作者机构：
[Sheng, Wen] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410000, Peoples R China.;[Lu, Baowei; Sheng, Wen; Liu, Lumei; Ding, Jin; He, Qinghu] Hunan Univ Chinese Med, Androl Lab, Changsha 410000, Peoples R China.;[Xu, Wenjing] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Dermatol, Changsha 410000, Peoples R China.;[Ding, Jin] Guangzhou Univ Tradit Chinese Med, Affiliated Baoan Hosp Tradit Chinese Med, Clin Med Coll 7, Dept Androl, Shenzhen 518000, Peoples R China.;[Lu, Baowei; Liu, Lumei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410000, Peoples R China.
通讯机构：
[Zhou, Q ; He, QH ] H;Hunan Univ Chinese Med, Androl Lab, Changsha 410000, Peoples R China.;Hunan Univ Med, Coll Tradit Chinese Med, Changsha 410000, Peoples R China.;Hunan Univ Chinese Med, Hosp 1, Dept Androl, Changsha 410000, Peoples R China.
关键词：
Colla Carapacis et Plastri;Fecal microbiota transplantation;Male infertility;Gut microbiota;Spermatogenesis ability
摘要：
[ABSTRACT] Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semiautomatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-10), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-10 in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.
作者机构：
[Chen, Xi; Liu, Ying; Cao, Hui; Qiu, Huiwen; Xu, Caijuan; Li, Sixin; Li, Xinyu; Tan, Rongrong] Hunan Univ Chinese Med, Sch Clin Med, Dept Psychiat, Changsha, Hunan, Peoples R China.;[Chen, Xi; Liu, Ying; Cao, Hui; Qiu, Huiwen; Xu, Caijuan; Li, Sixin; Li, Xinyu; Tan, Rongrong] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Dept Psychiat, Changsha, Hunan, Peoples R China.;[Huang, Wei] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Cheng, Quan] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Hunan, Peoples R China.;[Cheng, Quan] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Hunan, Peoples R China.
通讯机构：
[Hui Cao; Quan Cheng] D;Department of Psychiatry, The School of Clinical Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China<&wdkj&>Department of Psychiatry, Brain Hospital of Hunan Province (The Second People’s Hospital of Hunan Province), Changsha, Hunan, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, China
摘要：
Disorders of central nervous system (CNS) disorders are considered serious health issues. The most common CNS diseases include neurodegenerative diseases, mental disorders, demyelinating disease, ischemia-reperfusion injury, and neuroinflammation. As a natural phenolic compound, hesperidin is a flavanone glycoside with various biological effects. Increasing evidence show that the growth of CNS diseases is hindered by hesperidin. Here, we have reviewed the related literature on neuropharmacological mechanisms for the preventive and therapeutic effects of hesperidin on CNS diseases. Several cellular and animal models have been developed to evaluate the underlying neuropharmacological mechanisms of hesperidin. Additionally, clinical evidence has confirmed its neuroprotective function. Hesperidin exerts its neuroprotective properties by decreasing neuro-inflammatory and apoptotic pathways. Hesperidin function has been studied in preclinical models for CNS diseases, but little is known about its definite effect in humans. Hesperidin can effectively alleviate depression and improve cognition and memory. It is urgent to explore and discover clinical trials for further confirmation of the neuroprotective efficacy of hesperidin and to evaluate its safety profile.
摘要：
BACKGROUND: The efficacy of acupoint application in the treatment of ulcerative colitis (UC) is still controversial. The purpose of this study is to systematically evaluate the clinical efficacy and safety of acupoint application in the treatment of ulcerative colitis. METHODS: The databases of China National Knowledge Infrastructure (CNKI), Chinese Biology Medicine (CBM), VIP, Wanfang, Embase, PubMed, the Cochrane Library and Web of Science were searched. The time limit was from the establishment of the database to July 2022. The published randomized controlled trials of acupoint application in the treatment of UC were analyzed by meta-analysis and trial sequential analysis. RESULTS: A total of 13 studies were included, with a total sample size of 878 cases. Compared with conventional western medicine, acupoint application can effectively improve the effective rates of clinical comprehensive (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.06-1.20, P = .0003), syndrome (RR 1.13, 95% CI 1.03-1.24, P = .009), and interleukin-4 (IL-4) (mean differences 2.62, 95% CI 1.96-3.28, P < .00001) in the treatment of UC, and reduce interferon-γ (mean differences -5.38, 95% CI -6.81 to -3.94, P < .00001). The effective rates of colonoscopy (RR 0.94, 95% CI 0.84-1.05, P = .25), pathological examination (RR 1.04, 95% CI 0.90-1.20, P = .60) and rate of adverse reaction (RR 0.55, 95% CI 0.25-1.21, P = .14) were the same. Trial sequential analysis indicated that the benefits of effective rates of clinical comprehensive and syndrome, IL-4, and interferon-γ were conclusive. Harbord regression showed no publication bias (P = .98). The evaluation of evidence quality suggested that the evidence quality of effective rates of clinical comprehensive and syndrome was moderate and the evidence quality of other indicators was low or very low. CONCLUSION: Acupoint application is a safe and effective method for the treatment of UC, and has the prospect of clinical application.
