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1.
Association of air pollution and risk of chronic kidney disease: A systematic review and meta-analysis.
Xu, W, Jia, L, Lin, Y, Zhang, C, Sun, X, Jiang, L, Yao, X, Wang, N, Deng, H, Wang, S, et al
Journal of biochemical and molecular toxicology. 2024;(1):e23610
Abstract
Although epidemiological studies have evaluated the association between ambient air pollution and chronic kidney disease (CKD), the results remain mixed. To clarify the nature of the association, we conducted a comprehensive systematic review and meta-analysis to assess the global relationship between air pollution and CKD. The Web of Science, PubMed, Embase and Cochrane Library databases systematically were searched for studies published up to July 2023 and included 32 studies that met specific criteria. The random effects model was used to derive overall risk estimates for each pollutant. The meta-analysis estimated odds ratio (ORs) of risk for CKD were 1.42 (95% confidence interval [CI]: 1.31-1.54) for each 10 μg/m3 increase in PM2.5 ; 1.20 (95% CI: 1.14-1.26) for each 10 μg/m3 increase in PM10 ; 1.07 (95% CI: 1.05-1.09) for each 10 μg/m3 increase in NO2 ; 1.03 (95% CI: 1.02-1.03) for each 10 μg/m3 increase in NOX ; 1.07 (95% CI: 1.01-1.12) for each 1 ppb increase in SO2 ; 1.03 (95% CI: 1.00-1.05) for each 0.1 ppm increase in CO. Subgroup analysis showed that this effect varied by gender ratio, age, study design, exposure assessment method, and income level. Furthermore, PM2.5 , PM10 , and NO2 had negative effects on CKD even within the World Health Organization-recommended acceptable concentrations. Our results further confirmed the adverse effect of air pollution on the risk of CKD. These findings can contribute to enhance the awareness of the importance of reducing air pollution among public health officials and policymakers.
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2.
Structural biology of voltage-gated calcium channels.
Yao, X, Gao, S, Yan, N
Channels (Austin, Tex.). 2024;(1):2290807
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Abstract
Voltage-gated calcium (Cav) channels mediate Ca2+ influx in response to membrane depolarization, playing critical roles in diverse physiological processes. Dysfunction or aberrant regulation of Cav channels can lead to life-threatening consequences. Cav-targeting drugs have been clinically used to treat cardiovascular and neuronal disorders for several decades. This review aims to provide an account of recent developments in the structural dissection of Cav channels. High-resolution structures have significantly advanced our understanding of the working and disease mechanisms of Cav channels, shed light on the molecular basis for their modulation, and elucidated the modes of actions (MOAs) of representative drugs and toxins. The progress in structural studies of Cav channels lays the foundation for future drug discovery efforts targeting Cav channelopathies.
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Decaffeinated green tea polyphenols supplementation had no adverse health effects in girls with obesity: a randomized controlled trial.
Yao, D, Xie, L, Du, K, Yao, X, Shen, X
Asia Pacific journal of clinical nutrition. 2024;(1):111-117
Abstract
BACKGROUND AND OBJECTIVES While the health promoting effects of green tea polyphenols have been identi-fied among adult, research on children is scarce probably due to safety concerns about caffeine. This study aims to evaluate the safety of decaffeinated green tea polyphenols (DGTP) supplementation in girls with obesity and lay the foundation for its application in children population. METHODS AND STUDY DESIGN This 12-week randomized, double-blinded, parallel-controlled trial was performed among 62 girls with obesity aged 6 to 10 years old. Participants were allocated to take 400 mg/d DGTP (DGTP group, n = 31) or isodose placebo (Control group, n = 31) at random. Anthropometric measurements and biochemical parameters including hepatic and renal function indicators, serum minerals concentrations, and routine blood parameters, were measured at baseline and the end of this trial. DGTP intake diary was required for each participant to record any abnormal reactions. RESULTS After the 12-week supplementation, compared to Control group, the uric acid concentration in DGTP group showed a significant decrease (-48.0 ± 83.2 vs -0.01 ± 69.1, μmol/L), within the normal range. Regarding other biochemical indicators, there were no significant differences in changed values between the two groups. Throughout the trial, no adverse effects were reported in either group. CONCLUSIONS This study indicated that the supplementation of 400 mg/d DGTP for 12 weeks had no adverse health effects in girls with obesity, providing evidence for the DGTP adoption in children research.
