摘要：
A novel near-infrared induced upconversion sensor for the detection of uranyl ions was successfully constructed using (beta-NaYF4: Yb, Tm, Gd upconversion nanoparticles (UCNPs) and specific DNAzyme. Characterization of the UCNPs@DNAzyme was conducted using XRD, TEM, FT-IR and fluorescence testing, and it was shown that the (beta-NaYF4: Yb, Tm, Gd nanoparticles were successfully prepared (similar to 27 nm). Upon 980 nm excitation, the UCNPs@DNAzyme emitted green light at lambda = 475 nm. Furthermore, Forster resonance energy transfer was observed between the UCNPs@DNAzyme (doner) and uranyl (acceptor) present on the substrate chain. This resulted in fluorescence quenching, which was used to quantify the concentration of uranyl. The developed method was found to be highly selective and sensitive, with a detection limit as low as 43 nM. This method also demonstrated excellent specificity and sensitivity for the determination of uranyl in water samples, indicating its potential application in near-infrared fluorescence detection and imaging of uranyl in vivo.
作者机构：
[Yang, Shengyuan; Tan, Yan; Su, Wenen; Liu, Jinquan; Fan, Pengfei; Li, Qianji] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Hunan, Peoples R China.;[Wu, Xiwen] Yueyang Cty Ctr Dis Control & Prevent, Yueyang 414100, Hunan, Peoples R China.;[Zhang, Xiaohuan] Yongding Dist Ctr Dis Control & Prevent, Zhangjiajie 427000, Hunan, Peoples R China.
通讯机构：
[Li, Qianji] D;Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
作者机构：
[Feng, Jie; Yang, Lichen; Cao, Yang; Shan, Xiaoyun; Lu, Jiaxi; Wang, Lijuan] Chinese Ctr Dis Control & Prevent, Key Lab Trace Element Nutr Natl Hlth Comm, Natl Inst Nutr & Hlth, Beijing 100050, Peoples R China.;[Shan, Xiaoyun] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 241001, Peoples R China.
通讯机构：
[Lichen Yang] K;Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China<&wdkj&>Author to whom correspondence should be addressed.
关键词：
iron storage biomarkers;type 2 diabetes mellitus;association;women of childbearing age
摘要：
High iron stores have been reported to be associated with type 2 diabetes mellitus (T2DM). However, evidence for the associations of iron metabolism with T2DM is inconsistent, and whether there is a threshold effect remains controversial. In the present study, we aimed to examine the associations between various iron biomarkers and the risk of T2DM as well as impaired glucose metabolism (IGM) and hyperglycemia in Chinese women of childbearing age. A total of 1145 women were divided into three groups (normal blood glucose metabolism group; IGM group; T2DM group). Biomarkers of iron metabolism (serum ferritin (SF), transferrin, soluble transferrin receptor (sTfR), transferrin saturation, serum iron, total body iron, and sTfR-to-lgferritin index) were measured. After adjusting for various confounding risk factors, SF and sTfR were positively associated with the risk of IGM (fourth vs. first quartile: SF odds ratio (OR) = 1.93 (95% CI 1.17–3.20) and sTfR OR = 3.08 (95% CI 1.84–5.14)) and T2DM (SF OR = 2.39 (95% CI 1.40–4.06) and sTfR OR = 3.84 (95% CI 2.53–5.83)). There was a nonlinear relationship between SF and risk of T2DM and hyperglycemia (p for nonlinearity < 0.01). Our findings suggested that SF and sTfR could be independent predictors of T2DM risk.