通讯机构：
[Meng Qin; Yi Hou] B;[Mingyuan Gao] C;Beijing Advanced Innovation Centre for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China<&wdkj&>National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, Department of Psychiatry, West China Hospital, Sichuan University, Chengdu 610041, China<&wdkj&>Beijing Advanced Innovation Centre for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China<&wdkj&>Centre for Molecular Imaging and Nuclear Medicine, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, State Key Laboratory of Radiation Medicine and Protection, and the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215000, China
摘要：
Ischemic stroke is currently one of the biggest threats to global health due to its high mortality and dis-ability rate. Thrombolysis with intravenous alteplase remains a primary therapy for acute ischemic stroke. Nevertheless, haemorrhage may be triggered to cause secondary victimization to the patients. On the other hand, the compensatory cerebral collaterals developing in response to ischemia stroke help preserve the penumbral area where the neurons are considered to be salvageable. In this context, precisely evaluating the collateral circulation and predicting the thrombolytic risk of stroke are extremely important not only for treatment decision making but also for a good prognosis. Aiming at identifying the ischemic penumbra and precisely predicting the possible thrombolytic haemorrhage risk prior to thrombolytic therapy, we herein report a dual-targeted magnetic resonance imaging (MRI) nanoprobe based on magnetic iron oxide na-noparticles for visualizing both cerebral collateral circulation and ischemic inflammation. Focal cerebral ischemia rat models were adopted for imaging studies on 7.0 Tesla MRI with different sequences. The imaging results revealed that the nanoprobe could target the newly formed collateral vessels and in-flammatory lesions in the cerebral ischemic region, which enabled the visualization of the potential hae-morrhage sites of thrombolytic therapy apart from the ischemic penumbra. The current studies therefore offer for the first time a noninvasive approach for precisely predicting potential reperfusion haemorrhage through MRI.(c) 2022 Elsevier Ltd. All rights reserved.
作者机构：
[Wang, Xiaofan; Wu, Hongzheng; Chen, Zhenni; Peng, Huanqie; Chen, Wanxin; Wang, Bingqi; Wang, Min] Cent South Univ, Dept Lab Med, Second Xiangya Hosp, Changsha 410011, Hunan, Peoples R China.;[Huang, Yiran] Hunan Univ Chinese Med, Sch Clin Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Wang, M ] C;Cent South Univ, Dept Lab Med, Second Xiangya Hosp, Changsha 410011, Hunan, Peoples R China.
摘要：
Bipolar disorder (BD) is a distinctly heterogeneous and multifactorial disorder with a high individual and social burden. Immune pathway dysregulation is an important pathophysiological feature of BD. Recent studies have suggested a potential role for T lymphocytes in the pathogenesis of BD. Therefore, greater insight into T lymphocytes' functioning in patients with BD is essential. In this narrative review, we describe the presence of an imbalance in the ratio and altered function of T lymphocyte subsets in BD patients, mainly in T helper (Th) 1, Th2, Th17 cells and regulatory T cells, and alterations in hormones, intracellular signaling, and microbiomes may be potential causes. Abnormal T cell presence explains the elevated rates of comorbid inflammatory illnesses in the BD population. We also update the findings on T cell-targeting drugs as potentially immunomodulatory therapeutic agents for BD disease in addition to classical mood stabilizers (lithium, valproic acid). In conclusion, an imbalance in T lymphocyte subpopulation ratios and altered function may be involved in the development of BD, and maintaining T cell immune homeostasis may provide an overall therapeutic benefit.
