Inflammatory bowel disease(IBD)is a chronic digestive disease that requires continuous monitoring by healthcare professionals to determine the appropriate therapy and monitor short-term and long-term complications.The...Inflammatory bowel disease(IBD)is a chronic digestive disease that requires continuous monitoring by healthcare professionals to determine the appropriate therapy and monitor short-term and long-term complications.The progressive development of information technology has enabled healthcare personnel to deliver care services to patients remotely.Therefore,various applications of telemedicine in IBD management have evolved,including telemonitoring,teleconsulting,teleducation,telenursing,telenutrition,and telepathology.While evidence has been provided for some telemedicine applications,targeted studies are still required.This review summarises the major studies that have evaluated telemedicine and its application in the management of IBD.展开更多
BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to deco...BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.展开更多
BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to asce...BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.展开更多
An adequate bowel preparation in patients with inflammatory bowel disease(IBD)is a prerequisite for successful colonoscopy for screening,diagnosis,and surveillance.Several bowel preparation formulations are available,...An adequate bowel preparation in patients with inflammatory bowel disease(IBD)is a prerequisite for successful colonoscopy for screening,diagnosis,and surveillance.Several bowel preparation formulations are available,both high-and low-volume based on polyethylene glycol.Generally,low-volume formulations are also based on several compounds such as magnesium citrate preparations with sodium picosulphate,oral sulphate solution,and oral sodium phosphatebased solutions.Targeted studies on the quality of bowel preparation prior to colonoscopy in the IBD population are still required,with current evidence from existing studies being inconclusive.New frontiers are also moving towards the use of alternatives to anterograde ones,using preparations based on retrograde colonic lavage.展开更多
Clostridioides difficile(formerly called Clostridium difficile,C.difficile)infection(CDI)is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease C...Clostridioides difficile(formerly called Clostridium difficile,C.difficile)infection(CDI)is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease Control and Prevention.Early detection and appropriate disease management appear to be essential.Meanwhile,although the majority of cases are hospital-acquired CDI,community-acquired CDI cases are also on the rise,and this vulnerability is not limited to immunocompromised patients.Gastrointestinal treatments and/or gastrointestinal tract surgeries may be required for patients diagnosed with digestive diseases.Such treatments could suppress or interfere with the patient’s immune system and disrupt gut flora homeostasis,creating a suitable microecosystem for C.difficile overgrowth.Currently,stool-based non-invasive screening is the first-line approach to CDI diagnosis,but the accuracy is varied due to different clinical microbiology detection methods;therefore,improving reliability is clearly required.In this review,we briefly summarised the life cycle and toxicity of C.difficile,and we examined existing diagnostic approaches with an emphasis on novel biomarkers such as microRNAs.These biomarkers can be easily detected through noninvasive liquid biopsy and can yield crucial information about ongoing pathological phenomena,particularly in CDI.展开更多
Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including pa...Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.展开更多
The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties ...The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment.Altogether,this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes,and offers information regarding the available scientific data and possible applications.展开更多
BACKGROUND Retroperitoneal liposarcoma(RLPS)is a rare malignant tumor of the connective tissue and usually grows to a large size,undetected.Diagnosis is currently based on collective findings from clinical examination...BACKGROUND Retroperitoneal liposarcoma(RLPS)is a rare malignant tumor of the connective tissue and usually grows to a large size,undetected.Diagnosis is currently based on collective findings from clinical examinations and computed tomography(CT)and magnetic resonance imaging,the latter of which show a fat density mass and possible surrounding organ involvement.Surgical resection is the main therapeutic strategy.The efficacy and safety of further therapeutic choices,such as chemotherapy and radiotherapy,are still controversial.CASE SUMMARY A 61-year-old man presented with complaint of a large left inguinal mass that had appeared suddenly,after a slight exertion.Ultrasonography revealed an omental inguinal hernia.During further clinical examination,an enormous palpable abdominal mass,continuing from the left inguinal location,was observed.CT revealed a giant RLPS,with remarkable mass effect and wide visceral dislocation.After multidisciplinary consultation,surgical intervention was performed.Subsequent neoadjuvant chemotherapy and radiotherapy were precluded by the mass’large size and retroperitoneal localization,features typically associated with non-response to these types of treatment.Instead,the patient underwent conservative treatment via radical surgical excision.After 1 year,his clinical condition remained good,with no radiological signs of recurrence.CONCLUSION Conservative treatment via surgery resulted in a successful outcome for a large RLPS.展开更多
Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success rates.Nevertheless,BC might acquire drug resistance and sometimes relapse.Current knowledge about the most...Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success rates.Nevertheless,BC might acquire drug resistance and sometimes relapse.Current knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC,the so-called“BC stem cells”(BCSCs).The role of BCSCs in cancer formation,growth,invasiveness,therapy resistance and tumor recurrence is becoming increasingly clear.The growth and metastatic properties of BCSCs are regulated by different pathways,which are only partially known.Sex steroid receptors(SSRs),which are involved in BC etiology and progression,promote BCSC proliferation,dedifferentiation and migration.However,in the literature,there is incomplete information about their roles.Particularly,there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers,such as estrogen receptor alpha(ERα),together with scant,albeit promising information concerning ER beta(ERβ)and androgen receptor(AR)properties that control different transduction pathways in BCSCs.In this review,we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.展开更多
Due to their special anatomical and physiological features,central nervous system diseases still presented challenges,despite the fact that some advances have been made in early diagnosis and precision medicine.One of...Due to their special anatomical and physiological features,central nervous system diseases still presented challenges,despite the fact that some advances have been made in early diagnosis and precision medicine.One of the complexities in treating tumors is the tumor microenvironment,which includes mesenchymal stem cells(MSCs)that exhibit tumor tropism and can be used for cell therapy.However,whether MSCs promote or suppress gliomas is still unclear,especially in glioma microenvironments.In this study,a coaxial microfiber was designed to mimic the tumor microenvironment and to reveal the effect of MSCs on glioma cells.The fiber shell was composed of MSCs and alginate,and the core was filled with U87 MG(glioblastoma)cells and gelatin methacrylate.This Shell-MSC/Core-U87 MG microenvironment improved the proliferation,survival,invasion,metastasis,and drug resistance of glioma cells,while simultaneously maintaining the stemness of glioma cells.In summary,coaxial extrusion bioprinted Shell-MSC/Core-U87 MG microfiber is an ideal platform for tumor and stromal cell coculture to observe tumor biological behavior in vitro.展开更多
A relevant gradual reduction of both the incidence rate of acute hepatitis B(AHB)and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years,due to substantial epidemiological changes:Improvement ...A relevant gradual reduction of both the incidence rate of acute hepatitis B(AHB)and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years,due to substantial epidemiological changes:Improvement in socioeconomic and hygienic conditions,reduction of the family unit,accurate screening of blood donations,abolition of re-usable glass syringes,hepatitis B virus(HBV)-universal vaccination started in 1991,use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998,and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections.As an example,AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020.Unfortunately,the coronavirus disease 2019(COVID-19)pandemic has interrupted the trend towards HBV eradication.In fact,several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening,diagnosis,clinical management,and nucleo(t)side analogue therapy in the COVID-19 pandemic,mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),movement restrictions,and reduced gains from job loss.In addition,one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.展开更多
The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cl...The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan,China in December 2019.Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines,based on scientific evidence and experts’opinions with clinical experience,are constantly being updated.On January 30,2020,the World Health Organization declared the SARS-CoV-2 outbreak as a"Public Health Emergency of International Concern".The total lack of immune protection brought about a severe spread of the contagion all over the world.For this reason,diagnostic tools,patient management and therapeutic approaches have been tested along the way,in the desperate race to break free from the widespread infection and its fatal respiratory complications.Current medical knowledge and research on severe and critical patients’management and experimental treatments are still evolving,but several protocols on minimizing risk of infection among the general population,patients and healthcare workers have been approved and diffused by International Health Authorities.展开更多
