Cell Biochemistry and Biophysics最新文献

{"title":"Proteostasis and Its Role in Disease Development.","authors":"Manisha Shukla, Mahesh Narayan","doi":"10.1007/s12013-024-01581-6","DOIUrl":"https://doi.org/10.1007/s12013-024-01581-6","url":null,"abstract":"<p><p>Proteostasis (protein homeostasis) refers to the general biological process that maintains the proper balance between the synthesis of proteins, their folding, trafficking, and degradation. It ensures proteins are functional, locally distributed, and appropriately folded inside cells. Genetic information enclosed in mRNA is translated into proteins. To ensure newly synthesized proteins take on the exact three-dimensional conformation, molecular chaperones assist in proper folding. Misfolded proteins can be refolded or targeted for elimination to stop aggregation. Cells utilize different degradation pathways, for instance, the ubiquitin-proteasome system, the autophagy-lysosome pathway, and the unfolded protein response, to degrade unwanted or damaged proteins. Quality control systems of the cell monitor the folding of proteins. These checkpoint mechanisms are aimed at degrading or refolding misfolded or damaged proteins. Under stress response pathways, such as heat shock response and unfolded protein response, which are triggered under conditions that perturb proteostasis, the capacity for folding is increased, and degradation pathways are activated to help cells handle stressful conditions. The deregulation of proteostasis is implicated in a variety of illnesses, comprising cancer, metabolic diseases, cardiovascular diseases, and neurological disorders. Therapeutic strategies with a deeper insight into the mechanism of proteostasis are crucial for the treatment of illnesses linked with proteostasis and to support cellular health. Thus, proteostasis is required not only for the maintenance of cellular homeostasis and function but also for proper protein function and prevention of injurious protein aggregation. In this review, we have covered the concept of proteostasis, its mechanism, and how disruptions to it can result in a number of disorders.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ensuring Clinical Excellence: The Mindray SAL9000 Biochemical Immunoassay System.","authors":"Zhenzhen Zou, Honghui Tang, Erya Xiao, Yu Zhou, Xuebei Yin, Zhen Hu, Yang Cai, Qingzhen Han, Lin Wang","doi":"10.1007/s12013-024-01568-3","DOIUrl":"https://doi.org/10.1007/s12013-024-01568-3","url":null,"abstract":"<p><p>This study aimed to evaluate the performance and clinical laboratory adaptability of the Mindray SAL9000 biochemical immunoassay automation system, ensuring compliance with ISO 15189 standards and relevant national requirements. We conducted comprehensive performance verification tests on 21 biochemical analytes and 15 immunoassays, including precision, accuracy, linear bias, measurement range assessments, interference testing, reference range validation, inter-instrument comparison, and carryover verification. The Mindray SAL9000 demonstrated high performance across various parameters, with all analytes showing good linearity and minimal bias. While specific interfering substances affected some analytes, the system showed excellent resistance to common interferences such as hemolysis, ascorbic acid, and jaundice. The inter-instrument comparison with the BS2000M and Roche 702 indicated a good correlation, with most parameters showing biases of less than 10%, although exceptions were noted for ALT and AST. In conclusion, the Mindray SAL9000 meets clinical requirements through its high precision, excellent accuracy, and broad measurement range, making it a reliable and adaptable choice for clinical outpatient and emergency laboratories.