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Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

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Neural Regeneration Research 2024年第10期19卷 2219-2228页

作者： Paula Maria Neufeld Ralf A.Nettersheim Veronika Matschke Matthias Vorgerd Sarah Stahlke Carsten Theiss department of Cytology Institute of AnatomyMedical FacultyRuhr-University BochumBochumGermany department of visceral Surgery University Hospital BergmannsheilRuhr-University BochumBochumGermany department of Neurology Heimer Institute for Muscle ResearchUniversity Hospital BergmannsheilRuhr-University BochumBochumGermany

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurode

关键词： diet gut-brain axis microbiome neurodegenerative diseases nutrition Parkinson's disease progesterone steroid hormones

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

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Oncology Research 2024年第7期32卷 1163-1172页

作者： LISANNE K.A.NEIJENHUIS LEUTA L.NAUMANN SONIA A.M.FERKEL SAMUEL J.S.RUBIN STEPHAN ROGALLA Division of Gastroenterology and Hepatology Department of MedicineSchool of MedicineStanford UniversityStanford94305USA department of Surgery Leiden University Medical CenterLeiden2333 ZAThe Netherlands Centre for Human Drug Research Leiden2333 CLThe Netherlands department of General VisceralVascular and Thoracic SurgeryCharite University Medicine BerlinBerlin10117Germany

Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a signiﬁcant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety proﬁles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was signiﬁcantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was signiﬁcantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no signiﬁcant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic proﬁle grants further evaluation.Given these observations,further research is necessary to reﬁne the use of taurolidine in osteosarcoma tre

关键词： Osteosarcoma Taurolidine Cancer treatment Chemotherapy Murine models

Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

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Oncology Research 2024年第1期32卷 227-239页

作者： WEI HU THOMAS WARTMANN MARCO STRECKER ARISTOTELIS PERRAKIS ROLAND CRONER ARPAD SZALLASI WENJIE SHI ULF D.KAHLERT The Fourth Clinical Medical College of Yangzhou University Nantong Rich HospitalNantongChina Molecular and Experimental Surgery Clinic for General-Visceral-Vascular and Transplant SurgeryFaculty of Medicine and University Hospital MagdeburgOtto-von-Guericke UniversityMagdeburgGermany department of Pathology and Experimental Cancer Research Semmelweis UniversityBudapestHungary

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformati

关键词： Colon cancer Transient receptor potential channels Prognostic signature Chemotherapy efficiency TRPM5

Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

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World Journal of Gastroenterology 2024年第11期30卷 1488-1493页

作者： Alessandro Parente Keyue Sun Philipp Dutkowski AM James Shapiro Andrea Schlegel department of Surgery Division of TransplantationUniversity of Alberta HospitalEdmonton T6G 2B7Canada Immunity and Inflammation Lerner Research InstituteClevelandOH 44195United States Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryUniversity Hospital ZurichZurich 8091Switzerland Immunity and Inflammation Digestive Disease and Surgery InstituteClevelandOH 44195United States

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

关键词： Liver transplantation Machine perfusion Viability assessment Hypothermic oxygenated perfusion Normothermic machine perfusion

Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

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Current Medical Science 2024年第1期44卷 180-186页

作者： Jin-cheng FENG Ying HE Georgios Polychronidis Jian XIN Shen YOU Jun XIONG department of Liver Transplantation Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Key Laboratory of Transplant Engineering and Immunology Laboratory of Liver TransplantationFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China department of General Visceral and Transplant SurgeryUniversity of HeidelbergIm Neuenheimer Feld 110Heidelberg 69120Germany department of Hepatobiliary and Pancreatic Surgery Fujian Provincial HospitalFuzhou 350001China

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

关键词： brain metastases hepatocellular carcinoma age-related incidence cancer-specific survival overall survival

Fetal lung growth predicts the risk for early-life respiratory infections and childhood asthma

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World Journal of Pediatrics 2024年第5期20卷 481-495页

作者： Dimitra E.Zazara Olympia Giannou Steven Schepanski Mirja Pagenkemper Anastasios D.Giannou Maike Pincus Ioannis Belios Stefan Bonn Ania C.Muntau Kurt Hecher Anke Diemert Petra Clara Arck Division for Experimental Feto-Maternal Medicine Department of Obstetrics and Fetal MedicineUniversity Medical Center Hamburg-Eppendorf(UKE)Martinistraße 5220251HamburgGermany University Children’s Hospital UKEHamburgGermany Computer Engineering and Informatics department Polytechnic SchoolUniversity of PatrasPatrasGreece Institute of Developmental Neurophysiology Center for Molecular Neurobiology Hamburg(ZMNH)UKEHamburgGermany department of Obstetrics and Fetal Medicine UKEHamburgGermany department of General Visceral and Thoracic SurgeryUKEHamburgGermany Section of Molecular Immunology and Gastroenterology I.Department of MedicineUKEHamburgGermany Pediatrics and Pediatric Pneumology Practice BerlinGermany Institute of Medical Systems Biology ZMNHUKEHamburgGermany Hamburg Center for Translational Immunology UKEHamburgGermany

