摘要：
Background: Diabetic nephropathy (DN) is one of the most serious complications of diabetes. Rhein has been reported to be effective in treating DN. This study aimed to investigate the role and mechanism of rhein in the treatment of DN. Methods: High glucose-induced (HG) podocyte injury model and streptozocin-induced (STZ) DN mouse model were constructed and intervened with rhein. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) level was measured by flow cytometry. The expression of Ras-related C3 botulinum toxin substrate 1 (Rac1), NADPH Oxidase 1 (NOX1), and beta-catenin were measured by quantitative real-time PCR (RT-qPCR). The contents of glutathione peroxidase 4 (GPX4), alpha-smooth muscle actin (alpha-SMA), Nephrin, and Podocin were characterized by immunofluorescence (IF) staining. Hematoxylineosin (HE) staining and Masson staining were employed to observe the renal morphological changes and tubulointerstitial fibrosis. The contents of alpha-SMA and Nephrin were detected by immunohistochemistry (IHC) staining. The kits were utilized to analyze various biochemical indicators. Results: Rhein inhibited the HG-induced accumulation of ROS, malondialdehyde (MDA), and Fe2+, and the expression of alpha-SMA, Transferrin Receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), Vimentin, Snail, and Desmin. Rhein inhibited the expression of Rac1 and its downstream targets NOX1 and beta-catenin. Rac1 silencing (si-Rac1) inhibited the accumulation of MDA and Fe2+ and the expression of Rac1, NOX1, beta-catenin, alpha-SMA, TFR1, and ACSL4. Rac1 overexpression (oe-Rac1) resulted in the inhibition of superoxide dismutase (SOD), glutathione (GSH), GPX4 synthesis, and down-regulation of Recombinant Solute Carrier Family 7, Member 11 (SLC7A11) and Nephrin expression in HG-treated podocytes. Rac1 Lentivirus (LV-Rac1) injection significantly promoted the accumulation of MDA and Fe2+ and increased the expression of RAC1, NOX1, beta-catenin, TFR1, ACSL4, and alpha-SMA in DN mice. Conclusions: Rhein inhibited ferroptosis and epithelial-mesenchymal transition (EMT) to attenuate DN by regulating the Rac1/NOX1/beta-catenin axis.
摘要：
OBJECTIVE: Trimethoprim sulfamethoxazole (TMP-SMX) is related to aseptic meningitis. However, a detailed description of its phenotype is lacking, which easily leads to misdiagnosis. The purpose of this article is to explore the clinical characteristics of TMP-SMX-induced aseptic meningitis (TSIAM). METHODS: We collected literature related to TSIAM published before July 31, 2023, by searching Chinese and English databases. Data were extracted and analyzed descriptively. RESULTS: The 55 patients were mostly female (60.0%), with a median age of 43 years (range: 2.5-90 years). The first onset time was from a few minutes to 3 months after administration, and the time of reonset was within 12 hours. Fever (98.2%), headache (78.2%), altered mental status (42.3%), nausea and vomiting (41.8%), and neck pain (34.5%) were the most common symptoms. In severe cases, patients presented with low blood pressure, seizures, unconsciousness, or coma. Typical cerebrospinal fluid analysis showed elevated white blood cell counts, with polymorphonuclear leukocytes predominating, elevated protein levels, and normal glucose levels. Brain imaging usually showed no abnormalities. Symptoms resolved rapidly after the discontinuation of TMP-SMX, within a median time of 2 days (range: 1, 60). Readministration of TMP-SMX led to another relapse of aseptic meningitis. Aseptic meningitis usually culminated in a full recovery, although one patient experienced permanent paraplegia. CONCLUSION: Clinicians should be aware that aseptic meningitis is a rare adverse effect of TMP-SMX. TMP-SMX should be discontinued in patients with TSIAM to reduce unnecessary testing and treatment, and readministration of TMP-SMX should be avoided.
