Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies.Methods:The peptide/polypeptide fraction from Aloe vera was obtained through tric...Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies.Methods:The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation.The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation,membrane stabilization assays.The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays.The nitric oxide level was determined through Griess reagent.TNF-αand IL-6 levels were estimated using ELISA kits.In vivo studies were carried out in male Wistar rats through injection of Freund’s adjuvant in the hind paw.Paw edema was measured through the Vernier scale and levels of alanine aminotransferase,aspartate transaminase,TNF-α,IL-6,and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment.Graph Pad Prism6 was used for analyzing the results.Results:The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of(218.9±15.6)μg/m L and stabilized the membrane of red blood cells with an IC50 value of(275.9±19.1)μg/m L.The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20μg/mL in MTT assays.The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies.Conclusions:The results indicate that the peptide/polypeptide fraction of Aloe vera has antiinflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways.展开更多
Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limite...Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.展开更多
The preparation of polypeptide materials in continuous flow reactors shows great potential with improved reproducibility and scalability.However,conventional polypeptide synthesis from the polymerization of N-carboxya...The preparation of polypeptide materials in continuous flow reactors shows great potential with improved reproducibility and scalability.However,conventional polypeptide synthesis from the polymerization of N-carboxyanhydride(NCA)is conducted at relatively slow rates,requiring long tubing or ending up with low-molecular-weight polymers.Inspired by recent advances in accelerated NCA polymerization,we report the crown-ether-catalyzed,rapid synthesis of polypeptide materials in cosolvents in flow reactors.The incorporation of low-polarity dichloromethane and the use of catalysts enabled fast conversion of monomers in 30 min,yielding well-defined polypeptides(up to 30 k Da)through a 20-cm tubing reactor.Additionally,random or block copolypeptides were efficiently prepared by incorporating a second NCA monomer.We believe that this work highlights the accelerated polymerization design in flow polymerization processes,offering the continuous production of polypeptide materials.展开更多
BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CC...BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.展开更多
The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch...The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch processing.Using c-Fos immunolabeling and in vivo Ca2+imaging,we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide(VIP)-expressing interneuron activity in the ACC.Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch.Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis.Together,this study highlights the importance of ACC VIP+neurons in modulating itch-related affect and behavior,which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.展开更多
Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the...Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.展开更多
Signaling peptides are known for their prominent roles in plant growth, development, and environmental adaptation(Zhang et al., 2025). However, their extremely low natural abundance and highly dynamic expression patte...Signaling peptides are known for their prominent roles in plant growth, development, and environmental adaptation(Zhang et al., 2025). However, their extremely low natural abundance and highly dynamic expression patterns pose significant technical challenges to extract sufficient amounts with good purity for biological studies and practical applications.Consequently, chemical synthesis and microbial systems offer attractive alternatives to obtain potent peptides at higher quantities and purity. Incorporating modifications or substitutions, chemically synthetic approaches enable the creation of more effective engineered peptides such as agonists,antagonists, chemically modified peptides, or peptide-like molecules with novel functions compared to native peptides.展开更多
Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face wit...Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed Csingle bondH activation has been employed for the functionalization of amino acids and peptides.Through domino Csingle bondH 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 Csingle bondH activation/annulation.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
