摘要：
Diaporthe and its anamorph Phomopsis, a genus of endophytic, saprotrophic, and plant pathogenic fungi, are found in many different ecosystems worldwide. Diaporthe (Phomopsis) fungi generate natural products such as pyrones, polyketides, alkaloids, and terpenoids. Most of these natural products show antibacterial, anti-inflammatory, and/or cytotoxic activity. In this review, we describe the 331 bioactive secondary metabolites isolated from 75 known species and various unidentified species of Diaporthe and Phomopsis from 2016 to 2021. These products comprise 143 bioactive compounds from Diaporthe and 188 from Phomopsis, including quinones, alkaloids, terpenoids, pyrones, polyketides, diphenyl ketones, diphenyl ethers, steroids, and fatty acids. The major activities of these compounds are as cytotoxic, antibacterial, and anti-inflammatory chemi-cals. All 21 fungi in the genus Diaporthe (Phomopsis) with available whole genome sequencing data contain several gene clusters for secondary metabolite biosynthesis. Such gene clusters and biosyn-thetic mechanisms have been identified for rugulosin A, terpestacin, and sch-642305. Diaporthe (Phomopsis) fungi produce abundant novel active natural products with great potential for drug development. In addition, these fungi provide important resources for research on the biosynthesis of secondary metabolites.& COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
期刊：
Journal of the Electrochemical Society,2023年170(1):017503 ISSN：0013-4651
作者机构：
[Ji, Limin; Chen, Huiting; Tao, Jia; Ouyang, Sixue; Chen, Yuying; Zou, Xun] South China Univ Technol, Sch Chem & Chem Engn, Guangzhou 510640, Peoples R China.;[Sun, Mingyan; Zhao, Peng; Zou, Xun; Zheng, Zhiyuan] Southern Med Univ, Sch Pharmaceut Sci, NMPA Key Lab Res & Evaluat Drug Metab, Guangdong Prov Key Lab NewDrug Screening,Guangdong, Guangzhou 510515, Peoples R China.;[Deng, Zilong] Southern Med Univ, Nanfang Hosp, Dept Stomatol, Guangzhou 510515, Peoples R China.;[Yuan, Zhiying] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
摘要：
In this report, a novel electrochemical and colorimetric dual-mode sensing system was developed for the sensitive and selective detection of DA. The large surface area of CoOOH and the excellent conductivity of CB endow the electrochemical sensing system with high sensitivity. CoOOH with oxidase-like activity will convert the colorless TMB into the blue oxidation product OXTMB, appearing an absorption peak at 652 nm correspondingly. And the addition of DA will inhibit the activity of oxidase followed by a reducing in the absorption. Our device provided a wider detection range for DA from 1 to 30 mu M and 1 to 950 mu M through colorimetric and electrochemical methods, respectively. Furthermore, this biosensor with good biocompatibility has been successfully used for in-vitro tracking of DA efflux from live PC12 cell after being stimulated, which has important scientific and practical value for clinical diagnosis and monitoring.
摘要：
Pyroptosis is a novel pro-inflammatory cell programmed death dependent on Gasdermin (GSMD) family-mediated membrane pore formation and subsequent cell lysis, accompanied by the release of inflammatory factors and expanding inflammation in multiple tissues. All of these processes have impacts on a variety of metabolic disorders. Dysregulation of lipid metabolism is one of the most prominent metabolic alterations in many diseases, including the liver, cardiovascular system, and autoimmune diseases. Lipid metabolism produces many bioactive lipid molecules, which are important triggers and endogenous regulators of pyroptosis. Bioactive lipid molecules promote pyroptosis through intrinsic pathways involving reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lysosomal disruption, and the expression of related molecules. Pyroptosis can also be regulated during the processes of lipid metabolism, including lipid uptake and transport, de novo synthesis, lipid storage, and lipid peroxidation. Taken together, understanding the correlation between lipid molecules such as cholesterol and fatty acids and pyroptosis during metabolic processes can help to gain insight into the pathogenesis of many diseases and develop effective strategies from the perspective of pyroptosis.
