摘要：
OBJECTIVE: This study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC). METHODS: Traditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice. RESULTS: The major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8(+) and IFN-γ(+)/CD4(+) T cell levels while decreasing the PD-1(+)/CD8(+) T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-γ, and TNF-α levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated. CONCLUSION: BP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Lower back pain (LBP) is a common and frequent clinical condition, and intervertebral disc degeneration (IDD) is recognized as the leading cause of LBP, typically manifested by increased nucleus pulposus cell (NPC) senescence and death. In recent years, the treatment of IDD with stem cell injections has had great potential compared to surgical treatment. Combining the two may achieve better results, as BuShenHuoXueFang (BSHXF) is an herbal formula that improves the survival rate of transplanted stem cells and enhances their efficacy. AIM OF THE STUDY: We aimed to qualitatively and quantitatively analyze BSHXF-medicated serum and investigate the molecular mechanism of BSHXF-mediated serum in promoting the differentiation of adipose mesenchymal stem cells (ADSCs) into NPCs and delaying the senescence of NPCs by regulating the TGF-β1/Smad pathway. MATERIALS AND METHODS: In this study, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF-MS) was used to establish a method for the analysis of rat serum samples to track the active components in vivo; the oxidative damage model of NPCs was induced by T-BHP, and a Transwell chamber was used to construct a coculture system of ADSCs and NPCs. Flow cytometry was used to determine the cell cycle; SA-β-Gal staining was used to assess cell senescence; ELISA was used to detect IL-1β, IL-6 inflammatory factors, CXCL-1, CXCL-3, CXCL-10 chemokines, and TGF-β1 in the supernatants of ADSCs and NPCs. WB was used to detect COL2A1, COL1A1, and Aggrecan in ADSCs to assess the manifestation of NP differentiation in ADSCs, and the WB method was used to detect COL2A1, COL1A1, Aggrecan, p16, p21, p53, and p-p53 protein expression in NPCs to reflect the cellular senescence status and to detect TGF-β1, Smad2, Smad3, p- Smad2, and p- Smad3 protein expression in NPCs to reflect the pathway condition. RESULTS: We finally identified 70 blood components and their metabolites, including 38 prototypes, from the BSHXF-medicated serum. Compared with that in the nonmedicated serum group, the TGF-β1/Smad pathway was activated in the medicated serum group, ADSCs moved toward NPC characteristics, the number of NPCs in the S/G2M phase increased, the number of senescent NPCs decreased, IL-1β and IL-6 inflammatory factors in the Transwell decreased, CXCL-1, CXCL-3, and CXCL-10 chemokines decreased, and the expression of p16, p21, p53 and p-p53 proteins in NPCs was inhibited. CONCLUSION: By regulating the TGF-β1/Smad pathway, BSHXF-medicated serum promoted ADSCs to NPCs, effectively alleviated the cycle blockage of NPCs after oxidative damage, encouraged the growth and proliferation of NPCs, delayed the aging of NPCs, improved the deteriorating microenvironment around NPCs, and repaired oxidatively damaged NPCs. The combination of BSHXF or its compounds with ADSCs has great potential for the treatment of IDD in the future.
摘要：
AIM OF THE STUDY: To assess the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and to explore the mechanisms by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP. METHODS: Hydrogen peroxide(H(2)O(2)) was used to induce oxidative stress in 661W cells, which were then examined using flow cytometry and enzyme linked immunosorbent assay (ELISA). Changes in mitochondria were observed by using an electron microscope to characterize the ferroptosis of the cells. The protective effect of FSE on the retina function and structure of rd10 mice was evaluated using histopathological examination, fundus photographs, and electroretinography (ERG). Protein expression levels of Tumor Protein p53 (P53), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione peroxidase 4 (GPX4), Arachidonate-12-Lipoxygenase (ALOX12), and Dipeptidyl peptidase 4 (DPP4) were evaluated by Western blot assays in Vivo and in Vitro. RESULTS: H(2)O(2)-induced 661W cells increased oxidative stress products and P53 and ALOX12, decreasing the expression of SLC7A11, GPX4, and DPP4. GPX4 activator does not reduce reactive oxygen species (ROS) generation and has little effect on ferroptosis. Fer-1 and FSE attenuate ROS generation and inhibit ferroptosis of photoreceptors in RP via inhibited P53 expression and increased SLC7A11 and GPX4 expression. CONCLUSION: FSE may be available in clinical therapeutics to alleviating RP and the mechanism by which inhibits ferroptosis of photoreceptors following oxidative stress via the P53/ SLC7A11 pathway.