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SESN2 Ameliorates Dihydrotestosterone-induced Human Ovarian Granulosa Cell Damage by Activating AMPK/ULK1-mediated Mitophagy.","authors":"Xiaojing Hua, Qing Lu, Li Zeng","doi":"10.1007/s12013-024-01589-y","DOIUrl":"https://doi.org/10.1007/s12013-024-01589-y","url":null,"abstract":"<p><p>Sestrin 2 (SESN2) has been reported to participate in the regulation of granulosa cell function in ovarian tissues. However, the role of SESN2 in polycystic ovarian syndrome (PCOS) is still incompletely understood. Here, we investigated the functional role and mechanism of SESN2 in dihydrotestosterone (DHT)-induced granulosa cells. In this study, DHT was utilized to induce PCOS cell model and the AMP-activated protein kinase (AMPK) inhibitor Compound C (CC) was utilized to inhibit the AMPK pathway. qRT-PCR was performed to detect the expression of SESN2 in HGLS cells. Cell apoptosis was evaluated by flow cytometry. Oxidative stress was detected by DCFH-DA staining, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) kits. The expression of SESN2, cell apoptosis, oxidative stress, mitophagy and AMPK/ULK1 signaling-related proteins were measured by western blot. The results showed that SESN2 was downregulated in DHT-induced granulosa cells. Overexpression of SESN2 inhibited the DHT-induced apoptosis and oxidative stress of HGLS cells. DHT induction aggravated HGLS cell apoptosis and oxidative stress. SESN2 overexpression inhibited the DHT-induced apoptosis and oxidative stress of HGLS cells. In addition, overexpression of SESN2 activated the AMPK/ULK1 signaling pathway and promoted mitophagy. Treatment of CC reversed the regulatory effect of SESN2 on mitophagy. CC also reversed the influences of SESN2 overexpression on apoptosis and oxidative stress in DHT-induced HGLS cells. Overall, SESN2 suppressed DHT-induced apoptosis and oxidative stress in PCOS through AMPK/ULK1-mediated mitophagy.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance Training and Resveratrol Supplementation Improve Cancer Cachexia and Tumor Volume in Muscle Tissue of Male Mice Bearing Colon Cancer CT26 Cell Tumors.","authors":"Mahdi Samadi, Farhad Daryanoosh, Zahra Mojtahedi, Afrooz Samsamy Pour, Hadi Nobari, Amir Hossein Zarifkar, Kayvan Khoramipour","doi":"10.1007/s12013-024-01491-7","DOIUrl":"https://doi.org/10.1007/s12013-024-01491-7","url":null,"abstract":"<p><p>Losing muscle functions due to reducing muscle mass and quality is one of the main features of cancer cachexia that impairs patients' quality of life and decrease their survival. This study aimed to investigate the synergistic effects of resistance training and resveratrol supplementation on cachexia induced by CT26 tumors in male mice. Forty-eight mice were divided into eight groups randomly: healthy sedentary vehicle (HSV), healthy exercise vehicle (HEV), healthy sedentary resveratrol (HSR), healthy exercise resveratrol (HER), CT-26 tumor-bearing sedentary vehicle (TSV), CT-26 tumor-bearing exercise vehicle (TEV), CT-26 tumor-bearing sedentary resveratrol (TSR) and CT-26 tumor-bearing exercise resveratrol (TER). Training groups performed ladder climbing with weights tied to their tails, for six weeks. Resveratrol-treated groups received 50 mg/kg daily by gavage. The results showed muscle weight, and mTORC1 phosphorylation decreased in TSV compared to the HSV group. mTORC1 phosphorylation was increased in TER compared to TSV, TEV, and TSR. In addition, AMPK phosphorylation was more elevated in HER compared to HSV, HEV, and HSR. LC3BII/I ratio was higher in TSV than HSV group. Tumor volume was increased in all groups, with the lowest increase in TER group. In tumor tissue, mTORC1 phosphorylation was decreased in TER than in TSV, TEV, and TSR groups; AMPK phosphorylation and LC3BII/I ratio were increased in TSV than in TEV, TSR, and TER groups. In conclusion, the synergistic effect of resistance training and resveratrol supplementation is the most effective in reducing tumor volume. These advantages were mostly in line with molecular findings.