the high toxic environment. The proportion of Trichococcus reached 43.6 %, which played an important role in denitrification and Cr(VI) reduction. Meanwhile, the prediction of microbial COG function reflected its excellent metabolic ability and defense mechanism.
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3.
Polyphenol supplementation boosts aerobic endurance in athletes: systematic review.
Cao, G, Zuo, J, Wu, B, Wu, Y
Frontiers in physiology. 2024;:1369174
Abstract
In recent years, an increasing trend has been observed in the consumption of specific polyphenols, such as flavonoids and phenolic acids, derived from green tea, berries, and other similar sources. These compounds are believed to alleviate oxidative stress and inflammation resulting from exercise, potentially enhancing athletic performance. This systematic review critically examines the role of polyphenol supplementation in improving aerobic endurance among athletes and individuals with regular exercise habits. The review involved a thorough search of major literature databases, including PubMed, Web of Science, SCOPUS, SPORTDiscus, and Embase, covering re-search up to the year 2023. Out of 491 initially identified articles, 11 met the strict inclusion criteria for this review. These studies specifically focused on the incorporation of polyphenols or polyphenol-containing complexes in their experimental design, assessing their impact on aerobic endurance. The methodology adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the risk of bias was evaluated using the Cochrane bias risk assessment tool. While this review suggests that polyphenol supplementation might enhance certain aspects of aerobic endurance and promote fat oxidation, it is important to interpret these findings with caution, considering the limited number of studies available. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023453321.
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Efficacy and safety of low-dose aspirin on preventing transplant renal artery stenosis: a prospective randomized controlled trial.
Tian, X, Ji, B, Niu, X, Duan, W, Wu, X, Cao, G, Zhang, C, Zhao, J, Wang, Z, Gu, Y, et al
Chinese medical journal. 2023;(5):541-549
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Abstract
BACKGROUND Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS. METHODS After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People's Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). RESULTS In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan-Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09-0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. CONCLUSION Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects. TRIAL REGISTRATION Clinicaltrials.gov, NCT04260828.
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The Effects of Probiotics/Synbiotics on Glucose and Lipid Metabolism in Women with Gestational Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.
Mu, J, Guo, X, Zhou, Y, Cao, G
Nutrients. 2023;15(6)
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Women with gestational diabetes mellitus (GDM) are at an increased risk of complications during pregnancy and type 2 diabetes, pancreatic cancer, and heart disease after pregnancy. There is some controversy over the research surrounding current treatments of GDM and as such new treatment strategies are being researched and developed. Amongst these is the possibility of using probiotics and synbiotics to alleviate the driving factors of GDM, however the research is inconclusive as some studies have shown a benefit whereas others have not. This meta-analysis of 11 randomised control trials (RCTs) containing 779 participants aimed to determine the effect of probiotic/synbiotics on sugar and lipid levels in the blood. The results showed that amongst 8 of the RCTs, Lactobacillus was the most researched probiotic gut bacteria, with 6 species researched. In addition, Bifidobacterium bifidum and Streptococcus thermophilus were also used as a probiotic. 3 RCTs looked at synbiotics including 5 Lactobacillus species and 3 Bifidobacterium species. Supplementation with probiotics/synbiotics significantly improved blood sugar levels, measures of insulin resistance, and total cholesterol in pregnant women with GDM. Other blood lipids such as triglycerides, high density lipoprotein, low density lipoprotein, weight at the end of the trial, and weight gain during pregnancy were unaffected by supplementation. It was concluded that probiotics/synbiotics are of benefit to women with GDM especially if they contain L. acidophilus and B. bifidum. However, there may be more research required to better inform GDM management. This study could be used by healthcare professionals to understand that the gut microbiota may have a pivotal role in GDM. More research is required before this forms part of a regular management strategy.