摘要：
Sweet syndrome is a rare complication of azathioprine treatment with unelucidated clinical features. The purpose of this study was to investigate the clinical characteristics of azathioprine-induced Sweet syndrome (AISS) and provide a reference for diagnosis, treatment and prognosis. We collected relevant case reports of AISS by searching Chinese and English databases from 1960 to December 31, 2022, extracted the data and carried out a retrospective analysis. The median age of the 44 patients was 50 (range 9-89) years, and they included 32 males (72.7%). Fever (86.4%) and arthralgia (31.8%) were the most common clinical symptoms. The skin lesions were mainly pustules (54.5%), papules (40.9%), plaques (40.9%) and nodules (31.8%), which were mainly distributed on the extremities (54.5%), face (38.6%) and hands (36.4%). Laboratory examination revealed neutropenia (65.9%) as well as elevated C-reactive protein (63.6%) and erythrocyte sedimentation (40.9%) rates. Histopathology of the lesioned skin showed neutrophil infiltration (93.2%) and dermal edema (38.6%). Symptom relief was achieved at a median time of 7days (range 2-28days) after azathioprine discontinuation in all patients. Nine patients (20.5%) had skin lesions that recurred within 24h after taking azathioprine again. Clinicians and pharmacists should grasp the regularity and characteristics of AISS and should not recommend the readministration of azathioprine, to avoid the recurrence of Sweet syndrome.
作者机构：
[Meng, Pan; Zhao, Hongqing; Li, Ping; Wang, Yuhong; Zhang, Xi; Li, Dandan] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Meng, Pan; Zhao, Hongqing; Lin, Xiaoyuan; Wang, Yuhong; Yang, Hui] Hunan Key Lab Tradit Chinese Med Prevent & Treatme, Changsha, Hunan, Peoples R China.;[Zhang, Xi; Wang, Xiaoye] Second Peoples Hosp Hunan Prov, Changsha, Hunan, Peoples R China.;[Lin, Xiaoyuan; Yang, Hui] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[Ge, Jinwen] Hunan Acad Chinese Med, Changsha, Hunan, Peoples R China.
关键词：
Introduction;Materials and Methods;Results;Discussion;Conclusion;Abstract;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interests;Authors’ Contributions;Funding Statement;Acknowledgements;Acknowledgments;Supplementary Materials;Reference;Dataset Description;Dataset Files;Abstract;Introduction;Introduction and Materials;Introduction and Methods;Materials;Materials and Methods;Methods;Results;Discussion;Results and Discussion;Discussion and Conclusion;Results and Conclusion;Conclusion;Conclusions;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interest;Authors’ Contributions;Funding Statement;Acknowledgements;Supplementary Materials;References;Appendix;Abbreviations;Preliminaries;Introduction and Preliminaries;Notation;Proof of Theorem;Proofs;Analysis of Results;Examples;Numerical Example;Applications;Numerical Simulation;Model;Model Formulation;Systematic Palaeontology;Nomenclatural Acts;Taxonomic Implications;Experimental;Synthesis;Overview;Characterization;Background;Experimental;Theories;Calculations;Model Verification;Model Implementation;Geographic location;Study Area;Geological setting;Data Collection;Field Testing;Data and Sampling;Dataset;Literature Review;Related Works;Related Work;System Model;Methods and Data;Experimental Results;Results and Analysis;Evaluation;Implementation;Case Presentation;Case Report;Search Terms;Case Description;Case Series;Background;Limitations;Additional Points;Case;Case 1;Case 2 etc.;Concern Details;Retraction Details;Copyright;Related Articles
摘要：
Depression is a highly prevalent and heterogeneous disorder that requires new strategies to overcome depression. In this study, we aimed to investigate whether leonurine modulated hippocampal nerve regeneration in chronic and unpredictable mild stress (CUMS) rats through the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis. The CUMS rat model was constructed and treated with leonurine. The body weight of rats was recorded, and a series of tests were performed. Western blot was utilized to measure the expression of BDNF and 5-HT in the hippocampus. Then the expression of SHH, GLI, PTCH, and SMO were measured by qRT-PCR and western blot. The colocalization of BrdU+DCX and BrdU+NeuN was evaluated by IF. 16S rDNA high-throughput sequencing was applied to detect the composition and distribution of gut microbiota. The differential metabolites were analyzed by untargeted metabolomics. The correlation between gut microbiota and microbial metabolites was analyzed by Pearson correlation coefficient. After CUMS modeling, the body weight of rats was decreased, and the expression of BDNF and 5-HT were decreased, while the body weight was recovered, and the expression of BDNF and 5-HT were increased after leonurine treatment. Leonurine reversed the reduction in the colocalization of BrdU+DCX and BrdU+NeuN and the reduction in the levels of SHH, GLI, PTCH, and SMO induced by CUMS modeling. Leonurine also restored gut microbiota and microbial metabolites homeostasis in CUMS rats. Furthermore, Prevotellaceae_Ga6A1_group was negatively correlated with 3-Oxocholic acid, nutriacholic acid, and cholic acid. Collectively, leonurine regulated hippocampal nerve regeneration in CUMS rats by activating the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis.
