摘要：
Metabolic syndrome (MS) has become a health concern worldwide. Gut microbiota and metabolites play an important role in human health. The pathogenesis of gut microbiota and their metabolites in the development of metabolic syndrome (MS) remains unclear. This study aimed to evaluate the signatures of gut microbiota and metabolites as well as their functions in obese children with MS. A case-control study was conducted based on 23 MS children and 31 obese controls. The gut microbiome and metabolome were measured using 16S rRNA gene amplicon sequencing and liquid chromatography-mass spectrometry. An integrative analysis was conducted, combining the results of the gut microbiome and metabolome with extensive clinical indicators. The biological functions of the candidate microbial metabolites were validated in vitro. We identified 9 microbiota and 26 metabolites that were significantly different from the MS and the control group. The clinical indicators of MS were correlated with the altered microbiota Lachnoclostridium, Dialister, and Bacteroides, as well as with the altered metabolites all-trans-13,14-dihydroretinol, DL-dipalmitoylphosphatidylcholine (DPPC), LPC 24: 1, PC (14:1e/10:0), and 4-phenyl-3-buten-2-one, etc. The association network analysis further identified three MS-linked metabolites, including all-trans-13,14-dihydroretinol, DPPC, and 4-phenyl-3-buten-2-one, that were significantly correlated with the altered microbiota. Bio-functional validation showed that all-trans-13, 14-dihydroretinol could significantly upregulate the expression of lipid synthesis genes and inflammatory genes. This study identified a new biomarker that may contribute to MS development. These findings provided new insights regarding the development of efficient therapeutic strategies for MS. IMPORTANCE Metabolic syndrome (MS) has become a health concern worldwide. Gut microbiota and metabolites play an important role in human health. We first endeavored to comprehensively analyze the microbiome and metabolome signatures in obese children and found the novel microbial metabolites in MS. We further validated the biological functions of the metabolites in vitro and illustrated the effects of the microbial metabolites on lipid synthesis and inflammation. The microbial metabolite all-trans-13, 14-dihydroretinol may be a new biomarker in the pathogenesis of MS, especially in obese children. These findings were not available in previous studies, and they provide new insights regarding the management of metabolic syndrome.
作者机构：
[Zheng, Xingyu; Qu, Xiaowang; He, Rongzhang; Liu, Wenpei] Univ South China, Hengyang Med Sch, Coll Basic Med Sci, Hengyang 421001, Peoples R China.;[Zheng, Xingyu; Qu, Xiaowang; He, Rongzhang; Liu, Wenpei] MOE Key Lab Rare Pediat Dis, Hengyang 421001, Peoples R China.;[Zheng, Xingyu; Zhang, Jian; Wang, You; Pan, Dong; Liu, Ziyan; Liu, Bo; Lu, Rui; Chen, Jun; Wu, Qian; Qu, Xiaowang; Teng, Shishan; Peng, Liting; He, Rongzhang; Hu, Yabin; Yang, Jing; Liu, Wenpei] Univ South China, Translat Med Inst, Peoples Hosp Chenzhou 1, Chenzhou 423000, Peoples R China.;[Xie, Ting; Wang, Qijie] Cent Hosp Shaoyang, Shaoyang 422000, Peoples R China.;[Liu, Yongchen; Li, Yi-Ping; Chang, Fangfang; Wu, Qian; Li, YP] Sun Yat Sen Univ, Inst Human Virol, Zhongshan Sch Med, Guangzhou 501180, Peoples R China.
通讯机构：
[Qu, XW ] U;[Li, YP ] S;[Wang, YC ] N;Univ South China, Hengyang Med Sch, Coll Basic Med Sci, Hengyang 421001, Peoples R China.;MOE Key Lab Rare Pediat Dis, Hengyang 421001, Peoples R China.