期刊：
Current Neuropharmacology,2023年21(10):2079-2096 ISSN：1570-159X
通讯作者：
Mei, ZG;Zhang, WL
作者机构：
[Mei, Zhigang; Luo, Haoyue; Guo, Hanjing; Fang, Rui; Zhou, Yue] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese Med & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Zhang, Wenli; Zhang, WL] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Mei, Zhigang] China Three Gorges Univ, Grade Pharmacol Lab Chinese Med Approved State Adm, Med Coll, Yichang 443002, Hubei, Peoples R China.
通讯机构：
[Mei, ZG ; Zhang, WL ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese Med & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要：
Cerebral ischemic injury, one of the leading causes of morbidity and mortality worldwide, triggers various central nervous system (CNS) diseases, including acute ischemic stroke (AIS) and chronic ischemia-induced Alzheimer's disease (AD). Currently, targeted therapies are urgently needed to address neurological disorders caused by cerebral ischemia/reperfusion injury (CI/RI), and the emergence of neutrophil extracellular traps (NETs) may be able to relieve the pressure. Neutrophils are precursors to brain injury following ischemic stroke and exert complicated functions. NETs extracellularly release reticular complexes of neutrophils, i.e., double-stranded DNA (dsDNA), histones, and granulins. Paradoxically, NETs play a dual role, friend and foe, under different conditions, for example, physiological circumstances, infection, neurodegeneration, and ischemia/reperfusion. Increasing evidence indicates that NETs exert anti-inflammatory effects by degrading cytokines and chemokines through protease at a relatively stable and moderate level under physiological conditions, while excessive amounts of NETs release (NETosis) irritated by CI/RI exacerbate the inflammatory response and aggravate thrombosis, disrupt the blood-brain barrier (BBB), and initiates sequential neuron injury and tissue damage. This review provides a comprehensive overview of the machinery of NETs formation and the role of an abnormal cascade of NETs in CI/RI, as well as other ischemia-induced neurological diseases. Herein, we highlight the potential of NETs as a therapeutic target against ischemic stroke that may inspire translational research and innovative clinical approaches.
摘要：
BACKGROUND: This study investigated the correlation among kidney function, intestinal enzyme activities, and microbial activity of adenine and Folium sennae-induced diarrhea model in mice, which provided a basis for clinical treatment of kidney-intestinal correlation. METHODS: We performed different doses of adenine combined with Folium sennae intragastric administration to establish the animal model of diarrhea. We assessed thymus and spleen indexes, serum creatinine, urea nitrogen and uric acid contents, intestinal contents and mucosal enzyme activities, and microbial activity. RESULTS: After modeling, mice presented increased serum creatinine and decreased urea nitrogen. Uric acid showed different changes in the different model groups. The thymus index in the model mice was trending downward, whereas the spleen index was the opposite. Moreover, model mice induced a non-significant increase in xylanase activity of the intestinal contents and mucosa compared to the control performance. Sucrase content of the intestinal contents increased considerably in the model groups but decreased in the intestinal mucosa. Lactase and amylase induced different trends in the different modeling methods. As well, the microbial activity of intestinal contents increased significantly, while that of intestinal mucosa decreased. CONCLUSION: Adenine combined with Folium sennae successfully replicated diarrhea in mice models. Using 50 mg/ (kg/day) adenine for 14 days in combination with 10 g/(kg/day) Folium sennae decoction for 7 days caused kidney function injury in diarrhea mice. In addition, kidney function injury was accompanied by changing in intestinal functional enzyme activity and microbial activity.
