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1.
Microbiol Spectr ; 12(4): e0234223, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38391229

ABSTRACT

Seed metabolites are the combination of essential compounds required by an organism across various potential environmental conditions. The seed metabolites screening framework based on the network topology approach can capture important biological information of species. This study aims to identify comprehensively the relationship between seed metabolites and pathogenic bacteria. A large-scale data set was compiled, describing the seed metabolite sets and metabolite sets of 124,192 pathogenic strains from 34 genera, by constructing genome-scale metabolic models. The enrichment analysis method was used to screen the specific seed metabolites of each species/genus of pathogenic bacteria. The metabolites of pathogenic microorganisms database (MPMdb) (http://qyzhanglab.hzau.edu.cn/MPMdb/) was established for browsing, searching, predicting, or downloading metabolites and seed metabolites of pathogenic microorganisms. Based on the MPMdb, taxonomic and phylogenetic analyses of pathogenic bacteria were performed according to the function of seed metabolites and metabolites. The results showed that the seed metabolites could be used as a feature for microorganism chemotaxonomy, and they could mirror the phylogeny of pathogenic bacteria. In addition, our screened specific seed metabolites of pathogenic bacteria can be used not only for further tapping the nutritional resources and identifying auxotrophies of pathogenic bacteria but also for designing targeted bactericidal compounds by combining with existing antimicrobial agents.IMPORTANCEMetabolites serve as key communication links between pathogenic microorganisms and hosts, with seed metabolites being crucial for microbial growth, reproduction, external communication, and host infection. However, the large-scale screening of metabolites and the identification of seed metabolites have always been the main technical bottleneck due to the low throughput and costly analysis. Genome-scale metabolic models have become a recognized research paradigm to investigate the metabolic characteristics of species. The developed metabolites of pathogenic microorganisms database in this study is committed to systematically predicting and identifying the metabolites and seed metabolites of pathogenic microorganisms, which could provide a powerful resource platform for pathogenic bacteria research.


Subject(s)
Anti-Infective Agents , Seeds , Phylogeny , Bacteria , Databases, Factual , Anti-Infective Agents/metabolism
2.
Quant Imaging Med Surg ; 13(12): 8383-8394, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38106324

ABSTRACT

Background: Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke. The fetal-type posterior cerebral artery (FTP) affects intracranial collateral circulation, which is closely related to the occurrence and development of ICAD. Knowledge of the relationship between FTP and ICAD is important for developing treatment strategies for FTP patients diagnosed with atherosclerotic diseases. This study aims to quantitatively analyze the association between the FTP and intracranial atherosclerotic plaques using magnetic resonance vessel wall imaging (VW-MRI). Methods: This retrospective study enrolled patients with recent cerebrovascular symptoms (stroke or transient ischemic attack <2 weeks) who were diagnosed with atherosclerotic plaque(s) by VW-MRI in one hospital from October 2018 to March 2022. They were classified into the FTP group and the non-FTP group. Plaque characteristics and vascular-related parameters in intracranial arteries were compared between the two groups. Univariate and multivariate logistic regressions were performed to determine the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of the plaque characteristics between the two groups. Results: A total of 104 patients (mean age: 61.8±9.8 years, 57 males) were included for VW-MRI scan analysis. 40 (38.46%) and 64 (61.54%) were classified into the FTP and the non-FTP groups, respectively. The plaques of middle cerebral artery (MCA) in the FTP group were more likely to occur on the dorsal and superior walls of the lumen compared with the non-FTP group (37.50% vs. 17.19%, P=0.001). The remodeling index (RI) of MCA was statistically different between the two groups (1.071±0.267 vs. 0.886±0.235, P=0.007). No significant differences were found in vertebrobasilar artery (VBA) plaque distributions (17.50% vs. 9.38%, 10.00% vs. 12.50%, 20.00% vs. 17.19%, P>0.05) and characteristics between the two groups (RI: 1.095±0.355 vs. 0.978±0.251; eccentricity index: 0.539±1.622 vs. 0.550±0.171, P>0.05). Conclusions: The plaques in the FTP group were more likely to occur on the dorsal and superior walls of the MCA, and the presentence of FTP was found to be significantly correlated with vascular remodeling of MCA atherosclerotic plaques. The relationship between the severity of intracranial atherosclerosis and the presence of FTP can provide valuable information for clinicians to intervene early and prevent the occurrence of stroke.

