New avenues for the treatment of immunotherapy-resistant pancreatic cancer

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.

Personalized medicine:Clinical oncology on molecular view of treatment

Cancer,the second leading global cause of death,impacts both physically and emotionally.Conventional treatments such as surgeries,chemotherapy,and radiotherapy have adverse effects,driving the need for more precise approaches.Precision medicine enables more targeted treatments.Genetic mapping,alongside other molecular biology approaches,identifies specific genes,contributing to accurate prognoses.The review addresses,in clinical use,a molecular perspective on treatment.Biomarkers like alpha-fetoprotein,beta-human chorionic gonadotropin,5-hydroxyindoleacetic acid,programmed death-1,and cytotoxic T lymphocyte-associated protein 4 are explored,providing valuable information.Bioinformatics,with an emphasis on artificial intelligence,revolutionizes the analysis of biological data,offering more accurate diagnoses.Techniques like liquid biopsy are emphasized for early detection.Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor,as evidenced in the molecular subtypes of breast cancer.Classifications allow personalized treatments,highlighting the role of trastuzumab and endocrine therapies.Despite the benefits,challenges persist,including high costs,tumor heterogeneity,and ethical issues.Overcoming obstacles requires collaboration,ensuring that advances in molecular biology translate into accessible benefits for all.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

BACKGROUND Helicobacter pylori(H.pylori)infection has been well-established as a significant risk factor for several gastrointestinal disorders.The urea breath test(UBT)has emerged as a leading non-invasive method for detecting H.pylori.Despite numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent limitations.These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H.pylori infection.AIM To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H.pylori infection in adult patients with dyspepsia.METHODS We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April 2022.Our search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference standard.We used the QUADAS-2 tool to assess the methodo-logical quality of the studies.We utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence intervals.We conducted subgroup analyses based on urea dosing,time after urea administration,and assessment technique.To investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess heterogeneity.Finally,we visually inspected a funnel plot and used Egger’s test to evaluate publication bias.endorsing both as reliable diagnostic tools in clinical practice.CONCLUSION In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic approach.Additionally,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enhance diagnostic precision.Nevertheless,it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.

Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori

BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phenolic compounds.The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality(C-score=0.09)and was validated using parameters from the MolProbity platform.The GRaSP online platform identified 24 residues(phenylalanine and leucine)as potential binding sites on the CagA oncoprotein.Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein.No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds;however,all phenolic compounds interacted with the central region of the oncoprotein.Phenolic compounds and CagA exhibited significant affinity energy(-7.9 to-9.1 kcal/mol):CagA/kaempferol formed 28 chemical bonds,CagA/myricetin formed 18 chemical bonds,CagA/quercetin formed 16 chemical bonds,CagA/ponciretin formed 13 chemical bonds,and CagA/chlorogenic acid formed 17 chemical bonds.Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif,all of them bound to residues,mostly positively or negatively charged,located near this region.CONCLUSION In silico,the tested phenolic compounds formed stable complexes with CagA.Therefore,they could be tested in vitro and/or in vivo to validate the findings,and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

Long chikungunya?An overview to immunopathology of persistent arthralgia

Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses.Generally,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and extent.Around 40%to 60%of affected individuals report persistent arthralgia,which can last from months to years.The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system.The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone resorption.This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines.The term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P<0.01 and I²>50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-positive early-stage GML after bacterial eradication was 75.18%(95%CI:70.45%-79.91%).P-MA indicated the substantial heterogeneity in CR reported across studies(I2=92%;P<0.01).Meta-regression analysis identified statistically significant effect modifiers,including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.CONCLUSION Comprehensive synthesis of available evidence suggests that H.pylori eradication is effective as the sole initial therapy for early-stage GML.Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR,the present study is a relevant to informing clinical practice.

Immunotherapy in glioblastoma treatment:Current state and future prospects

Glioblastoma remains as the most common and aggressive malignant brain tumor,standing with a poor prognosis and treatment prospective.Despite the aggressive standard care,such as surgical resection and chemoradiation,median survival rates are low.In this regard,immunotherapeutic strategies aim to become more attractive for glioblastoma,considering its recent advances and approaches.In this review,we provide an overview of the current status and progress in immunotherapy for glioblastoma,going through the fundamental knowledge on immune targeting to promising strategies,such as Chimeric antigen receptor T-Cell therapy,immune checkpoint inhibitors,cytokine-based treatment,oncolytic virus and vaccine-based techniques.At last,it is discussed innovative methods to overcome diverse challenges,and future perspectives in this area.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection

Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Epidemiological and clinical characteristics of COVID-19 in a Brazilian public hospital