作者机构：
[Tang, Chenguang; Xu, Guangning; Zhang, Ying; Luo, Jing; Tan, Min; Lin, Huining] Shenzhen Qianhai Shekou Free Trade Zone Hosp, Dept Tradit Chinese Med, Shenzhen, Peoples R China.;[Deng, Yijue; Wang, MQ; Wang, Mengqing; Luo, Jing] Hunan Univ Chinese Med, Dept Paediat, Hosp 1, Changsha, Peoples R China.;[Ding, Yi] Changsha Social Work Coll, Sch Rehabil, Changsha, Peoples R China.
通讯机构：
[Tang, CG ] S;[Wang, MQ ] H;Shenzhen Qianhai Shekou Free Trade Zone Hosp, Dept Tradit Chinese Med, Shenzhen, Peoples R China.;Hunan Univ Chinese Med, Dept Paediat, Hosp 1, Changsha, Peoples R China.
关键词：
Post-infectious cough;Xiebai and Zengye decoction;Fecal water content;Cough sensitivity;Inflammation;Gut microbiota
摘要：
This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut microbiota and the exploration of the intestinal microecological mechanisms of XBZY decoction in the treatment of PIC. Using a random number table, the rats that were successfully modelled were assigned to the PIC, XBZY group (14.8g/kg/d), and montelukast sodium treatment (MAS) group (1mg/kg/d). The cough sensitivity of rats and changes in fecal water content were assessed, and serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels were determined by ELISA. The histopathological changes in the bronchus and colon tissues were observed under the microscope after hematoxylin-eosin staining. Short-chain fatty acids (SCFAs) in fecal samples were measured by gas chromatography, and changes in gut microbiota were observed using 16S rRNA sequencing. The PIC rats showed decreased fecal water content, increased cough sensitivity, elevated serum TNF-α and IL-8 levels, and higher bronchitis scores comparing to normal control group. The PIC rats showed reductions in SCFAs and significant changes in the structure of gut microbiota. XBZY decoction intervention led to increased fecal water content in rats, reduced cough sensitivity, decreased serum IL-8 and TNF-α levels, decreased bronchitis scores, and alleviated inflammatory cell infiltration was observed in the colonic mucosa. Additionally, elevated SCFAs levels were observed in the PIC rats. XBZY decoction intervention improved alpha-/beta-diversity, and corrected microbiota imbalance in PIC rats. SCFAs, TNF-α and IL-8, acetic acid was revealed to be positively associated with Allobaculum but inversely correlated with unclassified_f_Oscillospiraceae; propanoic acid was positively associated with Lactobacilli but negatively associated with Romboutsia; butanoic acid exhibited positive correlations with Akkermansia and Lactobacilli, but negative correlations with unclassified_f_Oscillospiraceae, Eubacterium_xylanophilum_group, and Lachnospiraceae_NK4A136_group; Additionally, TNF-α was inversely linked to Allobaculum, while IL-8 was positively related to Romboutsia and Turicibacter. In conclusion, XBZY decoction significantly reduced cough sensitivity and airway inflammation in PIC rats while ameliorating stool dryness and colonic inflammation. The protective effects of XBZY decoction could be linked to modulat gut microbiota in PIC rats, and regulat SCFAs contents in PIC rats, while the regulator mechanisms of XBZY decoction in gut microbiota still requires further in-depth investigation.
通讯机构：
[Peng, QH; Peng, QH ; Yao, XL ] H;Hunan Univ Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Dept Ophthalmol, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.
