摘要:
Diabetic nephropathy (DN) is one of the most serious and general complications of diabetes, while schedules for prevention and treatment are unsatisfactory. Leucine aminopeptidase (LAP) as one of the biomarkers of DN is associated with glomerular and/or tubular injury. Imaging of LAP activity in DN disease model in vivo is thus beneficial for early diagnosis and prevention of DN, but such a strategy is still lacking. Herein, an enzyme-activated probe HD-LAP with a NIR fluorescence emission for specific detection of LAP activity in the DN model is designed and synthesized. HD-LAP has a significant fluorescence enhancement after reacted with LAP and shows a NIR fluorescence emission at 704 nm based on intramolecular charge transfer mechanism. Moreover, HD-LAP can be employed to image LAP activity in HK-2 and HepG2 cells. More importantly, HD-LAP is the first example to real-time image LAP in DN mice and clinical serum samples. These results demonstrated that HD-LAP is promising as a powerful tool for the research on LAP associated diabetic diseases in future.
期刊:
FRONTIERS IN NEUROLOGY,2024年15:1322228 ISSN:1664-2295
通讯作者:
Zhu, Shuzhen;Wang, Q
作者机构:
[Zhu, Shuzhen; Li, Fangyi; Zhang, Wenjie; Deng, Bin; Zhu, SZ; Wang, Qing; Zhou, Hang; Wang, Q; Weng, Guomei; Luo, Yuqi] Southern Med Univ, Dept Neurol, Zhujiang Hosp, Guangzhou, Peoples R China.;[Li, Fangyi] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Neurol, Changsha, Peoples R China.;[Weng, Guomei] First Peoples Hosp Zhaoqing, Dept Neurol, Zhaoqing, Peoples R China.;[Tao, Xi] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Neurol Rehabil, Affiliated Hosp 1, Changsha, Peoples R China.;[Deng, Mingzhu] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Dept Neurol, Changsha, Peoples R China.
通讯机构:
[Wang, Q ; Zhu, SZ] S;Southern Med Univ, Dept Neurol, Zhujiang Hosp, Guangzhou, Peoples R China.
关键词:
Parkinson’s disease;inflammation;lymphocyte-to-monocyte ratio;neutrophil-to-high-density lipoprotein ratio;neutrophil-to-lymphocyte ratio
摘要:
BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). However, the correlation between peripheral inflammatory markers and the severity of PD remains unclear. METHODS: The following items in plasma were collected for assessment among patients with PD (n = 303) and healthy controls (HCs; n = 303) were assessed for the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-high-density-lipoprotein ratio (NHR) in plasma, and neuropsychological assessments were performed for all patients with PD. Spearman rank or Pearson correlation was used to evaluate the correlation between the NLR, the LMR and the NHR and the severity of PD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the NLR, LMR and NHR for PD. RESULTS: The plasma NLR and NHR were substantially higher in patients with PD than in HCs, while the plasma LMR was substantially lower. The plasma NLR was positively correlated with Hoehn and Yahr staging scale (H&Y), Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-I, UPDRS-II, and UPDRS-III scores. Conversely, it exhibited a negative relationship with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Furthermore, the plasma NHR was positively correlated with H&Y, UPDRS, UPDRS-I, UPDRS-II and UPDRS-III scores. Moreover, negative associations were established between the plasma LMR and H&Y, UPDRS, UPDRS-I, UPDRS-II, and UPDRS-III scores. Finally, based on the ROC curve analysis, the NLR, LMR and NHR exhibited respectable PD discriminating power. CONCLUSION: Our research indicates that a higher NLR and NHR and a lower LMR may be relevant for assessing the severity of PD and appear to be promising disease-state biomarker candidates.