BACKGROUND The place regular physical activity(PA)should occupy in managing patients with inflammatory bowel diseases(IBD)is unclear.AIM To assess PA levels and barriers in a southern Italian IBD population.METHODS IB...BACKGROUND The place regular physical activity(PA)should occupy in managing patients with inflammatory bowel diseases(IBD)is unclear.AIM To assess PA levels and barriers in a southern Italian IBD population.METHODS IBD patients with non-severe disease activity[assessed with partial Mayo score for ulcerative colitis(UC)and Harvey-Bradshaw index for Crohn’s disease]were approached to receive an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire(IPAQ)and to assess disease activity as patient-reported outcomes 2(PRO-2)and finally to assess habits,beliefs and barriers in conducting regular PA.Clinical,anthropometric and demographic data of patients were also collected.PA was expressed as continuous units of resting metabolic rate(Met)in min/wk.Three PA groups were identified:Inactive(<700 Met min/wk),sufficiently active(700-2500 Met min/wk)and health enhancing PA(HEPA)(i.e.,HEPA active,>2500 Met min/wk)patients.RESULTS Included patients(219)showed overall PA levels of 834.5 Met min/wk,with a large proportion(94,42.9%)classified as inactive while only a minority(9,4.1%)as health-enhancing PA.Patients without dyslipidaemia(P<0.0001)or on biologics therapy(P=0.022)showed better IPAQ scores in moderate activities.UC PRO-2 correlated negatively with IPAQ intense activities scores(τ=-0.156,P=0.038).PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity(AUC<0.6).IBD activity did not differ between active and inactive patients(P>0.05).Active patients expressed the need to discuss PA with their gastroenterologist.Some barriers(e.g.,diagnosis of IBD and fear of flare-ups after PA)are significantly more reported by inactive patients.CONCLUSION A significant rate of physical inactivity was recorded in this setting.IPAQ showed good feasibility.PA should be an element of discussion in IBD visits assessed quickly with non-invasive questionnaires.展开更多
The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during life.Those intestinal microorganis...The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during life.Those intestinal microorganisms called microbiota and are involved in a variety of mechanisms of the organism,they interact with the host and therefore are in contact with the organs of the various systems.However,they play a crucial role in maintaining host homeostasis,also influencing its behaviour.Thus,microorganisms perform a series of biological functions important for human well-being.The host provides the microorganisms with the environment and nutrients,simultaneously drawing many benefits such as their contribution to metabolic,trophic,immunological,and other functions.For these reasons it has been reported that its quantitative and qualitative composition can play a protective or harmful role on the host health.Therefore,a dysbiosis can lead to an association of unfavourable factors which lead to a dysregulation of the physiological processes of homeostasis.Thus,it has previously noted that the gut microbiota can participate in the pathogenesis of autoimmune diseases,chronic intestinal inflammation,diabetes mellitus,obesity and atherosclerosis,neurological disorders(e.g.,neurological diseases,autism,etc.)colorectal cancer,and more.展开更多
Patients with inflammatory bowel diseases(IBDs)require repeated endoscopic evaluations over time by colonoscopy to weigh disease activity but also for different and additional indications(e.g.,evaluation of postoperat...Patients with inflammatory bowel diseases(IBDs)require repeated endoscopic evaluations over time by colonoscopy to weigh disease activity but also for different and additional indications(e.g.,evaluation of postoperative recurrence,colorectal cancer surveillance).Colonoscopy,however,requires adequate bowel preparation to be of quality.The latter is achieved as long as the patient takes a certain amount of product to have a number of bowel movements suitable to clean the colon and allow optimal visualization of the mucosa during endoscopy.However,significant guidelines recommend preparations for patients with IBD not excelling in palatability.This recommendation originates from the fact that most of the studies conducted on bowel preparations in patients with IBD have been done with isosmolar preparations based on polyethylene glycol(PEG),for which,therefore,more safety data exist.As a result,the low-volume non-PEG preparations(e.g.,magnesium citrate plus picosulphate,oral sulphate solutions)have been set aside for the whole range of warnings to be heeded because of their hyperosmolarity.New studies,however,are emerging,leaning in overall for a paradigm shift in this matter.Indeed,such non-PEG preparations seem to show a particularly encouraging and engaging safety profile when considering their broad potential for tolerability and patient preference.Indeed,such evidence is insufficient to indicate such preparations in all patients with IBD but may pave the way for those with remission or well-controlled disease.This article summarizes the central studies conducted in IBD settings using non-PEG preparations by discussing their results.展开更多
The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study o...The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual's particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pharmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.展开更多