摘要：
Simultaneous and high-performance detection of pesticides is still a considerable challenge and urgent need. Herein, a dual-emission carbon dots (CDs)-based nonenzymatic fluorescent sensing platform has been developed, which shows excellent sensitivity and selectivity in simultaneously detecting parathion-methyl (MP) and glyphosate. CDs with emissions at 440 nm (bCDs) and 660 nm (rCDs) were prepared by hydrothermal treatment of mulberry leaves and sodium hydroxide. bCDs response to hydrolyzed MP via inner filter effect, while rCDs sense glyphosate with the aid of Cu2+ by static quenching effect. Excellent linear correlations were found for MP (0.3-65.0 & mu;M) and glyphosate (1.0-110.0 & mu;M) with limits of detection at 0.14 and 0.60 & mu;M. Notably, the pre-sented dual-channel strategy was successfully applied in simultaneously detecting MP and glyphosate in food/ herbal samples with acceptable recoveries, good precision, and high selectivity. Moreover, an OR logic gate was achieved for estimating food, herbal, or environmental safety.
摘要：
BACKGROUND: Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity. METHODS: Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. RESULTS: A total of 66 patients were included, with a median age of 71.5 years (range 40-92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1-14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin <3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1-42) after intervention including antiepileptic administration, or hemodialysis. CONCLUSION: Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.
作者机构：
[Ou, Liang] Hunan Acad Chinese Med, Changsha 410006, Peoples R China.;[Huang, Weichen; Kong, Dezhong; Ou, Liang; Xu, Daoqing; Meng, Yingfu] Guizhou Univ Chinese Med, Affiliated Hosp 2, Dept Orthoped, Guiyang 550003, Guizhou Provinc, Peoples R China.;[Zhang, Tiantian] Hunan Univ Chinese Med, Dept Grad Sch, Changsha 410208, Hunan Province, Peoples R China.
通讯机构：
[Yingfu Meng] D;Department of Orthopedic, The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou Province 550003, China
摘要：
BACKGROUND: Osteoarthritis (OA) was a chronic degenerative joint disease. The dysregulation of circular RNAs (circRNAs) has been identified in OA progression. However, the function and regulation mechanism of circ_0114876 in OA remains largely unknown. METHOD: Firstly, we used LPS-treated C28/I2 cells as a cellular model of OA. Quantificational real-time polymerase chain reaction (qRT-PCR) was used to determine the expression levels of circ_0114876, miRNA-1227-3p, and ADAM10 in OA chondrocytes. Cell Counting Kit-8 (CCK8), 5-ethynyl-20-deoxyuridine (EdU) incorporation assays, flow cytometry, Enzyme-linked immunosorbent assay (ELISA) kit, and western blot were applied to confirm cell proliferation, apoptosis, inflammation, and extracellular matrix. of circ_0114876 in vitro. The interaction between circ_0114876 and its downstream target (miR-1227-3p) and mRNA target ADAM metallopeptidase domain 10 (ADAM10), was evaluated by luciferase assay and RNA immunoprecipitation (RIP) assay. RESULT: Circ_0114876 and ADAM10 were upregulated and miR-1227-3p was decreased in OA tissues and LPS-treated chondrocytes. Low expression of circ_0114876 promoted proliferation and inhibited apoptosis, inflammation, and extracellular matrix of the LPS-treated chondrocytes. Mechanistically, circ_0114876 functioned in human chondrocytes through targeting miR-1227-3p and ADAM10. Furthermore, miRNA-1227-3p inhibitor reversed the effect of circ_0114876 knockdown on the OA chondrocytes, and ADAM10 overexpression reversed the effect of miR-1227-3p mimic on the OA chondrocytes. CONCLUSION: Circ_0114876 was increased in OA tissues and cells. Circ_0114876 facilitated the progression in the LPS-induced OA cell model via regulating the miR-1227-3p/ADAM10 axis. This study would provide a potentially effective therapeutic strategy for OA progression.