摘要:
BACKGROUND: Depression is a highly prevalent comorbidity arising in patients with Parkinson's disease (PD). However, depression in patients with PD is poorly treated. Hydrogen sulfide (H(2)S), a neuromodulator, has the potential to relieve depression. OBJECTIVE: To investigate whether H(2)S attenuates depression-like behaviours in a rat model of PD and examine the underlying mechanisms. METHODS: We utilised rotenone to develop a PD model with subcutaneous injections in the dorsal cervical region of Sprague-Dawley rats. The depression-like behaviours in the rotenone-induced PD model rats were assessed through forced swimming, tail suspension, open field, novelty-suppressed feeding, and elevated plus-maze tests. The expression of postsynaptic density protein-95 and synapsin-1, related to synaptic plasticity, was detected using Western blot in the hippocampus. The hippocampal ultrastructure, including the synaptic density, length of the synaptic active zone, postsynaptic density thickness, and synaptic gap width, was detected using transmission electron microscopy. RESULTS: We proved that sodium hydrosulfide (NaHS; a donor of H(2)S) significantly attenuated the depression-like behaviours and disorders of hippocampal synaptic plasticity in rotenone-induced PD rats. Furthermore, inhibition of the hippocampal Warburg effect by 2-deoxyglucose abolished NaHS-enhanced hippocampal synaptic plasticity and reversed NaHS-attenuated depression-like behaviours in the rotenone-induced PD rats. CONCLUSION: H(2)S attenuates PD-associated depression by improving the hippocampal synaptic plasticity in a hippocampal Warburg effect-dependent manner.
摘要:
Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages.
摘要:
ATP-binding cassette protein A1 (ABCA1) is a key protein in the transport of intracellular cholesterol to the extracellular and plays an important role in reduc-ing cholesterol accumulation in surrounding tissues. Bibliometric analysis refers to the cross-science of quan-titative analysis of a variety of documents by mathemati-cal and statistical methods. It combines an analysis of structural and temporal patterns in scholarly publica-tions with a description of topic concentration and types of uncertainty. This paper analyzes the history, hotspot, and development trend of ABCA1 through bibliometrics. It will provide readers with the research status and development trend of ABCA1 and help the hot research in this field explore new research directions. After screening, the research on ABCA1 is still in a hot phase in the past 20 years. ABCA1 is emerging in previously unrelated disciplines such as cancer. There were 551 key-words and 6888 breakout citations counted by CiteSpace. The relationship between cancer and cardiovascular dis-ease has been linked by ABCA1. This review will guide readers who are not familiar with ABCA1 research to quickly understand the development process of ABCA1 and provide researchers with a possible future research focus on ABCA1. (Curr Probl Cardiol 2024;49:102036.)
期刊:
Scandinavian Journal of Immunology,2024年99(3):e13357- ISSN:0300-9475
通讯作者:
Lei, AH;Zhang, HJ
作者机构:
[Long, WeiXiang; Lei, AH; Lei, Aihua; Dai, Zhongling; Liu, Duo; Gong, Zhande; Wang, Cui] Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, 28 Changsheng Western Rd, Hengyang 421001, Hunan, Peoples R China.;[Long, WeiXiang; Lei, Aihua; Dai, Zhongling; Liu, Duo; Gong, Zhande; Wang, Cui] Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Con, Hengyang, Peoples R China.;[Long, WeiXiang; Lei, Aihua; Dai, Zhongling; Liu, Duo; Gong, Zhande; Wang, Cui] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang, Peoples R China.;[Zhang, Haijun] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Cardiol, 69 Chuanshan Ave, Hengyang 421000, Hunan, Peoples R China.
通讯机构:
[Lei, AH ; Zhang, HJ ] U;Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, 28 Changsheng Western Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Cardiol, 69 Chuanshan Ave, Hengyang 421000, Hunan, Peoples R China.
关键词:
allergic airway inflammation;hormones;ILC2s
摘要:
Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL-5 and IL-13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial-derived alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2-driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.
摘要:
BACKGROUND: Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. METHODS: STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe(2+) contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. RESULTS: Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe(2+), and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. CONCLUSION: Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.