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical therapy is the foundation of GDM management, for achieving optimal glycemic control often requires treatment with insulin or metformin. Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Probiotics are a relatively new intervention, which can reduce the mother's blood sugar levels and, furthermore, adjust glucose and lipid metabolism in both mother and offspring. OBJECTIVE The aim of this systematic review and meta-analysis is to explore the effect of probiotics/synbiotics on glucose and lipid metabolism in women with GDM. METHODS A systematic search of the literature was conducted using the electronic databases Cochrane Library, Web of Science, PubMed, and EBOSCO, published between 1 January 2012 and 1 November 2022. A total of 11 randomized controlled clinical trials (RCTs) were analyzed. The indicators included fasting plasma glucose (FPG), fasting serum insulin (FSI), the homoeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG), the mean weight at end of trial, and gestational weight gain (GWG). RESULTS Compared with the placebo, probiotics/synbiotics were associated with a statistically significant improvement in FPG (MD = -2.33, 95% CI = -4.27, -0.40, p = 0.02), FSI (MD = -2.47 95% CI = -3.82, -1.12, p = 0.0003), HOMA-IR (MD = -0.40, 95% CI = -0.74, -0.06, p = 0.02), and TC (MD = -6.59, 95% CI = -12.23,--0.95, p = 0.02), while other factors had no significant difference. The subgroup analysis revealed that the kind of supplement led to heterogeneity for FPG and FSI, while heterogeneity was not found for others. CONCLUSION Probiotics/synbiotics could control glucose and lipid metabolism in pregnant women with GDM. There was a significant improvement in FPG, FSI, HOMA-IR, and TC. The use of specific probiotic supplementation may be a promising prevention and therapeutic strategy for GDM. However, due to the heterogeneity among existing studies, further studies are warranted to address the limitations of existing evidence and better inform the management of GDM.
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Pharmacological Mechanisms and Clinical Applications of Curcumin: Update.
Hao, M, Chu, Y, Lei, J, Yao, Z, Wang, P, Chen, Z, Wang, K, Sang, X, Han, X, Wang, L, et al
Aging and disease. 2023;(3):716-749
Abstract
Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.
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Beneficial effect and mechanism of natural resourced polysaccharides on regulating bone metabolism through intestinal flora: A review.
Zhou, Y, Sheng, YJ, Li, CY, Zou, L, Tong, CY, Zhang, Y, Cao, G, Shou, D
International journal of biological macromolecules. 2023;(Pt 7):127428
Abstract
Bone metabolism is an important biological process for maintaining bone health. Polysaccharides of natural origin exert beneficial effects on bone metabolism. Polysaccharide molecules often have difficulty passing through the intestinal cell membrane and are directly absorbed in the gastrointestinal tract. Therefore, polysaccharides may affect intestinal flora and play a role in disease treatment. We performed a comprehensive review of the relevant literature published from 2003 to 2023. We found that several polysaccharides from traditional Chinese medicines, including Astragalus, Achyranthes bidentata and Eucommia ulmoides, and the polysaccharides from several dietary fibers mainly composed of inulin, resistant starch, and dextran could enrich the intestinal microbiota group to regulate bone metabolism. The promotion of polysaccharide decomposition by regulating the Bacteroides phylum is particularly critical. Studies on the structure-activity relationship showed that molecular weight, glycosidic bonds, and monosaccharide composition may affect the ability of polysaccharides. The mechanism by which polysaccharides regulate intestinal flora to enhance bone metabolism may be related to the regulation of short-chain fatty acids, immunity, and hormones, involving some signaling pathways, such as TGF-β, Wnt/β-catenin, BMP/Smads, and RANKL. This paper provides a useful reference for the study of polysaccharides and suggests their potential application in the treatment of bone metabolic disorders.
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Ethnic, Botanic, Phytochemistry and Pharmacology of the Acorus L. Genus: A Review.
Zhao, Y, Li, J, Cao, G, Zhao, D, Li, G, Zhang, H, Yan, M
Molecules (Basel, Switzerland). 2023;(20)
Abstract
The genus Acorus, a perennial monocotyledonous-class herb and part of the Acoraceae family, is widely distributed in the temperate and subtropical zones of the Northern and Southern Hemispheres. Acorus is rich in biological activities and can be used to treat various diseases of the nervous system, cardiovascular system, and digestive system, including Alzheimer's disease, depression, epilepsy, hyperlipidemia, and indigestion. Recently, it has been widely used to improve eutrophic water and control heavy-metal-polluted water. Thus far, only three species of Acorus have been reported in terms of chemical components and pharmacological activities. Previously published reviews have not further distinguished or comprehensively expounded the chemical components and pharmacological activities of Acorus plants. By carrying out a literature search, we collected documents closely related to Acorus published from 1956 to 2022. We then performed a comprehensive and systematic review of the genus Acorus from different perspectives, including botanical aspects, ethnic applications, phytochemistry aspects, and pharmacological aspects. Our aim was to provide a basis for further research and the development of new concepts.