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Deubiquitinating Enzyme USP4 Promotes Trophoblast Dysfunction by Stabilizing RYBP.","authors":"Xuandi Wu, Jia Hong, Liang Hong","doi":"10.1007/s12013-024-01525-0","DOIUrl":"https://doi.org/10.1007/s12013-024-01525-0","url":null,"abstract":"<p><p>Previous studies have suggested that impaired spiral artery remodeling, placental dysfunction, and insufficient trophoblast infiltration are the etiology and pathogenesis of Preeclampsia (PE). Ring 1 and YY1 binding protein (RYBP) has been reported to be associated with trophoblast dysfunction. However, the molecular mechanism of RYBP involved in trophoblasts in the pathogenesis of PE is poorly defined. RYBP and Ubiquitin-specific peptidase 4 (USP4) mRNA levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). RYBP, USP4, p-PI3K, PI3K, p-AKT, and AKT protein levels were measured using western blot assay. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. After ubibrowser database analysis, the interaction between USP4 and RYBP was verified using Co-immunoprecipitation (CoIP) assay. RYBP and USP4 expression were upregulated in placental tissues from PE patients. By using JEG-3 and HTR-8/SVneo trophoblast cells, RYBP overexpression or USP4 upregulation could hinder cell viability, proliferation, invasion, migration, and promote apoptosis. Mechanistically, USP4 could trigger the deubiquitination of RYBP and prevent its degradation. In addition, USP4 repressed the PI3K/AKT signaling pathway by regulating RYBP. In total, Decreased USP4-mediated ubiquitination results in an adverse impact on trophoblast function by enhancing RYBP expression, providing a novel therapeutic target for PE.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-proliferative Effect, Apoptotic Induction, and Cell Cycle Arrest of Tetra Halo Ruthenate Nanocomposites in Different Human Cancer Cell Lines.","authors":"Mariam Fathy, Salwa M El-Hallouty, Ahmed S Mansour, Mohamed Fahmy, Nourhan Hassan, Emad M ElZayat","doi":"10.1007/s12013-024-01519-y","DOIUrl":"https://doi.org/10.1007/s12013-024-01519-y","url":null,"abstract":"<p><p>Chemotherapy is the most common cancer treatment, and metallic anticancer compounds have generated increasing amounts of interest since the discovery of cisplatin. More recently, scientists have focused on ruthenium-based compounds as alternatives for platinum compounds, which seem like ideal therapeutic anticancer alternatives to platinum derivatives. The present study aims to assess whether one or more of three Ruthenium-based nanocomposites, namely Ru+Lysine+CTAB (RCTL), Ru+CTAB (RCT), and Ru+Lysine (RL) exhibit pronounced anti-proliferative properties against different cancer cells. Three Ruthenium nanocomposites have been synthesized by standard chemical methods and characterized by Dynamic light scattering (DLS) and Transmission electron microscopy (TEM). The cytotoxic effect of the three composites has been evaluated by MTT in-vitro assay for different human cancer cell lines, namely MCF7, HepG2, A549, and PC3 versus normal human skin cell line (BJ1). The molecular underlying mechanisms of cytotoxicity have been assessed via qRT-PCR for pro-apoptotic makers P53 and Casp-3, and anti-apoptotic marker Bcl-2 as well as flow cytometric analysis of the cell cycle. Among the 3 nanocomposites, RCTL gave the best sensitivity and cytotoxicity especially on HepG2 with IC₅₀ 0.55 µg/ml but was still toxic on normal cell line with dose <12.5 µg/ml. RCTL and RCT nanocomposites have demonstrated a significant increase in the expression of P53 and Casp-3 markers versus untreated controls, but a significant reduction in the expression of Bcl-2. There was a direct correlation between the cytotoxic effect and the degree of apoptosis in the different cancer cell lines. The present study has also proved cell cycle arrest at G2-M and pre-G1 phases under the effect of IC₅₀ of RCTL and RCT nanocomposites in different cancer lines with the best effect being achieved in HepG2 cells. Ruthenium nanocomposites seem to open a new avenue in cancer therapy.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirt4 Overexpression Modulates the JAK2/STAT3 and PI3K/AKT/mTOR Axes to Alleviate Sepsis-Induced Acute Lung Injury.","authors":"Cancan Xie, Ting Wang, Anmin Liu, Bing Huang, Weizhong Zeng, Zhengrong Li, Suna Peng, Shuanghua Wu","doi":"10.1007/s12013-024-01588-z","DOIUrl":"https://doi.org/10.1007/s12013-024-01588-z","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute lung injury (ALI) is a severe organ dysfunction characterized by lung inflammation and apoptosis. The mechanisms underlying sepsis-induced ALI remain poorly understood. Here, we determined the effects of sirtuin 4 (SIRT4) on sepsis-induced ALI.