摘要：
Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb) and B cell differentiation are tightly regulated by T follicular help (T(FH)) cells. However, the longevity and functional role of T(FH) cell subsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection and inactivated vaccine elicited both spike-specific CXCR3(+) T(FH) cell and CXCR3(-) T(FH) cell responses, which showed distinct response patterns. Spike-specific CXCR3(+) T(FH) cells exhibit a dominant and more durable response than CXCR3(-) T(FH) cells that positively correlated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3(+) T(FH) cell subset induced by two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3(+) T(FH) cells have a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3(-) T(FH) cells. In conclusion, the persistent and functional role of spike-specific CXCR3(+) T(FH) cells following SARS-CoV-2 infection and vaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. The findings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immune memory.
关键词：
DNA damage response;PARP1;chromatin accessibility;m(6)A methylation;radiosensitivity
摘要：
Chromatin remodeling and N(6)-methyladenosine (m(6)A) modification are two critical layers in controlling gene expressionand DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m(6)A methylation of poly(A)(+) RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, suppressed METTL3 expression and RNA m(6)A methylation. Lysophosphatidic Acid Receptor 5(LPAR5) mRNA was identified as a target of METTL3, and m(6)A methylation was located at A1881. The level of m(6)A methylation of LPAR5 significantly decreased, along with METTL3 depression, in cells after irradiation or PARP1 inhibition. Mutation of the LPAR5 A1881 locus in its 3' UTR results in loss of m(6)A methylation and, consequently, decreased stability of LPAR5 mRNA. METTL3-targeted small-molecule inhibitors depress murine xenograft tumor growth and exhibit a synergistic effect with radiotherapy invivo. These findings advance our comprehensive understanding of PARP-related biological roles, which may have implications for developing valuable therapeutic strategies for PARP1 inhibitors in oncology.
摘要：
Microcystin-LR (MC-LR) contamination is a worldwide environmental problem that poses a grave threat to the water ecosystem and public health. Exposure to MC-LR has been associated with the development of intestinal injury, but there are no effective treatments for MC-LR-induced intestinal disease. Probiotics are "live microorganisms that are beneficial to the health of the host when administered in sufficient quantities". It has been demonstrated that probiotics can prevent or treat a variety of human diseases; however, their ability to mitigate MC-LR-induced intestinal harm has not yet been investigated. The objective of this study was to determine whether probiotics can mitigate MC-LR-induced intestinal toxicity and its underlying mechanisms. We first evaluated the pathological changes in colorectal tissues using an animal model with sub-chronic exposure to low-dose MC-LR, HE staining to assess colorectal histopathologic changes, qPCR to detect the expression levels of inflammatory factors in colorectal tissues, and WB to detect the alterations on CSF1R signaling pathway proteins in colorectal tissues. Microbial sequencing analysis and screening of fecal microorganisms differential to MC-LR treatment in mice. To investigate the role of microorganisms in MC-LR-induced colorectal injury, an in vitro model of MC-LR co-treatment with microorganisms was developed. Our findings demonstrated that MC-LR treatment induced an inflammatory response in mouse colorectal tissues, promoted the expression of inflammatory factors, activated the CSF1R signaling pathway, and significantly decreased the abundance of Lactobacillus. In a model of co-treatment with MC-LR and Lactobacillus fermentum (L. fermentum), it was discovered that L. fermentum substantially reduced the incidence of the colorectal inflammatory response induced by MC-LR and inhibited the protein expression of the CSF1R signaling pathway. This is the first study to suggest that L. fermentum inhibits the CSF1R signaling pathway to reduce the incidence of MC-LR-induced colorectal inflammation. This research may provide an excellent experimental foundation for the development of strategies for the prevention and treatment of intestinal diseases in MC-LR.
作者机构：
[Wang, Xue; Min, Junxia; Wang, Fudi] Zhejiang Univ, Affiliated Hosp 2, Affiliated Hosp 1, Inst Translat Med,Sch Publ Hlth,State Key Lab Expt, Hangzhou 310058, Peoples R China.;[Wang, Xue; Wang, Fudi] Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang 421001, Peoples R China.;[Zhou, Ye] Ningbo First Hosp, Dept Endocrinol & Metab, Ningbo 315000, Peoples R China.
通讯机构：
[Junxia Min; Fudi Wang] 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, 310058, China.;The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China.