摘要：
Background: Endoplasmic reticulum stress (ERS) is an important pathophysiological mechanism in ulcerative colitis (UC) and Crohn's disease (CD). ERS-related genes may be influenced by genetic factors and intestinal inflammation. However, the role of ERS as a trigger or potential etiological factor for UC and CD is unclear, as the expression of ERS-related genes in UC and CD may be the cause or subsequent changes in intestinal inflammation. Here, we used a three-step summary data-based Mendelian randomization (SMR) approach integrating multi-omics data to identify putative causal effects of ERS-related genes in UC and CD.Methods: Genome-wide association study (GWAS) summary data for UC (6,968 cases and 20,464 controls) and CD (5,956 cases and 14,927 controls) were extracted as outcome, and DNA methylation quantitative trait loci (mQTL, 1,980 participants) data and expression QTL data (eQTL, 31,684 participants) from the blood were obtained as exposure. The ERS-related genes were extracted from the GeneCards database, and then the GWAS summary data were integrated with the mQTL and eQTL data associated with ERS genes by SMR. Sensitivity analysis included two-sample MR analysis, power calculations, Bayesian co-localization analysis, and phenotype scanning were performed to evaluate the robustness of the results.Results: A total of 1,193 ERS-related genes were obtained. The three-step SMR analysis showed that cg24011261 CpG site regulating GPX1 expression was associated with a low risk of UC, whereas GPX1 expression regulated by a combination of cg05055782, cg24011261, and cg05551922 CpG sites was associated with a low risk of CD. Sensitivity analysis further supports these findings.Conclusion: This multi-omics integration study identifies a causal relationship between the role of ERS in UC and CD and suggests potential new therapeutic targets for clinical practice.
摘要：
Polycrystalline silicon solar cells modified using biomass resources are promising candidates to accomplish the goal of carbon neutrality. Developing a device with high power conversion efficiency (PCE) is important to resolve the ever-increasing energy shortage issues. Therefore, we develop a facile solution-casting approach to synthesise ethylene-vinyl acetate (EVA) films modified with ultra-high fluorescent carbon quantum dots (CQDs). The films were coated on the surface of polycrystalline silicon solar cells and the PCE increased from 13.19% to 13.65%. The ultra-high fluorescent CQDs were prepared from Ginkgo biloba via a hydrothermal process, and different parts of Ginkgo biloba-based CQDs were investigated in various conditions. The ultra-high fluorescent CQDs obtained at 180 degrees C, 8 h and a reaction concentration of 0.048 g/mL from Ginkgo wood resulted in high fluorescence of up to 976.74 a.u.. At an excitation wavelength of 365 nm. This work substantially expands the potential of EVA films containing ultra-high fluorescent CQDs for applications in the photovoltaic, environment and energy fields.
作者机构：
[Liu, Jianjun; Liao, Xiaolin; Liu, JJ; Wang, Yuhong] Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Han, Yuanshan] Hunan Univ Chinese Med, Sci Res Dept, Hosp 1, Changsha, Peoples R China.;[Shen, Chuanpu; Shen, CP] Anhui Med Univ, Anhui Inst Innovat Drugs, Sch Pharm, Anhui Prov Key Lab Major Autoimmune Dis, Hefei 230032, Peoples R China.;[Shen, Chuanpu] Anhui Med Univ Hefei, Minist Educ, Key Lab Antiinflammatory & Immune Med, Inst Liver Dis, Hefei, Peoples R China.
通讯机构：
[Shen, CP ] A;[Liu, JJ; Wang, YH ] H;Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Changsha 410208, Hunan, Peoples R China.;Anhui Med Univ, Anhui Inst Innovat Drugs, Sch Pharm, Anhui Prov Key Lab Major Autoimmune Dis, Hefei 230032, Peoples R China.
关键词：
formulations;hypertension;natural products;NLRP3 inflammasome;target organ damage
摘要：
A schematic overview of the process of NLRP3 inflammasome action on hypertensive target organ damage and the intervention of natural products and formulations. Abstract Background and Aim Hypertension is a major global health problem that causes target organ damage (TOD) in the heart, brain, kidney, and blood vessels. The mechanisms of hypertensive TOD are not fully understood, and its treatment is challenging. This review provides an overview of the current knowledge on the role of Nod‐like receptor pyrin domain containing 3 (NLRP3) inflammasome in hypertensive TOD and the natural products and formulations that inhibit it. Methods We searched PubMed, Web of Science, Google Scholar, and CNKI for relevant articles using the keywords “hypertension,” “target organ damage,” “NLRP3 inflammasome,” “natural products,” and “formulations.” We reviewed the effects of the NLRP3 inflammasome on hypertensive TOD in different organs and discussed the natural products and formulations that modulate it. Key results In hypertensive TOD, the NLRP3 inflammasome is activated by various stimuli such as oxidative stress and inflammation. Activation of NLRP3 inflammasome leads to the production of pro‐inflammatory cytokines that exacerbate tissue damage and dysfunction. Natural products and formulations, including curcumin, resveratrol, triptolide, and allicin, have shown protective effects against hypertensive TOD by inhibiting the NLRP3 inflammasome. Conclusions and Implications The NLRP3 inflammasome is a promising therapeutic target in hypertensive TOD. Natural products and formulations that inhibit the NLRP3 inflammasome may provide novel drug candidates or therapies for hypertensive TOD. Further studies are needed to elucidate the molecular mechanisms and optimize the dosages of these natural products and formulations and evaluate their clinical efficacy and safety.
