Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors...Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors.Methods:110 cases of UC patients were divided into 2 groups according to the random number table method,with 55 cases in each group.The control group was treated with mesalazine,and the treatment group was given oral administration of Chinese medicine xiezhuojiedu decoction on the basis of the control group.Both groups received continuous treatment for 8 weeks.Integral of TCM syndromes,serum inflammatory factor and brain-gut peptide before and after treatment were compared between the two groups.The clinical efficiency,mucosal healing rate and endoscopic response rate of the two groups were compared.Results:After treatment,Integral of the main TCM syndromes abdominal pain,diarrhea,abdominal distention,mucous hematochezia,tenesmus of the treatment group were lower than the control group(P<0.01),the levels of serum(Tumor necrosis factor-α,(TNF-α),Interleukin(IL)-33,Substance P(SP)were lower than the control group(P<0.01),the levels of IL-10,vasoactive intestinal peptide(VIP),Somatostatin(SS)were higher than the control group(P<0.01),the clinical efficiency and mucosal healing rate were higher than control group(P<0.05),The difference was statistically significant.Conclusion:Based on the zhuodu theory,the xiezhuojiedu decoction can effectively regulate the levels of inflammatory factor and brain-gut peptide in the treatment of UC,improve the symptoms of patients,and promote the repair of intestinal mucosa.It's effective in treatment.展开更多
AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period...AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.展开更多
AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa...AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa)1(Saa1)and Saa3 were among the genes up-regulated upon CorNV induction in mice.METHODS:Microarray data obtained during our profiling project on CorNV were analyzed for the genes encoding the four SAA family members(Saa1-4),six reported SAA receptors(formyl peptide receptor 2,Tlr2,Tlr4,Cd36,Scarb1,P2rx7)and seven matrix metallopeptidases(Mmp)1a,1b,2,3,9,10,13reportedly to be expressed upon SAA pathway activation.The baseline expression or changes of interested genes were further confirmed in animals with CorNV using molecular or histological methods.CorNV was induced in Balb/c and C57BL/6 mice by placing either three interrupted 10-0 sutures or a 2 mm filter paper soaked with sodium hydroxide in the central area of the cornea.At desired time points,the corneas were harvested for histology examination or for extraction of mRNA and protein.The mRNA levels of Saa1,Saa3,Fpr2,Mmp2and Mmp3 in corneas were detected using quantitative reverse transcription-PCR,and SAA3 protein in tissues detected using immunohistochemistry or western blotting.RESULTS:Microarray data analysis revealed that Saa1,Saa3,Fpr2,Mmp2,Mmp3 messengers were readily detected in normal corneas and significantly upregulated upon CorNV induction.The changes of these five genes were confirmed with real-time PCR assay.Onthe contrary,other SAA members(Saa2,Saa4),other SAA receptors(Tlr2,Tlr4,Cd36,P2rx7,etc),or other Mmps(Mmp1a,Mmp1b,Mmp9,Mmp10,Mmp13)did not show consistent changes.Immunohistochemistry study and western blotting further confirmed the expression of SAA3 products in normal corneas as well as their upregulation in corneas with CorNV.CONCLUSION:SAA-FPR2 pathway composing genes were expressed in normal murine corneas and,upon inflammatory stimuli challenge to the corneas,their expressions were up-regulated,suggesting their roles in pathogenesis of CorNV.The potential usefulness of SAA-FPR2 targets in future management of CorNVrelated diseases deserves investigation.展开更多
Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided ...Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided into the control group,model group,SLBZS-treated group and Montmorillonite Powder-treated group (MP-treated group) (n =15/group).Rats received gavage after the establishment of functional diarrhea.An equal volume of SLBZS solution and Montmorillonite Powder (MP) solution was administered to the SLBZS-treated group and MP-treated group,respectively,and an equal volume of distilled water was administered to the control group and the model group.The chemical components and targets related to SLBZS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID).The effective chemical components were screened based on oral bioavailability (OB) and drug like-index (DL),and their biological functions were analyzed by GlueGO.Based on this screening,the expression of Cholecystokinin (CCK) and Ghrelin in the hypothalamus of rats was detected by real-time PCR (RT-PCR) and western blotting.Results:In this study,72 effective components and 190 core targets of SLBZS were screened.SLBZS may regulate smooth muscle contraction,energy metabolism and other biological processes.The results of RT-PCR showed that in the model group,the expression of CCK mRNA (P =.001) and Ghrelin mRNA (P =.000) increased significantly.Compared with the model group,CCK mRNA (P =.007) and Ghrelin mRNA (P =.001) levels in SLBZS-treated rats were decreased significantly.The results of western blotting showed that in the model group,the protein expression of CCK (P =.001) and Ghrelin (P =.000) increased significantly.The protein levels of CCK (P =.001) and Ghrelin (P =.005) in the SLBZS-treated group were decreased significantly compared with the model group.Conclusion:SLBZS improved functional diarrhea by regulating the brain-gut axis.Changes in the expressions of brain-gut peptide,CCK and Ghrelin might explain the pathogenesis of functional diarrhea related to brain-gut peptide and gastrointestinal hormone.展开更多