3.
J Org Chem ; 88(23): 16400-16409, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37983977

ABSTRACT

A mild chlorocyclization of pyrrole-tethered indoles has been realized using POCl3 as the chlorine source and tetramethylene sulfoxide as the promoter. A variety of chlorinated indolizino[8,7-b]indole derivatives have been constructed efficiently under this reaction system in moderate to good yields (19 examples, up to 93% yield).

4.
Fa Yi Xue Za Zhi ; 39(4): 399-405, 2023 Aug 25.
Article in English, Chinese | MEDLINE | ID: mdl-37859480

ABSTRACT

The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.


Subject(s)
Microbiota , Postmortem Changes , Humans , Artificial Intelligence , Autopsy , Cadaver
5.
Phytomedicine ; 121: 155119, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37801894

ABSTRACT

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.


Subject(s)
Sepsis-Associated Encephalopathy , Mice , Animals , Sepsis-Associated Encephalopathy/drug therapy , Sepsis-Associated Encephalopathy/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Microglia , Lipopolysaccharides/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/metabolism
6.
Eur J Radiol ; 168: 111107, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37776582

ABSTRACT

PURPOSE: To investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. METHOD: Eighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. RESULTS: Higher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). CONCLUSIONS: Culprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.


Subject(s)
Brain Ischemia , Intracranial Arteriosclerosis , Ischemic Stroke , Plaque, Atherosclerotic , Stroke , Humans , Middle Cerebral Artery/diagnostic imaging , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Brain Ischemia/etiology , Brain Ischemia/complications , Glycated Hemoglobin , Constriction, Pathologic , Retrospective Studies , Ischemic Stroke/complications , Stroke/etiology , Stroke/complications , Magnetic Resonance Angiography/methods , Intracranial Arteriosclerosis/complications , Intracranial Arteriosclerosis/diagnostic imaging , Magnetic Resonance Imaging/methods
7.
J Org Chem ; 88(19): 13598-13609, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37728513

ABSTRACT

Benzylation of pyrrolo[2,1-a]isoquinoline derivatives has been realized with various phenols by the use of ammonium acetate as a promoter (20 examples, up to 84% yield). DMSO served as the source of methylene and solvent. The employment of iron chloride as a catalyst can also afford the desired benzylated products in moderate to good yields (11 examples, up to a 74% yield).

8.
J Colloid Interface Sci ; 652(Pt B): 1665-1672, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37666198

ABSTRACT

The rational design of electrocatalysts with exceptional performance and durability for hydrogen production in alkaline medium is a formidable challenge. In this study, we have developed in-situ activated ruthenium nanoparticles dispersed on Ni3N nanosheets, forming a bifunctional electrocatalyst for hydrogen evolution and urea oxidation. The results of experimental analysis and theoretical calculations reveal that the enhanced hydrogen evolution reaction (HER) performance of O-Ru-Ni3N stems primarily from the optimized hydrogen adsorption and hydroxyl adsorption on Ru sites. The O-Ru-Ni3N on nickel foam (NF) electrode exhibits excellent HER performance, requiring only 29 mV to reach 10 mA cm-2 in an alkaline medium. Notably, when this O-Ru-Ni3N/NF catalyst is employed for both HER and urea oxidation reaction (UOR) to create an integrated H2 production system, a current density of 50 mA cm-2 can be generated at the cell voltage of 1.41 V. This report introduces an energy-efficient catalyst for hydrogen production and proposes a viable strategy for anodic activation in energy chemistry.

9.
J Org Chem ; 88(16): 11935-11944, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37550603

ABSTRACT

We have developed an efficient chlorination of pyrrolo[2,1-a]isoquinoline derivatives using POCl3 as the chlorine source and tetramethylene sulfoxide as a promoter. A series of pyrrolo[2,1-a]isoquinolines, polysubstituted pyrroles, and naphthols have been readily chlorinated under mild reaction conditions (26 examples, up to >99% yield). AcCl can also act as the chlorine source competently in this chlorination reaction.

10.
J Colloid Interface Sci ; 651: 760-768, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37572613

ABSTRACT

Studying interfacial charge transfer is of great significance for the preparation of electrocatalysts with high activity for the hydrogen evolution reaction (HER). Particularly, exploring the in-depth catalytic mechanisms and facile fabrication methods of narrow bandgap metal phosphides remains worthwhile. This work successfully combined catalytically inert n-type Nb2O5 with p-type CoP to prepare a p-n heterojunction (CoP-Nb2O5). The self-supporting heterojunction was fabricated by gas-phase phosphorization of the Co(OH)2-Nb2O5 precursor obtained through hydrothermal-electrodeposition strategy. By analyzing the electronic and band structures of CoP and Nb2O5, it was found that there exists a built-in electric field (BEF) in the heterojunction. This BEF can modulate the electronic structure of CoP at the interface, enhance its intrinsic activity and accelerate charge migration. The subsequent experimental results also demonstrate that Nb2O5 can significantly enhance the activity and stability of CoP. Our findings can serve as a novel perspective on the application of p-n heterojunction in the field of energy storage and conversion.

