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Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats

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Chinese Journal of Natural Medicines 2017年第5期15卷 341-346页

作者： WANG Yu-Rong XU Yuan jiang zhen-zhou ZHANG Lu-Yong WANG Tao State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing 210009 China Center for Molecular Metabolism School of Environmental and Biological Engineering Nanjing University of Science andTechnology Nanjing 210014 China jiangsu Key Laboratory of Drug Screening and jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Nanjing 210009 China jiangsu Key Laboratory of TCM Evaluation and Translational Research China Pharmaceutical University Nanjing 210009China

Benign prostatic hyperplasia(BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate(TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg×kg^(-1) for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone(DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.

关键词： Triptolide Benign prostatic hyperplasia Androgen

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The role of neutrophils in triptolide-induced liver injury

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Chinese Journal of Natural Medicines 2018年第9期16卷 653-664页

作者： WANG Xin-Zhi ZHANG Shen-Ye XU Yao ZHANG Lu-Yong jiang zhen-zhou jiangsu Key Laboratory of Drug Screening Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Nanjing 210009 China Faculty of Health and Medical Science University of Copenhagen Copenhagen Denmark Key Laboratory of Drug Quality Control and Pharmacovigilance China Pharmaceutical University Ministry of Education Nanjing 210009 China jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research Nanjing 210009 China

Triptolide(TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57 BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11 b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.

关键词： Triptolide Liver injury Inflammatory response Neutrophil Depletion

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Inhibitory effects of Tripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats

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Chinese Journal of Natural Medicines 2015年第6期13卷 421-427页

作者： SHEN Hai-Nan XU Yuan jiang zhen-zhou HUANG Xin ZHANG Lu-Yong WANG Tao jiangsu Center of Drug Screening China Pharmaceutical University Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University) Ministry of Education jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University

The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside(GTW) against testosterone-induced benign prostatic hyperplasia(BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group(sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg-1; and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg-1, respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone(DHT) levels in serum and prostate, and the serum prostate specific antigen(PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.

关键词： Tripterygium wilfordii Multiglycoside Benign prostatic hyperplasia Testosterone Dihydrotestosterone

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Organic anion transporter 1 and 3 contribute to traditional Chinese medicine-induced nephrotoxicity

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Chinese Journal of Natural Medicines 2020年第3期18卷 196-205页

作者： SHEN Qing-Qing WANG Jing-Jing ROY Debmalya SUN Li-Xin jiang zhen-zhou ZHANG Lu-Yong HUANG Xin jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Quality Control and Pharmacovigilance Ministry of EducationChina Pharmaceutical UniversityNanjing 210009China Center for Drug Screening and Pharmacodynamics Evaluation School of PharmacyGuangdong Pharmaceutical UniversityGuangzhou 510006China

With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to ***-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.

关键词： Traditional Chinese medicine Nephrotoxicity Renal tubular epithelial cell Organic anion transporter Aristolochic acid Tripterygium wilfordii Hook.f. Rheum officinale Baill

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Tripterygium wilfordii multiglycoside-induced hepatotoxicity via inflammation and apoptosis in zebrafish

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Chinese Journal of Natural Medicines 2021年第10期19卷 750-757页

作者： DUAN Xiu-Ying MA Rui-Jiao HSIAO Chung-Der jiang zhen-zhou ZHANG Lu-Yong ZHANG Yun LIU Ke-Chun Biology Institute Qilu University of Technology(Shandong Academy of Sciences)Jinan 250103China Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province Jinan 250103China Department of Bioscience Technology Chung Yuan Christian UniversityTaoyuan 32023China jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China

