BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),h...BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),have relatively low accuracy for predicting EH,especially in small intestinal lesions in Crohn’s disease(CD);thus,noninvasive and more accurate biomarkers are required.Leucine-rich alpha-2 glycoprotein(LRG),a 50-kD protein,is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease.However,the usefulness of LRG in small intestinal lesions in CD remains inconclusive.AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.METHODS This study included 133 consecutive patients with CD who underwent balloonassisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital(Otsu,Japan).We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG,CRP,albumin,and Harvey-Bradshaw index(HBI).Spearman’s rank correlation coefficient and receiver operating characteristic analysis were performed.RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG,CRP,albumin,and HBI compared with EH.CRP,albumin,and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon;however,LRG did not show a worse correlation(colon,r=0.5218;ileum,r=0.5602).Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4μg/mL.Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG(95%confidence interval,0.017-0.194;P=0.024),whereas the two showed no significant difference in the colon.CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.展开更多
The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodo...The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodological challenges hinder its immediate use in clinical practice.Notably,the current research was retrospective,lacks comparative studies with fecal calprotectin,and did not provide long-term predictive data.Further prospective studies are needed to improve the applicability of LRG.Moreover,integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring.Future research should address interobserver variability,assess LRG's cost-effectiveness,and standardize endoscopic healing definitions to ensure broader applicability.Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.展开更多
BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant m...BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.展开更多
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood ...Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood disorders. A hallmark of PD is the accumulation of alpha-synuclein, a presynaptic neuronal protein that aggregates to form Lewy bodies, leading to neuronal dysfunction and cell death. The study of alpha-synuclein and its pathological forms is crucial for understanding the etiology of PD and developing effective diagnostic and therapeutic strategies. Analytical techniques play a pivotal role in elucidating the structure, function, and aggregation mechanisms of alpha-synuclein. Biochemical methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA) are employed to detect and quantify alpha-synuclein in biological samples, offering insights into its expression levels and post-translational modifications. Imaging techniques like immunohistochemistry and positron emission tomography (PET) allow for the visualization of alpha-synuclein aggregates in tissue samples and in vivo, respectively, facilitating the study of its spatial distribution and progression in PD Spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, provide detailed structural information on alpha-synuclein and its isoforms, aiding in the identification of conformational changes associated with aggregation. Emerging techniques such as cryo-electron microscopy (Cryo-EM) and single-molecule fluorescence enable high-resolution structural analysis and real-time monitoring of alpha-synuclein aggregation dynamics, respectively. The application of these analytical techniques has significantly advanced our understanding of the pathophysiological role of alpha-synuclein in PD. They have contributed to the identification of potential biomarkers for early diagnosis and the evaluation of therapeutic interventions targeting alpha-synuclein aggregation. Despite technical limitations and challenges in clinical translation, ongoing advancements in analytical methodologies hold promise for improving the diagnosis, monitoring, and treatment of Parkinson’s disease through a deeper understanding of alpha-synuclein pathology.展开更多
Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which ...Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation(OD)and OS in BMSCs.Methods:The expression of Runt-related transcription factor 1(RUNX1)and alpha-2 macroglobulin(A2M)was assessed in Dex-treated BMSCs using qRTPCR and Western Blot.Following the functional rescue experiments,cell proliferation was determined by MTT assay,reactive oxygen species(ROS)expression by DCFH-DA fluorescent probe,lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(Gpx)expression by kits,OD by alkaline phosphatase(ALP)staining and activity quantification,and the expression of OD-related proteins RUNX2,collagen type 1 alpha 1(COL1A1),and osteocalcin(OCN)by qRT-PCR and Western Blot.The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays.Results:Dextreated BMSCs had low RUNX1 and A2M expression.Dex treatment apparently elevated ROS and LDH levels,diminished cell proliferation rate and SOD,CAT,and Gpx expression,lightened intensity of ALP staining,and declined calcified nodules,ALP activity,and RUNX2,COL1A1,and OCN expression in BMSCs,which was counterweighed by RUNX1 or A2M overexpression.RUNX1 positively targeted A2M.A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs.Conclusions:Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.展开更多
基金Supported by the Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.21K15947 and No.23K07435.