关键词:
autophagy;seizure-induced brain injury;SIRT3;Xyloketal B
摘要:
Brain damage in children due to seizures is irreversible and has been a major public health concern. The herbal monomer Xyloketal B (Xyl-B) can be used as a neuroprotective drug because of its antioxidant, antiapoptotic, and anti-inflammatory effects but with few adverse effects. In this article, we constructed a rat developmental convulsion model and a primary hippocampal neuronal cell convulsion model, through which we studied hippocampal neuronal morphology and neuronal apoptosis using H&E staining and TUNEL staining, respectively. Moreover, we measured TNF-α, IL-6, and IL-1β inflammatory factor levels using ELISA, MDA, and SOD kits. The expression of SIRT3 in hippocampal tissues was determined by qPCR and Western blotting. The expression of autophagy-related proteins such as LC3, p62, and Beclin-1 was evaluated by Western blotting or immunohistochemistry. The role of SIRT3 and autophagic activity with Xyl-B in convulsive seizure-induced brain injury was investigated by knocking down SIRT3 expression levels. Our results showed that Xyl-B plays a neuroprotective role in convulsive seizure-induced brain injury by increasing SIRT3 expression and activating the autophagy pathway. The regulatory role of SIRT3 in the autophagy pathway with Xyl-B treatment was explored by knocking down SIRT3 expression and inhibiting autophagy. Our results revealed that SIRT3 enhances the protective effect of Xyl-B against postconvulsive brain injury by regulating AMPK/mTOR signaling-mediated autophagy.
摘要:
Asparagine, an important amino acid in mammals, is produced in several organs and is widely used for the production of other nutrients such as glucose, proteins, lipids, and nucleotides. Asparagine has also been reported to play a vital role in the development of cancer cells. Although several types of cancer cells can synthesise asparagine alone, their synthesis levels are insufficient to meet their requirements. These cells must rely on the supply of exogenous asparagine, which is why asparagine is considered a semi-essential amino acid. Therefore, nutritional inhibition by targeting asparagine is often considered as an anti-cancer strategy and has shown success in the treatment of leukaemia. However, asparagine limitation alone does not achieve an ideal therapeutic effect because of stress responses that upregulate asparagine synthase (ASNS) to meet the requirements for asparagine in cancer cells. Various cancer cells initiate different reprogramming processes in response to the deficiency of asparagine. Therefore, it is necessary to comprehensively understand the asparagine metabolism in cancers. This review primarily discusses the physiological role of asparagine and the current progress in the field of cancer research.
摘要:
Curcumin (CUR) exhibits a definite curative effect in the treatment of depression. To identify potential antidepressant targets and mechanisms of action of CUR. This study used network pharmacology to explore the signaling pathways and CUR-related targets in depression. C57BL/6J mice (male,12-14weeks old) were randomly divided into four groups (n = 8): saline-treated (control mice), lipopolysaccharide (LPS, 2mg/kg/day, intraperitoneally), LPS + CUR (50mg/kg/day, intragastrically), and LPS + CUR + LY294002 (7.5mg/kg/day, intraperitoneally). After 1week, behavioral tests were performed. Then, neuronal damage in the prefrontal cortex of mice was evaluated by hematoxylin-eosin (HE) staining. We uncovered the main active mechanism of CUR against depression using Western blotting and enzyme-linked immunosorbent assay (ELISA). Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the most significantly enriched pathway in CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with the PI3K-Akt signaling pathway and CUR-related targets. In addition, among the top 50 targets ranked by degree in the protein-protein interaction (PPI) network, there were 23 targets involved in the 52 intersection targets. Administration of LPS alone extended immobility time in the open field test (OFT) and tail suspension test (TST) and decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR relieved LPS-induced changes in the behavioral tests, activity of the PI3K-Akt signaling pathway, neuronal damage in the prefrontal cortex (PFC), and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 blocked the therapeutic effects of CUR. Our study indicates that CUR may be an effective antidepressant agent in an LPS-induced mouse model, partly because of its anti-inflammatory action through the PI3K-Akt signaling pathway.