摘要：
IntroductionDue to the poor taste of Qiweibaizhu powder (QWBZP), patients have difficulty taking medicine, which leads to poor compliance and limits clinical use to a certain extent. In the trend of restricting sugar intake, sweeteners have gained massive popularity, among which sucrose is a commonly used sweetener in preparations. This study aimed to investigate the effect of different sucrose dose addition with antibiotic-associated diarrhea (AAD) by intervened QWBZP on intestinal mucosal microbiota. MethodsThirty specific-pathogen-free (SPF) Kunming (KM) male mice were randomly divided into normal group (N), natural recovery group (M), QWBZP group (Q), low dose sucrose group (LQ), medium dose sucrose group (MQ), and high dose sucrose group (HQ). Subsequently, 16S rRNA amplicon sequencing and GC-MS techniques were used to analyze the intestinal mucosal microbiota and short-chain fatty acid (SCFAs) in intestinal contents, respectively, and enzyme-linked immunosorbent assay was used to determine mucin 2 (MUC2) and interleukin 17 (IL-17). ResultsCompared with the Q group, the results showed that with the increase of sucrose dose, the intestinal microbial structure of mice was significantly altered, and the intestinal microbial diversity was elevated, with the poor restoration of the intestinal biological barrier, decreased content of SCFAs, high expression of inflammatory factor IL-17 and decreased content of mucosal protective factor MUC2. In conclusion, we found that the addition of sucrose had an effect on the efficacy of the AAD intervented by QWBZP, which was less effective than QWBZP, showing a certain dose-response relationship. In this experiment, it was concluded that the addition of sucrose might also further lead to intestinal inflammation and the disruption of the intestinal mucosal barrier, and the production of metabolites SCFAs. DiscussionThe addition of sucrose might also further lead to intestinal inflammation and the disruption of the intestinal mucosal barrier, and the production of metabolites SCFAs. However, these findings still need to be verified in a more extensive study. The effect of adding the sweetener sucrose on the efficacy of Chinese herbal medicine in treating diseases also still needs more research.
作者机构：
[Zhou, Kang; Tan, Zhoujin; Zhu, Jiayuan] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Li, Xiaoya; Qiao, Bo; Deng, Na; Li, Dandan] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Tan, ZJ ; Li, DD ] H;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.
关键词：
Sishen Pill;Diarrhea with kidney-yang deficiency syndrome;Intestinal mucosal flora;Kidney;Energy metabolism
摘要：
This study aims to investigate the effect of Sishen Pill on the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Fifteen Kunming male mice were randomly divided into Normal control group (C), Model self-healing group (X) and Sishen Pill group (S), with 5 mice/cages. Hematoxylin eosin (HE) staining was used to observe the kidney structure. Serum Na(+)-K(+)-ATP-ase and Ca(2+)-Mg(2+)-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA), Analysis of intestinal mucosal flora using third-generation high-throughput sequencing. The relative abundance results in the three groups revealed that the dominant bacterial genera: Lactobacillus, Muribaculum and Candidatus-Arthromitus; bacterial species: Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus murinus, and Lactobacillus intestinalis, and differences in the presence of major microbiota between the X and S groups. A positive correlation between Lactobacillus johnsonii and both Ca(2+)-Mg(2+)-ATP-ase and Na(+)-K(+)-ATP-ase was found via correlation analysis. Sishen Pill also changed the manufacture of other secondary metabolites, as well as the metabolism of carbohydrates, glycans, energy, lipids, and other amino acids, and xenobiotics biodegradation and metabolism. In conclusion, Sishen Pill improved kidney structure, energy metabolism and the diversity and structure of intestinal mucosal flora. In addition, Lactobacillus johnsonii may be a characteristic species of Sishen Pill in treating diarrhea with kidney-yang deficiency syndrome.
关键词：
atherosclerosis;endothelial cell;endothelial cell senescence;endothelial cell death
摘要：
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
摘要：
(1) Background: Ginsenoside Rb1-PLGA nanoparticles (GRb1@PLGA@NPs) represent a novel nanotherapeutic system, yet their therapeutic efficacy and underlying mechanisms for treating heart failure (HF) remain unexplored. This study aims to investigate the potential mechanisms underlying the therapeutic effects of GRb1@PLGA@NPs in HF treatment; (2) Methods: The left anterior descending coronary artery ligation was employed to establish a HF model in Sprague-Dawley rats, along with an in vitro oxidative stress model using H9c2 myocardial cells. Following treatment with GRb1@PLGA@NPs, cardiac tissue pathological changes and cell proliferation were observed. Additionally, the serum levels of biomarkers such as NT-proBNP, TNF-alpha, and IL-1 beta were measured, along with the expression of the ROS/PPAR alpha/PGC1 alpha pathway; (3) Results: GRb1@PLGA@NPs effectively ameliorated the pathological status of cardiac tissues in HF rats, mitigated oxidative stress-induced myocardial cell damage, elevated SOD and MMP levels, and reduced LDH, MDA, ROS, NT-proBNP, TNF-alpha, and IL-1 beta levels. Furthermore, the expression of PPAR alpha and PGC1 alpha proteins was upregulated; (4) Conclusions: GRb1@PLGA@NPs may attenuate myocardial cell injury and treat HF through the ROS/PPAR alpha/PGC1 alpha pathway.