文摘BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),have relatively low accuracy for predicting EH,especially in small intestinal lesions in Crohn’s disease(CD);thus,noninvasive and more accurate biomarkers are required.Leucine-rich alpha-2 glycoprotein(LRG),a 50-kD protein,is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease.However,the usefulness of LRG in small intestinal lesions in CD remains inconclusive.AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.METHODS This study included 133 consecutive patients with CD who underwent balloonassisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital(Otsu,Japan).We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG,CRP,albumin,and Harvey-Bradshaw index(HBI).Spearman’s rank correlation coefficient and receiver operating characteristic analysis were performed.RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG,CRP,albumin,and HBI compared with EH.CRP,albumin,and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon;however,LRG did not show a worse correlation(colon,r=0.5218;ileum,r=0.5602).Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4μg/mL.Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG(95%confidence interval,0.017-0.194;P=0.024),whereas the two showed no significant difference in the colon.CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.
文摘The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodological challenges hinder its immediate use in clinical practice.Notably,the current research was retrospective,lacks comparative studies with fecal calprotectin,and did not provide long-term predictive data.Further prospective studies are needed to improve the applicability of LRG.Moreover,integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring.Future research should address interobserver variability,assess LRG's cost-effectiveness,and standardize endoscopic healing definitions to ensure broader applicability.Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.
文摘BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.
文摘Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood disorders. A hallmark of PD is the accumulation of alpha-synuclein, a presynaptic neuronal protein that aggregates to form Lewy bodies, leading to neuronal dysfunction and cell death. The study of alpha-synuclein and its pathological forms is crucial for understanding the etiology of PD and developing effective diagnostic and therapeutic strategies. Analytical techniques play a pivotal role in elucidating the structure, function, and aggregation mechanisms of alpha-synuclein. Biochemical methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA) are employed to detect and quantify alpha-synuclein in biological samples, offering insights into its expression levels and post-translational modifications. Imaging techniques like immunohistochemistry and positron emission tomography (PET) allow for the visualization of alpha-synuclein aggregates in tissue samples and in vivo, respectively, facilitating the study of its spatial distribution and progression in PD Spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, provide detailed structural information on alpha-synuclein and its isoforms, aiding in the identification of conformational changes associated with aggregation. Emerging techniques such as cryo-electron microscopy (Cryo-EM) and single-molecule fluorescence enable high-resolution structural analysis and real-time monitoring of alpha-synuclein aggregation dynamics, respectively. The application of these analytical techniques has significantly advanced our understanding of the pathophysiological role of alpha-synuclein in PD. They have contributed to the identification of potential biomarkers for early diagnosis and the evaluation of therapeutic interventions targeting alpha-synuclein aggregation. Despite technical limitations and challenges in clinical translation, ongoing advancements in analytical methodologies hold promise for improving the diagnosis, monitoring, and treatment of Parkinson’s disease through a deeper understanding of alpha-synuclein pathology.
基金the Natural Science Foundation of Fujian Province(No.2023J011558)the Innovation of Science and Technology of Fujian Province(No.2021Y9098)Fujian Provincial Finance Project(No.BPB-2022FSH).
文摘Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation(OD)and OS in BMSCs.Methods:The expression of Runt-related transcription factor 1(RUNX1)and alpha-2 macroglobulin(A2M)was assessed in Dex-treated BMSCs using qRTPCR and Western Blot.Following the functional rescue experiments,cell proliferation was determined by MTT assay,reactive oxygen species(ROS)expression by DCFH-DA fluorescent probe,lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(Gpx)expression by kits,OD by alkaline phosphatase(ALP)staining and activity quantification,and the expression of OD-related proteins RUNX2,collagen type 1 alpha 1(COL1A1),and osteocalcin(OCN)by qRT-PCR and Western Blot.The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays.Results:Dextreated BMSCs had low RUNX1 and A2M expression.Dex treatment apparently elevated ROS and LDH levels,diminished cell proliferation rate and SOD,CAT,and Gpx expression,lightened intensity of ALP staining,and declined calcified nodules,ALP activity,and RUNX2,COL1A1,and OCN expression in BMSCs,which was counterweighed by RUNX1 or A2M overexpression.RUNX1 positively targeted A2M.A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs.Conclusions:Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.
