Biodegradable scaffolds have a major therapeutic advantage in regenerative medicine with their ability to include multiple compounds of drugs, growth factors and more recently, stem cells within the matrix. The scaffo...Biodegradable scaffolds have a major therapeutic advantage in regenerative medicine with their ability to include multiple compounds of drugs, growth factors and more recently, stem cells within the matrix. The scaffold can be programmed with mechanoresistive parameters targeted to the tissue to be replaced. Direct chemoattraction of <em>in vivo </em>stem cells to the implanted scaffold would be advantageous in the clinical setting. Large peptides such as vasculo-endothelial growth factor have demonstrated chemotaxis for angiogenesis from endothelial cells. This suggests other endogenous peptides may be present to directly attract stem cells to a scaffold. This exploratory study assessed if peptides from the blood peptidome would display chemotaxis to stem cells. Results showed that several short N-mer peptides demonstrated remarkable chemotaxis to blood and adipose tissue derived stem cells. Sodium alginate hydrogel was placed into 6-well, 24-well plate, and partitioned plates with channels between the wells. Connected wells were in series and spiked with peptides, biofluids containing stem cells and control wells. Images were recorded between three and nine days after incubation at 37<span style="white-space:nowrap;">°</span>C. There were rapid migration and expansion of stem cells into the peptide wells. Cell analysis revealed activated stem cells on a number of parameters including autophagy, Ki67 and nitric oxide. Potentially, this enhanced method to bioscaffold design utilizing peptide chemoattraction could result in an improved approach for stem cell therapy and regenerative medicine applications. Specific patient groups (e.g. blood coagulation disorders) where surgery to acquire adipose tissue or bone marrow is contraindicated may benefit. In addition, the technology is portable and safe by using “on demand” peripheral blood derived stem cells and would be particularly suitable for specialized environments such as space medicine.展开更多
Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with...Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.展开更多
Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,...Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,and high content of cationic amino acids,which hinder functional expression in prokaryotic systems such as Escherichia coli.To establish a eukaryotic recombinant expression system for the AMPs of mussel and obtain recombinant mussel AMPs for subsequent studies,we reported the successful recombinant expression of myticofensin B1,a novel defensin-like AMP identified previously in Mytiluscoruscus,using the eukaryotic host Pichia pastoris.The codon-optimized gene encoding the mature myticofensin-B1(composed of 65 amino acid residues,including 6 conserved cysteine residues)was cloned into a pPICZαA vector and expressed in P.pastoris GS115.Structural fidelity of the recombinant peptide was confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS),showing a molecular weight of 8849.9 Da,which was consistent with the theoretical prediction.Functional assays demonstrated a broad-spectrum antimicrobial activity of the recombinant myticofensin-B1,with stronger inhibition against Gram-negative bacteria.Scanning electron microscopy revealed different effects of the recombinant myticofensin-B1 against different bacteria.In addition,the recombinant myticofensin-B1 exhibited a very low hemolytic activity against sheep red blood cells and weak cytotoxicity against human A549 lung cancer cells.This study establishes P.pastoris as a powerful platform to produce functional mussel AMP and highlights the potential of the recombinant myticofensin-B1 as a therapeutic agent for aquaculture pathogens and infections.展开更多
The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion...The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several...Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).展开更多
Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized on...Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.展开更多
Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face wit...Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed C–H activation has been employed for the functionalization of amino acids and peptides.Through domino C–H activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed C–H activation/annulation.展开更多
The escalating global crisis of antibiotic resistance necessitates urgent development of novel antimicrobial agents.In this context,antimicrobial peptides(AMPs)derived from fish emerge as a highly promising strategic ...The escalating global crisis of antibiotic resistance necessitates urgent development of novel antimicrobial agents.In this context,antimicrobial peptides(AMPs)derived from fish emerge as a highly promising strategic resource,owing to their unique structural diversity and the exceptional adaptability and tolerance conferred by evolutionary pressures in aquatic environments.This review systematically synthesizes key advances in fish-derived AMP research.It details their diverse sourcing avenues,encompassing tissues from live fish(e.g.,skin,mucus,gills,intestines)and processing byproducts(e.g.,scales,skins,viscera).The discussion covers efficient isolation,purification,and synthesis strategies,and critically examines their defining feature:unique multi-target synergistic antimicrobial mechanisms(including