作者机构:
[Li, Jun; Yan, Wen; Chen, Xiguang; Zu, Xuyu; Luo, Yan; Xiang, Shasha; Wang, Qi; Feng, Jianbo; Zhu, Qingyun] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Zu, XY ; Feng, JB] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
摘要:
Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related death among females. Metastasis accounts for the majority of BC related deaths. One feasible strategy to solve this challenging problem is to disrupt the capabilities required for tumor metastasis. Herein, we verified a novel metastasis suppressive circRNA, circPOKE in BC. circPOKE was downregulated in primary and metastatic BC tissues and overexpression of circPOKE inhibited the metastatic potential but not the proliferative ability of BC cells in vitro and in vivo. Mechanistically, circPOKE competitively binds to USP10, and reduces its binding to Snail, a key transcriptional regulator of EMT, thereby inhibiting Snail stability via the protein-ubiquitination degradation pathway. In addition, we found that circPOKE could be secreted into the extracellular space via exosomes and that exosome-carried circPOKE significantly inhibited the invasive capabilities of BC cells in vitro and in vivo. Furthermore, the levels of circPOKE, USP10 and Snail are clinically relevant in BC, suggesting that circPOKE may be used as a potential therapeutic target for patients with BC metastasis.
摘要:
Tyrosine-protein phosphatase non-receptor type 2(PTPN2), an important member of the protein tyrosine phosphatase family, can regulate various signaling pathways and biological processes by dephosphorylating receptor protein tyrosine kinases. Accumulating evidence has demonstrated that PTPN2 is involved in the occurrence and development of atherosclerotic cardiovascular disease. Recently, it has been reported that PTPN2 exerts an anti-atherosclerotic effect by regulating vascular endothelial injury, monocyte proliferation and migration, macrophage polarization, T cell polarization, autophagy, pyroptosis, and insulin resistance. In this review, we summarize the latest findings on the role of PTPN2 in the pathogenesis of atherosclerosis to provide a rationale for better future research and therapeutic interventions.
作者机构:
[Wang, Yan Xia; Tian, Zhen; Zheng, Hong Yu; Liu, Hui Ting; Deng, Nian Hua; Wu, Ze Fan; Liu, Xi Yan; Jiang, Zhi Sheng] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerosis Hunan Prov, Hengyang, Hunan, Peoples R China.;[Zhou, Zhan Yang] Chinese Acad Med Sci & Peking Union Med Coll, Fu Wai Hosp, Dept Cardiol, Beijing, Peoples R China.;[Ou, Yang Shao] Univ South China, Hosp 2, Hengyang, Hunan, Peoples R China.;[Jiang, Zhi Sheng] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerosis Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Zhi Sheng Jiang PhD; Zhi Sheng Jiang PhD Zhi Sheng Jiang PhD Zhi Sheng Jiang PhD] I;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerosis of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan, PR China
摘要:
Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti-hypertensive. Using a meta-analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002-2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (Delta SBP) was -1.42 (95% CI: -2.38, -0.46; p = .004) and diastolic blood pressure (Delta DBP) was 0.82 (95% CI: -1.28, -0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non-significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi-ethnic, large sample pool size, and a long period follow-up study is still required to assert these claims.
期刊:
Public Health Nursing,2023年40(5):782-789 ISSN:0737-1209
通讯作者:
Zeng, Y
作者机构:
[Huang, Yu-ting; Yue, Qian-qian; Tang, Tian; Zeng, Ying; Hu, Li-feng; Sun, Ying-xue; Zou, Jin-yu] Univ South China, Hengyang Med Sch, Dept Int & Humanist Nursing, Sch Nursing,Hunan Sci Popularizat Educ Base, Hengyang, Peoples R China.;[Zeng, Ying; Zeng, Xi] Univ South China, Canc Res Inst, Hengyang Med Sch, Key Lab Tumor Cellular & Mol Pathol, Hengyang, Peoples R China.;[Zeng, Ying] Univ South China, Hengyang Med Sch, Sch Nursing, Dept Int & Humanist Nursing, Hengyang, Peoples R China.
通讯机构:
[Zeng, Y ] U;Univ South China, Canc Res Inst, Hengyang Med Sch, Key Lab Tumor Cellular & Mol Pathol, Hengyang, Peoples R China.;Univ South China, Hengyang Med Sch, Sch Nursing, Dept Int & Humanist Nursing, Hengyang, Peoples R China.