摘要：
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
摘要：
Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored. Protein–protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry. Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling. Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.
摘要：
In developing a bisulfite-free methylation assay with the use of restriction enzymes, self-ligation of next generation sequencing adapters (NGS-adapter) is a technological bottleneck to be overcome. In the experiments of this study, a variety of strategies designed to limit or abolish adapter's self-ligation has been tested. Experimental data have showed that the three strategies tested can either substantially decrease or completely abolish the self-ligation of NGS-adapters. Minimization or elimination of NGS-adapter's self-ligation is of importance in increasing the sensitivity, efficiency, and reproducibility of enzyme-mediated methylation assay. The strategies reported in the present study may find applica-tions in some other nanotechnologies. In combination with nanotechnologies, either drop-digit PCR or microarray-based sequencing, the methylation-dependent endonuclease mediated methylation assays will facilitate applications of methy-lation analysis in both fundamental research and clinical epigenetic studies, particularly in early diagnosis of cancer.
作者机构：
[Wang, Shengmei; Li, Lingjiao; Zhou, Wenhu] Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Peoples R China.;[Wang, Shengmei] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.;[Zhou, Wenhu] Changsha Med Univ, Changsha 410219, Peoples R China.
通讯机构：
[Wenhu Zhou] X;Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China<&wdkj&>Academician Workstation, Changsha Medical University, Changsha 410219, China
关键词：
chemotherapy;therapeutic index;GSDME;targeting;cell death
摘要：
Simple Summary Chemotherapy has been widely used in clinic to treat various types of tumors, although severe side effects have been the most critical limitation of this treatment modality. For a long time, it has been believed that toxicity derives from the apoptosis of normal cells induced by the use of chemotherapeutic drugs due to their off-target biodistribution. In 2017, a breakthrough finding by Shao Feng's group showed that the side effects were related to pyroptosis caused by chemotherapeutic-drug-induced GSDME activation, and, interestingly, pyroptosis shares the same upstream signaling molecule with apoptosis, i.e., the caspase-3 activation. From then on, great research attention has been paid to chemotherapy-induced pyroptosis. In reality, pyroptosis is a "double-edged sword", causing side effects in normal tissue, but also being able to promote antitumor effects, owing to its regulation of antitumor immunity. Therefore, rationally balancing the cell apoptosis and pyroptosis of caspase-3-activating chemotherapy is critically important for better antitumor therapy. This critical review aims to summarize recent progress in the field, focusing on how to balance cell apoptosis and pyroptosis for better tumor chemotherapy. Chemotherapy is a standard treatment modality in clinic that exerts an antitumor effect via the activation of the caspase-3 pathway, inducing cell death. While a number of chemotherapeutic drugs have been developed to combat various types of tumors, severe side effects have been their common limitation, due to the nonspecific drug biodistribution, bringing significant pain to cancer patients. Recently, scientists found that, besides apoptosis, chemotherapy could also cause cell pyroptosis, both of which have great influence on the therapeutic index. For example, cell apoptosis is, generally, regarded as the main mechanism of killing tumor cells, while cell pyroptosis in tumors promotes treatment efficacy, but in normal tissue results in toxicity. Therefore, significant research efforts have been paid to exploring the rational modulation mode of cell death induced by chemotherapy. This critical review aims to summarize recent progress in the field, focusing on how to balance cell apoptosis and pyroptosis for better tumor chemotherapy. We first reviewed the mechanisms of chemotherapy-induced cell apoptosis and pyroptosis, in which the activated caspase-3 is the key signaling molecule for regulating both types of cell deaths. Then, we systematically discussed the rationale and methods of switching apoptosis to pyroptosis for enhanced antitumor efficacy, as well as the blockage of pyroptosis to decrease side effects. To balance cell pyroptosis in tumor and normal tissues, the level of GSDME expression and tumor-targeting drug delivery are two important factors. Finally, we proposed potential future research directions, which may provide guidance for researchers in the field.