通讯机构：
[Wang F.] T;The Second Affiliated Hospital, The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China<&wdkj&>The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China
摘要：
<b><i>Background:</i></b> Cardiovascular disease (CVD) remains the leading cause of disease burden worldwide. Ferroptosis, an iron-dependent form of programmed cell death, is characterized by the lethal accumulation of lipid peroxidation, which is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and pyroptosis. Emerging evidence provides exciting novel insights to allow for a deeper understanding of the physiology and pathology of ferroptosis in CVD. <b><i>Summary:</i></b> The rapidly evolving insights into ferroptosis have revealed its role in the pathogenesis of diverse forms of CVD, including cardiomyopathy, heart failure, atherosclerosis, pulmonary arterial hypertension, and cerebrovascular disease. Various types of metabolic pathways are involved in the regulation of ferroptosis, including iron metabolism, lipid metabolism, and redox metabolism. Modulators of ferroptosis, such as several clinical drugs, preclinical compounds, and other emerging materials, have been applied as promising approaches in the prevention and treatment of CVD. <b><i>Key Message:</i></b> In this review, we provide a 360 degree view of the latest progress in the field of ferroptosis in CVD, highlight the pathogenic role of ferroptosis in CVD, and also discuss the importance and future directions of targeting ferroptosis in CVD.
通讯机构：
[Liang, GY ] S;Southeast Univ, Minist Educ, Sch Publ Hlth, Key Lab Environm Med Engn, Nanjing, Peoples R China.
关键词：
AOP;Hepatotoxicity;MNPLs;New toxicological methodologies;Organoids and organ-on-chips;“Trojan horse” effect
摘要：
Plastic pollution has become a significant global problem over the years, leading to the continuous decomposition and accumulation of micro/nanoplastics (MNPLs) in the environment. As a result, human exposure to these MNPLs is inevitable. The liver, in particular, is highly susceptible to potential MNPL toxicity. In this study, we systematically reviewed the current literature on MNPLs-induced hepatotoxicity and collected data on toxic events occurring at different biological levels. Then, to better understand the cause-mechanism causality, we developed an Adverse Outcome Pathway (AOP) framework for MNPLs-induced hepatotoxicity. The AOP framework provided insights into the mechanism of MNPL-induced hepatotoxicity and highlighted potential health risks such as liver dysfunction and inflammation, metabolism disorders and liver fibrosis. Moreover, we discussed the potential application of emerging toxicological models in the hepatotoxicity study. Liver organoids and liver-on-chips, which can simulate the structure and function of the liver in vitro, offer a promising alternative platform for toxicity testing and risk assessment. We proposed combining the AOP framework with these emerging toxicological models to improve our understanding of the hepatotoxic effects of MNPLs. Overall, this study performed a preliminary exploration of novel toxicological methodologies to assess the hepatotoxicity of MNPLs, providing a deeper understanding of environmental toxicology.
作者机构：
[Qin, Xinru; Liu, Xiaocheng; Li, Guojuan; Tang, Yonghong; Rang, Ouyan; Wang, Mu; Cao, Lin] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Mass Spectrometry Lab,Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Qin, Xinru; Liu, Xiaocheng; Li, Guojuan; Tang, Yonghong; Rang, Ouyan; Wang, Mu; Cao, Lin] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Basic Med,Nucl Ind Hyg Sch, Hengyang 421001, Hunan, Peoples R China.;[Qin, Xinru] Univ South China, Sch Publ Hlth, Hengyang 421001, Hunan, Peoples R China.;[Zhong, Jing; Zhong, J] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Canc Res Inst,Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhong, J ; Wang, M ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Mass Spectrometry Lab,Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Basic Med,Nucl Ind Hyg Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Canc Res Inst,Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.
摘要：
The consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.
作者机构：
[Peng, Yousong; You, Ruina; Ma, Huan; Tuo, Chaohao; Li, Huiru; Zhu, Zhaozhong; Meng, Xiangxian] Hunan Univ, Coll Biol, Changsha, Peoples R China.;[Zhu, Zhaozhong; Feng, Shuidong] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Feng, Shuidong; Feng, Song] Cent South Univ, Xiangya Hosp, Changsha, Peoples R China.
通讯机构：
[Peng, YS ] H;[Feng, S ] C;Hunan Univ, Coll Biol, Changsha, Peoples R China.;Cent South Univ, Xiangya Hosp, Changsha, Peoples R China.