摘要:
INTRODUCTION: Colorectal cancer (CRC) is associated with a high incidence and mortality rate. Fecal occult blood test (FOBT) is effective in the prevention of CRC. OBJECTIVE: This study aimed to assess knowledge and beliefs regarding FOBT-based screening. METHODS: This study used PubMed, Cochrane Library, MEDLINE Complete, and Web of Science to search for articles. Original full-text studies in English language focusing on knowledge and beliefs of FOBT screening were included. RESULTS: A total of 32 articles were included. This study indicated that the population in most studies had inadequate knowledge and lacked beliefs toward FOBT-based screening. Most of the extracted studies showed that less than half of the participants had heard of FOBT-based screening. Six studies showed that less than 50% of participants had knowledge of FOBT age. Three studies found that less than 40% of participants were aware of the screening interval. Some participants perceived the benefits of FOBT-based screening, while others perceived many barriers to the test. CONCLUSION: Participants' knowledge and belief in FOBT-based screening were insufficient. This review highlights the importance of educational programs to increase knowledge and beliefs regarding FOBT-based screening. It is important to include FOBT-based screening in the health care system to promote the secondary prevention of CRC.
作者:
Chen, Li-jun;Tan, Feng-hua;Li, Zhe-zhi;Liu, Wei;Lyu, Bo
期刊:
Ecotoxicology and Environmental Safety,2023年255:114832 ISSN:0147-6513
通讯作者:
Li-jun Chen<&wdkj&>Bo Lyu
作者机构:
[Chen, Li-jun; Li, Zhe-zhi] Shaoyang Univ, Coll Urban & Rural Construction, Shaoyang 422099, Peoples R China.;[Tan, Feng-hua] Univ South China, Peoples Hosp ChenZhou 1, Translat Med Inst, Hengyang Med Sch, Chenzhou 423000, Hunan, Peoples R China.;[Liu, Wei] Hunan Univ Technol, Coll Urban & Environm Sci, Zhuzhou 412007, Peoples R China.;[Lyu, Bo] Univ Missouri, Div Plant Sci & Technol, Columbia, MO 65211 USA.
通讯机构:
[Li-jun Chen] C;[Bo Lyu] D;Division of Plant Science and Technology, University of Missouri, Columbia, MO 65211, USA<&wdkj&>College of Urban and Rural Construction, Shaoyang University, 422099 Shaoyang, China
摘要:
Although research into how spiders respond to cadmium (Cd)-induced toxicity is ongoing, little is known about the effects of Cd contamination on the exogenous microorganisms of spiders. The current study used 16S rRNA gene sequencing to evaluate the richness and structure of external bacterial communities in the wolf spider Pardosa pseudoannulata under long- and short-term Cd stress. Our results showed that Proteobacteria and Acidibacter were the dominating bacterial phylum and genus. The alpha diversity analysis showed that the high background of Cd concentration (Cd) reduced bacterial alpha diversity, and short-term Cd (SCd) stress elevated bacterial richness and diversity. Hub bacterial genera, including Stenotrophobacter, Hymenobacter, Chitinophaga, and Bryobacter, were identified by co-occurrence network analysis and showed high connectance with other bacterial genera. Further investigation revealed 15 and 14 bacterial taxa that were classified distinctively under SCd and Cd stresses. Interestingly, functional prediction analysis showed that Cd stress enhanced some crucial pathways involved in specialized functions, including manganese oxidation and aromatic compound degradation. Random forest and correlation analyses found that the spider's molting time was the dominant driver affecting bacterial phyla (i.e., Proteobacteria and Planctomycetes) and genera (e.g., Acidibacter, Reyranella, and Haliangium). Collectively, this comprehensive analysis creates new perspectives to investigate the divergent responses of microbial communities in the spiders' external habitat under Cd stress, and provides valuable viewpoints for Cd pollution evaluation and control.
通讯机构:
[Hu, Hengjing] D;Department of Cardiology, The First Affiliated Hospital of University of South China, Hunan Province, Hengyang, China.;Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan, China.