microbial membrane disruption,intracellular targeting,and immunomodulation),which contribute to a reduced propensity for resistance development.To address inherent limitations of natural AMPs(such as susceptibility to proteolysis and potential toxicity),the review highlights innovative optimization approaches,including computational-aided rational design,amino acid modification,cyclization,and hybrid peptide construction.Furthermore,the review elaborates on their significant application potential across crucial domains:food preservation(inhibiting spoilage organisms,extending shelf-life),sustainable aquaculture(as antibiotic alternatives,enhancing disease resistance,improving water quality),and the development of novel anti-infective therapeutics(particularly against drug-resistant infections).Therefore,this work aims to provide a comprehensive theoretical foundation and innovative strategic insights to foster in-depth research and the sustainable exploitation of this vital strategic biological resource.展开更多
Peptide-and drug-protected gold nanoclusters(Au NCs)with atomic precision have attracted research attention in the last few years owing to their ultrasmall size(<2 nm),well-defined structures,tunable photoluminesce...Peptide-and drug-protected gold nanoclusters(Au NCs)with atomic precision have attracted research attention in the last few years owing to their ultrasmall size(<2 nm),well-defined structures,tunable photoluminescence from the visible to near-infrared range,water solubility,and good biocompatibility.These features,combined with low toxicity and efficient renal clearance,make such Au NCs promising candidates for biomedical use,including diagnosis,therapy,and theranostic.The incorporation of peptides or drugs into Au NCs enhances the stability,targeting specificity,cellular uptake,and prolonged circulation,enabling precise modulation of biological responses.Despite notable advances in achieving atomic precision employing complex ligands such as peptides or drugs,the synthetic methods of this new class of NCs remain a challenge.Careful control of molar ratio(Au:peptide/drug),reducing agent,temperature,and reaction time is required,because these factors directly influence the cluster size,optical properties,and in vivo performance.In this review,we highlight different synthetic approaches of atomically precise peptide-and drug-protected Au NCs,emphasizing the role of rational ligand design and reaction conditions,as well as the challenges associated with structural determination.We further discuss the optical and photoluminescence properties of peptide-protected Au NCs-the mostly explored features for biomedical applications.Finally,we conclude by outlining the current challenges,opportunities for scale-up synthesis,and future design perspectives for these emerging nanomaterials.展开更多
Children with autism often exhibit abnormalities in body weight,but the underlying mechanism remains unclear.SH3 and multiple ankyrin repeat domains protein 3(SHANK3),a scaffold protein of the postsynaptic density,has...Children with autism often exhibit abnormalities in body weight,but the underlying mechanism remains unclear.SH3 and multiple ankyrin repeat domains protein 3(SHANK3),a scaffold protein of the postsynaptic density,has been reported to be associated with autism.This study aimed to investigate whether and how SHANK3 influences body weight in the hypothalamic neuronal regulation of energy homeostasis.Adeno-associated viruses 9(AAV9)carrying CMV-Cre and Agrp-Cre were stereotactically injected to restore SHANK3 expression in the arcuate nucleus(ARC)and agouti-related peptide(AgRP)neurons,respectively.Agrp-Cre mice were injected with AAV9-p38αflox/flox to overexpress p38α.Activated p38αwas generated by mutating both D176A and F327S in p38α.Inactivated p38αwas constructed by mutating both T180A and Y182F in p38α.Metabolic analysis,immunoblotting,histological analysis,the glucose tolerance test,the insulin tolerance test,and body fat mass analysis were applied to investigate the underlying mechanisms by which SHANK3 regulates body weight.We reveal that SHANK3 regulates body weight via the p38αsignaling pathway in the AgRP neurons of the hypothalamus.Shank3 knockout(Shank3−/−)mice exhibit resistance to diet-induced obesity.Shank3 re-expression in the ARC or AgRP neurons increases body weight in Shank3 knock-in mice with an inverted allele(SKO).Overexpression or activation of p38αin AgRP neurons elicits resistance to diet-induced obesity.Inactivated p38αin AgRP neurons abolished the resistance to diet-induced obesity due to SHANK3 deficiency.Our findings suggest that the SHANK3-p38αsiganling pathway in AgRP neurons regulates body weight balance in autism,revealing a promising therapeutic target for obesity in children with autism.展开更多
The blood-brain barrier(BBB)is a major challenge in drug delivery for the treatment of central nervous system diseases.Walnut derived peptide TWLPLPR(TW-7)has been proved to promote neuronal mitochondrial autophagy an...The blood-brain barrier(BBB)is a major challenge in drug delivery for the treatment of central nervous system diseases.Walnut derived peptide TWLPLPR(TW-7)has been proved to promote neuronal mitochondrial autophagy and enhance hippocampal neuronal synaptic plasticity,thereby improving learning and memory abilities in mice.We investigated the internalization mechanism and intracellular transport pathway for the walnut-derived peptide,TW-7,using b End.3 cells in an in vitro BBB model system.TW-7 was taken up by the b End.3 cells in a concentration-,temperature-,and energy-dependent manner;this involved increases in caveolin-1 and caveolin-2 protein expression and phosphorylation and inhibition of P-glycoprotein-mediated efflux.Subcellular localization of TW-7 in b End.3 cells was observed,indicating that the plasma membrane,endoplasmic reticulum,Golgi apparatus,lysosomes,and mitochondria participated in intracellular trafficking and that the peptide escaped from lysosomes over time.Caveolae may be critical for TW-7 uptake by brain microvascular endothelial cells,assisting TW-7 to cross the BBB.The results of this study provide a theoretical basis for the mechanism of active peptide penetrating the BBB,and provide a reference for developing neuroprotective active peptide products.展开更多