摘要：
Diabetic foot ulcer (DFU) is a break in the skin of the foot caused by diabetes. It is one of the most serious and debilitating complications of diabetes. The previous study suggested that dominant M1 polarization during DFU could be the leading reason behind impaired wound healing. This study concluded that macrophage M1 polarization predominates in DFU skin tissue. iNOS was increased in HG-induced M1-polarized macrophages; conversely, Arg-1 was decreased. Macrophage pellets after HG stimulation can impair endothelial cell (EC) function by inhibiting cell viability, tube formation and cell migration, indicating M1 macrophage-derived small extracellular vesicles (sEVs) -mediated HUVEC dysfunction. sEVs miR-503 was significantly upregulated in response to HG stimulation, but inhibition of miR-503 in HG-stimulated macrophages attenuated M1 macrophage-induced HUVEC dysfunction. ACO1 interacted with miR-503 and mediated the miR-503 package into sEVs. Under HG stimulation, sEVs miR-503 taken in by HUVECs targeted IGF1R in HUVECs and inhibited IGF1R expression. In HUVECs, miR-503 inhibition improved HG-caused HUVEC dysfunction, whereas IGF1R knockdown aggravated HUVEC dysfunction; IGF1R knockdown partially attenuated miR-503 inhibition effects on HUVECs. In the skin wound model in control or STZ-induced diabetic mice, miR-503-inhibited sEVs improved, whereas IGF1R knockdown further hindered wound healing. Therefore, it can be inferred from the results that the M1 macrophage-derived sEVs miR-503 targets IGF1R in HUVECs, inhibits IGF1R expression, leads to HUVEC dysfunction, and impedes wound healing in diabetic patients, while packaging miR-503 as an M1 macrophage-derived sEVs may be mediated by ACO1.
作者机构：
[Zeng, Fukang; Liu, Lijuan; Guo, Chun; Zhou, Desheng; Li, Zhong; Zhang, Ying; Zhang, Yuxing] Hunan Univ Chinese Med, Hosp 1, Dept Neurol, Changsha 410007, Peoples R China.;[Zeng, Fukang; Zhang, Yuxing] Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.;[Shao, Le; Zeng, Fukang; Yin, Qian; Zhao, Xin; Zhang, Ying; Zhang, Yuxing] Hunan Univ Chinese Med, Changsha 410006, Peoples R China.;[Shao, Le] Lab Prevent & Transformat Major Dis Internal Med T, Changsha 410007, Peoples R China.
通讯机构：
[Desheng Zhou; Lijuan Liu] D;Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
摘要：
Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
作者机构：
[Liu, Ying-Fei; Yi, Jian; Ou-yang, Yin; Liu, Bai-Yan; Chen, Bo-Wei; Tang, Rong-Mei; Long, Hong-Ping; Tian, Feng-Ming] Hunan Univ Chinese Med, Affiliated Hosp 1, 95 Shaoshan Rd, Changsha, Peoples R China.;[Yi, Jian; Liu, Bai-Yan] Hunan Acad Chinese Med, 58 Lushan Rd, Changsha, Peoples R China.;[Liu, Ying-Fei; Yi, Jian; Ou-yang, Yin; Chen, Bo-Wei; Tang, Rong-Mei; Tian, Feng-Ming] Hunan Univ Chinese Med, 300 Xueshi Rd, Changsha, Peoples R China.;[Tang, Yan] Yiyang Med Coll, 516 Yingbin Rd, Yiyang, Peoples R China.;[Zhang, Wen-Jiang] Shaanxi Univ Chinese Med, Xixian Ave,Xixian New Area, Xianyang, Peoples R China.
