Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.展开更多
The rising prevalence of drug-resistant Gram-positive pathogens,particularly methicillin-resistant Staphy-lococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE),poses a substantial clinical challenge.Biofilm-a...The rising prevalence of drug-resistant Gram-positive pathogens,particularly methicillin-resistant Staphy-lococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE),poses a substantial clinical challenge.Biofilm-associated infections exacerbate this problem due to their inherent antibiotic resistance and complex structure.Current antibiotic treatments struggle to penetrate biofilms and eradicate persister cells,leading to prolonged antibiotic use and increased resistance.Host defense peptides(HDPs)have shown promise,but their clinical application is limited by factors such as enzymatic degradation and difficulty in largescale preparation.Synthetic HDP mimics,such as poly(2-oxazoline),have emerged as effective alter-natives.Herein,we found that the poly(2-oxazoline),Gly-POX_(20),demonstrated rapid and potent activity against clinically isolated multidrug-resistant Gram-positive strains.Gly-POX_(20) showed greater stability under physiological conditions compared to natural peptides,including resistance to protease degradation.Importantly,Gly-POX_(20) inhibited biofilm formation and eradicated mature biofilm and demonstrated superior in vivo therapeutic efficacy to vancomycin in a MRSA biofilm-associated mouse keratitis model,suggesting its potential as a novel antimicrobial agent against drug-resistant Gram-positive bacteria,especially biofilm-associated infections.展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
In order to study the effects of Saussurea laniceps polysaccharides(SLPs)on the expression of inflammatory factors and antimicrobial peptide LL-37 in UVB-induced keratinocytes,SLPs were extracted by the ethanol therma...In order to study the effects of Saussurea laniceps polysaccharides(SLPs)on the expression of inflammatory factors and antimicrobial peptide LL-37 in UVB-induced keratinocytes,SLPs were extracted by the ethanol thermal reflux method,and SLPs at different concentrations were used to examine the inhibitory effect of COX-2(a key mediator of inflammatory pathway).A cell model of UVB irradiation-induced inflammation was established to determine the influence of SLPs on prostaglandin E2(PGE-2),TNF-αand IL-1βinflammatory factors,as well as the relationships of SLPs with LL-37 expression.An enzyme-linked immunosorbent assay(ELISA)and western blot analysis were used to detect the production of inflammatory factors and LL-37 antimicrobial peptide.The results showed that the inhibition rate of COX-2 was 82.41%at 1000μg/mL,and the expression of PGE-2,TNF-αand IL-1βinflammatory factors in HaCaT cells was significantly downregulated at 100μg/mL(P<0.01).In addition,SLPs at 50μg/mL and 100μg/mL concentrations enhanced the expression of LL-37 antimicrobial peptide(P<0.01),thereby down-regulating the expression of TNF-αand IL-1βinflammatory factors,then reducing skin inflammation.Conclusion:SLP can significantly inhibit the inflammatory response induced by UVB,and can further slow down the damage caused by inflammation to the skin by regulating LL-37 antimicrobial peptides,which has the potential to prevent skin inflammatory damage caused by UVB irradiation.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
This study explores the broad-spectrum application of OsRALF26,a small secreted peptide belonging to the rapid alkalinization factor(RALF)family in rice.We found that the rice genome carries numerous lineage-specific ...This study explores the broad-spectrum application of OsRALF26,a small secreted peptide belonging to the rapid alkalinization factor(RALF)family in rice.We found that the rice genome carries numerous lineage-specific OsRALFs,suggesting that this evolutionary expansion could be the result of an arms race with pathogens.Among them,we focused on the Oryza-specific Os RALF26 and its closest homolog,OsRALF27,analyzing their effects across a range of plant species from monocots to dicots.The exogenous application of OsRALF26 significantly reduced bacterial populations in rice challenged with Xanthomonas oryzae pv.oryzae(Xoo)and in Arabidopsis and tomato challenged with Pseudomonas syringae pv.tomato DC3000(Pst DC3000),whereas Os RALF27 did not enhance resistance.展开更多
Rosa roxburghii seeds are by-products of R.roxburghii processing,and their protein hydrolysates(RTSPHs)were found to possess a variety of biological activities.This study aimed to rapidly identify pancreatic lipase(PL...Rosa roxburghii seeds are by-products of R.roxburghii processing,and their protein hydrolysates(RTSPHs)were found to possess a variety of biological activities.This study aimed to rapidly identify pancreatic lipase(PL)and cholesterol esterase(CE)inhibitory peptides in RTSPHs and to elucidate their molecular mechanisms by combining peptidomics and virtual screening.The simulated intestinal environment worsened the peptide’s inhibition of PL but catalyzed the inhibition of CE.The fraction less than 3 kDa in RTSPHs was found to have the highest PL/CE inhibitory activity,among which 17 promising inhibitory peptides were identified and screened by peptidomics and virtual screening.LFCMH,RIPAGSPF,and YFRPR showed good inhibitory abilities against both PL and CE.Molecular docking showed that peptides inhibited PL and CE mainly by hydrogen bonding and hydrophobic interactions with residues in the active site and surface loop.Inhibition kinetic revealed that the peptides were competitive and mixed-type inhibitors of PL/CE.Further,the three peptides,LFCMH,RIPAGSPF,and YFRPR,could effectively inhibit 3T3-L1 preadipocytes differentiation,increase high-density lipoprotein cholesterol content and decrease low-density lipoprotein cholesterol content.This study suggests that combining peptidomics with virtual screening is an effective strategy for rapid screening of PL/CE inhibitory peptides.展开更多
