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[This corrects the article DOI: 10.3389/fimmu.2022.1028953.].

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IL-39 (Interleukin-39) is a heterodimeric cytokine composed of IL-23p19 and EBI3 (Epstein-Barr virus-induced gene 3) subunits. Despite the evidence that correlates the role of IL-39 in regulating inflammation, its expression in the intestinal microenvironment of IBD (inflammatory bowel disease) patients is still unknown. Thus, this work was focused on characterizing relative mRNA (messenger RNA) IL-39 expression and intestinal synthesis in IBD patients. This study includes 37 patients diagnosed with ulcerative colitis (UC), 15 with Chron's disease (CD), and 22 controls. Gene expression of IL-39 subunits (IL-23p19/EBI3) was measured by RT-PCR (real time polymerase chain reaction). Intestinal synthesis was evaluated by immunohistochemistry and serum levels by ELISA. Statistical analysis was done using Prism GraphPad V6. Relative mRNA IL-39 expression was increased in patients with active UC and active CD compared to the remission UC, remission CD, and control group. High levels of relative mRNA expression of IL-39 (IL-23p19 subunit) were associated with histological activity. IHQ analysis showed increased IL-39 production in mucosa, submucosa, muscular, and serosa layer of patients with active disease. IL-39 serum production was increased in patients with UC. IL-39 gene's upregulation was found in patients with active IBD and was associated with severe histological activity in UC. This is the first report regarding the role of IL-39 in patients with IBD. The findings suggest that IL-39 might play a role as an inflammatory mediator in active IBD and could be considered a new alternative in treating this condition.

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OBJECTIVE: Past studies have demonstrated that women with inflammatory bowel disease (IBD) have a higher risk of gynecological conditions than do women without it. We aimed to characterize the gynecological histories of Hispanic Women living in Puerto Rico with IBD. METHODS: We identified women, aged 21 to 55 years, with a confirmed IBD diagnosis and receiving follow-up care from the University of Puerto Rico IBD clinics from 2017 through 2020. A questionnaire was administered to acquire sociodemographics, family history, past medical history, IBD diagnosis, and gynecologic aspects. RESULTS: One hundred eighty-six women were recruited. Fifty-three (28%) patients had ulcerative colitis, while 133 (72%) had Crohn's disease. Fifty-six percent of all the participants had a chronic illness in addition to than their IBD. Seventy-four out of 186 patients reported having had at least 1 late period within the last 12 months. Fifty-three (28%) described their period patterns as irregular. Thirty-nine (21%) of the patients reported having been vaccinated against human papillomavirus (HPV), and 8 (4%) had been infected by it. Nine out of 186 (5%) patients reported suffering from infertility. CONCLUSION: The results showed that our Hispanic patients (living in Puerto Rico) had a prevalence of irregular menstrual cycles that was similar to that observed in other populations. On the other hand, the presence of HPV, infertility, and cervical cancer were lower and the frequency of Papanicolaou smears performed higher than what has been seen in the continental United States, suggesting that this topic should be investigated in future studies.

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Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor related to stress response and cellular homeostasis that plays a key role in maintaining the redox system. The imbalance of the redox system is a triggering factor for the initiation and progression of non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). Nrf2 and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are the main regulators of oxidative stress and their activation has been recognized as a promising strategy for the treatment or prevention of several acute and chronic diseases. Moreover, activation of Nrf2/keap signaling pathway promotes inhibition of NF-κB, a transcriptional factor related to pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have been reported as potent antioxidant and intestinal anti-inflammatory compounds, acting by different mechanisms, mainly as a modulator of Nrf2/keap signaling pathway. Based on in vivo and in vitro studies, this review focuses on the natural coumarins obtained from both plant products and fermentative processes of food plants by gut microbiota, which activate Nrf2/keap signaling pathway and produce intestinal anti-inflammatory activity. Although gut metabolites urolithin A and urolithin B as well as other plant-derived coumarins display intestinal anti-inflammatory activity modulating Nrf2 signaling pathway, in vitro and in vivo studies are necessary for better pharmacological characterization and evaluation of their potential as lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, and imperatorin are the most promising coumarin derivatives as lead compounds for the design and synthesis of Nrf2 activators with intestinal anti-inflammatory activity. However, further structure-activity relationships studies with coumarin derivatives in experimental models of intestinal inflammation and subsequent clinical trials in health and disease volunteers are essential to determine the efficacy and safety in IBD patients.

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Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.