通讯机构：
[Bai-Yan Liu] T;The First Affiliated Hospital, Hunan University of Chinese Medicine, 95 Shaoshan Road, Changsha, China<&wdkj&>Hunan Academy of Chinese Medicine, 58 Lushan Road, Changsha, China
摘要：
The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.
摘要：
BACKGROUND: Glaucoma is the leading cause of irreversible blindness worldwide. The aim of this study was to evaluate the efficacy and safety of Fufang Xueshuantong Capsules (FFXST) in combination with conventional drugs in the treatment of glaucoma using meta-analysis and trial sequential analysis (TSA). METHODS: Clinical trials of FFXST for glaucoma were identified in 8 databases until November 2022, and studies were included for meta-analysis and trial sequential analysis. RESULTS: In terms of efficacy endpoints, meta-analysis showed that the combination group of FFXST significantly improved clinical effective rate (RR 1.29, 95% CI 1.20-1.39, P < .00001), visual function (MD 0.04, 95% CI 0.04-0.05, P < .00001), light sensitivity (MD 6.07, 95% CI 4.63-7.51, P < .00001), end-systolic blood flow velocity (MD 2.68, 95% CI 2.19-3.16, P < .00001) and end-diastolic blood flow velocity (MD 2.07, 95% CI 1.86-2.28, P < .00001), and significantly reduced total gray-scale value (MD -64.38, 95% CI -69.08 to -59.68, P < .00001) and defect of visual field (MD -3.40, 95% CI -4.11 to -2.69, P < .00001) compared with the conventional regimen group, while the pulsatility index and resistance index were comparable. The TSA indicated that these benefits were conclusive. In terms of safety endpoints, meta-analysis demonstrated that total drug-related adverse events in the combination group of FFXST were comparable to those in the conventional regimen group, with TSA showing that more studies are needed to validate the current results. CONCLUSION: FFXST may be a safety and effective supplementary strategy for the treatment of glaucoma, which is worthy of further research.
期刊：
Frontiers in Pharmacology,2023年14:1173747 ISSN：1663-9812
通讯作者：
Long, HP
作者机构：
[Zhou, Siqian; Long, HP; Liu, Jian; Long, Hongping] Hunan Univ Chinese Med, Ctr Med Res & Innovat, Hosp 1, Changsha, Peoples R China.;[Ding, Changsong; Zhou, Siqian; Wang, Yajing; Long, HP; Long, Hongping] Hunan Univ Chinese Med, Changsha, Peoples R China.;[Tan, Leihong] Hunan Univ Chinese Med, Dept Pharm, Hosp 2, Changsha, Peoples R China.;[Wang, Yikun] Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China.;[Li, Jing] Cent South Univ, Xiangya Hosp, Dept Pharm, Changsha, Peoples R China.
通讯机构：
[Long, HP ] H;Hunan Univ Chinese Med, Ctr Med Res & Innovat, Hosp 1, Changsha, Peoples R China.;Hunan Univ Chinese Med, Changsha, Peoples R China.