Hericium erinaceus is an edible and medicinal mushroom commonly used in traditional Chinese medicine for centuries.Several studies have highlighted its therapeutic potential for gastrointestinal disorders such as gast...Hericium erinaceus is an edible and medicinal mushroom commonly used in traditional Chinese medicine for centuries.Several studies have highlighted its therapeutic potential for gastrointestinal disorders such as gastritis and inflammatory bowel diseases.In addition,some components of this mushroom appear to possess strong antineoplastic capabilities against gastric and colorectal cancer.This review aims to analyse all available evidence on the digestive therapeutic potential of this fungus as well as the possible underlying molecular mechanisms.展开更多
Hereditary gingival fibromatosis(HGF)is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity.Five distinct loci related to non-syndromic HGF have bee...Hereditary gingival fibromatosis(HGF)is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity.Five distinct loci related to non-syndromic HGF have been identified;however,only two diseasecausing genes,SOS1 and REST,inducing HGF have been identified at two loci,GINGF1 and GINGF5,respectively.Here,based on a family pedigree with 26 members,including nine patients with HGF,we identified double heterozygous pathogenic mutations in the ZNF513(c.C748T,p.R250W)and KIF3C(c.G1229A,p.R410H)genes within the GINGF3 locus related to HGF.Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo.ZNF513,a transcription factor,binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts.Furthermore,a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513(p.R250W)or Kif3c(p.R412H)alone do not led to clear phenotypes with gingival fibromatosis,whereas the double mutations led to gingival hyperplasia phenotypes.In addition,we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1.Moreover,the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels.ZNF513 combined with KIF3C regulates gingival fibroblast proliferation,migration,and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways.In summary,these results demonstrate ZNF513+KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.展开更多
BACKGROUND Mallory-Weiss syndrome(MWS),representing a linear mucosal laceration at the gastroesophageal junction,is a quite frequent cause of upper gastrointestinal bleeding,usually induced by habitual vomiting.The su...BACKGROUND Mallory-Weiss syndrome(MWS),representing a linear mucosal laceration at the gastroesophageal junction,is a quite frequent cause of upper gastrointestinal bleeding,usually induced by habitual vomiting.The subsequent cardiac ulceration in this condition is likely due to the concomitance of increased intragastric pressure and inappropriate closure of the gastroesophageal sphincter,collectively inducing ischemic mucosal damage.Usually,MWS is associated with all vomiting conditions,but it has also been described as a complication of prolonged endoscopic procedures or ingested foreign bodies.CASE SUMMARY We described herein a case of upper gastrointestinal bleeding in a 16-year-old girl with MWS and chronic psychiatric distress,the latter of which deteriorated following her parents’divorce.The patient,who was residing on a small island during the coronavirus disease 2019 pandemic lockdown period,presented with a 2-mo history of habitual vomiting,hematemesis,and a slight depressive mood.Ultimately,a huge intragastric obstructive trichobezoar was detected and discovered to be due to a hidden habit of continuously eating her own hair;this habit had persisted for the past 5 years until a drastic reduction in food intake and corresponding weight loss occurred.The relative isolation in her living status without school attendance had worsened her compulsory habit.The hair agglomeration had reached such enormous dimensions and its firmness was so hard that its potential for endoscopic treatment was judged to be impossible.The patient underwent surgical intervention instead,which culminated in complete removal of the mass.CONCLUSION According to our knowledge,this is the first-ever described case of MWS due to an excessively large trichobezoar.展开更多
Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese MSC.In this study,w...Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese MSC.In this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of MSC.Diet-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese ADSC.Similar effects were also observed in lean ADSC.In addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis.Mechanistically,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a axis.These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.展开更多
文摘Inflammatory bowel disease(IBD)is a chronic digestive disease that requires continuous monitoring by healthcare professionals to determine the appropriate therapy and monitor short-term and long-term complications.The progressive development of information technology has enabled healthcare personnel to deliver care services to patients remotely.Therefore,various applications of telemedicine in IBD management have evolved,including telemonitoring,teleconsulting,teleducation,telenursing,telenutrition,and telepathology.While evidence has been provided for some telemedicine applications,targeted studies are still required.This review summarises the major studies that have evaluated telemedicine and its application in the management of IBD.