摘要：
Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation. In the past decade, it has been implicated in the pathogenesis of various diseases that together involve almost every organ of the body, including various cancers, neurodegenerative diseases, cardiovascular diseases, lung diseases, liver diseases, kidney diseases, endocrine metabolic diseases, iron-overload-related diseases, orthopedic diseases and autoimmune diseases. Understanding the underlying molecular mechanisms of ferroptosis and its regulatory pathways could provide additional strategies for the management of these disease conditions. Indeed, there are an expanding number of studies suggesting that ferroptosis serves as a bona-fide target for the prevention and treatment of these diseases in relevant pre-clinical models. In this review, we summarize the progress in the research into ferroptosis and its regulatory mechanisms in human disease, while providing evidence in support of ferroptosis as a target for the treatment of these diseases. We also discuss our perspectives on the future directions in the targeting of ferroptosis in human disease.
摘要：
Slc39a10 (Zip10), as a zinc transporter, plays an essential role in the survival of fetal hematopoietic stem/progenitor cells in both zebrafish and mice. Loss of Slc39a10 causes impaired hematopoiesis that can be rescued by zinc supplementation or inhibiting necroptosis. This study shows that Slc39a10 promotes the development of fetal hematopoietic stem cells by maintaining zinc homeostasis. Abstract The role of zinc in hematopoiesis is currently unclear. Here, SLC39A10 (ZIP10) is identified as a key zinc transporter in hematopoiesis. The results show that in zebrafish, Slc39a10 is a key regulator of the response to zinc deficiency. Surprisingly, both slc39a10 mutant zebrafish and hematopoietic Slc39a10‐deficient mice develop a more severe form of impaired hematopoiesis than animals lacking transferrin receptor 1, a well‐characterized iron gatekeeper, indicating that zinc plays a larger role than iron in hematopoiesis, at least in early hematopoietic stem cells (HSCs). Furthermore, it is shown that loss of Slc39a10 causes zinc deficiency in fetal HSCs, which in turn leads to DNA damage, apoptosis, and G1 cell cycle arrest. Notably, zinc supplementation largely restores colony formation in HSCs derived from hematopoietic Slc39a10‐deficient mice. In addition, inhibiting necroptosis partially restores hematopoiesis in mouse HSCs, providing mechanistic insights into the requirement for zinc in mediating hematopoiesis. Together, these findings indicate that SLC39A10 safeguards hematopoiesis by protecting against zinc deficiency‐induced necroptosis, thus providing compelling evidence that SLC39A10 and zinc homeostasis promote the development of fetal HSCs. Moreover, these results suggest that SLC39A10 may serve as a novel therapeutic target for treating anemia and zinc deficiency‐related disorders.
作者机构：
[Yu, Wenzhan; Xiao, Xilin] Univ South China, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;[Li, Qian; Liao, Lifu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.;[He, Liqiong; Zhou, Renlong; Xue, Jinhua] Univ South China, Sch Publ Hlth, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Jinhua Xue; Xilin Xiao] S;School of Public Health, University of South China, Hengyang 421001, Hunan, PR China<&wdkj&>School of Pharmaceutical Science, University of South China, Hengyang 421001, Hunan, PR China
通讯机构：
[Lili Chen] D;Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Hengyang Engineering Technology Research Center, Hengyang, China
摘要：
Helicobacter pylori is a kind of Gram-negative bacteria that parasitizes on human gastric mucosa. Helicobacter pylori infection is very common in human beings, which often causes gastrointestinal diseases, including chronic gastritis, duodenal ulcer and gastric cancer. MicroRNAs are a group of endogenous non-coding single stranded RNAs, which play an important role in cell proliferation, differentiation, autophagy, apoptosis and inflammation. In recent years, relevant studies have found that the expression of microRNA is changed after Helicobacter pylori infection, and then regulate the biological process of host cells. This paper reviews the regulation role of microRNAs on cell biological behavior through different signal pathways after Helicobacter pylori infection.