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Natural products for combating multidrug resistance in cancer.
Chen, T, Xiao, Z, Liu, X, Wang, T, Wang, Y, Ye, F, Su, J, Yao, X, Xiong, L, Yang, DH
Pharmacological research. 2024;:107099
Abstract
Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
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Brassinolide as potential rescue agent for Pinellia ternata grown under microplastic condition: Insights into their modulatory role on photosynthesis, redox homeostasis, and AsA-GSH cycling.
Zhang, D, Zhang, L, Yuan, C, Zhai, K, Xia, W, Duan, Y, Zhao, B, Chu, J, Yao, X
Journal of hazardous materials. 2024;:134116
Abstract
Microplastic (MP), as a new pollutant, not only affects the growth and development of plants but also may affect the secondary metabolites of plants. The anti-tumor role of Pinellia ternata is related to secondary metabolites. The role of brassinolide (BR) in regulating plant resistance is currently one of the research hotspots. The paper mainly explores the regulation of BR on growth and physiology of Pinellia ternata under MP stress. The experimental design includes two levels of MP (0, 1%) and two levels of BR (0, 0.1 mg/L). MP led to a marked reduction in plant height (15.0%), Fv/Fm (3.2%), SOD and APX activity (15.0%, 5.1%), whereas induced an evident raise in the rate of O2·- production (29.6%) and GSH content (4.4%), as well as flavonoids (6.8%), alkaloids (75%), and β-sitosterol (26.5%) contents. Under MP addition, BR supply significantly increased plant height (15.7%), aboveground and underground biomass (16.1%, 10.3%), carotenoid and GSH content (11.8%, 4.2%), Fv/Fm (2.9%), and activities of SOD, GR, and MDHAR (32.2%, 21.08%, 20.9%). These results indicate that MP suppresses the growth of P. ternata, although it promotes secondary metabolism. BR can alleviate the inhibitory effect of MP on growth by improving photosynthesis, redox homeostasis, and the AsA-GSH cycle.
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Population Pharmacokinetic/Pharmacodynamic Analysis of the Glucokinase Activator PB201 in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus: Facilitating the Clinical Development of PB201 in China.
Song, L, Cao, F, Niu, S, Xu, M, Liang, R, Ding, K, Lin, Z, Yao, X, Liu, D
Clinical pharmacokinetics. 2024;(1):93-108
Abstract
PB201 is an orally active, partial glucokinase activator targeting both pancreatic and hepatic glucokinase. As the second glucokinase activator studied beyond phase I, PB201 has demonstrated promising glycemic effects as well as favorable pharmacokinetic (PK) and safety profiles in patients with type 2 diabetes mellitus (T2DM). This study aims to develop a population PK/pharmacodynamic (PD) model for PB201 using the pooled data from nine phase I/II clinical trials conducted in non-Chinese healthy volunteers and a T2DM population and to predict the PK/PD profile of PB201 in a Chinese T2DM population. We developed the PK/PD model using the non-linear mixed-effects modeling approach. All runs were performed using the first-order conditional estimation method with interaction. The pharmacokinetics of PB201 were well fitted by a one-compartment model with saturable absorption and linear elimination. The PD effects of PB201 on reducing the fasting plasma glucose and glycosylated hemoglobin levels in the T2DM population were described by indirect response models as stimulating the elimination of fasting plasma glucose, where the production of glycosylated hemoglobin was assumed to be stimulated by fasting plasma glucose. Covariate analyses revealed enhanced absorption of PB201 by food and decreased systemic clearance with ketoconazole co-administration, while no significant covariate was identified for the pharmacodynamics. The population PK model established for non-Chinese populations was shown to be applicable to the Chinese T2DM population as verified by the PK data from the Chinese phase I study. The final population PK/PD model predicted persistent and dose-dependent reductions in fasting plasma glucose and glycosylated hemoglobin levels in the Chinese T2DM population receiving 50/50 mg, 100/50 mg, and 100/100 mg PB201 twice daily for 24 weeks independent of co-administration of metformin. Overall, the proposed population PK/PD model quantitatively characterized the PK/PD properties of PB201 and the impact of covariates on its target populations, which allows the leveraging of extensive data in non-Chinese populations with the limited data in the Chinese T2DM population to successfully supported the waiver of the clinical phase II trial and facilitate the optimal dose regimen design of a pivotal phase III study of PB201 in China.