The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a se...The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.展开更多
Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The ...Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.展开更多
Progranulin(PGRN),encoded by the GRN gene,is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides(granulin A-G)capable of exerting distinct biological functions.PGRN is ...Progranulin(PGRN),encoded by the GRN gene,is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides(granulin A-G)capable of exerting distinct biological functions.PGRN is widely expressed in multiple tissues,including the central nervous and immune systems.Within the central nervous system,PGRN is highly expressed in the hippocampus,cerebral cortex,and hypothalamus,and has been detected in various neuronal subtypes,including Purkinje cells and motor neurons,where it plays a crucial role in neuronal functions,such as neurite outgrowth and synaptic plasticity.In addition to neurons,PGRN is expressed in glial cells,particularly in microglia,where it regulates phagocytosis.Furthermore,PGRN is presented in peripheral immune cells,including macrophages,and contributes to the regulation of inflammatory responses.PGRN exerts its diverse functions via binding partners,including receptors such as sortilin,EphA2,Notch,death receptor 3,and toll-like receptor 9(Chitramuthu et al.,2017).展开更多
Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
Heart failure(HF)is a complex clinical syndrome that promotes high morbidity and multi-systemic damage.Skeletal muscle can be directly affected by HF through a loss of physical capacity and various inflammatory,hormon...Heart failure(HF)is a complex clinical syndrome that promotes high morbidity and multi-systemic damage.Skeletal muscle can be directly affected by HF through a loss of physical capacity and various inflammatory,hormonal,and metabolic mechanisms observed in this cardiac condition,which collectively contribute to a high prevalence of sarcopenia in HF patients.Therefore,the aim of this review was to compile the main recent clinical and epidemiological data on muscle health in HF patients.Nine studies were selected from systematic reviews and clinical trials,which demonstrated a high prevalence of sarcopenia in patients with HF,particularly in males,hospitalized patients,the elderly,and those with HF with reduced ejection fraction.Oxidative stress markers and higher levels of natriuretic peptides were also observed in HF patients who exhibited damaged muscle parameters.Furthermore,the overall deterioration of prognosis in HF was associated with criteria defining sarcopenia,such as low muscle strength and lean mass loss.These findings reinforce the importance of evaluating skeletal muscle in HF patients,which can provide improvements in morbidity and functionality.展开更多
文摘Biodegradable scaffolds have a major therapeutic advantage in regenerative medicine with their ability to include multiple compounds of drugs, growth factors and more recently, stem cells within the matrix. The scaffold can be programmed with mechanoresistive parameters targeted to the tissue to be replaced. Direct chemoattraction of <em>in vivo </em>stem cells to the implanted scaffold would be advantageous in the clinical setting. Large peptides such as vasculo-endothelial growth factor have demonstrated chemotaxis for angiogenesis from endothelial cells. This suggests other endogenous peptides may be present to directly attract stem cells to a scaffold. This exploratory study assessed if peptides from the blood peptidome would display chemotaxis to stem cells. Results showed that several short N-mer peptides demonstrated remarkable chemotaxis to blood and adipose tissue derived stem cells. Sodium alginate hydrogel was placed into 6-well, 24-well plate, and partitioned plates with channels between the wells. Connected wells were in series and spiked with peptides, biofluids containing stem cells and control wells. Images were recorded between three and nine days after incubation at 37<span style="white-space:nowrap;">°</span>C. There were rapid migration and expansion of stem cells into the peptide wells. Cell analysis revealed activated stem cells on a number of parameters including autophagy, Ki67 and nitric oxide. Potentially, this enhanced method to bioscaffold design utilizing peptide chemoattraction could result in an improved approach for stem cell therapy and regenerative medicine applications. Specific patient groups (e.g. blood coagulation disorders) where surgery to acquire adipose tissue or bone marrow is contraindicated may benefit. In addition, the technology is portable and safe by using “on demand” peripheral blood derived stem cells and would be particularly suitable for specialized environments such as space medicine.