通讯机构：
[Shanshan Gao; Hua Guan] A;Authors to whom correspondence should be addressed.<&wdkj&>Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Beijing Key Laboratory for Radiobiology, Department of Radiation Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>Beijing Key Laboratory for Radiobiology, Department of Radiation Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China
摘要：
Mitochondrion is an important organelle of eukaryotic cells and a critical target of ionizing radiation (IR) outside the nucleus. The biological significance and mechanism of the non-target effect originating from mitochondria have received much attention in the field of radiation biology and protection. In this study, we investigated the effect, role, and radioprotective significance of cytosolic mitochondrial DNA (mtDNA) and its associated cGAS signaling on hematopoietic injury induced by IR in vitro culture cells and in vivo total body irradiated mice in this study. The results demonstrated that gamma-ray exposure increases the release of mtDNA into the cytosol to activate cGAS signaling pathway, and the voltage-dependent anion channel (VDAC) may contribute to IR-induced mtDNA release. VDAC1 inhibitor DIDS and cGAS synthetase inhibitor can alleviate bone marrow injury and ameliorate hematopoietic suppression induced by IR via protecting hematopoietic stem cells and adjusting subtype distribution of bone marrow cells, such as attenuating the increase of the F4/80(+) macrophage proportion in bone marrow cells. The present study provides a new mechanistic explanation for the radiation non-target effect and an alternative technical strategy for the prevention and treatment of hematopoietic acute radiation syndrome.
摘要：
Mycoplasma fermentans can cause respiratory diseases, arthritis, genitourinary tract infections, and chronic fatigue syndrome and have been linked to the development of the human immunodeficiency virus. Because mycoplasma lacks a cell wall, its outer membrane lipoproteins are one of the main factors that induce inflammation in the organism and contribute to disease development. Macrophage-activating lipopeptide-2 (MALP-2) modulates the inflammatory response of monocytes/macrophages in a bidirectional fashion, indirectly enhances the cytotoxicity of NK cells, promotes oxidative bursts in neutrophils, upregulates surface markers on lymphocytes, enhances antigen presentation on dendritic cells and induces immune inflammatory responses in sebocytes and mesenchymal cells. MALP-2 is a promising vaccine adjuvant for this application. It also promotes vascular healing and regeneration, accelerates wound and bone healing, suppresses tumors and metastasis, and reduces lung infections and inflammation. MALP-2 has a simple structure, is easy to synthesize, and has promising prospects for clinical application. Therefore, this paper reviews the mechanisms of MALP-2 activation in immune cells, focusing on the application of MALP-2 in animals/humans to provide a basis for the study of pathogenesis in Mycoplasma fermentans and the translation of MALP-2 into clinical applications.
期刊：
Sensors and Actuators B-Chemical,2023年380:133407 ISSN：0925-4005
通讯作者：
Hongfen Yang<&wdkj&>Run Li<&wdkj&>Ren Cai
作者机构：
[Li, Jingxian; Li, Run; Wang, Song; Cai, Ren; Tan, Weihong] Hunan Univ, Coll Mat Sci & Engn, Coll Chem & Chem Engn,Mol Sci & Biomed Lab, Coll Biol,State Key Lab Chemo Biosensing & Chemome, Changsha 410082, Peoples R China.;[Yang, Hongfen] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;[Tan, Weihong] Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp,Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China.;[Tan, Weihong] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med, Shanghai 200240, Peoples R China.;[Tan, Weihong] Shanghai Jiao Tong Univ, Coll Chem & Chem Engn, Shanghai 200240, Peoples R China.
