Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically s...Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically significant for improving health.This weight loss can be achieved through pharmacotherapy,including glucagon-like peptide 1(GLP-1)receptor agonists,GLP-1/glucosedependent insulinotropic peptide dual receptor agonists,and GLP-1/glucosedependent insulinotropic peptide/glucagon triple receptor agonists(such as semaglutide,tirzepatide,and retatrutide,respectively).While much of the weight loss comes from fat mass,these treatments also result in the loss of lean mass,including muscle.This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia.Therefore,the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass,ideally promoting muscle gain.Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction,which may play a crucial role in preserving both muscle mass and function.We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes.Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.展开更多
Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in devel...Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in development,peptides stand out for their unique advantages,including minimal immunogenicity,high tissue penetration,and ease of modification.Their small size,specificity,and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively.Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery,improving tumor imaging,and reducing adverse effects.With cancer responsible for millions of deaths worldwide,the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments.As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development,this review provides a comprehensive overview of the literature on tumor-targeting peptides,including their structure,sources,modes of action,and their application in cancer therapy—both as standalone agents and in fusion drugs.Additionally,various computational tools for peptide-based tumor-targeting drug design and validation are explored.The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies,offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.展开更多
Central nervous system disorders constitute a major global public health burden,contributing substantially to morbidity and mortality.Advances in elucidating their underlying pathogenesis have facilitated the approval...Central nervous system disorders constitute a major global public health burden,contributing substantially to morbidity and mortality.Advances in elucidating their underlying pathogenesis have facilitated the approval of an increasing number of proprietary drugs for clinical management of neurological conditions.A critical challenge in drug delivery lies in achieving appropriate tissue distribution,particularly within the brain,where effective therapeutic intervention requires traversing the blood-brain barrier and precisely targeting localized regions.Nanodelivery systems have emerged as a promising approach in biomedicine to address these challenges.Among these,peptides-characterized by their high specificity and relatively small size-are extensively employed to functionalize nanocarriers,thereby enhancing targeted tissue distribution.The conjugation of diverse functional peptides onto heterogeneous nanoscale carriers enables precise,efficient,and multidimensional targeting.This review highlights several representative neurological diseases and systematically discusses strategies for peptide-based functionalization of nanocarriers tailored to these pathological contexts.展开更多
Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural ...Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously reported.However,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.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
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-ad...Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.展开更多
Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In ...Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.展开更多
The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidom...The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.展开更多
The global mortality rate due to liver diseases,particularly liver fibrosis,is increasing.Among various treatment methods,stem cell therapy using placenta-derived mesenchymal stem cells(PDMSCs)offers distinct benefits...The global mortality rate due to liver diseases,particularly liver fibrosis,is increasing.Among various treatment methods,stem cell therapy using placenta-derived mesenchymal stem cells(PDMSCs)offers distinct benefits,including ease of isolation and superior proliferative potential.To enhance the therapeutic efficacy of PDMSCs,the WKYMVm peptide was selected for cell engineering.Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes,thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment.Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines,which in turn improves liver function and vascular repair in both in vitro and in vivo models.This approach not only enhances the angiogenic and therapeutic capacities of stem cells,but also enables efficient peptide utilization,minimizing potential side effects and costs associated with high peptide dosages.Overall,our study demonstrates significant promise of stem cell therapy for treating liver fibrosis.Thus,stem cell therapy offers considerable prospects for clinical applications.展开更多
Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is ge...Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.展开更多
