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
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
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
Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid po...Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.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
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
OBJECTIVE: To investigate the efficacy and safety of intravenous cervus and cucumis polypeptides for treating avascular necrosis of the femoral head(ANFH) in regard to pain and hip function in a randomized clinical tr...OBJECTIVE: To investigate the efficacy and safety of intravenous cervus and cucumis polypeptides for treating avascular necrosis of the femoral head(ANFH) in regard to pain and hip function in a randomized clinical trial.METHODS: A total of 96 subjects with ANFH who were recruited at the Orthopaedic Hospital Affiliated with Hebei United University and Qian Hai Femoral Head Hospital of Beijing were assigned by lottery to an intervention group(n = 48) or a control group(n = 48). All subjects underwent physical therapy and rehabilitation exercises. In addition,subjects in the intervention group were given intravenous infusions of cervus and cucumis polypeptides. Visual analogue scale(VAS), Harris hip score,and radiography or magnetic resonance imaging were applied to assess all subjects at the beginning of treatment and 3, 6, and 9 months afterward. All the subjects were followed up for 2 years.RESULTS: At the beginning of treatment, there were no statistically significant differences between the two groups in terms of the general condition of patients or the VAS and Harris hip scores(all P > 0.05). At 3, 6, and 9 months after treatment,however, the VAS score decreased and the Harris hip score increased in all patients, with the improvement of intervention group significantly greater than that of the control group(P < 0.05).The total effectiveness rates for the intervention and control groups were 89.58% and 70.83%, respectively, with the difference being statistically significant(P < 0.05). There was no statistically significant difference between the two groups in terms of the safety of the injections(P > 0.05).CONCLUSION: Intravenous infusion of cervus and cucumis polypeptides relieved pain and improved hip function of subjects with ANFH.Thus, the intravenous infusion of cervus and cucumis polypeptides was a safe, effective treatment for ANFH.展开更多
AIM: To investigate the effects of psychological stress on small intestinal motility and expression of cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in plasma and small intestine, and to explore th...AIM: To investigate the effects of psychological stress on small intestinal motility and expression of cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in plasma and small intestine, and to explore the relationship between small intestinal motor disorders and gastrointestinal hormones under psychological stress. METHODS: Thirty-six mice were randomly divided into psychological stress group and control group. A mouse model with psychological stress was established by housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. CCK and VIP levels in plasma and small intestine in mice were measured by radioimmunoassay (RIA). RESULTS: Small intestinal transit was inhibited (52.18±19.15% vs70.19±17.79%, P<0.01) in mice after psychological stress, compared to the controls. Small intestinal CCK levels in psychological stress mice were significantly lower than those in the control group (0.75±0.53 μg/g vs1.98±1.17 μg/g, P<0.01), whereas plasma CCK concentrations were not different between the groups. VIP levels in small intestine were significantly higher in psychological stress mice than those in the control group (8.45±1.09 μg/g vs7.03±2.36 μg/g, P<0.01), while there was no significant difference in plasma VIP levels between the two groups. CONCLUSION: Psychological stress inhibits the small intestinal transit, probably by down-regulating CCK and up-regulating VIP expression in small intestine.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
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
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
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
Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions worldwide.Due to population ageing,the incidence of AD is increasing.AD patients develop cognitive decline and dementia,features for which ...Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions worldwide.Due to population ageing,the incidence of AD is increasing.AD patients develop cognitive decline and dementia,features for which is known,requiring permanent care.This poses a major socio-economic burden on healthcare systems as AD patients’relatives and healthcare workers are forced to cope with rising numbers of affected people.Despite recent advances,AD pathological mechanisms are not fully understood.Nevertheless,it is clear that the amyloid beta(Aβ)peptide,which forms amyloid plaques in AD patients’brains,plays a key role.Type 2 diabetes,the most common form of diabetes,affects hundreds of million people globally.Islet amyloid polypeptide(IAPP)is a hormone coproduced and secreted with insulin in pancreaticβ-cells,with a key role in diabetes,as it helps regulate glucose levels and control adiposity and satiation.Similarly to Aβ,IAPP is very amyloidogenic,generating intracellular amyloid deposits that causeβ-cell dysfunction and death.It is now clear that IAPP can also have a pathological role in AD,decreasing cognitive function.IAPP harms the blood-brain barrier,directly interacts and co-deposits with Aβ,promoting diabetes-associated dementia.IAPP can cause a metabolic dysfunction in the brain,leading to other diabetes-related forms of AD.Thus,here we discuss IAPP association with diabetes,Aβand dementia,in the context of what we designate a“diabetes brain phenotype”AD hypothesis.Such approach helps to set a conceptual framework for future IAPP-based drugs against AD.展开更多
Polypeptide from Chlamys farreri(PCF) is a novel marine bioactive product that was isolated from the gonochoric Chinese scallop Chlamys farreri,and was found to be an effective antioxidant in our recent studies.In thi...Polypeptide from Chlamys farreri(PCF) is a novel marine bioactive product that was isolated from the gonochoric Chinese scallop Chlamys farreri,and was found to be an effective antioxidant in our recent studies.In this study,we investigated the effect of PCF on ultraviolet B(UVB)-induced apoptosis of HaCaT cells and the intracellular signaling pathways involved.Pretreatment with the inducible nitric oxide synthase(iNOS) inhibitor S-methylisothiourea sulfate inhibited UVB-induced apoptosis,indicating that iNOS and NO play important roles in apoptosis.On the other hand,the inhibition of UVB-induced apoptosis in the immortalized keratinocyte(HaCaT) cells by PCF was estimated using a DNA ladder.PCF treatment inhibited UVB-induced iNOS activation,as determined by RT-PCR,NO production,as determined by ESR,and up-regulated heat shock protein(HSP) 90 activation,as determined by Western blotting.Our results indicate that iNOS and NO are involved in UVB-induced apoptosis of HaCaT cells and the protective effect of PCF against UVB irradiation is exerted by suppressing the expression of iNOS,followed by inhibition of NO release and enhanced activation of HSP90.展开更多
Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)...Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)of α-amino acid N-carboxyanhydrides(NCAs)by Leuchs and Hermann in 1906.In the past decades,several effective strategies,including the selection of initiators,the adjustment of reaction conditions,and the introduction of catalysts,have been reported to improve the controllability of the ROP of various a-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes.In this Review,the strategies,mechanisms,challenges,and opportunities for controlled synthesis of polypeptides by the ROP of differentα-amino acid NCAs have been declared.展开更多
Polypeptides have been widely utilized in the fields of biomaterials and biomedicine.Ever since N-carboxyanhydride(NCA)was reported by Hermann Leuchs in 1906,ring-opening polymerization of NCAS has been extensively us...Polypeptides have been widely utilized in the fields of biomaterials and biomedicine.Ever since N-carboxyanhydride(NCA)was reported by Hermann Leuchs in 1906,ring-opening polymerization of NCAS has been extensively used to prepare polypeptides.Despite continuous innovations,it is still challenging to synthesize polypeptides in high molecular weight fficiently.To address this challenge,we developed KHMDS/NaHMDS initiated fast NCA polymerization that is also moisture tolerant,open-flask amenable and terminal tunable.This NCA polymerization was able to proceed in most common solvents and meet the solubility requirement of variable NCA monomers and corresponding polypeptides.KHMDS can initiate r benzy-L glutamate-N carboxyanhydride(BLG NCA)polymerization in a reaction rate 92 times faster than does hexylamine and 80 times faster than does triethylamine.This NCA polymerization also demonstrated easy and fast synthesis of gram-scale long chain polypeptides in an open flask.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
AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at c...AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.展开更多
We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To ide...We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.展开更多
Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri , was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ...Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri , was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH px) in the dorsal skin were determined using biochemical methods. The results showed:(1)PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration dependent manner.(2)PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH px.(3)The differences among the PCF groups and UV model group were significant ( P <0.05, P <0.01). These results indicated that topical application of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.展开更多
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 The Mike Hogg FundBaylor College of Medicine Medical Scientist Training Program,NICHD R01HD099252(to RJP)and R01HD098131(to RJP)the NHLBI T32 HL092332(to ASB)。
文摘Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.