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Dysbiosis and disturbances in gut homeostasis may result in dysregulated responses, which are common in inflammatory bowel diseases (IBD). These conditions may be refractory to the usual treatments and novel therapies are still necessary to reach a more successful regulation of intestinal immunity. The hormone melatonin (MLT) has been raised as a therapeutic alternative because of its known interactions with immune responses and gut microbiota. Hence, we evaluated the effects of MLT in experimental colitis that evolves with intestinal dysbiosis, inflammation and bacterial translocation. C57BL/6 mice were exposed to dextran sulfate sodium and treated with MLT. In acute colitis, the hormone led to increased clinical, systemic and intestinal inflammatory parameters. During remission, continued MLT administration delayed recovery, increased TNF, memory effector lymphocytes and diminished spleen regulatory cells. MLT treatment reduced Bacteroidetes and augmented Actinobacteria and Verrucomicrobia phyla in mice feces. Microbiota depletion resulted in a remarkable reversion of the colitis phenotype after MLT administration, including a counter-regulatory immune response, reduction in TNF and colon macrophages. There was a decrease in Actinobacteria, Firmicutes and, most strikingly, Verrucomicrobia phylum in recovering mice. Finally, these results pointed to a gut-microbiota-dependent effect of MLT in the potentiation of intestinal inflammation.

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Inflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for activating the inflammasome-mediated response. Mitochondrial alterations, such as reduced respiratory complex activities and reduced production of tricarboxylic acid (TCA) cycle intermediates (e.g., citric acid, fumarate, isocitric acid, malate, pyruvate, and succinate) have been described in in vitro and clinical studies. Under inflammatory conditions, mitochondrial architecture in intestinal epithelial cells is dysmorphic, with cristae destruction and high dynamin-related protein 1 (DRP1)-dependent fission. Likewise, these alterations in mitochondrial morphology and bioenergetics promote metabolic shifts towards glycolysis and down-regulation of antioxidant Nuclear erythroid 2-related factor 2 (Nrf2)/Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling. Although the mechanisms underlying the mitochondrial dysfunction during mucosal inflammation are not fully understood at present, metabolic intermediates and cholesterol may act as signals activating the NLRP3 inflammasome in IBD. Notably, dietary phytochemicals exhibit protective effects against cholesterol imbalance and mitochondrial function alterations to maintain gastrointestinal mucosal renewal in vitro and in vivo conditions. Here, we discuss the role of cholesterol and mitochondrial metabolism in IBD, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function.

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BACKGROUND: Inflammatory bowel diseases (IBDs) are chronic diseases that demand continuous interaction between patients and healthcare providers. Quality of care (QoC) is a factor that contributes to a patient's adherence to treatment and its success. AIM: To evaluate QoC in patients from a single IBD reference center. METHODS: This cross-sectional study included 133 patients from a single Brazilian IBD public health center. QoC was evaluated through the QoC Through the Eyes of Patients with IBD (QUOTE-IBD) questionnaire (based on patient perspectives), which measures eight dimensions of care. We compared QoC among patients with Crohn's disease and ulcerative colitis and analyzed the clinical and psychological factors associated with QoC satisfaction. Clinical evaluations assessed disease characteristics, quality of life, anxiety, and depression levels. RESULTS: Sixty-nine patients with Crohn's disease and 64 with ulcerative colitis were interviewed. The mean age was 37.26 years ± 13.05 years, and 63.91% of the patients were women. The mean duration of the disease was 8.44 years ± 7.59 years, where most patients were in remission (70.31% of patients with ulcerative colitis and 62.32% with Crohn's disease). The total QoC score of the sample was 8.61 years ± 1.31 points, indicating that the QoC provided by the center was unsatisfactory. According to univariate logistic regression, patients with Crohn's disease had higher satisfaction rates than those with ulcerative colitis [odds ratio (OR): 2.746; 95% confidence interval (CI): 1.360-5.541; P = 0.0048] and patients on infliximab (OR: 2.175; 95%CI: 1.037-4.562; P = 0.0398). CONCLUSION: Patients from the IBD public center reported good doctor-patient relationships, but had problems related to the healthcare structure. Evaluation of healthcare centers is of paramount to improve QoC for the patients involved.

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OBJECTIVE: Determine the variables associated with hospitalisations in patients with Crohn's disease and those associated with surgery, intestinal resection, hospital readmission, need for multiple operations and immunobiological agent use. DESIGN: A cross-sectional study was conducted from 2019 to 2021, using two centres for inflammatory bowel diseases in the Brazilian Public Health System. RESULTS: This study included 220 patients. Only perianal disease was associated with hospitalisation (31.6% vs 13.0%, p=0.012). Stricturing or penetrating behaviour (35.8% vs 12.6%, p<0.001) and perianal disease (45.9% vs 9.9%, p<0.001) were associated with surgery. Ileal or ileocolonic location (80.0% vs 46.5%, p=0.044) and stricturing or penetrating behaviour (68.0% vs 11.2%, p<0.001) were associated with intestinal resection. Steroids use at first Crohn's disease occurrence and postoperative complications were associated with hospital readmission and need for multiple operations, respectively. Age below 40 years at diagnosis (81.3% vs 62.0%, p=0.004), upper gastrointestinal tract involvement (21.8% vs 10.3%, p=0.040) and perianal disease (35.9% vs 16.3%, p<0.001) were associated with immunobiological agent use. CONCLUSION: Perianal disease and stricturing or penetrating behaviour were associated with more than one significant outcome. Other variables related to Crohn's disease progression were age below 40 years at diagnosis, an ileal or ileocolonic disease localisation, an upper gastrointestinal tract involvement, the use of steroids at the first Crohn's disease occurrence and history of postoperative complications. These findings are similar to those in the countries with a high prevalence of Crohn's disease.

