ROSE is a method for fast sample evaluation that does not compromise sensitivity and specificity in the hospital environment when establishing the diagnosis and the therapeutic protocol. The technique is already well-...ROSE is a method for fast sample evaluation that does not compromise sensitivity and specificity in the hospital environment when establishing the diagnosis and the therapeutic protocol. The technique is already well-established in human medicine as it operates within the standard operational procedure, reducing the rates of inconclusive results and cancelled cytopathology assays in the hospital environment. However, its application is scarce in Veterinary Medicine, including in hospitals where intensive care is available. This study aims at conducting a case-by-case assessment of inconclusive and cancelled examinations in the Cytopathology Outpatient Clinic at UNESP (HV), Botucatu, Brazil, from 2012 to 2016 and ascertains the causes. For this purpose, a retrospective study was conducted for 9587 examinations in canines, of which 4.1% and 10.44% were inconclusive and cancelled, respectively. These results are not in line with ROSE, which foresees a total rate of 5% for these occurrences. The reasons for these high rates in the outpatient clinic were the lack of a Standard Operating Procedure (SOP) and the relative inexperience of the residents in a university hospital. Therefore, with the adoption of the ROSE protocol for veterinary cytopathological examinations, together with adequate training for the outpatient professionals responsible for the examinations, the goals set forth by the ROSE protocol would be met and the rates of inconclusive and cancelled examinations would decrease considerably. Lastly, this study hopes to contribute towards the diagnosis and therapeutic protocols of the main diseases affecting dogs.展开更多
Here we compare the efficacy of anti-obesity drugs alone or combined with exercise training on body weight and exercise capacity of obese patients.Randomized clinical trials that assessed the impact of any anti-obesit...Here we compare the efficacy of anti-obesity drugs alone or combined with exercise training on body weight and exercise capacity of obese patients.Randomized clinical trials that assessed the impact of any anti-obesity drug alone or combined with exercise training on body weight,body fat,fat-free mass and cardiorespiratory fitness in obese patients were retrieved from Pubmed and EMBASE up to May 2024.Risk of bias assessment was performed with RoB 2.0,and the GRADE approach assessed the certainty of evidence(CoE)of each main outcome.We included four publications summing up 202 patients.Two publications used orlistat as an anti-obesity drug treatment,while the other two adopted GLP-1 receptor agonist(liraglutide or tirzepatide)as a pharmacotherapy for weight management.Orlistat combined with exercise was superior to change body weight(mean difference(MD):−2.27 kg;95%CI:−2.86 to−1.69;CoE:very low),fat mass(MD:−2.89;95%CI:−3.87 to−1.91;CoE:very low),fat-free mass(MD:0.56;95%CI:0.40–0.72;CoE:very low),and VO_(2)Peak(MD:2.64;95%CI:2.52–2.76;CoE:very low).GLP-1 receptor agonist drugs combined with exercise had a great effect on body weight(MD:−3.96 kg;95%CI:−5.07 to−2.85;CoE:low),fat mass(MD:−1.76;95%CI:−2.24 to−1.27;CoE:low),fat-free mass(MD:0.50;95%CI:−0.98 to 1.98;CoE:very low)and VO_(2)Peak(MD:2.47;95%CI:1.31–3.63;CoE:very low).The results reported here suggest that exercise training remains an important approach in weight management when combined with pharmacological treatment.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory bowel disease treated with immunosuppressants to control inflammation.Drugs like azathioprine(AZA)and anti-tumor necrosis factor agents increase the risk of e...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory bowel disease treated with immunosuppressants to control inflammation.Drugs like azathioprine(AZA)and anti-tumor necrosis factor agents increase the risk of extraintestinal malignancies.However,no association has been established between these therapies and endometrial stromal sarcoma.This report presents a rare case of endometrial stromal sarcoma in a patient with UC undergoing immunosuppressive treatment and includes a literature review to explore any possible correlation between the disease,the therapies used,and the development of this rare tumor.CASE SUMMARY Female,49 years old,with UC pancolitis extension since 2017.She used aminosalicylates and AZA with non-response.She started infliximab and AZA combination therapy in 2020,with optimization in 2021 due to endoscopic activity.In the same year,the patient presented to the emergency room with ascitis and underwent diagnostic paracentesis,which showed serum-ascites albumin gradient<1.1 g/dL,absence of neoplastic cells,and abdominal and pelvic tomography reported a hypoechoic nodular lesion in the posterior wall of the uterus and elevated carbohydrate antigen 125.Given the suspicion of neoplasia,the suspension of immunosuppressive therapy was indicated.The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy,and the pathological result reported low-grade endometrial sarcoma.It was decided to introduce vedolizumab for the management of UC;however,even after induction therapy,intense clinical and endoscopic disease activity was maintained,with total proctocolectomy being indicated due to clinical refractoriness and a history of neoplasia.CONCLUSION Patients with inflammatory bowel disease have a higher risk of cancer due to inflammation or treatment.Proper screening with multidisciplinary care can improve outcomes.展开更多
Adult Still's Disease(ASD)is a systemic inflammatory disorder of unknown etiology,thought to be triggered by infectious agents in genetically susceptible individuals,resulting in aberrant cytokine production inclu...Adult Still's Disease(ASD)is a systemic inflammatory disorder of unknown etiology,thought to be triggered by infectious agents in genetically susceptible individuals,resulting in aberrant cytokine production including interleukin(IL)−1,IL-6,AND IL-18.The disease severity varies and may include macrophage activation syndrome(mas),a potentially life-threatening complication.It is associated with seronegative chronic polyarthritis,predominantly affecting young individuals.It is a rare condition with a complex diagnosis due to its overlapping clinical features with more common diseases.展开更多
Peripheral nerve injuries are clinical conditions that often result in functional deficits,compromising patient quality of life.Given the relevance of these injuries,new treatment strategies are constantly being inves...Peripheral nerve injuries are clinical conditions that often result in functional deficits,compromising patient quality of life.Given the relevance of these injuries,new treatment strategies are constantly being investigated.Although mesenchymal stem cells already demonstrate therapeutic potential due to their paracrine action,the transdifferentiation of these cells into Schwann-like cells(SLCs)represents a significant advancement in nerve injury therapy.Recent studies indicate that SLCs can mimic the functions of Schwann cells,with promising results in animal models.However,challenges remain,such as the diversity of transdifferentiation protocols and the scalability of these therapies for clinical applications.A recent study by Zou et al provided a comprehensive overview of the role of bone marrow-derived mesenchymal stem cells in the treatment of peripheral nerve injuries.Therefore,we would like to discuss and explore the use of SLCs derived from bone marrow-derived mesenchymal stem cells in more detail as a promising alternative in the field of nerve regeneration.展开更多
