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Emerging role of the gut microbiome in post-infectious irritable bowel syndrome:A literature review

World Journal of Gastroenterology 2023年第21期29卷 3241-3256页

作者： Vasile Valeriu Lupu Cristina Mihaela Ghiciuc Gabriela Stefanescu Cristina Maria Mihai Alina Popp Maria Oana Sasaran Laura Bozomitu Iuliana Magdalena Starcea Anca Adam Raileanu Ancuta Lupu Faculty of General medicine “Grigore T.Popa”University of Medicine and PharmacyIasi 700115Romania Faculty of General medicine Ovidius UniversityConstanta 900470Romania Faculty of General medicine “Carol Davila”University of Medicine and PharmacyBucharest 020021Romania Faculty of General medicine “George Emil Palade”University of MedicinePharmacyScience and TechnologyTargu Mures 540142Romania

Post-infectious irritable bowel syndrome(PI-IBS)is a particular type of IBS,with symptom onset after an acute episode of infectious *** infectious disease resolution and clearance of the inciting pathogen agent,10%of patients will develop *** susceptible individuals,the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota *** changes can affect the gut-brain axis and the visceral sensitivity,disrupting the intestinal barrier,altering neuromuscular function,triggering persistent low inflammation,and sustaining the onset of IBS *** is no specific treatment strategy for *** drug classes can be used to treat PI-IBS similar to patients with IBS in general,guided by their clinical *** review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS *** also discusses the current state of evidence on therapies targeting the microbiome in the management of *** results of microbial modulation strategies used in relieving IBS symptomatology are *** studies on PI-IBS animal models reported promising ***,published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are *** research is required.

关键词： Gut microbiome Infectious gastroenteritis Irritable bowel syndrome Post infection syndrome Pathophysiology Inflammation

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Key questions about the checkpoint blockade-are microRNAs an answer?

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Cancer Biology & medicine 2018年第2期15卷 103-115页

作者： Mihnea Dragomir Baoqing Chen Xiao Fu George A.Calin Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Research Center for Functional Genomics Biomedicine and Translational MedicineIuliu Hatieganu University of Medicine and Pharmacy Department of Surgery Fundeni Clinical HospitalCarol Davila University of Medicine and Pharmacy Center for RNA Interference and Non-coding RNAs The University of Texas MD Anderson Cancer Center

The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.

关键词： MicroRNA PD-1 PD-L1 CTLA-4 checkpoint inhibitors

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Techniques of Surgery for Lumbar Spinal Stenosis: A Comparative Study

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Open Journal of Modern Neurosurgery 2019年第1期9卷 78-104页

作者： Abdul Salam Abdul Rahman Hawis Iacob Gabriel carol davila university of medicine and pharmacy Bucharest Romania

Aim: To compare between classic open surgeries and minimally invasive surgeries in Lumbar Spinal Stenosis. Methods: A comparative descriptive study, involved 117 patients suffering from lumbar canal stenosis, aged between 40 - 70 years;admitted to department of Neurosurgery from March 2011 till august 2016 in King Fahad Hospital in Saudi Arabia. Study groups are consisted of group A as patients managed with classical laminectomy, group B as patients managed with endoscopic spinal procedures and group C as patients managed with microscopic decompression facilitated by the Metrex Tubular System. SPSS was used in data entry and analysis, and ethical considerations taken into consideration and participants filled the required inform consents. Results: Age of particaoncet ranged from 45 - 63 years, Mean +/‒50. The degenerative canal stenosis with acute disc single level (cauda equina syndrome) was the most common type of lumbar canal stenosis encountered in group A;the unilateral foraminal and lateral recess stenosis without disc prolapse was the most common type of lumbar canal stenosis encountered in group B;while the unilateral foraminal and lateral recess stenosis without disc prolapse was the most common type of lumbar canal stenosis encountered in group C. Classic laminectomy and disectomy used mostly in group A;endoscopic unilateral decompression lamino-foraminotomy without discectomy used mostly in group B and bilateral microscopic laminectomy without discectomy followed by unilateral microscopic laminoforaminotomy without discectomy used mostly in group C. Mean of operation duration was the highest in both gender of group A, followed by group B, then group C. Unintended durotomy was the most common intra operative complications occurred in the whole study especially in group A. Mean of blood lost was the highest in both gender of group A, followed by group B, then group C. Postop complications in the patients of study groups were the highest in group A (33

