摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Lower back pain (LBP) is a common and frequent clinical condition, and intervertebral disc degeneration (IDD) is recognized as the leading cause of LBP, typically manifested by increased nucleus pulposus cell (NPC) senescence and death. In recent years, the treatment of IDD with stem cell injections has had great potential compared to surgical treatment. Combining the two may achieve better results, as BuShenHuoXueFang (BSHXF) is an herbal formula that improves the survival rate of transplanted stem cells and enhances their efficacy. AIM OF THE STUDY: We aimed to qualitatively and quantitatively analyze BSHXF-medicated serum and investigate the molecular mechanism of BSHXF-mediated serum in promoting the differentiation of adipose mesenchymal stem cells (ADSCs) into NPCs and delaying the senescence of NPCs by regulating the TGF-β1/Smad pathway. MATERIALS AND METHODS: In this study, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF-MS) was used to establish a method for the analysis of rat serum samples to track the active components in vivo; the oxidative damage model of NPCs was induced by T-BHP, and a Transwell chamber was used to construct a coculture system of ADSCs and NPCs. Flow cytometry was used to determine the cell cycle; SA-β-Gal staining was used to assess cell senescence; ELISA was used to detect IL-1β, IL-6 inflammatory factors, CXCL-1, CXCL-3, CXCL-10 chemokines, and TGF-β1 in the supernatants of ADSCs and NPCs. WB was used to detect COL2A1, COL1A1, and Aggrecan in ADSCs to assess the manifestation of NP differentiation in ADSCs, and the WB method was used to detect COL2A1, COL1A1, Aggrecan, p16, p21, p53, and p-p53 protein expression in NPCs to reflect the cellular senescence status and to detect TGF-β1, Smad2, Smad3, p- Smad2, and p- Smad3 protein expression in NPCs to reflect the pathway condition. RESULTS: We finally identified 70 blood components and their metabolites, including 38 prototypes, from the BSHXF-medicated serum. Compared with that in the nonmedicated serum group, the TGF-β1/Smad pathway was activated in the medicated serum group, ADSCs moved toward NPC characteristics, the number of NPCs in the S/G2M phase increased, the number of senescent NPCs decreased, IL-1β and IL-6 inflammatory factors in the Transwell decreased, CXCL-1, CXCL-3, and CXCL-10 chemokines decreased, and the expression of p16, p21, p53 and p-p53 proteins in NPCs was inhibited. CONCLUSION: By regulating the TGF-β1/Smad pathway, BSHXF-medicated serum promoted ADSCs to NPCs, effectively alleviated the cycle blockage of NPCs after oxidative damage, encouraged the growth and proliferation of NPCs, delayed the aging of NPCs, improved the deteriorating microenvironment around NPCs, and repaired oxidatively damaged NPCs. The combination of BSHXF or its compounds with ADSCs has great potential for the treatment of IDD in the future.
作者机构：
[Hu, Zhuoyu; Hu, Qi; Chen, Xiangdong] Hunan Univ Chinese Med, Dept ophthalmol, Hosp 1, Changsha, Peoples R China.;[Wang, Xuan] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Chen, Xiangdong] Hunan Univ Chinese Med, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Chen, XD ] H;Hunan Univ Chinese Med, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
关键词：
apoptosis;autophagy;diabetes retinopathy;traditional Chinese medicine monomer
摘要：
Diabetic retinopathy (DR) has become one of the top 3 blinding eye diseases in the world. In spite of recent therapeutic breakthroughs, it is not yet possible to cure DR through pharmacotherapy. Cell death is thought to play a key role in the pathogenesis of DR. Moderate modulation of cellular autophagy and inhibition of apoptosis have been identified as effective targets for the treatment of DR. Numerous phytochemicals have emerged as potential new drugs for the treatment of DR. We collected basic DR research on herbal monomers through keywords such as autophagy and apoptosis, and conducted a systematic search for relevant research articles published in the PubMed database. This review provides the effects and reports of herbal monomers on various DR cellular and animal models in vivo and in vitro in the available literature, and emphasizes the importance of cellular autophagy and apoptosis as current DR therapeutic targets. Based on our review, we believe that herbal monomers that modulate autophagy and inhibit apoptosis may be potentially effective candidates for the development of new drugs in the treatment of DR. It provides a strategy for further development and application of herbal medicines for DR treatment.