This study investigated forest recovery in the Atlantic Rainforest and Rupestrian Grassland of Brazil using the diffusive-logistic growth(DLG)model.This model simulates vegetation growth in the two mountain biomes con...This study investigated forest recovery in the Atlantic Rainforest and Rupestrian Grassland of Brazil using the diffusive-logistic growth(DLG)model.This model simulates vegetation growth in the two mountain biomes considering spatial location,time,and two key parameters:diffusion rate and growth rate.A Bayesian framework is employed to analyze the model's parameters and assess prediction uncertainties.Satellite imagery from 1992 and 2022 was used for model calibration and validation.By solving the DLG model using the finite difference method,we predicted a 6.6%–51.1%increase in vegetation density for the Atlantic Rainforest and a 5.3%–99.9%increase for the Rupestrian Grassland over 30 years,with the latter showing slower recovery but achieving a better model fit(lower RMSE)compared to the Atlantic Rainforest.The Bayesian approach revealed well-defined parameter distributions and lower parameter values for the Rupestrian Grassland,supporting the slower recovery prediction.Importantly,the model achieved good agreement with observed vegetation patterns in unseen validation data for both biomes.While there were minor spatial variations in accuracy,the overall distributions of predicted and observed vegetation density were comparable.Furthermore,this study highlights the importance of considering uncertainty in model predictions.Bayesian inference allowed us to quantify this uncertainty,demonstrating that the model's performance can vary across locations.Our approach provides valuable insights into forest regeneration process uncertainties,enabling comparisons of modeled scenarios at different recovery stages for better decision-making in these critical mountain biomes.展开更多
Shrimps of the genus Synalpheus(Caridea)are commonly found in subtropical and tropical marine habitats around the world.The present work aims to provide the first description of the reproductive system of this genus u...Shrimps of the genus Synalpheus(Caridea)are commonly found in subtropical and tropical marine habitats around the world.The present work aims to provide the first description of the reproductive system of this genus using histological,histochemical,and morphological perspectives to elucidate the gonochoric or hermaphrodite sexual system in this genus.Males have a slender and very translucent reproductive system that is challenging to observe.The entire cephalothorax was histologically sectioned to ensure that all regions of the reproductive system could be identified.This non-gambarelloides group shows a gonochoric condition.The caridean pattern of the reproductive system was observed where the male has a pair of testes and a pair of very thin vasa deferentia,ending at the opening of the gonopore.Spermatophore structure is absent,without any layers surrounding the spermatozoa that are aggregated in a sperm mass.In females,the reproductive system consists of a pair of ovaries that extend to the end of the pleon.The extension of the ovary has a particular pattern compared to other caridean shrimps.Here,we hypothesize that males invest energy on somatic morphological structures to protect the host and female,using the larger pistol-like cheliped,while females invest energy in reproduction since all the members of this group are typical"pair-bond"examples.The observed pattern of the reproductive male morphology could also be evidence of a possible synapomorphy for this genus within theinfraorder.展开更多
Roads are a leading cause of habitat fragmentation and may reduce bird populations by increasing nest predation rates.However,few studies have investigated the effects of traffic volume on the reproductive success of ...Roads are a leading cause of habitat fragmentation and may reduce bird populations by increasing nest predation rates.However,few studies have investigated the effects of traffic volume on the reproductive success of roadside birds in the neotropics.Our goal was to evaluate the effects of spatial,temporal,and vehicle flow variations on the survival of artificial open-cup nests.The study was carried out in a nature reserve on the side of a highway during the breeding season(from October to March)in two restinga(sand-coastal plain)phytophysiognomies in southeastern Brazil:non-floodable(open)and floodable(closed).One hundred thirty nests were distributed along transects ranging from 3 m to 300 m from the highway in each vegetation type(totaling 260 nests).The nests were checked every three days for their status(depredated or intact)over 12 days,and new nests were subsequently placed near sampling points of depredated or successful nests.We estimated survival using logistic exposure generalized linear and additive mixed models.At the end of the 180 days of the experiment,33%of 6202 nests were successful.Nest survival was higher in open restinga than in closed restinga.In both habitats,nest survival was lowest mid-season and highest at the beginning and end.Survival rates peaked near the highway,declined up to 50 m away,then showed a slight increase.Finally,survival increased at moderate-to-high traffic volumes(∼22,000 vehicles/day),particularly in open restinga.We suggest that spatial,temporal,and habitat-specific highway impacts(e.g.,noise,vibration,visual stimuli)can lead to variations in the activity of nest predators,generating fluctuations in nest survival associated with predator behavior.展开更多
Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,is a chronic condition marked by relapsing inflammation of the gastro-intestinal tract.Metabolic dysfunction-associated steatotic live...Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,is a chronic condition marked by relapsing inflammation of the gastro-intestinal tract.Metabolic dysfunction-associated steatotic liver disease(MASLD)emphasizes the interplay between metabolic alterations and modern lifestyle factors in its pathogenesis.Emerging evidence suggests that individuals with IBD are at increased risk for MASLD,driven by shared mechanisms,including gut dysbiosis,chronic systemic inflammation,and compromised intestinal barrier function.However,MASLD frequently remains underdiagnosed in this popu-lation.The gut microbiota plays a central role in modulating these interactions,influencing both intestinal permeability and metabolic regulation.Key patho-physiological mechanisms include alterations in short-chain fatty acid production,particularly reduced butyrate synthesis;disruption of bile acid signaling path-ways via farnesoid X receptor and Takeda G protein–coupled receptor 5 receptors;and activation of pro-inflam-matory cascades through toll-like receptor 4 in the liver.These events lead to increased intestinal permeability,translocation of microbial products,and amplification of hepatic inflammation.This review synthesizes current knowledge on the shared pathophysiological pathways linking IBD and MASLD–focusing on dysbiosis,barrier dysfunction,and inflammation–and underscores their clinical relevance.Understanding the gut–liver axis provides opportunities for early diagnosis and integrated management strategies,aiming to reduce disease burden and im-prove patient outcomes.展开更多
