关键词:
Acute toxicity;Behavioral analysis;Danggui Shaoyao San;Danio rerio;Histopathological alteration index
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. AIM OF THE STUDY: To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. MATERIALS AND METHODS: The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. RESULTS: Compared with the control group, 25, 50 and 100mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio, only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. CONCLUSION: A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation.
摘要:
A549 cells were treated with different concentrations of anlotinib to create anlotinib‐resistant A549 cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. Meanwhile, A549 and A549/anlotinib cells were treated with β‐sitosterol at different concentrations. Cell Counting Kit‐8 (CCK‐8) was used to measure cell proliferation. The apoptosis level was detected by flow cytometry. Real‐time fluorescence quantitative PCR was used to detect the expression of miR‐181a‐3p. miR‐181a‐3p interaction with H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted by miRDB and TargetScan Human databases and verified by luciferase reporter assay. The expressions of SHQ1, activating transcription factor 6 (ATF6) and glucose regulated protein 78 (GRP78) were detected by western blot. Our results show that β‐Sitosterol markedly promoted anlotinib‐resistant A549 cells apoptosis and inhibited the cell proliferation via activating SHQ1/UPR signaling via inhibiting miR‐181a‐3p. Abstract Anlotinib is used for the treatment of advanced non‐small cell lung cancer; however, the emergence of drug resistance limits its clinical application. β‐sitosterol may also be used to treat lung cancer, but there have been no studies evaluating β‐sitosterol against anlotinib‐resistant lung cancer. The purpose of this study was to determine the mechanism by which β‐sitosterol enhances the sensitivity of lung cancer cells to anlotinib. A549 cells were treated with different concentrations of anlotinib to generate anlotinib‐resistant cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. A549 and A549/anlotinib cells were treated with β‐sitosterol at various concentrations. The Cell Counting Kit‐8 (CCK‐8) assay was used to measure cell proliferation. Apoptosis was assessed by flow cytometry. Real‐time quantitative PCR was used to measure the expression of miR‐181a‐3p. The interaction of miR‐181a‐3p with the H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted using the miRDB and TargetScan Human databases and verified with a luciferase reporter assay. The expression of SHQ1, activating transcription factor 6 (ATF6), and glucose‐regulated protein 78 (GRP78) were measured by western blot analysis. β‐Sitosterol effectively suppressed A549/anlotinib cell proliferation and promoted apoptosis. SHQ1 is a downstream target of miR‐181a‐3p. The expression of miR‐181a‐3p was inhibited; however, SHQ1 expression was increased by β‐sitosterol treatment of A549/anlotinib cells. The inhibition of SHQ1, ATF6, and GRP78 protein expression by β‐sitosterol in A549/anlotinib cells was rescued by increased miR‐181a‐3p. β‐Sitosterol markedly promotes anlotinib‐resistant A549 cell apoptosis and inhibits cell proliferation by activating SHQ1/UPR signaling through miR‐181a‐3p inhibition.
作者机构:
[Wu, Qin; Zhang, Ya-nan] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Deng, YH; Deng, Yi-hui] Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Deng, YH ] H;Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Hunan, Peoples R China.
摘要:
Gestational diabetes mellitus (GDM) is a common complication that occurs during pregnancy. Emerging evidence suggests that immune abnormalities play a pivotal role in the development of GDM. Specifically, regulatory T cells (Tregs) are considered a critical factor in controlling maternal-fetal immune tolerance. However, the specific characteristics and alterations of Tregs during the pathogenesis of GDM remain poorly elucidated. Therefore, this study aimed to investigate the changes in Tregs among pregnant women diagnosed with GDM compared to healthy pregnant women. A prospective study was conducted, enrolling 23 healthy pregnant women in the third trimester and 21 third-trimester women diagnosed with GDM. Participants were followed up until the postpartum period. The proportions of various Treg, including Tregs, mTregs, and nTregs, were detected in the peripheral blood of pregnant women from both groups. Additionally, the expression levels of PD-1, HLA-G, and HLA-DR on these Tregs were examined. The results revealed no significant differences in the proportions of Tregs, mTregs, and nTregs between the two groups during the third trimester and postpartum period. However, GDM patients exhibited significantly reduced levels of PD-1(+) Tregs (P < 0.01) and HLA-G(+) Tregs (P < 0.05) in the third trimester compared to healthy pregnant women in the third trimester. Furthermore, GDM patients demonstrated significantly lower levels of PD-1(+) mTregs (P < 0.01) and HLA-G(+) (P < 0.05) mTregs compared to healthy pregnant women in the third trimester. Overall, the proportion of Tregs did not exhibit significant changes during the third trimester in GDM patients compared to healthy pregnant women. Nevertheless, the observed dysregulation of immune regulation function in Tregs and mTregs may be associated with the development of GDM in pregnant women.