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Single-Ascending-Dose, Food-Effect, and Multiple-Dose Study of the Safety, Tolerability, and Pharmacokinetics of the Pangenotypic Anti-Hepatitis C Virus Drug Holybuvir in Healthy Chinese Subjects.
Cao, Y, Wu, X, Wang, Z, Huang, Y, Wu, J, Cao, G, Yu, J, Wang, J, Yang, H, Zhang, W, et al
Antimicrobial agents and chemotherapy. 2023;(3):e0129522
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Holybuvir is a novel pangenotypic hepatitis C virus NS5B inhibitor. This first in-human study aimed to evaluate the pharmacokinetics (PK), safety, and tolerability of holybuvir and its metabolites and the effect of food on the PK of holybuvir and its metabolites in healthy Chinese subjects. A total of 96 subjects were enrolled in this study which included (i) a single-ascending-dose (SAD) study (100 to 1,200 mg), (ii) a food-effect (FE) study (600 mg), and (iii) a multiple-dose (MD) study (400 and 600 mg once daily for 14 days). The results showed that single oral administration of holybuvir at doses up to 1,200 mg was well tolerated. Holybuvir was rapidly absorbed and metabolized in the human body, which was consistent with the characteristics of holybuvir as a prodrug. PK analysis showed that Cmax and area under the curve (AUC) increased with dose in no dose-proportional manner after a single-dose administration (100 to 1,200 mg). Although high-fat meals did change the PK of holybuvir and its metabolites, clinical significance of changes in PK parameters induced by eating a high-fat diet would be further confirmed. Following multiple-dose administration, accumulation of metabolites SH229M4 and SH229M5-sul was observed. The favorable PK and safety results support the further development of holybuvir for patients with HCV. (This study was registered at Chinadrugtrials.org under identifier CTR20170859.).
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Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Mirogabalin in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Study.
Li, Y, Toyama, K, Nakatsu, T, Ishizuka, H, Wu, H, Cao, G, Yu, J, Wang, Y, Liu, X, Guo, B, et al
Advances in therapy. 2023;(4):1628-1643
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INTRODUCTION Mirogabalin is a treatment option for patients with neuropathic pain; however, safety, tolerability, and pharmacokinetics (PK) data specifically for Chinese individuals are limited to a single-dose study. We aimed to assess these for both single- and multiple-dose mirogabalin in healthy Chinese participants. METHODS In this randomized, double-blind, placebo-controlled, phase I study, 54 healthy Chinese men and women aged 18-45 years were randomly allocated to receive single- (5, 10, or 15 mg, daily) or multiple-dose (5 mg titrated to 15 mg, twice-daily, over 22 days) oral mirogabalin or placebo. In each of three single-dose groups, 10 participants received mirogabalin and 2 received placebo; in the multiple-dose group, 14 participants received mirogabalin and 4 received placebo. The primary endpoints were PK, safety, and tolerability variables, including treatment-emergent adverse events (TEAEs), laboratory tests, and vital signs. PK data were collected for both single- and multiple-dose cohorts and evaluated by non-compartmental analysis. RESULTS Single- and multiple-dose mirogabalin was generally well tolerated with no deaths, serious TEAEs, or TEAEs leading to treatment discontinuation. Frequently reported TEAEs included dizziness, nystagmus, increased blood triglycerides, headache, and increased blood uric acid and creatine phosphokinase. Single-dose mirogabalin was rapidly absorbed (median time to maximum plasma concentration, 1.00 h) and eliminated (mean terminal elimination half-life, 2.57-3.08 h). The exposure was approximately dose-proportional. In the multiple-dose cohort, the trough plasma concentration increased dose-proportionally, and exposure and clearance were comparable to that following a single 15-mg dose. The mean cumulative amount excreted into urine up to 48 h post-dose increased in a dose-proportional manner, the mean cumulative percentage excreted into urine was 61.9%-74.3%, and renal clearance remained relatively constant. CONCLUSION Consistent with previous phase I studies in other populations, mirogabalin was safe and well tolerated in healthy Chinese participants at single and multiple doses of up to 15 mg twice-daily.