Objectives:As the Duchenne Muscular Dystrophy(DMD)is a progressive neuromuscular disorder frequently associated with cardiac dysfunction,this study aimed to evaluate the influence of beta-blocker therapy on cardiac au...Objectives:As the Duchenne Muscular Dystrophy(DMD)is a progressive neuromuscular disorder frequently associated with cardiac dysfunction,this study aimed to evaluate the influence of beta-blocker therapy on cardiac autonomic modulation in adolescents withDMDby analyzing heart rate variability(HRV)indices in patients with and without betablockers.Methods:A cross-sectional study was conducted with 90 participants divided into three groups:(1)participants with DMD receiving beta-blocker therapy(DMDB,n=30),(2)participants with DMD without beta-blocker therapy(GMDM,n=30),and(3)age-and sex-matched typically developing participants(GDT,n=30).HRV was assessed using validated beat-to-beat heart rate monitoring(RS800CX,Polar)under controlled conditions.Linear and non-linear HRV indices(including Detrended Fluctuation Analysis and Symbolic Dynamics)were analysed using Kubios HRV software.Results:DMD patients exhibited autonomic impairment,characterized by decreased HRV,increased sympathetic dominance,and reduced parasympathetic modulation.Betablocker therapy was associated with significantly higher Mean Beat-to-beat interval(RR)and lower Mean Heart Rate(HR)compared to the non-beta-blocker DMD group,with values approaching those observed in typically developing participants.Non-linear indices suggested thatDMDpatients receiving beta-blockers demonstrated increased HRV complexity and fractal properties compared to those not receiving beta-blockers,although differences remained between the DMD and control groups.Conclusions:Autonomic dysfunction in DMD is characterized by reduced HRV and altered sympathovagal balance.In our results,beta-blocker therapy was associated with improved HRV and enhanced autonomic control.These findings highlight the potential cardioprotective role of betablockers in DMD management and emphasize the need for further research into optimizing autonomic function in DMD.展开更多
The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the host.Dysbiosis,characterized by an imbalance between the beneficial and opportunisti...The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the host.Dysbiosis,characterized by an imbalance between the beneficial and opportunistic gut microbiota,is associated with several gastrointestinal disorders,such as irritable bowel syndrome(IBS);inflammatory bowel disease(IBD),represented by ulcerative colitis and Crohn’s disease;and colorectal cancer(CRC).Dysbiosis can disrupt the mucosal barrier,resulting in perpetuation of inflammation and carcinogenesis.The increase in some specific groups of harmful bacteria,such as Escherichia coli(E.coli)and enterotoxigenic Bacteroides fragilis(ETBF),has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators,increasing the chance of developing CRC,following the inflammationdysplasia-cancer sequence in IBD patients.Therefore,the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD,CRC,and IBD-associated CRC.Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals,with enrichment of Firmicute sand Bacteroidetes.Specific bacteria are also associated with the onset and progression of CRC,such as Fusobacterium nucleatum,E.coli,Enterococcus faecalis,Streptococcus gallolyticus,and ETBF.Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients,directly affecting the prognosis of the disease and the quality of life of patients.展开更多
Hepatic encephalopathy(HE)is a cognitive disturbance characterized by neuropsychiatric alterations.It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts.The presence of these po...Hepatic encephalopathy(HE)is a cognitive disturbance characterized by neuropsychiatric alterations.It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts.The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration.Therefore,the embolization of these shunts has been performed tocontrol HE manifestations,but the presence of portal vein thrombosis is considered a contraindication.In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt.Case report:a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma,even without precipitant factors.She had a wide portosystemic shunt and also portal vein thrombosis.The abdominal angiography confirmed the splenorenal shunt and showed other shunts.The larger shunt was embolized through placement of microcoils,and the patient had no recurrence of overt HE.There was a little increase of esophageal and gastric varices,but no endoscopic treatment was needed.Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients,portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization.However,in particular cases with many shunts and severe HE,we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery.In conclusion,we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis.As the patient had other shunts,she was successfully treated by embolization of the larger shunt.展开更多
BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellu...BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene expression.AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its relationship.METHODS Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.展开更多
Peritonitis continues to be a major complication of peritoneal dialysis （PD）, and adequate treatment is crucial for a favorable outcome. There is no consensus regarding the optimal therapeutic regimen, and few prosp...Peritonitis continues to be a major complication of peritoneal dialysis （PD）, and adequate treatment is crucial for a favorable outcome. There is no consensus regarding the optimal therapeutic regimen, and few prospective controlled studies have been published. The objectiveof this manuscript is to review the results of PD peritonitis treatment reported in narrative reviews, systematic reviews, and proportional meta-analyses. Two narrative reviews, the only existing systematic review and its update published between 1991 and 2014 were included. In addition, we reported the results of a proportional meta-analysis published by our group. Results from systematic reviews of randomized control trials （RCT） and quasi-RCT were not able to identify any optimal antimicrobial treatment, but glycopeptide regimens were more likely to achieve a complete cure than a first generationcephalosporin. Compared to urokinase, simultaneous catheter removal and replacement resulted in better outcomes. Continuous and intermittent IP antibiotic use had similar outcomes. Intraperitoneal antibiotics were superior to intravenous antibiotics in reducing treatment failure. In the proportional meta-analysis of RCTs and the case series, the resolution rate （86%） of ceftazidime plus glycopeptide as initial treatment was signifcantly higher than frst generation cephalosporin plus aminoglycosides （66%） and glycopeptides plus aminoglycosides （75%）. Other comparisons of regimens used for either initial treatment or treatment of gram-positive rods or gram-negative rods did not show statistically significant differences. The superiority of a combination of a glycopeptide and a third generation cephalosporin was also reported by a narrative review study published in 1991, which reported an 88% resolution rate.展开更多