Tripterygium wilfordii multiglycoside(GTW)is a commonly used compound for the treatment of rheumatoid arthritis(RA)and immune diseases in clinical ***,it can induce liver injury and the mechanism of hepatotoxicity is still not *** study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism *** 72 hpf(hours post fertilization)zebrafish larvae were administered with different concentrations of GTW for three days and their mortality,malformation rate,morphological changes in the liver,transaminase levels,and histopathological changes in the liver of zebrafish larvae were *** reverse transcription-polymerase chain reaction(RT-PCR)was used to examine the levels of microRNA-122(miR-122)and genes related to inflammation,apoptosis,cell proliferation and liver *** results showed that GTW increased the mortality of zebrafish larvae,while significant malformations and liver damage *** main manifestations were elevated levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),significant liver atrophy,vacuoles in liver tissue,sparse cytoplasm,and unclear hepatocyte ***-PCR results showed that the expression of miR-122 significantly decreased by GTW;the mRNA levels of inflammation-related genes il1β,il6,tnfα,il10,cox2 and ptges significantly increased;the mRNA level of tgfβsignificantly decreased;the mRNA levels of apoptosis-related genes,caspase-8 and caspase-9,significantly increased;the mRNA level of bcl2 significantly decreased;the mRNA levels of cell proliferation-related genes,top2αand uhrf1,significantly reduced;the mRNA levels of liver function-related genes,alr and cyp3c1,significantly increased;and the mRNA level of cyp3a65 significantly *** zebrafish,GTW can cause increased inflammation,enhanced apoptosis,decreased cell proliferation,and abnormal expression of liver function-related genes,leading to abnormal liver structure and funct

关键词： Tripterygium wilfordii multiglycoside Zebrafish Hepatotoxicity Inflammation Apoptosis

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Advanced 3D ordered electrodes for PEMFC applications: From structural features and fabrication methods to the controllable design of catalyst layers

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Green Energy & Environment 2024年第9期9卷 1336-1365页

作者： Kaili Wang Tingting zhou zhen Cao Zhimin Yuan Hongyan He Maohong Fan Zaiyong jiang School of Chemistry & Chemical Engineering and Environmental Engineering Weifang University Beijing Key Laboratory of Ionic Liquids Clean Process State Key Laboratory of Multiphase Complex Systems CAS Key Laboratory of Green Process and Engineering Institute of Process Engineering Chinese Academy of Sciences College Engineering and Physical Sciences and School of Energy Resources University of Wyoming

The catalyst layers(CLs) electrode is the key component of the membrane electrode assembly(MEA) in proton exchange membrane fuel cells(PEMFCs). Conventional electrodes for PEMFCs are composed of carbon-supported, ionomer, and Pt nanoparticles, all immersed together and sprayed with a micron-level thickness of CLs. They have a performance trade-off where increasing the Pt loading leads to higher performance of abundant triple-phase boundary areas but increases the electrode cost. Major challenges must be overcome before realizing its wide commercialization. Literature research revealed that it is impossible to achieve performance and durability targets with only high-performance catalysts, so the controllable design of CLs architecture in MEAs for PEMFCs must now be the top priority to meet industry goals. From this perspective, a 3D ordered electrode circumvents this issue with a support-free architecture and ultrathin thickness while reducing noble metal Pt loadings. Herein, we discuss the motivation in-depth and summarize the necessary CLs structural features for designing ultralow Pt loading electrodes. Critical issues that remain in progress for 3D ordered CLs must be studied and characterized. Furthermore, approaches for 3D ordered CLs architecture electrode development, involving material design, structure optimization, preparation technology, and characterization techniques, are summarized and are expected to be next-generation CLs for PEMFCs. Finally, the review concludes with perspectives on possible research directions of CL architecture to address the significant challenges in the future.

关键词： PEMFC 3D ordered electrode Structural features Preparation technology Ultralow Pt loading

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Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts

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Chinese Journal of Natural Medicines 2014年第8期12卷 590-598页

作者： CHEN Mi WANG Tao jiang zhen-zhou SHAN Chun WANG Hao WU Mei-Juan ZHANG Shuang ZHANG Yun ZHANG Lu-Yong jiangsu Center for Drug Screening China Pharmaceutical University jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Department of Natural Medicinal Chemistry China Pharmaceutical University Biology Institute of Shandong Academy of Sciences Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University) Ministry of Education

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts(AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride(CCl4)-induced hepatitis in mice, D-galactosamine(D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.

