Carnosine(β-alanyl-L-histidine)is a naturally occurring endogenous peptide widely distributed in excitable tissues,such as the heart and brain.Over the years,several beneficial effects of carnosine have been discusse...Carnosine(β-alanyl-L-histidine)is a naturally occurring endogenous peptide widely distributed in excitable tissues,such as the heart and brain.Over the years,several beneficial effects of carnosine have been discussed well in scientific literature.In particular,this dipeptide is well-known for its antioxidant,anti-inflammatory,and anti-aggregation activities.It is of great interest in the context of numerous systemic and neurodegenerative diseases,besides performing important“side activities”such as metal chelation and pH-buffering.Despite a plethora of preclinical and clinical data supporting carnosine’s therapeutic potential,researchers are still searching for new pharmacological targets that better highlight carnosine’s overall multimodal mechanism of action and allow its disease-specific use.The aim of the present mini-review,after quickly summarizing the current knowledge of carnosine biological properties,is to pinpoint the role of some non-canonical factors/pathways positively modulated by this dipeptide,highlighting their perspective role as future pharmacological targets.展开更多
Objectives: As therapeutic modalities for rheumatoid arthritis (RA) advance, immediate and quantitative determination of RA disease status is becoming increasingly important. The purpose of this study was to validate ...Objectives: As therapeutic modalities for rheumatoid arthritis (RA) advance, immediate and quantitative determination of RA disease status is becoming increasingly important. The purpose of this study was to validate the usefulness of a ring gauge as a simple semiquantitative method for assessing hand swelling in patients with RA. Methods: We enrolled patients diagnosed with RA either initiated or switched to a biological therapeutic agent. The circumference of the interphalangeal (IP) joint and the proximal interphalangeal (PIP) joint was measured using a ring gauge. Assessments of the joint echocardiography, incorporating both Gray Scale (GS) and Power Doppler (PD) imaging, were conducted. These evaluations were performed both before the initiation of biological agent treatment and 28 days after the initial dose. Results: Following the treatment intervention, a significant reduction was observed in the circumference of the joint from the thumb to the little finger (p Conclusions: Our study demonstrated the effectiveness of using a ring gauge as a simple assessment tool for RA, revealing that a change in the ring gauge number by 2 or more corresponded to either improvement or deterioration in synovial thickening detected via joint echocardiography.展开更多
According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence abou...According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.展开更多
Ophiocordyceps sinensis and Cordyceps militaris both contain many bioactive compounds that confer potential therapeutic benefits. This review discusses the possible use of cultivated C. militaris as an effective subst...Ophiocordyceps sinensis and Cordyceps militaris both contain many bioactive compounds that confer potential therapeutic benefits. This review discusses the possible use of cultivated C. militaris as an effective substitute for native O. sinensis in the face of ever-increasing prices of O. sinensis because of its short supply. On the one hand, cultivated C. militaris contains higher levels of cordycepin when compared with that of wild-type O. sinensis and cultivation of C. militaris has been shown to be capable of reducing the risk of heavy metal contamination. On the other hand, there is a paucity of robust in vivo studies and randomized controlled tests comparing the pharmacology and use of C. militaris and O. sinensis. For extraction of cordycepin as western-style tablets, the use of cultivated C. militaris rather than O. sinensis represents the most appropriate future approach. For many other purposes, comparative pharmacology and clinical trials are in urgent needs.展开更多
Accurate and reproducible analysis of murine small and large intestinal tissue is key for preclinical models involving intestinal pathology.Currently,there is no easily ac-cessible,standardized method that allows rese...Accurate and reproducible analysis of murine small and large intestinal tissue is key for preclinical models involving intestinal pathology.Currently,there is no easily ac-cessible,standardized method that allows researchers of different skill levels to con-sistently dissect intestines in a time-efficient manner.Here,we describe the design and use of the 3D-printed“Mouse Intestinal Slicing Tool”(MIST),which can be used to longitudinally dissect murine intestines for further analysis.We benchmarked the MIST against a commonly used procedure involving scissors to make a longitudinal cut along the intestines.Use of the MIST halved the time per mouse to prepare the intestines and outperformed alternative methods in smoothness of the cutting edge and overall reproducibility.By sharing the plans for printing the MIST,we hope to contribute a uniformly applicable method for saving time and increasing consistency in studies of the mouse gastrointestinal tract.展开更多