摘要:
Immunotherapy, particularly immune checkpoint inhibitor (ICIs) therapy, stands as an innovative therapeutic approach currently garnering substantial attention in cancer treatment. It has become a focal point of numerous studies, showcasing significant potential in treating malignancies, including lung cancer and melanoma. The objective of this research is to analyze publications regarding immunotherapy for colorectal cancer (CRC), investigating their attributes and identifying the current areas of interest and cutting-edge advancements. We took into account the publications from 2002 to 2022 included in the Web of Science Core Collection. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel. The quantity of publications associated with this domain has been steadily rising over the years, encompassing 3753 articles and 1498 reviews originating from 573 countries and regions, involving 19,166 institutions, 1011 journals, and 32,301 authors. In this field, China, the United States, and Italy are the main countries that come forward for publishing. The journal with the greatest impact factor is CA-A Cancer Journal for Clinicians. Romain Cohen leads in the number of publications, while Le Dt stands out as the most influential author. The immune microenvironment and immune infiltration are emerging as key hotspots and future research directions in this domain. This research carries out an extensive bibliometric examination of immunotherapy for colorectal cancer, aiding researchers in understanding current focal points, investigating possible avenues for research, and recognizing forthcoming development trends.
作者机构:
[Yang, Renyi; Zeng, Puhua; Jian, Huiying; Xue, Peisen; Li, Kexiong; Li, KX; Yu, Xiaopeng; Peng, Wei; Peng, W] Hunan Acad Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Canc Res Inst, Hunan Acad Tradit Chinese Med, Changsha 410006, Hunan, Peoples R China.;[Gao, Wenhui; Peng, Lian] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Wang, Zhibing] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Li, KX; Zeng, PH ; Peng, W] H;Hunan Acad Chinese Med, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Canc Res Inst, Hunan Acad Tradit Chinese Med, Changsha 410006, Hunan, Peoples R China.
关键词:
Ferroptosis;Hepatocellular carcinoma;Mitochondrial dysfunction;Nrf2/HO-1/GPX4 axis;Polyphyllin I
摘要:
BACKGROUND: Ferroptosis is an emerging iron-dependent programmed cell death mode characterized by lipid peroxidation and iron accumulation, closely associated with Hepatocellular Carcinoma (HCC) progression. Although the impact of Polyphyllin I (PPI), a prominent bioactive constituent derived from Paris polyphylla, on diverse malignancies has been established, the specific role and potential mechanistic pathways through which PPI modulates ferroptosis in HCC remain elusive. PURPOSE: This study aimed to elucidate the anti-cancer properties and potential mechanisms of PPI in inducing ferroptosis and triggering mitochondrial injury in HCC. METHODS: Cell viability was assessed using CCK-8 assays. EdU proliferation and colony formation assays were employed to evaluate cell proliferation. A wound-healing assay was performed to assess cell migration. Transwell assay was utilized to evaluate cell invasion. Ferroptosis was evaluated through the utilization of a FerroOrange fluorescent probe, malondialdehyde (MDA) and reduced glutathione (GSH) assay kits, DCFH-DA fluorescent probe, western blotting, and transmission electron microscopy (TEM) analysis. Molecular docking, immunofluorescence, and western blotting were employed to predict and validate the binding and interaction of PPI with Nrf2, HO-1, xCT, and GPX4. Mitochondrial structure and membrane potential changes were evaluated using JC-1 and Mito Tracker Green fluorescent probes. A nude mice xenograft model was constructed to determine the inhibitory effects and the levels of ferroptosis of PPI on HCC through hematoxylin and eosin (H&E), Prussian blue reaction, immunofluorescence staining, immunohistochemistry, and western blotting analysis, in vivo. RESULTS: PPI exhibited dose-dependent inhibitory effects on the proliferation, invasion, and metastasis of HCC cells mediated by increasing reactive oxygen species (ROS) and MDA levels, promoting Fe(2+) accumulation, depleting GSH, and suppressing the expression of xCT and GPX4, thereby inducing ferroptosis in HCC. The induction of ferroptosis by PPI was associated with the binding of PPI to Nrf2, HO-1, and GPX4 proteins, modulating the Nrf2/HO-1/GPX4 antioxidant axis. PPI also induced mitochondrial structural damage and decreased mitochondrial membrane potential (MMP). Inhibition of ferroptosis by ferrostatin-1 (Fer-1) mitigated the mitochondrial disruption induced by PPI. In vivo, PPI inhibited Nrf2/HO-1/GPX4 axis-induced ferroptosis, impeding HCC growth similar to the effects of sorafenib. CONCLUSION: These results demonstrated that PPI intervention can suppress the proliferation, invasion, and metastasis of HCC cells by enhancing mitochondrial disruption and inducing ferroptosis via the Nrf2/HO-1/GPX4 axis. Consequently, our research advances the frontiers of pharmacodynamics and deepens our comprehension of the intricate mechanisms underpinning PPI. Furthermore, it has yielded an innovative treatment stratagem rooted in the tenets of Traditional Chinese Medicine (TCM), thereby furnishing a novel therapeutic avenue for addressing HCC.