11.
J Org Chem ; 88(11): 7347-7361, 2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37167603

ABSTRACT

We have developed a mild sulfenylation of pyrrolo[2,1-a]isoquinolines with acetyl bromide and dimethyl sulfoxide. A wide range of functionalized pyrrolo[2,1-a]isoquinolines could be prepared efficiently through the formation of a C-S bond with thiophenols (27 examples, 36-94% yields). The current strategy can also be utilized for functionalization of pyrrolo[1,2-a]quinolines and indole.

12.
Comput Struct Biotechnol J ; 21: 2973-2984, 2023.
Article in English | MEDLINE | ID: mdl-37235186

ABSTRACT

Transporters are the main determinant for pharmacokinetics characteristics of drugs, such as absorption, distribution, and excretion of drugs in humans. However, it is difficult to perform drug transporter validation and structure analysis of membrane transporter proteins by experimental methods. Many studies have demonstrated that knowledge graphs (KG) could effectively excavate potential association information between different entities. To improve the effectiveness of drug discovery, a transporter-related KG was constructed in this study. Meanwhile, a predictive frame (AutoInt_KG) and a generative frame (MolGPT_KG) were established based on the heterogeneity information obtained from the transporter-related KG by the RESCAL model. Natural product Luteolin with known transporters was selected to verify the reliability of the AutoInt_KG frame, its ROC-AUC (1:1), ROC-AUC (1:10), PR-AUC (1:1), PR-AUC (1:10) are 0.91, 0.94, 0.91 and 0.78, respectively. Subsequently, the MolGPT_KG frame was constructed to implement efficient drug design based on transporter structure. The evaluation results showed that the MolGPT_KG could generate novel and valid molecules and that these molecules were further confirmed by molecular docking analysis. The docking results showed that they could bind to important amino acids at the active site of the target transporter. Our findings will provide rich information resources and guidance for the further development of the transporter-related drugs.

13.
Syst Appl Microbiol ; 46(3): 126419, 2023 May.
Article in English | MEDLINE | ID: mdl-37030242

ABSTRACT

Two novel strains GSK1Z-4-2T and MQZ15Z-1 were isolated from branches of mangrove plants collected from Guangxi Zhuang Autonomous Region, China. Both strains were Gram-negative, aerobic, non-flagellated and non-spore-forming bacteria. The comparison of 16S rRNA gene sequences initially indicated that the two strains were assigned to the genus Ancylobacter with sharing the highest similarity to Ancylobacter pratisalsi DSM 102029T (97.3%). The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strains GSK1Z-4-2T and MQZ15Z-1 were 99.9%, 97.4% and 77.4%, respectively, which revealed that the two strains belonged to the same species. Phylogenetic analyses based on 16S rRNA gene sequences and the core proteome showed that the two strains formed a well-supported cluster with A. pratisalsi DSM 102029T. Moreover, the ANI and isDDH values between strain GSK1Z-4-2T and A. pratisalsi DSM 102029T were 83.0% and 25.8%, respectively, demonstrating that strain GSK1Z-4-2T was a previously undescribed species. Meanwhile, strains GSK1Z-4-2T and MQZ15Z-1 exhibited most of chemotaxonomic and phenotypic features consistent with the description of the genus Ancylobacter. Based on the polyphasic data, strains GSK1Z-4-2T and MQZ15Z-1 should represent a novel species of the genus Ancylobacter, for which the name Ancylobacter mangrovi sp. nov. is proposed. The type strain is GSK1Z-4-2T (=MCCC 1K07181T = JCM 34924T).