Changes in plasma atrial natriuretic peptide(ANP)and serum lipids were observed us-ing dietetic atherosclerosis(AS)models.The results showed that plasma ANP level of the ASgroup was significantly higher than that of t...Changes in plasma atrial natriuretic peptide(ANP)and serum lipids were observed us-ing dietetic atherosclerosis(AS)models.The results showed that plasma ANP level of the ASgroup was significantly higher than that of the control group(14.33±3.58μg/L vs 9.43±3.14μg/L).There was also a marked increase in serum Tch,TG,LDL-ch and VLDL-ch comparedwith the control group(P【0.01),suggesting that release of ANP increased with disturbance ofthe serum lipids and during AS formation,and that change in ANP was closely related to Tchand LDL-ch(P【0.05).Possible mechanisms causing these changes are also discussed.展开更多
Calcitonin gene-related peptide(CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury(TBI) remains poorly understood. In t...Calcitonin gene-related peptide(CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury(TBI) remains poorly understood. In this study, 96 adult patients with TBI(enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group(36 males and 25 females, aged 38 ± 13 years) and severe TBI group(22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls(15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.展开更多
An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were ran...An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were randomly divided into 2 treatments for 8 weeks (16 replicates/group and 1 rabbit/replicate). The treatments were fed a basal diet (control, measured pyridoxine content is 4.51 mg/kg) and the basal diet with a pyridoxine supplementation at 10 mg/kg (pyridoxine, measured pyridoxine content is 14.64 mg/kg). The results showed that dietary pyridoxine did not significantly alter the mRNA levels of neuropeptide Y, agouti related peptide, pro-opiomelanocortin and cocaine, amphetamine regulated transcript, peptide YY and cholecystokinin in arcuate nucleus, peptide YY in jejunum and ileum, and cholecystokinin in duodenum, jejunum and ileum (P > 0.05). Compared with the control, the mRNA levels of corticotropin-releasing hormone and melanocortin 4 receptor in paraventricular nuclei and peptide YY in duodenum were significantly decreased after pyridoxine treatment (P 0.05). In conclusion, the appetite genes of melanocortin 4 receptor and corticotropin-releasing hormone in paraventricular nuclei and peptide YY in duodenum are involved in the pyridoxine-caused hyperphagia.展开更多
Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals...Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.展开更多
基金Doctor’s initial funding project in Liaoning province(No.20111093).
文摘Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors.Methods:110 cases of UC patients were divided into 2 groups according to the random number table method,with 55 cases in each group.The control group was treated with mesalazine,and the treatment group was given oral administration of Chinese medicine xiezhuojiedu decoction on the basis of the control group.Both groups received continuous treatment for 8 weeks.Integral of TCM syndromes,serum inflammatory factor and brain-gut peptide before and after treatment were compared between the two groups.The clinical efficiency,mucosal healing rate and endoscopic response rate of the two groups were compared.Results:After treatment,Integral of the main TCM syndromes abdominal pain,diarrhea,abdominal distention,mucous hematochezia,tenesmus of the treatment group were lower than the control group(P<0.01),the levels of serum(Tumor necrosis factor-α,(TNF-α),Interleukin(IL)-33,Substance P(SP)were lower than the control group(P<0.01),the levels of IL-10,vasoactive intestinal peptide(VIP),Somatostatin(SS)were higher than the control group(P<0.01),the clinical efficiency and mucosal healing rate were higher than control group(P<0.05),The difference was statistically significant.Conclusion:Based on the zhuodu theory,the xiezhuojiedu decoction can effectively regulate the levels of inflammatory factor and brain-gut peptide in the treatment of UC,improve the symptoms of patients,and promote the repair of intestinal mucosa.It's effective in treatment.
文摘AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.
基金Supported by National Natural Science Foundation of China(No.8120066481271050)
文摘AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa)1(Saa1)and Saa3 were among the genes up-regulated upon CorNV induction in mice.METHODS:Microarray data obtained during our profiling project on CorNV were analyzed for the genes encoding the four SAA family members(Saa1-4),six reported SAA receptors(formyl peptide receptor 2,Tlr2,Tlr4,Cd36,Scarb1,P2rx7)and seven matrix metallopeptidases(Mmp)1a,1b,2,3,9,10,13reportedly to be expressed upon SAA pathway activation.The baseline expression or changes of interested genes were further confirmed in animals with CorNV using molecular or histological methods.CorNV was induced in Balb/c and C57BL/6 mice by placing either three interrupted 10-0 sutures or a 2 mm filter paper soaked with sodium hydroxide in the central area of the cornea.At desired time points,the corneas were harvested for histology examination or for extraction of mRNA and protein.The mRNA levels of Saa1,Saa3,Fpr2,Mmp2and Mmp3 in corneas were detected using quantitative reverse transcription-PCR,and SAA3 protein in tissues detected using immunohistochemistry or western blotting.RESULTS:Microarray data analysis revealed that Saa1,Saa3,Fpr2,Mmp2,Mmp3 messengers were readily detected in normal corneas and significantly upregulated upon CorNV induction.The changes of these five genes were confirmed with real-time PCR assay.Onthe contrary,other SAA members(Saa2,Saa4),other SAA receptors(Tlr2,Tlr4,Cd36,P2rx7,etc),or other Mmps(Mmp1a,Mmp1b,Mmp9,Mmp10,Mmp13)did not show consistent changes.Immunohistochemistry study and western blotting further confirmed the expression of SAA3 products in normal corneas as well as their upregulation in corneas with CorNV.CONCLUSION:SAA-FPR2 pathway composing genes were expressed in normal murine corneas and,upon inflammatory stimuli challenge to the corneas,their expressions were up-regulated,suggesting their roles in pathogenesis of CorNV.The potential usefulness of SAA-FPR2 targets in future management of CorNVrelated diseases deserves investigation.