This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of gluc...This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.展开更多
Objective:To evaluate the therapeutic efficacy of the umbilical acupuncture’s“Wind-Thunder Interaction Method”in treating schizophrenia(SCH)patients with liver stagnation and spleen deficiency.Methods:A total of 12...Objective:To evaluate the therapeutic efficacy of the umbilical acupuncture’s“Wind-Thunder Interaction Method”in treating schizophrenia(SCH)patients with liver stagnation and spleen deficiency.Methods:A total of 120 SCH patients with liver stagnation and spleen deficiency were selected and evenly divided by ball drawing.The umbilical acupuncture group received the“Wind-Thunder Interaction Method”,while the Western medicine group received pure Western medicine treatment.The outcomes were compared in terms of efficacy and other indicators.Results:The umbilical acupuncture group showed a higher total effective rate,a decrease in disease symptom scores,lower scores on the side effect rating scale,improved cognitive function scores,and excellent laboratory indicators,with p<0.05 between the groups.Conclusion:The“Wind-Thunder Interaction Method”of umbilical acupuncture demonstrated a relatively high effectiveness in treating SCH patients with liver stagnation and spleen deficiency,alleviating symptoms,reducing side effects,improving cognitive function,and facilitating the recovery of neuro-vascular regulatory peptide groups.展开更多
Pretreatment of Low-Density Polyethylene(LDPE)with physicochemical methods before biodegradation has been demonstrated as an effective strategy.The pretreatment of LDPE exhibited alterations in molecular structure,red...Pretreatment of Low-Density Polyethylene(LDPE)with physicochemical methods before biodegradation has been demonstrated as an effective strategy.The pretreatment of LDPE exhibited alterations in molecular structure,reducing hydrophobicity and decreasing tensile strength.Additionally,pretreating LDPE enhanced microbial biodegradability to improve biofilm formation and significantly reduced the physical weight of LDPE film.AS3–8 consortia exhibited a maximum weight loss of 8.0%±0.5%after 45 days of incubation.While Bacillus sp.AS3 and Sphingobacterium sp.AS8 demonstrated LDPE weight loss of 5.03%±1.6%and 1.6%±0.5%,respectively.The structure of LDPE was altered after incubation with the bacterial strains,resulting in a reduction in the intensity of functional groups,including C=O,C=C,N–H,and C–N.The carbonyl index(CI)of LDPE also decreased by 7.17%after the consortia AS3–8 degradation.Consortia AS3–8 significantly impacted the physical properties of LDPE by reducing the water contact angle(WCA),decreasing to 64.21°±3.69°,and tensile strength(TS),decreasing to 17.97±0.3 MPa.Moreover,the esterase activity was measured through 45 days of incubation.SDS-PAGE analysis of the AS3–8 consortia revealed bands at 35,48,and 70 kDa molecular weights,similar to known enzymes like laccase and esterase.Furthermore,SEM observations showed rough,cracked surfaces on pretreated LDPE,with biofilms present after incubation with the bacterial strains.GC–MS analysis revealed that AS3–8 consortia produced depolymerized chemicals,including alkanes,aldehydes,and esters.The LDPE biodegradation pathway was elucidated.This study addresses critical knowledge gaps in improving plastic degradation efficiency.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
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
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
Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.1In contrast,lack of exercise contributes to adverse events,especially in...Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.1In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.2Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.3Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.4-6These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.展开更多
根据《实施卫生与植物卫生措施协定》(Agreementon the Application of Sanitary and Phytosanitary Measures,简称《SPS协定》)中的透明度原则,成员应保证迅速公布所有拟采用的但尚没有对应的国际标准、指南或建议或与其在内容实质上...根据《实施卫生与植物卫生措施协定》(Agreementon the Application of Sanitary and Phytosanitary Measures,简称《SPS协定》)中的透明度原则,成员应保证迅速公布所有拟采用的但尚没有对应的国际标准、指南或建议或与其在内容实质上不同的,且可能对其他成员贸易产生重大影响的卫生与植物卫生措施,以使利益相关方知晓。展开更多
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
基金financially supported by the National Key Research and Development Program of China(no.2022YFC2303100)National Natural Science Foundation of China(nos.T2325010,22305082,52203162,and 22075078)+1 种基金Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission),the Fundamental Research Funds for the Central Universities(nos.JKVD1241029 and JKD01241701)Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry(Changchun Institute of Applied Chemistry,Chinese Academy of Sciences),the Open Project of Engineering Research Center of Dairy Quality and Safety Control Technology(Ministry of Education,no.R202201).