摘要：
Thyroid eye disease (TED), an autoimmune inflammatory disorder affecting the orbit, exhibits a range of clinical manifestations. While the disease presentation can vary, cases that adhere to a prototypical pattern typically commence with mild symptoms that subsequently escalate in severity before entering a phase of stabilization. Notably, the metabolic activity of cells implicated in the disease substantially deviates from that of healthy cells, with purine metabolism representing a critical facet of cellular material metabolism by supplying components essential for DNA and RNA synthesis. Nevertheless, the precise involvement of Purine Metabolism Genes (PMGs) in the defensive mechanism against TED remains largely unexplored. The present study employed a bioinformatics approach to identify and validate potential PMGs associated with TED. A curated set of 65 candidate PMGs was utilized to uncover novel PMGs through a combination of differential expression analysis and a PMG dataset. Furthermore, GSEA and GSVA were employed to explore the biological functions and pathways associated with the newly identified PMGs. Subsequently, the Lasso regression and SVM-RFE algorithms were applied to identify hub genes and assess the diagnostic efficacy of the top 10 PMGs in distinguishing TED. Additionally, the relationship between hub PMGs and clinical characteristics was investigated. Finally, the expression levels of the identified ten PMGs were validated using the GSE58331 and GSE105149 datasets. This study revealed ten PMGs related with TED. PRPS2, PFAS, ATIC, NT5C1A, POLR2E, POLR2F, POLR3B, PDE3A, ADSS, and NTPCR are among the PMGs. The biological function investigation revealed their participation in processes such as RNA splicing, purine-containing chemical metabolism, and purine nucleotide metabolism. Furthermore, the diagnostic performance of the 10 PMGs in differentiating TED was encouraging. This study was effective in identifying ten PMGs linked to TED. These findings provide light on potential new biomarkers for TED and open up possibilities for tracking disease development.
作者机构：
[Hu, Zhuoyu; Hu, Qi; Chen, Xiangdong] Hunan Univ Chinese Med, Dept ophthalmol, Hosp 1, Changsha, Peoples R China.;[Wang, Xuan] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Chen, Xiangdong] Hunan Univ Chinese Med, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Chen, XD ] H;Hunan Univ Chinese Med, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
关键词：
apoptosis;autophagy;diabetes retinopathy;traditional Chinese medicine monomer
摘要：
Diabetic retinopathy (DR) has become one of the top 3 blinding eye diseases in the world. In spite of recent therapeutic breakthroughs, it is not yet possible to cure DR through pharmacotherapy. Cell death is thought to play a key role in the pathogenesis of DR. Moderate modulation of cellular autophagy and inhibition of apoptosis have been identified as effective targets for the treatment of DR. Numerous phytochemicals have emerged as potential new drugs for the treatment of DR. We collected basic DR research on herbal monomers through keywords such as autophagy and apoptosis, and conducted a systematic search for relevant research articles published in the PubMed database. This review provides the effects and reports of herbal monomers on various DR cellular and animal models in vivo and in vitro in the available literature, and emphasizes the importance of cellular autophagy and apoptosis as current DR therapeutic targets. Based on our review, we believe that herbal monomers that modulate autophagy and inhibit apoptosis may be potentially effective candidates for the development of new drugs in the treatment of DR. It provides a strategy for further development and application of herbal medicines for DR treatment.
摘要：
BACKGROUND: As the population ages, the prevalence of cerebral small vessel disease (CSVD) steadily increases, resulting in a significant economic burden on society. In East Asian nations, Chinese medicine has been used extensively to teat CSVD and has been reported to improve the cognitive function of patients. The present study aimed to comprehensively assess the efficacy and safety of Chinese medicine as adjuvant therapy for CSVD. METHODS: A literature search of the CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library, and ChiCTR databases were searched for RCTs investigating the use of TCM as an adjuvant in the treatment of CSVD, published up to July 27, 2023, was performed. Based on the Cochrane Collaboration Network bias risk assessment criteria, Review Manager version 5.3 was used to perform a meta-analysis. RESULTS: Meta-analysis of 27 RCTs, including 2554 subjects, revealed that the majority of the RCTs exhibited risk for ambiguous bias. The findings demonstrated that the use of Chinese medicine as an adjuvant treatment for CSVD effectively enhanced the cognitive function, as evidenced by improvements in the MMSE score (mean difference (MD) = 2.42, 95% confidence interval (CI) [1.79,3.17], P < .00001), MoCA score (MD = 2.39, 95% CI [1.78,2.99], P < .00001) and ADL score (MD = 4.13, 95% CI [1.74,6.51], P = .0007). Furthermore, the study also demonstrated the advantages of Chinese medicine adjuvant therapy in enhancing the Chinese medicine syndrome score (MD = -2.57, 95% CI [-3.31, -1.83], P < .00001), CRP (MD = -1.35, 95% CI [-2.27, -0.43], P = .004), Hcy (MD = -3.44,95% CI [-4.05, -2.83], P < .00001), and blood flow velocity (CBV) (MD = 1.37,95% CI [0.24,2.50], P = .02). Moreover, there was no statistical difference in the incidence of adverse reactions between the 2 groups. CONCLUSION: Findings of the present study indicate that the Chinese medicine, as an adjuvant to conventional treatment, appeared to be efficacious in enhancing cognitive function, reducing Chinese medicine syndrome score, improving blood biochemical markers, and improving cerebral blood flow perfusion in patients with CSVD, without any notable adverse reactions. However, it is imperative to validate these conclusions in future high-quality investigations.
