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
Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2...Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.展开更多
In order to study the action mechanism of Sacha Inchi polypeptide in liquid crystal emulsion,oil-in-water liquid crystal emulsions with Sacha Inchi fermented polypeptide as the active component were prepared.The micro...In order to study the action mechanism of Sacha Inchi polypeptide in liquid crystal emulsion,oil-in-water liquid crystal emulsions with Sacha Inchi fermented polypeptide as the active component were prepared.The microstructures,particle sizes,stabilities,thermodynamic properties,and rheological properties of liquid crystal emulsions with different concentrations of the fermentation products were observed by Polarizing microscope,Particle size meter,Thermogravimetric differential thermal synchronous measurement system,and Rheometer,respectively.The results showed that the average particle size of fermented peptide liquid crystal emulsion was(25.7±2.8)μm,and the liquid crystal structure was complete and stable.The content of bound water and liquid crystal in the emulsion with 1%Sacha Inchi polypeptide were higher than those in the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide.Rheological results indicated that the viscosity of liquid crystal emulsion with the change curve of shear rate registered the shear thinning phenomenon,which belongs to non-Newtonian fluid.The hysteresis area,energy storage modulus,and loss modulus of the 1%additive amount of liquid crystal emulsion were larger than those of the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide,indicating greater thixotropy and stronger shear resistance.The hydrophilic amino acid residues of the peptide in the 1%additive amount of the emulsion were combined with the water phase,while the hydrophobic amino acid residues of the peptide entered the oil phase,which formed a viscoelastic film at the oil-water interface,so that the liquid crystal emulsion had a more stable gel network structure.展开更多
Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases ...Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.展开更多
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biologi...The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biological actions,such as feeding behavior,bone formation,and hormone secretion of QRFPR have been largely described in chordate species,while no research on QRFPR has been reported in non-chordate species.Here,the first non-chordates QRFP-like peptide receptor gene in the cephalopod Sepiella japonica(Sj_QRFPLR)was identified and characterized.Evidence from multiple alignments,phylogenetic analysis,and in vitro subcellular localization analysis indicated that Sj_QRFPLR is a class A GPCR and it belongs to the QRFPR family.Meanwhile,QRFPR is likely to be structurally conserved in cephalopod species.In situ hybridization and RT-PCR data revealed a widespread distribution pattern of Sj_QRFPLR in multiple function lobes of the female brain and numerous peripheral tissues in both male and female cuttlefish.Subsequently,a food deprivation and refeeding experiment showed that Sj_QRFPLR is likely to stimulate food intake in cuttlefish.Additionally,a possible link between Sj_QRFPLR and immune response was briefly detected in cuttlefish.The results will contribute to our understanding of QRFPR in the cephalopod as well as the peptidergic regulation of the QRFP/QRFPR system in non-chordates.展开更多
This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of gluc...This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.展开更多
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
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
A novel polypeptide having stimulant effect on some cell proliferation was isolated from the velvet antler (Cervus elaphus Linnaeus). The velvet antler polypeptide consists of a single chain of 32 amino acid residues...A novel polypeptide having stimulant effect on some cell proliferation was isolated from the velvet antler (Cervus elaphus Linnaeus). The velvet antler polypeptide consists of a single chain of 32 amino acid residues. Amino acid sequence of the polypeptide was identified as: VLSAADKSNVKAAWGKVGGNAPAFGAEALLRM.展开更多
Two kinds of polypeptides were tethered onto the surface of polypropylene microporous membrane (PPMM) through a ring opening polymerization of L-glutamate N-carboxyanhydride initiated by amino groups which were intr...Two kinds of polypeptides were tethered onto the surface of polypropylene microporous membrane (PPMM) through a ring opening polymerization of L-glutamate N-carboxyanhydride initiated by amino groups which were introduced by ammonia plasma and y-aminopropyl triethanoxysilane treatments. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (FT-IR/ATR), scanning electron microscopy (SEM), together with water contact angle measurements were used to characterize the modified membranes. XPS analyses and FT-IR/ATR spectra demonstrated that polypeptides are actually grafted onto the membrane surface. The wettability of the membrane surface increases at first and then decreases with the increase in grafting degrees of polypeptide. Platelet adhesion and murine macrophage attachment experiments reveal an enhanced hemocompatibility for the polypeptide modified PPMMs. All these results give evidence that polypeptide grafting can simultaneously improve the hemocompatibility as well as reserve the hydrophobicity for the membrane, which will provide a potential approach to improve the performance of polypropylene hollow fiber microporous membrane used in artificial oxygenator.展开更多