期刊：
Journal of Biochemical and Molecular Toxicology,2023年37(6):e23344 ISSN：1095-6670
作者机构：
[Xiao, Guiying; Xiong, Liguang; Li, Yuan; Yuan, Fang; Deng, Yang; Xiang, Debiao; Li, Xin] Third Hosp Changsha, Dept Pharm, Changsha, Hunan, Peoples R China.;[Xiao, Guiying; Xiong, Liguang; Li, Yuan; Yuan, Fang; Deng, Yang; Xiang, Debiao; Li, Xin] Third Hosp Changsha, Inst Clin Applicat Antibiot, Changsha, Hunan, Peoples R China.;[Xiao, Guiying; Xiong, Liguang; Li, Xin] Hunan Univ Chinese Med, Hosp Changsha 3, Dept Pharm, Changsha, Hunan, Peoples R China.;[Li, Yuan; Li, Xin] Third Hosp Changsha, Dept Pharm, 176 Western Laodong Rd, Changsha 410015, Hunan, Peoples R China.
关键词：
Nrf2/NQO1 pathway;apoptosis;nephrotoxicity;oxidative stress;polymyxin B
摘要：
Polymyxin B (PMB) is a polypeptide antibiotic widely used in treating multidrug-resistant Gram-negative bacteria. However, nephrotoxicity is a serious adverse effect that limits its clinical use. Therefore, clarification of the molecular mechanism of PMB-induced renal injury is essential. Our study aimed to explore possible mechanisms of PMB-induced nephrotoxicity in vivo and in vitro. Mice were treated with PMB to construct the kidney injury model. The antioxidant capacity was assessed by measuring the superoxide dismutase (SOD) and catalase (CAT) activities and the glutathione (GSH)and malondialdehyde (MDA) contents. The pathway of the nuclear factor erythroid 2-related factor 2/NADH quinone oxidoreductase 1 (Nrf2/NQO1) was examined after PMB treatment in NRK-52E cells and mice. Finally, the expressions of genes and proteins (Bax, Bcl-2, Caspase-3, Caspase-9) related to apoptosis were evaluated through quantitative polymerasechain reaction and western blot assay. The study verified PMB-induced nephrotoxicity in mice and NRK-52E cells in a dose- and time-dependent manner. PMB treatment significantly decreased the expression of Nrf2 and its downstream target gene NQO1 and increased the apoptosis-related proteins expression. In summary, our results suggested that PMB-induced oxidative stress damage by inhibiting the Nrf2/NQO1 pathway and promoting apoptosis in kidney tissues.
期刊：
Cell Death Discovery,2023年9(1):155 ISSN：2058-7716
通讯作者：
Ai, Qidi;Chen, NH
作者机构：
[Ai, Qidi; Lin, Yuting; Yao, Jiao; Sun, Yang; Ai, QD; Chen, Naihong; Lin, Meiyu; Meng, Lei; Yang, Songwei; Yang, Yantao; Yan, Qian; Pei, Gang; Long, Junpeng] Hunan Univ Chinese Med, Coll Pharm, Hunan Engn Technol Ctr Standardizat & Funct Chines, Changsha, Peoples R China.;[Liu, Shasha] Changsha Hosp Matemal & Child Hlth Care, Dept Pharm, Changsha, Peoples R China.;[Chen, Chen] Lanzhou Univ, Hosp 1, Dept Pharm, Lanzhou, Peoples R China.;[Zhang, Zhao; Chen, Naihong; Chu, Shifeng] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China.;[Zhang, Zhao; Chen, Naihong; Chu, Shifeng] Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing, Peoples R China.
通讯机构：
[Ai, QD; Chen, NH ] H;Hunan Univ Chinese Med, Coll Pharm, Hunan Engn Technol Ctr Standardizat & Funct Chines, Changsha, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing, Peoples R China.