基金Supported by National Natural Science Foundation of China(30672496 and 30801413)Guangdong Medical Research Grant(A201032)Guangdong International Cooperation Grant(2011B050200006)
文摘Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.
基金supported by the National Natural Science Foundation of China(32271580,42020104009)the Fundamental Research Funds for Zhejiang Provincial Universities and Research Institutes(JX6311101923)。
文摘Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,and high content of cationic amino acids,which hinder functional expression in prokaryotic systems such as Escherichia coli.To establish a eukaryotic recombinant expression system for the AMPs of mussel and obtain recombinant mussel AMPs for subsequent studies,we reported the successful recombinant expression of myticofensin B1,a novel defensin-like AMP identified previously in Mytiluscoruscus,using the eukaryotic host Pichia pastoris.The codon-optimized gene encoding the mature myticofensin-B1(composed of 65 amino acid residues,including 6 conserved cysteine residues)was cloned into a pPICZαA vector and expressed in P.pastoris GS115.Structural fidelity of the recombinant peptide was confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS),showing a molecular weight of 8849.9 Da,which was consistent with the theoretical prediction.Functional assays demonstrated a broad-spectrum antimicrobial activity of the recombinant myticofensin-B1,with stronger inhibition against Gram-negative bacteria.Scanning electron microscopy revealed different effects of the recombinant myticofensin-B1 against different bacteria.In addition,the recombinant myticofensin-B1 exhibited a very low hemolytic activity against sheep red blood cells and weak cytotoxicity against human A549 lung cancer cells.This study establishes P.pastoris as a powerful platform to produce functional mussel AMP and highlights the potential of the recombinant myticofensin-B1 as a therapeutic agent for aquaculture pathogens and infections.
基金supported by the Russian Science Foundation(Grant No.24-25-20087 to V.K.)。
文摘The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
文摘Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).
基金supported by the Vall d’Hebron Research Institute(PI23/01345)the Networking Research Centre on Bioengineering,Biomaterials,and Nanomedicine(CIBER-BBN),which is financed by the Instituto de Salud Carlos III(ISCIII)with assistance from the European Regional Development Fund(ERDF)+4 种基金supported by ANID FONDECYT REGULAR(Chile)through project No.1250634,and FOVI230019 granted to Esteban Duran-LaraDiana Rafael was supported by Marie Skłodowska-Curie Actions(MSCA-PF ID 101107735),“La Caixa Foundation”(LCF/BQ/PR24/12050008),and ISCIII(PI24/00745)Fernanda Andrade was granted by the Fundación Científica de la Asociación Española Contra el Cáncer(FCAECC Refs.INVES211530DASI and SNRGS247164DASI)“La Caixa Foundation”(HR24-00927).Júlia German-Cortés was granted by the 791 FAECC(PRDBA258393GERM)The authors also thank the denomination of Consolidated group from Generalitat de Catalunya(2021 SGR 01173)granted to the CB-DDT group。
文摘Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20220409)the National Natural Science Foundation of China(No.22401153)+2 种基金the FWO[Fund for Scientific Research-Flanders(Belgium)]for financial support(recipient Erik V.Van der Eycken)the Research Council of the KU Leuven(recipient Erik V.Van der Eycken)the support of the"RUDN University Strategic Academic Leadership Program"(recipient Erik V.Van der Eycken).
文摘Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed C–H activation has been employed for the functionalization of amino acids and peptides.Through domino C–H activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed C–H activation/annulation.