Objective: To estimate the normal circumference of the interphalangeal (IP) thumb joint and the proximal IP (PIP) joints from the index finger to the little finger using individual physical parameters such as body hei...Objective: To estimate the normal circumference of the interphalangeal (IP) thumb joint and the proximal IP (PIP) joints from the index finger to the little finger using individual physical parameters such as body height and body weight. Methods: The maximum size on the ring gauge was recorded which caused resistance when the IP joint of the thumb or PIP joints of the index to small fingers were passed through the gauge. RG was defined as the ring gauge number with the same diameter as the circumference of the IP thumb joint and PIP finger joints from the index finger to the little finger. There were 300 healthy subjects and 600 hands. Univariate and multivariate analyses were used to analyze the relationships between RG and the parameters of age, sex, height, weight, and dominant hand, and regression equations were derived. Results: Age, sex and body weight were all statistically significant predictive factors of RG in all fingers. R2, the coefficient of determination in the regression equation, was almost 0.7 for all fingers, indicating that a moderate or strong correlation was observed between RG and the regression equation. Conclusions: The circumference of the IP thumb joint and PIP finger joints from the index finger to the little finger can be estimated in healthy individuals using a calculation formula that takes age, sex, body height and body weight into account.展开更多
Objective: Early and accurate evaluation of the presence and activity of synovitis is extremely important in the diagnosis and treatment of rheumatoid arthritis. Myeloid related protein 8/14 (MRP8/14), also known as c...Objective: Early and accurate evaluation of the presence and activity of synovitis is extremely important in the diagnosis and treatment of rheumatoid arthritis. Myeloid related protein 8/14 (MRP8/14), also known as calprotectin or S100A8/A9 is considered as a sensitive marker for local inflammatory activity in rheumatoid arthritis. The aim of this study is to demonstrate the efficacy of MRP8/14 as a marker of disease activity in RA. Methods: Thirty-one patients with diagnosis of RA who received treatment without biological drugs at our institution were included in this study. Serum MRP8/14, CRP and MMP-3 were tested in all patients. Disease activity was evaluated using DAS28-CRP and SDAI. Ultrasonography was performed on the wrists and MCP joints of both hands using semi-quantitative scale of power Doppler signal. The sum of scales in joints was calculated as the PD score. The correlation of MRP8/14 with serum biomarkers, disease activity and ultrasonography examination was investigated. Result: Serum MRP8/14 was strongly correlated with CRP (r = 0.63) and MMP-3 (r = 0.69). A correlation was observed between serum MRP8/14 and DAS28-CRP (r = 0.53) and SDAI (r = 0.66). No significant correlation was found between PD scores and MRP8/14. Conclusion: This study demonstrated that MRP8/14 is correlated with evaluated disease activity and markers of serum inflammatory response in patients not using biological drugs. MRP8/14 is considered an effective new method for objective evaluation of synovitis in RA.展开更多
Background and Aims:End-stage liver disease is associated with disruptions in gut microbiota composition and function,which may facilitate gut-to-liver bacterial translocation,impacting liver graft integrity and clini...Background and Aims:End-stage liver disease is associated with disruptions in gut microbiota composition and function,which may facilitate gut-to-liver bacterial translocation,impacting liver graft integrity and clinical outcomes following liver transplantation.This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.Methods:This single-center,non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion(NMP).Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3,6,and 12.Stool microbiota was profiled via 16S rRNA gene sequencing,stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry,and breath volatile organic compounds(VOCs)were analyzed with selected-ion flow-tube mass spectrometry.Results:Both cohorts experienced a loss of microbiota diversity and dominance by single taxa.The NMP cohort demonstrated enrichment of several beneficial gut taxa,while the static cold storage cohort showed depletion of such taxa.Various gut bacteria were found to correlate with stool short-chain fatty acids(e.g.,lactic acid,butyric acid)and several VOCs.Conclusions:Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation.However,notable differences in microbiota composition and function were observed between liver graft preservation methods.Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.展开更多
Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases,but no effective anti-fibrotic therapy is currently available.Glucagon receptor(GCGR)and glucagon-like peptide 1 receptor(GLP1R)ar...Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases,but no effective anti-fibrotic therapy is currently available.Glucagon receptor(GCGR)and glucagon-like peptide 1 receptor(GLP1R)are both peptide hormone receptors involved in energy metabolism of epithelial cells.However,their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored.Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn’s disease as well as in the fibrotic colon of mice with chronic colitis.The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate,resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition(EMT).Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo.We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation.Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.展开更多
AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated fro...AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.展开更多
AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric ar...AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.展开更多
Pseudomembranous colitis (PMC) usually manifests asfever and diarrhea in hospitalized patients treated withsystemic antibiotics. We described a case of PMC withintestinal obstruction but without diarrhea. A 60-yearold...Pseudomembranous colitis (PMC) usually manifests asfever and diarrhea in hospitalized patients treated withsystemic antibiotics. We described a case of PMC withintestinal obstruction but without diarrhea. A 60-yearold man was hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the stomach. The patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. Plain abdominal radiography showed some intestinal gas and niveau. Because stool cytotoxin assay for clostridium difficile was positive and colon fiberscopic examination showed a pseudomembrane at the left side of the colon,and a diagnosis of PMC was made. Treatment with intracolonic vancomycin administration by colonoscopy and nasoileus tube was successful. Physicians should take into account the possibility of bowel obstruction due to PMC occurring in patients undergoing chemotherapy and perform emergency colonoscopy examination of suspected cases.展开更多
Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and c...Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some extent.Here,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH.Multiple cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease inflammation.In addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous system.We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections.Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.展开更多
Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversit...Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.展开更多
Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Zhang Zemin(张泽民)from the Biodynamic Optical Imaging Center(BIOPIC),Pekin...Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Zhang Zemin(张泽民)from the Biodynamic Optical Imaging Center(BIOPIC),Peking University,Prof.Peng Jirun(彭吉润)from Beijing Shijitan Hospital,Capital展开更多
Background:Placement of a transjugular intrahepatic portosystemic shunt(TIPS)is a relatively common procedure used to treat complications of portal hypertension.However,only limited data exist regarding the hospital-r...Background:Placement of a transjugular intrahepatic portosystemic shunt(TIPS)is a relatively common procedure used to treat complications of portal hypertension.However,only limited data exist regarding the hospital-readmission rate after TIPS placement and no studies have addressed the causes of hospital readmission.We therefore sought to identify the 30-day hospital-readmission rate after TIPS placement at our institution and to determine potential causes and predictors of readmission.Methods:We reviewed our electronic medical-records system at our institution between 2004 and 2017 to identify patients who had undergone primary TIPS placement with polytetrafluoroethylene-covered stents and to determine the 30-day readmission rate among these patients.A series of univariable logistic-regression models were fit to assess potential predictors of 30-day readmission.Results:A total of 566 patients were included in the analysis.The 30-day readmission rate after TIPS placement was 36%.The most common causes for readmission were confusion(48%),infection(15%),bleeding(11%),and fluid overload(7%).A higher Model for End-Stage Liver Disease(MELD)score corresponded with a higher rate of readmission(odds ratio associated with each 1-unit increase in MELD score:1.06;95%confidence interval:1.02–1.09;P=0.001).Other potential predictors,including indication for TIPS placement,were not significantly associated with a higher readmission rate.Conclusions:The 30-day readmission rate after TIPS placement with covered stents is high,with nearly half of these readmissions due to hepatic encephalopathy—a known complication of TIPS placement.Novel interventions to help reduce the TIPS readmission rate should be prioritized in future research.展开更多
Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 days.The angiopoietin-Tie 2 system regulates angiogenesis and inflammatio...Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 days.The angiopoietin-Tie 2 system regulates angiogenesis and inflammation,both of which are implicated in the pathogenesis of ALD.This study examined plasma and hepatic gene expression of angiopoietin 1(ANG1)and angiopoietin 2(ANG2)in patients with SAH and ALD and investigated their roles as prognostic biomarkers.Methods:A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay(ELISA)from 30 patients with SAH(Maddrey's discriminant function32),32 patients with ALD cirrhosis and 15 healthy controls(HC).RNA sequencing for ANG1,ANG2,TIE1(codes for Tie1 receptor)and TEK(codes for Tie2 receptor)gene expression from a separate cohort study of 79 patients was also performed.Results:Plasma levels of ANG1 were lower(P=0.010)and ANG2 were higher(P<0.0001)in patients with ALD/SAH compared to HC.The ANG2:ANG1 ratio was higher in those with ALD/SAH compared to HC(P<0.0001).ANG2 levels were the highest in patients who developed sepsis(P=0.030)and those dying within 90 days(P=0.020).ANG2 levels correlated positively with model for end-stage liver disease(MELD)score(r=0.30,P=0.020),Child-Pugh score(r=0.38,P=0.003),international normalized ratio(r=0.41,P=0.001)and white blood cell count(r=0.28,P=0.040)and inversely correlated with albumin(r=0.26,P=0.040).ANG1 gene expression from liver biopsies was higher in SAH than that in HC(P<0.0001),and greater in severe disease(P<0.0001).ANG2 gene expression trended towards being lower in SAH than that in HC(P=0.070)though was upregulated in severe disease(P=0.0003).Conclusions:Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.展开更多