作者机构:
[Zeng, Puhua; Jian, Xiaolan; Peng, Wei] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Changsha 410006, Peoples R China.;[Peng, Wei] Hunan Univ Tradit Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410006, Peoples R China.;[Yang, Renyi; Yu, Xiaopeng] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Nie, Sha] Fourth Hosp Changsha, Changsha 410006, Hunan, Peoples R China.;[Zeng, Puhua] Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha, Hunan, Peoples R China.
通讯机构:
[Zeng, PH ; Jian, XL] H;Hunan Acad Tradit Chinese Med, Affiliated Hosp, Changsha 410006, Peoples R China.;Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha, Hunan, Peoples R China.
关键词:
Postoperative patients with pancreatic cancer;Nomogram;Cancer specific survival;Prediction model;SEER database
摘要:
The recurrence rate and mortality rate among postoperative pancreatic cancer patients remain elevated. This study aims to develop and validate the cancer-specific survival period for individuals who have undergone pancreatic cancer surgery. We extracted eligible data from the Surveillance, Epidemiology, and End Results database and randomly divided all patients into a training cohort and an internal validation cohort. External validation was performed using a separate Chinese cohort. The nomogram was developed using significant risk factors identified through univariate and multivariate Cox proportional hazards regression. The effectiveness of the nomogram was assessed using the area under the time-dependent curve, calibration plots, and decision curve analysis. Kaplan–Meier survival curves were utilized to visualize the risk stratification of nomogram and AJCC stage. Seven variables were identified through univariate and multivariate analysis to construct the nomogram. The consistency index of the nomogram for predicting overall survival was 0.683 (95% CI: 0.675–0.690), 0.689 (95% CI: 0.677–0.701), and 0.823 (95% CI: 0.786–0.860). The AUC values for the 1- and 2-year time-ROC curves were 0.751 and 0.721 for the training cohort, 0.731 and 0.7554 for the internal validation cohort, and 0.901 and 0.830 for the external validation cohorts, respectively. Calibration plots demonstrated favorable consistency between the predictions of the nomogram and actual observations. Moreover, the decision curve analysis indicated the clinical utility of the nomogram, and the risk stratification of the nomogram effectively identified high-risk patients. The nomogram guides clinicians in assessing the survival period of postoperative pancreatic cancer patients, identifying high-risk groups, and devising tailored follow-up strategies.
摘要:
Recent studies have highlighted the significant involvement of tryptophan metabolism in the pathogenesis of Alzheimer's disease (AD). However, a comprehensive investigation of the precise role of tryptophan metabolism in the context of AD is still lacking. This study employed a bioinformatics approach to identify and validate potential tryptophan metabolism-related genes (TrpMgs) associated with AD. The discovery of TrpMgs was facilitated through the intersection of the Weighted Gene Co-expression Network Analysis (WGCNA) test and 17 known tryptophan metabolism pathways. Subsequently, the putative biological functions and pathways of the TrpMgs were elucidated using Gene Set Variation Analysis (GSVA). Furthermore, the Least Absolute Shrinkage and Selection Operator (LASSO) method was applied to identify hub genes and evaluate the diagnostic efficiency of the 5 TrpMgs in distinguishing AD. The relationship between hub TrpMgs and clinical characteristics was also investigated. Finally, in vivo verification of the five TrpMgs was performed using APP/PS1 mice. We identified 5 TrpMgs associated with AD, including propionyl-CoA carboxylase subunit beta (PCCB), TEA Domain Transcription Factor 1 (TEAD1), Phenylalanyl-TRNA Synthetase Subunit Beta (FARSB), Neurofascin (NFASC), and Ezrin (EZR). Among these genes, PCCB, FARSB, NFASC, and TEAD1 showed correlations with age. In the hippocampus of APP/PS1 mice, we observed down-regulation of FARSB, PCCB, and NFASC mRNA expressions. Furthermore, PCCB and NFASC protein expressions were also down-regulated in the cerebral cortex and hippocampus of APP/PS1 mice. Our study paves the way for future research aimed at unraveling the intricate mechanisms underlying tryptophan metabolism dysregulation in AD and its therapeutic implications.
