Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular le...Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular level,many small molecules play crucial roles in balancing growth and defense,and stable high yields can be achieved by fine-tuning the responses to external stimuli.Therefore,it is essential to understand the molecular mechanisms underlying plant growth in response to heat stress and how plants can adjust their biological processes to survive heat stress conditions.In this review,we summarize the heat-responsive genetic networks in plants and crop plants based on recent studies.We focus on how plants sense the elevated temperatures and initiate the cellular and metabolic responses that allow them to adapt to the adverse growing conditions.We also describe the trade-off between plant growth and responses to heat stress.Specifically,we address the regulatory network of plant responses to heat stress,which will facilitate the discovery of novel thermotolerance genes and provide new opportunities for agricultural applications.展开更多
The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally le...The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.展开更多
OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling ...Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.展开更多
Ca^(2+)signaling plays crucial roles in plant stress responses,including defense against insects.To counteract insect feeding,different parts of a plant deploy systemic signaling to communicate and coordinate defense ...Ca^(2+)signaling plays crucial roles in plant stress responses,including defense against insects.To counteract insect feeding,different parts of a plant deploy systemic signaling to communicate and coordinate defense responses,but little is known about the underlying mechanisms.In this study,micrografting,in vivo imaging of Ca^(2+)and reactive oxygen species(ROS),quantification of jasmonic acid(JA)and defensive metabolites,and bioassay were used to study how Arabidopsis seedlings regulate systemic responses in leaves after hypocotyls are wounded.We show that wounding hypocotyls rapidly activated both Ca^(2+)and ROS signals in leaves.RBOHD,which functions to produce ROS,along with two glutamate receptors GLR3.3 and GLR3.6,but not individually RBOHD or GLR3.3 and GLR3.6,in hypocotyls regulate the dynamics of systemic Ca^(2+)signals in leaves.In line with the systemic Ca^(2+)signals,after wounding hypocotyl,RBOHD,GLR3.3,and GLR3.6 in hypocotyl also cooperatively regulate the transcriptome,hormone jasmonic acid,and defensive secondary metabolites in leaves of Arabidopsis seedlings,thus controlling the systemic resistance to insects.Unlike leaf-to-leaf systemic signaling,this study reveals the unique regulation of wounding-induced hypocotyl-to-leaf systemic signaling and sheds new light on how different plant organs use complex signaling pathways to modulate defense responses.展开更多
OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and ...OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.展开更多
Inspired by the light-dependent signal transduction in nature, we herein report a fully synthetic receptor AZO with the capacity of transmembrane signaling, working by photo-induced change of molecular conformation. O...Inspired by the light-dependent signal transduction in nature, we herein report a fully synthetic receptor AZO with the capacity of transmembrane signaling, working by photo-induced change of molecular conformation. Our receptor has an anchoring group, a rigid and photoresponsive transmembrane unit and a precatalyst tailgroup. After doping in lipid membranes, AZO is membrane anchored and the extended trans-isomer enables the tailgroup to bind with intravesicular Zn^(2+), thereby achieving enzyme activation and triggering downstream events(ester hydrolysis). However, the shortened cis-isomer pulls the tailgroup into lipids, thereby preventing the complexation and all transduction processes. Upon alternative irradiation of ultraviolet(UV) and visible light, the transduction process can be reversible switch between“ON” and “OFF”, achieving light signal transduction. This study provides a new strategy for future design of artificial signal transduction receptors.展开更多
OBJECTIVES:To investigate the therapeutic effect of Huluan decotion(护卵汤,HLD)on cyclophosphamideinduced premature ovarian failure(POF)in mice and its regulatory mechanisms.METHODS:Female BALB/c mice were administere...OBJECTIVES:To investigate the therapeutic effect of Huluan decotion(护卵汤,HLD)on cyclophosphamideinduced premature ovarian failure(POF)in mice and its regulatory mechanisms.METHODS:Female BALB/c mice were administered cyclophosphamide and administered received different doses of HLD for 28 d.Levels of sex hormone,such as estradiol(E2),follicle stimulating hormone(FSH)and luteinizing hormone(LH)in the sera,were assessed using enzyme-linked immunosorbent assay(ELISA).Follicular structure variances were observed through hematoxylin and eosin(HE)staining,while Forkhead box L2(FOXL2)expression were analyzed via immuneohistochemical staining.The primary mechanism of POF were investigated through Western blot analysis.RESULTS:E2 levels decreased,and FSH and LH levels increased in POF model mice,but these trends were reversed with HLD or premarin administration,the expressions of WNT family member 4(Wnt4),β-Catenin and FOXL2 were downregulated in POF model mice,whereas high expression levels were observed in control mice and other groups.CONCLUSION:HLD effectively treats POF induced with cyclophosphamide in mice by enhancing expressions of Wnt4,β-Catenin and FOXL2.展开更多
OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in ...OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.METHODS:The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice.Cytokines were detected by enzyme-linked immuneosorbent assay(ELISA),macrophages in lung tissue were determined by immunofluorescence,and pathwayrelated data were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot.RESULTS:The liver,thymus,and spleen index values and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)obviously increased in LPS-treated mice.FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS.The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure,alleviate interstitial oedema and alveolar wall thickening,and reduce inflammatory cell infiltration.Moreover,FZXF markedly reduced the expression of proinflammatory cytokines.FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung.By immunofluorescence,we found that FZXF could reduce macrophage infiltration.The mRNA expression levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),toll-like receptor 4(TLR4)and nuclear transcription factorκB(NF-κB)in the lung tissue of mice were decreased by treatment with FZXF.In addition,FZXF inhibited the protein expression of TLR4,p-p65 and COX-2.These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.CONCLUSION:These findings were suggested that FZXF prescription suppresses inflammation in LPSinduced pneumonia in mice via TLR4/NF-κB and COX-2/PGE2 pathway.展开更多
Infertility has become one of the most serious diseases worldwide,and 50% of this disease can be attributed to male-related factors.Spermatogenesis,by definition,is a complex process by which spermatogonial stem cells...Infertility has become one of the most serious diseases worldwide,and 50% of this disease can be attributed to male-related factors.Spermatogenesis,by definition,is a complex process by which spermatogonial stem cells(SSCs)self-renew to maintain stem cell population within the testes and differentiate into mature spermatids.It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility.Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs.In this review,we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal,differentiation,and apoptosis of SSCs,and we illustrate the networks of genes and signaling pathways in SSC fate determinations.We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways.This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.展开更多
OBJECTIVE:To confirm the therapeutic effect and mechanism of Jingui Shenqi pill(金匮肾气丸,JGSQP)on cardiorenal syndrome.METHODS:Doxorubicin was used to build heart-kidney coinjury rat model.After the modeling was com...OBJECTIVE:To confirm the therapeutic effect and mechanism of Jingui Shenqi pill(金匮肾气丸,JGSQP)on cardiorenal syndrome.METHODS:Doxorubicin was used to build heart-kidney coinjury rat model.After the modeling was completed,JGSQP gavage intervention was performed.The cardiac function of rats in each group was evaluated by ultrasound detection.Serum of rats was collected and examined for markers of heart and kidney damage.Enzyme linked immunosorbent assay detected serum inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)expression.Quantitative real-time polymerase chain reaction(PCR)and Western blot detected the changes of related genes and proteins.RESULTS:JGSQP significantly increased left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)values,decreased the heart and kidney damage markers and fibrosis levels(P<0.05).Furthermore,it can reduce IL-1β,IL-6,and TNF-αinflammatory expression(P<0.05).Mechanistically,JGSQP significantly inhibited the expression of key genes and proteins of mitogen-activated protein kinase(MAPK)signaling pathway(P<0.05).CONCLUSIONS:Jingui Shenqi pill can exert therapeutic effects on cardiorenal syndrome by inhibiting the activation of the MAPK signaling pathway and inflammatory responses.展开更多
Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrat...Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrates in response to various stress conditions. Beyond their role in stress adaptation, certain GSTs are integral regulators of plant growth and development, contributing to a range of physiological processes. Most GST proteins exhibit dual enzymatic activities, functioning as both transferases and peroxidases, which enables their involvement in diverse cellular processes, including detoxification and stress responses. Recent advancements, particularly in X-ray crystallography, have enabled detailed structural analysis of GST proteins, significantly enhancing our understanding of their biological functions. This review offers a comprehensive overview of the classification and structural characteristics of GSTs in plants. It also highlights recent findings on their roles in plant growth and development, cell signaling, catalytic transport, and stress tolerance. Furthermore, key scientific challenges related to GSTs are discussed, focusing on their potential applications in agriculture. These insights aim to facilitate the screening of functional GST genes and support molecular breeding efforts across diverse crop species.展开更多