Trophoblast cell surface antigen 2(Trop2)has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors,significantly impacting tumor growth,invasion,and metastasis.In this ...Trophoblast cell surface antigen 2(Trop2)has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors,significantly impacting tumor growth,invasion,and metastasis.In this study,we develop Trop2 targeting peptide-based radiotracer[^(68)Ga]Ga-NOTA-GL10 for accurately detecting the Trop2 expression levels through positron emission tomography(PET)imaging.The Trop2-targeting peptide GL10 was rationally designed through computational methods based on the T2-2 peptide,and conjugated with the 1,4,7-triazacyclononane-N,N′,N″-triacetic acid(NOTA)chelator to synthesize the precursor NOTA-GL10 with nanomolar affinity for Trop2(K_(D)=12.9 nM).The radiosynthesis of[^(68)Ga]Ga-NOTA-GL10 was achieved via conventional methods with high radiochemical yield(RCY),good stability,and favorable pharmacokinetics.Dynamic PET imaging revealed that the tracer presented a significantly higher tumor uptake((5.03±0.49)%ID/mL)and tumor-to-muscle ratio(4.44±0.30)in Trop2-positive BxPC-3 xenografts compared to that in Trop2-negative PANC-1 xenografts((1.41±0.13)%ID/mL,1.23±0.27).Moreover,near-infrared(NIR)fluorescence imaging of the probe ICG-GL10 further confirmed the ability of GL10 to specifically target Trop2-positive tumors.The peptide-based Trop2 targeting radiotracer[^(68)Ga]Ga-NOTA-GL10 demonstrated high specificity and sensitivity in detecting Trop2 expression,which revealed the potential of Trop2-based non-invasive imaging for cancer diagnosis.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
Gram-negative bacteria can cause serious infections and are well known problems in biomedical practices. Biofilms of gramnegative bacteria are notorious for their frequently encountered resistance toward antibiotics. ...Gram-negative bacteria can cause serious infections and are well known problems in biomedical practices. Biofilms of gramnegative bacteria are notorious for their frequently encountered resistance toward antibiotics. We demonstrate that α/β chimeric polypeptide molecular brush (α/β CPMB) exerts potent activities against antibiotic-resistant gram-negative bacteria. MTT viability assay, bacterial colony counting, and live/dead staining all indicate that α/β CPMB not only inhibits biofilm formation of gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, but also effectively disrupts mature biofllms that are highly resistant to one of the most active antibiotics-colistin. The superior antibacterial performance of the α/β CPMB implies its potential topical applications in treating biofilms.展开更多
Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function a...Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day （n = 10 mice per dose）. Control animals （n = 10） received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein （STAR）, cytochrome P450 cholesterol side-chain cleavage enzyme （P450scc）, and 3β-hydroxysteroid dehydrogenase （3βHSD） in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone （ITT） concentration also increased in the VAP-treated groups. The expression of STAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis （STAR, P450scc, and 3β-HSD） and the following promotion of testosterone syothesis in vivo.展开更多
We developed one-pot photoreduction strategy to prepare near infrared light(NIR)-absorbing plasmonic gold nanoparticles(Au NPs) tethered by amphiphilic polypeptide copolymer poly(L-cysteine)-b-poly(ethylene oxide)(PLC...We developed one-pot photoreduction strategy to prepare near infrared light(NIR)-absorbing plasmonic gold nanoparticles(Au NPs) tethered by amphiphilic polypeptide copolymer poly(L-cysteine)-b-poly(ethylene oxide)(PLC-b-PEO). The PLC-b-PEO@Au NPs possessed strong NIR absorption at 700–1100 nm and ultrahigh photothermal conversion efficiency of 62.1%. Upon the NIR irradiation(808nm,2 W/cm^2,5 min), the PLC-b-PEO@Au NPs(1mg/mL) sharply attained an elevation of 30.8℃ and the hyperthermia effect could efficiently kill cancer cells in vitro. As for the PT-CT treatment, the doxorubicin(DOX)-loaded nanoparticles of DOX-PLC-b-PEO@Au NPs gave a combination index of 0.9 compared to single chemotherapy(CT) or photothermal therapy(PT), demonstrating a synergistic effect.展开更多
AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for pati...AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P < 0.05). HIF-1α and P4 HB overexpression have a significant correlation with TNM staging(χ2 = 23.32, P = 0.00; χ2 = 65.64, P = 0.00) and peritoneum cavity metastasis(χ2 = 12.67, P = 0.00; χ2 = 39.29, P = 0.00). In univariate analysis, patients with a high HIF-1α expression trend had a shorter disease-free survival(DFS: 44.80 mo vs 22.06 mo) and overall survival(OS: 49.58 mo vs 39.92 mo). P4 HB overexpression reflected similar results: patients with over-expression of P4 HB had a shorter survival time than those with weak-expression(DFS: 48.03 mo vs 29.64 mo, OS: 52.48 mo vs 36.87 mo). Furthermore, HIF-1α is also a clinicopathological predictor of dismal prognosis according to multivariate analysis(DFS, 95%c I: 0.52-0.88, P < 0.00; OS, 95%c I: 0.50-0.85, P < 0.00). However, P4 HB was meaningful in DFS(95%c I: 0.58-1.00, P < 0.05) but not in OS(95%c I: 0.72-1.23, P > 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.展开更多
We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly（ethylene oxide）, poly（L-lysine）, and poly（e-caprolactone） arms, PEO（-b-PLL）-...We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly（ethylene oxide）, poly（L-lysine）, and poly（e-caprolactone） arms, PEO（-b-PLL）-b-PCL, and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors, PEO（-b-PZLL）-b-PCL, were synthesized at first via the combination of consecutive ＂click＂ reactions and ring-opening polymerizations （ROP）, where PZLL is poly（e-benzyloxycarbonyl-L-lysine）. Subsequently, the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers, PEO（-b-PLL）-b-PCL. In aqueous media at pH 7.4, PEO（-b-PLL）-b-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug, paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA （pDNA） at N/P ratios higher than ca. 2. Thus, PEO（-b-PLL）-b-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore, polyplexes of pDNA with paclitaxel-loaded PEO（-b- PLL）-b-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting, imaging, and diagnostics.展开更多