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS)-induced injury cell and cecal ligation and puncture (CLP) animal models were established. Overexpression vectors and lentiviral transfections were used to upregulate SIRT4 expression. Lung cell apoptosis, inflammation, and the levels of associated factors were evaluated. Changes in the PI3K/AKT/mTOR and JAK2/STAT3 pathways were measured, and their potential involvement was examined using LY294002 (PI3K inhibitor), 740 Y-P (PI3K agonist), AG490 (JAK2 inhibitor), and coumermycin A1 (JAK2 agonist).</p><p><strong>Results: </strong>Lower SIRT4 expression was observed in LPS-exposed A549 cells and CLP rats. In LPS-induced A549 cells, Sirt4 overexpression enhanced cell viability, resisted apoptosis, restored the expression of apoptosis-associated proteins (HMB1, cleaved CASP3, BAX, and BCL), and reduced the secretion of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). In CLP rats, Sirt4 overexpression prolonged survival time, alleviated lung histopathological damage, reduced pulmonary edema, mitigated lung infection, decreased lung apoptosis, and lowered serum levels of inflammatory cytokines. Furthermore, Sirt4 overexpression blocked JAK2/STAT3/AKT/mTOR phosphorylation. 740 Y-P and coumermycin A1 reversed the protective effects of Sirt4 overexpression in LPS-treated A549 cells, resulting in decreased cell viability and increased apoptosis. LY294002 and AG490 enhanced the protective effects of Sirt4 overexpression in LPS-treated A549 cells.</p><p><strong>Conclusion: </strong>SIRT4 alleviates sepsis-induced ALI by inhibiting JAK2/STAT3/PI3K/AKT/mTOR signaling. Upregulating SIRT4 expression may serve as an innovative therapeutic approach for lung injury management in sepsis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GBP2 Regulates Lipid Metabolism by Inhibiting the HIF-1 Pathway to Alleviate the Progression of Allergic Rhinitis.","authors":"Yunsong An, Jun Xu, Xiaoqi Hu, MiMi Xu, Xuechun Yang, Tao Liu","doi":"10.1007/s12013-024-01578-1","DOIUrl":"https://doi.org/10.1007/s12013-024-01578-1","url":null,"abstract":"<p><p>Allergic rhinitis (AR) is a prevalent allergic disorder instigated by a variety of allergenic stimuli. The study aims to elucidate the mechanistic underpinnings of Guanylate-binding protein 2 (GBP2) in modulating AR. Bioinformatics analysis was used to identify hub genes in AR, and GBP2 was identified. Mice were injected with ovalbumin (OVA) to create AR model. The pathological changes of the nasal mucosa were observed by hematoxylin-eosin staining. ELISA and western blot demonstrated that in OVA-induced AR mice, high IgE and IgG1 levels, inflammation (increased TNF-α, IL-5 and IFN-γ), oxidative stress (high ROS, low TAOC and GSH) and abnormal lipid metabolism (increased TC and LDL-C, decreased HLD-C) were observed. Mouse nasal mucosal epithelial cells (MNECs) were treated with TNF-α to simulate AR. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometer, respectively. In vitro assay revealed that GBP2 inhibited total IgE, OVA-IgE and IgG1 levels and suppressed abnormal lipid metabolism, inflammation and oxidative stress to alleviate AR. Furthermore, HIF-1 pathway was screened as the downstream pathway of GBP2. GBP2 inhibited the HIF-1 pathway, and Fenbendazole-d3, the activator of HIF-1 pathway, weakened the inhibitory effects of GBP2 on apoptosis, inflammation, oxidative stress and abnormal lipid metabolism in vitro. In summary, GBP2 alleviated abnormal lipid metabolism, inflammation and oxidative stress by inhibiting the HIF-1 pathway, providing a direction for the treatment of AR.