Putrescine supplementation limits the expansion of pks+ Escherichia coli and tumor development in the colon.

Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development (CRC). Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli. We found that culture supernatants of the probiotic strain E. coli Nissle 1917 were able to inhibit the growth of the murine pathogenic strain pks+ E. coli NC101 (EcNC101). We performed a non-targeted analysis of the metabolome in supernatants from several E. coli strains and identified putrescine as a potential postbiotic capable of suppressing EcNC101 growth in vitro. The effect of putrescine supplementation was then evaluated in the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of CRC in mice colonized with EcNC101. Putrescine supplementation inhibited the growth of pks+ E. coli; reduced the number and size of colonic tumors; and downmodulated the release of inflammatory cytokines in the colonic lumen. Additionally, putrescine supplementation led to shifts in the composition and function of gut microbiota, characterized by an increase of the Firmicutes/Bacteroidetes ratio and enhanced acetate production. The effect of putrescine was further confirmed in vitro using a pks+ E. coli strain isolated from a CRC patient. These results suggest that probiotic-derived metabolites can be used as an alternative to live bacteria in individuals at risk of developing CRC due to the presence of pks+ bacteria in their colon.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

PURPOSE: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Clinical and Laboratory Findings on Glycogen Storage Disease Type V: Results from a Retrospective Observational Study in a Tertiary Hospital.

Introduction - Glycogen storage disease type V (GSDV, MIM #232600) is an autosomal recessive metabolic myopathy caused by pathogenic variants in the PYGM gene. The characteristic symptoms of exercise intolerance, myalgia, and cramps, which improve after a few minutes of rest, are frequently unrecognized in affected children. When there is clinical suspicion, the initial approach with a forearm exercise test has diagnostic value by detecting low post-exercise plasma lactate-to-ammonia ratio values. The diagnostic algorithm is followed by genetic testing if the results suggest myophosphorylase deficiency. Methods - This was a retrospective observational study conducted based on reviewing medical records of patients with GSDV in a tertiary hospital. We assessed demographic variables, including the timing of onset and diagnosis, relevant clinical characteristics, and whether genetic testing was performed, including its results. Results/Case Report - Our goal was to review the GSDV cases in our center to assess our cohort's diagnostic timing and clinical and genetic characteristics. We identified 28 patients from 24 families, three with consanguinity. The mean age at the time of the study was 43 years. While most (26/28; 93%) recalled their first symptoms in childhood/adolescence, only 25% (7/28) were diagnosed then. All patients had exercise intolerance and CK elevation, while about half reported the second wind phenomenon. Genetic testing was performed in 22 patients, revealing biallelic PYGM variants (9 homozygous, 13 compound heterozygous) as the most common (p.R50*). Conclusion - GSDV is rare and presents in the pediatric age, with subtle manifestations often underestimated for decades. A late diagnosis may negatively impact the psychosocial development of affected children. It is essential to recognize some unique features that facilitate diagnosis: history of exercise intolerance, the second wind sign, and high resting serum CK levels. Identifying the disease-causing variants in PYGM is currently the gold standard for diagnosis as it is less invasive than performing a muscle biopsy, and may promptly diagnose the condition and avoid wrongful labelling of patients.

Inulin impacts tumorigenesis promotion by colibactin-producing Escherichia coli in ApcMin/+ mice.

Introduction: The prebiotic inulin has previously shown both protective and tumor-promoting effects in colorectal cancer (CRC). These inconsistencies may be due to the gut microbial composition as several bacteria have been associated with CRC. Specifically, polyketide synthase-positive (pks+) Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). We investigated whether colibactin-producing Escherichia coli changed the protection conferred by inulin against tumor growth and progression using the ApcMin/+ mouse model of CRC. Methods: Mice received a 2% dextran sodium sulfate (DSS) solution followed by oral gavage with the murine pks + E. coli strain NC101 (EcNC101) and were fed a diet supplemented with 10% cellulose as control or 10% inulin for 4 weeks. Results: Inulin supplementation led to increase EcNC101 colonization compared to mice receiving the control diet. The increased colonization of EcNC101 resulted in more DSBs, tumor burden, and tumor progression in ApcMin/+ mice. The tumorigenic effect of EcN101 in ApcMin/+ mice mediated by inulin was dependent on colibactin production. Pasteurized E. coli Nissle 1917 (EcN), a probiotic, suppressed the inulin-driven EcNC101 expansion and impacted tumor progression. Discussion: Our results suggest that the presence of pks + E. coli influences the outcome of inulin supplementation in CRC and that microbiota-targeted interventions may mitigate this effect. Given the prevalence of pks + E. coli in both healthy and CRC populations and the importance of a fiber-rich diet, inulin supplementation in individuals colonized with pks + bacteria should be considered with caution.

Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.

OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo. RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.