关键词：
Bioinformatics;Influenza virus;Multi-omics data
摘要：
Influenza viruses pose a significant and ongoing threat to human health. Many host factors have been identified to be associated with influenza virus infection. However, there is currently a lack of an integrated resource for these host factors. This study integrated human genes and proteins associated with influenza virus infections for 14 subtypes of influenza A viruses, as well as influenza B and C viruses, and built a database named H2Flu to store and organize these genes or proteins. The database includes 28,639 differentially expressed genes (DEGs), 1,850 differentially expressed proteins, and 442 proteins with differential posttranslational modifications after influenza virus infection, as well as 3,040 human proteins that interact with influenza virus proteins and 57 human susceptibility genes. Further analysis showed that the dynamic response of human cells to virus infection, cell type and strain specificity contribute significantly to the diversity of DEGs. Additionally, large heterogeneity was also observed in protein-protein interactions between humans and different types or subtypes of influenza viruses. Overall, the study deepens our understanding of the diversity and complexity of interactions between influenza viruses and humans, and provides a valuable resource for further studies on such interactions.
作者机构：
[Yang, Fei; Veerabadhran, Maruthanayagam] Univ South China, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.;[Veerabadhran, Maruthanayagam] Cent South Univ, Xiangya Sch Publ Hlth, Hunan Prov Key Lab Clin Epidemiol, Hunan 410078, Peoples R China.;[Manivel, Nagarajan] ICAR Cent Marine Fisheries Res Inst, Chennai 6000028, India.;[Sarvalingam, Barathkumar] Minist Earth Sci, Natl Ctr Coastal Res NCCR, NIOT Campus, Chennai 600100, India.;[Seenivasan, Boopathi] SRM Inst Sci & Technol, Coll Sci & Humanities, Dept Biotechnol, Chennai, India.
通讯机构：
[MubarakAli Davoodbasha] S;[Fei Yang] H;School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600 0048, India<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang, China
通讯机构：
[Tao, L.; Luo, C.] D;[Wang, F.] T;Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou, 215123, China
摘要：
Although traumatic brain injury (TBI) is a common cause of death and disability worldwide, there is currently a lack of effective therapeutic drugs and targets. To reveal the complex pathophysiologic mechanisms of TBI, we performed transcriptome analysis of the mouse cerebral cortex and immunohistochemical analysis of human cerebral tissues. The genes Mt1, Mt2, Il33, and Fth1 were upregulated post-TBI and enriched in pathways associated with the inflammatory response, oxidative phosphorylation, and ferroptosis. As an agonist of MT1/2, melatonin (MLT) confers anti-oxidant, anti-inflammatory, and anti-ferroptosis effects after TBI. However, whether these upregulated genes and their corresponding pathways are involved in the neuroprotective effect of MLT remains unclear. In this study, interventions to inhibit MT1/2, IL-33, and ferroptosis (i.e., ferritin H (Fth)-KO) were applied post-TBI. The results showed that MLT attenuated TBI-induced cerebral edema and neurological outcomes by inhibiting inflammation and ferroptosis. Mechanistically, MLT mainly suppressed inflammatory responses and ferroptosis via the activation of MT2 and IL-33 pathways. Building on the previous finding that Fth deletion increases susceptibility to ferroptosis post-TBI, we demonstrated that Fth depletion remarkably exacerbated the post-TBI inflammatory response, and abolished the anti-inflammatory effects of MLT both in vivo and in vitro. Furthermore, the post-TBI anti-inflammatory effect of MLT, which occurs by promoting the polarization of CD206(+) macrophages, was dependent on Fth. Taken together, these results clarified that MLT alleviates inflammation- and ferroptosis-mediated brain edema and neurological deficits by activating the MT2/IL-33/Fth pathway, which provides a novel target and theoretical basis for MLT to treat TBI patients.
关键词：
"On-off";Self-powered biosensor;Enzymatic biofuel cells;Capture and release
摘要：
A “on–off” self-powered biosensor was developed based on enzymatic biofuel cells (EBFCs) for sequential detection of microRNA-21 (miRNA-21) and miRNA-155 by capture and release of a single-bioanode enzyme, i.e., glucose oxidase. When miRNA-21 is present, it hybridizes with DNA1 and the glucose oxidase (GOD)-modified DNA2, i.e., DNA2-GOD. Then, GOD oxidizes glucose to produce a large number of electrons, and a significantly increased open-circuit voltage (E1OCV) is observed, corresponding to the “on” state. If miRNA-155 is present, it hybridizes with DNA1 and DNA3-functionalized SiO2 [email protected] nanoparticles, i.e., SiO2@AuNPs-DNA3, and replaces miRNA-21 to release GOD at the bioanode, thus leading to decreased E2OCV, corresponding to the “off” state. The “on–off” self-powered biosensor shows ultra-sensitive detection of miRNA-21 and miRNA-155 with detection limits of 0.17 fM and 0.37 fM, respectively. It is believed that this study provides a feasible model for designing self-powered biosensors for multi-targets detection.