BACKGROUND Inflammatory bowel disease(IBD)comprises two distinct diseases,Crohn’s disease(CD)and ulcerative colitis(UC),both of which are chronic,relapsing inflammatory disorders of the gastrointestinal tract with a ...BACKGROUND Inflammatory bowel disease(IBD)comprises two distinct diseases,Crohn’s disease(CD)and ulcerative colitis(UC),both of which are chronic,relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology.The incidence and prevalence of IBD are continually increasing,indicating the need for further studies to investigate the genetic determinants of these diseases.Since microRNAs(miRNAs)regulate protein translation via complementary binding to mRNA,discovering differentially expressed miRNAs(DE)in UC or CD patients could be important for diagnostic biomarker identification,assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis.AIM To determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA.METHODS A total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University(Unesp).The diagnosis of UC or CD was based on clinical,endoscopic,radiologic,and histological criteria and confirmed by histopathological analysis at the time of selection.The TaqMan™Array Human MicroRNA A+B Cards Set v3.0(Applied Biosystems™)platform was used to analyze 754 miRNAs.Targets of DE-miRNAs were predicted using miRNA Data Integration Portal(mirDIP)and the miRNA Target Interaction database(MiRTarBase).All statistical analyses were conducted using GraphPad Prism software.Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests,respectively.RESULTS The results showed that of the 754 miRNAs that were initially evaluated,643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC;the remaining 111 miRNAs were not considered to be expressed in these patients.The expression levels of 28 miRNAs were significantly different between the CD and UC patients(P≤0.05);13 miRNAs demonstrated a fold-change in expression level greater than 1.Five miRNAs with a downregulated expression were selected for enrichment analysis.The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers.CONCLUSION MiRNAs could be used to differentiate UC from CD,and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.展开更多
MicroRNAs(miRNAs)are non-coding RNA molecules composed of 19–25 nucleotides that regulate gene expression and play a central role in the regulation of several immune-mediated disorders,including inflammatory bowel di...MicroRNAs(miRNAs)are non-coding RNA molecules composed of 19–25 nucleotides that regulate gene expression and play a central role in the regulation of several immune-mediated disorders,including inflammatory bowel diseases(IBD).IBD,represented by ulcerative colitis and Crohn’s disease,is characterized by chronic intestinal inflammation associated with an increased risk of colorectal cancer(CRC).CRC is one of the most prevalent tumors in the world,and its main risk factors are obesity,physical inactivity,smoking,alcoholism,advanced age,and some eating habits,in addition to chronic intestinal inflammatory processes and the use of immunosuppressants administered to IBD patients.Recent studies have identified miRNAs associated with an increased risk of developing CRC in this population.The identification of miRNAs involved in this tumorigenic process could be useful to stratify cancer risk development for patients with IBD and to monitor and assess prognosis.Thus,the present review aimed to summarize the role of miRNAs as biomarkers for the diagnosis and prognosis of IBD-associated CRC.In the future,therapies based on miRNA modulation could be used both in clinical practice to achieve remission of the disease and restore the quality of life for patients with IBD,and to identify the patients with IBD at high risk for tumor development.展开更多
AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP)leaves on gastric ulcer healing.METHODS In this rat study involving males,intact(cycling)females,and ovariectomized fe...AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP)leaves on gastric ulcer healing.METHODS In this rat study involving males,intact(cycling)females,and ovariectomized females,gastric ulcers were induced using acetic acid.A vehicle,lansoprazole,or HEEP was administered for 14 d after ulcer induction.Body weight was monitored throughout the treatment period.At the end of treatment,the rats were euthanized and the following in vivo and in vitro investigations were performed:macroscopic examination of the lesion area and organ weights,biochemical analysis,zymography,and evaluation of protein expression levels.Additionally,the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle,HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%),intact females(85.22%),and ovariectomized females(65.47%),confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones.The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats.Overall,the beneficial effect of HEEP was the highest in intact females.Notably,HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females)and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female).Additionally,HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro,confirming its healing effect.Finally,no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers,HEEP-induced healing(modulated by female sex hormones;in males,mediated by prostaglandin)involves extracellular matrix remodeling,with gastric mucosa cell proliferation and migration.展开更多
AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cy...AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.展开更多
文摘ROSE is a method for fast sample evaluation that does not compromise sensitivity and specificity in the hospital environment when establishing the diagnosis and the therapeutic protocol. The technique is already well-established in human medicine as it operates within the standard operational procedure, reducing the rates of inconclusive results and cancelled cytopathology assays in the hospital environment. However, its application is scarce in Veterinary Medicine, including in hospitals where intensive care is available. This study aims at conducting a case-by-case assessment of inconclusive and cancelled examinations in the Cytopathology Outpatient Clinic at UNESP (HV), Botucatu, Brazil, from 2012 to 2016 and ascertains the causes. For this purpose, a retrospective study was conducted for 9587 examinations in canines, of which 4.1% and 10.44% were inconclusive and cancelled, respectively. These results are not in line with ROSE, which foresees a total rate of 5% for these occurrences. The reasons for these high rates in the outpatient clinic were the lack of a Standard Operating Procedure (SOP) and the relative inexperience of the residents in a university hospital. Therefore, with the adoption of the ROSE protocol for veterinary cytopathological examinations, together with adequate training for the outpatient professionals responsible for the examinations, the goals set forth by the ROSE protocol would be met and the rates of inconclusive and cancelled examinations would decrease considerably. Lastly, this study hopes to contribute towards the diagnosis and therapeutic protocols of the main diseases affecting dogs.