关键词： Invasive Microscopic Techniques Surgery Lumbar Spinal Stenosis

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Cancer stem cells: Involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics

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World Journal of Gastroenterology 2014年第31期20卷 10790-10801页

作者： Cristiana Pistol Tanase Ana Iulia Neagu Laura Georgiana Necula Cristina Mambet Ana-Maria Enciu Bogdan Calenic Maria Linda Cruceru Radu Albulescu Department of Biochemistry-Proteomics Victor Babes National Institute of Pathology Stefan S Nicolau Institute of Virology carol davila university of medicine and pharmacy National Institute for Chemical Pharmaceutical Research and Development

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells(CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

关键词： Cancer stem cells Pancreatic cancer Cancer stem cells signaling pathways Targeted therapy miRNA

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Could there be an interplay between periodontal changes and pancreatic malignancies?

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World Journal of Clinical Cases 2023年第3期11卷 545-555页

作者： Bogdan Silviu Ungureanu Dorin Nicolae Gheorghe Flavia Mirela Nicolae Sandu Ramboiu Petru Adrian Radu Valeriu MarinȘurlin Victor Dan Eugen Strambu Dan Ionut Gheonea Alexandra Roman PetraȘurlin Department of Gastroenterology University of Medicine and Pharmacy of CraiovaCraiova 200349Romania Department of Periodontology Research Center of Periodontal-Systemic ImplicationsUniversity of Medicine and Pharmacy of CraiovaCraiova 200349Romania Department 1st of Surgery University of Medicine and Pharmacy of CraiovaCraiova 200349Romania Department of General Surgery “Carol Davila”University of Medicine and PharmacyBucharest 020021Romania Department of Periodontology "Iuliu Hațieganu"University of Medicine and PharmacyCluj-Napoca 400012Romania

The term"periodontal disease"refers to a group of chronic inflammatory illnesses caused by specific microorganisms from subgingival biofilm,that affect the toothsupporting *** research has also shown that periodontal infection plays a role in aggravating systemic disease states at distal sites,reinforcing the significance of the oral cavity for general ***,it has been suggested that gastroenterological malignancies may be promoted by hematogenous,enteral or lymphatic translocation of *** the past 25 years,the global burden of pancreatic cancer(PC)has more than doubled,making it one of the major causes of cancer-related *** has been linked to at least 50%increased risk of PC and it could be considered a risk factor for this malignancy.A recent study performed on 59000 African American women with a follow up of 21 years showed that participants who had poor dental health had higher chances of *** findings,according to researchers,might be related to the inflammation that some oral bacteria *** the mortality of PC,periodontitis considerably raises the chance of dying from *** alterations in the gut,oral cavity and pancreatic tissues of PC patients occur when compared to healthy flora,demonstrating a link between PC and *** may also contribute to PC development,although the underlying pathway is not yet *** function of the microbiome in PC risk has drawn more focus over the last *** risk of PC has been linked to the oral microbiome,specifically increased levels of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and decreased relative abundance of Leptotrichia and Fusobacteria,suggesting that it may have an impact on the inflammatory condition by expanding,altering,and regulating the commensal *** who received periodontal treatment had significantly decreased incidence rate ratios for *** analyzing patterns in

关键词： Periodontal disease Pancreatic cancer Microbiome Periodontitis Periopathogens Periodontal medicine

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Occult hepatitis B—the result of the host immune response interaction with different genomic expressions of the virus