摘要：
BACKGROUND: The motor symptoms in patients with Parkinson's disease (PD) are commonly preceded by gastrointestinal (GI) symptoms. The enteric nervous system (ENS) has also been reported to exhibit neuropathological characteristics of PD. OBJECTIVES: To evaluate the relationship between the incidence of parkinsonism and alteration in gut microbiota and pathogens. MATERIAL AND METHODS: Studies in different languages that evaluate the relationship between gut microorganisms and PD were included into this meta-analysis. The outcomes of these studies were analyzed using a random effects model; it was also used to calculate the mean difference (MD) with 95% confidence interval (95% CI) in order to quantify the impact of different rehabilitation techniques on clinical parameters. Dichotomous and continuous models were used for the analysis of extracted data. RESULTS: A total of 28 studies were included in our analysis. The analysis of small intestinal bacterial overgrowth showed a significant correlation with Parkinson's subjects compared with controls (p < 0.001). In addition, the presence of Helicobacter pylori (HP) infection was significantly related to the Parkinson's group (p < 0.001). On the other hand, there was a significantly higher abundance level of Bifidobacteriaceae (p = 0.008), Verrucomicrobiaceae (p < 0.001) and Christensenellaceae (p = 0.003) in Parkinson's subjects. In contrast, a significantly lower abundance levels in Parkinson's subjects were found in Faecalibacterium (p = 0.03), Lachnospiraceae (p = 0.005) and Prevotellaceae (p = 0.005). No significant difference was related to Ruminococcaceae. CONCLUSION: Parkinson's subjects showed a higher degree of alteration of gut microbiota and pathogens compared with normal human subjects. Future multicenter randomized trials are needed.
期刊：
Journal of Nanobiotechnology,2023年21(1):1-21 ISSN：1477-3155
通讯作者：
Long, Y;Liu, B
作者机构：
[Qin, Zhang; Zhang, Yi; Li, Zhenxian; Peng, Yuan; Xu, Yijia; Long, Yun; Liu, Jianhe; Jiang, Jiazheng] Hunan Univ Chinese Med, Hosp 1, Branch Natl Clin Res Ctr Chinese Med Cardiol, Dept Cardiol, Changsha 410007, Peoples R China.;[Liu, B; Liu, Bin] Hunan Univ, Coll Biol, Changsha 410082, Peoples R China.;[Liu, Hao] Cent South Univ, Xiangya Hosp 2, Dept Rehabil, Changsha 410011, Peoples R China.;[Liu, B; Liu, Dayue; Liu, Bin] Ningxia Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, NHC Key Lab Metab Cardiovasc Dis Res, Yinchuan 750004, Peoples R China.;[Zhu, Haimei] Hunan Univ Chinese Med, Hosp 1, Dept Pain, Changsha 410007, Peoples R China.
通讯机构：
[Liu, B ; Long, Y ] H;Hunan Univ Chinese Med, Hosp 1, Branch Natl Clin Res Ctr Chinese Med Cardiol, Dept Cardiol, Changsha 410007, Peoples R China.;Hunan Univ, Coll Biol, Changsha 410082, Peoples R China.;Ningxia Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, NHC Key Lab Metab Cardiovasc Dis Res, Yinchuan 750004, Peoples R China.
关键词：
Atherosclerosis;Evolocumab;Proprotein convertase subtilisin/Kexin type 9;Liposome;Phenotypic transition
摘要：
PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within theplaque of ApoE(-/-) mice.