文摘Carnosine(β-alanyl-L-histidine)is a naturally occurring endogenous peptide widely distributed in excitable tissues,such as the heart and brain.Over the years,several beneficial effects of carnosine have been discussed well in scientific literature.In particular,this dipeptide is well-known for its antioxidant,anti-inflammatory,and anti-aggregation activities.It is of great interest in the context of numerous systemic and neurodegenerative diseases,besides performing important“side activities”such as metal chelation and pH-buffering.Despite a plethora of preclinical and clinical data supporting carnosine’s therapeutic potential,researchers are still searching for new pharmacological targets that better highlight carnosine’s overall multimodal mechanism of action and allow its disease-specific use.The aim of the present mini-review,after quickly summarizing the current knowledge of carnosine biological properties,is to pinpoint the role of some non-canonical factors/pathways positively modulated by this dipeptide,highlighting their perspective role as future pharmacological targets.
文摘Objectives: As therapeutic modalities for rheumatoid arthritis (RA) advance, immediate and quantitative determination of RA disease status is becoming increasingly important. The purpose of this study was to validate the usefulness of a ring gauge as a simple semiquantitative method for assessing hand swelling in patients with RA. Methods: We enrolled patients diagnosed with RA either initiated or switched to a biological therapeutic agent. The circumference of the interphalangeal (IP) joint and the proximal interphalangeal (PIP) joint was measured using a ring gauge. Assessments of the joint echocardiography, incorporating both Gray Scale (GS) and Power Doppler (PD) imaging, were conducted. These evaluations were performed both before the initiation of biological agent treatment and 28 days after the initial dose. Results: Following the treatment intervention, a significant reduction was observed in the circumference of the joint from the thumb to the little finger (p Conclusions: Our study demonstrated the effectiveness of using a ring gauge as a simple assessment tool for RA, revealing that a change in the ring gauge number by 2 or more corresponded to either improvement or deterioration in synovial thickening detected via joint echocardiography.
文摘According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.
文摘Ophiocordyceps sinensis and Cordyceps militaris both contain many bioactive compounds that confer potential therapeutic benefits. This review discusses the possible use of cultivated C. militaris as an effective substitute for native O. sinensis in the face of ever-increasing prices of O. sinensis because of its short supply. On the one hand, cultivated C. militaris contains higher levels of cordycepin when compared with that of wild-type O. sinensis and cultivation of C. militaris has been shown to be capable of reducing the risk of heavy metal contamination. On the other hand, there is a paucity of robust in vivo studies and randomized controlled tests comparing the pharmacology and use of C. militaris and O. sinensis. For extraction of cordycepin as western-style tablets, the use of cultivated C. militaris rather than O. sinensis represents the most appropriate future approach. For many other purposes, comparative pharmacology and clinical trials are in urgent needs.
基金This study was supported by a research grant from the Prevent Cancer Foundation(PCF2019J.C.)+8 种基金seed funding from the Cleveland Clinic Foundation(J.C.)a National Institutes of Health grant(R01 AI153173J.C.)an American Cancer Society Institutional Research Grant(IRG-16-186-21J.C.)a Jump Start Award from the Case Comprehensive Cancer Center(CA043703J.C.)funding from the Office of the Assistant Secretary of Defense for Health Affairs through the Congressionally Directed Medical Research Programs Peer Reviewed Medical Research Program under award no.W81XWH-19-1-0488(PR181846C.M.)。
文摘Accurate and reproducible analysis of murine small and large intestinal tissue is key for preclinical models involving intestinal pathology.Currently,there is no easily ac-cessible,standardized method that allows researchers of different skill levels to con-sistently dissect intestines in a time-efficient manner.Here,we describe the design and use of the 3D-printed“Mouse Intestinal Slicing Tool”(MIST),which can be used to longitudinally dissect murine intestines for further analysis.We benchmarked the MIST against a commonly used procedure involving scissors to make a longitudinal cut along the intestines.Use of the MIST halved the time per mouse to prepare the intestines and outperformed alternative methods in smoothness of the cutting edge and overall reproducibility.By sharing the plans for printing the MIST,we hope to contribute a uniformly applicable method for saving time and increasing consistency in studies of the mouse gastrointestinal tract.