通讯机构：
[Hongfen Yang] H;[Run Li; Ren Cai] M;Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Material Science and Engineering, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
摘要：
This work describes a novel "off-on" biosensor for super-sensitive and selective detection of aflatoxin B1 (AFB1). In the biosensor, electrochemiluminescence (ECL) and aggregation-induced emission (AIE) work together to enhance ECL performance by a dibenzo-[b,d]thiophene sulfone-based conjugated microporous polymer, and hairpin DNA1 (H1) and ferrocene (Fc)-apt act as the switches for the "off-on" mode. In the absence of target AFB1, the ECL signal is inhibited because of the steric-hindrance effect, and the biosensor remains in the "off" state. In the presence of AFB1, ECL signal recovery is observed caused by the specific recognition between the AFB1 and Fc-apt, i.e., the biosensor changes to the "on" state. Under optimal experimental conditions, AFB1 can be quantified from 1 pg center dot mL-1 to 1 mu g center dot mL-1 with an ultralow detection limit of 0.46 pg center dot mL-1 by the "off-on" biosensor. The biosensor exhibited good practicability for AFB1 assay in corn samples, thus providing a simple and sensitive method for monitoring food safety.
通讯机构：
[Wang, DQ; Wang, DQ ; Lin, YS ] X;Xian Univ Technol, Shaanxi Key Lab Water Resources & Environm, Xian 710048, Shaanxi, Peoples R China.;Xian Univ Technol, State Key Lab Ecohydraul Northwest Arid Reg, Xian 710048, Shaanxi, Peoples R China.;Xian Univ Technol, Sch Water Resources & Hydroelect Engn, Dept Municipal & Environm Engn, Xian 710048, Shaanxi, Peoples R China.;Northwest Univ, Coll Urban & Environm Sci, Shaanxi Key Lab Earth Surface Syst & Environm Carr, Xian 710127, Shaanxi, Peoples R China.
关键词：
Bioelectrochemical system;Sulfate-reducing bacteria;Heavy metal wastewater;Electroactive microorganism;Heavy metals recovery
摘要：
Heavy metal wastewater (HMW) has resulted in many adverse environmental issues. However, bioelectrochemical system (BES) has been recognized as an effective technology for HMW treatment. This technology generates electricity and removes heavy metals and high concentrations of sulfate. In the sulfate-reducing bacteria-based BES, sulfate-reducing bacteria can anaerobically reduce sulfate to produce sulfide, which reacts with heavy metal ions and forms their corresponding sulfide precipitates, or the heavy metals can be reduced by obtaining electrons at the anode or cathode of the BES. Therefore, this study comprehensively reviews the removal mechanisms of HMW at the anodes and cathodes of the BES. The effects of several key factors, such as electrode materials, biocathode, initial heavy metal concentration, external resistance, and pH, on electricity generation performance and removal efficiency were evaluated. Furthermore, the treatment effects of the microbial fuel cell-microbial electrolytic cell system and the coupled system of BES with plants, artificial wetlands, and electrolytic reactors on HMW and the recovery efficiencies of BES for sulfur and heavy (precious) metals were discussed. Therefore, this review provides a theoretical basis and technical support to broaden the prospects of BES application in HMW remediation.
摘要：
This work aimed to investigate photocatalytic properties of GQDs@PEG@Mg-ZnFe2O4 nanocomposite, composed of graphene quantum dots (GQDs), polyethylene glycol (PEG), and Mg-ZnFe2O4, for the degradation of methylene blue (MB) and crystal violet (CV). This nanocomposite was synthesized using facile ultrasonics-assisted methodology. XRD analysis confirmed the formation of the spinel structure of the Mg-ZnFe2O4 in the nanocomposite, whereas the presence of GQDs and PEG was confirmed by Fourier transform infrared spectroscopy. Scanning electron microscopy (SEM) revealed a reduction in agglomeration and particle size in the ternary nanocomposite. The GQDs@PEG@Mg-ZnFe2O4 nanocomposite demonstrates a remarkable degradation efficiency of 98 % for CV and MB dyes in the presence of sunlight in 120 min, indicating its potential as an efficient photocatalyst. Vibrating sample magnetometer (VSM) analysis confirmed the superparamagnetic behavior of the GQDs@PEG@Mg-ZnFe2O4 nanocomposite which enables magnetic recovery of the photocatalyst after the degradation process. Overall, this study emphasizes the utilization of an environmentally friendly approach to effectively eliminate organic pollutants from wastewater, addressing a crucial environmental concern.