Analysis of the secondary metabolite biosynthesis gene cluster(BGC)from marine Streptomyces sp.SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase(NRPS),predicted to produce a depsipeptide c...Analysis of the secondary metabolite biosynthesis gene cluster(BGC)from marine Streptomyces sp.SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase(NRPS),predicted to produce a depsipeptide compound.The NRPS gene cluster was captured by transformation-associated recombination and heterologously expressed in Streptomyces albus.The production of the new compound was confirmed using high-resolution liquid chromatography-mass spectrometry,and its structure was elucidated using nuclear magnetic resonance spectroscopy.The structure of the new depsipeptide was more similar to the monomeric structure of cyclic depsipeptides derived from fungi than to other Streptomyces-derived dep-sipeptides.In addition,the bacterial depsipeptide,which we named jejumide,showed promising anti-inflammatory activity.These results demonstrate that genome mining and successful heterologous expression of cryptic nonlinear NRPS BGCs from marine bacteria will facilitate the discovery of novel nonribosomal peptides and understanding of the complicated biosynthetic mechanism of nonlinear NRPS.展开更多
The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biologi...The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biological actions,such as feeding behavior,bone formation,and hormone secretion of QRFPR have been largely described in chordate species,while no research on QRFPR has been reported in non-chordate species.Here,the first non-chordates QRFP-like peptide receptor gene in the cephalopod Sepiella japonica(Sj_QRFPLR)was identified and characterized.Evidence from multiple alignments,phylogenetic analysis,and in vitro subcellular localization analysis indicated that Sj_QRFPLR is a class A GPCR and it belongs to the QRFPR family.Meanwhile,QRFPR is likely to be structurally conserved in cephalopod species.In situ hybridization and RT-PCR data revealed a widespread distribution pattern of Sj_QRFPLR in multiple function lobes of the female brain and numerous peripheral tissues in both male and female cuttlefish.Subsequently,a food deprivation and refeeding experiment showed that Sj_QRFPLR is likely to stimulate food intake in cuttlefish.Additionally,a possible link between Sj_QRFPLR and immune response was briefly detected in cuttlefish.The results will contribute to our understanding of QRFPR in the cephalopod as well as the peptidergic regulation of the QRFP/QRFPR system in non-chordates.展开更多
This article examines the growing prevalence of pediatric obesity and its con-nection to metabolic dysfunction-associated steatotic liver disease(MASLD)in children and adolescents,focusing on the role of glucagon-like...This article examines the growing prevalence of pediatric obesity and its con-nection to metabolic dysfunction-associated steatotic liver disease(MASLD)in children and adolescents,focusing on the role of glucagon-like peptide-1 receptor agonists in treatment.Pediatric obesity and MASLD present significant long-term health risks,making early intervention crucial.The article reviews the patho-physiology of both pediatric obesity and MASLD,explores current therapeutic strategies,and discusses the emerging role of glucagon-like peptide-1 receptor agonists,such as liraglutide,semaglutide,exenatide,and dulaglutide,in managing obesity,as well as explores current limited pediatric literature on the use of these medications in MASLD.展开更多
Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sh...Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.展开更多
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
Bicyclic peptides,a class of polypeptides with two loops within their structure,have emerged as powerful tools in the development of new peptide drugs.They have the potential to bind to challenged drug targets,with an...Bicyclic peptides,a class of polypeptides with two loops within their structure,have emerged as powerful tools in the development of new peptide drugs.They have the potential to bind to challenged drug targets,with antibody-like affinity and selectivity.Meanwhile,bicyclic peptides possess small molecule-like access to chemical synthesis,which is conducive to large-scale synthesis and screening.In the last five years,bicyclic peptide technology has been increasingly developed,and researchers have carried out a variety of studies to elucidate the potential functions of bicyclic peptides.With the continuous development of synthetic methods and the advances of new technology to build bicyclic peptide libraries,bicyclic peptides are now becoming widely used in the development of new drugs for various diseases.This perspective provides an overview of the structure types,synthesis and applications of bicyclic peptides in current drug development,and our own views on future challenges of bicyclic peptides.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
This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use o...This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.展开更多
Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence b...Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development.The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.After in ovo delivery in the amniotic fluid during embryonic development carvacrol is known to migrate to the yolk sac.However,it is unknown whether carvacrol in the yolk could enhance defence responsiveness in the yolk sac.Therefore,the aim of this study was to improve early immune function in chicken embryos,and it was hypothesized that in ovo delivery of carvacrol would result in immunomodulatory effects in the yolk sac,potentially improving post-hatch resilience.Methods On embryonic day(E)17.5,either a saline(control)or carvacrol solution was injected into the amniotic fluid.Yolk sac tissue samples were collected at E19.5,and transcriptomic analyses using RNA sequencing were performed,following functional enrichment analyses comparing the control(saline)and carvacrol-injected groups.Results The results showed that 268 genes were upregulated and 174 downregulated in the carvacrol group compared to the control(P<0.05;logFC<-0.5 or log FC>0.5).Functional analyses of these differentially expressed genes,using KEGG,REACTOME,and Gene Ontology databases,showed enrichment of several immune-related pathways.This included the pathways‘Antimicrobial peptides’(P=0.001)and‘Chemoattractant activity’(P=0.004),amongst others.Moreover,the‘NOD-like receptor signaling’pathway was enriched(P=0.002).Antimicrobial peptides are part of the innate immune defence and are amongst the molecules produced after the nucleotide oligomeriza-tion domain(NOD)-like receptor pathway activation.While these responses may be associated with an inflammatory reaction to an exogenous threat,they could also indicate that in ovo delivery of carvacrol could prepare the newly hatched chick against bacterial pathogens by potentially promoting antimicrobial peptide production through acti-vation of NOD-like receptor signaling in the yolk sac.Conclusion In conclusion,these findings suggest that in ovo delivery of carvacrol has the potential to enhance anti-pathogenic and pro-inflammatory responses in the yolk sac via upregulation of antimicrobial peptides,and NOD-like receptor pathways.展开更多
文摘Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically significant for improving health.This weight loss can be achieved through pharmacotherapy,including glucagon-like peptide 1(GLP-1)receptor agonists,GLP-1/glucosedependent insulinotropic peptide dual receptor agonists,and GLP-1/glucosedependent insulinotropic peptide/glucagon triple receptor agonists(such as semaglutide,tirzepatide,and retatrutide,respectively).While much of the weight loss comes from fat mass,these treatments also result in the loss of lean mass,including muscle.This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia.Therefore,the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass,ideally promoting muscle gain.Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction,which may play a crucial role in preserving both muscle mass and function.We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes.Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.
文摘Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in development,peptides stand out for their unique advantages,including minimal immunogenicity,high tissue penetration,and ease of modification.Their small size,specificity,and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively.Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery,improving tumor imaging,and reducing adverse effects.With cancer responsible for millions of deaths worldwide,the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments.As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development,this review provides a comprehensive overview of the literature on tumor-targeting peptides,including their structure,sources,modes of action,and their application in cancer therapy—both as standalone agents and in fusion drugs.Additionally,various computational tools for peptide-based tumor-targeting drug design and validation are explored.The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies,offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.
基金supported by the National Key Research and Development Program of China(No.2024YFF1106600).
文摘Central nervous system disorders constitute a major global public health burden,contributing substantially to morbidity and mortality.Advances in elucidating their underlying pathogenesis have facilitated the approval of an increasing number of proprietary drugs for clinical management of neurological conditions.A critical challenge in drug delivery lies in achieving appropriate tissue distribution,particularly within the brain,where effective therapeutic intervention requires traversing the blood-brain barrier and precisely targeting localized regions.Nanodelivery systems have emerged as a promising approach in biomedicine to address these challenges.Among these,peptides-characterized by their high specificity and relatively small size-are extensively employed to functionalize nanocarriers,thereby enhancing targeted tissue distribution.The conjugation of diverse functional peptides onto heterogeneous nanoscale carriers enables precise,efficient,and multidimensional targeting.This review highlights several representative neurological diseases and systematically discusses strategies for peptide-based functionalization of nanocarriers tailored to these pathological contexts.
文摘Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously reported.However,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.
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Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
基金the financial support from the Zhejiang Provincial Natural Science Foundation of China(No.LBY24H040012)Discipline Cluster of Oncology of Wenzhou Medical University(No.z1-2023007)+1 种基金the financial support from the National Natural Science Foundation of China(No.32401107)the financial support from the Discipline Cluster of Oncology of Wenzhou Medical University(No.z3-2023027)。
文摘Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.
基金supported by National Natural Science Foundation of China(Nos.82322015,82171006)Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)+3 种基金Sichuan Science and Technology Program(No.2022NSFSC0002)West China Hospital of Stomatology Sichuan University(No.RCDWJS2024-3)Sichuan Science and Technology Program(Nos.2023NSFSC1706,2024NSFSC1589)Postdoctoral Science Foundation of China(No.BX20220220)。
文摘Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.