文摘The escalating global crisis of antibiotic resistance necessitates urgent development of novel antimicrobial agents.In this context,antimicrobial peptides(AMPs)derived from fish emerge as a highly promising strategic resource,owing to their unique structural diversity and the exceptional adaptability and tolerance conferred by evolutionary pressures in aquatic environments.This review systematically synthesizes key advances in fish-derived AMP research.It details their diverse sourcing avenues,encompassing tissues from live fish(e.g.,skin,mucus,gills,intestines)and processing byproducts(e.g.,scales,skins,viscera).The discussion covers efficient isolation,purification,and synthesis strategies,and critically examines their defining feature:unique multi-target synergistic antimicrobial mechanisms(including microbial membrane disruption,intracellular targeting,and immunomodulation),which contribute to a reduced propensity for resistance development.To address inherent limitations of natural AMPs(such as susceptibility to proteolysis and potential toxicity),the review highlights innovative optimization approaches,including computational-aided rational design,amino acid modification,cyclization,and hybrid peptide construction.Furthermore,the review elaborates on their significant application potential across crucial domains:food preservation(inhibiting spoilage organisms,extending shelf-life),sustainable aquaculture(as antibiotic alternatives,enhancing disease resistance,improving water quality),and the development of novel anti-infective therapeutics(particularly against drug-resistant infections).Therefore,this work aims to provide a comprehensive theoretical foundation and innovative strategic insights to foster in-depth research and the sustainable exploitation of this vital strategic biological resource.
基金RGM is grateful to CNPq for the PDE fellowship(200437/2025-9),MTM acknowledges CNPq research scholarship(314470/2023-9)FAPESP fundings(2022/01825-22025/063196).
文摘Peptide-and drug-protected gold nanoclusters(Au NCs)with atomic precision have attracted research attention in the last few years owing to their ultrasmall size(<2 nm),well-defined structures,tunable photoluminescence from the visible to near-infrared range,water solubility,and good biocompatibility.These features,combined with low toxicity and efficient renal clearance,make such Au NCs promising candidates for biomedical use,including diagnosis,therapy,and theranostic.The incorporation of peptides or drugs into Au NCs enhances the stability,targeting specificity,cellular uptake,and prolonged circulation,enabling precise modulation of biological responses.Despite notable advances in achieving atomic precision employing complex ligands such as peptides or drugs,the synthetic methods of this new class of NCs remain a challenge.Careful control of molar ratio(Au:peptide/drug),reducing agent,temperature,and reaction time is required,because these factors directly influence the cluster size,optical properties,and in vivo performance.In this review,we highlight different synthetic approaches of atomically precise peptide-and drug-protected Au NCs,emphasizing the role of rational ligand design and reaction conditions,as well as the challenges associated with structural determination.We further discuss the optical and photoluminescence properties of peptide-protected Au NCs-the mostly explored features for biomedical applications.Finally,we conclude by outlining the current challenges,opportunities for scale-up synthesis,and future design perspectives for these emerging nanomaterials.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0506800).
文摘Children with autism often exhibit abnormalities in body weight,but the underlying mechanism remains unclear.SH3 and multiple ankyrin repeat domains protein 3(SHANK3),a scaffold protein of the postsynaptic density,has been reported to be associated with autism.This study aimed to investigate whether and how SHANK3 influences body weight in the hypothalamic neuronal regulation of energy homeostasis.Adeno-associated viruses 9(AAV9)carrying CMV-Cre and Agrp-Cre were stereotactically injected to restore SHANK3 expression in the arcuate nucleus(ARC)and agouti-related peptide(AgRP)neurons,respectively.Agrp-Cre mice were injected with AAV9-p38αflox/flox to overexpress p38α.Activated p38αwas generated by mutating both D176A and F327S in p38α.Inactivated p38αwas constructed by mutating both T180A and Y182F in p38α.Metabolic analysis,immunoblotting,histological analysis,the glucose tolerance test,the insulin tolerance test,and body fat mass analysis were applied to investigate the underlying mechanisms by which SHANK3 regulates body weight.We reveal that SHANK3 regulates body weight via the p38αsignaling pathway in the AgRP neurons of the hypothalamus.Shank3 knockout(Shank3−/−)mice exhibit resistance to diet-induced obesity.Shank3 re-expression in the ARC or AgRP neurons increases body weight in Shank3 knock-in mice with an inverted allele(SKO).Overexpression or activation of p38αin AgRP neurons elicits resistance to diet-induced obesity.Inactivated p38αin AgRP neurons abolished the resistance to diet-induced obesity due to SHANK3 deficiency.Our findings suggest that the SHANK3-p38αsiganling pathway in AgRP neurons regulates body weight balance in autism,revealing a promising therapeutic target for obesity in children with autism.