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has become a major health concern worldwide.In that context,the understanding of epidemiological and clinical features associated with the disease and its severity is crucial for the establishment of strategies aimed at disease control and remedy.AIM To describe epidemiological features,signs,symptoms,and laboratory findings among severely ill COVID-19 patients from an inten-sive care unit in northeastern Brazil as well as to evaluate predictor factors for disease outcomes.METHODS This is a prospective single-center study that evaluated 115 patients admitted to the intensive care unit in a northeastern Brazilian hospital.RESULTS The patients had a median age of 65.60±15.78 years.Dyspnea was the most frequent symptom,affecting 73.9%of the patients,followed by cough(54.7%).Fever was reported in approximately one-third of patients and myalgia in 20.8%of the patients.At least two comorbidities were found in 41.7%of the patients,and hypertension was the most prevalent(57.3%).In addition,having two or more comorbidities was a predictor of mortality,and lower platelet count was positively associated with death.Nausea and vomiting were two symptoms that were predictors of death,and the presence of a cough was a protective factor.CONCLUSION This is the first report of a negative correlation between cough and death in severely ill severe acute respiratory syndrome coronavirus 2-infected individuals.The associations between comorbidities,advanced age,and low platelet count and the outcomes of the infection were similar to the results of previous studies,highlighting the relevance of these features.

Crohn's disease and clinical management today:How it does?

Crohn’s Disease(CD)is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature.Its etiology results from the interaction between genetic,enviromental and microbial factors.Regarding pathophysiology,it involves high levels of interleukin(IL)-12,IL-17,and Th1 profile,along with loss of tolerance mechanisms,an increase in pro-inflammatory interleukins,beyond the possibility to affect any part of the gastrointestinal tract.Its symptoms include abdominal pain,chronic diarrhea,weight loss,anorexia,and fatigue,as well as blood in the stool or rectum.Additionally,conditions comprising musculoskeletal,cutaneous,ocular,hepatic,and hematological alterations may be associated with this scenario and extra-intestinal presentation,such as erythema nodosum,anterior uveitis,osteoporosis,and arthritis can also occur.Today,clinical history,exams as fecal calprotectin,ileocolonocopy,and capsule endoscopy can be performed in the diagnosis investigation,along with treatments to induce and maintain remission.In this sense,anti-inflammatory drugs,such as corticosteroids,immunomodulators,and biological agents,as well as surgery and non-pharmacological interventions plays a role in its therapy.The aim of this review is to bring more current evidence to clinical management of CD,as well as to briefly discuss aspects of its pathophysiology,surveillance,and associated disorders.

Haploidentical hematopoietic stem cell transplantation as promising therapy in the improved survival of pediatric patients with leukemias and myelodysplasias

BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.

Pediatric multisystem inflammatory syndrome associated with COVID-19: Insights in pathogenesis and clinical management

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been a major challenge to be faced in recent years.While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019,children were thought to be exclusively asymptomatic or to present with mild conditions.However,around April 2020,there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children-multisystemic inflam-matory syndrome in children(MIS-C)-which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan involvement.The Centers for Disease Control and Prevention considers a suspected case of MIS-C an individual aged<21 years presenting with fever,high inflammatory markers levels,and evidence of clinically severe illness,with multisystem(>2)organ involvement,no alternative plausible diagnoses,and positive for recent SARS-CoV-2 infection.Despite its severity,there are no definitive disease management guidelines for this condition.Conversely,the complex pathogenesis of MIS-C is still not completely understood,although it seems to rely upon immune dysregu-lation.Hence,in this study,we aim to bring together current evidence regarding the pathogenic mechanisms of MIS-C,clinical picture and management,in order to provide insights for clinical practice and implications for future research directions.

Helicobacter pylori infection in pregnant women:Gastrointestinal symptoms and pregnancy-related disorders

Helicobacter pylori(H.Pylori)is a gram-negative,flagellated and spiral-shaped bacterial pathogen that impacts approximately 46%among pregnant women globally and has been associated with various maternal-fetal complications.Iron deficiency anemia,fetal growth restriction,cardiovascular diseases,and insufficient nutrient absorption can be observed in pregnant women,as well as miscarriages and pregnancy-specific hypertensive disease,such as pre-eclampsia.Thus,the evidence supports the influence of H.pylori infection on fetal implantation/placentation failure,and positive strains of the cytotoxin-associated gene A of H.Pylori were reported as the most prevalent in these conditions.However,current knowledge indicates a relationship between this infection and the occurrence of hyperemesis gravidarum,characterized by frequent nausea and vomiting.Regarding the diagnosis of this bacterial infection,non-invasive approaches such as stool antigen test,urea breath test,and serological tests are more accepted during pregnancy,as they are easy to carry out and cost-effective.Finally,the bacteria eradication therapy should consider the risks and benefits for the pregnant woman and her child,with pharmacological intervention depending on the clinical presentation.