通讯机构：
[Peng, QH; Peng, QH ; Yao, XL ] H;Hunan Univ Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Dept Ophthalmol, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.
摘要：
Thyroid eye disease (TED), an autoimmune inflammatory disorder affecting the orbit, exhibits a range of clinical manifestations. While the disease presentation can vary, cases that adhere to a prototypical pattern typically commence with mild symptoms that subsequently escalate in severity before entering a phase of stabilization. Notably, the metabolic activity of cells implicated in the disease substantially deviates from that of healthy cells, with purine metabolism representing a critical facet of cellular material metabolism by supplying components essential for DNA and RNA synthesis. Nevertheless, the precise involvement of Purine Metabolism Genes (PMGs) in the defensive mechanism against TED remains largely unexplored. The present study employed a bioinformatics approach to identify and validate potential PMGs associated with TED. A curated set of 65 candidate PMGs was utilized to uncover novel PMGs through a combination of differential expression analysis and a PMG dataset. Furthermore, GSEA and GSVA were employed to explore the biological functions and pathways associated with the newly identified PMGs. Subsequently, the Lasso regression and SVM-RFE algorithms were applied to identify hub genes and assess the diagnostic efficacy of the top 10 PMGs in distinguishing TED. Additionally, the relationship between hub PMGs and clinical characteristics was investigated. Finally, the expression levels of the identified ten PMGs were validated using the GSE58331 and GSE105149 datasets. This study revealed ten PMGs related with TED. PRPS2, PFAS, ATIC, NT5C1A, POLR2E, POLR2F, POLR3B, PDE3A, ADSS, and NTPCR are among the PMGs. The biological function investigation revealed their participation in processes such as RNA splicing, purine-containing chemical metabolism, and purine nucleotide metabolism. Furthermore, the diagnostic performance of the 10 PMGs in differentiating TED was encouraging. This study was effective in identifying ten PMGs linked to TED. These findings provide light on potential new biomarkers for TED and open up possibilities for tracking disease development.
摘要：
BACKGROUND: As the population ages, the prevalence of cerebral small vessel disease (CSVD) steadily increases, resulting in a significant economic burden on society. In East Asian nations, Chinese medicine has been used extensively to teat CSVD and has been reported to improve the cognitive function of patients. The present study aimed to comprehensively assess the efficacy and safety of Chinese medicine as adjuvant therapy for CSVD. METHODS: A literature search of the CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library, and ChiCTR databases were searched for RCTs investigating the use of TCM as an adjuvant in the treatment of CSVD, published up to July 27, 2023, was performed. Based on the Cochrane Collaboration Network bias risk assessment criteria, Review Manager version 5.3 was used to perform a meta-analysis. RESULTS: Meta-analysis of 27 RCTs, including 2554 subjects, revealed that the majority of the RCTs exhibited risk for ambiguous bias. The findings demonstrated that the use of Chinese medicine as an adjuvant treatment for CSVD effectively enhanced the cognitive function, as evidenced by improvements in the MMSE score (mean difference (MD) = 2.42, 95% confidence interval (CI) [1.79,3.17], P < .00001), MoCA score (MD = 2.39, 95% CI [1.78,2.99], P < .00001) and ADL score (MD = 4.13, 95% CI [1.74,6.51], P = .0007). Furthermore, the study also demonstrated the advantages of Chinese medicine adjuvant therapy in enhancing the Chinese medicine syndrome score (MD = -2.57, 95% CI [-3.31, -1.83], P < .00001), CRP (MD = -1.35, 95% CI [-2.27, -0.43], P = .004), Hcy (MD = -3.44,95% CI [-4.05, -2.83], P < .00001), and blood flow velocity (CBV) (MD = 1.37,95% CI [0.24,2.50], P = .02). Moreover, there was no statistical difference in the incidence of adverse reactions between the 2 groups. CONCLUSION: Findings of the present study indicate that the Chinese medicine, as an adjuvant to conventional treatment, appeared to be efficacious in enhancing cognitive function, reducing Chinese medicine syndrome score, improving blood biochemical markers, and improving cerebral blood flow perfusion in patients with CSVD, without any notable adverse reactions. However, it is imperative to validate these conclusions in future high-quality investigations.