To construct an eukaryotic expressing vector that expresses CH50, a recombinant CellⅠ HepⅡ bifunctional domain polypeptide of human fibronectin, and to investigate the chemotaxis to immune cells and the inhibitor...To construct an eukaryotic expressing vector that expresses CH50, a recombinant CellⅠ HepⅡ bifunctional domain polypeptide of human fibronectin, and to investigate the chemotaxis to immune cells and the inhibitory effect on the growth of tumor by the expression of the plasmid in vivo , the plasmid was constructed by DNA recombination. Gene transfection was performed in vitro and in vivo . The expressed product was identified by Western blot. The chemotaxis after gene transfection in vivo was observed by histotomy and staining of muscle tissues. The inhibition of gene transfection on solid tumor was observed in mice. The results showed that plasmid pCH510 was constructed by the recombination of the 5′ terminal noncoding region and signal peptide coding region of human fibronectin cDNA and cDNA fragment coding CH50 polypeptide with a 3′ terminal noncoding region of human FN cDNA, and the insertion of the recombinated fragment into plasmid pcDNA3.1. After transfection with plasmid pCH510, NIH3T3 cells could produce CH50 polypeptide. The transfection of plasmid pCH510 by the injection in muscle of mouse could produce the effects of chemotaxis on immune cells and the inhibition on the growth of solid tumor. It is concluded that plasmid pCH510 can express in cells and in vivo in mouse. The expression of the plasmid in vivo has a chemotactic effect on immune cells and can inhibit the growth of solid tumor.展开更多
Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological funct...Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological functional damage caused by middle cerebral artery occlusion,but the underlying neuroprotective mechanisms and the relationship to glutamate-induced excitotoxicity remain unclear.Therefore,in the current study,we investigated the protective effects of Achyranthes bidentata polypeptides against glutamate-induced excitotoxicity in cultured hippocampal neurons.Hippocampal neurons were treated with Mg^2+-free extracellular solution containing glutamate(300μM)for 3 hours as a model of glutamate-mediated excitotoxicity(glutamate group).In the normal group,hippocampal neurons were incubated in Mg^2+-free extracellular solution.In the Achyranthes bidentata polypeptide group,hippocampal neurons were incubated in Mg^2+-free extracellular solution containing glutamate(300μM)and Achyranthes bidentata polypeptide at different concentrations.At 24 hours after exposure to the agents,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst 33258 staining were used to assess neuronal viability and nuclear m'orphology,respectively.Caspase-3 expression and activity were evaluated using western blot assay and colorimetric enzymatic assay,respectively.At various time points after glutamate treatment,reactive oxygen species in cells were detected by H2 DCF-DA,and mitochondrial membrane potential was detected by rhodamine 123 staining.To examine the effect of Achyranthes bidentata polypeptides on glutamate receptors,electrophysiological recording was used to measure the glutamate-induced inward current in cultured hippocampal neurons.Achyranthes bidentata polypeptide decreased the percentage of apoptotic cells and reduced the changes in caspase-3 expression and activity induced by glutamate.In addition,Achyranthes bidentata polypeptide attenuated the amplitude of the glutamate-induced current.Furthermore,the glutamate-induced increase in intracellular reactive oxygen species and reduction in mitochondrial membrane potential were attenuated by Achyranthes bidentata polypeptide treatment.These findings collectively suggest that Achyranthes bidentata polypeptides exert a neuroprotective effect in cultured hippocampal neurons by suppressing the overactivation of glutamate receptors and inhibiting the caspase-3-dependent mitochondrial apoptotic pathway.All animal studies were approved by the Animal Care and Use Committee,Nantong University,China(approval No.20120216-001)on February 16,2012.展开更多
文摘Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies.Methods:The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation.The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation,membrane stabilization assays.The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays.The nitric oxide level was determined through Griess reagent.TNF-αand IL-6 levels were estimated using ELISA kits.In vivo studies were carried out in male Wistar rats through injection of Freund’s adjuvant in the hind paw.Paw edema was measured through the Vernier scale and levels of alanine aminotransferase,aspartate transaminase,TNF-α,IL-6,and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment.Graph Pad Prism6 was used for analyzing the results.Results:The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of(218.9±15.6)μg/m L and stabilized the membrane of red blood cells with an IC50 value of(275.9±19.1)μg/m L.The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20μg/mL in MTT assays.The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies.Conclusions:The results indicate that the peptide/polypeptide fraction of Aloe vera has antiinflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways.