摘要：
Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10-20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1β before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway, providing additional therapeutic strategies for the clinical management of stroke. The role of pyroptosis after stroke. After stroke, microglia first rush to the damaged area and polarize into M1 and M2 types. Under the influence of various stimuli, microglia undergo pyroptosis, release pro-inflammatory factors, and are converted to the M1 type; astrocytes and neuronal cells also undergo pyroptosis under the stimulation of various pro-inflammatory factors, leading to astrocyte death due to increased osmotic pressure in the membrane, resulting in water absorption and swelling until rupture. BMECs, the main structural component of the BBB, also undergo pyroptosis when stimulated by pro-inflammatory factors released from microglia and astrocytes, leading to the destruction of the structural integrity of the BBB, ultimately causing more severe brain damage. In addition, GSDMD in neutrophils mainly mediate the release of NETs rather than pyroptosis, which also aggravates brain injury. IL-10=interleukin-10; TGF-β = transforming growth factor-β; IL-18=interleukin-18; IL-1β = interleukin-1β; TNF-α = tumor necrosis factor-α; iNOS=induced nitrogen monoxide synthase; MMPs=Matrix metalloproteinases; GSDMD = gasdermin D; BMECs=brain microvascular endothelial cells; BBB = blood-brain barrier.
摘要：
Evidence is mounting that abnormal vascular remodeling leads to many cardiovascular diseases (CVDs). This suggests that vascular remodeling can be a crucial target for the prevention and treatment of CVDs. Recently, celastrol, an active ingredient of the broadly used Chinese herb Tripterygium wilfordii Hook F, has attracted extensive interest for its proven potential to improve vascular remodeling. Substantial evidence has shown that celastrol improves vascular remodeling by ameliorating inflammation, hyperproliferation, and migration of vascular smooth muscle cells, vascular calcification, endothelial dysfunction, extracellular matrix remodeling, and angiogenesis. Moreover, numerous reports have proven the positive effects of celastrol and its therapeutic promise in treating vascular remodeling diseases such as hypertension, atherosclerosis, and pulmonary artery hypertension. The present review summarizes and discusses the molecular mechanism of celastrol regulating vascular remodeling and provides preclinical proof for future clinical applications of celastrol.
摘要：
BACKGROUND AND AIMS: The increasing prevalence of metabolic and cardiovascular diseases poses a significant challenge to global healthcare systems. Regular physical activity (PA) is recognized for its positive impact on cardiovascular risk factors. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA), sedentary behavior (SB), and abdominal aortic calcification (AAC) using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study used data from NHANES participants aged 40 and above during the 2013-2014 cycle. AAC scores were assessed using the Kauppila scoring system, and MVPA and SB were self-reported. Sociodemographic variables were considered, and multivariable linear regression models were used to analyze associations between MVPA, SB, and AAC scores. Subgroup analyses were conducted based on age, sex, BMI, hypertension, and diabetes. RESULTS: The study included 2843 participants. AAC prevalence was higher in older age groups, smokers, and those with diabetes or hypertension. Lower socioeconomic status was associated with higher AAC prevalence. Individuals engaged in any level of MVPA exhibited lower AAC rates compared to inactive individuals. Not engaging in occupational MVPA (β = 0.46, 95% confidence interval = 0.24‒0.67, p < .001) and prolonged SB (β = 0.28, 95% confidence interval = 0.04‒0.52, p = .023) were associated with higher AAC scores. However, no significant associations were found for transportation and leisure time MVPA. Subgroup analysis revealed age and hypertension as effect modifiers in the MVPA-AAC relationship. CONCLUSIONS: This study highlights the potential benefits of engaging in occupational MVPA and reducing SB in mitigating AAC scores, particularly among older individuals and those with hypertension.