作者机构：
[易展; 贲定严] Xiangxing College, Hunan University of Chinese Medicine, Changsha 410208, China;[王佳怡; 徐寅] Department of Internal Medicine, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410000
作者机构：
[刘梨; 龚志贤] The First Affiliated Hospital /The First Clinical College of Hunan University of Chinese Medicine, Changsha 410007, China;[张亮; 艾坤; 祁芳] College of Acupuncture-Moxibustion and Tuina, Hunan University of Chinese Medicine, Changsha 410208;[李鑫] Hunan Provincial Key Laboratory of Diagnostics of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208;[王文怡; 徐美丽] College of Nursing, Hunan University of Chinese Medicine, Changsha 410208
摘要：
OBJECTIVE: This study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC). METHODS: Traditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice. RESULTS: The major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8(+) and IFN-γ(+)/CD4(+) T cell levels while decreasing the PD-1(+)/CD8(+) T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-γ, and TNF-α levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated. CONCLUSION: BP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC.
摘要：
Three undescribed methylsuccinic acid derivatives, xylaril acids A-C, and two undescribed enoic acid derivatives, xylaril acids D-E, were isolated from the fungus Xylaria longipes. The structures of the undescribed compounds were deduced by spectroscopic means, including HRESIMS and 1D/2D NMR spectroscopy, as well as ECD calculations. The absolute configuration of xylaril acids A was further determined by single-crystal X-ray diffraction experiments. All the isolated compounds displayed neuroprotective activities against oxygen-glucose deprivation/reperfusion injury in PC12cells by enhancing cell viability and inhibiting cell apoptosis.
期刊：
Environmental Science and Pollution Research,2023年30(52):112943-112958 ISSN：0944-1344
通讯作者：
Guo, ZH
作者机构：
[Zheng, Huizhen; Yin, Ziwei; Luo, Xi; Zhou, Yingli] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Cardiol, Changsha 410007, Peoples R China.;[Zheng, Huizhen; Yin, Ziwei; Zhang, Fei; Luo, Xi; Guo, Zhihua; Zhou, Yingli] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.;[Guo, Zhihua] Hunan Key Lab Coll Intelligent Tradit Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Guo, ZH ] H;Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.;Hunan Key Lab Coll Intelligent Tradit Chinese Med, Changsha 410208, Peoples R China.
关键词：
Per- and polyfluoroalkyl substances;Metabolic syndrome;NHANES;Metabolism;Cardiovascular risk factors;Population-based study
摘要：
Per- and polyfluoroalkyl substances (PFAS) are widespread contaminants, but few studies have explored the relationship between PFAS and levels of metabolic syndrome (MetS) in the population. The available evidence of an association is also conflicting. We selected adults and adolescents with complete PFAS data from the National Health and Nutrition Examination Survey conducted between 2003 and 2018. We analyzed the association between PFAS and MetS using multivariate logistic regression models and evaluated potential nonlinear relationships with restricted cubic spline models. Additionally, we employed weighted quantile sum (WQS) regressions to uncover the multiple exposure effects and relative weights of each PFAS. Finally, we conducted a series of sensitivity analyses to test the robustness of our findings. In this population-based study, we analyzed data from a total of 4,973 adults, aged 20-85 years, and 1,381 adolescents, aged 12-19 years. Using fully adjusted multivariate logistic regression models, we found that serum levels of perfluorodecanoate (PFDA) [0.65 (0.50, 0.85)] and total PFAS [0.92 (0.85, 0.99)] were negatively associated with the prevalence of MetS in adults. Similarly, in adolescents, we observed negative correlations between the prevalence of MetS and levels of PFDA [0.55 (0.38, 0.80)], perfluorooctanoic acid (PFOA) [0.62 (0.39, 1.00)], perfluorooctane sulfonic acid (PFOS) [0.59 (0.36, 0.96)], and total PFAS [0.61 (0.37, 0.99)]. Additionally, our study identified statistically significant negative associations between serum levels of PFAS and certain components of MetS, primarily elevated fasting glucose and lower high-density lipoprotein cholesterol. Our study found that PFAS was associated with a lower prevalence of MetS in both adults and adolescents, offering new insights into the relationship between PFAS and metabolic health. Interestingly, however, we observed conflicting findings across the components of MetS. Specifically, we observed that PFAS had a negative correlation with some metrics and a positive correlation with others. These conflicting results point to a complex interplay between PFAS and various metrics of metabolic health.