作者：
Cao, Wandi;Liu, Mingkang;Wang, Canyang;Jing, Guoxing;Cao, Yi
期刊：
Journal of Applied Toxicology,2023年43(5):706-718 ISSN：0260-437X
通讯作者：
Guoxing Jing<&wdkj&>Yi Cao
作者机构：
[Liu, Mingkang; Jing, Guoxing; Cao, Wandi] Xiangtan Univ, Sch Chem Engn, Xiangtan, Peoples R China.;[Wang, Canyang; Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.;[Jing, Guoxing] Xiangtan Univ, Sch Chem Engn, Xiangtan 511105, Peoples R China.;[Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
通讯机构：
[Guoxing Jing] S;[Yi Cao] H;School of Chemical Engineering, Xiangtan University, Xiangtan, China<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China
关键词：
3D Caco-2 spheroids;Kruppel-like factors (KLFs);mouse intestines;RNA-sequencing;TiO2 nanoparticles (NPs)
摘要：
Kruppel-like factors (KLFs) are a set of transcription factors (TFs) involved in the regulation of many basic biological processes, and recent studies suggested that nanoparticles (NPs) were capable to change KLFs in different models even at non-cytotoxic concentrations. In this study, we repeatedly exposed 3D Caco-2 spheroids and mice to TiO(2) NPs, one of the most frequently used metal oxide NPs, and investigated the changes of KLF-signaling pathways based on RNA-sequencing. Although the internalization of TiO(2) NPs did not induce cytotoxicity in vitro, repeated exposure (three times within 7 days) to 15.7 ng/ml TiO(2) NPs increased KLF4 but decreased KLF6. Consistently, KLF4/KLF6-regulated gene ontology terms were altered, including those involved in the regulation of gene expression. We further verified that repeated exposure to 15.7 ng/ml TiO(2) NPs increased the expression of KLF4 and proto-oncogene, bHLH transcription factor (MYC), but decreased the expression of KLF6 and activating transcription factor 3 (ATF3). But with the increase of NP concentrations, the expression of these genes was decreased. In mice following intragastrical exposure to 4.39 and 43.9 mg/kg TiO(2) NPs (once a day for 5 continuous days), we observed increased expression of klf4, klf6, myc, and atf3, along with morphological changes of intestines. We concluded that repeated exposure to low levels of TiO(2) NPs altered KLF-signaling pathways in intestinal cells both in vitro and in vivo.
期刊：
Journal of Hazardous Materials,2023年451:131110 ISSN：0304-3894
通讯作者：
Fei Yang
作者机构：
[Feng, Xiangling; Chen, Jihua; Liu, Wenya; Yang, Fei; Yang, Yue; Chen, Mengshi] Cent South Univ, Xiangya Sch Publ Hlth, Hunan Prov Key Lab Clin Epidemiol, Changsha, Peoples R China.;[Wang, Hui; Deng, Shuxiang; Chu, Hanyu; Cao, Yi; Liu, Ying; Long, Dingxin; Cai, Danping; Cao, Deliang; Yang, Fei] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.;[Wang, Xiaoyan] Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China.;[Chen, Ling] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang, Peoples R China.;[Wang, Chengkun] Univ South China, Sch Basic Med, Hengyang Med Sch, Dept Med Pathol, Hengyang, Peoples R China.