Subject(s)
Fatty Acids , Phylogeny , RNA, Ribosomal, 16S/genetics , China , DNA, Bacterial/genetics , Nucleic Acid Hybridization , Sequence Analysis, DNA , Bacterial Typing Techniques
14.
Yi Chuan ; 45(4): 341-353, 2023 Apr 20.
Article in English | MEDLINE | ID: mdl-37077167

ABSTRACT

Fracture healing is a rigorous and orderly process with multiple steps that are mediated by multiple cells. During this process, osteoclast-mediated bone remodeling plays a critical role, and its abnormal activity leads not only to fracture susceptibility but also to impaired fracture healing. However, few studies have focused on impaired healing caused by osteoclast defects, and clinical drugs for this type of impaired fracture healing are still lacking. The cell types and regulatory pathways in the zebrafish skeletal system are highly similar to those of mammals, making the zebrafish skeletal system being widely used for skeletal-related studies. To study the process of fracture healing disorders caused by osteoclast defects and discover potential therapeutic drugs, we established an in vivo osteoclast-deficient fracture model using a previously generated fms gene mutant zebrafish (fmsj4e1). The results showed that reduced functional osteoclasts could affect fracture repair in the early stages of fracture. Then we applied an in vitro scale culture system to screen for osteoclast-activating drugs. We found the small molecule compound allantoin (ALL) being able to activate osteoclasts. Subsequently, we verified the activation role of ALL on osteoclasts and the promotion of fracture repair in an in vivo fmsj4e1 fracture defect model. Finally, by examining the osteoclastogenesis and maturation process, we found that ALL may promote osteoclast maturation by regulating RANKL/OPG, thus promoting fmsj4e1 fracture healing. Our study provides a potential new approach for the future improvement of fracture healing disorders caused by osteoclast defects.


Subject(s)
Osteoclasts , Zebrafish , Animals , Osteoclasts/metabolism , Fracture Healing , Allantoin/metabolism , Osteogenesis , Cell Differentiation/genetics , Mammals
15.
Article in English | MEDLINE | ID: mdl-36884384

ABSTRACT

A endospore-forming bacterium, designated strain KQZ6P-2T, was isolated from surface-sterilized bark of the mangrove plant Kandelia candel, collected from Maowei Sea Mangrove Nature Reserve in Guangxi Zhuang Autonomous Region, China. Strain KQZ6P-2T was able to grow at NaCl concentrations in the range of 0-3 % (w/v) with optimum growth at 0-1 % (w/v) NaCl. Growth occurred at 20-42 °C (optimal growth at 30-37 °C) and pH 5.5-6.5 (optimal growth at pH 6.5). The 16S rRNA gene sequence similarity between strain KQZ6P-2T and its closest phylogenetic neighbour Paenibacillus chibensis JCM 9905T was 98.2 %. Phylogenetic analyses using 16S rRNA gene sequences showed that strain KQZ6P-2T formed a distinct lineage with Paenibacillus chibensis JCM 9905T. The draft genome of strain KQZ6P-2T was 5 937 633 bp in size and its DNA G+C content was 47.2mol%. Comparative genome analysis revealed that the average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values among strain KQZ6P-2T and its related species were below the cut-off levels of 95, 70 and 95.5%, respec-tively. The cell-wall peptidoglycan of strain KQZ6P-2T contained meso-diaminopimelic acid as the diagnostic diamino acid. Major cellular fatty acids were anteiso-C15:0 and C16:0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified aminophospholipids, four unidentified phospholipids, an unidentified aminolipid and five unidentified lipids. Based on phylogenetic, phenotypic and chemotaxonomic data, strain KQZ6P-2T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus mangrovi sp. nov. is proposed. The type strain is KQZ6P-2T (=MCCC 1K07172T =JCM 34931T).


Subject(s)
Paenibacillus , Rhizophoraceae , Fatty Acids/chemistry , Phylogeny , RNA, Ribosomal, 16S/genetics , Sodium Chloride , Plant Bark , DNA, Bacterial/genetics , Base Composition , China , Bacterial Typing Techniques , Sequence Analysis, DNA , Phospholipids/chemistry , Comparative Genomic Hybridization
16.
J Org Chem ; 88(7): 4649-4661, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-36947692

ABSTRACT

We have successfully modified a series of pyrrolo[2,1-a]isoquinolines via direct nitration under mild reaction conditions. Easily accessible nitrates including CAN, Cu(NO3)2·H2O, and Fe(NO3)3·9H2O all can serve as effective nitrating reagents for functionalizing pyrrolo[2,1-a]isoquinolines. Various nitro-bearing pyrrolo[2,1-a]isoquinolines have been efficiently prepared in acceptable to good yields.

17.
Physiol Genomics ; 55(3): 147-153, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36847439

ABSTRACT

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.