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 Tangshan Science and Technology Research Project(No.13130242b)
文摘OBJECTIVE: To investigate the efficacy and safety of intravenous cervus and cucumis polypeptides for treating avascular necrosis of the femoral head(ANFH) in regard to pain and hip function in a randomized clinical trial.METHODS: A total of 96 subjects with ANFH who were recruited at the Orthopaedic Hospital Affiliated with Hebei United University and Qian Hai Femoral Head Hospital of Beijing were assigned by lottery to an intervention group(n = 48) or a control group(n = 48). All subjects underwent physical therapy and rehabilitation exercises. In addition,subjects in the intervention group were given intravenous infusions of cervus and cucumis polypeptides. Visual analogue scale(VAS), Harris hip score,and radiography or magnetic resonance imaging were applied to assess all subjects at the beginning of treatment and 3, 6, and 9 months afterward. All the subjects were followed up for 2 years.RESULTS: At the beginning of treatment, there were no statistically significant differences between the two groups in terms of the general condition of patients or the VAS and Harris hip scores(all P > 0.05). At 3, 6, and 9 months after treatment,however, the VAS score decreased and the Harris hip score increased in all patients, with the improvement of intervention group significantly greater than that of the control group(P < 0.05).The total effectiveness rates for the intervention and control groups were 89.58% and 70.83%, respectively, with the difference being statistically significant(P < 0.05). There was no statistically significant difference between the two groups in terms of the safety of the injections(P > 0.05).CONCLUSION: Intravenous infusion of cervus and cucumis polypeptides relieved pain and improved hip function of subjects with ANFH.Thus, the intravenous infusion of cervus and cucumis polypeptides was a safe, effective treatment for ANFH.
文摘AIM: To investigate the effects of psychological stress on small intestinal motility and expression of cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in plasma and small intestine, and to explore the relationship between small intestinal motor disorders and gastrointestinal hormones under psychological stress. METHODS: Thirty-six mice were randomly divided into psychological stress group and control group. A mouse model with psychological stress was established by housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. CCK and VIP levels in plasma and small intestine in mice were measured by radioimmunoassay (RIA). RESULTS: Small intestinal transit was inhibited (52.18±19.15% vs70.19±17.79%, P<0.01) in mice after psychological stress, compared to the controls. Small intestinal CCK levels in psychological stress mice were significantly lower than those in the control group (0.75±0.53 μg/g vs1.98±1.17 μg/g, P<0.01), whereas plasma CCK concentrations were not different between the groups. VIP levels in small intestine were significantly higher in psychological stress mice than those in the control group (8.45±1.09 μg/g vs7.03±2.36 μg/g, P<0.01), while there was no significant difference in plasma VIP levels between the two groups. CONCLUSION: Psychological stress inhibits the small intestinal transit, probably by down-regulating CCK and up-regulating VIP expression in small intestine.
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 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.
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supported by iNOVA4Health-UID/Multi/04462/2019,a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência,through national funds and co-funded by FEDER under the PT2020 Partnership Agreement,Funding from INTERFACE Programme,through the Innovation,Technology and Circular Economy Fund(FITEC),FCT via PTDC/BIA-MOL/31104/2017 and UID/Multi/04462/2019-SubProj iNOVA4Health C44(to RM),PD/BD/135504/2018(to AFR)Sociedade Portuguesa de Diabetologia for the Nuno Castelo-Branco Prize-2016(to RM),and ICM acknowledges FCT-MCTES Program“Concurso de Estímulo ao Emprego Científico”(CEECIND/01670/2017).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions worldwide.Due to population ageing,the incidence of AD is increasing.AD patients develop cognitive decline and dementia,features for which is known,requiring permanent care.This poses a major socio-economic burden on healthcare systems as AD patients’relatives and healthcare workers are forced to cope with rising numbers of affected people.Despite recent advances,AD pathological mechanisms are not fully understood.Nevertheless,it is clear that the amyloid beta(Aβ)peptide,which forms amyloid plaques in AD patients’brains,plays a key role.Type 2 diabetes,the most common form of diabetes,affects hundreds of million people globally.Islet amyloid polypeptide(IAPP)is a hormone coproduced and secreted with insulin in pancreaticβ-cells,with a key role in diabetes,as it helps regulate glucose levels and control adiposity and satiation.Similarly to Aβ,IAPP is very amyloidogenic,generating intracellular amyloid deposits that causeβ-cell dysfunction and death.It is now clear that IAPP can also have a pathological role in AD,decreasing cognitive function.IAPP harms the blood-brain barrier,directly interacts and co-deposits with Aβ,promoting diabetes-associated dementia.IAPP can cause a metabolic dysfunction in the brain,leading to other diabetes-related forms of AD.Thus,here we discuss IAPP association with diabetes,Aβand dementia,in the context of what we designate a“diabetes brain phenotype”AD hypothesis.Such approach helps to set a conceptual framework for future IAPP-based drugs against AD.