通讯机构：
[Fei Yang] H;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, China<&wdkj&>Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
作者机构：
[Long, Xizi] Univ South China, Sch Key Lab Typ Environm Pollut & Hlth Hazards Hun, Sch Basic Med, Sch Publ Hlth,Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Tokunou, Yoshihide; Long, Xizi; Okamoto, Akihiro] Int Ctr Mat Nanoarchitecton WPI MANA, Natl Inst Mat Sci, Tsukuba, Ibaraki 3050044, Japan.;[Tokunou, Yoshihide] Univ Tsukuba, Fac Life & Environm Sci, Tsukuba, Ibaraki 3058577, Japan.;[Okamoto, Akihiro] Hokkaido Univ, Grad Sch Chem Sci & Engn, Sapporo, Hokkaido 0608628, Japan.
通讯机构：
[Akihiro Okamoto] I;International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan<&wdkj&>Graduate School of Chemical Sciences and Engineering, Hokkaido University, North 13 West 8, Kitaku, Sapporo, Hokkaido 060-8628, Japan
关键词：
circular dichroism;electron transport;exciton coupling;mechanobiology;multi-heme cytochrome C
摘要：
Holmium (Ho) modified TiO2 (Ho-TiO2) nanocomposites have been prepared by a sol-gel process, and Copyright: American Scientific Publishers were used as an effective adsorbent and matrix for the erichment and analysis of bisphenol S and Indigo Delivered by Ingenta by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The low detection limits of bisphenol S (BPS) and Indigo (ID) are 0.1 pg center dot mL-1 and 5 pg center dot mL-1, respectively. Extremely BPS detection could be achieved in tea samples with good recovery (81.5-93.0%).
期刊：
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2023年 ISSN：0021-972X
通讯作者：
Zheng, MH;Valenti, L
作者机构：
[Liu, Wen-Yue] Wenzhou Med Univ, Affiliated Hosp 1, Dept Endocrinol, Wenzhou 325000, Peoples R China.;[Liu, Wen-Yue] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou Key Lab Diabet Res, Wenzhou 325000, Peoples R China.;[Zhang, Ni; Lian, Li-You; Ye, Chen-Hui; Zheng, Ming-Hua; Chen, Wen-Ying] Wenzhou Med Univ, Affiliated Hosp 1, MAFLD Res Ctr, Dept Hepatol, Wenzhou 325000, Peoples R China.;[Zhang, Ni; Lian, Li-You; Ye, Chen-Hui; Zheng, Ming-Hua; Chen, Wen-Ying] Wenzhou Med Univ, Inst Hepatol, Wenzhou 325000, Peoples R China.;[Zhang, Ni; Lian, Li-You; Ye, Chen-Hui; Zheng, Ming-Hua; Chen, Wen-Ying] Key Lab Diag & Treatment Dev Chron Liver Dis, Wenzhou, Zhejiang, Peoples R China.
通讯机构：
[Zheng, MH ] W;[Valenti, L ] U;Wenzhou Med Univ, Affiliated Hosp 1, MAFLD Res Ctr, Dept Hepatol, 2 Fuxue Lane, Wenzhou 325000, Peoples R China.;Univ Milan, Dept Pathophysiol & Transplantat, Via Festa Perdono 7, I-20121 Milan, Italy.
关键词：
Iron overload;Metabolic dysfunction-associated fatty liver disease;Metabolic hyperferritinemia;Metabolic syndrome
摘要：
BACKGROUND: There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. We aimed to validate the clinical outcomes of MHF in general population and biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) patients. METHODS: NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males] - 550 ng/ml; grade 2: 550 - 1000 ng/ml; grade 3: > 1000 ng/ml). The clinical outcomes, including all-cause death, comorbidities and liver histology were compared between non-MHF and MHF in adjusted models. RESULTS: In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (FIB-4, P = 0.036), elevated albumin-creatinine ratio (UACR, P = 0.001) and sarcopenia (P = 0.013). Although the association between all grades of MHF and mortality was insignificant (P = 0.122), grades 2/3 was associated with increased mortality (P = 0.029). While comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P < 0.001), elevated UACR (P < 0.001), cardiovascular disease (P = 0.028), and sarcopenia (P < 0.001). In PERSONS cohort, MHF was associated with more advanced grades of steatosis (P < 0.001), lobular inflammation (P < 0.001), advanced fibrosis (P = 0.017), and more severe hepatocellular iron deposition (P < 0.001). CONCLUSIONS: Both in general population and at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes.