摘要：
Introduction: Corni Fructus (CF) is a Chinese herbal medicine used for medicinal and dietary purposes. It is available commercially in two main forms: raw CF (unprocessed CF) and wine-processed CF. Clinical observations have indicated that wine-processed CF exhibits superior hypoglycemic activity compared to its raw counterpart. However, the mechanisms responsible for this improvement are not well understood. Methods: To address this gap in knowledge, we conducted metabolomics analysis using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS) to compare the chemical composition of raw CF and wine-processed CF. Subsequently, network analysis, along with immunofluorescence assays, was employed to elucidate the potential targets and mechanisms underlying the hypoglycemic effects of metabolites in CF. Results: Our results revealed significant compositional differences between raw CF and wine-processed CF, identifying 34 potential markers for distinguishing between the two forms of CF. Notably, wine processing led to a marked decrease in iridoid glycosides and flavonoid glycosides, which are abundant in raw CF. Network analysis predictions provided clues that eight compounds might serve as hypoglycemic metabolites of CF, and glucokinase (GCK) and adenylate cyclase (ADCYs) were speculated as possible key targets responsible for the hypoglycemic effects of CF. Immunofluorescence assays confirmed that oleanolic acid and ursolic acid, two bioactive compounds present in CF, significantly upregulated the expression of GCK and ADCYs in the HepG2 cell model. Discussion: These findings support the notion that CF exerted hypoglycemic activity via multiple components and targets, shedding light on the impact of processing methods on the chemical composition and hypoglycemic activity of Chinese herbal medicine.
摘要：
PlncRNA- 1 has an anti-cancer property. Liposome nanoparticles (LNPs) are used as carriers of targeted drugs and contribute to tumor-targeted drug delivery. However, the interaction between LNPs containing PlncRNA-1 and beta-catenin, a key component of Wnt signaling pathway, and its role in liver cancer have not yet been confirmed. Human liver cancer cells were exposed to LNPs containing PlncRNA-1 at different concentrations followed by analysis of cell proliferation, cell cycle distribution and apoptosis. Wnt/beta-catenin pathway-related gene expression was determined. LNPs containing PlncRNA-1 dose-dependently suppressed the proliferation of liver cancer HepG2 cells with IC50 at 24 h, 48 h and 72 h of 12.8 +/- 0.67 mu mol/L, 8.8 +/- 0.43 mu mol/L and 4.6 +/- 0.42 mu mol/L, respectively. PlncRNA-1-loaded LNPs (5, 10, and 20 mu mol/L) dosedependently arrested HepG2 cells in G2/M phase and induced apoptosis ( p > 0.05). Administration of LNPs carrying PlncRNA-1 decreased the expression of overall, cytoplasmic, and nuclear beta-catenin, thereby suppressing Wnt/ beta-catenin pathway. Protein expression levels of GSK-3 (p-tyr216) and Axin-2 were increased, while protein expression levels of Dvl-2, Dvl-3, GSK-3 beta, c-myc and survivin were significantly decreased. Invasion and metastasis of malignant tumors is an important factor. Inhibiting invasion of cancer cells effectively might improve the prognosis of cancer patients. LNPs carrying PlncRNA-1 promoted cell cycle transition and cell apoptosis by decreasing the expression of Dvl-2, Dvl-3, intracellular beta-catenin, cytoplasmic beta-catenin, and total beta-catenin protein, which may relate to the inhibition of Wnt/beta- catenin pathway.
摘要：
Resistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMβ, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases.
摘要：
ObjectiveTo detect the effect and safety of massage therapy on infants with congenital muscular torticollis. MethodsA total of 56 infants with unilateral congenital muscular torticollis were enrolled in this retrospective comparative study. The subjects were divided in two groups, namely, the control group and the massage group. The control group (n = 28) received the treatment of sternocleidomastoid muscle (SCM) stretching, while the massage group (n = 28) received massage therapy combined with SCM stretching. The following parameters were compared: the cervical range of motion (ROM) and functional level (muscle function scale and ratio of muscle function scale scores). Complications, if any, were also recorded. ResultsOf the 56 infants, 7 infants (12.5%) underwent surgery with little functional improvement. The total effective rate of conservative treatment was 87.5%. No significance was found in terms of the surgery rate between both groups (14.29 vs. 10.71%, P = 0.693). After treatment, the ROM (including rotation and lateral flexion) and the ratio of muscle function scale scores improved significantly (P < 0.05). In the latest follow-up, the massage group showed a greater improvement in rotation and lateral flexion. However, no significant difference in the muscle function scale score ratio was found (P = 0.126). Importantly, no adverse events related to blood vessels, nerves, and SCM occurred. ConclusionsProviding massage therapy in infants with congenital muscular torticollis is a safe and effective method to improve the cervical range of motion and function. However, this study did not find any decrease in the surgical rate between two groups of patients despite adding such therapy.