Related to ABI3 and VP1(RAV)transcription factors belong to the AP2 and B3 superfamily.RAVs genes have been reported to be involved in plant growth and development regulation.This study screened three RAV genes from M...Related to ABI3 and VP1(RAV)transcription factors belong to the AP2 and B3 superfamily.RAVs genes have been reported to be involved in plant growth and development regulation.This study screened three RAV genes from Medicago truncatula and named one of them MtRAV1.The MtRAV1 overexpressing plants exhibits traits such as plant dwarfing,delayed flowering,reduced leaf and floral organs,increased branching,and reduced pods and seeds.Gene expression analysis results showed that overexpression of Mt RAV1 inhibited the expression of Flowering Locus T(MtFTa1),Suppressor of Overexpression of CO1(MtSOC1),GA3-oxidase1(MtGA3OX1),DWARF14(MtD14)and Carotenoid Cleavage Dioxygenase7(MtCCD7).To further investigate the regulation pathway involved by MtRAV1,RNA-sequencing(RNA-seq)and DNA affinity purification sequencing(DAP-seq)analysis were conducted.RNA-seq results indicated that MtRAV1 might affect plant growth and development by regulating some genes in photosynthesis,circadian rhythm and plant hormone signaling pathways,especially the auxin signaling pathway.Conjoint analysis of DAP-seq and RNA-seq revealed that Mt RAV1 might inhibit the expression of Ferredoxin(Mt Fd-l3),Light-harvesting Chlorophyll a/b Binding Protein 1(Mt Lhcb-l2)and Small Auxin Up-regulated RNA(Mt SAUR-l),which related to photosystem II and auxin signaling pathway.Summarily,MtRAV1 was preliminarily proven to be a key growth inhibitory factor in M.truncatula.展开更多
OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential ...OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM.Initially,we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom Mapping(Sym Map),and gathered targets of TFK and T2DM.Subsequently,we constructed a protein-protein interaction(PPI)network,enriched core targets through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and adopted molecular docking to study the binding mode of compounds and the signaling pathway.Finally,we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM.Biochemical assay,histology assay,and Western blot(WB)were used to assess the mechanism.RESULTS:There were 492 bioactive compounds of TFK screened,and 1226 overlapping targets of TFK against T2DM identified.A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed.KEGG enrichment analysis identified some core pathways related to T2DM,including adenosine 5-monophosphate-activated protein kinase(AMPK)signaling pathway.Molecular docking study revealed that compounds of TFK,including citric acid,could bind to the active pocket of AMPK crystal structure with free binding energy of-4.8,-8 and-7.9,respectively.Animal experiments indicated that TFK decreased body weight,fasting blood glucose,fasting serum insulin,homeostasis model of insulin resistance,glycosylated serum protein,total cholesterol,triglyceride,and low-density lipoprotein cholesterol,and improve oral glucose tolerance test results.TFK reduced steatosis in liver tissue,and infiltration of inflammatory cells,and protected liver cells to a certain extent.WB analysis revealed that,TFK upregulated the phosphorylation of AMPK and branchedchainα-ketoacid dehydrogenase proteins.CONCLUSION:TFK has the potential to effectively manage T2DM,possibly by regulating the AMPK signaling pathway.The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.展开更多
OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic tar...OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.展开更多
OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)trea...OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)treated with platelet-derived growth factor(PDGF)-BB to establish a asthma model in vivo and in vitro.The cell morphology was observed with microscope and immunofluorescence staining.The cell viability was assessed with methyl thiazolyl tetrazolium assay.The tumor necrosis factor-αlpha(TNF-α),interleukin-1beta(IL-1β),laminin,fibronectin and collagen IV levels in the ASMCs were detected with corresponding enzyme linked immunosorbent assay kits.Transwell and wound healing assays were conducted to test the cell migration.The TGF-β1,Smad2 and Smad3 levels were measured with Western blot.RESULTS:We found that QFJJ formula treatment dramatically decreased the cell viability,TNF-α,IL-1β,laminin,fibronectin and collagen IV levels in the PDGFBB stimulated ASMCs.Additionally,the protein levels of TGF-β1,Smad2 and Smad3 in the PDGF-BB stimulated ASMCs were prominently depleted after QFJJ formula treatment.Besides,SRI treatment neutralized the role of QFJJ formula in the PDGF-BB stimulated ASMCs.CONCLUSION:QFJJ formula effectively relieved the asthma progression through ameliorate the ASMCs function,which was achieved through suppressing the TGF-β1/Smads signaling pathway.展开更多
OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was establishe...OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.展开更多
Piezoelectric transduction technology enables the direct conversion between mechanical and electrical energy,finding extensive applications in sensing,acoustics,imaging,actuation,and energy harvesting[1].Previous stud...Piezoelectric transduction technology enables the direct conversion between mechanical and electrical energy,finding extensive applications in sensing,acoustics,imaging,actuation,and energy harvesting[1].Previous studies on piezoelectric materials have primarily focused on ceramics or single-crystal materials characterized by wide band gaps(E_(g)>2.0 e V[2])and low electrical conductivity.In contrast,narrow-bandgap(E_(g)<0.5 eV[3])semiconductor materials typically exhibit high electrical conductivity,which is unfavorable for the effective accumulation of charges required to establish a stable voltage response.Consequently,experimental investigations into the piezoelectric effect of narrow-bandgap semiconductors are scarce.展开更多
Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in hu...Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in humans and other species have demonstrated its pivotal role in regulating the sodium ion balance and mediating sodium and water reabsorption in the kidney's proximal tubules.However,the impact of EGFR gene in how the Yarkand hare(Lepus yarkandensis)adapts to extreme environmental habitat remains unclear,The Yarkand hare is a desert-dwelling animal with multiple adaptations to cope with drought.Given the important physiological function of EGFR gene,we strived to understand its role in arid environment and explore the molecular mechanism of drought tolerance in the Yarkand hare.We first performed segmental cloning of the CDS of the Yarkand hare EGFR gene.Then,We constructed the phylogenetic tree of the Yarkand hare's EGFR gene and compared it with that of other species.The results showed that the Yarkand hare was most closely related to the Tolai hare(Lepus tolai).Through quantitative reverse transcription polymerase chain reaction(RT-qPCR),we discovered that EGFR expression in the kidneys of the Yarkand hare was higher than in the allopatric Tolai hare from non-arid areas.Therefore,we hypothesized that EGFR gene overexpression in the kidney of the Yarkand hare may play a crucial role in drought adaptability.Subsequently,we inserted CDS of EGFR gene into a pcDNA3.1-EGFP expression vector to construct recombinant plasmid,which was transfected into HeLa cells and overexpressed.RT-qPCR demonstrated a notable and statistically significant increase in EGFR mRNA expression and western blot proved stable expression of this protein in HeLa cells.Through cell experiments,EGFR gene overexpression markedly enhanced the survival of Hela cells subjected to NaCl,H_(2)O_(2),and heat stresses,increased superoxide dismutase activity,and decreased malondialdehyde content.In conclusion,these findings preliminarily suggest that EGFR might help the Yarkand hare adapt to extreme environmental conditions.EGFR manipulation in vivo could be a promising strategy to enhance the resilience of animals to extreme conditions.展开更多
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
基金supported by the National Natural Science Foundation of China(32171945,32301760)the Program for Innovative Research Team(in Science and Technology)in University of Henan Province,China(22IRTSTHN023)+2 种基金the Scientific and Technological Research Project of Henan Province,China(242102111116)the National Science Foundation for Postdoctoral Scientists of China(2023M731003)the Postdoctoral Research Subsidize Fund of Henan Province,China(HN2022139)。
文摘Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular level,many small molecules play crucial roles in balancing growth and defense,and stable high yields can be achieved by fine-tuning the responses to external stimuli.Therefore,it is essential to understand the molecular mechanisms underlying plant growth in response to heat stress and how plants can adjust their biological processes to survive heat stress conditions.In this review,we summarize the heat-responsive genetic networks in plants and crop plants based on recent studies.We focus on how plants sense the elevated temperatures and initiate the cellular and metabolic responses that allow them to adapt to the adverse growing conditions.We also describe the trade-off between plant growth and responses to heat stress.Specifically,we address the regulatory network of plant responses to heat stress,which will facilitate the discovery of novel thermotolerance genes and provide new opportunities for agricultural applications.
基金supported by the Deutsche Forschungsgemeinschaft (ME1922/14-1) to AM。
文摘The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
基金supported by the National Natural Science Foundation of China,No.82101115(to JY)the Wuhan University Independent Innovation Fund Youth Project,No.2042021kf0094(to JY).
文摘Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.
基金National Natural Science Foundation of China(U23A20199)Yunnan Revitalization Talent Support Program“Yunling Scholar”and Yunnan Fundamental Research Projects(202201AS070056)。
文摘Ca^(2+)signaling plays crucial roles in plant stress responses,including defense against insects.To counteract insect feeding,different parts of a plant deploy systemic signaling to communicate and coordinate defense responses,but little is known about the underlying mechanisms.In this study,micrografting,in vivo imaging of Ca^(2+)and reactive oxygen species(ROS),quantification of jasmonic acid(JA)and defensive metabolites,and bioassay were used to study how Arabidopsis seedlings regulate systemic responses in leaves after hypocotyls are wounded.We show that wounding hypocotyls rapidly activated both Ca^(2+)and ROS signals in leaves.RBOHD,which functions to produce ROS,along with two glutamate receptors GLR3.3 and GLR3.6,but not individually RBOHD or GLR3.3 and GLR3.6,in hypocotyls regulate the dynamics of systemic Ca^(2+)signals in leaves.In line with the systemic Ca^(2+)signals,after wounding hypocotyl,RBOHD,GLR3.3,and GLR3.6 in hypocotyl also cooperatively regulate the transcriptome,hormone jasmonic acid,and defensive secondary metabolites in leaves of Arabidopsis seedlings,thus controlling the systemic resistance to insects.Unlike leaf-to-leaf systemic signaling,this study reveals the unique regulation of wounding-induced hypocotyl-to-leaf systemic signaling and sheds new light on how different plant organs use complex signaling pathways to modulate defense responses.