期刊:
Journal of Cancer Research and Clinical Oncology,2023年149(12):10099-10108 ISSN:0171-5216
通讯作者:
Zeng, PH
作者机构:
[Yang, Renyi] Hunan Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Yu, Xiaopeng] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Zeng, Puhua] Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha 410006, Peoples R China.
通讯机构:
[Zeng, PH ] H;Hunan Acad Tradit Chinese Med, Canc Res Inst, Changsha 410006, Peoples R China.
关键词:
Hepatocellular carcinoma;Young and middle-aged male;Nomogram;Overall survival;Predict;Risk stratification
摘要:
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common digestive tumor, and we aimed to develop and validate nomogram models, predicting the overall survival (OS) of young and middle-aged male patients with HCC. METHODS: We extracted eligible data from relevant patients between 2000 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. In addition, randomly divided all patients into two groups (training and validation = 7:3). The nomogram was established using effective risk factors based on univariate and multivariate analysis. The area under the time-dependent curve, calibration plots, and decision curve analysis (DCA) were used to evaluate the effective performance of the nomogram. The risk stratifications of the nomogram and the AJCC criteria-based tumor stage were compared. RESULTS: 11 variables were selected by univariate and multivariate analysis to establish the nomogram of HCC. The AUC values of 3, 4, and 5 years of the time-ROC curve are 0.858, 0.862 and 0.859 for the training cohort, and 0.858, 0.877 and 0.869 for the validation cohort, respectively, indicating that the nomogram has a good ability of discrimination. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts. In addition, the decision curve DCA showed that the nomogram was clinically useful and had better discriminative ability to recognize patients at high risk than the AJCC criteria-based tumor stage. CONCLUSION: Prognostic nomogram of young and middle-aged male patients with HCC was developed and validated to help clinicians evaluate the prognosis of patients.
期刊:
FRONTIERS IN ENDOCRINOLOGY,2023年14:1292011 ISSN:1664-2392
通讯作者:
Tian, XF
作者机构:
[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Univ Chinese Med, Hunan Key Lab Tradit Chinese Med Prescript & Syndr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Prov Univ Key Lab Oncol Tradit Chinese Med, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF; Chen, Yating; Liu, Mengsi; Feng, Ting] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Zhang, Zhen] Hunan Acad Tradit Chinese Med, Dept Oncol, Affiliated Hosp, Changsha, Peoples R China.
通讯机构:
[Tian, XF ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Hunan Key Lab Tradit Chinese Med Prescript & Syndr, Changsha, Peoples R China.;Hunan Prov Univ Key Lab Oncol Tradit Chinese Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.
摘要:
Recent research has emphasized the interaction between the circadian clock and lipid metabolism, particularly in relation to tumors. This review aims to explore how the circadian clock regulates lipid metabolism and its impact on carcinogenesis. Specifically, targeting key enzymes involved in fatty acid synthesis (SREBP, ACLY, ACC, FASN, and SCD) has been identified as a potential strategy for cancer therapy. By disrupting these enzymes, it may be possible to inhibit tumor growth by interfering with lipid metabolism. Transcription factors, like SREBP play a significant role in regulating fatty acid synthesis which is influenced by circadian clock genes such as BMAL1, REV-ERB and DEC. This suggests a strong connection between fatty acid synthesis and the circadian clock. Therefore, successful combination therapy should target fatty acid synthesis in addition to considering the timing and duration of drug use. Ultimately, personalized chronotherapy can enhance drug efficacy in cancer treatment and achieve treatment goals
作者机构:
[Yang, Kailin; Ge, Jinwen] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Zeng, Liuting] Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Peking Union Med Coll, Grad Sch,Dept Rheumatol & Immunol, Nanjing, Peoples R China.;[Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.;[Long, Zhiyong; Zhen, Huang] Guangzhou Panyu Cent Hosp, Dept Rehabil Med, Guangzhou, Peoples R China.;[Xiao, Wei] Peoples Hosp Ningxiang City, Ningxiang, Peoples R China.