文摘Objective: To estimate the normal circumference of the interphalangeal (IP) thumb joint and the proximal IP (PIP) joints from the index finger to the little finger using individual physical parameters such as body height and body weight. Methods: The maximum size on the ring gauge was recorded which caused resistance when the IP joint of the thumb or PIP joints of the index to small fingers were passed through the gauge. RG was defined as the ring gauge number with the same diameter as the circumference of the IP thumb joint and PIP finger joints from the index finger to the little finger. There were 300 healthy subjects and 600 hands. Univariate and multivariate analyses were used to analyze the relationships between RG and the parameters of age, sex, height, weight, and dominant hand, and regression equations were derived. Results: Age, sex and body weight were all statistically significant predictive factors of RG in all fingers. R2, the coefficient of determination in the regression equation, was almost 0.7 for all fingers, indicating that a moderate or strong correlation was observed between RG and the regression equation. Conclusions: The circumference of the IP thumb joint and PIP finger joints from the index finger to the little finger can be estimated in healthy individuals using a calculation formula that takes age, sex, body height and body weight into account.
文摘Objective: Early and accurate evaluation of the presence and activity of synovitis is extremely important in the diagnosis and treatment of rheumatoid arthritis. Myeloid related protein 8/14 (MRP8/14), also known as calprotectin or S100A8/A9 is considered as a sensitive marker for local inflammatory activity in rheumatoid arthritis. The aim of this study is to demonstrate the efficacy of MRP8/14 as a marker of disease activity in RA. Methods: Thirty-one patients with diagnosis of RA who received treatment without biological drugs at our institution were included in this study. Serum MRP8/14, CRP and MMP-3 were tested in all patients. Disease activity was evaluated using DAS28-CRP and SDAI. Ultrasonography was performed on the wrists and MCP joints of both hands using semi-quantitative scale of power Doppler signal. The sum of scales in joints was calculated as the PD score. The correlation of MRP8/14 with serum biomarkers, disease activity and ultrasonography examination was investigated. Result: Serum MRP8/14 was strongly correlated with CRP (r = 0.63) and MMP-3 (r = 0.69). A correlation was observed between serum MRP8/14 and DAS28-CRP (r = 0.53) and SDAI (r = 0.66). No significant correlation was found between PD scores and MRP8/14. Conclusion: This study demonstrated that MRP8/14 is correlated with evaluated disease activity and markers of serum inflammatory response in patients not using biological drugs. MRP8/14 is considered an effective new method for objective evaluation of synovitis in RA.
基金supported in part by a grant from the Lerner Research Institute,Cleveland Clinic to GAMC and CQ.
文摘Background and Aims:End-stage liver disease is associated with disruptions in gut microbiota composition and function,which may facilitate gut-to-liver bacterial translocation,impacting liver graft integrity and clinical outcomes following liver transplantation.This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.Methods:This single-center,non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion(NMP).Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3,6,and 12.Stool microbiota was profiled via 16S rRNA gene sequencing,stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry,and breath volatile organic compounds(VOCs)were analyzed with selected-ion flow-tube mass spectrometry.Results:Both cohorts experienced a loss of microbiota diversity and dominance by single taxa.The NMP cohort demonstrated enrichment of several beneficial gut taxa,while the static cold storage cohort showed depletion of such taxa.Various gut bacteria were found to correlate with stool short-chain fatty acids(e.g.,lactic acid,butyric acid)and several VOCs.Conclusions:Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation.However,notable differences in microbiota composition and function were observed between liver graft preservation methods.Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.
基金supported by the National Key R&D Program of China(2023YFC2507300)the National Natural Science Foundation of China(82273761,81970483,82170537 and 82222010)the Medical Innovation and Development Project of Lanzhou University(lzuyxcx-2022-156,China).
文摘Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases,but no effective anti-fibrotic therapy is currently available.Glucagon receptor(GCGR)and glucagon-like peptide 1 receptor(GLP1R)are both peptide hormone receptors involved in energy metabolism of epithelial cells.However,their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored.Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn’s disease as well as in the fibrotic colon of mice with chronic colitis.The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate,resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition(EMT).Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo.We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation.Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
文摘AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.
文摘AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.