基金supported by the National Natural Science Foundation of China(22378368).
文摘The blood-brain barrier(BBB)is a major challenge in drug delivery for the treatment of central nervous system diseases.Walnut derived peptide TWLPLPR(TW-7)has been proved to promote neuronal mitochondrial autophagy and enhance hippocampal neuronal synaptic plasticity,thereby improving learning and memory abilities in mice.We investigated the internalization mechanism and intracellular transport pathway for the walnut-derived peptide,TW-7,using b End.3 cells in an in vitro BBB model system.TW-7 was taken up by the b End.3 cells in a concentration-,temperature-,and energy-dependent manner;this involved increases in caveolin-1 and caveolin-2 protein expression and phosphorylation and inhibition of P-glycoprotein-mediated efflux.Subcellular localization of TW-7 in b End.3 cells was observed,indicating that the plasma membrane,endoplasmic reticulum,Golgi apparatus,lysosomes,and mitochondria participated in intracellular trafficking and that the peptide escaped from lysosomes over time.Caveolae may be critical for TW-7 uptake by brain microvascular endothelial cells,assisting TW-7 to cross the BBB.The results of this study provide a theoretical basis for the mechanism of active peptide penetrating the BBB,and provide a reference for developing neuroprotective active peptide products.
基金Financial support from the National Natural Science Foundation of China(32502106)One health Interdisciplinary Research Project,Institute of One Health Science,Ningbo University(NBUOH202502)the Ningbo Top Talent Project(215-432094250).
文摘The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.
基金supported by the National Research Foundation of Korea grant funded by the Korean government(Grant no.:RS-2022-NR070862).
文摘Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.
基金SENSHIN Medical Research Foundation,Takeda Science Foundation,Taiju Life Social Welfare Foundation,Mitsui Sumitomo Insurance Welfare Foundation,Research Foundation for Pharmaceutical Sciences,Tokyo Medical University Research Grant,JSPS KAKENHI(23K06369)to SKJSPS KAKENHI(24K02187)to KK.
文摘Progranulin(PGRN),encoded by the GRN gene,is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides(granulin A-G)capable of exerting distinct biological functions.PGRN is widely expressed in multiple tissues,including the central nervous and immune systems.Within the central nervous system,PGRN is highly expressed in the hippocampus,cerebral cortex,and hypothalamus,and has been detected in various neuronal subtypes,including Purkinje cells and motor neurons,where it plays a crucial role in neuronal functions,such as neurite outgrowth and synaptic plasticity.In addition to neurons,PGRN is expressed in glial cells,particularly in microglia,where it regulates phagocytosis.Furthermore,PGRN is presented in peripheral immune cells,including macrophages,and contributes to the regulation of inflammatory responses.PGRN exerts its diverse functions via binding partners,including receptors such as sortilin,EphA2,Notch,death receptor 3,and toll-like receptor 9(Chitramuthu et al.,2017).
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
文摘Heart failure(HF)is a complex clinical syndrome that promotes high morbidity and multi-systemic damage.Skeletal muscle can be directly affected by HF through a loss of physical capacity and various inflammatory,hormonal,and metabolic mechanisms observed in this cardiac condition,which collectively contribute to a high prevalence of sarcopenia in HF patients.Therefore,the aim of this review was to compile the main recent clinical and epidemiological data on muscle health in HF patients.Nine studies were selected from systematic reviews and clinical trials,which demonstrated a high prevalence of sarcopenia in patients with HF,particularly in males,hospitalized patients,the elderly,and those with HF with reduced ejection fraction.Oxidative stress markers and higher levels of natriuretic peptides were also observed in HF patients who exhibited damaged muscle parameters.Furthermore,the overall deterioration of prognosis in HF was associated with criteria defining sarcopenia,such as low muscle strength and lean mass loss.These findings reinforce the importance of evaluating skeletal muscle in HF patients,which can provide improvements in morbidity and functionality.