通讯机构:
[Ge, JW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.
关键词:
Total glucosides of paeony;Inflammatory arthritis;Rheumatoid arthritis;Ankylosing spondylitis;Osteoarthritis;Juvenile idiopathic arthritis;Psoriatic arthritis
摘要:
OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)-6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.
期刊:
Ageing Research Reviews,2023年91:102063 ISSN:1568-1637
通讯作者:
Yang, Kailin;Ge, JW;Zeng, LT
作者机构:
[Wang, Shanshan; He, Qi; Yang, Kailin; Ge, Jinwen] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Yang, Kailin; Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.;[Zeng, Liuting; Zeng, LT] Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Grad Sch, Peking Union Med Coll,Dept Rheumatol & Immunol, Nanjing, Peoples R China.;[Zeng, Jinsong; Ge, Anqi] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[He, Qi; Deng, Ying] Peoples Hosp Ningxiang City, Ningxiang, Peoples R China.
通讯机构:
[Zeng, LT ] C;[Yang, KL; Ge, JW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Grad Sch, Peking Union Med Coll,Dept Rheumatol & Immunol, Nanjing, Peoples R China.
摘要:
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptosis have been seen in the brain tissues of PD patients, including alterations in iron metabolism, lipid peroxidation, and increased levels of reactive oxygen species. Preclinical research has demonstrated the neuroprotective qualities of certain iron chelators, antioxidants, Fer-1, and conditioners in Parkinson's disease. Natural plant products have shown significant potential in balancing ferroptosis-related factors and adjusting their expression levels. Therefore, it is vital to understand the mechanisms by which natural plant products inhibit ferroptosis and relieve PD symptoms. This review provides a comprehensive look at ferroptosis, its role in PD pathology, and the mechanisms underlying the therapeutic effects of natural plant products focused on ferroptosis. The insights from this review can serve as useful references for future research on novel ferroptosis inhibitors and lead compounds for PD treatment.
期刊:
Molecular and Cellular Biochemistry,2023年478(8):1791-1802 ISSN:0300-8177
通讯作者:
Qinghu He
作者机构:
[Luo, Min; Chen, Jisong; Hu, Zongren; He, Qinghu] Hunan Univ Med, Dept Rehabil & Healthcare, 492 Jinxi South Rd, Huaihua City, Hunan, Peoples R China.;[Wang, Neng; Hu, Zongren; He, Qinghu] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhang, Yuanting] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Luo, Min] Cent South Univ, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.;[Xiao, Yinfu] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Qinghu He] D;Department of Rehabilitation and Healthcare, Hunan University of Medicine, Huaihua City, China<&wdkj&>School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要:
Erectile dysfunction (ED) is a major health problem affecting a large proportion of the general population. Testosterone also plays a key role in sexual dysfunction. In this study, we found that testosterone can inhibit cavernous fibrosis by affecting the expression of miR-22-3p, providing a new basis for research and treatment of ED. Old and young rats were used to study the effects of testosterone on cavernous fibrosis. Hematoxylin and eosin (HE) and Masson's staining were used to observe the cavernous tissue. A luciferase assay was used to analyze the relationship between the miR-22-3p, TGF beta R1, and Galectin-1 signaling pathways. CCK-8 and flow cytometry were used to detect the proliferation and apoptosis rates of cavernosum smooth muscle cells (CSMCs) following testosterone intervention. Immunohistochemical analysis was performed to examine the positive rate of caspase 3 and Ki67. IF was used to analyze the expression of collagen IV, MMP2, and alpha-SMA. The levels of GnRH, tT, LH, and F-TESTO in old rats increased after testosterone intervention. miR-22-3p inhibits the expression of TGF beta R1 and Galectin-1. The protein expression of TGF beta R1, Galectin-1, SMAD2, and p-SMAD2 was reduced by testosterone. The expression levels of alpha-SMA, collagen I, collagen IV, FN, and MMP2 in the cavernous tissues of old rats treated with testosterone were significantly reduced. The levels of caspase 3 and collagen IV decreased, and the levels of MMP2, Ki67, and alpha-SMA increased. Testosterone and miR-22-3p inhibit CSMC apoptosis and promote cell proliferation. Testosterone promoted the expression of miR-22-3p to interfere with the expression of the cavernous TGF beta R1 and Galectin-1 signaling pathways. Testosterone can reduce cavernous fibrosis during the treatment of functional ED.