Background Early-life respiratory infections and asthma are major health burdens during childhood.Markers predicting an increased risk for early-life respiratory diseases are sparse.Here,we identified the predictive value of ultrasound-monitored fetal lung growth for the risk of early-life respiratory infections and asthma.Methods Fetal lung size was serially assessed at standardized time points by transabdominal ultrasound in pregnant women participating in a pregnancy cohort.Correlations between fetal lung growth and respiratory infections in infancy or early-onset asthma at five years were examined.Machine-learning models relying on extreme gradient boosting regressor or classifier algorithms were developed to predict respiratory infection or asthma risk based on fetal lung growth.For model development and validation,study participants were randomly divided into a training and a testing group,respectively,by the employed algorithm.Results Enhanced fetal lung growth throughout pregnancy predicted a lower early-life respiratory infection risk.Male sex was associated with a higher risk for respiratory infections in infancy.Fetal lung growth could also predict the risk of asthma at five years of age.We designed three machine-learning models to predict the risk and number of infections in infancy as well as the risk of early-onset asthma.The models’R2 values were 0.92,0.90 and 0.93,respectively,underscoring a high accuracy and agreement between the actual and predicted values.Influential variables included known risk factors and novel predictors,such as ultrasound-monitored fetal lung growth.Conclusion Sonographic monitoring of fetal lung growth allows to predict the risk for early-life respiratory infections and asthma.

关键词： Asthma Child risk Early-life respiratory infections Prenatal lung development Sexual dimorphism

Propofol sedation in routine endoscopy:A case series comparing target controlled infusion vs manually controlled bolus concept

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World Journal of Gastrointestinal Endoscopy 2024年第1期16卷 11-17页

作者： Riad Sarraj Lorenz Theiler Nima Vakilzadeh Niklas Krupka Reiner Wiest department of visceral Surgery and Medicine Inselspital University HospitalBern 3010Switzerland Clinic for Anesthesia PerioperativeEmergency&Intensive Care MedicineKantonsspital AarauAarau 5001Switzerland department of Nephrology and Hypertension University Hospital LausanneLausanne 1011Switzerland

BACKGROUND Many studies have addressed safety and effectiveness of non-anaesthesiologist propofol sedation(NAPS)for gastrointestinal(GI)endoscopy Target controlled infusion(TCI)is claimed to provide an optimal sedation regimen by avoiding under-or oversedation.AIM To assess safety and performance of propofol TCI sedation in comparison with nurse-administered bolus-sedation.METHODS Fouty-five patients undergoing endoscopy under TCI propofol sedation were prospectively included from November 2016 to May 2017 and compared to 87 patients retrospectively included that underwent endoscopy with NAPS.Patients were matched for age and endoscopic procedure.We recorded time of sedation and endoscopy,dosage of medication and adverse events.RESULTS There was a significant reduction in dose per time of propofol administered in the TCI group,compared to the NAPS group(8.2±2.7 mg/min vs 9.3±3.4 mg/min;P=0.046).The time needed to provide adequate sedation levels was slightly but significantly lower in the control group(5.3±2.7 min vs 7.7±3.3 min;P<0.001),nonetheless the total endoscopy time was similar in both groups.No differences between TCI and bolus-sedation was observed for mean total-dosage of propofol rate as well as adverse events.CONCLUSION This study indicates that sedation using TCI for GI endoscopy reduces the dose of propofol necessary per minute of endoscopy.This may translate into less adverse events.However,further and randomized trials need to confirm this trend.

关键词： Sedation Endoscopy Propofol Target controlled infusion Non-anaesthesiologist propofol sedation Adverse event

The value of the INFECTIONS scoring system in identifying bacterial infections among patients presenting at the emergency department of a middle-income country:A pilot study

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Chinese Journal of Traumatology 2024年第2期27卷 77-82页

作者： Dooshanveer C.Nuckchady department of Internal Medicine Victoria HospitalCandosMauritius

Purpose:To investigate which scoring system is the most accurate tool in predicting mortality among the infected patients who present to the emergency department in a middle-income country,and to validate a new scoring system to predict bacterial infections.Methods:This was a retrospective,single-center study among patients who were admitted via the emergency department of a public hospital.All patients who were started on antibiotics were included in the study,while patients aged0.85;however,these scoring systems failed to predict whether patients were truly infected.The INFECTIONS(short for impaired mental status,not conscious,fast heart rate,elevated creatinine,high temperature,on inotrope,low oxygen,high neutrophils and high sugar)model reached an AUROC of 0.88 to more accurately predict the infectious state of a patient.Conclusions:Middle-income countries should use the qSOFA or universal vital assessment score to identify the sickest patients in emergency department.The INFECTIONS score may help recognize patients with bacterial infections,but it should be further validated in multiple countries prior to widely use.

关键词： Prognosis Mortality Bacterial infection INFECTIONS scoring system Sequential organ failure assessment Prediction

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

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Oncology Research 2024年第3期32卷 563-576页

作者： YANG ZHANG NANNAN QIN XIJUN WANG RUI LIANG QUAN LIU RUOYI GENG TIANXIAO JIANG YUNFEI LIU JINWEI LI Graduate School Kunming Medical UniversityKunming650000China Depatment of Vascular Surgery Fuwai Yunnan Cardiovascular HospitalAfliated Cardiovascular Hospital of Kunming Medical UniversityKunming650000China department of Neurosurgery West China HospitalSichuan UniversityChengdu610000China department of Neurosurgery The Fourth Afiliated Hospital of Guangxi Medical UniversityLiuzhou545000China Depatment of Gynecology Oncology The Fourth Afliated Hospital of Guangxi Medical UniversityLiuzhou545000China School of Basic Medical Sciences Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China College of Bioengineering Chongqing UniversityChongqing400030China department of General Visceraland Transplant SurgeryLudwig Maximilians University MunichMunich81377Germany

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

关键词： Glycogen metabolism Metabolic map Single cell Tumor microenvironment Liver cancer Prognosis Immunotherapy