关键词： Abrus mollis Flavonoid C-glycosides Inflammation Liver injury

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Bivariate attribution of the compound hot and dry summer of 2022 on the Tibetan Plateau

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Science China Earth Sciences 2024年第7期67卷 2122-2136页

作者： Baiquan zhou Panmao ZHAI zhen LIAO State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081China

The extraordinarily high temperatures experienced during the summer of 2022 on the Tibetan Plateau(TP)demand attention when compared with its typical climatic *** absence of precipitation alongside the elevated temperatures resulted in 2022 being the hottest and driest summer on record on the TP since at least *** the susceptibility of the TP to climate change,this study employed large-ensemble simulations from the HadGEM3-A-N216 attribution system,together with a copula-based joint probability distribution,to investigate the influence of anthropogenic forcing,primarily global greenhouse gas emissions,on this unprecedented compound hot and dry event(CHDE).Findings revealed that the return period for the 2022 CHDE on the TP exceeds 4000 years,as determined from the fitted joint distributions derived using observational data spanning *** CHDE was directly linked to large-scale circulation anomalies,including the control of equivalent-barotropic high-pressure anomalies and the northward displacement of the subtropical westerly jet ***,anthropogenic forcing has,to some extent,promoted the surface warming and increased variability in precipitation on the TP in summer,establishing conditions conducive for the 2022 CHDE from a long-term climate change *** return period for a 2022-like CHDE on the TP was estimated to be approximately 283 years(142-613 years)by the large ensemble forced by both anthropogenic activities and natural ***,ensemble simulations driven solely by natural forcing indicated that the likelihood of occurrence of a 2022-like CHDE was almost *** outcomes underscore that the contribution of anthropogenic forcing to the probability of a 2022-like CHDE was 100%,implying that without anthropogenically induced global warming,a comparable CHDE akin to that observed in 2022 on the TP would not be possible.

关键词： Compound hot and dry event Tibetan Plateau Bivariate event attribution Anthropogenic forcing

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Energy-information trade-off induces continuous and discontinuous phase transitions in lateral predictive coding

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 79-85页

作者： zhen-Ye Huang Ruyi zhou Miao Huang Hai-Jun zhou Key Laboratory for Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China School of Optics and Photonics Beijing Institute of TechnologyBeijing 100081China Minjiang Collaborative Center for Theoretical Physics Minjiang UniversityFuzhou 350108China

Lateral predictive coding is a recurrent neural network that creates energy-efficient internal representations by exploiting statistical regularity in sensory ***,we analytically investigate the trade-off between information robustness and energy in a linear model of lateral predictive coding and numerically minimize a free energy *** observed several phase transitions in the synaptic weight matrix,particularly a continuous transition that breaks reciprocity and permutation symmetry and builds cyclic dominance and a discontinuous transition with the associated sudden emergence of tight balance between excitatory and inhibitory *** optimal network follows an ideal gas law over an extended temperature range and saturates the efficiency upper bound of energy *** results provide theoretical insights into the emergence and evolution of complex internal models in predictive processing systems.

关键词： predictive coding recurrent neural network phase transition internal model free energy

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Energy-Preserving Parareal-RKN Algorithms for Hamiltonian Systems

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Numerical Mathematics(Theory,Methods and Applications) 2024年第1期17卷 121-144页

作者： zhen Miao Bin Wang Yaolin jiang School of Mathematics and Statistics Northwestern Polytechnical UniversityXi’an 710072P.R.China School of Mathematics and Statistics Xi’an Jiaotong UniversityXi’an 710049P.R.China

In this paper,we formulate and analyse a kind of parareal-RKN algo-rithms with energy conservation for Hamiltonian *** proposed algorithms are constructed by using the ideas of parareal methods,Runge-Kutta-Nystr¨om(RKN)methods and projection *** is shown that the algorithms can exactly pre-serve the energy of Hamiltonian ***,the convergence of the integra-tors is rigorously *** numerical experiments are carried out to support the theoretical results presented in this paper and show the numerical behaviour of the derived algorithms.

关键词： Parareal methods Runge-Kutta-Nystr¨om methods Hamiltonian systems energy conservation

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