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 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.
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.)
摘要：
HNRNPA2B1 and HNRNPR stabilize ASCL1 mRNA in neuroblastoma, but whether their regulatory effects depend on m6A modification and whether their function involves ASCL1 remain unknown. This study investigated the m6A-dependent binding of HNRNPA2B1 and HNRNPR to ASCL1 and subsequent regulation, as well as the expression, clinical significance, and function of HNRNPA2B1 and HNRNPR in neuroblastoma. We revealed that METTL14 mediated ASCL1 m6A modification to stabilize ASCL1. HNRNPA2B1 and HNRNPR significantly enriched ASCL1 mRNA by binding to the 5' and 3' untranslated regions, respectively, and METTL14 knockdown reduced this enrichment. Mutations in m6A sites in the untranslated regions of ASCL1 mRNA considerably decreased probe capacity to engage HNRNPA2B1 and HNRNPR. HNRNPR interacts with IGF2BP1, and knocking down either impaired binding to ASCL1 mRNA. HNRNPA2B1 and HNRNPR knockdown suppressed neuroblastoma cell growth and invasion, while ASCL1 overexpression restored these effects. The high HNRNPA2B1 and HNRNPR expression in neuroblastoma correlated with ASCL1 expression. Thus, HNRNPA2B1 and HNRNPR bind and stabilize ASCL1 mRNA in an m6A-dependent manner to promote neuroblastoma progression. This study not only discovered a new mechanism underlying the high ASCL1 expression in neuroblastoma but also identified the HNRNPA2B1/HNRNPR/ASCL1 axis as a promising target for inhibiting neuroblastoma progression.
摘要：
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. 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 Fe2+ 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. Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, 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. 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：
Cardiovascular disease (CVD) has a high incidence and low cure rate worldwide, and atherosclerosis (AS) is the main factor inducing cardiovascular disease, of which lipid deposition in the vessel wall is the main marker of AS. Currently, although statins can be used to lower lipids and low-density lipoprotein (LDL) in AS, the cure rate for AS remains low. Therefore, there is an urgent need to develop new therapeutic approaches, and stem cells are now widely studied, while stem cells are a class of cell types that always maintain the ability to differentiate and can differentiate to form other cells and tissues, and stem cell transplantation techniques have shown efficacy in the treatment of other diseases. With the establishment of cellular therapies and continued research in stem cell technology, stem cells are also being used to address the problem of AS. In this paper, we focus on recent research advances in stem cell therapy for AS and briefly summarize the relevant factors that induce the formation of AS. We mainly discuss the efficacy and application prospects of mesenchymal stem cells (MSCs) for the treatment of AS, in addition to the partial role and potential of exosomes in the treatment of AS. Further, provide new ideas for the clinical application of stem cells.
期刊：
Brain and Behavior,2024年14(2):e3373- ISSN：2162-3279
通讯作者：
Chen, YJ
作者机构：
[Chen, Liang; Chen, Yongjun; Xie, Yangzhi] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Peoples R China.;[Chen, Jiacheng] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Intens Care Unit, Hengyang, Peoples R China.
通讯机构：
[Chen, YJ ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Peoples R China.
关键词：
M1/M2 polarization;neuroinflammation;Parkinson's disease;regulatory T cell;vitamin D receptor
摘要：
We explored the therapeutic effects of vitamin receptor activation by calcitriol in a mouse model of PD. We found that calcitriol is potent to protect against neuroinflammation and neuronal degeneration by boosting Treg. Vitamin D receptor may be a therapeutic option for PD. Abstract Objective Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg. Methods Hemiparkinsonian mice model was established through the injection of 6‐OHDA into the striatum. Mice were pretreated with calcitriol before 6‐OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro‐inflammatory cytokines levels, T‐cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo. Results We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6‐OHDA‐induced PD model. Mechanistically, calcitriol promoted anti‐inflammatory/neuroprotective Treg and inhibited pro‐inflammatory/neurodestructive effector T‐cell generation in this model. This process significantly inhibited T‐cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro‐inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti‐inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody‐mediated Treg depletion assay. As predicted, the anti‐inflammatory effects of calcitriol in the PD model were diminished following Treg depletion. Conclusion These findings suggest that calcitriol's anti‐inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.