摘要：
Conventional chemotherapy lacks the ability to specifically target cancer cells, thus although it eliminates tumor tissues to some extent, it also damages normal tissues and organs. Meanwhile, cancer stem cells (CSCs)-induced tumor regrowth and drug resistance limits the application of some chemotherapy drugs. In this study, the CD71/ CD44 dual-aptamer-gemcitabine (CD71-CD44-GEMs) conjugate was designed to treat bladder cancer through the co-targeting by CD71 of bladder cancer cells and by CD44 of bladder CSCs. A series of studies were used to evaluate the binding specificity and the in vitro and in vivo anti-cancer effects. We observed that CD71-CD44GEMs selectively bound to and exerted a high inhibitory effect on bladder cancer in vitro and in vivo. Besides, CD71-CD44-GEMs can inhibit the formation of the tumorsphere and demonstrated a higher binding affinity and inhibitory efficacy than CD71-GEMs or CD44-GEMs (GEM delivered by a single target aptamer) in bladder cancer. Hence, CD71-CD44-GEMs represents a promising approach to treating bladder cancer for its high efficacy in drug delivery and ability to eliminate both bladder cancer cells and CSCs.
期刊：
Frontiers in Pharmacology,2023年13:4847 ISSN：1663-9812
作者机构：
[Peng, Xiwen; Shang, Hongcai; She, Ruining; Ge, Jinwen; Meng, Pan; Cheng, Shaowu; Wang, Shanshan; Fang, Rui; Wang, Xiangyuan; Lin, Hongyuan; Mei, Zhigang; Zhou, Yue] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Ge, Jinwen; Fang, Rui] Hunan Acad Chinese Med, Inst Clin Pharmacol Chinese Mat Med, Changsha, Hunan, Peoples R China.;[Hu, Hua] Hunan Univ Chinese Med, Neurol Dept, Hosp 1, Changsha, Hunan, Peoples R China.;[Jiang, Qiling; Liu, Litao] Shaoyang Univ, Sch Food & Chem Engn, Shaoyang, Hunan, Peoples R China.;[Wu, Dahua; Xie, Yao; Xie, Le] Hunan Prov Hosp Integrated Chinese & Western Med, Hunan Acad Chinese Med Affiliated Hosp, Neurol Dept, Changsha, Hunan, Peoples R China.
关键词：
Hypertensive cerebral small vessel disease;randomized controlled trial;Chinese medicine;Naotaifang capsule;Treatment
摘要：
Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25-30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease. Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively. Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research.
作者机构：
[He, Min; Zhang, Chi; Zhang, Xianan] Capital Med Univ, Sch Tradit Chinese Med, Beijing 100069, Peoples R China.;[Guo, Siyuan] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China.;[Yin, Yan] Hunan Acad Chinese Med, Changsha 410600, Hunan, Peoples R China.
通讯机构：
[Zhang, Xianan] S;School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
关键词：
Paris polyphylla var. yunnanensis;Pennogenin;Polyphyllin biosynthetic pathway;Sterol glycosyltransferases
摘要：
BACKGROUND: Paris polyphylla var. yunnanensis is an important medicinal plant, and the main active ingredient of the plant is polyphyllin, which is a steroid saponin with pharmacological activities. The central enzyme genes participating in the biosynthesis of polyphyllin are increasingly being uncovered; however, UGTs are rarely illustrated. METHODS AND RESULTS: In this study, we cloned a new sterol glycosyltransferase from Paris polyphylla var. yunnanensis and identified its catalytic function in vitro. PpUGT6 showed the ability to catalyse the C-3 glycosylation of pennogenin sapogenin of polyphyllin, and PpUGT6 showed catalytic promiscuity towards steroids at the C-17 position of testosterone and methyltestosterone and the triterpene at the C-3 position of glycyrrhetinic acid. Homology modelling of the PpUGT6 protein and virtual molecular docking of PpUGT6 with sugar acceptors and donors were performed, and we predicted the key residues interacting with ligands. CONCLUSIONS: Here, PpUGT6, a novel sterol glycosyltransferase related to the biosynthesis of polyphyllin from P. polyphylla, was characterized. PpUGT6 catalysed C-3 glycosylation to pennogenin sapogenin of polyphyllin, which is the first glycosylation step of the biosynthetic pathway of polyphyllins. Interestingly, PpUGT6 demonstrated glycodiversification to testosterone and methyltestosterone at C-17 and triterpene of glycyrrhetinic acid at the C-3 position. The virtual molecular docking of PpUGT6 protein with ligands predicted the key residues interacting with them. This work characterized a novel SGT glycosylating pennogenin sapogenin at C-3 of polyphyllin from P. polyphylla and provided a reference for further elucidation of the phytosterol glycosyltransferases in catalytic promiscuity and key residues interacting with substrates.