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP5 Stabilizes IKBKG Through Deubiquitination to Suppress Ferroptosis and Promote Growth in Non-small Cell Lung Cancer.","authors":"Yufu Li, Gan Qiu, Min Zhou, Qianzhi Chen, Xiaoyong Liao","doi":"10.1007/s12013-024-01574-5","DOIUrl":"https://doi.org/10.1007/s12013-024-01574-5","url":null,"abstract":"<p><p>Ferroptosis, a distinctive modality of cell mortality, has emerged as a critical regulator in non-small cell lung cancer (NSCLC). The deubiquitinating enzyme USP5 has established an oncogenic role in NSCLC. However, its biological relevance in NSCLC cell ferroptosis is currently unexplored. Expression analysis was performed by quantitative PCR (qPCR), immunohistochemistry (IHC) and immunoblotting. Animal xenograft studies were used to detect USP5's role in tumor growth. Cell proliferation, colony formation and apoptotic ratio were assessed by CCK-8, colony formation and flow cytometry assays, respectively. Cell ferroptosis was evaluated by gauging ROS, MDA, GSH, SOD, and Fe²⁺ contents. The USP5/IKBKG relationship and the ubiquitinated IKBKG were evaluated by Co-IP experiments. USP5 expression was elevated in human NSCLC. USP5 depletion suppressed NSCLC cell in vitro and in vivo growth and enhanced cell apoptosis. Moreover, USP5 depletion induced ferroptosis in NSCLC cell lines. Mechanistically, USP5 could enhance the stability of IKBKG protein through deubiquitination. Re-expression of IKBKG partially but significantly abolished USP5 depletion-mediated anti-growth and pro-ferroptosis effects in NSCLC cells. Our study demonstrates that USP5 suppresses ferroptosis and enhances growth in NSCLC cells by stabilizing IKBKG protein through deubiquitination. Targeting USP5 expression is an encouraging strategy to block NSCLC progression.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cimifugin Alleviates Chronic Constriction Injury of the Sciatic Nerve by Suppressing Inflammatory Response and Schwann Cell Apoptosis.","authors":"Qijuan Zhang, Xiaoli Zhang, Qing He, Yu Tian, Zhengmao Liu","doi":"10.1007/s12013-024-01513-4","DOIUrl":"https://doi.org/10.1007/s12013-024-01513-4","url":null,"abstract":"<p><p>Inflammation and Schwann cell apoptosis play critical roles in neuropathic pain after sciatic nerve injury. This study aimed to explore the function and mechanism of cimifugin in lipopolysaccharide (LPS)-stimulated rat Schwann cells and sciatic nerves of rats treated with chronic constriction injury (CCI). Thermal, mechanical and cold hyperalgesia of rats in response to cimifugin or mecobalamin (the positive drug control) treatment were evaluated through behavioral tests. H&E staining of sciatic nerves was performed for pathological observation. ELISA was conducted to assess concentrations of inflammatory cytokines in rat serum and sciatic nerves. The intensity of S100β in sciatic nerves was determined using immunohistochemistry. Flow cytometry analysis was conducted for detection of Schwann cell apoptosis. RT-qPCR was performed to measure mRNA levels of inflammatory factors in Schwann cells. Immunofluorescence staining was performed to detect cellular p65/NF-κB activity. Western blotting was performed to quantify protein levels of apoptotic markers and factors associated with the NF-κB and MAPK pathways in rat nerves and Schwann cells. As shown by experimental data, cimifugin mitigated thermal, mechanical and cold hyperalgesia of CCI rats. Cimifugin repressed inflammatory cell infiltration, reduced proinflammatory cytokine levels while increasing anti-inflammatory factor (IL-10) level in serum or sciatic nerves of CCI rats. Cimifugin enhanced S100β expression and downregulated apoptotic markers in vivo. The anti-inflammatory and anti-apoptotic properties of cimifugin were verified in the LPS-stimulated Schwann cells. Moreover, cimifugin suppressed nuclear translocation of p65 NF-κB in vitro and repressed the phosphorylation of IκB, p65 NF-κB, p38 MAPK, ERK1/2, as well as JNK in CCI rats. In conclusion, cimifugin alleviates neuropathic pain after sciatica by suppressing inflammatory response and Schwann cell apoptosis via inactivation of NF-κB and MAPK pathways.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}