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World Journal of Clinical Cases 2022年第17期10卷 5518-5530页

作者： George Sebastian Gherlan Department of Infectious Diseases “Carol Davila”University of Medicine and PharmacyBucharest 030303Romania Department of Infectious Diseases “Dr.Victor Babes”Hospital of Infectious and Tropical DiseasesBucharest 030303Romania

With over 40 years of history,occult hepatitis B infection(OBI)continues to remain an important and challenging public health *** as the presence of replication-competent hepatitis B virus(HBV)DNA(i.e.,episomal HBV covalently closed circular DNA)in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen(HBsAg)in currently available assays,OBI is currently diagnosed using polymerase chain reaction(PCR)and real-time PCR ***,all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of *** recent years,significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult *** factors are mainly related to the host immune system and,to a smaller proportion,to the *** innate and adaptive immune responses are important in HBV infection management,and epigenetic changes driven by host mechanisms(acetylation,methylation,and microRNA implication)are added to such *** greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection,the mechanisms of OBI are not mainly viral mutations.

关键词： Hepatitis B virus Occult hepatitis B Covalently closed circular DNA Epigenetic factors Immune factors MicroRNA

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Transient immune hepatitis as post-coronavirus disease complication:A case report

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World Journal of Clinical Cases 2021年第16期9卷 4032-4039页

作者： Anca Cristina Drăgănescu Oana Săndulescu Anuța Bilașco Camelia Kouris Anca Streinu-Cercel Monica Luminos Adrian Streinu-Cercel Infectious Diseases Department National Institute for Infectious Diseases“Prof.Dr.Matei Balș”Bucharest 021105Romania Infectious Diseases Department Carol Davila University of Medicine and PharmacyBucharest 021105Romania

BACKGROUND We report a case of post-coronavirus disease(COVID)immune hepatitis occurring in a young male with no pre-existing *** SUMMARY A previously healthy 21-year-old male patient was admitted to our hospital with mild *** the course of in-hospital isolation and monitoring,he developed an alanine aminotransferase(ALT)and aspartate aminotransferase(AST)increase,with the enzymes peaking at day 24(ALT 15 times the upper normal limit),with preserved liver *** liver enzyme increase occurred 20 d after the complete clinical remission of COVID-19,and ALT dynamics paralleled the increase in total antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The case was interpreted as post-COVID immune hepatitis,with extensive laboratory investigations excluding other potential *** hepatocytolysis remitted 20 d after the peak ALT,without further intervention,with complete recovery,but the total anti-SARS-CoV-2 antibodies continued to increase the next 5 mo following the acute *** Close attention should also be paid to young patients with mild forms of disease,and a high index of suspicion should be maintained for post-COVID complications.

关键词： COVID-19 Complications Liver Case report

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Ethanol exposed maturing rat cerebellar granule cells show impaired energy metabolism and increased cell death after oxygen-glucose deprivation

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Neural Regeneration Research 2019年第3期14卷 485-490页

作者： Ana Spataru Diana Le Duc Leon Zagrean Ana-Maria Zagrean Division of Physiology and Neuroscience Carol Davila University of Medicine and Pharmacy King's College Hospital London UK Institute of Human Genetics University of Leipzig Hospitals and Clinics Leipzig GermanyDepartment of Evolutionary Genetics Max Planck Institute for Evolutionary Anthropology

Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells(CGCs) and on their response to oxygen-glucose deprivation(OGD). Primary CGC cultures were exposed to ethanol(100 mM in culture medium) or to control ethanol-free medium starting day one in vitro(DIV1). At DIV8, the expression of ATP synthase gene ATP5 g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5 g3 expression was reduced by 12-fold(P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values(P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values(P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.