文摘Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided into the control group,model group,SLBZS-treated group and Montmorillonite Powder-treated group (MP-treated group) (n =15/group).Rats received gavage after the establishment of functional diarrhea.An equal volume of SLBZS solution and Montmorillonite Powder (MP) solution was administered to the SLBZS-treated group and MP-treated group,respectively,and an equal volume of distilled water was administered to the control group and the model group.The chemical components and targets related to SLBZS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID).The effective chemical components were screened based on oral bioavailability (OB) and drug like-index (DL),and their biological functions were analyzed by GlueGO.Based on this screening,the expression of Cholecystokinin (CCK) and Ghrelin in the hypothalamus of rats was detected by real-time PCR (RT-PCR) and western blotting.Results:In this study,72 effective components and 190 core targets of SLBZS were screened.SLBZS may regulate smooth muscle contraction,energy metabolism and other biological processes.The results of RT-PCR showed that in the model group,the expression of CCK mRNA (P =.001) and Ghrelin mRNA (P =.000) increased significantly.Compared with the model group,CCK mRNA (P =.007) and Ghrelin mRNA (P =.001) levels in SLBZS-treated rats were decreased significantly.The results of western blotting showed that in the model group,the protein expression of CCK (P =.001) and Ghrelin (P =.000) increased significantly.The protein levels of CCK (P =.001) and Ghrelin (P =.005) in the SLBZS-treated group were decreased significantly compared with the model group.Conclusion:SLBZS improved functional diarrhea by regulating the brain-gut axis.Changes in the expressions of brain-gut peptide,CCK and Ghrelin might explain the pathogenesis of functional diarrhea related to brain-gut peptide and gastrointestinal hormone.
文摘Changes in plasma atrial natriuretic peptide(ANP)and serum lipids were observed us-ing dietetic atherosclerosis(AS)models.The results showed that plasma ANP level of the ASgroup was significantly higher than that of the control group(14.33±3.58μg/L vs 9.43±3.14μg/L).There was also a marked increase in serum Tch,TG,LDL-ch and VLDL-ch comparedwith the control group(P【0.01),suggesting that release of ANP increased with disturbance ofthe serum lipids and during AS formation,and that change in ANP was closely related to Tchand LDL-ch(P【0.05).Possible mechanisms causing these changes are also discussed.
文摘Calcitonin gene-related peptide(CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury(TBI) remains poorly understood. In this study, 96 adult patients with TBI(enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group(36 males and 25 females, aged 38 ± 13 years) and severe TBI group(22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls(15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.
文摘An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were randomly divided into 2 treatments for 8 weeks (16 replicates/group and 1 rabbit/replicate). The treatments were fed a basal diet (control, measured pyridoxine content is 4.51 mg/kg) and the basal diet with a pyridoxine supplementation at 10 mg/kg (pyridoxine, measured pyridoxine content is 14.64 mg/kg). The results showed that dietary pyridoxine did not significantly alter the mRNA levels of neuropeptide Y, agouti related peptide, pro-opiomelanocortin and cocaine, amphetamine regulated transcript, peptide YY and cholecystokinin in arcuate nucleus, peptide YY in jejunum and ileum, and cholecystokinin in duodenum, jejunum and ileum (P > 0.05). Compared with the control, the mRNA levels of corticotropin-releasing hormone and melanocortin 4 receptor in paraventricular nuclei and peptide YY in duodenum were significantly decreased after pyridoxine treatment (P 0.05). In conclusion, the appetite genes of melanocortin 4 receptor and corticotropin-releasing hormone in paraventricular nuclei and peptide YY in duodenum are involved in the pyridoxine-caused hyperphagia.
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
基金supported by the National Natural Science Foundation of China(82173773,82273893,82373829)the Natural Science Foundation of Guangdong Province,China(2021A0505030039,2021A0505020014)+1 种基金the High-End Foreign Experts Project,China(G2021199005L)the Science and Technology Program of Guangdong Provincial Medical Products Administration,China(2023TDZ11)。
文摘Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.