摘要：
OBJECTIVE: Diminished ovarian reserve (DOR) refers to the decreased number and quality of oocytes in the ovary. Acupuncture and moxibustion has a certain effect on DOR; however, the number of studies and reports of research evidence are limited. This study aimed to conduct a scoping review of the clinical research status of acupuncture and moxibustion for treating patients with DOR. METHOD: PubMed, Cochrane Library, Excerpta Medica database, Allied and Complementary Medicine Database, Chinese Biological Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, and Wanfang database were searched from January 2010 to May 2022 using keywords and medical subject heading terms. After applying the inclusion and exclusion criteria, relevant studies were selected. Structured tables and descriptive charts were made to visually express research features by using Excel, Original, IBM SPSS Model 18.0, Adobe Illustrator and other software packages. Report quality was evaluated for Cochrane bias using Review Manager 5.3. RESULTS: Overall, 851 studies were identified; of these, 90 met the inclusion criteria. The results extracted from these studies were classified into four categories: research characteristics, study type, acupuncture and moxibustion prescriptions, and efficacy observation. CONCLUSIONS: The quality assessment of acupuncture and moxibustion for DOR is not ideal. Therefore, standardisation and normalisation should be strengthened, and high-quality evidence is needed to further demonstrate the effectiveness of this approach. Due to heterogeneity in DOR diagnosis, the observation index should be updated with reference to the latest research to improve efficacy evaluation.
摘要：
Background: Psoralidin (PL) could affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of PL is still unclear in adipose-derived stem cells (ADSCs). Aims: This study aimed to investigate the effects of PL on ADSCs differentiation into nucleus pulposus-like cells and the TGF-beta/Smad signaling pathway. Methods: The proliferation and apoptosis of ADSCs were detected. The nucleus pulposus cell-related markers (CD24, BASP1, KRT19, and Aggrecan) and TGF-beta/Smad signaling pathway indexes were analyzed. Results: The results showed that compared to the control group, the cell activity was increased in the PL group, and the apoptosis rate was decreased. The mRNA and protein levels of nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) and TGF-beta/Smad signaling pathway-related indexes (TGF-beta, SMAD2, and SMAD3) were increased in PL group. After treatment with PL and TGF-beta silencing, the TGF- beta/Smad signaling pathway-related indicators (TGF-beta, SMAD2, and SMAD3) and nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) were found to be higher in the sh-TGF-beta +PL group than in the sh-TGF-beta group. Conclusion: In conclusion, our study showed that PL might induce the differentiation of ADSCs to nucleus pulposus cells through the TGF-beta/Smad signaling pathway. It might have the potential application value in the treatment of intervertebral disc degeneration.
期刊：
Journal of Ethnopharmacology,2023年314:116611 ISSN：0378-8741
通讯作者：
Hu, GH
作者机构：
[Zhang, Tiantian; Liu, Kan; Li, Jiamin; Hu, Guoheng] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410021, Peoples R China.;[Zhang, Tiantian; Li, Jiamin; Hu, Guoheng] Hunan Univ Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Hu, GH ] H;Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410021, Peoples R China.
关键词：
Angiogenesis;Cerebral ischemic stroke;Microglia;Network pharmacology;PPARG;Yi Qi Huo Xue Fang
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Yi Qi Huo Xue Fang (YQHXF) is an effective formula for treating cerebral ischemic stroke (CIS). However, its active ingredients and mechanism of action remain unclear. AIM OF THE STUDY: This study aimed to reveal the mechanism of action of YQHXF in the treatment of ischemic stroke based on network pharmacology and experimental validation. MATERIALS AND METHODS: This study identified the chemical components in YQHXF and the components absorbed by rat serum based on UPLC-Q-TOF/MS technology and used network pharmacology to predict key candidate targets. A protein-protein-interaction (P-P-I) network was constructed using String 11.0 database and Cytoscape, and R software for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Finally, molecular docking combined with animal experiments was used to verify network pharmacology results. RESULTS: This study identified and confirmed 36 chemical components of YQHXF and five chemical ingredients that were absorbed into the blood of rats and screened 66 key candidate targets. All targets in the P-P-I network were mainly related to inflammation and vascular processes. KEGG enrichment results revealed that these 66 key candidate targets were primarily involved in the "AGE-RAGE signaling pathway," "TNF-α signaling pathway, and "T cell receptor signaling pathway." Molecular docking results revealed that Prostaglandin-endoperoxidase synthase 2(PTGS-2), Nitric oxide synthase, endothelial (NOS3), and peroxisome proliferator-activated receptor gamma (PPARG) were more stably bound to their active ingredients. Animal experiments demonstrated that YQHXF promoted M2 polarization, inhibited M1 polarization in microglia, and promoted angiogenesis, which may be related to the PPARG pathway. CONCLUSION: This study revealed the key active components and effective targets of YQHXF, identified the mechanism of action of YQHXF, laid the foundation for further research on YQHXF, and provided ideas for developing new drugs for CIS.