文摘The rising prevalence of drug-resistant Gram-positive pathogens,particularly methicillin-resistant Staphy-lococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE),poses a substantial clinical challenge.Biofilm-associated infections exacerbate this problem due to their inherent antibiotic resistance and complex structure.Current antibiotic treatments struggle to penetrate biofilms and eradicate persister cells,leading to prolonged antibiotic use and increased resistance.Host defense peptides(HDPs)have shown promise,but their clinical application is limited by factors such as enzymatic degradation and difficulty in largescale preparation.Synthetic HDP mimics,such as poly(2-oxazoline),have emerged as effective alter-natives.Herein,we found that the poly(2-oxazoline),Gly-POX_(20),demonstrated rapid and potent activity against clinically isolated multidrug-resistant Gram-positive strains.Gly-POX_(20) showed greater stability under physiological conditions compared to natural peptides,including resistance to protease degradation.Importantly,Gly-POX_(20) inhibited biofilm formation and eradicated mature biofilm and demonstrated superior in vivo therapeutic efficacy to vancomycin in a MRSA biofilm-associated mouse keratitis model,suggesting its potential as a novel antimicrobial agent against drug-resistant Gram-positive bacteria,especially biofilm-associated infections.
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
文摘In order to study the effects of Saussurea laniceps polysaccharides(SLPs)on the expression of inflammatory factors and antimicrobial peptide LL-37 in UVB-induced keratinocytes,SLPs were extracted by the ethanol thermal reflux method,and SLPs at different concentrations were used to examine the inhibitory effect of COX-2(a key mediator of inflammatory pathway).A cell model of UVB irradiation-induced inflammation was established to determine the influence of SLPs on prostaglandin E2(PGE-2),TNF-αand IL-1βinflammatory factors,as well as the relationships of SLPs with LL-37 expression.An enzyme-linked immunosorbent assay(ELISA)and western blot analysis were used to detect the production of inflammatory factors and LL-37 antimicrobial peptide.The results showed that the inhibition rate of COX-2 was 82.41%at 1000μg/mL,and the expression of PGE-2,TNF-αand IL-1βinflammatory factors in HaCaT cells was significantly downregulated at 100μg/mL(P<0.01).In addition,SLPs at 50μg/mL and 100μg/mL concentrations enhanced the expression of LL-37 antimicrobial peptide(P<0.01),thereby down-regulating the expression of TNF-αand IL-1βinflammatory factors,then reducing skin inflammation.Conclusion:SLP can significantly inhibit the inflammatory response induced by UVB,and can further slow down the damage caused by inflammation to the skin by regulating LL-37 antimicrobial peptides,which has the potential to prevent skin inflammatory damage caused by UVB irradiation.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
基金supported by the National Research Foundation of Korea grant funded by the Korea government(Grant Nos.NRF-2020R1A2C1007778 and RS-2024-00454908)。
文摘This study explores the broad-spectrum application of OsRALF26,a small secreted peptide belonging to the rapid alkalinization factor(RALF)family in rice.We found that the rice genome carries numerous lineage-specific OsRALFs,suggesting that this evolutionary expansion could be the result of an arms race with pathogens.Among them,we focused on the Oryza-specific Os RALF26 and its closest homolog,OsRALF27,analyzing their effects across a range of plant species from monocots to dicots.The exogenous application of OsRALF26 significantly reduced bacterial populations in rice challenged with Xanthomonas oryzae pv.oryzae(Xoo)and in Arabidopsis and tomato challenged with Pseudomonas syringae pv.tomato DC3000(Pst DC3000),whereas Os RALF27 did not enhance resistance.
基金supported by Yunnan Fundamental Research Project(202301AS070014)Science and Technology Plan Project in Guizhou Province([2020]1Y022).
