作者机构:
[Gu, Wenping; Zheng, Lan; Huang, Qianyi; Sun, Xinyu; Gu, WP; Song, Mingyu] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Gu, Wenping; Yi, Fang; Gu, WP; Song, Mingyu] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Gu, Wenping; Gu, WP; Song, Mingyu] Cent South Univ, Clin Res Ctr Cerebrovasc Dis Hunan Prov, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.;[Wang, Hong; Yi, Fang] Cent South Univ, Xiangya Hosp, Dept Geriatr Neurol, Changsha 410008, Hunan, Peoples R China.;[Zeng, Feiyue] Cent South Univ, Xiangya Hosp, Dept Radiol, Changsha 410008, Hunan, Peoples R China.
通讯机构:
[Gu, WP ] C;Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Clin Res Ctr Cerebrovasc Dis Hunan Prov, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.
关键词:
Ischemic stroke;Mitophagy;USP18;FTO;SIRT6
摘要:
Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Delta psi m), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1 alpha/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1 alpha/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1 alpha/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.
通讯机构:
[Peng, QH ] H;Hunan Univ Chinese Med, Hunan Prov Key Lab TCM Diagnost, Changsha 410208, Hunan, Peoples R China.
关键词:
Cornea;Dry eye disease (DED);Fc gamma R-mediated phagocytosis pathway;Modified Danzhi Xiaoyao Powder (MDXP);Traditional Chinese medicine (TCM)
摘要:
Ethnopharmacological relevance: Modified Danzhi Xiaoyao Powder (MDXP) is a traditional Chinese medicine formula remedy for treating Dry Eye Disease (DED). It showed the function of dispersing stagnated liver Qi for relieving Qi stagnation and clearing heat, which can be effective in treating conditions such as Dry Eye Disease (DED) and irregular menstruation due to liver depression and fire transformation. Aim of the study: This study investigated the mechanism of the effect of MDXP in mice with DED. Materials and methods: A DED model was induced in mice using chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops administered in a dry box for 28 days. After modeling, the MDXP groups were given Chinese medicine with different dosages by gavage for 14 days. The following parameters were recorded in each group: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. Behavioral changes were evaluated by elevating cross -maze and open-field experiments. The levels of inflammatory factors serum tumor necrosis factor-alpha (TNF-alpha), interleukin 18 (IL -18), fc gamma Rmediated phagocytosis pathway cell division control protein 42 homolog (CDC42), actin -related protein 2/3 complex subunit 2 (ARPC2), and actin -related protein 3 (ACTR3) were measured by using Enzyme -linked immunoassay (ELISA), immunohistochemical staining, and real-time fluorescent qualitative polymerase chain reaction (RT-qPCR). Results: MDXP increased body mass and lowered body temperature, prolonged tear film break-up time, promoted tear secretion, repaired corneal damage, decreased horizontal and vertical scores, elevated percentage of open arm times and boom opening time percentage, and reduced the expression levels of inflammatory factors of TNF alpha, IL -18 and pathway -related proteins CDC42, ARPC2, and ACTR3 in mice. MDXP also reduced the expression levels of inflammatory factors of TNF-alpha and IL -18 in human corneal endothelial cells (HCECs), mouse mononuclear macrophage cells (RAW264.7), and human myeloid leukemia mononuclear cells (THP-1). Conclusions: MDXP can relieve tension and anxiety, inhibit apoptosis, reduce phagocytosis, reduce the expression of pro -inflammatory factors, repair corneal damage, and improve the symptoms in DED mice. The mechanism of action may be through the fc gamma R-mediated phagocytosis pathway.
摘要:
Heart failure (HF) can damage various organs, including the liver, a phenomenon known as "cardiohepatic syndrome." The latter is characterized by liver congestion and hepatic artery hypoperfusion, which can lead to liver damage. In this study, we aimed to assess liver damage quantitatively in chronic HF (CHF) with sound touch elastography (STE). A total of 150 subjects were enrolled, including HF with reduced ejection fraction (HFrEF) groups (left ventricular ejection fraction <= 40%, n = 45), HF with mildly reduced ejection fraction (HFmrEF) groups (left ventricular ejection fraction between 41% and 49%, n = 40), and right -sided HF (RHF) groups (n = 25); normal groups (n = 40). Liver stiffness measurement (LSM) was performed in all subjects by STE. The other hepatic parameters were also measured. The LSM was 5.4 +/- 1.1 kPa in normal subjects and increased slightly to 5.9 +/- 0.7 kPa in patients with HFmrEF. However, the HFrEF and RHF groups had significantly higher LSMs of 8.4 +/- 2.0 kPa and 10.3 +/- 2.7 kPa, respectively. The LSM of HFrEF was significantly higher than that of HFmrEF, whereas the increase in LSM in patients with RHF was significant relative to HFmrEF and HFrEF. In addition, the other parameters showed abnormal values in only RHF and HFrEF. In conclusion, STE is a useful clinical technique for the noninvasive evaluation of liver stiffness associated with CHF, which could help patients with CHF manage their treatment regimens. (c) 2023 Elsevier Inc. All rights reserved. (Am J Cardiol 2024;212:127-132)
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.