摘要:
OBJECTIVE: To evaluate the efficacy of Baishao Luoshi decoction ((sic), BD) on synaptic plasticity in rats with post stroke spasticity (PSS), and to study the mechanism behind the action. METHODS: The PSS model of rat was established by middle cerebral artery occlusion (MCAO). The neurological deficit symptoms were evaluated by modified neurological deficit score (mNSS). Muscle tension were evaluated by Modified Ashworth score (MAS). Transmission electron microscopy (TEM) was used to observe the synaptic ultrastructure. The expression of synaptic plasticity-related protein brain derived neurotrophic factor (BDNF), growth associatedprotein-43 (GAP43), synaptophysin (p38) and microtubule-associated protein 2 (MAP2) in the brain tissue around the infarct were detected by Western blotting. RESULTS: We found that mNSS were significantly improved and limb spasticity was ameliorated treated by BD. The thickness of postsynaptic density and the synaptic curvature increased significantly. The expression of synaptic plasticity-related protein BDNF, GAP43, p38, MAP2 in the brain tissue around the infarct were raised remarkably after treated by BD. CONCLUSIONS: Alleviating PSS by BD may be related to rescuing the synaptic plasticity, which provides a probable new therapeutic method for PSS. (c) 2023 JTCM. All rights reserved.
作者机构:
[Shen, Hongrong; Wang, Jinling; Gao, Hui; Li, Ping; Zhou, Shuwei; Li, Jianyu; Zhong, Zeya; You, Tian; Hu, Xiaoli; Luo, Muqing; Yan, Luyou; Zhang, Kun; He, Yewen] Hunan Univ Chinese Med, Hosp 1, Dept Radiol, 95 Shaoshan Middle Rd, Changsha 410007, Peoples R China.;[Wang, Jinling; Zhou, Shuwei; Zhang, Kun] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Peoples R China.;[Chen, Suping] GE Healthcare Shanghai Co Ltd, Shanghai 201203, Peoples R China.
通讯机构:
[Kun Zhang] D;Department of Radiology, The First Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China<&wdkj&>College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
摘要:
With the aging population of society, the incidence rate of osteoporosis is increasing year by year. Early diagnosis of osteoporosis plays a significant role in the progress of disease prevention. As newly developed technology, computed tomography (CT) radiomics could discover radiomic features difficult to recognize visually, providing convenient, comprehensive and accurate osteoporosis diagnosis. This study aimed to develop and validate a clinical-radiomics model based on the monochromatic imaging of single source dual-energy CT for osteoporosis prediction. One hundred sixty-four participants who underwent both single source dual-energy CT and quantitative computed tomography (QCT) lumbar-spine examination were enrolled in a study cohort including training datasets (n = 114 [30 osteoporosis and 84 non-osteoporosis]) and validation datasets (n = 50 [12 osteoporosis and 38 non-osteoporosis]). One hundred seven radiomics features were extracted from 70-keV monochromatic CT images. With QCT as the reference standard, a radiomics signature was built by using least absolute shrinkage and selection operator (LASSO) regression on the basis of reproducible features. A clinical-radiomics model was constructed by incorporating the radiomics signature and a significant clinical predictor (age) using multivariate logistic regression analysis. Model performance was assessed by its calibration, discrimination and clinical usefulness. The radiomics signature comprised 14 selected features and showed good calibration and discrimination in both training and validation cohorts. The clinical-radiomics model, which incorporated the radiomics signature and a significant clinical predictor (age), also showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.938 (95% confidence interval, 0.903–0.952) in the training cohort and an AUC of 0.988 (95% confidence interval, 0.967–0.998) in the validation cohort, and good calibration. The clinical-radiomics model stratified participants into groups with osteoporosis and non-osteoporosis with an accuracy of 94.0% in the validation cohort. Decision curve analysis (DCA) demonstrated that the radiomics signature and the clinical-radiomics model were clinically useful. The clinical-radiomics model incorporating the radiomics signature and a clinical parameter had a good ability to predict osteoporosis based on dual-energy CT monoenergetic imaging.