In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment

BACKGROUND Coronavirus disease 2019(COVID-19)has demonstrated several clinical manifestations which include not only respiratory system issues but also liver,kidney,and other organ injuries.One of these abnormalities is coagulopathies,including thrombosis and disseminated intravascular coagulation.Because of this,the administration of low molecular weight heparin is required for patients that need to be hospitalized.In addition,Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome,Ebola,Acute Respiratory Syndrome,and other diseases,showing satisfactory results on recovery.Besides,there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19.AIM To investigate in silico the interaction between Remdesivir and clotting factors,pursuing a possibility of using it as medicine.METHODS In this in silico study,the 3D structures of angiotensin-converting enzyme 2(ACE2),Factor I(fibrinogen),Factor II(prothrombin),Factor III(thromboplastin),Factor V(proaccelerin),Factor VII(proconvertin),Factor VIII(antihemophilic factor A),Factor IX(antihemophilic factor B),Factor X(Stuart-Prower factor),and Factor XI(precursor of thromboplastin(these structures are technically called receptors)were selected from the Protein Data Bank.The structures of the antivirals Remdesivir and Osetalmivir(these structures are called ligands)were selected from the PubChem database,while the structure of Atazanavir was selected from the ZINC database.The software AutoDock Tools(ADT)was used to prepare the receptors for molecular docking.Ions,peptides,water molecules,and other ones were removed from each ligand,and then,hydrogen atoms were added to the structures.The grid box was delimited and calculated using the same software ADT.A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors,and still the software Marvin sketch®(ChemAxon®)was used to forecast the protonation state.To perform molecular docking,ADT and Vina software was connected.Using PyMol®software and Discovery studio®software from BIOVIA,it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands.Ligand tortions,atoms that participated in the interactions,and the type,strength,and duration of the interactions were also analyzed using those software.RESULTS Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of-8.8 kcal/moL,forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2.Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor.Similar to that,Remdesivir and thromboplastin presented interactions via seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor.While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor,and Factor VII connected with the drug by four hydrogen bonds,which involved three atoms of the drug and three residues of amino acids of the factor.The complex between Remdesivir and Factor IX formed an interaction via 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor,plus one electrostatic bond and three hydrophobic interactions.Factor X and Remdesivir had an affinity energy of-9.6 kcal/moL,and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor.The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms.CONCLUSION Because of the in silico significant affinity,Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.

Correction to“Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil”

Correction to“Freire de Melo F,Martins Oliveira Diniz L,Nélio Januário J,Fernando Gonçalves Ferreira J,Dórea RSDM,de Brito BB,Marques HS,Lemos FFB,Silva Luz M,Rocha Pinheiro SL,de Magalhães Queiroz DM.Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil.World J Exp Med 2022;12(5):100-103[PMID:36196438 DOI:10.5493/wjem.v12.i5.100]”.In this article,we identified an issue with the“Acknowledgments”section.Here,we then provide a recognition section for our supporting institutions.

Pathogenesis and clinical management of Helicobacter pylori gastric infection

Helicobacter pylori(H.pylori)is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide.However,its prevalence varies among different geographic areas,and is influenced by several factors.The infection can be acquired by means of oral-oral or fecal-oral transmission,and the pathogen possesses various mechanisms that improve its capacity of mobility,adherence and manipulation of the gastric microenvironment,making possible the colonization of an organ with a highly acidic lumen.In addition,H.pylori presents a large variety of virulence factors that improve its pathogenicity,of which we highlight cytotoxin associated antigen A,vacuolating cytotoxin,duodenal ulcer promoting gene A protein,outer inflammatory protein and gamma-glutamyl transpeptidase.The host immune system,mainly by means of a Th1-polarized response,also plays a crucial role in the infection course.Although most H.pylori-positive individuals remain asymptomatic,the infection predisposes the development of various clinical conditions as peptic ulcers,gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas.Invasive and non-invasive diagnostic methods,each of them with their related advantages and limitations,have been applied in H.pylori detection.Moreover,bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection,and new therapy alternatives are being tested to improve H.pylori eradication.Last but not least,the development of effective vaccines against H.pylori infection have been the aim of several research studies.

Helicobacter pylori infection: Beyond gastric manifestations

Helicobacter pylori(H.pylori)is a bacterium that infects more than a half of world’s population.Although it is mainly related to the development of gastroduodenal diseases,several studies have shown that such infection may also influence the development and severity of various extragastric diseases.According to the current evidence,whereas this bacterium is a risk factor for some of these manifestations,it might play a protective role in other pathological conditions.In that context,when considered the gastrointestinal tract,H.pylori positivity have been related to Inflammatory Bowel Disease,Gastroesophageal Reflux Disease,Non-Alcoholic Fatty Liver Disease,Hepatic Carcinoma,Cholelithiasis,and Cholecystitis.Moreover,lower serum levels of iron and vitamin B12 have been found in patients with H.pylori infection,leading to the emergence of anemias in a portion of them.With regards to neurological manifestations,a growing number of studies have associated that bacterium with multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,and Guillain-Barrésyndrome.Interestingly,the risk of developing cardiovascular disorders,such as atherosclerosis,is also influenced by the infection.Besides that,the H.pylori-associated inflammation may also lead to increased insulin resistance,leading to a higher risk of diabetes mellitus among infected individuals.Finally,the occurrence of dermatological and ophthalmic disorders have also been related to that microorganism.In this sense,this minireview aims to gather the main studies associating H.pylori infection with extragastric conditions,and also to explore the main mechanisms that may explain the role of H.pylori in those diseases.