作者机构：
[Ai, Qidi; Lin, Yuting; Yao, Jiao; Sun, Yang; Lin, Meiyu; Meng, Lei; Yang, Songwei; Yan, Qian; Yang, Yantao; Chen, Naihong; Pei, Gang; Long, Junpeng] Hunan Univ Chinese Med, Coll Pharm, Hunan Engn Technol Ctr Standardizat & Funct Chines, R China, Changsha, Peoples R China.;[Liu, Shasha] Changsha Hosp Matemal & Child Hlth Care, Dept Pharm, R China, Changsha, Peoples R China.;[Chen, Chen] First Hosp Lanzhou Univ, Dept Pharm, R China, Lanzhou, Peoples R China.;[Wang, Ting] Zhuzhou Cent Hosp, Dept Rehabil Med, Zhuzhou, Peoples R China.;[Yi, Fan] Beijing Technol & Business Univ, Key Lab Cosmet, China Natl Light Ind, Beijing, Peoples R China.
通讯机构：
[Ai, Qidi; Chen, Naihong; Yang, Yantao] H;Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, P. R. China<&wdkj&>Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, P. R. China<&wdkj&>State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
摘要：
Pulmonary hypertension (PH) was a cardiovascular disease with high morbidity and mortality. PH was a chronic disease with complicated pathogenesis and uncontrollable factors. PH was divided into five groups according to its pathogenesis and clinical manifestations. Although the treatment and diagnosis of PH has made great progress in the past ten years. However, the diagnosis and prognosis of the PAH had a great contrast, which was not conducive to the diagnosis and treatment of PH. If not treated properly, it will lead to right ventricular failure or even death. Therefore, it was necessary to explore the pathogenesis of PH. The problem we urgently need to solve was to find and develop drugs for the treatment of PH. We reviewed the PH articles in the past 10 years or so as well as systematically summarized the recent advance. We summarized the latest research on the key regulatory factors (pyroptosis, apoptosis, necroptosis, ferroptosis, and endoplasmic reticulum stress) involved in PH. To provide theoretical basis and basis for finding new therapeutic targets and research directions of PH.
摘要：
Introduction: Shuanghuanglian injection (lyophilized) (SHLI) is commonly used to treat respiratory tract infection. Shenmai injection (SMI) is mainly used to treat cardiovascular diseases. Despite their widespread clinical use, anaphylactoid reactions (ARs) induced by SHLI and SMI have been reported, which have attracted broad attention. However, the impact of ARs on metabolic changes and the underlying mechanisms are still unclear.Methods: ICR mice were used as model animals and were treated with normal saline, C48/80, SHLI and SMI, respectively. The behavior of mice, auricle blue staining and Evans Blue exudation were used as indexes to evaluate the sensitization of SHLI and SMI and determine the optimal sensitization dose. Anaphylactoid mice model was established based on the optimal dose and enzyme-linked immunosorbent assay (ELISA) was used to model verification. Afterwards, plasma samples of administered mice were profiled by LC-MS metabolomics and analyzed to evaluate the changes in metabolites.Results: High doses of both SHLI and SMI can induce severe anaphylactoid reactions while the reaction induced by SMI was weaker. A Partial Least-Squares Discriminant Analysis (PLS-DA) score plot indicated that following administration, significant metabolic changes occurred in mice. 23 distinct metabolites, including deoxycholic acid, histamine, and 5-hydroxytryptophan, were identified in the SHLI groups. 11 distinct metabolites, including androsterone, 17a-hydroxypregnenolone, and 5-hydroxyindoleacetate, were identified in the SMI groups. Meanwhile, different metabolic pathways of SHLI and SMI were predicted by different metabolites. The associated metabolic pathways include steroid hormone biosynthesis, tryptophan metabolism, histidine metabolism, arachidonic acid metabolism, nicotinate and nicotinamide metabolism, and primary bile acid biosynthesis.Conclusion: Study showed that both SHLI and SMI can induce varying degrees of anaphylactoid reactions, a positive correlation between response intensity and dose was observed. Metabolomics showed that SHLI and SMI may promote the simultaneous release of hormones and inflammatory factors by disturbing relevant metabolic pathways, while SMI may also inhibit the release of inflammatory factors in arachidonic acid metabolic pathway, indicating both pro-inflammatory and anti-inflammatory effects. This study will serve as a reference for developing a new approach to evaluate the safety of SHLI and SMI from perspective of susceptible drug varieties. However, ARs mechanism requires further verification.