期刊：
Frontiers in Immunology,2023年13:1047550 ISSN：1664-3224
通讯作者：
Ge, J.
作者机构：
[Zeng, Jinsong; Ge, Anqi] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[Bao, Tingting] China Acad Chinese Med Sci, Guanganmen Hosp, Inst Metab Dis, Beijing, Peoples R China.;[Zeng, Liuting; Yang, Kailin; Wang, Shanshan; Ge, Jinwen] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Zhu, Xiaofei] Fudan Univ, Shanghai, Peoples R China.;[Xiang, Wang] First Peoples Hosp Changde City, Dept Rheumatol, Changde, Hunan, Peoples R China.
通讯机构：
[Ge, J.] K;Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, China
摘要：
Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms of IS. In particular, the early proinflammatory response resulting from the overactivation of resident microglia and the infiltration of circulating monocytes and macrophages in the brain after cerebral ischemia leads to secondary brain injury. Microglia are innate immune cells in the brain that constantly monitor the brain microenvironment under normal conditions. Once ischemia occurs, microglia are activated to produce dual effects of neurotoxicity and neuroprotection, and the balance of the two effects determines the fate of damaged neurons. The activation of microglia is defined as the classical activation (M1 type) or alternative activation (M2 type). M1 type microglia secrete pro-inflammatory cytokines and neurotoxic mediators to exacerbate neuronal damage, while M2 type microglia promote a repairing anti-inflammatory response. Fine regulation of M1/M2 microglial activation to minimize damage and maximize protection has important therapeutic value. This review focuses on the interaction between M1/M2 microglia and other immune cells involved in the regulation of IS phenotypic characteristics, and the mechanism of natural plant components regulating microglia after IS, providing novel candidate drugs for regulating microglial balance and IS drug development.
期刊：
Journal of Cancer Research and Clinical Oncology,2023年149(11):8593-8603 ISSN：0171-5216
通讯作者：
Li, J
作者机构：
[Nie, Duorui; Li, Jing] Hunan Univ Chinese Med, Hosp 1, Dept Oncol, Changsha 410007, Hunan, Peoples R China.;[Zheng, Hao] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou, Peoples R China.;[An, Guilin] Ningxia Med Univ, Sch Tradit Chinese Med, Yinchuan, Peoples R China.
通讯机构：
[Li, J ] H;Hunan Univ Chinese Med, Hosp 1, Dept Oncol, Changsha 410007, Hunan, Peoples R China.
关键词：
Nomograms;Postoperative survival;SEER database;Signet ring cell carcinoma;Survival analysis
摘要：
BACKGROUND: Gastric signet ring cell carcinoma (GSRCC) is a highly malignant subtype of gastric cancer. We tried to establish and validate a nomogram using common clinical variables to achieve more personalized management. METHODS: We analyzed patients with GSRCC in the Surveillance, Epidemiology, and End Results database between 2004 and 2017. The survival curve was calculated by the Kaplan-Meier method, and the difference in survival curve was tested by log-rank test. We used the cox proportional hazard model to evaluate independent factors of prognosis, and established a nomogram to predict 1-, 3- and 5- overall survival (OS). Harrell's consistency index and calibration curve were used to measure the discrimination and calibration of the nomogram. In addition, we used decision curve analysis (DCA) to compare the net clinical benefits of the nomogram and American Joint Committee on Cancer (AJCC) staging system. RESULTS: The prognosis nomogram predicting 1-, 3- and 5-years OS for patients with GSRCC is established for the first time. The C-index and AUC of nomogram were higher than that of the American Joint Committee on Cancer (AJCC) staging system in the training set. Our model also shows better performance than the AJCC staging system in the validation set, and importantly, DCA shows that our model has a better net benefit than the AJCC stage. CONCLUSIONS: We have developed and validated a new nomogram and risk classification system, which is better than the AJCC staging system. It will help clinicians manage postoperative patients with GSRCC more accurately.