通讯机构：
[Chen, LL ; Liang, H] U;Univ South China, Hengyang Med Sch, Sch Publ Hlth, Dept Publ Hlth Lab Sci, Hengyang 421001, Hunan, Peoples R China.
摘要：
Folic acid (FA) is one of the essential vitamins for the growth and reproduction of human cells, and it is of great significance to detect FA in real time. In this study, we designed double-stranded DNA (dsDNA)-templated copper nanoclusters (CuNCs) as a nanoprobe for rapid, highly sensitive and selective detection of FA via the inner filter effect (IFE). The dsDNA-CuNCs nanoprobe with strong stability could be prepared facilely in only 5 min at room temperature and testing could be completed in 12.5 min. This method exhibited a satisfactory linear response to FA in the concentration range of 1.25-50.00 mu M and a low limit of detection (LOD) of 0.34 mu M. The dsDNA-CuNCs sensing probe exhibited excellent selectivity and was successfully applied in serum and tablets for FA detection with recoveries of 97.87% to 105.41%. This fluorescence method provides a straightforward label-free biosensor platform for rapid detection of FA, indicating great potential in biological applications for point-of-care testing. Folic acid (FA) is one of the essential vitamins for the growth and reproduction of human cells, and it is of great significance to detect FA in real time.
期刊：
Journal of Applied Toxicology,2023年43(8):1169-1182 ISSN：0260-437X
通讯作者：
Zhaohui Zhang
作者机构：
[Zhang, Zhaohui; Liu, Xiaodong; Jin, Huiyun; Zhang, Linfang; Chen, Shaoxiong; Liu, Xiuli; Li, Guilan] Univ South China, Sch publ Hlth, Hengyang Med Sch, Dept Prevent Med, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Zhaohui; Liu, Xiaodong; Jin, Huiyun; Chen, Shaoxiong; Liu, Xiuli; Li, Guilan] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhaohui Zhang] D;Department of Preventive Medicine, School of public health, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001 China<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001 China
摘要：
Beryllium sulfate (BeSO4) can result to lung injuries, such as leading to lipid peroxidation and autophagy, and the treatment of beryllium disease has not been well improved. Ferroptosis is a regulated cell death process driven by iron-dependent and lipid peroxidation, while ferritinophagy is a process mediated by nuclear receptor coactivator 4 (NCOA4), combined with ferritin heavy chain 1 (FTH1) degradation and release Fe2+, which regulated intracellular iron metabolism and ferroptosis. Hydrogen sulfide (H2S) has the effects of antioxidant, antiautophagy, and antiferroptosis. This study aimed to investigate the effect of H2S on BeSO4-induced ferroptosis and ferritinophagy in 16HBE cells and the underlying mechanism. In this study, BeSO4-induced 16HBE cell injury model was established based on cellular level and pretreated with deferoxamine (DFO, a ferroptosis inhibitor), sodium hydrosulfide (NaHS, a H2S donor), or NCOA4 siRNA and, subsequently, performed to detect the levels of lipid peroxidation and Fe2+ and the biomarkers of ferroptosis and ferritinophagy. More importantly, our research found that DFO, NaHS, or NCOA4 siRNA alleviated BeSO4-induced ferroptosis and ferritinophagy by decreasing the accumulation of Fe2+ and lipid peroxides. Furthermore, the relationship between ferroptosis, ferritinophagy, H2S, and beryllium disease is not well defined; therefore, our research is innovative. Overall, our results provided a new theoretical basis for the prevention and treatment of beryllium disease and suggested that the application of H2S, blocking ferroptosis, and ferritinophagy may be a potential therapeutic direction for the prevention and treatment of beryllium disease.
期刊：
CELL DEATH & DISEASE,2023年14(2) ISSN：2041-4889
通讯作者：
Chang, S.;Chang, Y.-Z.