摘要：
OBJECTIVE: This study aimed to evaluate the association of serum zinc with periodontitis in non-diabetics based on smoking status, using a representative sample of adults in the United States. METHODS: A total of 1051 participants who underwent full-mouth periodontal examination and serum zinc testing were enrolled from NHANES 2011 to 2014. The covariate-adjusted association of serum zinc concentrations with periodontitis was explored using multivariable logistic regression, restricted cubic spines, and sensitivity analysis. RESULTS: The mean age of the 1051 adults was 54.5 years, 59.37% were male, and 20.65% had periodontitis. Analysis of the results showed that serum zinc was associated with periodontitis. The overall adjusted odds of periodontitis were 9% (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83-1.00) and 14% (OR: 0.86; 95% CI: 0.75-0.98) for nonsmokers and smokers, respectively. Smokers with T3 serum zinc exhibited a 53% reduction in the fully adjusted odds of periodontitis (OR: 0.47; 95% CI: 0.23-0.96), when compared to the reference group (T1 serum zinc), with serum zinc as the categorical variable. CONCLUSIONS: Serum zinc levels were associated with the risk of periodontitis in non-diabetic smokers but not non-smokers.
期刊：
Journal of Cheminformatics,2023年15(1):1-14 ISSN：1758-2946
通讯作者：
Cao, DS;Hou, TJ
作者机构：
[Yang, Su-Qing; Cao, Dong-Sheng; Cao, DS] Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China.;[Yang, Su-Qing; Shen, Cheng-Ying; Ge, You-Jin; Hu, Jian-Xin] Nanchang Med Coll, Jiangxi Prov Peoples Hosp, Dept Pharm, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China.;[Zhang, Liu-Xia] Hunan Univ Chinese Med, Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Zhang, Jin-Wei] Cent South Univ, Sch Basic Med Sci, Dept Biomed Engn, Changsha 410013, Hunan, Peoples R China.;[Zhang, Jin-Wei] Cent South Univ, Sch Basic Med Sci, Dept Pathol, Changsha 410013, Hunan, Peoples R China.
通讯机构：
[Hou, TJ ] Z;[Cao, DS ] C;Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China.;Hong Kong Baptist Univ, Inst Adv Translat Med Bone & Joint Dis, Sch Chinese Med, Hong Kong, Peoples R China.;Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China.
关键词：
Target prediction;Chemogenomic;XGBoost;Ensemble model
摘要：
Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.
摘要：
Background: A statin alone or non-statins as add-ons have been introduced to intensive low-density lipoprotein cholesterol (LDL-C) -lowering therapy in patients at risk for high cardiovascular disease (CVD). The purpose of this study was to evaluate the effectiveness and safety of different rosuvastatin-based regimens for patients at high risk. Methods: Three hundred patients at high CVD risk were randomly assigned to the statin group (rosuvastatin, 20 mg/d), statin_EZ group (statin 10 mg/d + ezetimibe 10 mg/d), statin_pcsk group (statin 10 mg/d + alirocumab 75 mg/2 weeks) or combine3 group (statin 10 mg/d + ezetimibe 10 mg/d + alirocumab 75 mg/2 weeks). The primary outcome measure was cholesterol levels after 24 weeks of follow-up. Secondary outcomes included safety markers and the proportion of patients achieving the 70 mg/dL (1.8 mmol/L) target for LDL-C. A logistic regression model was performed to explore the factors affecting lipid target achievement. Results: The total cholesterol (TC) and LDL-C levels in the four groups after treatment were significantly lower than those before treatment. TC and LDL-C levels after treatment were significantly different among the four groups (p < 0.05). The levels in both the combine3 and statin_pcsk9 groups were significantly lower than those in the statin and statin_EZ groups (p < 0.05), but there was no significant difference between the combine3 and statin_pcsk9 groups. Fifty-one participants (69%) in the statin_pcsk9 group and 56 participants (78%) in the combine3 group achieved the target. Body mass index (BMI) and hypertensive status were related to LDL-C target achievement. The incidence of adverse events in the four groups was low. Conclusions: The combination of a statin and a PCSK9 inhibitor was safe and more effective for the treatment of high-risk CVD patients, while the addition of ezetimibe was unable to significantly lower lipid levels any further. The rate of achieving the target was higher in patients with hypertension and a low BMI. Clinical Trial Registration: Chinese Clinical Trial Registry, Identifier: ChiCTR2200058389, Date of Registration: 2022-04-08.