基金Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases (20MC1920600)Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901)+3 种基金The Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"[Letter of the People's Education of Traditional Chinese Medicine (2019) No.62]Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team [No.3 of Shanghai Education Commission (2022)]Program for Shanghai High-Level Local University Innovation Team (SZY20220315)Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan (SHDC2020CR3090B)。
文摘OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.
基金supported by the National Natural Science Foundation of China (No. 22171085)Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, No. 2021 Sci & Tech 03–28)。
文摘Inspired by the light-dependent signal transduction in nature, we herein report a fully synthetic receptor AZO with the capacity of transmembrane signaling, working by photo-induced change of molecular conformation. Our receptor has an anchoring group, a rigid and photoresponsive transmembrane unit and a precatalyst tailgroup. After doping in lipid membranes, AZO is membrane anchored and the extended trans-isomer enables the tailgroup to bind with intravesicular Zn^(2+), thereby achieving enzyme activation and triggering downstream events(ester hydrolysis). However, the shortened cis-isomer pulls the tailgroup into lipids, thereby preventing the complexation and all transduction processes. Upon alternative irradiation of ultraviolet(UV) and visible light, the transduction process can be reversible switch between“ON” and “OFF”, achieving light signal transduction. This study provides a new strategy for future design of artificial signal transduction receptors.
基金Fujian Natural Science:Study on Potential Protein Targets of Huluan Decotion in the Intervention of Premature Ovarian Failure(No.2021J011173)Major Project Cultivation Plan Project of Ningde Normal University:the Effect of Huluan Decotion on the Decreased Ovarian Reserve Function Induced by Cyclophosphamide is Studied based on Forkhead box L2(No.2019ZDK06)。
文摘OBJECTIVES:To investigate the therapeutic effect of Huluan decotion(护卵汤,HLD)on cyclophosphamideinduced premature ovarian failure(POF)in mice and its regulatory mechanisms.METHODS:Female BALB/c mice were administered cyclophosphamide and administered received different doses of HLD for 28 d.Levels of sex hormone,such as estradiol(E2),follicle stimulating hormone(FSH)and luteinizing hormone(LH)in the sera,were assessed using enzyme-linked immunosorbent assay(ELISA).Follicular structure variances were observed through hematoxylin and eosin(HE)staining,while Forkhead box L2(FOXL2)expression were analyzed via immuneohistochemical staining.The primary mechanism of POF were investigated through Western blot analysis.RESULTS:E2 levels decreased,and FSH and LH levels increased in POF model mice,but these trends were reversed with HLD or premarin administration,the expressions of WNT family member 4(Wnt4),β-Catenin and FOXL2 were downregulated in POF model mice,whereas high expression levels were observed in control mice and other groups.CONCLUSION:HLD effectively treats POF induced with cyclophosphamide in mice by enhancing expressions of Wnt4,β-Catenin and FOXL2.
基金Emergency Corona Virus Disease 2019(COVID-19)Response Project of Dongguan:Clinical Efficacy Observation and Mechanism Study of Fuzheng Xuanfei Huashi Formula in the Treatment of COVID-19 Based on the Lingnan Theory of Epidemic Diseases(No.202071715002124)National Natural Science Foundation of China:Study on the Mechanism of Lung Inflammatory Injury Induced by Gut-derived Lipopolysaccharide and Skatole in Spleen Deficiency Animals based on Pulmonary Alveolus Macrophage Heterogeneity(No.82274381)Guangdong Basic and Applied Basic Research Foundation:Development and Industrialization of Traditional Chinese Medicine Classic and Famous Prescription Compound Formulations(No.2021ZD006)。
文摘OBJECTIVE:To determine the effect of Traditional Chinese Medicine(TCM)Fuzheng Xuanfei Huashi prescription(扶正宣肺化湿方,FZXF)on lipopolysaccharide(LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.METHODS:The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice.Cytokines were detected by enzyme-linked immuneosorbent assay(ELISA),macrophages in lung tissue were determined by immunofluorescence,and pathwayrelated data were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot.RESULTS:The liver,thymus,and spleen index values and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)obviously increased in LPS-treated mice.FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS.The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure,alleviate interstitial oedema and alveolar wall thickening,and reduce inflammatory cell infiltration.Moreover,FZXF markedly reduced the expression of proinflammatory cytokines.FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung.By immunofluorescence,we found that FZXF could reduce macrophage infiltration.The mRNA expression levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),toll-like receptor 4(TLR4)and nuclear transcription factorκB(NF-κB)in the lung tissue of mice were decreased by treatment with FZXF.In addition,FZXF inhibited the protein expression of TLR4,p-p65 and COX-2.These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.CONCLUSION:These findings were suggested that FZXF prescription suppresses inflammation in LPSinduced pneumonia in mice via TLR4/NF-κB and COX-2/PGE2 pathway.