文摘BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.
基金The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of University of Campania Luigi Vanvitelli(Protocol code 795 on December 23,2019).
文摘BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.
文摘An adequate bowel preparation in patients with inflammatory bowel disease(IBD)is a prerequisite for successful colonoscopy for screening,diagnosis,and surveillance.Several bowel preparation formulations are available,both high-and low-volume based on polyethylene glycol.Generally,low-volume formulations are also based on several compounds such as magnesium citrate preparations with sodium picosulphate,oral sulphate solution,and oral sodium phosphatebased solutions.Targeted studies on the quality of bowel preparation prior to colonoscopy in the IBD population are still required,with current evidence from existing studies being inconclusive.New frontiers are also moving towards the use of alternatives to anterograde ones,using preparations based on retrograde colonic lavage.
文摘Clostridioides difficile(formerly called Clostridium difficile,C.difficile)infection(CDI)is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease Control and Prevention.Early detection and appropriate disease management appear to be essential.Meanwhile,although the majority of cases are hospital-acquired CDI,community-acquired CDI cases are also on the rise,and this vulnerability is not limited to immunocompromised patients.Gastrointestinal treatments and/or gastrointestinal tract surgeries may be required for patients diagnosed with digestive diseases.Such treatments could suppress or interfere with the patient’s immune system and disrupt gut flora homeostasis,creating a suitable microecosystem for C.difficile overgrowth.Currently,stool-based non-invasive screening is the first-line approach to CDI diagnosis,but the accuracy is varied due to different clinical microbiology detection methods;therefore,improving reliability is clearly required.In this review,we briefly summarised the life cycle and toxicity of C.difficile,and we examined existing diagnostic approaches with an emphasis on novel biomarkers such as microRNAs.These biomarkers can be easily detected through noninvasive liquid biopsy and can yield crucial information about ongoing pathological phenomena,particularly in CDI.
文摘Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.
文摘The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment.Altogether,this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes,and offers information regarding the available scientific data and possible applications.
文摘BACKGROUND Retroperitoneal liposarcoma(RLPS)is a rare malignant tumor of the connective tissue and usually grows to a large size,undetected.Diagnosis is currently based on collective findings from clinical examinations and computed tomography(CT)and magnetic resonance imaging,the latter of which show a fat density mass and possible surrounding organ involvement.Surgical resection is the main therapeutic strategy.The efficacy and safety of further therapeutic choices,such as chemotherapy and radiotherapy,are still controversial.CASE SUMMARY A 61-year-old man presented with complaint of a large left inguinal mass that had appeared suddenly,after a slight exertion.Ultrasonography revealed an omental inguinal hernia.During further clinical examination,an enormous palpable abdominal mass,continuing from the left inguinal location,was observed.CT revealed a giant RLPS,with remarkable mass effect and wide visceral dislocation.After multidisciplinary consultation,surgical intervention was performed.Subsequent neoadjuvant chemotherapy and radiotherapy were precluded by the mass’large size and retroperitoneal localization,features typically associated with non-response to these types of treatment.Instead,the patient underwent conservative treatment via radical surgical excision.After 1 year,his clinical condition remained good,with no radiological signs of recurrence.CONCLUSION Conservative treatment via surgery resulted in a successful outcome for a large RLPS.