基金supported by Brazilian agencies CAPES(Finance Code 001)CNPq through PQ productivity scholarship.
文摘Here we compare the efficacy of anti-obesity drugs alone or combined with exercise training on body weight and exercise capacity of obese patients.Randomized clinical trials that assessed the impact of any anti-obesity drug alone or combined with exercise training on body weight,body fat,fat-free mass and cardiorespiratory fitness in obese patients were retrieved from Pubmed and EMBASE up to May 2024.Risk of bias assessment was performed with RoB 2.0,and the GRADE approach assessed the certainty of evidence(CoE)of each main outcome.We included four publications summing up 202 patients.Two publications used orlistat as an anti-obesity drug treatment,while the other two adopted GLP-1 receptor agonist(liraglutide or tirzepatide)as a pharmacotherapy for weight management.Orlistat combined with exercise was superior to change body weight(mean difference(MD):−2.27 kg;95%CI:−2.86 to−1.69;CoE:very low),fat mass(MD:−2.89;95%CI:−3.87 to−1.91;CoE:very low),fat-free mass(MD:0.56;95%CI:0.40–0.72;CoE:very low),and VO_(2)Peak(MD:2.64;95%CI:2.52–2.76;CoE:very low).GLP-1 receptor agonist drugs combined with exercise had a great effect on body weight(MD:−3.96 kg;95%CI:−5.07 to−2.85;CoE:low),fat mass(MD:−1.76;95%CI:−2.24 to−1.27;CoE:low),fat-free mass(MD:0.50;95%CI:−0.98 to 1.98;CoE:very low)and VO_(2)Peak(MD:2.47;95%CI:1.31–3.63;CoE:very low).The results reported here suggest that exercise training remains an important approach in weight management when combined with pharmacological treatment.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory bowel disease treated with immunosuppressants to control inflammation.Drugs like azathioprine(AZA)and anti-tumor necrosis factor agents increase the risk of extraintestinal malignancies.However,no association has been established between these therapies and endometrial stromal sarcoma.This report presents a rare case of endometrial stromal sarcoma in a patient with UC undergoing immunosuppressive treatment and includes a literature review to explore any possible correlation between the disease,the therapies used,and the development of this rare tumor.CASE SUMMARY Female,49 years old,with UC pancolitis extension since 2017.She used aminosalicylates and AZA with non-response.She started infliximab and AZA combination therapy in 2020,with optimization in 2021 due to endoscopic activity.In the same year,the patient presented to the emergency room with ascitis and underwent diagnostic paracentesis,which showed serum-ascites albumin gradient<1.1 g/dL,absence of neoplastic cells,and abdominal and pelvic tomography reported a hypoechoic nodular lesion in the posterior wall of the uterus and elevated carbohydrate antigen 125.Given the suspicion of neoplasia,the suspension of immunosuppressive therapy was indicated.The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy,and the pathological result reported low-grade endometrial sarcoma.It was decided to introduce vedolizumab for the management of UC;however,even after induction therapy,intense clinical and endoscopic disease activity was maintained,with total proctocolectomy being indicated due to clinical refractoriness and a history of neoplasia.CONCLUSION Patients with inflammatory bowel disease have a higher risk of cancer due to inflammation or treatment.Proper screening with multidisciplinary care can improve outcomes.
文摘Adult Still's Disease(ASD)is a systemic inflammatory disorder of unknown etiology,thought to be triggered by infectious agents in genetically susceptible individuals,resulting in aberrant cytokine production including interleukin(IL)−1,IL-6,AND IL-18.The disease severity varies and may include macrophage activation syndrome(mas),a potentially life-threatening complication.It is associated with seronegative chronic polyarthritis,predominantly affecting young individuals.It is a rare condition with a complex diagnosis due to its overlapping clinical features with more common diseases.
文摘Peripheral nerve injuries are clinical conditions that often result in functional deficits,compromising patient quality of life.Given the relevance of these injuries,new treatment strategies are constantly being investigated.Although mesenchymal stem cells already demonstrate therapeutic potential due to their paracrine action,the transdifferentiation of these cells into Schwann-like cells(SLCs)represents a significant advancement in nerve injury therapy.Recent studies indicate that SLCs can mimic the functions of Schwann cells,with promising results in animal models.However,challenges remain,such as the diversity of transdifferentiation protocols and the scalability of these therapies for clinical applications.A recent study by Zou et al provided a comprehensive overview of the role of bone marrow-derived mesenchymal stem cells in the treatment of peripheral nerve injuries.Therefore,we would like to discuss and explore the use of SLCs derived from bone marrow-derived mesenchymal stem cells in more detail as a promising alternative in the field of nerve regeneration.