基金funded by the National Natural Science Foundation of China (No. 81960334)the Guiding Plan of Xinjiang Production Construction Corps (No. 2022ZD007)+4 种基金the Science and Technology Innovation Leading Talents Program of Guangdong Province (No. 2019TX05C343)the Basic and Applied Basic Research Foundation of Guangdong Province-Regional Joint Fund-Key Projects (No. 2019B1515120043)the Project supported by the State Key Laboratory of Luminescence and Applications (No. SKLA-2020-03)the support from Instrumental Analysis Center of Shenzhen University (Xili Campus)Instrumental Analysis Center of Shihezi University.
文摘Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.
基金financially supported by the National Natural Science Foundation of China(No.22101194)Natural Science Foundation of Jiangsu Province(No.BK20210733)+3 种基金Suzhou Municipal Science and Technology Bureau(No.ZXL2021447)Collaborative Innovation Center of Suzhou Nano Science&Technologythe 111 ProjectJoint International Research Laboratory of Carbon-Based Functional Materials and Devices。
文摘The preparation of polypeptide materials in continuous flow reactors shows great potential with improved reproducibility and scalability.However,conventional polypeptide synthesis from the polymerization of N-carboxyanhydride(NCA)is conducted at relatively slow rates,requiring long tubing or ending up with low-molecular-weight polymers.Inspired by recent advances in accelerated NCA polymerization,we report the crown-ether-catalyzed,rapid synthesis of polypeptide materials in cosolvents in flow reactors.The incorporation of low-polarity dichloromethane and the use of catalysts enabled fast conversion of monomers in 30 min,yielding well-defined polypeptides(up to 30 k Da)through a 20-cm tubing reactor.Additionally,random or block copolypeptides were efficiently prepared by incorporating a second NCA monomer.We believe that this work highlights the accelerated polymerization design in flow polymerization processes,offering the continuous production of polypeptide materials.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2023MH329Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program,No.2023KJ263and Natural Science Foundation of Gansu Province,China,No.22JR5RA953.
文摘BACKGROUND As a member of the chaperonin-containing tailless complex polypeptide 1(TCP1)complex,which plays a pivotal role in ensuring the accurate folding of numerous proteins,chaperonin-containing TCP1 subunit 6A(CCT6A)participates in various physiological and pathological processes.However,its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer(CRC)cells.AIM To explore the effects of CCT6A on cell death and cancer therapy and the underlying mechanisms in CRC.METHODS Cell proliferation was evaluated using the MTS assay,EdU staining,and colony growth assays.The expression of CCT6A was monitored by immunoblotting and quantitative PCR.CCT6A was knocked out by CRISPR-Cas9,and overexpressed by transfecting plasmids.Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay.To monitor apoptosis and necroptosis,immunoblotting,co-immunoprecipitation,and flow cytometry were employed.RESULTS Cisplatin(DDP)exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A.Depletion of CCT6A amplified the cytotoxic effects of DDP,whereas overexpression of CCT6A attenuated these adverse effects.CCT6A suppressed autophagy,apoptosis,and necroptosis under both basal and DDP-treated conditions.Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP,whereas a necroptosis inhibitor partially reversed the cell viability loss induced by DDP.Furthermore,inhibiting autophagy enhanced both apoptosis and necroptosis induced by DDP.CONCLUSION CCT6A negatively modulates autophagy,apoptosis,and necroptosis,and CCT6A confers resistance to DDP therapy in CRC,suggesting its potential as a therapeutic target.