基金supported by the central government and guides local funds for science and technology development(2022ZY0109).
文摘The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.
基金supported by grants from the Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korean government(the Ministry of Science and ICT,the Ministry of Health and Welfare)(RS-2022-00070304)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00398030).
文摘The global mortality rate due to liver diseases,particularly liver fibrosis,is increasing.Among various treatment methods,stem cell therapy using placenta-derived mesenchymal stem cells(PDMSCs)offers distinct benefits,including ease of isolation and superior proliferative potential.To enhance the therapeutic efficacy of PDMSCs,the WKYMVm peptide was selected for cell engineering.Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes,thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment.Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines,which in turn improves liver function and vascular repair in both in vitro and in vivo models.This approach not only enhances the angiogenic and therapeutic capacities of stem cells,but also enables efficient peptide utilization,minimizing potential side effects and costs associated with high peptide dosages.Overall,our study demonstrates significant promise of stem cell therapy for treating liver fibrosis.Thus,stem cell therapy offers considerable prospects for clinical applications.
基金funded by the National Natural Science Foundation of China(22478438,32401048,and 82273882)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
基金supported by the Korea Institute of Planning and Evaluation for Technology in Food,Agriculture and For-estry(IPET)through“Crop Viruses and Pests Response Industry Tech-nology Development”Program(No.321110-4)funded by the Ministry of Agriculture,Food and Rural Affairs(MAFRA),National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2022R1 A2 C3004621)+1 种基金the Ministry of Education(2022R1I1 A1 A01068507)Bio&Medical Technology Develop-ment Program of the NRF funded by MSIT(No.RS-2024-00352229,No.2022M3 A9 F3017371).
文摘Analysis of the secondary metabolite biosynthesis gene cluster(BGC)from marine Streptomyces sp.SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase(NRPS),predicted to produce a depsipeptide compound.The NRPS gene cluster was captured by transformation-associated recombination and heterologously expressed in Streptomyces albus.The production of the new compound was confirmed using high-resolution liquid chromatography-mass spectrometry,and its structure was elucidated using nuclear magnetic resonance spectroscopy.The structure of the new depsipeptide was more similar to the monomeric structure of cyclic depsipeptides derived from fungi than to other Streptomyces-derived dep-sipeptides.In addition,the bacterial depsipeptide,which we named jejumide,showed promising anti-inflammatory activity.These results demonstrate that genome mining and successful heterologous expression of cryptic nonlinear NRPS BGCs from marine bacteria will facilitate the discovery of novel nonribosomal peptides and understanding of the complicated biosynthetic mechanism of nonlinear NRPS.
基金supported by the National Natural Science Foundation of China(No.31872547)the Natural Science Foundation of Zhejiang Province,China(No.LTGN24C190015)the Excellent Postdoctoral Program of Jiangsu Province(No.314865)。
文摘The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biological actions,such as feeding behavior,bone formation,and hormone secretion of QRFPR have been largely described in chordate species,while no research on QRFPR has been reported in non-chordate species.Here,the first non-chordates QRFP-like peptide receptor gene in the cephalopod Sepiella japonica(Sj_QRFPLR)was identified and characterized.Evidence from multiple alignments,phylogenetic analysis,and in vitro subcellular localization analysis indicated that Sj_QRFPLR is a class A GPCR and it belongs to the QRFPR family.Meanwhile,QRFPR is likely to be structurally conserved in cephalopod species.In situ hybridization and RT-PCR data revealed a widespread distribution pattern of Sj_QRFPLR in multiple function lobes of the female brain and numerous peripheral tissues in both male and female cuttlefish.Subsequently,a food deprivation and refeeding experiment showed that Sj_QRFPLR is likely to stimulate food intake in cuttlefish.Additionally,a possible link between Sj_QRFPLR and immune response was briefly detected in cuttlefish.The results will contribute to our understanding of QRFPR in the cephalopod as well as the peptidergic regulation of the QRFP/QRFPR system in non-chordates.