文摘Rosa roxburghii seeds are by-products of R.roxburghii processing,and their protein hydrolysates(RTSPHs)were found to possess a variety of biological activities.This study aimed to rapidly identify pancreatic lipase(PL)and cholesterol esterase(CE)inhibitory peptides in RTSPHs and to elucidate their molecular mechanisms by combining peptidomics and virtual screening.The simulated intestinal environment worsened the peptide’s inhibition of PL but catalyzed the inhibition of CE.The fraction less than 3 kDa in RTSPHs was found to have the highest PL/CE inhibitory activity,among which 17 promising inhibitory peptides were identified and screened by peptidomics and virtual screening.LFCMH,RIPAGSPF,and YFRPR showed good inhibitory abilities against both PL and CE.Molecular docking showed that peptides inhibited PL and CE mainly by hydrogen bonding and hydrophobic interactions with residues in the active site and surface loop.Inhibition kinetic revealed that the peptides were competitive and mixed-type inhibitors of PL/CE.Further,the three peptides,LFCMH,RIPAGSPF,and YFRPR,could effectively inhibit 3T3-L1 preadipocytes differentiation,increase high-density lipoprotein cholesterol content and decrease low-density lipoprotein cholesterol content.This study suggests that combining peptidomics with virtual screening is an effective strategy for rapid screening of PL/CE inhibitory peptides.
基金Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,No.0932204294929829CNPq Research Productivity Fellow,No.4357511882624145.
文摘This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.
文摘Objective:To evaluate the therapeutic efficacy of the umbilical acupuncture’s“Wind-Thunder Interaction Method”in treating schizophrenia(SCH)patients with liver stagnation and spleen deficiency.Methods:A total of 120 SCH patients with liver stagnation and spleen deficiency were selected and evenly divided by ball drawing.The umbilical acupuncture group received the“Wind-Thunder Interaction Method”,while the Western medicine group received pure Western medicine treatment.The outcomes were compared in terms of efficacy and other indicators.Results:The umbilical acupuncture group showed a higher total effective rate,a decrease in disease symptom scores,lower scores on the side effect rating scale,improved cognitive function scores,and excellent laboratory indicators,with p<0.05 between the groups.Conclusion:The“Wind-Thunder Interaction Method”of umbilical acupuncture demonstrated a relatively high effectiveness in treating SCH patients with liver stagnation and spleen deficiency,alleviating symptoms,reducing side effects,improving cognitive function,and facilitating the recovery of neuro-vascular regulatory peptide groups.
文摘Pretreatment of Low-Density Polyethylene(LDPE)with physicochemical methods before biodegradation has been demonstrated as an effective strategy.The pretreatment of LDPE exhibited alterations in molecular structure,reducing hydrophobicity and decreasing tensile strength.Additionally,pretreating LDPE enhanced microbial biodegradability to improve biofilm formation and significantly reduced the physical weight of LDPE film.AS3–8 consortia exhibited a maximum weight loss of 8.0%±0.5%after 45 days of incubation.While Bacillus sp.AS3 and Sphingobacterium sp.AS8 demonstrated LDPE weight loss of 5.03%±1.6%and 1.6%±0.5%,respectively.The structure of LDPE was altered after incubation with the bacterial strains,resulting in a reduction in the intensity of functional groups,including C=O,C=C,N–H,and C–N.The carbonyl index(CI)of LDPE also decreased by 7.17%after the consortia AS3–8 degradation.Consortia AS3–8 significantly impacted the physical properties of LDPE by reducing the water contact angle(WCA),decreasing to 64.21°±3.69°,and tensile strength(TS),decreasing to 17.97±0.3 MPa.Moreover,the esterase activity was measured through 45 days of incubation.SDS-PAGE analysis of the AS3–8 consortia revealed bands at 35,48,and 70 kDa molecular weights,similar to known enzymes like laccase and esterase.Furthermore,SEM observations showed rough,cracked surfaces on pretreated LDPE,with biofilms present after incubation with the bacterial strains.GC–MS analysis revealed that AS3–8 consortia produced depolymerized chemicals,including alkanes,aldehydes,and esters.The LDPE biodegradation pathway was elucidated.This study addresses critical knowledge gaps in improving plastic degradation efficiency.
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).
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.
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 National Key Research and Development Project(2022YFA1104500 to JX)the National Natural Science Foundation of China(82020108002 and82225005 to JX and 82370277 to HW)+1 种基金the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to HW and 23410750100 to JX)supported by a Biotechnology and Biological Sciences Research Council(BBSRC)International Partnering Award。
文摘Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.1In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.2Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.3Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.4-6These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.
文摘根据《实施卫生与植物卫生措施协定》(Agreementon the Application of Sanitary and Phytosanitary Measures,简称《SPS协定》)中的透明度原则,成员应保证迅速公布所有拟采用的但尚没有对应的国际标准、指南或建议或与其在内容实质上不同的,且可能对其他成员贸易产生重大影响的卫生与植物卫生措施,以使利益相关方知晓。