基金supported by the grants from the National Nature Science Foundation of China(No.32170862)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defect in Hunan Province(No.2019SK1012)+1 种基金the Research Team for Reproduction Health and Translational Medicine of Hunan Normal University(No.2023JC101)Graduate Scientific Research Innovation Project of Hunan Province,China(No.CX2022520).
文摘Infertility has become one of the most serious diseases worldwide,and 50% of this disease can be attributed to male-related factors.Spermatogenesis,by definition,is a complex process by which spermatogonial stem cells(SSCs)self-renew to maintain stem cell population within the testes and differentiate into mature spermatids.It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility.Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs.In this review,we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal,differentiation,and apoptosis of SSCs,and we illustrate the networks of genes and signaling pathways in SSC fate determinations.We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways.This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.
基金Supported by Shanghai Putuo District Health System Science and Technology Innovation Project:Study on the Effect and Mechanism of Jinkui Shenqi Pills on Renal Water Metabolism via provirus integration site for moloney murine leukemia virus 3/aquaporin 2 Regulation (No. PTKWS202104)Chengdu University of Traditional Chinese Medicine "Xinglin Scholar" Discipline Talent Research Enhancement Plan:Based on provirus integration site for moloney murine leukemia virus 3 to Explore the Molecular Mechanism of Jingui Shenqi pill in Regulating Water Metabolism in Renal Tubular Cells (No. YYZX2022165)the Clinical Advantage Discipline of Health System of Putuo District in Shanghai (2019ysxk01)
文摘OBJECTIVE:To confirm the therapeutic effect and mechanism of Jingui Shenqi pill(金匮肾气丸,JGSQP)on cardiorenal syndrome.METHODS:Doxorubicin was used to build heart-kidney coinjury rat model.After the modeling was completed,JGSQP gavage intervention was performed.The cardiac function of rats in each group was evaluated by ultrasound detection.Serum of rats was collected and examined for markers of heart and kidney damage.Enzyme linked immunosorbent assay detected serum inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)expression.Quantitative real-time polymerase chain reaction(PCR)and Western blot detected the changes of related genes and proteins.RESULTS:JGSQP significantly increased left ventricular ejection fraction(EF)and left ventricular shortening fraction(FS)values,decreased the heart and kidney damage markers and fibrosis levels(P<0.05).Furthermore,it can reduce IL-1β,IL-6,and TNF-αinflammatory expression(P<0.05).Mechanistically,JGSQP significantly inhibited the expression of key genes and proteins of mitogen-activated protein kinase(MAPK)signaling pathway(P<0.05).CONCLUSIONS:Jingui Shenqi pill can exert therapeutic effects on cardiorenal syndrome by inhibiting the activation of the MAPK signaling pathway and inflammatory responses.
基金funded by National Natural Science Foundation of China(grant no.32301870 to Chen Lin)Natural Science Foundation of Jiangsu Province(grant no.BK20230568 to Chen Lin)+3 种基金the Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund(grant no.CX(24)3124 to Chen Lin)Outstanding Ph.D.Programin Yangzhou(grant no.YZLYJFJH2022YXBS147 to Chen Lin)the General Project of Basic Scientific Research to colleges and universities in Jiangsu Province(grant no.22KJB210019 toChen Lin)the Priority Academic Program Development of Jiangsu Higher Education Institutions is greatly acknowledged.
文摘Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrates in response to various stress conditions. Beyond their role in stress adaptation, certain GSTs are integral regulators of plant growth and development, contributing to a range of physiological processes. Most GST proteins exhibit dual enzymatic activities, functioning as both transferases and peroxidases, which enables their involvement in diverse cellular processes, including detoxification and stress responses. Recent advancements, particularly in X-ray crystallography, have enabled detailed structural analysis of GST proteins, significantly enhancing our understanding of their biological functions. This review offers a comprehensive overview of the classification and structural characteristics of GSTs in plants. It also highlights recent findings on their roles in plant growth and development, cell signaling, catalytic transport, and stress tolerance. Furthermore, key scientific challenges related to GSTs are discussed, focusing on their potential applications in agriculture. These insights aim to facilitate the screening of functional GST genes and support molecular breeding efforts across diverse crop species.