作者机构:
[Liu, Li; He, Jingzhe; Wang, Jiaren; Li, Ruining; Li, Qimei; Zeng, Lin; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Hepatol Unit, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Li, Ruining; Li, Qimei; Zeng, Lin; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.;[Liu, Li; Wang, Jiaren; Xiao, Lushan] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou, Peoples R China.;[Wang, Weizhen] Southern Med Univ, Nanfang Hosp, Dept Ultrasound, Guangzhou, Peoples R China.;[Zhu, Hongbo] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.
通讯机构:
[Xiao, LS ; Liu, L ; Zhu, H ] S;Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Hepatol Unit, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.
关键词:
CCR;MSFLD;risk factor;UK Biobank
摘要:
OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD. PATIENTS AND MEASUREMENTS: This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI ≥60. RESULTS: We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95%CI: 1.053-1.088, p < .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95%CI: 1.077-1.660, p = .009; CCR tertile 2 OR: 1.217, 95%CI: 1.021-1.450, p = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95%CI: 1.160-2.317, p = .005; CCR tertile 2 OR: 1.322, 95%CI: 1.073-1.628, p = .005, respectively). CONCLUSION: Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.
作者机构:
[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Zhang, Qinyi; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Affiliated Hosp 1, Cardiovasc Lab Big Data & Imaging ArtificialIntell, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.
关键词:
genes;mice;candidate disease gene;inference;multiomics;oncogenes;enhancer of transcription;cell lines;transcription factor
摘要:
Gene regulatory networks (GRNs) are interpretable graph models encompassing the regulatory interactions between transcription factors (TFs) and their downstream target genes. Making sense of the topology and dynamics of GRNs is fundamental to interpreting the mechanisms of disease etiology and translating corresponding findings into novel therapies. Recent advances in single-cell multi-omics techniques have prompted the computational inference of GRNs from single-cell transcriptomic and epigenomic data at an unprecedented resolution. Here, we present scGRN (https://bio.liclab.net/scGRN/), a comprehensive single-cell multi-omics gene regulatory network platform of human and mouse. The current version of scGRN catalogs 237 051 cell type-specific GRNs (62 999 692 TF-target gene pairs), covering 160 tissues/cell lines and 1324 single-cell samples. scGRN is the first resource documenting large-scale cell type-specific GRN information of diverse human and mouse conditions inferred from single-cell multi-omics data. We have implemented multiple online tools for effective GRN analysis, including differential TF-target network analysis, TF enrichment analysis, and pathway downstream analysis. We also provided details about TF binding to promoters, super-enhancers and typical enhancers of target genes in GRNs. Taken together, scGRN is an integrative and useful platform for searching, browsing, analyzing, visualizing and downloading GRNs of interest, enabling insight into the differences in regulatory mechanisms across diverse conditions. Graphical Abstract
期刊:
Journal of the European Academy of Dermatology and Venereology,2024年 ISSN:0926-9959
通讯作者:
Zhao, FJ;Liu, SQ
作者机构:
[Xiong, Shun; Zhao, Feijun; Liu, Shuangquan; Liu, Zhaoping; Ding, Xuan; Huang, Shaobin; Yao, Jiangchen; Zhang, Xiaohong; Xu, Man] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hengyang, Peoples R China.;[Xiong, Shun; Zhao, Feijun; Liu, Shuangquan; Liu, Zhaoping; Ding, Xuan; Huang, Shaobin; Yao, Jiangchen; Zhang, Xiaohong; Xu, Man] Univ South China, Hengyang Med Coll, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang, Peoples R China.;[Xiong, Shun; Zhao, Feijun; Liu, Shuangquan; Liu, Zhaoping; Ding, Xuan; Huang, Shaobin; Yao, Jiangchen; Zhang, Xiaohong; Xu, Man] Univ South China, Affiliated Hosp 1, Hengyang Med Coll, Dept Clin Lab Med, Hengyang, Peoples R China.;[Zhao, Feijun; Zhao, FJ] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;[Zhao, Feijun; Zhao, FJ] Univ South China, Hengyang Med Coll, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Peoples R China.