关键词： cell culture chronic ethanol exposure oxygen-glucose deprivation cerebellar granule cells toxicity gene expression cellular ATP cellular metabolism metabolic impairment cell death

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Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing:A cohort analysis

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World Journal of Gastroenterology 2023年第18期29卷 2864-2874页

作者： Stefania Bunduc Bianca Varzaru Razvan Andrei Iacob Andrei Sorop Ioana Manea Andreea Spiridon Raluca Chelaru Adina Emilia Croitoru Gabriel Becheanu Mona Dumbrava Simona Dima Irinel Popescu Cristian Gheorghe Faculty of medicine Carol Davila University of Medicine and PharmacyBucharest 020021Romania Digestive Diseases and Liver Transplantation Center Fundeni Clinical InstituteBucharest 022328Romania Center of Excellence in Translational medicine Fundeni Clinical InstituteBucharest 022328Romania

BACKGROUND Genetic tests are increasingly performed for the management of unresectable pancreatic *** genotyping aimed samples current guidelines recommend using core specimens,although based on moderate quality ***,in clinical practice among the endoscopic ultrasound(EUS) guided tissue acquisition methods,fine needle aspiration(FNA) is the most widely *** To assess the adequacy for next generation sequencing(NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma(PDAC) *** Between November 2018 and December 2021,105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology *** 22 gauge(G) or 19G FNA needles were *** pass was dedicated to DNA *** concentration and purity(A260/280,A260/230) were assessed by *** assessed the differences in DNA parameters according to needle size and tumor characteristics(size,location) and the adequacy of the extracted DNA for NGS(defined as A260/280 ≥ 1.7,and DNA yield:≥ 10 ng for amplicon based NGS,≥ 50 ng for whole exome sequencing [WES],≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and ttest ***,we compared DNA purity parameters across the different DNA yield *** Our cohort included 49% male patients,aged 67.02 ± 8.38 *** 22G needle was used in 71%of the *** DNA parameters across our samples varied as follows:DNA yield:1289 ng(inter quartile range:534.75-3101),A260/280 = 1.85(1.79-1.86),A260/230 = 2.2(1.72-2.36).DNA yield was > 10 ng in all samples and > 100 ng in 93% of them(one sample < 50 ng).There were no significant differences in the concentration and A260/280 between samples by needle *** size was the only independent predictor of A260/230 which was higher in the 22G samples(P =0.038).NGS adequacy rate was 90% for 19G samples regardless of NGS type,and for 22G samples it reached 89% for WGS adequacy and 91% for WES and

关键词： Pancreatic adenocarcinoma Endoscopic ultrasound guided fine needle aspiration Next generation sequencing DNA yield Needle size Genetic testing

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New Clues that May Link Osteoporosis to the Circulating Lipid Profile

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Bone Research 2013年第3期1卷 260-266页

作者： Catalina Poiana Valentin Radoi Mara Carsote John P. Bilezikian "C. I. Parhon" National Institute of Endocrinology Bucharest Bucharest Romania university of medicine and pharmacy"carol davila" Bucharest Bucharest Romania College of Physicians and Surgeons Columbia UniversityNew York NY USA

Bone Mineral Density （BMD） is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination： 610 women with osteo- porosis （mean lumbar spine T-score -3.16±0.81, mean yrs. since menopause 15.79±8.9） were grouped according to age at evaluation （〈 50 years, 51-60 years, 61-70 years, 〉 70 years）, the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index （BMI： P〉0.05, r2〈0.02）. However, when BMD was correlated with both BMI and the lipid profile （Triglycerides, Cholesterol, LDLc, HDLc）, significant correlations were found in 5 cohorts： 51-60 years with fractures （n=61, r2=0.14, P〈0.01）, 61-70 years （n=201, r2=0.09, P〈0.01） with fractures （n=88, r2=0.14, P〈0.01） or without fractures （n=113, r2=0.24, P=0.02） and over 70 years （n=247, r2=0.11, P〈0.01）.

关键词： osteoporosis bone mineral density lipid cholesterol triglycerides HDL-cholesterol

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