摘要：
Pulmonary fibrosis represents the advanced phase of diverse pulmonary ailments, and at present, a definitive cure for these ailments is lacking. Furthermore, underlying mechanisms causative of these ailments remain elusive. Macrophages are immune cells that resist external stimuli in the early stages after birth. These cells can polarize into the classically (M1) and alternatively (M2) activated macrophages. When stimulated owing to the presence of toxic factors, M1 macrophages produce several pro-inflammatory factors, which mediate the inflammatory injury response of the alveolar tissue. The secretion of diverse growth factors by M2 macrophages contributes to the pathogenesis of aberrant alveolar structural fibrosis and remodeling. The abnormal activity of M2 macrophages is considered a critical factor in the formation of pulmonary fibrosis. In this mini-review, to highlight the clinical implications of research studies, we summarize the role and therapeutic targets of polarized subtypes of macrophages in pulmonary fibrosis and the role of targeting macrophages for the treatment of pulmonary fibrosis. M1-type macrophages and M2-type macrophages can transform into each other.M1-type macrophages participate in the early stage of pulmonary fibrosis by producing inflammatory cytokines, ROS and MMP.M2-type macrophages mediate abnormal alveolar tissue repair and tissue remodeling through the production of TGF-& beta;, FGF, and exosomes.Three therapeutic ideas were summarized in this paper: inhibition of the number and activity of lung macrophages, inhibition of M2-type macrophage polarization, inhibition of TGF-& beta; expression and its signalling pathway.
作者机构：
[Min, Junxia; Yu, Yingying; Wang, Fudi; Cheng, Xihao; Su, Yunxing; Wu, Xiaotian; Cai, Zhaoxian; Song, Zijun; Yu, Chao; Min, JX; Sun, Shumin] Zhejiang Univ, Affiliated Hosp 2, Affiliated Hosp 1, Inst Translat Med,Sch Publ Hlth,Canc Ctr,Sch Med, Hangzhou, Zhejiang, Peoples R China.;[Wang, Fudi; Wang, Tianyi; Cai, Zhaoxian] Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang, Hunan, Peoples R China.;[Chen, Wenteng; Yu, Yongping; Chen, En] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China.;[Linkermann, Andreas] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Internal Med 3, Div Nephrol, Dresden, Germany.;[Linkermann, Andreas] Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY USA.
通讯机构：
[Wang, FD ; Min, JX] Z;Zhejiang Univ, Affiliated Hosp 2, Affiliated Hosp 1, Inst Translat Med,Sch Publ Hlth,Canc Ctr,Sch Med, Hangzhou, Zhejiang, Peoples R China.;Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang, Hunan, Peoples R China.
摘要：
Given the rapidly aging population, aging-related diseases are becoming an excessive burden on the global healthcare system. Metformin has been shown to be beneficial to many age-related disorders, as well as increase lifespan in preclinical animal models. During the aging process, kidney function progressively declines. Currently, whether and how metformin protects the kidney remains unclear. In this study, among longevity drugs, including metformin, nicotinamide, resveratrol, rapamycin, and senolytics, we unexpectedly found that metformin, even at low doses, exacerbated experimentally-induced acute kidney injury (AKI) and increased mortality in mice. By single-cell transcriptomics analysis, we found that death of renal parenchymal cells together with an expansion of neutrophils occurs upon metformin treatment after AKI. We identified programmed cell death by ferroptosis in renal parenchymal cells and blocking ferroptosis, or depleting neutrophils protects against metformin-induced nephrotoxicity. Mechanistically, upon induction of AKI, ferroptosis in renal parenchymal cells initiates the migration of neutrophils to the site of injury via the surface receptor CXCR4-bound to metformin-iron-NGAL complex, which results in NETosis aggravated AKI. Finally, we demonstrated that reducing iron showed protective effects on kidney injury, which supports the notion that iron plays an important role in metformin-triggered AKI. Taken together, these findings delineate a novel mechanism underlying metformin-aggravated nephropathy and highlight the mechanistic relationship between iron, ferroptosis, and NETosis in the resulting AKI.