作者机构:
[Liu, Li; Xiao, Lu-shan; Xiao, LS; Liu, L; Hu, Cheng-yi; Hong, Chang] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou, Peoples R China.;[Liu, Li; Xiao, Lu-shan; Xiao, LS; Huang, Chao-yi; Zou, Xue-jing; Liu, L; Zou, Xue-Jing; Li, Rui-ning; Hong, Chang; Cui, Hao; Li, Qi-mei] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.;[Dong, Han-zhi] Jiangxi Canc Hosp, Nanchang Med Coll, Jiangxi Clin Res Ctr Canc, Dept Med Oncol,Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China.;[Zhu, Hong-bo] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Med Oncol, Hengyang, Peoples R China.;[Peng, Jie; Hu, Cheng-yi] Guangzhou First Peoples Hosp, Dept Infect Dis, Guangzhou, Peoples R China.
通讯机构:
[Xiao, LS ; Zou, XJ; Liu, L] S;Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou, Peoples R China.;Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.
关键词:
Alpha-fetoprotein;Hepatic immune predictive index;Immune checkpoint inhibitors;Neutrophil-lymphocyte ratio;Primary liver cancer
摘要:
BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival outcomes and resulted in long-term responses in primary liver cancer in some patients. However, its efficacy is limited by the risk of tumor recurrence, resulting in rapid death and graft loss if patients are not selected appropriately. Therefore, it is necessary to identify patients suitable for such therapy. METHODS: 215 patients with primary liver cancer with immunotherapy were screened between August 2018 and October 2020 as a training set and our validation set were included 71 patients of hepatocellular carcinoma from Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College from May 2019 to July 2021. The primary endpoint was the disease control rate (DCR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: In the traing set, Neutrophil-leukocyte ratio (NLR) >3, Alpha-fetoprotein (AFP) level >20 ng/ml, distant metastasis at baseline, and absence of combination with targeted therapy were associated with non-DCR in the training set. Moreover, NLR >3 and AFP level >20 ng/ml were also independently associated with OS. Furthermore, a hepatic immune predictive index (HIPI) based on NLR >3 and AFP level >20 ng/mL was developed and associated with worse clinical outcomes. In validation set, HIPI was associated with overall survival. CONCLUSION: Baseline hepatic immune predictive index based on NLR and AFP level is an effective indicator in ICI-treated patients with primary liver cancer. Our findings may help guide the selection and on-treatment strategies for immunotherapies for primary liver cancer patients.
期刊:
Journal of Translational Medicine,2023年21(1):1-13 ISSN:1479-5876
通讯作者:
Xiao, ZJ
作者机构:
[He, Bing; Deng, Limin; Zhou, Guijuan; Xu, Yan; Xie, Juan; Chen, Shuangxi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Xiao, ZJ; Wu, Lin] Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang 421001, Hunan, Peoples R China.;[He, Bing; Deng, Limin; Zhou, Guijuan; Xu, Yan; Xie, Juan; Chen, Shuangxi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Xiao, ZJ; Wu, Lin] Univ South China, Affiliated Hosp 1, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Wu, Lin] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang 421000, Hunan, Peoples R China.
通讯机构:
[Xiao, ZJ ] U;Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
摘要:
Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms. Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting. NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA. NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.
作者机构:
[Huang, Yun; Huang, Weiguo; Xiao, Shengjun] Guilin Med Univ, Guangxi Key Lab Tumor Immun & Microenvironm Regula, Guilin 541199, Peoples R China.;[Cheng, Ailan; Huang, Yun; Huang, Weiguo] Univ South China, Canc Res Inst, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Wei, Dengshuai; Tang, Dongsheng; Wang, Bin] Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, State Key Lab Polymer Phys & Chem, Beijing 100190, Peoples R China.;[Yu, Yingjie] Beijing Univ Chem Technol, State Key Lab Organ Inorgan Composites, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China.