基金supported by the Key Projects in Science and Technology of Inner Mongolia,China(2021ZD0031)the China Agriculture Research System of MOF and MARA(CARS-34)+1 种基金the Performance Incentive and Guidance Special Project of Scientific Research Institution,Chongqing Science and Technology Committee,China(cstc2022jxjl80019)the Natural Science Foundation of Chongqing,China(CSTB2022NSCQ-BHX0744)。
文摘Related to ABI3 and VP1(RAV)transcription factors belong to the AP2 and B3 superfamily.RAVs genes have been reported to be involved in plant growth and development regulation.This study screened three RAV genes from Medicago truncatula and named one of them MtRAV1.The MtRAV1 overexpressing plants exhibits traits such as plant dwarfing,delayed flowering,reduced leaf and floral organs,increased branching,and reduced pods and seeds.Gene expression analysis results showed that overexpression of Mt RAV1 inhibited the expression of Flowering Locus T(MtFTa1),Suppressor of Overexpression of CO1(MtSOC1),GA3-oxidase1(MtGA3OX1),DWARF14(MtD14)and Carotenoid Cleavage Dioxygenase7(MtCCD7).To further investigate the regulation pathway involved by MtRAV1,RNA-sequencing(RNA-seq)and DNA affinity purification sequencing(DAP-seq)analysis were conducted.RNA-seq results indicated that MtRAV1 might affect plant growth and development by regulating some genes in photosynthesis,circadian rhythm and plant hormone signaling pathways,especially the auxin signaling pathway.Conjoint analysis of DAP-seq and RNA-seq revealed that Mt RAV1 might inhibit the expression of Ferredoxin(Mt Fd-l3),Light-harvesting Chlorophyll a/b Binding Protein 1(Mt Lhcb-l2)and Small Auxin Up-regulated RNA(Mt SAUR-l),which related to photosystem II and auxin signaling pathway.Summarily,MtRAV1 was preliminarily proven to be a key growth inhibitory factor in M.truncatula.
基金Tsinghua Precision Medicine Foundation:Tangfukang Plays the Therapeutic Role in Type 2 Diabetes Patients with Qi and Yin Deficiency Syndrome by Regulating the Intestinal Flora Mediated Branched-chain Amino Acids-Phosphatidylinositide 3-Kinases-Protein Kinase B Signaling Pathway(grant number 10001020105)National Natural Science Foundation of China:Tangfukang Plays the Therapeutic Role in Type 2 Diabetes Mellitus by Regulating the Intestinal Flora Mediated Adiponectin-adenosine 5-Monophosphate-activated Protein Kinase-branched-chain Amino Acids Signaling Pathway(grant number 82104812)。
文摘OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM.Initially,we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom Mapping(Sym Map),and gathered targets of TFK and T2DM.Subsequently,we constructed a protein-protein interaction(PPI)network,enriched core targets through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and adopted molecular docking to study the binding mode of compounds and the signaling pathway.Finally,we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM.Biochemical assay,histology assay,and Western blot(WB)were used to assess the mechanism.RESULTS:There were 492 bioactive compounds of TFK screened,and 1226 overlapping targets of TFK against T2DM identified.A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed.KEGG enrichment analysis identified some core pathways related to T2DM,including adenosine 5-monophosphate-activated protein kinase(AMPK)signaling pathway.Molecular docking study revealed that compounds of TFK,including citric acid,could bind to the active pocket of AMPK crystal structure with free binding energy of-4.8,-8 and-7.9,respectively.Animal experiments indicated that TFK decreased body weight,fasting blood glucose,fasting serum insulin,homeostasis model of insulin resistance,glycosylated serum protein,total cholesterol,triglyceride,and low-density lipoprotein cholesterol,and improve oral glucose tolerance test results.TFK reduced steatosis in liver tissue,and infiltration of inflammatory cells,and protected liver cells to a certain extent.WB analysis revealed that,TFK upregulated the phosphorylation of AMPK and branchedchainα-ketoacid dehydrogenase proteins.CONCLUSION:TFK has the potential to effectively manage T2DM,possibly by regulating the AMPK signaling pathway.The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.
基金Supported by Guangzhou Science and Technology Bureau Research Fund:the Mechanism of Action of Huangqi Guizhi Decoction on Precancerous Lesions in Cag Rats was Studied based on the Phosphatidylinositol 3-Kinase-Protein Kinase B-Mechanistic Target of Rapamycin Complex 2 Pathway(No.202102080643)Guangzhou Traditional Chinese Medicine and Integrative Medicine Research Project:Observation on the Therapeutic Effect of Wenyang Jianpi Ointment on Chronic Atrophic Gastritis of Spleen and Stomach Weakness Type and Study on its Regulatory Effect on Transforming Growth Factor Beta 3(No.20222A010079)Panyu District Science and Technology Project:the Mechanism by which the Modified Huangqi Guizhi Decoction Regulates the Transforming Growth Factor-β3 Signaling Pathway to Improve Precancerous Lesions in Rats with Chronic Atrophic Gastritis(No.2020-Z04-025)。
文摘OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.