通讯机构:
[Zhao, FJ ; Liu, SQ ] U;Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Coll, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Inst Microbiol & Infect Dis,Dept Clin Lab Med, Hengyang 421001, Peoples R China.
摘要:
Treponema pallidum is the causative factor of syphilis, a sexually transmitted disease (STD) characterized by perivascular infiltration of inflammatory cells, vascular leakage, swelling and proliferation of endothelial cells (ECs). The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of T. pallidum. In this review, we focus on how T. pallidum establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of T. pallidum across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol-dependent, respectively. Herein, clarifying the relationship between T. pallidum and endothelial dysfunction is of great significance to provide novel strategies for diagnosis and prevention of syphilis, and has a great potential prospect of clinical application.
摘要:
BACKGROUND: We previously revealed that hydrogen sulfide (H(2)S) attenuates chronic stress-induced cognitive impairment, but the underlying mechanism needs to be further clarified. Growth differentiation factor 11 (GDF11) plays an important regulatory role in cognitive function and that hippocampal NLRP3/caspase-1-mediated pyroptosis contributes to the pathogenesis of cognitive impairment. Hence, this research aimed to explore whether promoting GDF11 levels and suppressing hippocampal NLRP3/caspase-1-mediated pyroptosis mediate H(2)S to alleviate chronic stress-induced cognitive impairment. METHODS: Sprague-Dawley rats were subjected to unpredictable chronic mild stress lasting four weeks to establish an animal model of chronic stress-induced cognitive impairment. Behavioral performance was assessed by the Y-maze test and the novel object recognition test. The expression levels of proteins were analyzed by Western blot analysis. The levels of IL-1β and IL-18 in the hippocampus were measured by ELISA. RESULTS: NaHS upregulated the expression of GDF11 in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed rats. Silencing GDF11 blocked NaHS-improved cognitive impairment in CUMS-exposed rats, according to the Y-maze test and the novel object recognition test. Furthermore, NaHS mitigated NLRP3/caspase-1-mediated pyroptosis in the hippocampus of CUMS-exposed rats and this effect was reversed by silencing GDF11. Moreover, overexpression of GDF11 alleviated CUMS-induced cognitive impairment and NLRP3/caspase-1-mediated hippocampal pyroptosis. CONCLUSIONS: GDF11 mediates H(2)S to attenuate chronic stress-induced cognitive impairment via inhibiting hippocampal NLRP3/caspase-1-mediated pyroptosis.
期刊:
JOURNAL OF MATERIALS CHEMISTRY B,2024年12(6):1530-1537 ISSN:2050-750X
通讯作者:
Cheng, D;He, Longwei
作者机构:
[Cheng, Dan; He, Longwei; He, LW; Jiang, Renfeng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.;[Cheng, Dan; Zhang, Hongshuai; Yang, Xuefeng] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Gastroenterol, Hengyang 421002, Hunan Prov, Peoples R China.;[Cheng, Dan; Liu, Qian; Zhang, Hongshuai; Yang, Xuefeng; Xia, Yuqing] Univ South China, Affiliated Nanhua Hosp, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.
通讯机构:
[Cheng, D ; He, LW] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Gastroenterol, Hengyang 421002, Hunan Prov, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.
摘要:
Carboxylesterases (CESs) are critical for metabolizing ester-containing biomolecules and are specifically important in liver metabolic disorders. The modulation of CESs is also an important issue in pharmacology and clinical applications. Herein, we present a near-infrared (NIR) CES fluorescent probe (NCES) based on the protection-deprotection of the hydroxyl group for monitoring CES levels in living systems. The NCES probe has good selectivity and sensitivity for CESs with a limit of detection (LOD) of 5.24 mU mL-1, which allows for tracing the fluctuation of cellular CES after treatment with anticancer drugs and under inflammation and apoptosis states. Furthermore, NCES can be successfully applied for guiding liver cancer surgery with high-contrast in vivo imaging and detecting clinical serum samples from liver cancer patients. This work showed that the NCES probe has great potential in drug development, imaging applications for medical diagnosis, and early-stage detection for clinical liver diseases. A carboxylesterase-activated near-infrared fluorescent probe with high sensitivity and selectivity was developed to guide surgical resection of liver tumors and monitor clinical serum samples from liver cancer patients.