通讯机构:
[Yingjie Yu] S;[Weiguo Huang] G;State Key Laboratory of Organic-Inorganic Composites;Beijing Laboratory of Biomedical Materials;Beijing University of Chemical Technology, Beijing 100029, China<&wdkj&>Guangxi Key Laboratory of Tumor Immunity and Microenvironment Regulation, Guilin Medical University, Guilin 541199, China<&wdkj&>Cancer Research Institute, Hengyang Medical College of University of South China, Hengyang 421001, China
关键词:
DNA damage;Immunogenic cell death;Immunotherapy;Mild hyperthermia;Oxaliplatin
期刊:
CANCER BIOMARKERS,2023年38(2):225-239 ISSN:1574-0153
通讯作者:
Zeng, Zhong;Huang, HF
作者机构:
[Li, Zhitao; Zeng, Zhong; Li, Na; Huang, Hanfei; Wei, Benkai; Fang, Yuan; Jin, Li] Kunming Med Univ, Affiliated Hosp 1, Organ Transplantat Ctr, 295 Xichang Rd, Kunming 650032, Yunnan, Peoples R China.;[Tang, Weiqiang] Univ South China, Hengyang Med Sch, Inst Clin Med, Affiliated Hosp 1, Hengyang, Hunan, Peoples R China.;[Zhao, Dan] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, Lab Oncogenes & Related Genes,Sch Med, Shanghai, Peoples R China.;[Zhang, Xiaoli] Kunming Med Univ, Gastrointestinal & Hernia Surg, Affiliated Hosp 1, Kunming, Yunnan, Peoples R China.;[Yang, Yang] Baoshan Peoples Hosp, Otorhinolaryngol Head & Neck Surg, Baoshang, Yunnan, Peoples R China.
通讯机构:
[Zeng, Z; Huang, HF ] K;Kunming Med Univ, Affiliated Hosp 1, Organ Transplantat Ctr, 295 Xichang Rd, Kunming 650032, Yunnan, Peoples R China.
关键词:
DNA methylation;HELLS;immune;liver hepatocellular carcinoma;prognosis;tumor-infiltrating
摘要:
BACKGROUND: Lymphoid-specific helicase (HELLS), a SNF2-like chromatin-remodeling enzyme, plays a key role in tumor progression via its DNA methylation function. However, the effects of HELLS on immune infiltration and prognosis in liver hepatocellular carcinoma (LIHC) remain uncertain. METHODS: The Tumor Immune Estimation Resource (TIMER) database was employed to explore the pan-cancer mRNA expression of HELLS and its correlation with immunity. GEPIA2 was used to verify the correlation between HELLS expression and survival. The role of HELLS in cancer was explored via gene set enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) and the construction of gene-gene and protein-protein interaction networks (PPI). Additionally, correlations between DNA methylation, HELLS expression, and immune-related genes were explored in LIHC. HELLS expression in LIHC clinical samples was determined using qRT-PCR and western blotting. The effects of downregulated HELLS expression in hepatocellular carcinoma cells was explored via transfection experiments in vitro. RESULTS: High HELLS mRNA expression was identified in several cancers and was significantly associated with poorer prognosis in LIHC. Furthermore, HELLS expression was positively correlated with tumor-infiltrating lymphocytes and immune checkpoint genes in LIHC. Bioinformatics analysis suggested that DNA methylation of HELLS may be associated with the immune response. Results from the TCGA-LIHC dataset, clinical samples, and functional analysis indicated that HELLS contributed to tumor progression in LIHC. CONCLUSION: The study findings demonstrate that HELLS is an important factor in promoting LIHC malignancy and might serve as a potential biomarker for LIHC.
作者机构:
[Fu, Yuting; Jiang, Binyuan; Yuan, Yeqin] Univ South China, Affiliated Changsha Cent Hosp, Med Res Ctr, Hengyang Med Sch, Changsha 410004, Peoples R China.;[Zhou, Ziwei; Long, Huizhi] Univ South China, Sch Pharm, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Jiang, Binyuan] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Peoples R China.
通讯机构:
[Binyuan Jiang] M;Medical Research Center, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China<&wdkj&>Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China<&wdkj&>Author to whom correspondence should be addressed.
关键词:
breast cancer;clinical trial drugs;natural products;PI3K–AKT pathway
摘要:
Glioblastoma multiform (GBM), one of the most common, aggressive primary brain tumours, demonstrates resistance to radiotherapy and chemotherapy after surgical resection and treatment failure. Metformin (MET) has been shown to suppress the proliferative capacity and invasion ability of GBM cells by activating AMPK and inhibiting mTOR, but the effective dose exceeded the maximum tolerated dose. Artesunate (ART) can exert certain anti-tumour effects by activating the AMPK-mTOR axis and inducing autophagy in tumour cells. Therefore, this study investigated the effects of MET combined with ART combination therapy on autophagy and apoptosis in GBM cells. MET combined with ART treatment effectively suppressed the viability, mono-cloning ability, migration and invasion capacities, as well as metastatic ability of GBM cells. The underlying mechanism involved modulation of the ROS-AMPK-mTOR axis, which was confirmed using 3-methyladenine and rapamycin to inhibit or promote the effects of MET combined with ART, respectively. The study findings suggest that MET used in combination with ART can induce autophagy-dependent apoptosis in GBM cells by activating the ROS-AMPK-mTOR pathway, providing a potential new treatment for GBM.