基金Supported by the National Ministry of University and Research,Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale,No.2017EKMFTN_002,No.2015B7M39T_003Umberto Veronesi Foundation Post-doctoral Fellowship 2019Program VALERE(Vanvitelli per la RicercaUniversity of Campania"L.Vanvitelli")
文摘Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success rates.Nevertheless,BC might acquire drug resistance and sometimes relapse.Current knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC,the so-called“BC stem cells”(BCSCs).The role of BCSCs in cancer formation,growth,invasiveness,therapy resistance and tumor recurrence is becoming increasingly clear.The growth and metastatic properties of BCSCs are regulated by different pathways,which are only partially known.Sex steroid receptors(SSRs),which are involved in BC etiology and progression,promote BCSC proliferation,dedifferentiation and migration.However,in the literature,there is incomplete information about their roles.Particularly,there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers,such as estrogen receptor alpha(ERα),together with scant,albeit promising information concerning ER beta(ERβ)and androgen receptor(AR)properties that control different transduction pathways in BCSCs.In this review,we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.
基金Jiangxi Provincial People’s Government and Shangrao East China Institute of Digital Medical Engineering for their support。
文摘Due to their special anatomical and physiological features,central nervous system diseases still presented challenges,despite the fact that some advances have been made in early diagnosis and precision medicine.One of the complexities in treating tumors is the tumor microenvironment,which includes mesenchymal stem cells(MSCs)that exhibit tumor tropism and can be used for cell therapy.However,whether MSCs promote or suppress gliomas is still unclear,especially in glioma microenvironments.In this study,a coaxial microfiber was designed to mimic the tumor microenvironment and to reveal the effect of MSCs on glioma cells.The fiber shell was composed of MSCs and alginate,and the core was filled with U87 MG(glioblastoma)cells and gelatin methacrylate.This Shell-MSC/Core-U87 MG microenvironment improved the proliferation,survival,invasion,metastasis,and drug resistance of glioma cells,while simultaneously maintaining the stemness of glioma cells.In summary,coaxial extrusion bioprinted Shell-MSC/Core-U87 MG microfiber is an ideal platform for tumor and stromal cell coculture to observe tumor biological behavior in vitro.
文摘A relevant gradual reduction of both the incidence rate of acute hepatitis B(AHB)and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years,due to substantial epidemiological changes:Improvement in socioeconomic and hygienic conditions,reduction of the family unit,accurate screening of blood donations,abolition of re-usable glass syringes,hepatitis B virus(HBV)-universal vaccination started in 1991,use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998,and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections.As an example,AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020.Unfortunately,the coronavirus disease 2019(COVID-19)pandemic has interrupted the trend towards HBV eradication.In fact,several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening,diagnosis,clinical management,and nucleo(t)side analogue therapy in the COVID-19 pandemic,mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),movement restrictions,and reduced gains from job loss.In addition,one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.
文摘The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan,China in December 2019.Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines,based on scientific evidence and experts’opinions with clinical experience,are constantly being updated.On January 30,2020,the World Health Organization declared the SARS-CoV-2 outbreak as a"Public Health Emergency of International Concern".The total lack of immune protection brought about a severe spread of the contagion all over the world.For this reason,diagnostic tools,patient management and therapeutic approaches have been tested along the way,in the desperate race to break free from the widespread infection and its fatal respiratory complications.Current medical knowledge and research on severe and critical patients’management and experimental treatments are still evolving,but several protocols on minimizing risk of infection among the general population,patients and healthcare workers have been approved and diffused by International Health Authorities.
基金The study was conducted in compliance with the Declaration of Helsinki and received approval from the Ethics Committee of the University of Campania Luigi Vanvitelli(protocol number 7892,15 March 2023).