基金supported by grants from the National Natural Science Foundation of China(82271243 and 82101318)Shaanxi Province Key Research and Development Plan(2024SF-ZDCYL-01-13)+1 种基金the support funding from Fourth Military Medical University(2024JC005,2020AXJHHJ,and XJZT24JC27)Liaoning Provincial Joint Science and Technology Program(2023-MSLH-345).
文摘The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch processing.Using c-Fos immunolabeling and in vivo Ca2+imaging,we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide(VIP)-expressing interneuron activity in the ACC.Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch.Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis.Together,this study highlights the importance of ACC VIP+neurons in modulating itch-related affect and behavior,which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026,China).
文摘Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.
基金supported by National Natural Science Foundation of China(32370850,32460081)Leading Talent of Technological Innovation of Shaanxi Special Support Program(20249)+3 种基金the Natural Science Foundation of Shaanxi(2020JC-29,2023-JCZD-09)Central Universities Funds(GK202402003)the Jiangxi Agricultural University(9232308314)the Science and Technology Department of Jiangxi Province(20223BCJ25037)。
文摘Signaling peptides are known for their prominent roles in plant growth, development, and environmental adaptation(Zhang et al., 2025). However, their extremely low natural abundance and highly dynamic expression patterns pose significant technical challenges to extract sufficient amounts with good purity for biological studies and practical applications.Consequently, chemical synthesis and microbial systems offer attractive alternatives to obtain potent peptides at higher quantities and purity. Incorporating modifications or substitutions, chemically synthetic approaches enable the creation of more effective engineered peptides such as agonists,antagonists, chemically modified peptides, or peptide-like molecules with novel functions compared to native peptides.
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 Csingle bondH activation has been employed for the functionalization of amino acids and peptides.Through domino Csingle bondH 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 Csingle bondH activation/annulation.
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.
基金supported by the National Natural Science Foundation of China(22407052)the Jiangsu Provincial Natural Science Foundation(BK20240300)+4 种基金the Scientific Research Project of Jiangsu Commission of Health(MQ2024007,H2023150,K2024007)the Wuxi Science and Technology Development Fund(K20241060)the Major Project of Wuxi Municipal Health Commission(Z202303)the Wuxi Association for Science and Technology(TJXD-2024-102)the Jiangsu Province Capability Improvement Project through Science,Technology and Education(ZDXYS202211)。
文摘Trophoblast cell surface antigen 2(Trop2)has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors,significantly impacting tumor growth,invasion,and metastasis.In this study,we develop Trop2 targeting peptide-based radiotracer[^(68)Ga]Ga-NOTA-GL10 for accurately detecting the Trop2 expression levels through positron emission tomography(PET)imaging.The Trop2-targeting peptide GL10 was rationally designed through computational methods based on the T2-2 peptide,and conjugated with the 1,4,7-triazacyclononane-N,N′,N″-triacetic acid(NOTA)chelator to synthesize the precursor NOTA-GL10 with nanomolar affinity for Trop2(K_(D)=12.9 nM).The radiosynthesis of[^(68)Ga]Ga-NOTA-GL10 was achieved via conventional methods with high radiochemical yield(RCY),good stability,and favorable pharmacokinetics.Dynamic PET imaging revealed that the tracer presented a significantly higher tumor uptake((5.03±0.49)%ID/mL)and tumor-to-muscle ratio(4.44±0.30)in Trop2-positive BxPC-3 xenografts compared to that in Trop2-negative PANC-1 xenografts((1.41±0.13)%ID/mL,1.23±0.27).Moreover,near-infrared(NIR)fluorescence imaging of the probe ICG-GL10 further confirmed the ability of GL10 to specifically target Trop2-positive tumors.The peptide-based Trop2 targeting radiotracer[^(68)Ga]Ga-NOTA-GL10 demonstrated high specificity and sensitivity in detecting Trop2 expression,which revealed the potential of Trop2-based non-invasive imaging for cancer diagnosis.