基金financial support from the Brazilian National Council for Scientific and Technological Development(CNPq)and the Federal University of Ouro PretoFinancial support from the Minas Gerais Research Foundation(FAPEMIG)under grant number APQ-06559-24 is also gratefully acknowledged。
文摘This study investigated forest recovery in the Atlantic Rainforest and Rupestrian Grassland of Brazil using the diffusive-logistic growth(DLG)model.This model simulates vegetation growth in the two mountain biomes considering spatial location,time,and two key parameters:diffusion rate and growth rate.A Bayesian framework is employed to analyze the model's parameters and assess prediction uncertainties.Satellite imagery from 1992 and 2022 was used for model calibration and validation.By solving the DLG model using the finite difference method,we predicted a 6.6%–51.1%increase in vegetation density for the Atlantic Rainforest and a 5.3%–99.9%increase for the Rupestrian Grassland over 30 years,with the latter showing slower recovery but achieving a better model fit(lower RMSE)compared to the Atlantic Rainforest.The Bayesian approach revealed well-defined parameter distributions and lower parameter values for the Rupestrian Grassland,supporting the slower recovery prediction.Importantly,the model achieved good agreement with observed vegetation patterns in unseen validation data for both biomes.While there were minor spatial variations in accuracy,the overall distributions of predicted and observed vegetation density were comparable.Furthermore,this study highlights the importance of considering uncertainty in model predictions.Bayesian inference allowed us to quantify this uncertainty,demonstrating that the model's performance can vary across locations.Our approach provides valuable insights into forest regeneration process uncertainties,enabling comparisons of modeled scenarios at different recovery stages for better decision-making in these critical mountain biomes.
基金I.R.R.M.andA.L.C.were fundedby"Conselho Nacional de Desenvolvimento Cientifico e Tecnologico"(CNPQ grantPQ311034/2018-7)"Coordenacaode Aperfeicoamento deNivelSuperior-CAPES,Brazil(CAPES PRINT 88881.310767/2018-01,CAPES PROEX 23038.000802/2018-25)+2 种基金FJ.Z.would like to thank the laboratory support provided by the_Sao Paulo Research Foundation-FAPESP(JP#2005/04707-5 and Biota Intercrusta#2018/13685-5)CAPES-Ciencias do Mar II program(grant#1989/2014,23038.004309/2014-51)CNPq Research Scholarship(PQ2#309298-2020-2,PQ1D#308324/2023-4),and CNPq PPBio 2023/0723.
文摘Shrimps of the genus Synalpheus(Caridea)are commonly found in subtropical and tropical marine habitats around the world.The present work aims to provide the first description of the reproductive system of this genus using histological,histochemical,and morphological perspectives to elucidate the gonochoric or hermaphrodite sexual system in this genus.Males have a slender and very translucent reproductive system that is challenging to observe.The entire cephalothorax was histologically sectioned to ensure that all regions of the reproductive system could be identified.This non-gambarelloides group shows a gonochoric condition.The caridean pattern of the reproductive system was observed where the male has a pair of testes and a pair of very thin vasa deferentia,ending at the opening of the gonopore.Spermatophore structure is absent,without any layers surrounding the spermatozoa that are aggregated in a sperm mass.In females,the reproductive system consists of a pair of ovaries that extend to the end of the pleon.The extension of the ovary has a particular pattern compared to other caridean shrimps.Here,we hypothesize that males invest energy on somatic morphological structures to protect the host and female,using the larger pistol-like cheliped,while females invest energy in reproduction since all the members of this group are typical"pair-bond"examples.The observed pattern of the reproductive male morphology could also be evidence of a possible synapomorphy for this genus within theinfraorder.
基金supports were provided by the Concessionária Rodovia do Sol/SA(RodoSol)the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,grant:45.6446/2014/1)+2 种基金the São Paulo Research Foundation(FAPESP,Process Number#2024/13237-3)PD received a postdoctoral fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,grant:88887.469218/2019-00)CD is grateful to CNPq(Bolsa de Produtividade em Pesquisa,grant:308997/2023-9).
文摘Roads are a leading cause of habitat fragmentation and may reduce bird populations by increasing nest predation rates.However,few studies have investigated the effects of traffic volume on the reproductive success of roadside birds in the neotropics.Our goal was to evaluate the effects of spatial,temporal,and vehicle flow variations on the survival of artificial open-cup nests.The study was carried out in a nature reserve on the side of a highway during the breeding season(from October to March)in two restinga(sand-coastal plain)phytophysiognomies in southeastern Brazil:non-floodable(open)and floodable(closed).One hundred thirty nests were distributed along transects ranging from 3 m to 300 m from the highway in each vegetation type(totaling 260 nests).The nests were checked every three days for their status(depredated or intact)over 12 days,and new nests were subsequently placed near sampling points of depredated or successful nests.We estimated survival using logistic exposure generalized linear and additive mixed models.At the end of the 180 days of the experiment,33%of 6202 nests were successful.Nest survival was higher in open restinga than in closed restinga.In both habitats,nest survival was lowest mid-season and highest at the beginning and end.Survival rates peaked near the highway,declined up to 50 m away,then showed a slight increase.Finally,survival increased at moderate-to-high traffic volumes(∼22,000 vehicles/day),particularly in open restinga.We suggest that spatial,temporal,and habitat-specific highway impacts(e.g.,noise,vibration,visual stimuli)can lead to variations in the activity of nest predators,generating fluctuations in nest survival associated with predator behavior.