期刊：
Journal of Ethnopharmacology,2023年307:116203 ISSN：0378-8741
通讯作者：
Xiaolong Lu
作者机构：
[Lu, Xiaolong] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Orthoped, Changsha 410005, Hunan, Peoples R China.;[Lu, Xuedi; Li, Wei; Li, Juan; Ouyang, Jian] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Orthoped, Changsha 410005, Hunan, Peoples R China.;[Zhou, Biao] Chinese Acad Chinese Med Sci, Wangjing Hosp, Dept Orthoped, Beijing 100102, Peoples R China.;[Zhou, Biao] Univ South China, Xiangtan Hosp, Dept Orthoped, Xiangtan 411101, Hunan, Peoples R China.;[Lu, Xiaolong] 233 Cai E Bei Rd, Changsha 410005, Hunan, Peoples R China.
通讯机构：
[Xiaolong Lu] D;Department of Orthopedics, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is a conventional traditional Chinese prescription aiming at promoting blood circulation and alleviating blood stasis. It is widely prescribed in instances of ischemic strokes, cardiovascular diseases, osteoporosis and bone fracture. However, its molecular functions in bone formation remain uncharacterized. AIM OF STUDY: This study aims to explore the potential effects of THSWD treatment on human bone marrow mesenchymal stem cells (BMSCs) proliferation, osteogenic differentiation, and migration. MATERIALS AND METHODS: BMSCs undergo osteogenic, adipogenic, and chondrogenic differentiation to determine cell stemness. BMSCs were treated with low dose (200μg/ml), medium dose (400μg/ml) and high dose (600μg/ml) THSWD. The cell viability was determined by CCK-8 assays, the osteogenic differentiation ability was determined by alizarin red staining and ALP staining, and cell migration was determined by wound healing and transwell assays. The effect of THSWD on the vascular endothelial growth factor (VEGF)/focal adhesion kinase (FAK) pathway was determined by immunoblotting. RESULTS: THSWD time-dependently and dose-dependently promoted BMSC viability. Moreover, THSWD also promoted BMSC osteogenic differentiation and migration. As opposed to THSWD, VEGF receptor inhibitor Bevacizumab suppressed BMSC osteogenic differentiation and migration. In BMSCs that have been co-treated with THSWD and Bevacizumab, THSWD effects on BMSC functions were partially eliminated by Bevacizumab. Moreover, THSWD treatment boosted VEGF content in the supernatant and was conducive to the phosphorylation of FAK and Src, whereas Bevacizumab exerted opposite effects; similarly, Bevacizumab partially abolished THSWD effects on VEGF and FAK (Tyr397) and Src (Tyr418) phosphorylation. CONCLUSION: THSWD enhances the capacities of BMSCs to proliferate, differentiate, and migrate, possibly through VEGF and the FAK-Src, thereby improving fracture healing.
摘要：
As one of the types of programmed cell death, pyroptosis has become a focus of research in recent years. Numerous studies have shown that pyroptosis plays a regulatory role in tumor cell invasiveness, differentiation, proliferation, and metastasis. It has been demonstrated that pyroptosis is involved in the regulation of signaling pathways implicated in the pathogenesis of prostate cancer (PCa). Furthermore, the loss of expression of pyroptosis-related genes in PCa has been reported, and pyroptosis-related genes have demonstrated a considerable ability in predicting the prognosis of PCa. Therefore, the potential role of pyroptosis in regulating the development of PCa warrants further investigation and attention. In this review, we summarize the basics of the role of pyroptosis and also discuss research into the mechanisms of action associated with pyroptosis in PCa. It is hoped that by exploring the potential of the pyroptosis pathway in intervening in PCa, it will provide a viable direction for the diversification of PCa treatment.
作者机构：
[朱莹; 谢超群; 陈凯; 董慧; 孙豪娴] Department of Spleen and Stomach Disease, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China
摘要：
Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.
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：
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.