作者机构:
[He, Run-Chao; Hu, YW; Zhang, Ting; Jiang, Min; Li, Shu; Song, Yu; Wu, Jia; Zhang, Ke-Lan; Hu, Yan-Wei; Tang, Mao-Lin; Dong, Xian-Hui] Guangzhou Med Univ, Guangzhou Women & Children Med Ctr, Dept Clin Lab, Guangzhou 510600, Guangdong, Peoples R China.;[Dai, Xiaoyan] Guangzhou Med Univ, Guangzhou, Guangdong, Peoples R China.;[Wu, Shao-Guo] Guangzhou Twelfth Peoples Hosp, Dept Clin Lab, Guangzhou, Guangdong, Peoples R China.;[Bei, Yan-Rou] Southern Med Univ, Nanfang Hosp, Lab Med Ctr, Guangzhou, Guangdong, Peoples R China.;[Ma, Xin] Southern Med Univ, Nanfang Hosp, Dept Anesthesiol, Guangzhou, Guangdong, Peoples R China.
通讯机构:
[Hu, YW ; Dai, XY ] G;Guangzhou Med Univ, Guangzhou Women & Children Med Ctr, Dept Clin Lab, Guangzhou 510600, Guangdong, Peoples R China.;Guangzhou Med Univ, Guangzhou, Guangdong, Peoples R China.
摘要:
BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe(-/-)PSMB8-AS1(KI)) and global Apoe and proteasome subunit-β type-9 (Psmb9) double knockout mice (Apoe(-/-)Psmb9(-/-)). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe(-/-)PSMB8-AS1(KI) mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe(-/-) mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe(-/-)PSMB8-AS1(KI) mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-β type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe(-/-) mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.
作者机构:
[Wei, Rui; Liu, Qingqing; Luo, Jun-Li; Wei, R; Sun, Yangqing; Luo, JL] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;[Zhong, Shangwei; Luo, Jun-Li; Luo, JL] Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Luo, Jun-Li; Luo, JL] Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
通讯机构:
[Wei, R; Luo, JL ] C;Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
关键词:
FTSJ1;tumor promotor;CD8+T cell infiltration;triple-negative breast cancer
摘要:
Simple Summary In this study, we found that high FTSJ1 expression in triple-negative breast cancer patients was associated with poor prognosis and was associated with reduced infiltration of CD8+T cells in the tumor microenvironment. By knocking down FTSJ1, we observed an inhibitory effect on the proliferation and migration of triple-negative breast cancer, while inducing apoptosis and increasing the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. This finding highlights the importance of FTSJ1 as a potential immunotherapy target in triple-negative breast cancer.Abstract FtsJ RNA 2 '-O-methyltransferase 1 (FTSJ1) is a member of the methyltransferase superfamily and is involved in the processing and modification of ribosomal RNA. We herein demonstrate that FTSJ1 favors TNBC progression. The knockdown of FTSJ1 inhibits TNBC cell proliferation and development, induces apoptosis of cancer cells, and increases the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. Furthermore, the high expression of FTSJ1 in TNBC attenuates CD8+T cell infiltration in the tumor microenvironment (TME) correlated with poorer prognosis for clinical TNBC patients. In this study, we establish that FTSJ1 acts as a tumor promotor, is involved in cancer immune evasion, and may serve as a potential immunotherapy target in TNBC.