基金Supported by The São Paulo Research Foundation(FAPESP),Brazil,No.2022/15527-3The Postdoctoral Scholarship Grant from Medical School,São Paulo State University,No.PROPG/PROPE N°06/2024The Master Scholarship Grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil(CAPES)-Programa de Excelência Acadêmica(PROEX),No.88887.807663/2023-00.
文摘Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,is a chronic condition marked by relapsing inflammation of the gastro-intestinal tract.Metabolic dysfunction-associated steatotic liver disease(MASLD)emphasizes the interplay between metabolic alterations and modern lifestyle factors in its pathogenesis.Emerging evidence suggests that individuals with IBD are at increased risk for MASLD,driven by shared mechanisms,including gut dysbiosis,chronic systemic inflammation,and compromised intestinal barrier function.However,MASLD frequently remains underdiagnosed in this popu-lation.The gut microbiota plays a central role in modulating these interactions,influencing both intestinal permeability and metabolic regulation.Key patho-physiological mechanisms include alterations in short-chain fatty acid production,particularly reduced butyrate synthesis;disruption of bile acid signaling path-ways via farnesoid X receptor and Takeda G protein–coupled receptor 5 receptors;and activation of pro-inflam-matory cascades through toll-like receptor 4 in the liver.These events lead to increased intestinal permeability,translocation of microbial products,and amplification of hepatic inflammation.This review synthesizes current knowledge on the shared pathophysiological pathways linking IBD and MASLD–focusing on dysbiosis,barrier dysfunction,and inflammation–and underscores their clinical relevance.Understanding the gut–liver axis provides opportunities for early diagnosis and integrated management strategies,aiming to reduce disease burden and im-prove patient outcomes.
文摘Objectives:As the Duchenne Muscular Dystrophy(DMD)is a progressive neuromuscular disorder frequently associated with cardiac dysfunction,this study aimed to evaluate the influence of beta-blocker therapy on cardiac autonomic modulation in adolescents withDMDby analyzing heart rate variability(HRV)indices in patients with and without betablockers.Methods:A cross-sectional study was conducted with 90 participants divided into three groups:(1)participants with DMD receiving beta-blocker therapy(DMDB,n=30),(2)participants with DMD without beta-blocker therapy(GMDM,n=30),and(3)age-and sex-matched typically developing participants(GDT,n=30).HRV was assessed using validated beat-to-beat heart rate monitoring(RS800CX,Polar)under controlled conditions.Linear and non-linear HRV indices(including Detrended Fluctuation Analysis and Symbolic Dynamics)were analysed using Kubios HRV software.Results:DMD patients exhibited autonomic impairment,characterized by decreased HRV,increased sympathetic dominance,and reduced parasympathetic modulation.Betablocker therapy was associated with significantly higher Mean Beat-to-beat interval(RR)and lower Mean Heart Rate(HR)compared to the non-beta-blocker DMD group,with values approaching those observed in typically developing participants.Non-linear indices suggested thatDMDpatients receiving beta-blockers demonstrated increased HRV complexity and fractal properties compared to those not receiving beta-blockers,although differences remained between the DMD and control groups.Conclusions:Autonomic dysfunction in DMD is characterized by reduced HRV and altered sympathovagal balance.In our results,beta-blocker therapy was associated with improved HRV and enhanced autonomic control.These findings highlight the potential cardioprotective role of betablockers in DMD management and emphasize the need for further research into optimizing autonomic function in DMD.
文摘The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the host.Dysbiosis,characterized by an imbalance between the beneficial and opportunistic gut microbiota,is associated with several gastrointestinal disorders,such as irritable bowel syndrome(IBS);inflammatory bowel disease(IBD),represented by ulcerative colitis and Crohn’s disease;and colorectal cancer(CRC).Dysbiosis can disrupt the mucosal barrier,resulting in perpetuation of inflammation and carcinogenesis.The increase in some specific groups of harmful bacteria,such as Escherichia coli(E.coli)and enterotoxigenic Bacteroides fragilis(ETBF),has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators,increasing the chance of developing CRC,following the inflammationdysplasia-cancer sequence in IBD patients.Therefore,the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD,CRC,and IBD-associated CRC.Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals,with enrichment of Firmicute sand Bacteroidetes.Specific bacteria are also associated with the onset and progression of CRC,such as Fusobacterium nucleatum,E.coli,Enterococcus faecalis,Streptococcus gallolyticus,and ETBF.Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients,directly affecting the prognosis of the disease and the quality of life of patients.
文摘Hepatic encephalopathy(HE)is a cognitive disturbance characterized by neuropsychiatric alterations.It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts.The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration.Therefore,the embolization of these shunts has been performed tocontrol HE manifestations,but the presence of portal vein thrombosis is considered a contraindication.In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt.Case report:a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma,even without precipitant factors.She had a wide portosystemic shunt and also portal vein thrombosis.The abdominal angiography confirmed the splenorenal shunt and showed other shunts.The larger shunt was embolized through placement of microcoils,and the patient had no recurrence of overt HE.There was a little increase of esophageal and gastric varices,but no endoscopic treatment was needed.Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients,portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization.However,in particular cases with many shunts and severe HE,we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery.In conclusion,we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis.As the patient had other shunts,she was successfully treated by embolization of the larger shunt.
基金Sao Paulo Research Foundation-FAPESP,grants Nos.2015/21464-0 and 2015/23392-7National Counsel of Technological and Scientific Development-CNPq,grant No.310120/2015-2
文摘BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene expression.AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its relationship.METHODS Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.