作者机构:
[Yang, Qinglai; He, Yuxuan] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Tang, Li; Yang, Qinglai; Li, Na; Tan, Xiaofeng; He, Yuxuan; Yang, Sha] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang Med Sch,Ctr Mol Imaging Probe, Hengyang 421001, Peoples R China.;[Tang, Li] Hainan Normal Univ, Coll Chem & Chem Engn, Key Lab Trop Med Plant Chem, Minist Educ, Haikou 571158, Peoples R China.
通讯机构:
[Qinglai Yang] D;Department of Biochemistry and Molecular Biology, Hengyang Medica School, University of South China, Hengyang 421001, China<&wdkj&>Center for Molecular Imaging Probe, Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Author to whom correspondence should be addressed.
摘要:
In recent years, pathogenic infections have been a growing health threat due to the proliferation of drug-resistant bacteria, so photothermal therapy (PTT) has gained considerable interest in biological and medical fields, owing to its noninvasive and highly effective properties. However, it is hard to achieve selective bacteria targeting while generating a large amount of heat at infected sites. Cationic electrostatic interaction is considered to be a common antimicrobial strategy. Herein, an organic molecule named RT-MN was synthesized with four positively charged quaternary ammonium salts that can bind to negatively charged bacteria. Under near-infrared 808 nm laser irradiation, RT-MN could be efficiently converted into a large amount of heat to eradicate bacteria. In addition, its good water solubility and biological safety proved that RT-MN has excellent biological application prospects. Overall, four such positively charged photosensitizer RT-MN, as a non-antibiotic treatment for resistant bacteria, could be promising for the exploration of highly effective antibacterial agents.
作者:
Zhao, Lan;Luo, Jun-Li;Ali, Mohammed Khadem;Spiekerkoetter, Edda;Nicolls, Mark R.
期刊:
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY,2023年68(3):245-255 ISSN:1044-1549
通讯作者:
Nicolls, Mark R
作者机构:
[Spiekerkoetter, Edda; Zhao, Lan; Ali, Mohammed Khadem; Nicolls, Mark R.] Stanford Univ, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, 1701 Page Mill Rd, Palo Alto, CA 94304 USA.;[Spiekerkoetter, Edda; Zhao, Lan; Ali, Mohammed Khadem; Nicolls, Mark R.] Stanford Univ, Sch Med, Vera Moulton Wall Ctr Pulm Vasc Dis, Stanford, CA 94305 USA.;[Zhao, Lan; Nicolls, Mark R.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.;[Luo, Jun-Li] Univ South China, Hengyang Med Sch, Canc Res Inst, Hengyang, Peoples R China.
摘要:
Background The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear. Objective This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells. Methods To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure. Results The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE. Conclusion This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.
摘要:
Atherosclerosis (AS), a chronic vascular inflammatory disease, has become a main focus of attention worldwide for its chronic progressing disease course and serious complications in the later period. Nevertheless, explanations for the exact molecular mechanisms of AS initiation and development remain to be an unsolved problem. The classic pathogenesis theories, such as lipid percolation and deposition, endothelium injury, inflammation and immune damage, provide the foundation for discovering the new key molecules or signaling mechanisms. Recently, indoxyl sulfate (IS), one of non-free uremia toxins, has been noticeable for its multiple atherogenic effects. IS exists at high concentration in plasma for its great albumin binding rate. Patients with uremia have markedly elevated serum levels of IS due both to the deterioration of renal function and to the high binding affinity of IS to albumin. Nowadays, elevated incidence of circulatory disease among patients with renal dysfunction indicates correlation of uremic toxins with cardiovascular damage. In this review, the atherogenic effects of IS and the underlying mechanisms are summarized with emphasis on several key pathological events associated with AS developments, such as vascular endothelium dysfunction, arterial medial lesions, vascular oxidative stress, excessive inflammatory responses, calcification, thrombosis and foam cell formation. Although recent studies have proved the great correlation between IS and AS, deciphering cellular and pathophysiological signaling by confirming key factors involved in IS-mediated atherosclerosis development may enable identification of novel therapeutic targets.