摘要：
BACKGROUND: Tirzepatide (TZP) is a novel drug for type 2 diabetes mellitus (T2DM), but the gastrointestinal (GI) adverse events (AEs) is a limiting factor in clinical application. Therefore, this study systematically evaluated the GI AEs of TZP for T2DM. METHODS: Clinical trials of TZP for T2DM were retrieved from eight databases published only from the establishment of the database to February 2023. Revman5.3 and TSA0.9.5.10 Beta were used for meta-analysis and trials sequential analysis (TSA). RESULTS: Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05). TSA showed that the differences in total GI AEs, nausea, decreased appetite and constipation were conclusive. Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05), and dyspepsia was significantly increased with TZP 15 mg (P < .05). TSA showed that these differences were all conclusive. Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg, total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05), while nausea, vomiting, dyspepsia and constipation were significantly different in all dose groups, abdominal pain were not significantly different (P < .05) and TSA showed no conclusive results in this group. CONCLUSION: The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA. Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose. GI AEs of TZP decrease gradually over time, so long-term steady medication may be expected to reduce GI AEs.
摘要：
OBJECTIVE: The present study aimed to systematically and quantitatively review evidence derived from both postmortem brain and PET studies to explore the pathological role of glia induced neuroinflammation in the pathogenesis of ASD, and discuss the implications of these findings in relation to disease pathogenesis and therapeutic strategies. METHOD: An online databases search was performed to collate postmortem studies and PET studies regarding glia induced neuroinflammation in ASD as compared to controls. Two authors independently conducted the literature search, study selection and data extraction. The discrepancies generated in these processes was resolved through robust discussions among all authors. RESULT: The literature search yielded the identification of 619 records, from which 22 postmortem studies and 3 PET studies were identified as eligible for the qualitative synthesis. Meta-analysis of postmortem studies reported increased microglial number and microglia density as well as increased GFAP protein expression and GFAP mRNA expression in ASD subjects as compared to controls. Three PET studies produced different outcomes and emphasized different details, with one reported increased and two reported decreased TSPO expression in ASD subjects as compared to controls. CONCLUSION: Both postmortem evidences and PET studies converged to support the involvement of glia induced neuroinflammation in the pathogenesis of ASD. The limited number of included studies along with the considerable heterogeneity of these studies prevented the development of firm conclusions and challenged the explanation of variability. Future research should prioritize the replication of current studies and the validation of current observations.
摘要：
Three undescribed methylsuccinic acid derivatives, xylaril acids A-C, and two undescribed enoic acid derivatives, xylaril acids D-E, were isolated from the fungus Xylaria longipes. The structures of the undescribed compounds were deduced by spectroscopic means, including HRESIMS and 1D/2D NMR spectroscopy, as well as ECD calculations. The absolute configuration of xylaril acids A was further determined by single-crystal X-ray diffraction experiments. All the isolated compounds displayed neuroprotective activities against oxygen-glucose deprivation/reperfusion injury in PC12cells by enhancing cell viability and inhibiting cell apoptosis.
期刊：
Environmental Science and Pollution Research,2023年30(52):112943-112958 ISSN：0944-1344
通讯作者：
Guo, ZH
作者机构：
[Zheng, Huizhen; Yin, Ziwei; Luo, Xi; Zhou, Yingli] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Cardiol, Changsha 410007, Peoples R China.;[Zheng, Huizhen; Yin, Ziwei; Zhang, Fei; Luo, Xi; Guo, Zhihua; Zhou, Yingli] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.;[Guo, Zhihua] Hunan Key Lab Coll Intelligent Tradit Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Guo, ZH ] H;Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.;Hunan Key Lab Coll Intelligent Tradit Chinese Med, Changsha 410208, Peoples R China.