文摘Pseudomembranous colitis (PMC) usually manifests asfever and diarrhea in hospitalized patients treated withsystemic antibiotics. We described a case of PMC withintestinal obstruction but without diarrhea. A 60-yearold man was hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the stomach. The patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. Plain abdominal radiography showed some intestinal gas and niveau. Because stool cytotoxin assay for clostridium difficile was positive and colon fiberscopic examination showed a pseudomembrane at the left side of the colon,and a diagnosis of PMC was made. Treatment with intracolonic vancomycin administration by colonoscopy and nasoileus tube was successful. Physicians should take into account the possibility of bowel obstruction due to PMC occurring in patients undergoing chemotherapy and perform emergency colonoscopy examination of suspected cases.
基金supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.
文摘Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some extent.Here,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH.Multiple cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease inflammation.In addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous system.We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections.Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.
基金supported by the Key R&D Program of Shandong Province(2020CXGC010503)Shandong Provincial Key Laboratory Platform Project(2021ZDSYS11)Major Program of National Natural Science Foundation of China(81991525).
文摘Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.
文摘Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Zhang Zemin(张泽民)from the Biodynamic Optical Imaging Center(BIOPIC),Peking University,Prof.Peng Jirun(彭吉润)from Beijing Shijitan Hospital,Capital
基金supported in part by NIH grants U01 DK 061732,U01 AA1026976,and P50 AA024333.
文摘Background:Placement of a transjugular intrahepatic portosystemic shunt(TIPS)is a relatively common procedure used to treat complications of portal hypertension.However,only limited data exist regarding the hospital-readmission rate after TIPS placement and no studies have addressed the causes of hospital readmission.We therefore sought to identify the 30-day hospital-readmission rate after TIPS placement at our institution and to determine potential causes and predictors of readmission.Methods:We reviewed our electronic medical-records system at our institution between 2004 and 2017 to identify patients who had undergone primary TIPS placement with polytetrafluoroethylene-covered stents and to determine the 30-day readmission rate among these patients.A series of univariable logistic-regression models were fit to assess potential predictors of 30-day readmission.Results:A total of 566 patients were included in the analysis.The 30-day readmission rate after TIPS placement was 36%.The most common causes for readmission were confusion(48%),infection(15%),bleeding(11%),and fluid overload(7%).A higher Model for End-Stage Liver Disease(MELD)score corresponded with a higher rate of readmission(odds ratio associated with each 1-unit increase in MELD score:1.06;95%confidence interval:1.02–1.09;P=0.001).Other potential predictors,including indication for TIPS placement,were not significantly associated with a higher readmission rate.Conclusions:The 30-day readmission rate after TIPS placement with covered stents is high,with nearly half of these readmissions due to hepatic encephalopathy—a known complication of TIPS placement.Novel interventions to help reduce the TIPS readmission rate should be prioritized in future research.
文摘Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 days.The angiopoietin-Tie 2 system regulates angiogenesis and inflammation,both of which are implicated in the pathogenesis of ALD.This study examined plasma and hepatic gene expression of angiopoietin 1(ANG1)and angiopoietin 2(ANG2)in patients with SAH and ALD and investigated their roles as prognostic biomarkers.Methods:A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay(ELISA)from 30 patients with SAH(Maddrey's discriminant function32),32 patients with ALD cirrhosis and 15 healthy controls(HC).RNA sequencing for ANG1,ANG2,TIE1(codes for Tie1 receptor)and TEK(codes for Tie2 receptor)gene expression from a separate cohort study of 79 patients was also performed.Results:Plasma levels of ANG1 were lower(P=0.010)and ANG2 were higher(P<0.0001)in patients with ALD/SAH compared to HC.The ANG2:ANG1 ratio was higher in those with ALD/SAH compared to HC(P<0.0001).ANG2 levels were the highest in patients who developed sepsis(P=0.030)and those dying within 90 days(P=0.020).ANG2 levels correlated positively with model for end-stage liver disease(MELD)score(r=0.30,P=0.020),Child-Pugh score(r=0.38,P=0.003),international normalized ratio(r=0.41,P=0.001)and white blood cell count(r=0.28,P=0.040)and inversely correlated with albumin(r=0.26,P=0.040).ANG1 gene expression from liver biopsies was higher in SAH than that in HC(P<0.0001),and greater in severe disease(P<0.0001).ANG2 gene expression trended towards being lower in SAH than that in HC(P=0.070)though was upregulated in severe disease(P=0.0003).Conclusions:Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.