文摘This article examines the growing prevalence of pediatric obesity and its con-nection to metabolic dysfunction-associated steatotic liver disease(MASLD)in children and adolescents,focusing on the role of glucagon-like peptide-1 receptor agonists in treatment.Pediatric obesity and MASLD present significant long-term health risks,making early intervention crucial.The article reviews the patho-physiology of both pediatric obesity and MASLD,explores current therapeutic strategies,and discusses the emerging role of glucagon-like peptide-1 receptor agonists,such as liraglutide,semaglutide,exenatide,and dulaglutide,in managing obesity,as well as explores current limited pediatric literature on the use of these medications in MASLD.
基金supported by the National Basic Research Program of China 973 Program(Nos.2021YFA0910803,2021YFC2103900)the National Natural Science Foundation of China(No.21977011)+4 种基金the Natural Science Foundation of Guangdong Province(Nos.2022A1515010996 and 2020A1515011544)the Shenzhen Science and Technology Innovation Committee(Nos.RCJC20200714114433053,JCYJ20180507181527112 and JCYJ20200109140406047)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)the Shenzhen Fundamental Research Program(No.GXWD20201231165807007–20200827170132001)Tian Fu Jin Cheng Laboratory(Advanced Medical Center)Group Racing Project(No.TFJC2023010008)。
文摘Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.
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.
文摘Bicyclic peptides,a class of polypeptides with two loops within their structure,have emerged as powerful tools in the development of new peptide drugs.They have the potential to bind to challenged drug targets,with antibody-like affinity and selectivity.Meanwhile,bicyclic peptides possess small molecule-like access to chemical synthesis,which is conducive to large-scale synthesis and screening.In the last five years,bicyclic peptide technology has been increasingly developed,and researchers have carried out a variety of studies to elucidate the potential functions of bicyclic peptides.With the continuous development of synthetic methods and the advances of new technology to build bicyclic peptide libraries,bicyclic peptides are now becoming widely used in the development of new drugs for various diseases.This perspective provides an overview of the structure types,synthesis and applications of bicyclic peptides in current drug development,and our own views on future challenges of bicyclic peptides.
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.
文摘This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.
基金support by AgriFutures Australia’s Chicken Meat Program[grant number PRJ-011584]is gratefully acknowledged.
文摘Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development.The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.After in ovo delivery in the amniotic fluid during embryonic development carvacrol is known to migrate to the yolk sac.However,it is unknown whether carvacrol in the yolk could enhance defence responsiveness in the yolk sac.Therefore,the aim of this study was to improve early immune function in chicken embryos,and it was hypothesized that in ovo delivery of carvacrol would result in immunomodulatory effects in the yolk sac,potentially improving post-hatch resilience.Methods On embryonic day(E)17.5,either a saline(control)or carvacrol solution was injected into the amniotic fluid.Yolk sac tissue samples were collected at E19.5,and transcriptomic analyses using RNA sequencing were performed,following functional enrichment analyses comparing the control(saline)and carvacrol-injected groups.Results The results showed that 268 genes were upregulated and 174 downregulated in the carvacrol group compared to the control(P<0.05;logFC<-0.5 or log FC>0.5).Functional analyses of these differentially expressed genes,using KEGG,REACTOME,and Gene Ontology databases,showed enrichment of several immune-related pathways.This included the pathways‘Antimicrobial peptides’(P=0.001)and‘Chemoattractant activity’(P=0.004),amongst others.Moreover,the‘NOD-like receptor signaling’pathway was enriched(P=0.002).Antimicrobial peptides are part of the innate immune defence and are amongst the molecules produced after the nucleotide oligomeriza-tion domain(NOD)-like receptor pathway activation.While these responses may be associated with an inflammatory reaction to an exogenous threat,they could also indicate that in ovo delivery of carvacrol could prepare the newly hatched chick against bacterial pathogens by potentially promoting antimicrobial peptide production through acti-vation of NOD-like receptor signaling in the yolk sac.Conclusion In conclusion,these findings suggest that in ovo delivery of carvacrol has the potential to enhance anti-pathogenic and pro-inflammatory responses in the yolk sac via upregulation of antimicrobial peptides,and NOD-like receptor pathways.