文摘BACKGROUND The place regular physical activity(PA)should occupy in managing patients with inflammatory bowel diseases(IBD)is unclear.AIM To assess PA levels and barriers in a southern Italian IBD population.METHODS IBD patients with non-severe disease activity[assessed with partial Mayo score for ulcerative colitis(UC)and Harvey-Bradshaw index for Crohn’s disease]were approached to receive an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire(IPAQ)and to assess disease activity as patient-reported outcomes 2(PRO-2)and finally to assess habits,beliefs and barriers in conducting regular PA.Clinical,anthropometric and demographic data of patients were also collected.PA was expressed as continuous units of resting metabolic rate(Met)in min/wk.Three PA groups were identified:Inactive(<700 Met min/wk),sufficiently active(700-2500 Met min/wk)and health enhancing PA(HEPA)(i.e.,HEPA active,>2500 Met min/wk)patients.RESULTS Included patients(219)showed overall PA levels of 834.5 Met min/wk,with a large proportion(94,42.9%)classified as inactive while only a minority(9,4.1%)as health-enhancing PA.Patients without dyslipidaemia(P<0.0001)or on biologics therapy(P=0.022)showed better IPAQ scores in moderate activities.UC PRO-2 correlated negatively with IPAQ intense activities scores(τ=-0.156,P=0.038).PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity(AUC<0.6).IBD activity did not differ between active and inactive patients(P>0.05).Active patients expressed the need to discuss PA with their gastroenterologist.Some barriers(e.g.,diagnosis of IBD and fear of flare-ups after PA)are significantly more reported by inactive patients.CONCLUSION A significant rate of physical inactivity was recorded in this setting.IPAQ showed good feasibility.PA should be an element of discussion in IBD visits assessed quickly with non-invasive questionnaires.
文摘The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during life.Those intestinal microorganisms called microbiota and are involved in a variety of mechanisms of the organism,they interact with the host and therefore are in contact with the organs of the various systems.However,they play a crucial role in maintaining host homeostasis,also influencing its behaviour.Thus,microorganisms perform a series of biological functions important for human well-being.The host provides the microorganisms with the environment and nutrients,simultaneously drawing many benefits such as their contribution to metabolic,trophic,immunological,and other functions.For these reasons it has been reported that its quantitative and qualitative composition can play a protective or harmful role on the host health.Therefore,a dysbiosis can lead to an association of unfavourable factors which lead to a dysregulation of the physiological processes of homeostasis.Thus,it has previously noted that the gut microbiota can participate in the pathogenesis of autoimmune diseases,chronic intestinal inflammation,diabetes mellitus,obesity and atherosclerosis,neurological disorders(e.g.,neurological diseases,autism,etc.)colorectal cancer,and more.
文摘Patients with inflammatory bowel diseases(IBDs)require repeated endoscopic evaluations over time by colonoscopy to weigh disease activity but also for different and additional indications(e.g.,evaluation of postoperative recurrence,colorectal cancer surveillance).Colonoscopy,however,requires adequate bowel preparation to be of quality.The latter is achieved as long as the patient takes a certain amount of product to have a number of bowel movements suitable to clean the colon and allow optimal visualization of the mucosa during endoscopy.However,significant guidelines recommend preparations for patients with IBD not excelling in palatability.This recommendation originates from the fact that most of the studies conducted on bowel preparations in patients with IBD have been done with isosmolar preparations based on polyethylene glycol(PEG),for which,therefore,more safety data exist.As a result,the low-volume non-PEG preparations(e.g.,magnesium citrate plus picosulphate,oral sulphate solutions)have been set aside for the whole range of warnings to be heeded because of their hyperosmolarity.New studies,however,are emerging,leaning in overall for a paradigm shift in this matter.Indeed,such non-PEG preparations seem to show a particularly encouraging and engaging safety profile when considering their broad potential for tolerability and patient preference.Indeed,such evidence is insufficient to indicate such preparations in all patients with IBD but may pave the way for those with remission or well-controlled disease.This article summarizes the central studies conducted in IBD settings using non-PEG preparations by discussing their results.