Subject(s)
Swine , Animals , Acetyl Coenzyme A , Genome , Polymorphism, Single Nucleotide , Swine/genetics , Swine/growth & development
18.
Cell Rep ; 42(2): 112078, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36735535

ABSTRACT

Complement activation is thought to underline the pathologic progression of obesity-related metabolic disorders; however, its role in adaptive thermogenesis has scarcely been explored. Here, we identify complement C3a receptor (C3aR) and C5a receptor (C5aR) as critical switches to control adipocyte browning and energy balance in male mice. Loss of C3aR and C5aR in combination, more than individually, increases cold-induced adipocyte browning and attenuates diet-induced obesity in male mice. Mechanistically, loss of C3aR and C5aR increases regulatory T cell (Treg) accumulation in the subcutaneous white adipose tissue during cold exposure or high-fat diet. Activated Tregs produce adenosine, which is converted to inosine by adipocyte-derived adenosine deaminases. Inosine promotes adipocyte browning in a manner dependent on activating adenosine A2a receptor. These data reveal a regulatory mechanism of complement in controlling adaptive thermogenesis and suggest that targeting the C3aR/C5aR pathways may represent a therapeutic strategy in treating obesity-related metabolic diseases.


Subject(s)
Receptor, Anaphylatoxin C5a , Signal Transduction , Animals , Male , Mice , Adipocytes , Diet , Obesity , Receptor, Anaphylatoxin C5a/metabolism
19.
Tissue Cell ; 81: 102039, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36805774

ABSTRACT

BACKGROUND: Accumulation of glutamate damages neurons via the reactive oxygen species (ROS) injury, which was involved in the development of neurodegenerative diseases. However, the mechanism of neuronal oxidative stress damage caused by glutamate and the intervention targets still needs to be further studied. This study explored whether 5' adenosine monophosphate-activated protein kinase (AMPK)-induced glucose metabolic and mitochondrial dysfunction were related to glutamate-dependent ROS injury of the neuron. METHODS: Neuronal oxidative stress injury was induced by glutamate treatment in HT-22 cells. Western blotting was used to evaluate the phosphorylation of the AMPK. The XF24 Flux Analyzer was used to measure the effect of glutamate and Compound C (a well-known pharmacological inhibitor of AMPK phosphorylation) on the cellular oxygen consumption rate (OCR) of HT-22 cells. Glucose uptake, intracellular ROS, mitochondrial potential, apoptosis and cell viability were quantified using biochemical assays. RESULTS: Glutamate caused the phosphorylation of AMPK and subsequently promoted the glucose uptake. Furthermore, AMPK-mediated glucose uptake enhanced OCR and increased the intracellular ROS levels in neurons. The pharmacological inhibition of AMPK phosphorylation by Compound C attenuated glutamate-induced toxicity in HT22 cells by regulating the glucose uptake/mitochondrial respiration/ROS pathway. CONCLUSIONS: The AMPK phosphorylation/glucose uptake/mitochondrial respiration/ROS pathway was involved in glutamate-induced excitotoxic injury in HT22 cells. The inhibition of AMPK phosphorylation may be a potential target for the development of therapeutic agents for treating the glutamate-induced neurotoxicity.


Subject(s)
Glutamic Acid , Neuroprotective Agents , Reactive Oxygen Species/metabolism , Glutamic Acid/metabolism , Glutamic Acid/pharmacology , AMP-Activated Protein Kinases/metabolism , Cell Line , Neuroprotective Agents/pharmacology , Oxidative Stress , Apoptosis , Mitochondria/metabolism , Glucose/metabolism
20.
World J Emerg Med ; 14(1): 10-16, 2023.
Article in English | MEDLINE | ID: mdl-36713343

ABSTRACT

BACKGROUND: Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure. Endothelial cells (ECs) exhibit specific metabolic traits and release metabolites to adapt to the septic state in the blood to maintain vascular homeostasis. METHODS: Web of Science and PubMed were searched from inception to October 1, 2022. The search was limited to the English language only. Two reviewers independently identified studies related to EC metabolism in sepsis. The exclusion criteria were duplicate articles according to multiple search criteria. RESULTS: Sixty articles were included, and most of them were cell and animal studies. These studies reported the role of glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism in EC homeostasis. including glycolysis, oxidative phosphorylation, fatty acid metabolism and amino acid metabolism. However, dysregulation of EC metabolism can contribute to sepsis progression. CONCLUSION: There are few clinical studies on EC metabolism in sepsis. Related research mainly focuses on basic research, but some scientific problems have also been clarified. Therefore, this review may provide an overall comprehension and novel aspects of EC metabolism in sepsis.

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