Pituitary adenylate cyclase activating polypeptide (PACAP) has a wide range of biological functions. We cloned the full-length cDNAs encoding PACAP and PACAP-related peptide (PRP) from the brain of largemouth bass...Pituitary adenylate cyclase activating polypeptide (PACAP) has a wide range of biological functions. We cloned the full-length cDNAs encoding PACAP and PACAP-related peptide (PRP) from the brain of largemouth bass (Micropterus salmoides) and used real-time quantitative PCR to detect PRP- PACAP mRNA expression. The PRP-PACAP cDNA has two variants expressed via alternative splicing: a long form, which encodes both PRP and PACAP, and a short form, which encodes only PACAR Sequence analysis results are consistent with a higher conservation of PACAP than PRP peptide sequences. The expression of PACAP-Iong and PACAP-short transcripts was highest in the forebrain, followed by the medulla, midbrain, pituitary, stomach, cerebellum, intestine, and kidney; however, these transcripts were either absent or were weakly expressed in the muscle, spleen, gill, heart, fatty tissue, and liver. The level of PACAP-short transcript expression was significantly higher than expression of the long transcript in the forebrain, cerebella, pituitary and intestine, but lower than that of the long transcript in the stomach. PA CAP- long and PACAP-short transcripts were first detected at the blastula stage of embryogenesis, and the level of expression increased markedly between the muscular contraction stage and 3 d post hatch (dph). The expression of PACAP-long and PACAP-short transcripts decreased significantly in the brain following 4 d fasting compared with the control diet group. The down-regulation effect was enhanced as fasting continued. Conversely, expression levels increased significantly after 3 d of re-feeding. Our results suggest that PRP- PA CAP acts as an important factor in appetite regulation in largemouth bass.展开更多
On the basis of preparation of anti-metastatic recombinant FN polypeptides, CH50 and CH56, we further studied the function of these polypeptides.The capacity of CH50 binding with melanoma cells (ED50 30 mM) was higher...On the basis of preparation of anti-metastatic recombinant FN polypeptides, CH50 and CH56, we further studied the function of these polypeptides.The capacity of CH50 binding with melanoma cells (ED50 30 mM) was higher than that of CH56 (ED50 45 mM). Both of the polypeptides could significantly suppress the binding of melanoma B16 cells to laminin. There was no significant difference in the inhibitory effect between two polypeptides. In the experimental metastasis of melanoma cells, both of CH50 and CH56 could significantly inhibit the metastasis of the tumor cells, and reduce the number of lung metastasis by about 80%. Our results suggest that Ⅲ-11 and ED-A repeats influenced, to some extent, the binding capacity of bifunctional-domain polypeptide to cells, but did not affect the inhibition of the polypeptide on the metastasis of melanoma cells. The presence and connection of cell Ⅰ and Hep Ⅱ domains are the elements which determine the ability of recoinbinant FN polypeptides to inhibit the metastasis of tumor cells.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
AIM: To clarify the associations between G-protein beta polypeptide 3 (GNB3) C825T polymorphism and risk of the irritable bowel syndrome (IBS) by a meta-analysis.
Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confir...Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confirmed by ^1H NMR, MS and IR.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.
文摘Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.
文摘In order to study the action mechanism of Sacha Inchi polypeptide in liquid crystal emulsion,oil-in-water liquid crystal emulsions with Sacha Inchi fermented polypeptide as the active component were prepared.The microstructures,particle sizes,stabilities,thermodynamic properties,and rheological properties of liquid crystal emulsions with different concentrations of the fermentation products were observed by Polarizing microscope,Particle size meter,Thermogravimetric differential thermal synchronous measurement system,and Rheometer,respectively.The results showed that the average particle size of fermented peptide liquid crystal emulsion was(25.7±2.8)μm,and the liquid crystal structure was complete and stable.The content of bound water and liquid crystal in the emulsion with 1%Sacha Inchi polypeptide were higher than those in the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide.Rheological results indicated that the viscosity of liquid crystal emulsion with the change curve of shear rate registered the shear thinning phenomenon,which belongs to non-Newtonian fluid.The hysteresis area,energy storage modulus,and loss modulus of the 1%additive amount of liquid crystal emulsion were larger than those of the blank emulsion and the emulsions with 3%and 5%Sacha Inchi polypeptide,indicating greater thixotropy and stronger shear resistance.The hydrophilic amino acid residues of the peptide in the 1%additive amount of the emulsion were combined with the water phase,while the hydrophobic amino acid residues of the peptide entered the oil phase,which formed a viscoelastic film at the oil-water interface,so that the liquid crystal emulsion had a more stable gel network structure.
基金sponsored by the National Key R&D Program of China (2018YFD0901102)the Natural Science Foundation of Zhejiang Province (LQ22D060002)+2 种基金the Fund of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products (ZS20190105)the Fundamental Research Funds for the Provincial Universities of Zhejiang (SJLY2021015)the K.C.Wong Magna Fund of Ningbo University。
文摘Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.
文摘Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
基金supported by the National Natural Science Foundation of China(No.31872547)the Natural Science Foundation of Zhejiang Province,China(No.LTGN24C190015)the Excellent Postdoctoral Program of Jiangsu Province(No.314865)。
文摘The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biological actions,such as feeding behavior,bone formation,and hormone secretion of QRFPR have been largely described in chordate species,while no research on QRFPR has been reported in non-chordate species.Here,the first non-chordates QRFP-like peptide receptor gene in the cephalopod Sepiella japonica(Sj_QRFPLR)was identified and characterized.Evidence from multiple alignments,phylogenetic analysis,and in vitro subcellular localization analysis indicated that Sj_QRFPLR is a class A GPCR and it belongs to the QRFPR family.Meanwhile,QRFPR is likely to be structurally conserved in cephalopod species.In situ hybridization and RT-PCR data revealed a widespread distribution pattern of Sj_QRFPLR in multiple function lobes of the female brain and numerous peripheral tissues in both male and female cuttlefish.Subsequently,a food deprivation and refeeding experiment showed that Sj_QRFPLR is likely to stimulate food intake in cuttlefish.Additionally,a possible link between Sj_QRFPLR and immune response was briefly detected in cuttlefish.The results will contribute to our understanding of QRFPR in the cephalopod as well as the peptidergic regulation of the QRFP/QRFPR system in non-chordates.