关键词：
Per- and polyfluoroalkyl substances;Metabolic syndrome;NHANES;Metabolism;Cardiovascular risk factors;Population-based study
摘要：
Per- and polyfluoroalkyl substances (PFAS) are widespread contaminants, but few studies have explored the relationship between PFAS and levels of metabolic syndrome (MetS) in the population. The available evidence of an association is also conflicting. We selected adults and adolescents with complete PFAS data from the National Health and Nutrition Examination Survey conducted between 2003 and 2018. We analyzed the association between PFAS and MetS using multivariate logistic regression models and evaluated potential nonlinear relationships with restricted cubic spline models. Additionally, we employed weighted quantile sum (WQS) regressions to uncover the multiple exposure effects and relative weights of each PFAS. Finally, we conducted a series of sensitivity analyses to test the robustness of our findings. In this population-based study, we analyzed data from a total of 4,973 adults, aged 20-85 years, and 1,381 adolescents, aged 12-19 years. Using fully adjusted multivariate logistic regression models, we found that serum levels of perfluorodecanoate (PFDA) [0.65 (0.50, 0.85)] and total PFAS [0.92 (0.85, 0.99)] were negatively associated with the prevalence of MetS in adults. Similarly, in adolescents, we observed negative correlations between the prevalence of MetS and levels of PFDA [0.55 (0.38, 0.80)], perfluorooctanoic acid (PFOA) [0.62 (0.39, 1.00)], perfluorooctane sulfonic acid (PFOS) [0.59 (0.36, 0.96)], and total PFAS [0.61 (0.37, 0.99)]. Additionally, our study identified statistically significant negative associations between serum levels of PFAS and certain components of MetS, primarily elevated fasting glucose and lower high-density lipoprotein cholesterol. Our study found that PFAS was associated with a lower prevalence of MetS in both adults and adolescents, offering new insights into the relationship between PFAS and metabolic health. Interestingly, however, we observed conflicting findings across the components of MetS. Specifically, we observed that PFAS had a negative correlation with some metrics and a positive correlation with others. These conflicting results point to a complex interplay between PFAS and various metrics of metabolic health.
作者机构：
[Nie, Duorui; Wang, Fei; Gong, Chun; Lai, Guihua] Hunan Univ Chinese Med, Hosp 1, Dept Oncol, Changsha, Peoples R China.;[Zheng, Hao; Yang, Jing] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou, Peoples R China.;[Cao, Jianxiong] Hunan Univ Chinese Med, Sch Continuing Educ, Changsha, Peoples R China.
通讯机构：
[Chun Gong] D;Department of Oncology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
关键词：
Nomogram;Pancreatic signet ring cell carcinoma;Prognosis;Survival;SEER
摘要：
This study aimed to compare the incidence, clinicopathological characteristics and survival results of pancreatic signet ring cell carcinoma (PSRCC) and pancreatic adenocarcinomas (PDAC), as well as to analyze the clinical characteristics related to the overall survival (OS) of PSRCC, and to establish an effective prognostic nomogram to predict the risks associated with patient outcomes. A total of 85,288 eligible patients including 425 PSRCC and 84,863 PDAC cases were retrieved from the Surveillance, Epidemiology, and End Results database. The survival curve was calculated using the Kaplan–Meier method and differences in them were measured by Log-rank tests. The Cox proportional hazards regression model was used to identify independent predictors of OS in patients with PSRCC. A nomogram was constructed to predict 1-, 3-, and 5-year OS. The performance of the nomogram was measured by C-index, receiver operating characteristic (ROC) curve, decision curve analysis (DCA). The incidence of PSRCC is much lower than that of PDAC (10.798 V.S. 0.349 per millions). PSRCC is an independent predictor of pancreatic cancer with a poorer histological grade, a higher rate of lymph node and distant metastasis, and a poorer prognosis. We identified four independent prognostic factors including grade, American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) stage, surgery and chemotherapy based on the Cox regression model. The C-index and DCA curves showed better performance of the nomogram than TNM stage. ROC curve analysis also showed that the nomogram had good discrimination, with an area under the curve of 0.840, 0.896, and 0.923 for 1-, 3-, and 5-year survival. The calibration curves showed good agreement between the prediction by the nomogram and actual observations. PSRCC is a rare but fatal subtype of pancreatic cancer. The constructed nomogram in this study accurately predicted the prognosis of PSRCC, performed better than the TNM stage.