作者机构:
[Lin, Mei-yu; Wang, Hui-qin; Yang, Yan-tao] Hunan Univ Chinese Med, Changsha, Peoples R China.;[Chen, Nai-hong] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China.;[Chen, Nai-hong] Chinese Acad Med Sci & Peking Union Med Coll, Neurosci Ctr, Beijing, Peoples R China.
会议名称:
19th World Congress of Basic and Clinical Pharmacology (WCP)
期刊:
Frontiers in Public Health,2023年11:1293134 ISSN:2296-2565
通讯作者:
Song, Zhenyan;Cheng, SW
作者机构:
[Song, Zhenyan; Guo, Minhua; Cheng, Shaowu; Song, ZY; He, Jiawei; Cheng, SW; Wang, Shiwei] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;[Song, Zhenyan; Guo, Minhua; Cheng, Shaowu; Song, ZY; He, Jiawei; Cheng, SW; Wang, Shiwei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.;[Wang, Weijie] Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
通讯机构:
[Song, ZY; Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.
关键词:
Barthel Index (BI);activities of daily living;machine learning algorithm;memory-related diseases;the China health and retirement longitudinal survey
摘要:
INTRODUCTION: Memory-related diseases (MDs) pose a significant healthcare challenge globally, and early detection is essential for effective intervention. This study investigates the potential of Activities of Daily Living (ADL) as a clinical diagnostic indicator for MDs. Utilizing data from the 2018 national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS), encompassing 10,062 Chinese individuals aged 45 or older, we assessed ADL using the Barthel Index (BI) and correlated it with the presence of MDs. Statistical analysis, supplemented by machine learning algorithms (Support Vector Machine, Decision Tree, and Logistic Regression), was employed to elucidate the relationship between ADL and MDs. BACKGROUND: MDs represent a significant public health concern, necessitating early detection and intervention to mitigate their impact on individuals and society. Identifying reliable clinical diagnostic signs for MDs is imperative. ADL have garnered attention as a potential marker. This study aims to rigorously analyze clinical data and validate machine learning algorithms to ascertain if ADL can serve as an indicator of MDs. METHODS: Data from the 2018 national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS) were employed, encompassing responses from 10,062 Chinese individuals aged 45 or older. ADL was assessed using the BI, while the presence of MDs was determined through health report questions. Statistical analysis was executed using SPSS 25.0, and machine learning algorithms, including Support Vector Machine (SVM), Decision Tree Learning (DT), and Logistic Regression (LR), were implemented using Python 3.10.2. RESULTS: Population characteristics analysis revealed that the average BI score for individuals with MDs was 70.88, significantly lower than the average score of 87.77 in the control group. Pearson's correlation analysis demonstrated a robust negative association (r = -0.188, p < 0.001) between ADL and MDs. After adjusting for covariates such as gender, age, smoking status, drinking status, hypertension, diabetes, and dyslipidemia, the negative relationship between ADL and MDs remained statistically significant (B = -0.002, β = -0.142, t = -14.393, 95% CI = -0.002, -0.001, p = 0.000). The application of machine learning models further confirmed the predictive accuracy of ADL for MDs, with area under the curve (AUC) values as follows: SVM-AUC = 0.69, DT-AUC = 0.715, LR-AUC = 0.7. Comparative analysis of machine learning outcomes with and without the BI underscored the BI's role in enhancing predictive abilities, with the DT model demonstrating superior performance. CONCLUSION: This study establishes a robust negative correlation between ADL and MDs through comprehensive statistical analysis and machine learning algorithms. The results validate ADL as a promising diagnostic indicator for MDs, with enhanced predictive accuracy when coupled with the Barthel Index. Lower levels of ADL are associated with an increased likelihood of developing memory-related diseases, underscoring the clinical relevance of ADL assessment in early disease detection.
摘要:
There are different views of how the immune system participates in the reaction to cancer. Here, we evaluated expression of DAMP proteins HSP70 and cancer-testis antigen SPAG9 in patients with hepatocellular carcinoma(HCC) and lung cancer to explore tumor immunity. Our analysis showed that levels of HSP70 and SPAG9 antibody were significantly higher in serum of lung cancer and HCC patients than in serum from healthy subjects(P < 0.001), but there were no differences in levels of HSP70 antibody in patients and controls. Levels of serum SPAG9 antibody in newly diagnosed lung cancer patients were significantly higher than in treated lung cancer patients(P < 0.05), but there were no differences in levels of HSP70 or HSP70 antibody. Levels of serum HSP70 and SPAG9 antibody, but not HSP70 antibody, were also higher in hepatitis/cirrhosis patients than in healthy subjects(P = 0.005, P < 0.001). Levels of serum SPAG9 antibody were significantly higher in HCC patients than in hepatitis/cirrhosis patients, but there were no differences in HSP70 or HSP70 antibody levels. Finally, levels of serum HSP70 and SPAG9 antibody were significantly higher in HCC patients than in lung cancer patients(P < 0.05, P < 0.001). These results indicate that cancer-testis antigen SPAG9 induces a strong humoral immune response in cancer patients but HSP70 does not. These results show that SPAG9 has potential as a tumor-specific biomarker.