基金Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,No.0932204294929829CNPq Research Productivity Fellow,No.4357511882624145.
文摘This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.
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.
文摘A novel polypeptide having stimulant effect on some cell proliferation was isolated from the velvet antler (Cervus elaphus Linnaeus). The velvet antler polypeptide consists of a single chain of 32 amino acid residues. Amino acid sequence of the polypeptide was identified as: VLSAADKSNVKAAWGKVGGNAPAFGAEALLRM.
基金This project was supported by the National Natural Science Foundation of China (No. 20074033)the National Basic Research Program of China (No. 2003CB15705).
文摘Two kinds of polypeptides were tethered onto the surface of polypropylene microporous membrane (PPMM) through a ring opening polymerization of L-glutamate N-carboxyanhydride initiated by amino groups which were introduced by ammonia plasma and y-aminopropyl triethanoxysilane treatments. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (FT-IR/ATR), scanning electron microscopy (SEM), together with water contact angle measurements were used to characterize the modified membranes. XPS analyses and FT-IR/ATR spectra demonstrated that polypeptides are actually grafted onto the membrane surface. The wettability of the membrane surface increases at first and then decreases with the increase in grafting degrees of polypeptide. Platelet adhesion and murine macrophage attachment experiments reveal an enhanced hemocompatibility for the polypeptide modified PPMMs. All these results give evidence that polypeptide grafting can simultaneously improve the hemocompatibility as well as reserve the hydrophobicity for the membrane, which will provide a potential approach to improve the performance of polypropylene hollow fiber microporous membrane used in artificial oxygenator.
基金Supported by the National Natural Science Foundation of China(No.31201985)the National Key Technology R&D Program of China(No.2012BAD26B03)
文摘Pituitary adenylate cyclase activating polypeptide (PACAP) has a wide range of biological functions. We cloned the full-length cDNAs encoding PACAP and PACAP-related peptide (PRP) from the brain of largemouth bass (Micropterus salmoides) and used real-time quantitative PCR to detect PRP- PACAP mRNA expression. The PRP-PACAP cDNA has two variants expressed via alternative splicing: a long form, which encodes both PRP and PACAP, and a short form, which encodes only PACAR Sequence analysis results are consistent with a higher conservation of PACAP than PRP peptide sequences. The expression of PACAP-Iong and PACAP-short transcripts was highest in the forebrain, followed by the medulla, midbrain, pituitary, stomach, cerebellum, intestine, and kidney; however, these transcripts were either absent or were weakly expressed in the muscle, spleen, gill, heart, fatty tissue, and liver. The level of PACAP-short transcript expression was significantly higher than expression of the long transcript in the forebrain, cerebella, pituitary and intestine, but lower than that of the long transcript in the stomach. PA CAP- long and PACAP-short transcripts were first detected at the blastula stage of embryogenesis, and the level of expression increased markedly between the muscular contraction stage and 3 d post hatch (dph). The expression of PACAP-long and PACAP-short transcripts decreased significantly in the brain following 4 d fasting compared with the control diet group. The down-regulation effect was enhanced as fasting continued. Conversely, expression levels increased significantly after 3 d of re-feeding. Our results suggest that PRP- PA CAP acts as an important factor in appetite regulation in largemouth bass.
文摘On the basis of preparation of anti-metastatic recombinant FN polypeptides, CH50 and CH56, we further studied the function of these polypeptides.The capacity of CH50 binding with melanoma cells (ED50 30 mM) was higher than that of CH56 (ED50 45 mM). Both of the polypeptides could significantly suppress the binding of melanoma B16 cells to laminin. There was no significant difference in the inhibitory effect between two polypeptides. In the experimental metastasis of melanoma cells, both of CH50 and CH56 could significantly inhibit the metastasis of the tumor cells, and reduce the number of lung metastasis by about 80%. Our results suggest that Ⅲ-11 and ED-A repeats influenced, to some extent, the binding capacity of bifunctional-domain polypeptide to cells, but did not affect the inhibition of the polypeptide on the metastasis of melanoma cells. The presence and connection of cell Ⅰ and Hep Ⅱ domains are the elements which determine the ability of recoinbinant FN polypeptides to inhibit the metastasis of tumor cells.
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AIM: To clarify the associations between G-protein beta polypeptide 3 (GNB3) C825T polymorphism and risk of the irritable bowel syndrome (IBS) by a meta-analysis.
文摘Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confirmed by ^1H NMR, MS and IR.