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financially supported by the National Natural Science Foundation of China (Nos. 21574038, 21774031, and 21861162010)the Natural Science Foundation of Shanghai (No. 18ZR1410300)+2 种基金the “Eastern Scholar Professorship” from Shanghai local government (No. TP2014034)the national special fund for State Key Laboratory of Bioreactor Engineering (No. 2060204)the Fundamental Research Funds for the Central Universities (No. 22221818014)
文摘Gram-negative bacteria can cause serious infections and are well known problems in biomedical practices. Biofilms of gramnegative bacteria are notorious for their frequently encountered resistance toward antibiotics. We demonstrate that α/β chimeric polypeptide molecular brush (α/β CPMB) exerts potent activities against antibiotic-resistant gram-negative bacteria. MTT viability assay, bacterial colony counting, and live/dead staining all indicate that α/β CPMB not only inhibits biofilm formation of gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, but also effectively disrupts mature biofllms that are highly resistant to one of the most active antibiotics-colistin. The superior antibacterial performance of the α/β CPMB implies its potential topical applications in treating biofilms.
基金This work was supported by the National Natural Science Foundation of China （No. 81302223） and the Medical Scientific Research Foundation of Guangdong Province, China （B2013104）.
文摘Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day （n = 10 mice per dose）. Control animals （n = 10） received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein （STAR）, cytochrome P450 cholesterol side-chain cleavage enzyme （P450scc）, and 3β-hydroxysteroid dehydrogenase （3βHSD） in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone （ITT） concentration also increased in the VAP-treated groups. The expression of STAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis （STAR, P450scc, and 3β-HSD） and the following promotion of testosterone syothesis in vivo.
基金The National Natural Science Foundation of China (No. 21474061)The Innovation Fund (No. IFPM2016B004) of Shanghai Jiao Tong University & Affiliated Sixth People's Hospital South Campus are appreciated
文摘We developed one-pot photoreduction strategy to prepare near infrared light(NIR)-absorbing plasmonic gold nanoparticles(Au NPs) tethered by amphiphilic polypeptide copolymer poly(L-cysteine)-b-poly(ethylene oxide)(PLC-b-PEO). The PLC-b-PEO@Au NPs possessed strong NIR absorption at 700–1100 nm and ultrahigh photothermal conversion efficiency of 62.1%. Upon the NIR irradiation(808nm,2 W/cm^2,5 min), the PLC-b-PEO@Au NPs(1mg/mL) sharply attained an elevation of 30.8℃ and the hyperthermia effect could efficiently kill cancer cells in vitro. As for the PT-CT treatment, the doxorubicin(DOX)-loaded nanoparticles of DOX-PLC-b-PEO@Au NPs gave a combination index of 0.9 compared to single chemotherapy(CT) or photothermal therapy(PT), demonstrating a synergistic effect.
基金Supported by Liaoning S and T Project,No.2015020269Doctor fund of Liaoning Province Cancer Hospital and Institute,No.Z1410
文摘AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P < 0.05). HIF-1α and P4 HB overexpression have a significant correlation with TNM staging(χ2 = 23.32, P = 0.00; χ2 = 65.64, P = 0.00) and peritoneum cavity metastasis(χ2 = 12.67, P = 0.00; χ2 = 39.29, P = 0.00). In univariate analysis, patients with a high HIF-1α expression trend had a shorter disease-free survival(DFS: 44.80 mo vs 22.06 mo) and overall survival(OS: 49.58 mo vs 39.92 mo). P4 HB overexpression reflected similar results: patients with over-expression of P4 HB had a shorter survival time than those with weak-expression(DFS: 48.03 mo vs 29.64 mo, OS: 52.48 mo vs 36.87 mo). Furthermore, HIF-1α is also a clinicopathological predictor of dismal prognosis according to multivariate analysis(DFS, 95%c I: 0.52-0.88, P < 0.00; OS, 95%c I: 0.50-0.85, P < 0.00). However, P4 HB was meaningful in DFS(95%c I: 0.58-1.00, P < 0.05) but not in OS(95%c I: 0.72-1.23, P > 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.
基金supported by the National Natural Science Foundation of China (Nos. 21274137, 91027026 and 51033005)Fundamental Research Funds for the Central UniversitiesSpecialized Research Fund for the Doctoral Program of Higher Education (SRFDP, 20123402130010)
文摘We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly（ethylene oxide）, poly（L-lysine）, and poly（e-caprolactone） arms, PEO（-b-PLL）-b-PCL, and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors, PEO（-b-PZLL）-b-PCL, were synthesized at first via the combination of consecutive ＂click＂ reactions and ring-opening polymerizations （ROP）, where PZLL is poly（e-benzyloxycarbonyl-L-lysine）. Subsequently, the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers, PEO（-b-PLL）-b-PCL. In aqueous media at pH 7.4, PEO（-b-PLL）-b-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug, paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA （pDNA） at N/P ratios higher than ca. 2. Thus, PEO（-b-PLL）-b-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore, polyplexes of pDNA with paclitaxel-loaded PEO（-b- PLL）-b-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting, imaging, and diagnostics.