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ABSTRACT Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder affecting the gastrointestinal tract. The etiology of this alarming condition is multifactorial. A Recently increasing trend in IBD is noted in our country. Objective: The present study was designed with the main objective to assess the incidence and to identify the associated risk factors including demographic, geographical areas, and dietary patterns of IBD population of Northern of Karnataka viz. Hubli-Dharwad city. Methods: A retrospective investigation was conducted on a cohort of 226 patients with a working diagnosis of IBD and those who were admitted between 2015 to 2019 the department of gastroenterology, SDMCMS&H. The diagnosis of IBD was made based on clinical, radiological, endoscopic, and histopathologic findings. The patients were categorized into IBD and those who have symptoms suggestive of IBD but did not fit into the diagnostic criteria into, non-IBD groups. The data about of on demography, diet patterns, and laboratory parameters were recorded. Results: Among 226 patients enrolled in this study 2015-2019, IBD was confirmed in 54 Ulcerative colitis - 44 (19.46%), Crohn's disease - 10 (4.42%) patients with varying distribution of disease among different age groups and both genders, Ulcerative colitis (UC) [M: F: 28 (63.6%): 16 (36.4%)] and Crohn's disease (CD) [M: F: 07 (70.0%):03 (30.0%)]. Dietary pattern and other habitats had no significant contribution to illness and its symptoms. Urban (U) and Rural (R) divide was UC [U: R: 32 (72.7%): 12 (27.3%)], CD [U:R:07(70.0%):03(30.0%)] maintained. Conclusion Incidence of IBD was high with UC as compared to CD. The incidence of IBD among patients presenting with symptoms suggestive of IBD is 19.46% with UC being major as compared to CD (4.42%). Male predominant patterns of IBD incidences were noted. Year by year increasing trend in disease burden was observed. The Dietary pattern has no direct correlation with IBD disease prevalence and incidences.

Resumo Contexto: A Doença inflamatória intestinal (DII) é uma doença inflamatória crônica que afeta o trato gastrointestinal. A etiologia desta condição alarmante é multifatorial. Uma tendência recentemente crescente na DII é notada em nosso país. Objetivo: O presente estudo foi desenhado com o objetivo principal de avaliar a incidência e identificar os fatores de risco associados, incluindo demográficos, áreas geográficas e padrões alimentares da população com DII do Norte de Karnataka viz. Cidade de Hubli-Dharwad. Metodos: Uma investigação retrospectiva foi realizada em uma coorte de 226 pacientes com diagnóstico de DII e que foram admitidos entre 2015 e 2019 no departamento de gastroenterologia, SDMCMS&H. O diagnóstico de DII foi feito com base em achados clínicos, radiológicos, endoscópicos e histopatológicos. Os pacientes foram categorizados em DII e aqueles que apresentam sintomas sugestivos de DII, mas não se enquadraram nos critérios diagnósticos em grupos sem DII. Os dados sobre a demografia, padrões de dieta e parâmetros laboratoriais foram registrados. Resultados: Entre os 226 pacientes inscritos neste estudo entre 2015-2019, DII foi confirmada em 54 [RCUI - 44 (19,46%), DC - 10 (4,42%)] com distribuição variada da doença entre diferentes faixas etárias e ambos os sexos, colite ulcerativa (RCUI) [M: F: 28 (63,6%):16 (36,4%)] e doença de Crohn (DC) [M: F: 07 (70,0%): 03 (30,0%)]. O padrão alimentar e outros hábitos não tiveram contribuição significativa para a doença e seus sintomas. Urbanos (U) e rurais (R) dividiram-se em RCUI [U: R: 32 (72,7%):12 (27,3%)], DC [07 (70,0%): 03 (30,0%)]. Conclusão A incidência de DII foi elevada para RCUI em relação a DC. A incidência de DII entre os pacientes com sintomas sugestivos de DIB é de 19,46% com a RCUI sendo maior em relação a DC (4,42%). Foram observados padrões predominantes masculinos de incidência de DII. Ano a ano foi observada tendência crescente de carga da doença. O padrão dietético não tem correlação direta com a prevalência e incidências da DII.