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
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
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
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
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
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
Vasoactive intestinal peptide (VIP) is a 28-amino acid polypeptide first isolated from swine duodenum. VIP is a neurotransmitter that is extensively distributed in tissues. According to published reports, VPAC1 and VP...Vasoactive intestinal peptide (VIP) is a 28-amino acid polypeptide first isolated from swine duodenum. VIP is a neurotransmitter that is extensively distributed in tissues. According to published reports, VPAC1 and VPAC2 act as VIP receptors and are widely present in the central nervous system and peripheral tissues. VIP exerts diverse actions on the cardiovascular system, pancreas, digestive tract, respiratory system, and urological system. Recent reports indicated that VIP has immunological and neuroprotective effects and also affects cell growth. While primary investigations for developing therapeutic applications for various pathological conditions and diseases are underway, the structure and function of VIP should be analyzed in more detail.展开更多
Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illne...Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illness. This illness, termed a chronic inflammatory response syndrome (CIRS-WDB), is systemic with symptoms acquired from multiple organ systems. Treatment of CIRS-WDB has progressed rapidly as a better understanding of the inflammatory pathophysiology has led to targeted, sequential therapies. The fundamental basis of uncontrolled innate immune responses, the humoral deficiency of regulatory neuropeptides melanocyte stimulating hormone (MSH) or vasoactive intestinal polypeptide (VIP), seen in over 98% of pa tients, has not consistently responded to any treatment modality. Use of replacement VIP has been attempted anecdotally;VIP replacement therapies show promise in short term studies but longer therapies have not been attempted. Here we report an open label trial of 20 patients with refractory CIRS-WDB illness who took replacement VIP in a nasal spray for at least 18 months with confirmation of durable efficacy and absence of significant side effects. These 20 patients were similar in symptoms and lab find- ings to three previously published cohorts in- volving 1829 patients and 169 controls. Dosage of VIP was titrated downwards from four to zero doses a day to determine minimum effective dose, and retitrated upwards for maximum improvement over time. The trial showed that VIP therapy safely 1) reduced refractory symptoms to equal controls;2) corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9;3) corrected estradiol, testosterone and 25-OH Vitamin D;4) returned pulmonary artery systolic pressure (PASP) during exercise to normal;and 5) enhanced quality of life in 100% of trial patients. Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.展开更多
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 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.
文摘Vasoactive intestinal peptide (VIP) is a 28-amino acid polypeptide first isolated from swine duodenum. VIP is a neurotransmitter that is extensively distributed in tissues. According to published reports, VPAC1 and VPAC2 act as VIP receptors and are widely present in the central nervous system and peripheral tissues. VIP exerts diverse actions on the cardiovascular system, pancreas, digestive tract, respiratory system, and urological system. Recent reports indicated that VIP has immunological and neuroprotective effects and also affects cell growth. While primary investigations for developing therapeutic applications for various pathological conditions and diseases are underway, the structure and function of VIP should be analyzed in more detail.
文摘Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illness. This illness, termed a chronic inflammatory response syndrome (CIRS-WDB), is systemic with symptoms acquired from multiple organ systems. Treatment of CIRS-WDB has progressed rapidly as a better understanding of the inflammatory pathophysiology has led to targeted, sequential therapies. The fundamental basis of uncontrolled innate immune responses, the humoral deficiency of regulatory neuropeptides melanocyte stimulating hormone (MSH) or vasoactive intestinal polypeptide (VIP), seen in over 98% of pa tients, has not consistently responded to any treatment modality. Use of replacement VIP has been attempted anecdotally;VIP replacement therapies show promise in short term studies but longer therapies have not been attempted. Here we report an open label trial of 20 patients with refractory CIRS-WDB illness who took replacement VIP in a nasal spray for at least 18 months with confirmation of durable efficacy and absence of significant side effects. These 20 patients were similar in symptoms and lab find- ings to three previously published cohorts in- volving 1829 patients and 169 controls. Dosage of VIP was titrated downwards from four to zero doses a day to determine minimum effective dose, and retitrated upwards for maximum improvement over time. The trial showed that VIP therapy safely 1) reduced refractory symptoms to equal controls;2) corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9;3) corrected estradiol, testosterone and 25-OH Vitamin D;4) returned pulmonary artery systolic pressure (PASP) during exercise to normal;and 5) enhanced quality of life in 100% of trial patients. Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.