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：
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.
摘要：
Knee osteoarthritis (KOA) is a common musculoskeletal condition affecting millions of people worldwide and posing a significant challenge to clinicians and researchers. Emerging evidence suggests that the multifaceted symptomatology of KOA may be alleviated by diacerein. With this in mind, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of diacerein in patients with KOA. We systematically searched Embase, PubMed, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), Wanfang Database (WanFang), China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) from their inception to August 2022 for randomized controlled trials (RCTs) of diacerein intervention on patients with KOA. Two reviewers independently performed the selection of eligible studies and the extraction of relevant data. The meta-analysis was performed using RevMan 5.4 and R 4.1.3 software tools. Depending on the type of outcome indicator selected, summary measures were expressed as mean differences (MD), standardized mean differences (SMD), or odds ratio (OR) with 95% confidence intervals (CI). Twelve RCTs with 1732 patients were included. The results revealed that diacerein had comparable efficacy to non-steroidal anti-inflammatory drugs (NSAIDs) in reducing pain indicators such as Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (SMD = 0.09, 95% CI [−0.10, 0.28], P = 0.34) and visual analogue scale (VAS) (SMD = −0.19, 95% CI [−0.65, 0.27], P = 0.42). However, diacerein outperformed NSAIDs in terms of global efficacy assessment by both patients and investigators (patients: 1.97, 95% CI [1.18, 3.29], P = 0.01; investigator: 2.18, 95% CI [0.99, 4.81], P = 0.05) at the end of treatment and sustained effectiveness in reducing WOMAC score and VAS score at four weeks after treatment. Moreover, there was no significant difference in adverse events incidence between the diacerein and NSAID groups. However, the GRADE evaluation indicated that the majority of the evidence quality was low. The results of this study suggest that diacerein could potentially be considered as a pharmacological agent with significant efficacy for the treatment of patients suffering from KOA, offering a potential alternative treatment strategy for those patients contraindicated to NSAIDs. However, further high-quality studies with longer follow-up are needed to make more informed decisions about its efficacy in the treatment of KOA.
通讯机构：
[Liu, HY; Zuo, YJ ] H;Hunan Univ Chinese Med, Dept Pharm, Hosp 1, Changsha, Peoples R China.
关键词：
4-hydroxylonchocarpin;Corylifol A;Hepatotoxicity;Network analysis;Oxidative stress;Psoralea corylifolia L.
摘要：
Psoralea corylifolia L. (P. corylifolia) has attracted increasing attention because of its potential hepatotoxicity. In this study, we used network analysis (toxic component and hepatotoxic target prediction, proteinprotein interaction, GO enrichment analysis, KEGG pathway analysis, and molecular docking) to predict the components and mechanism of P. corylifolia-induced hepatotoxicity and then selected 4-hydroxylonchocarpin and corylifol A for experimental verification. HepG2 cells were treated with low, medium, and high concentrations of 4-hydroxylonchocarpin or corylifol A. The activities of ALT, AST, and LDH in cell culture media and the MDA level, SOD activity, and GSH level in cell extracts were measured. Moreover, apoptosis, ROS levels, and mitochondrial membrane potential were evaluated. The results showed that the activities of ALT, AST, and LDH in the culture medium increased, and hepatocyte apoptosis increased. The level of MDA increased, and the activity of SOD and level of GSH decreased, and the ROS level increased with 4-hydroxylonchocarpin and corylifol A intervention. Furthermore, the mitochondrial membrane potential decreased in the 4-hydroxylonchocarpin and corylifol A groups. This study suggests that 4-hydroxylonchocarpin and corylifol A cause hepatocyte injury and apoptosis by inducing oxidative stress and mitochondrial dysfunction, suggesting that these compounds may be the potential hepatotoxic components of P. corylifolia.