作者机构：
[Zeng, Qiuming; Jiang, Fei; He, Ting; Dong, Xiaohua; Cai, Haobing; Yang, Huan] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Peoples R China.;[Liu, Yu] Second Peoples Hosp Hunan Prov, Brain Hosp Hunan Prov, Changsha, Peoples R China.;[Li, Hongliang] Hunan Univ Chinese Med, Acupuncture & Tuina Rehabil Dept, Hosp 1, Changsha, Peoples R China.;[Ouyang, Song] South China Univ, Hosp Changsha City 1, Med Ctr Neurol, Changsha, Peoples R China.;[Yin, Weifan] Cent South Univ, Xiangya Hosp 2, Changsha, Peoples R China.
通讯机构：
[Qiuming Zeng; Huan Yang] D;Department of Neurology, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
关键词：
Glycoprotein A repetitions predominant;Latency-associated peptide;Neuromyelitis optica spectrum disorders;Regulatory T cells;Transforming growth factor-β1
摘要：
INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP(+) or GARP(+) Treg subsets in NMOSD may help us deeply understand their immune mechanism. METHODS: This study reviewed 22 NMOSD patients and 20 normal controls. Flow cytometric analysis was utilized to detect subsets of Treg cells expressing Foxp3, Helios, LAP, or GARP in peripheral blood. ELISA was used to detect plasma TGF-β1 and IL-10. In addition, changes in the proportion of Treg cell subsets before and after glucocorticoid treatment in 10 patients were analyzed. RESULTS: Compared with healthy controls, LAP and GARP expressions were significantly downregulated in the peripheral blood of NMOSD patients. TGF-β1 expression in NMOSD patients was lower and was positively correlated with the ratio of CD4(+)GARP(+) Treg cells. After treatment with glucocorticoid, LAP and GARP expressions in the peripheral blood of NMOSD patients were upregulated. CONCLUSIONS: The proportion of Treg cells expressing LAP and GARP is downregulated, implying that Treg cells with the best inhibitory function are insufficient to maintain autoimmune homeostasis in NMOSD patients. Upregulation of Treg cells expressing LAP and GARP in NMOSD patients may be one of the mechanisms of glucocorticoid treatment.
摘要：
Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. β-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that β-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.
摘要：
We studied the effect of CCDC3 on the viability of human breast cancer cell line MDA-MB-231. The levels of CCDC3 mRNA and the corresponding protein in MDA-MB-231, MCF-7, T-47D, and HCC1937 cell lines were measured by reverse transcription quantitative real-time PCR and Western blotting. Since MDA-MB-231 cells had higher expression of mRNA CCDC3 and CCDC3 protein, we used this cell line for transfection with small interfering RNA by lentivirus. Cell Counting Kit-8 and clone formation assay were used to detect the effects of CCDC3 knockdown on cell viability; flow cytometry was used to detect the effects of CCDC3 knockdown on cell apoptosis and cell cycle. In MDA-MB-231 cell line, the CCDC3 protein level was significantly down-regulated after CCDC3 knockdown in comparison with the control group (p<0.05). The cell viability and the number of clones in the CCDC3 knockdown group were significantly reduced (p<0.05), while the apoptosis rate significantly increased (p<0.05). Thus, after CCDC3 knockdown, cell viability is weakened in MDA-MB-231 cells, and cell apoptosis rate is increased. Therefore, CCDC3 gene is promising as a new candidate target for BC treatment.