摘要:
The cardioprotective effect of microRNAs (miRNAs) on myocardial ischemic-reperfusion (I/R) injury has been documented. Here, we aim to decipher the mechanism of miR-24 delivered by human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in myocardial I/R injury after dexmedetomidine (DEX) preconditioning. We collected and identified hUC-MSCs and extracted EVs, which were co-cultured with DEX-preconditioned hypoxia/reoxygenation (H/R) cardiomyocyte models or injected into I/R mouse models. The cardiomyocytes and myocardial injury were evaluated by molecular biology experiments. miR-24 was highly expressed in hUC-MSC-EVs. hUC-MSC-EVs could transfer miR-24 into cardiomyocytes where miR-24 augmented cell viability and inhibited cell apoptosis after DEX preconditioning. In the co-culture system of RAW264.7 macrophages with hUC-MSC-EVs, miR-24 promoted M2-type polarization of macrophages and reduced M1-type macrophage polarization. Mechanistically, miR-24 targeted KEAP1 and inhibited its expression, resulting in disruption of the Nrf2/HO-1 signaling. In vivo data confirmed that miR-24 delivered by hUC-MSC-EVs enhanced the suppressing effect of DEX preconditioning on inflammation and apoptosis in rats following myocardial I/R injury. Overall, miR-24 delivered by hUC-MSC-EVs can promote M2 polarization of macrophages and enhance the protective effect of DEX preconditioning on myocardial I/R injury by down-regulating the KEAP1/Nrf2/HO-1 signaling axis.
摘要:
AKG protects against CTX‐induced POI by inhibiting NLRP3‐mediated pyroptosis of granulosa cells, restoring the glycolysis and improving ovarian reserve function.(Created with BioRender.com). Scope Premature ovarian insufficiency (POI) is a common female infertility problem, with its pathogenesis remains unknown. The NOD‐like receptor family pyrin domain‐containing 3 (NLRP3)‐mediated pyroptosis has been proposed as a possible mechanism in POI. This study investigates the therapeutic effect of α‐ketoglutarate (AKG) on ovarian reserve function in POI rats and further explores the potential molecular mechanisms. Methods and results POI rats are caused by administration of cyclophosphamide (CTX) to determine whether AKG has a protective effect. AKG treatment increases the ovarian index, maintains both serum hormone levels and follicle number, and improves the ovarian reserve function in POI rats, as evidence by increased the level of lactate and the expression of rate‐limiting enzymes of glycolysis in the ovaries, additionally reduced the expression of NLRP3, Gasdermin D (GSDMD), Caspase‐1, Interleukin‐18 (IL‐18), and Interleukin‐1 beta (IL‐1β). In vitro, KGN cells are treated with LPS and nigericin to mimic pyroptosis, then treated with AKG and MCC950. AKG inhibits inflammatory and pyroptosis factors such as NLRP3, restores the glycolysis process in vitro, meanwhile inhibition of NLRP3 has the same effect. Conclusion AKG ameliorates CTX‐induced POI by inhibiting NLRP3‐mediated pyroptosis, which provides a new therapeutic strategy and drug target for clinical POI patients.
通讯机构:
[Liu, LS ; Tang, ZH] U;Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Hunan, Peoples R China.
关键词:
Proprotein convertase subtilisin/kexin type 9;alzheimer's disease;amyloid beta;blood-brain barrier;neuroinflammation;neuronal cell death
摘要:
The proprotein convertase subtilisin/kexin type 9 (PCSK9) belongs to a member of the proprotein convertase (PC) family, which is mainly secreted by the liver and plays a central role in lipid metabolism. Furthermore, PCSK9 plays a multifunctional role in promoting the inflammatory response, inducing cell apoptosis and pyroptosis and affecting tumor homeostasis. The brain is the organ with the richest lipid content. Incidentally, PCSK9 increased in many brain diseases, including brain injury and Alzheimer's disease (AD). Consequently, the relationship between PCSK9 and brain diseases has attracted increasing research interest. Amyloid beta (A beta) accumulation is the central and initial event in the pathogenesis of AD. This study focuses on the effects of PCSK9 on A beta accumulation in the brain via multiple modalities to explore the potential role of PCSK9 in AD, which is characterized by progressive loss of brain cells by increasing A beta accumulation. The study also explores the new mechanism by which PCSK9 is involved in the pathogenesis of AD, providing interesting and innovative guidance for the future of PCSK9-targeted therapy for AD.