基金Supported by the National Natural Science Foundation of China (30471458)National Natural Science Foundation of Shandong Province (Z2007c09)
文摘Polypeptide from Chlamys farreri(PCF) is a novel marine bioactive product that was isolated from the gonochoric Chinese scallop Chlamys farreri,and was found to be an effective antioxidant in our recent studies.In this study,we investigated the effect of PCF on ultraviolet B(UVB)-induced apoptosis of HaCaT cells and the intracellular signaling pathways involved.Pretreatment with the inducible nitric oxide synthase(iNOS) inhibitor S-methylisothiourea sulfate inhibited UVB-induced apoptosis,indicating that iNOS and NO play important roles in apoptosis.On the other hand,the inhibition of UVB-induced apoptosis in the immortalized keratinocyte(HaCaT) cells by PCF was estimated using a DNA ladder.PCF treatment inhibited UVB-induced iNOS activation,as determined by RT-PCR,NO production,as determined by ESR,and up-regulated heat shock protein(HSP) 90 activation,as determined by Western blotting.Our results indicate that iNOS and NO are involved in UVB-induced apoptosis of HaCaT cells and the protective effect of PCF against UVB irradiation is exerted by suppressing the expression of iNOS,followed by inhibition of NO release and enhanced activation of HSP90.
基金the financial support from the National Natural Science Foundation of China(Nos.51973216,51873207,51803006,51833010,51673190 and 51520105004)the Science and Technology Development Program of Jilin Province(No.20190201068JC)+2 种基金the National Key Research and Development Program of China(No.2016YFC1100701)the Youth Talents Promotion Project of Jilin Province(No.181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019005)。
文摘Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)of α-amino acid N-carboxyanhydrides(NCAs)by Leuchs and Hermann in 1906.In the past decades,several effective strategies,including the selection of initiators,the adjustment of reaction conditions,and the introduction of catalysts,have been reported to improve the controllability of the ROP of various a-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes.In this Review,the strategies,mechanisms,challenges,and opportunities for controlled synthesis of polypeptides by the ROP of differentα-amino acid NCAs have been declared.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21774031 and 21861162010)the National Key Research and Development Program of China(No.2016YFC1100401)+1 种基金Research Program of State Key Laboratory of Bioreactor Enginering,State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Donghua University,the Fundamental Research Funds for the Central Universities(Nos.22221818014 and 50321041917001)The authors also thank Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization.
文摘Polypeptides have been widely utilized in the fields of biomaterials and biomedicine.Ever since N-carboxyanhydride(NCA)was reported by Hermann Leuchs in 1906,ring-opening polymerization of NCAS has been extensively used to prepare polypeptides.Despite continuous innovations,it is still challenging to synthesize polypeptides in high molecular weight fficiently.To address this challenge,we developed KHMDS/NaHMDS initiated fast NCA polymerization that is also moisture tolerant,open-flask amenable and terminal tunable.This NCA polymerization was able to proceed in most common solvents and meet the solubility requirement of variable NCA monomers and corresponding polypeptides.KHMDS can initiate r benzy-L glutamate-N carboxyanhydride(BLG NCA)polymerization in a reaction rate 92 times faster than does hexylamine and 80 times faster than does triethylamine.This NCA polymerization also demonstrated easy and fast synthesis of gram-scale long chain polypeptides in an open flask.
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.
文摘AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.
基金supported by a grant from National Key Basic Research Program of China(973 Program),No.2014CB542202a grant from Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)in China
文摘We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.
文摘Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri , was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH px) in the dorsal skin were determined using biochemical methods. The results showed:(1)PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration dependent manner.(2)PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH px.(3)The differences among the PCF groups and UV model group were significant ( P <0.05, P <0.01). These results indicated that topical application of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.