基金a grant from the NationalNatural Science Foundation of China(No. 39870 76 3) and aFunding Program for New- Century Talent of the Ministry ofEducation of China
文摘To construct an eukaryotic expressing vector that expresses CH50, a recombinant CellⅠ HepⅡ bifunctional domain polypeptide of human fibronectin, and to investigate the chemotaxis to immune cells and the inhibitory effect on the growth of tumor by the expression of the plasmid in vivo , the plasmid was constructed by DNA recombination. Gene transfection was performed in vitro and in vivo . The expressed product was identified by Western blot. The chemotaxis after gene transfection in vivo was observed by histotomy and staining of muscle tissues. The inhibition of gene transfection on solid tumor was observed in mice. The results showed that plasmid pCH510 was constructed by the recombination of the 5′ terminal noncoding region and signal peptide coding region of human fibronectin cDNA and cDNA fragment coding CH50 polypeptide with a 3′ terminal noncoding region of human FN cDNA, and the insertion of the recombinated fragment into plasmid pcDNA3.1. After transfection with plasmid pCH510, NIH3T3 cells could produce CH50 polypeptide. The transfection of plasmid pCH510 by the injection in muscle of mouse could produce the effects of chemotaxis on immune cells and the inhibition on the growth of solid tumor. It is concluded that plasmid pCH510 can express in cells and in vivo in mouse. The expression of the plasmid in vivo has a chemotactic effect on immune cells and can inhibit the growth of solid tumor.
基金supported by the National Natural Science Foundation of China,No.81073079(to HMS)the Natural Science Foundation of the Jiangsu Higher Education Institute of China,No.18KJA180009(to HMS)the Science Foundation of Nantong City of China,No.MS12018043(to HMS)
文摘Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological functional damage caused by middle cerebral artery occlusion,but the underlying neuroprotective mechanisms and the relationship to glutamate-induced excitotoxicity remain unclear.Therefore,in the current study,we investigated the protective effects of Achyranthes bidentata polypeptides against glutamate-induced excitotoxicity in cultured hippocampal neurons.Hippocampal neurons were treated with Mg^2+-free extracellular solution containing glutamate(300μM)for 3 hours as a model of glutamate-mediated excitotoxicity(glutamate group).In the normal group,hippocampal neurons were incubated in Mg^2+-free extracellular solution.In the Achyranthes bidentata polypeptide group,hippocampal neurons were incubated in Mg^2+-free extracellular solution containing glutamate(300μM)and Achyranthes bidentata polypeptide at different concentrations.At 24 hours after exposure to the agents,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst 33258 staining were used to assess neuronal viability and nuclear m'orphology,respectively.Caspase-3 expression and activity were evaluated using western blot assay and colorimetric enzymatic assay,respectively.At various time points after glutamate treatment,reactive oxygen species in cells were detected by H2 DCF-DA,and mitochondrial membrane potential was detected by rhodamine 123 staining.To examine the effect of Achyranthes bidentata polypeptides on glutamate receptors,electrophysiological recording was used to measure the glutamate-induced inward current in cultured hippocampal neurons.Achyranthes bidentata polypeptide decreased the percentage of apoptotic cells and reduced the changes in caspase-3 expression and activity induced by glutamate.In addition,Achyranthes bidentata polypeptide attenuated the amplitude of the glutamate-induced current.Furthermore,the glutamate-induced increase in intracellular reactive oxygen species and reduction in mitochondrial membrane potential were attenuated by Achyranthes bidentata polypeptide treatment.These findings collectively suggest that Achyranthes bidentata polypeptides exert a neuroprotective effect in cultured hippocampal neurons by suppressing the overactivation of glutamate receptors and inhibiting the caspase-3-dependent mitochondrial apoptotic pathway.All animal studies were approved by the Animal Care and Use Committee,Nantong University,China(approval No.20120216-001)on February 16,2012.