摘要：
Quinic acid (QA) and its derivatives have good lipid-lowering and hepatoprotective functions, but their role in atherosclerosis remains unknown. This study attempted to investigate the mechanism of QA on atherogenesis in Apoe−/− mice induced by HFD. HE staining and oil red O staining were used to observe the pathology. The PCSK9, Mac-3 and SM22a expressions were detected by IHC. Cholesterol, HMGB1, TIMP-1 and CXCL13 levels were measured by biochemical and ELISA. Lipid metabolism and the HMGB1-SREBP2-SR-BI pathway were detected by PCR and WB. 16 S and metabolomics were used to detect gut microbiota and serum metabolites. QA or low-frequency ABX inhibited weight gain and aortic tissue atherogenesis in HFD-induced Apoe−/− mice. QA inhibited the increase of cholesterol, TMA, TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe−/− mice induced by HFD. Meanwhile, QA or low-frequency ABX treatment inhibited the expression of CAV-1, ABCA1, Mac-3 and SM22α, and promoted the expression of SREBP-1 and LXR in the vascular tissues of HFD-induced Apoe−/− mice. QA reduced Streptococcus_danieliae abundance, and promoted Lactobacillus_intestinalis and Ileibacterium_valens abundance in HFD-induced Apoe−/− mice. QA altered serum galactose metabolism, promoted SREBP-2 and LDLR, inhibited IDOL, FMO3 and PCSK9 expression in liver of HFD-induced Apoe−/− mice. The combined treatment of QA and low-frequency ABX regulated microbe-related Glycoursodeoxycholic acid and GLYCOCHENODEOXYCHOLATE metabolism in HFD-induced Apoe−/− mice. QA inhibited TMAO or LDL-induced HCAECs damage and HMGB1/SREBP2 axis dysfunction, which was reversed by HMGB1 overexpression. QA regulated the gut-liver lipid metabolism and chronic vascular inflammation of TMA/TMAO through gut microbiota to inhibit the atherogenesis in Apoe−/− mice, and the mechanism may be related to the HMGB1/SREBP2 pathway.
摘要：
Coronavirus Disease 2019 (COVID-19) is generally susceptible to the population, highly infectious, rapidly transmitted, and highly fatal. There is a lack of specific drugs against the virus at present and vaccination is the most effective strategy to prevent infection. However, studies have found that some groups, particularly patients with diabetes, show varying degrees of weak immune reactivity to various COVID-19 vaccines, resulting in poor preventive efficacy against the novel coronavirus in patients with diabetes. Therefore, in this study, patients with type 2 diabetes mellitus (T2DM) who had weak immune response to the COVID-19 vaccine in recent years were analyzed. This article reviews the phenomenon, preliminary mechanism, and related factors affecting weak vaccine response in patients with T2DM, which is expected to help in the development of new vaccines for high-risk groups for COVID-19.
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.
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.
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.
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.
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：
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.
作者机构：
[Li, Chun-Quan; Tang, Hui-Fang; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Tang, Hui-Fang; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan] Univ South China, Hengyang Med Sch, Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Qian, Feng-Cui] Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, CQ ; Tang, HF ; Tang, HF] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
关键词：
chromatin;genes;software;epigenetics
摘要：
Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.
摘要：
Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.
摘要：
Gram-negative Bartonella species are facultative intracellular bacteria that can survive in the harsh intracellular milieu of host cells. They have evolved strategies to evade detection and degradation by the host immune system, which ensures their proliferation in the host. Following infection, Bartonella alters the initial immunogenic surface-exposed proteins to evade immune recognition via antigen or phase variation. The diverse lipopolysaccharide structures of certain Bartonella species allow them to escape recognition by the host pattern recognition receptors. Additionally, the survival of mature erythrocytes and their resistance to lysosomal fusion further complicate the immune clearance of this species. Certain Bartonella species also evade immune attacks by producing biofilms and anti-inflammatory cytokines and decreasing endothelial cell apoptosis. Overall, these factors create a challenging landscape for the host immune system to rapidly and effectively eradicate the Bartonella species, thereby facilitating the persistence of Bartonella infections and creating a substantial obstacle for therapeutic interventions. This review focuses on the effects of three human-specific Bartonella species, particularly their mechanisms of host invasion and immune escape, to gain new perspectives in the development of effective diagnostic tools, prophylactic measures, and treatment options for Bartonella infections.