期刊:
Naunyn-Schmiedeberg's Archives of Pharmacology,2023年396(5):831-849 ISSN:0028-1298
通讯作者:
Zhigang Mei
作者机构:
[Chen, Xiangyu; Yang, Tong; Ge, Jinwen; Fang, Rui; Mei, Zhigang] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Feng, Zhitao; Luo, Yanan] China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med, State Adm Tradit Chinese Med, Med Coll, Yichang 443002, Hubei, Peoples R China.
通讯机构:
[Zhigang Mei] T;The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
关键词:
ARRIVE;Buyang Huanwu decoction;Cerebral ischemia–reperfusion injury;Methodological and reporting quality;SYRCLE
摘要:
Buyang Huanwu decoction, a classic traditional Chinese prescription, has been used to prevent and treat stroke for hundreds of years. An increasing number of the laboratory research on Buyang Huanwu decoction used in treating cerebral ischemia-reperfusion injury have been published recently. However, the problem of methodological and reporting quality of some studies is lack of assessment. This study aims to evaluate the methodological and reporting quality of the research on Buyang Huanwu decoction against experimental cerebral ischemia-reperfusion injury. A comprehensive search on six databases was performed. Two researchers independently screened the literature considering the eligibility criteria. Methodological and reporting quality of the included studies were evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guideline. Forty-five studies met the inclusion criteria. No study achieved a decent overall rating in using the SYRCLE tool (percentage of items with "low risk" ≥ 50%). Of the 22 items on the SYRCLE tool, only 7 items (31.82%) were rated as "low risk" in more than 50% of the included studies. Of the 39 items of ARRIVE guideline, 14 (35.9%) items were rated as "yes" in more than 50% of the included studies. The methodological and reporting quality of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury was substandard, which needed to be further improved. The limitations should be addressed when planning similar studies in the future. Additionally, these findings provided evidence-based guidance for future preclinical studies evaluating the efficacy of Buyang Huanwu decoction in the treatment of cerebral ischemia-reperfusion injury.
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.
期刊:
Journal of Clinical Gastroenterology,2023年57(8):782-788 ISSN:0192-0790
通讯作者:
Tian, XF
作者机构:
[Huang, Caizhi; Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;[Huang, Caizhi] Hunan Childrens Hosp, Dept Lab Med, Changsha, Peoples R China.;[Mei, Si] Hunan Univ Chinese Med, Dept Physiol, Changsha, Peoples R China.;[Zhang, Xue] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构:
[Tian, XF ] H;Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
关键词:
gut microbiota, hepatocellular carcinoma, inflammation, dysbiosis
摘要:
Hepatocellular carcinoma (HCC) is an invasive primary liver cancer caused by multiple pathogenic factors and is a significant global health concern. With few effective therapeutic options, HCC is a heterogeneous carcinoma that typically arises in an inflammatory environment. Recent studies have suggested that dysbiotic gut microbiota is involved in hepatocarcinogenesis via multiple mechanisms. In this review, we discuss the effects of gut microbiota, microbial components, and microbiota-derived metabolites on the promotion and progression of HCC by feeding a persistent inflammatory milieu. In addition, we discuss the potential therapeutic modalities for HCC targeting the inflammatory status induced by gut microbiota. A better understanding of the correlation between the inflammatory milieu and gut microbiota in HCC may be beneficial for developing new therapeutic strategies and managing the disease.
作者机构:
[Long, Chunjiao; Liu, Chi; Qu, Xiangping; Liu, Huijun; Qin, Xiaoqun; Xiang, Yang; Ji, Ming; Liu, Lexin; Wu, Di; Zhu, Jiahui] Cent South Univ, Sch Basic Med Sci, Dept Physiol, Changsha 410008, Hunan, Peoples R China.;[Wu, Di] Foshan Univ, Sch Med, Foshan 528000, Guangdong, Peoples R China.;[Liu, Caixia] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Xiang, Y ] C;Cent South Univ, Sch Basic Med Sci, Dept Physiol, Changsha 410008, Hunan, Peoples R China.