作者机构：
[Yu, Peng; Tian, Tian; Kang, Shaomeng; Li, Zhongda; Chang, Yan-zhong; Li, Jianhua; Zheng, Huiwen] Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Minist Educ,Key Lab Mol & Cellular Biol,Hebei Key, Shijiazhuang 050024, Hebei, Peoples R China.;[Guo, Xin] Hebei Med Univ, Neuromed Technol Innovat Ctr Hebei Prov, Dept Neurol, Brain Aging & Cognit Neurosci Lab Hebei Prov,Hosp, Shijiazhuang 050000, Hebei, Peoples R China.;[Guo, Xin] Capital Med Univ, Hebei Hosp, Xuanwu Hosp, Dept Neurol, Shijiazhuang 050000, Hebei, Peoples R China.;[Wang, Fudi] Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, State Key Lab Expt Hematol,Sch Med, Hangzhou 310058, Zhejiang, Peoples R China.;[Wang, Fudi] Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Chang, Shiyang] D;[Chang, Yan-zhong] L;Laboratory of Molecular Iron Metabolism, Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, China<&wdkj&>Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, China
摘要：
Ischemic stroke is associated with high mortality and morbidity rates worldwide. However, the molecular mechanisms underlying the neuronal damage incurred by stroke victims remain unclear. It has previously been reported that ischemic stroke can induce an increase in the levels of brain iron, which is an important factor of in the associated brain damage. Ferroportin 1 (FPN1), the only known cellular iron export protein, is found in brain microvascular endothelial cells (BMVECs) at the blood-brain barrier, and is considered the gateway for entry of plasma iron into the central nervous system. Despite the connection of brain iron to neuronal damage, the role of BMVECs FPN1 in ischemic stroke remains unexplored. Herein, we conditionally deleted Fpn1 in mouse endothelial cells (ECs), using VE-cadherin-Cre transgenic mice, and explored the impact on brain iron homeostasis after stroke. Our data demonstrated that Fpn1 knockout in ECs decreased the brain iron levels in mice, attenuated the oxidative stress and inflammatory responses after stroke, and inhibited both ferroptosis and apoptosis, ultimately alleviating neurological impairment and decreasing cerebral infarct volume during the acute phase of ischemic stroke. By contrast, we found that Fpn1 knockout in ECs delayed the recovery of neurological function in mice following ischemic stroke. We also found that ECs Fpn1 knockout decreased the brain iron levels after stroke, exacerbated glial cell proliferation, and inhibited neuronal development, indicating that the diminished brain iron levels hindered the repair of neural injury in mice. In conclusion, our findings reveal a dual consequence of FPN1 deficiency in ECs in the development of ischemic stroke. More specifically, iron deficiency initially exerts a neuroprotective effect during the acute phase of ischemic stroke but inhibits recovery during the later stages. Our findings are important to the development of iron- or FPN1-targeting therapeutics for the treatment of ischemic stroke.
摘要：
Soybean (Glycine max L.), as an oil and protein crop, has attracted interest for its potential in the reclamation/ restoration of barren and contaminated habitats due to its ability to tolerate adverse environments. To investigate the effects of the growth (biomass and plant height), chlorophyll content, antioxidative capacity (per -oxidase and superoxide dismutase activities), and homeostasis of essential elements in soybean plants induced by cadmium (Cd), a pot experiment was performed. Soybean seeds were cultivated in six different levels of Cd-contaminated soil (0, 0.25, 0.50, 1.00, 2.50, 5.00, and 10.00 mg kg(-1)) for 27 days at 60 % humidity and 25-35 C-degrees in a greenhouse with natural light. Soybean seedling growth was stimulated and inhibited at low (<= 1.00 mg kg(-1)) and high (>= 2.50 mg kg(-1)) Cd concentrations, respectively. Essential metal elements (Mg, Fe, and Zn) and chlorophyll contents of leaves were increased and decreased at low and high Cd concentrations, respectively. Exposure to high Cd concentrations interfered with the homeostasis of essential elements in soybean plants. High Cd concentrations reduced antioxidant capacity and chlorophyll content, which inhibited soybean growth. The Cd accumulation level (>100 mg kg(-1)) in soybean plant organs was unsafe for producing soybean products. However, soybean seedlings appear to tolerate moderate Cd contamination.(c) 2023 SAAB. Published by Elsevier B.V. All rights reserved.