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7.
Unveiling the unique role of iron in the metabolism of methanogens: A review.
Ma, Y, Qu, Y, Yao, X, Xia, C, Lv, M, Lin, X, Zhang, L, Zhang, M, Hu, B
Environmental research. 2024;:118495
Abstract
Methanogens are the main participants in the carbon cycle, catalyzing five methanogenic pathways. Methanogens utilize different iron-containing functional enzymes in different methanogenic processes. Iron is a vital element in methanogens, which can serve as a carrier or reactant in electron transfer. Therefore, iron plays an important role in the growth and metabolism of methanogens. In this paper, we cast light on the types and functions of iron-containing functional enzymes involved in different methanogenic pathways, and the roles iron play in energy/substance metabolism of methanogenesis. Furthermore, this review provides certain guiding significance for lowering CH4 emissions, boosting the carbon sink capacity of ecosystems and promoting green and low-carbon development in the future.
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Efficacy and safety of upadacitinib for 16-week extended induction and 52-week maintenance therapy in patients with moderately to severely active ulcerative colitis.
Panaccione, R, Danese, S, Zhou, W, Klaff, J, Ilo, D, Yao, X, Levy, G, Higgins, PDR, Loftus, EV, Chen, S, et al
Alimentary pharmacology & therapeutics. 2024;(3):393-408
Abstract
BACKGROUND Upadacitinib is an oral, selective Janus kinase inhibitor. AIM: To assess the efficacy and safety of upadacitinib in patients with moderate-to-severe ulcerative colitis following 16-week extended induction therapy, and 52-week maintenance therapy in patients achieving clinical response after 16-week extended induction therapy METHODS Patients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re-randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52-week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout. RESULTS Overall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib. CONCLUSIONS Patients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy. CLINICAL TRIAL REGISTRATION NCT02819635; NCT03653026.
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9.
Antioxidant potential of chlorogenic acid in Age-Related eye diseases.
Tang, Y, Fang, C, Shi, J, Chen, H, Chen, X, Yao, X
Pharmacology research & perspectives. 2024;(1):e1162
Abstract
Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue-light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti-inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age-related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.
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Waterlogging faced by bulbil expansion improved the growth of Pinellia ternata and its effect reinforced by brassinolide.
Wu, D, Zhang, D, Geng, Z, Gao, W, Tong, M, Chu, J, Yao, X
Plant physiology and biochemistry : PPB. 2024;:108377
Abstract
The bulbil expansion of P. ternata is a key period for its yield formation, and the process of bulbil expansion is often subjected to short-term heavy precipitation. It is not clear whether the short-term waterlogging can affect bulbil expansion. Brassinolide (BR) is widely believed to enhance plant tolerance to abiotic stress. The study investigated the effects of normal water (C), waterlogging (W), waterlogging + BR (W + B), waterlogging + propiconazole (W + P) on P. ternata at the bulbil expansion period in order to assess P. ternata's ability to cope with waterlogging during the bulbil expansion stage and the regulation effects of BR on the process. The biomass of P. ternata was significantly increased after waterlogging. W treatment significantly reduced the H2O2 and MDA contents, the rate of O2⋅- production and the activities of antioxidant enzymes compared with the C group. AsA and GSH contents were significantly reduced by W treatment. However, the ratios of AsA/DHA and GSH/GSSG were slightly affected by W treatment. The rate of O2∙- production and H2O2 content in W + B group were significantly lower than those in W group. The POD, APX, and GR activities, and GSH content in W + B group were evidently increased compared with the W group. Soluble sugar and active ingredients contents were significantly increased after waterlogging, and the enhancement was reinforced by BR. In conclusion, waterlogging reduced oxidative stress in P. ternata under the experimental conditions. BR treatment under waterlogging had a positive effect on P. ternata by enhancing antioxidant capacity and promoting the accumulation of soluble sugars and active ingredients.