关键词:
CTNNAL1;Glucocorticoid sensitivity;Asthma;House dust mite;Heat shock protein 90
摘要:
AIMS: Adhesion molecules play vital roles in the induction of airway hyperresponsiveness (AHR) or airway inflammation. The down-regulation of catenin alpha-like 1 (CTNNAL1) in the bronchial epithelial cells of asthma patients and mice models has been noted in our previous study. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. MAIN METHODS: We constructed a house dust mite (HDM)-induced asthma animal model on control mice and applied CTNNAL1-siRNA transfection to create CTNNAL1-deficient mice. KEY FINDINGS: We documented much more severe airway inflammation and increased leukocyte infiltration in the lungs of the CTNNAL1-deficient mice comparing to control mice, along with elevated expression of inflammatory cytokines. Dexamethasone (DEX) treatment led to less reduced inflammation in CTNNAL1-deficient mice compared with control mice. Immunoprecipitation confirmed the interaction between heat shock protein90 (hsp90) and CTNNAL1. The expression of hsp90 was upregulated after CTNNAL1 silencing. Meanwhile, the use of hsp90 inhibitor geldanamycin significantly decreased the expression of NR3C1, ICAM-1 and the ratio of p-p65/p65 in CTNNAL1-silenced 16HBE14o- cells. Both geldanamycin and DEX could function to suppress the expression of ICAM-1 and the phosphorylation level of p65. Nevertheless, the anti-inflammatory effect of DEX proved less potent than geldanamycin in the CTNNAL1-silenced group. The combined therapy of geldanamycin and DEX significantly decreased the inflammatory responses in CTNNAL1-deficient HBE cells than DEX monotherapy. SIGNIFICANCE: Our study corroborates that CTNNAL1 deficiency induced aggravated airway inflammation and rendered insensitivity to glucocorticoids via triggering hsp90 signaling pathway.
作者机构:
[He, Chunxiang; Li, Ze; Song, Zhenyan; Cheng, Shaowu; Song, ZY; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[He, Chunxiang; Li, Ze; Song, Zhenyan; Cheng, Shaowu; Song, ZY; Zhong, Dayuan; Yu, Jingping; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Yu, Jingping] Baoshan Coll Tradit Chinese Med, Baoshan 678000, Yunnan, Peoples R China.;[Zhong, Dayuan] Guangdong Prov Hosp Integrated Tradit Chinese & We, Foshan 528000, Guangdong, Peoples R China.
通讯机构:
[Song, ZY; Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
关键词:
Alzheimer’s disease;RAGE;TLR4/NF-κB signaling pathway;neuroinflammation;traditional Chinese medicine
摘要:
The purpose of this study is to investigate the therapeutic effect of Qi Fu Yin (QFY) on Alzheimer's disease (AD) both computationally and experimentally. Network pharmacology analysis and molecular docking were conducted to identify potential targets and signaling pathways involved in QFY treating AD. Streptozotocin-induced AD rat model was used to verify important targets and predicted pathways. The components of QFY were identified using liquid chromatography-tandem mass spectrometry. The results indicate that the potential targets of QFY are highly enriched for anti-inflammatory pathways. Molecular docking analysis revealed stable structures formed between QFY's active compounds, including stigmasterol, β-sitosterol, and isorhamnetin, and the identified targets. In vivo, QFY improved cognitive memory in AD rats and reduced the mRNA expression levels of toll-like receptor 4 (TLR4), the receptor for advanced glycation end products (AGER), and the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brains of AD rats. Furthermore, QFY effectively reduced nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited NF-κB and microglia activation. In conclusion, QFY can ameliorate neuroinflammation in AD model rats, partly via the inhibition of TLR4 and RAGE/NF-κB pathway and microglia activation, thereby enhancing learning and memory in AD model rats.
摘要:
To investigate the role of miR-140/BCL2L2 axis on the formation of intracranial aneurysms. The expression of miR-140 in the serum of patients with intracranial aneurysms and healthy volunteers was detected. CCK-8 assay and Annexin V-FITC/PI double staining flow cytometry were used to evaluate the effect of miR-140 knockdown on the proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs). Meanwhile, the relationship between miR-140 and BCL2L2 was examined. MiR-140 was found to be upregulation in intracranial aneurysm patients. MiR-140 knock-out significantly inhibited the apoptosis of HBVSMCs and promoted cell proliferation. BCL2L2 was a direct target gene of miR-140 and suppressed its expression. Knockdown of miR-140 alleviates the development of intracranial aneurysms. MiR-140/BCL2L2 axis promotes the progression of intracranial aneurysms by regulating apoptosis of HBVSMCs. Therefore, miR-140 is a potential therapeutic target for intracranial aneurysms.