文摘Peritonitis continues to be a major complication of peritoneal dialysis （PD）, and adequate treatment is crucial for a favorable outcome. There is no consensus regarding the optimal therapeutic regimen, and few prospective controlled studies have been published. The objectiveof this manuscript is to review the results of PD peritonitis treatment reported in narrative reviews, systematic reviews, and proportional meta-analyses. Two narrative reviews, the only existing systematic review and its update published between 1991 and 2014 were included. In addition, we reported the results of a proportional meta-analysis published by our group. Results from systematic reviews of randomized control trials （RCT） and quasi-RCT were not able to identify any optimal antimicrobial treatment, but glycopeptide regimens were more likely to achieve a complete cure than a first generationcephalosporin. Compared to urokinase, simultaneous catheter removal and replacement resulted in better outcomes. Continuous and intermittent IP antibiotic use had similar outcomes. Intraperitoneal antibiotics were superior to intravenous antibiotics in reducing treatment failure. In the proportional meta-analysis of RCTs and the case series, the resolution rate （86%） of ceftazidime plus glycopeptide as initial treatment was signifcantly higher than frst generation cephalosporin plus aminoglycosides （66%） and glycopeptides plus aminoglycosides （75%）. Other comparisons of regimens used for either initial treatment or treatment of gram-positive rods or gram-negative rods did not show statistically significant differences. The superiority of a combination of a glycopeptide and a third generation cephalosporin was also reported by a narrative review study published in 1991, which reported an 88% resolution rate.
基金São Paulo Research Foundation(FAPESP)grants,No.2017/03959-8 and No.2015/15267-8.
文摘BACKGROUND Inflammatory bowel disease(IBD)comprises two distinct diseases,Crohn’s disease(CD)and ulcerative colitis(UC),both of which are chronic,relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology.The incidence and prevalence of IBD are continually increasing,indicating the need for further studies to investigate the genetic determinants of these diseases.Since microRNAs(miRNAs)regulate protein translation via complementary binding to mRNA,discovering differentially expressed miRNAs(DE)in UC or CD patients could be important for diagnostic biomarker identification,assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis.AIM To determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA.METHODS A total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University(Unesp).The diagnosis of UC or CD was based on clinical,endoscopic,radiologic,and histological criteria and confirmed by histopathological analysis at the time of selection.The TaqMan™Array Human MicroRNA A+B Cards Set v3.0(Applied Biosystems™)platform was used to analyze 754 miRNAs.Targets of DE-miRNAs were predicted using miRNA Data Integration Portal(mirDIP)and the miRNA Target Interaction database(MiRTarBase).All statistical analyses were conducted using GraphPad Prism software.Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests,respectively.RESULTS The results showed that of the 754 miRNAs that were initially evaluated,643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC;the remaining 111 miRNAs were not considered to be expressed in these patients.The expression levels of 28 miRNAs were significantly different between the CD and UC patients(P≤0.05);13 miRNAs demonstrated a fold-change in expression level greater than 1.Five miRNAs with a downregulated expression were selected for enrichment analysis.The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers.CONCLUSION MiRNAs could be used to differentiate UC from CD,and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.
文摘MicroRNAs(miRNAs)are non-coding RNA molecules composed of 19–25 nucleotides that regulate gene expression and play a central role in the regulation of several immune-mediated disorders,including inflammatory bowel diseases(IBD).IBD,represented by ulcerative colitis and Crohn’s disease,is characterized by chronic intestinal inflammation associated with an increased risk of colorectal cancer(CRC).CRC is one of the most prevalent tumors in the world,and its main risk factors are obesity,physical inactivity,smoking,alcoholism,advanced age,and some eating habits,in addition to chronic intestinal inflammatory processes and the use of immunosuppressants administered to IBD patients.Recent studies have identified miRNAs associated with an increased risk of developing CRC in this population.The identification of miRNAs involved in this tumorigenic process could be useful to stratify cancer risk development for patients with IBD and to monitor and assess prognosis.Thus,the present review aimed to summarize the role of miRNAs as biomarkers for the diagnosis and prognosis of IBD-associated CRC.In the future,therapies based on miRNA modulation could be used both in clinical practice to achieve remission of the disease and restore the quality of life for patients with IBD,and to identify the patients with IBD at high risk for tumor development.
基金Supported by the Sao Paulo Research Foundation(FAPESP),No.2015/14797-3 to Périco LL and No.2009/52237-9 to Laboratory of Biological Assays with Natural Products
文摘AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP)leaves on gastric ulcer healing.METHODS In this rat study involving males,intact(cycling)females,and ovariectomized females,gastric ulcers were induced using acetic acid.A vehicle,lansoprazole,or HEEP was administered for 14 d after ulcer induction.Body weight was monitored throughout the treatment period.At the end of treatment,the rats were euthanized and the following in vivo and in vitro investigations were performed:macroscopic examination of the lesion area and organ weights,biochemical analysis,zymography,and evaluation of protein expression levels.Additionally,the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle,HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%),intact females(85.22%),and ovariectomized females(65.47%),confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones.The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats.Overall,the beneficial effect of HEEP was the highest in intact females.Notably,HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females)and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female).Additionally,HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro,confirming its healing effect.Finally,no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers,HEEP-induced healing(modulated by female sex hormones;in males,mediated by prostaglandin)involves extracellular matrix remodeling,with gastric mucosa cell proliferation and migration.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2012/15036-8National Council for Scientific and Technological Development(CNPq),No.474.776/2013-1+2 种基金the Sao Paulo Research Foundation(FAPESP,NO.2015/21464-0)for the support for English revisionthe Coordination for the Improvement of Higher Education Personnel(CAPES)for the doctoral scholarshipthe National Council for Scientific and Technological Development(CNPq,NO.310120/2015-2)for the productivity research scholarship
文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.