基金supported by the Major National R&D Projects (Grant No.2012ZX09506001-004)National Natural Science Foundation of China (Grant No.81273578)
文摘The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual's particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pharmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.
文摘Hericium erinaceus is an edible and medicinal mushroom commonly used in traditional Chinese medicine for centuries.Several studies have highlighted its therapeutic potential for gastrointestinal disorders such as gastritis and inflammatory bowel diseases.In addition,some components of this mushroom appear to possess strong antineoplastic capabilities against gastric and colorectal cancer.This review aims to analyse all available evidence on the digestive therapeutic potential of this fungus as well as the possible underlying molecular mechanisms.
基金supported by National Natural Science Foundation of China(82302078,32170617,31970558,82170920)National Key R&D Program of China(2021YFC1005301,2022YFC2703303)+1 种基金Natural Science Foundation of Guangdong Province of China(2022A1515012621)Grant for joint research projects from Shenzhen Hospital,Southern Medical University(22H3AUN04).
文摘Hereditary gingival fibromatosis(HGF)is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity.Five distinct loci related to non-syndromic HGF have been identified;however,only two diseasecausing genes,SOS1 and REST,inducing HGF have been identified at two loci,GINGF1 and GINGF5,respectively.Here,based on a family pedigree with 26 members,including nine patients with HGF,we identified double heterozygous pathogenic mutations in the ZNF513(c.C748T,p.R250W)and KIF3C(c.G1229A,p.R410H)genes within the GINGF3 locus related to HGF.Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo.ZNF513,a transcription factor,binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts.Furthermore,a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513(p.R250W)or Kif3c(p.R412H)alone do not led to clear phenotypes with gingival fibromatosis,whereas the double mutations led to gingival hyperplasia phenotypes.In addition,we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1.Moreover,the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels.ZNF513 combined with KIF3C regulates gingival fibroblast proliferation,migration,and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways.In summary,these results demonstrate ZNF513+KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
文摘BACKGROUND Mallory-Weiss syndrome(MWS),representing a linear mucosal laceration at the gastroesophageal junction,is a quite frequent cause of upper gastrointestinal bleeding,usually induced by habitual vomiting.The subsequent cardiac ulceration in this condition is likely due to the concomitance of increased intragastric pressure and inappropriate closure of the gastroesophageal sphincter,collectively inducing ischemic mucosal damage.Usually,MWS is associated with all vomiting conditions,but it has also been described as a complication of prolonged endoscopic procedures or ingested foreign bodies.CASE SUMMARY We described herein a case of upper gastrointestinal bleeding in a 16-year-old girl with MWS and chronic psychiatric distress,the latter of which deteriorated following her parents’divorce.The patient,who was residing on a small island during the coronavirus disease 2019 pandemic lockdown period,presented with a 2-mo history of habitual vomiting,hematemesis,and a slight depressive mood.Ultimately,a huge intragastric obstructive trichobezoar was detected and discovered to be due to a hidden habit of continuously eating her own hair;this habit had persisted for the past 5 years until a drastic reduction in food intake and corresponding weight loss occurred.The relative isolation in her living status without school attendance had worsened her compulsory habit.The hair agglomeration had reached such enormous dimensions and its firmness was so hard that its potential for endoscopic treatment was judged to be impossible.The patient underwent surgical intervention instead,which culminated in complete removal of the mass.CONCLUSION According to our knowledge,this is the first-ever described case of MWS due to an excessively large trichobezoar.
基金This work was supported by the Basic Science Research Program of the National Research Foundation of Korea(NRF)(NRF-2021R1A2C1013132)Basic Science Research Program through the National Research Foundation of Korea(NRF)(2020R1A6A1A03044512).The authors thank the Core Research Support Center for Natural Products and Medical Materials(CRCNM)for the technical support regarding the confocal microscopic analysis.
文摘Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese MSC.In this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of MSC.Diet-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese ADSC.Similar effects were also observed in lean ADSC.In addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis.Mechanistically,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a axis.These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.