基金Supported by Science and Technology Innovation Project of China Academy of Chinese Medical Sciences of Study on the Mechanism of Qufeng Jiejing Formula in Regulating Mitogen-activated Protein Kinase Signaling Pathway to Inhibit Phenotypic Transformation of Airway Smooth Muscle Cells in Asthma(No.CI2021A01108)Cultivation Project of The National Natural Science Foundation of China of Xiyuan Hospital,China Academy of Chinese Medical Sciences of Research on the Role of Traditional Chinese Medicines-Qufeng Jiejing in the Proliferation,Migration and Phenotypic Transformation of Airway Smooth Muscle Cells in Asthma(No.XY20-17)。
文摘OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)treated with platelet-derived growth factor(PDGF)-BB to establish a asthma model in vivo and in vitro.The cell morphology was observed with microscope and immunofluorescence staining.The cell viability was assessed with methyl thiazolyl tetrazolium assay.The tumor necrosis factor-αlpha(TNF-α),interleukin-1beta(IL-1β),laminin,fibronectin and collagen IV levels in the ASMCs were detected with corresponding enzyme linked immunosorbent assay kits.Transwell and wound healing assays were conducted to test the cell migration.The TGF-β1,Smad2 and Smad3 levels were measured with Western blot.RESULTS:We found that QFJJ formula treatment dramatically decreased the cell viability,TNF-α,IL-1β,laminin,fibronectin and collagen IV levels in the PDGFBB stimulated ASMCs.Additionally,the protein levels of TGF-β1,Smad2 and Smad3 in the PDGF-BB stimulated ASMCs were prominently depleted after QFJJ formula treatment.Besides,SRI treatment neutralized the role of QFJJ formula in the PDGF-BB stimulated ASMCs.CONCLUSION:QFJJ formula effectively relieved the asthma progression through ameliorate the ASMCs function,which was achieved through suppressing the TGF-β1/Smads signaling pathway.
文摘OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.
文摘Piezoelectric transduction technology enables the direct conversion between mechanical and electrical energy,finding extensive applications in sensing,acoustics,imaging,actuation,and energy harvesting[1].Previous studies on piezoelectric materials have primarily focused on ceramics or single-crystal materials characterized by wide band gaps(E_(g)>2.0 e V[2])and low electrical conductivity.In contrast,narrow-bandgap(E_(g)<0.5 eV[3])semiconductor materials typically exhibit high electrical conductivity,which is unfavorable for the effective accumulation of charges required to establish a stable voltage response.Consequently,experimental investigations into the piezoelectric effect of narrow-bandgap semiconductors are scarce.
基金supported by the Central Guidance for Local Projects of Xinjiang(ZYYD2024ZY04)the National Natural Science Foundation of China(32260116).
文摘Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in humans and other species have demonstrated its pivotal role in regulating the sodium ion balance and mediating sodium and water reabsorption in the kidney's proximal tubules.However,the impact of EGFR gene in how the Yarkand hare(Lepus yarkandensis)adapts to extreme environmental habitat remains unclear,The Yarkand hare is a desert-dwelling animal with multiple adaptations to cope with drought.Given the important physiological function of EGFR gene,we strived to understand its role in arid environment and explore the molecular mechanism of drought tolerance in the Yarkand hare.We first performed segmental cloning of the CDS of the Yarkand hare EGFR gene.Then,We constructed the phylogenetic tree of the Yarkand hare's EGFR gene and compared it with that of other species.The results showed that the Yarkand hare was most closely related to the Tolai hare(Lepus tolai).Through quantitative reverse transcription polymerase chain reaction(RT-qPCR),we discovered that EGFR expression in the kidneys of the Yarkand hare was higher than in the allopatric Tolai hare from non-arid areas.Therefore,we hypothesized that EGFR gene overexpression in the kidney of the Yarkand hare may play a crucial role in drought adaptability.Subsequently,we inserted CDS of EGFR gene into a pcDNA3.1-EGFP expression vector to construct recombinant plasmid,which was transfected into HeLa cells and overexpressed.RT-qPCR demonstrated a notable and statistically significant increase in EGFR mRNA expression and western blot proved stable expression of this protein in HeLa cells.Through cell experiments,EGFR gene overexpression markedly enhanced the survival of Hela cells subjected to NaCl,H_(2)O_(2),and heat stresses,increased superoxide dismutase activity,and decreased malondialdehyde content.In conclusion,these findings preliminarily suggest that EGFR might help the Yarkand hare adapt to extreme environmental conditions.EGFR manipulation in vivo could be a promising strategy to enhance the resilience of animals to extreme conditions.