摘要：
The gut microbiota and their metabolites may participate in the development of diarrhea by regulating the expression of inflammatory factors. Therefore, the study concludes that the pathogenesis of diarrhea mainly depends on the following pathways: 1) gut contents microbiota disorder; 2) abnormal lipid metabolism; 3) inflammation; 4) metabolite‐SCFAs reduction; 5) brain‐gut peptide dysfunction. Scope Preliminary research finds that a high‐fat diet (HFD) in a fatigued state triggers diarrhea, but the exact mechanism has not been clarified. To address concerns about the pathogenesis of diarrhea, the study evaluates the composition and metabolomics of the gut microbiota. Methods and results The study uses the multiple platform apparatus device to induce fatigue in mice, combined with intragastric administration of lard‐caused diarrhea. Subsequently, the characteristics and interaction relationship of gut microbiota, short‐chain fatty acids (SCFAs), inflammatory biomarkers, brain‐gut peptides, and lipid metabolism are analyzed at the end of the experiment. HFD in a fatigued state results in a significant increase in interleukin‐17, interleukin‐6, cholecystokinin, somatostatin, and malondialdehyde content in mice (p < 0.05), along with a substantial decrease in high‐density lipoprotein (p < 0.05). Additionally, an HFD in a fatigued state causes changes in the structure and composition of the gut microbiota, with Lactobacillus murinus as its characteristic bacteria, and reduces the production of SCFAs. Conclusions An HFD in a fatigued state triggers diarrhea, possibly associated with gut content microbiota dysbiosis, SCFAs deprivation, increased inflammation, and dysregulated lipid metabolism.
作者：
Tan, Yan;Nie, Duo Rui;Cao, Yang;Ke, Chao;Pan, Jiang;...
期刊：
Neurological Sciences,2023年 ISSN：1590-1874
通讯作者：
Zhang, W
作者机构：
[Tan, Yan; Zhang, Wei; Ke, Chao; Cao, Yang; Pan, Jiang; Shi, Wen Ying] Hunan Univ Chinese Med, Dept Acupuncture Moxibust & Tuina, Affiliated Hosp 1, Changsha, Peoples R China.;[Nie, Duo Rui] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.
通讯机构：
[Zhang, W ] H;Hunan Univ Chinese Med, Dept Acupuncture Moxibust & Tuina, Affiliated Hosp 1, Changsha, Peoples R China.
关键词：
Alzheimer’s Disease;Bibliometrics;Omics;Trends;Web of Science
摘要：
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease with an insidious onset. The widespread application of omics techniques in AD has attracted considerable attention. We aimed to make a comprehensive analysis of published omics articles on AD in order to determine the research profile and application trends of omics techniques in AD. METHODS: This study utilizes bibliometric and visual methods including a map collaboration map, co-citations, and keywords to identify knowledge structures, hot topics, and research trends based on 6,828 publications from the Web of Science Core Collection (WoSCC) database. RESULTS: The results of this study showed that 5654 institutions from 91 countries published articles in this field. The USA, China, and the UK played a leading role in publishing numerous articles in relevant journals as well as prolific institutions and authors, respectively. This paper collects a large number of literatures on the application of AD omics technology from the WoSCC database and found the omics technology applied to AD is mainly based on genomics technology. The application of transcriptomics technology has shown an increasing trend in recent years, and the application of multi-omics technology will be the general trend in the future. CONCLUSION: The development status, frontier hotspots, and general trends of omics application technologies are reviewed. This article will provide intelligence support to researchers and institutions in the field of Alzheimer's omics research and applications from a practical perspective.
摘要：
Lipid metabolism disorders are pivotal in the development of various lipid-related diseases, such as obesity, atherosclerosis, non-alcoholic fatty liver disease, type 2 diabetes, and cancer. Celastrol, a bioactive compound extracted from the Chinese herb Tripterygium wilfordii Hook F, has recently demonstrated potent lipid-regulating abilities and promising therapeutic effects for lipid-related diseases. There is substantial evidence indicating that celastrol can ameliorate lipid metabolism disorders by regulating lipid profiles and related metabolic processes, including lipid synthesis, catabolism, absorption, transport, and peroxidation. Even wild-type mice show augmented lipid metabolism after treatment with celastrol. This review aims to provide an overview of recent advancements in the lipid-regulating properties of celastrol, as well as to elucidate its underlying molecular mechanisms. Besides, potential strategies for targeted drug delivery and combination therapy are proposed to enhance the lipid-regulating effects of celastrol and avoid the limitations of its clinical application.