Antifungal analysis of incorporation of the essential oil of Cymbopogon citratus (D.C.) Stapf into polymethyl methacrylate / Análise antifúngica da incorporação do óleo essencial de Cymbopogon citratus (d.c.) Stapf em polimetacrilato de metila

ABSTRACT Objective: Evaluated the antifungal effect of the incorporation of different concentrations of the essential oil Cymbopogon citratus (capim santo), into polymethylmethacrylate (PMMA) against Candida albicans. Methods: Fifty specimens were fabricated and divided into five groups: Group 1, PMMA + 10% essential oil (n=10); Group 2, PMMA + 15% essential oil (n=10); Group 3, PMMA + 20% essential oil (n=10); Group 4, PMMA + 25% essential oil (n=10); Group 5, PMMA (n=10). PMMA powder was mixed with the monomer and the mixture was placed in disc-shaped cavities measuring 15 mm in diameter, 2 mm thick. To evaluate the antifungal activity of the experimental specimens, the standard strain of Candida albicans was tested. After incubation, the colony count of each plate was performed using a digital colony counter, obtaining the number of colony forming units (CFU) and the Kruskal-Wallis test was applied. Results: There was statistically significant difference in the CFU count of Candida albicans as a consequence of the addition of Cymbopogon citratus essential oil to PMMA (p < 0.001) and values were significantly higher in comparison with those of all the other groups, when the essential oil was incorporated as incorporated into the PMMA in the concentration of 20%. In the other concentrations, no difference in values was observed in comparison with the Control Group without essential oil of Cymbopogon citratus. Conclusion: The acrylic resin with the essential oil incorporated into it in different concentrations provided no effect against development of the genus Candida.

RESUMO Objetivo: Avaliar o efeito antifúngico da incorporação de diferentes concentrações do óleo essencial Cymbopogon citratus (capim santo), em polimetilmetacrilato (PMMA) contra Candida albicans. Métodos: Cinquenta corpos de prova foram confeccionados e divididos em cinco grupos: Grupo 1, PMMA + 10% de óleo essencial (n=10); Grupo 2, PMMA + 15% de óleo essencial (n=10); Grupo 3, PMMA + 20% de óleo essencial (n=10); Grupo 4, PMMA + 25% de óleo essencial (n=10); Grupo 5, PMMA (n=10). O pó de PMMA foi misturado ao monômero e a mistura foi colocada em cavidades em forma de disco medindo 15 mm de diâmetro por 2 mm de espessura. Para avaliar a atividade antifúngica dos espécimes experimentais, foi testada a cepa padrão de Candida albicans. Após a incubação, foi realizada a contagem de colônias de cada placa por meio de um contador digital de colônias, obtendo-se o número de unidades formadoras de colônias (UFC) e para isso foi aplicado o teste de Kruskal-Wallis. Resultados: Houve diferença estatisticamente significativa na contagem de UFC de Candida albicans como consequência da adição do óleo essencial de Cymbopogon citratus ao PMMA (p < 0,001) e os valores foram significativamente maiores em comparação com todos os outros grupos, quando o essencial óleo foi incorporado como incorporado ao PMMA na concentração de 20%. Nas demais concentrações, não houve diferença nos valores em relação ao Grupo Controle sem óleo essencial de Cymbopogon citratus. Conclusão: A resina acrílica com o óleo essencial incorporado a ela em diferentes concentrações não apresentou efeito contra o desenvolvimento do gênero Candida.

Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. METHODS: Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR. RESULTS: We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%). CONCLUSIONS: Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages.

GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects. During different stress conditions, such as hemolysis, amino acid deficiency or hypoxia, GCN2 knockout (GCN2-/-) mice displayed resistance to anemia compared with wild-type (GCN2+/+) mice. GCN2-/- liver macrophages exhibited defective erythrophagocytosis and lysosome maturation. Molecular analysis of GCN2-/- cells demonstrated that the ATF4-NRF2 pathway is a critical downstream mediator of GCN2 in regulating red blood cell clearance and iron recycling.

Vitamin D supplementation modulates autophagy in the pristane-induced lupus model

Abstract Introduction/objectives: Clinical evidence of skeletal muscle involvement is not uncommon in systemic lupus erythematosus (SLE). Because of the poor understanding of signaling pathways involved in SLE muscle wasting, the aim of this study was to evaluate the effects of vitamin D supplementation on skeletal muscle in mice with pristane-induced lupus. Methods: Balb/c mice with lupus-like disease induced by pristane injection were randomized into three groups: pristane-induced lupus (PIL; n = 10), pristane-induced lupus + vitamin D supplementation (PIL + VD; n = 10) and healthy controls (CO; n = 8). Physical function was evaluated on days 0, 60, 120 and 180. The tibialis anterior and gastrocnemius muscles were collected to evaluate myofiber cross-sectional area (CSA) and protein expression. Results: The PIL + VD group showed lower muscle strength compared to the CO and PIL groups at different time points. PIL mice showed similar myofiber CSA compared to CO and PIL + VD groups. LC3-II expression was higher in PIL compared to CO and PIL + VD groups. MyoD expression was higher in PIL mice compared to PIL + VD, while myostatin expression was higher in PIL + VD than PIL group. Myogenin expression levels were decreased in the PIL + VD group compared with the CO group. The Akt, p62 and MuRF expressions and mobility assessment showed no significance. Conclusions: Changes in skeletal muscle in PIL model happen before CSA reduction, possibly due to autophagy degradation, and treatment with Vitamin D has a impact on physical function by decreasing muscle strength and time of fatigue.. Vitamin D supplementation has a potential role modulating physical parameters and signaling pathways in muscle during pristane-induced lupus model.

Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota.

BACKGROUND: Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure. RESULTS: Mice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylum-dominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron. CONCLUSIONS: Oral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.

Improvement of colonic healing and surgical recovery with perioperative supplementation of inulin and galacto-oligosaccharides.

BACKGROUND AND AIMS: Anastomotic leak (AL) is a major complication in colorectal surgery. Recent evidence suggests that the gut microbiota may affect healing and may cause or prevent AL. Butyrate is a beneficial short-chain fatty acid (SCFA) that is produced as a result of bacterial fermentation of dietary oligosaccharides and has been described as beneficial in the maintenance of colonic health. To assess the impact of oligosaccharides on colonic anastomotic healing in mice, we propose to modulate the microbiota with oligosaccharides to increase butyrate production via enhancement of butyrate-producing bacteria and, consequently, improve anastomotic healing in mice. METHODS: Animal experiments were conducted in mice that were subjected to diets supplemented with inulin, galacto-oligosaccharides (GOS) or cellulose, as a control, for two weeks before undergoing a surgical colonic anastomosis. Macroscopic and histological assessment of the anastomosis was performed. Extent of epithelial proliferation was assessed by Ki-67 immunohistochemistry. Gelatin zymography was used to evaluate the extent of matrix metalloproteinase (MMP) hydrolytic activity. RESULTS: Inulin and GOS diets were associated with increased butyrate production and better anastomotic healing. Histological analysis revealed an enhanced mucosal continuity, and this was associated with an increased re-epithelialization of the wound as determined by increased epithelial proliferation. Collagen concentration in peri-anastomotic tissue was higher with inulin and GOS diets and MMP activity, a marker of collagen degradation, was lower with both oligosaccharides. Inulin and GOS diets were further associated with lower bacterial translocation. CONCLUSIONS: Dietary supplementation with inulin and GOS may improve anastomotic healing and reinforce the gut barrier in mice.

Rastreamento e manejo da Síndrome da Apneia e Hipopneia Obstrutiva do Sono. Desafios para profissionais da Atenção Primária à Saúde / Screening and management of Obstructive Sleep Apnea and Hypopnea Syndrome. Challenges for Primary Health Care Professionals

A Síndrome da Apneia e Hipopneia Obstrutiva do Sono (SAHOS) é condição clínica importante com incidência crescente nos países desenvolvidos e em desenvolvimento. É condição negligenciada, com prevalência entre 30 e 56%, responsável por 80% dos casos de hipertensão arterial resistente, causa de sonolência diurna, hiperutilização de serviços de saúde, incapacidade laboral, sintomas depressivos, acidentes de trânsito e de trabalho e fator de risco para doenças cardiovasculares. Este artigo tem como objetivo atualizar informações e com isso alertar sobre a importância do rastreamento e manejo da SAHOS em população com hipertensão arterial sistêmica assistida na atenção primária à saúde.

Obstructive Sleep Apnea and Hypopnea Syndrome (OSAHS) is an important clinical condition with increasing incidence in developed and developing countries. It is a neglected condition, with prevalence between 30 and 56%, responsible for 80% of cases of resistant hypertension, causes daytime sleepiness, hyper-utilization of health services, work incapacity, depressive symptoms, traffic and work accidents, and risk factor for cardiovascular diseases. The aim of this article is to update information and thus alert about the importance of the screening and management of OSAHS in a population with high blood pressure assisted in Primary Health Care.

A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies.

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.

Oligosaccharides increase the genotoxic effect of colibactin produced by pks+ Escherichia coli strains.

BACKGROUND: Colibactin is a genotoxin that induces DNA double-strand breaks that may lead to carcinogenesis and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. METHODS: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 µM, 25 µM and 125 µM of ferrous sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immunofluorescence analysis. RESULTS: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 µM of ferrous sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and DNA double-strand breaks in Caco-2 cells compared to untreated cells. CONCLUSION: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether oligosaccharide supplementation may lead to increased colorectal tumorigenesis in animal models colonized with pks+ E. coli.

The role of butyrate in surgical and oncological outcomes in colorectal cancer.

Butyrate is a short-chain fatty acid produced by colonic gut bacteria as a result of fermentation of dietary fibers. In the colon, butyrate is a major energy substrate and contributes to the nutritional support and proliferation of a healthy mucosa. It also promotes the intestinal barrier function by enhancing mucus production and tight junctions. In addition to its pro-proliferative effect in healthy colonocytes, butyrate inhibits the proliferation of cancer cells. The antineoplastic effect of butyrate is associated with the inhibitory effect of butyrate on histone deacetylase (HDAC) enzymes, which promote carcinogenesis. Due to the metabolic shift of cancer cells toward glycolysis, unused butyrate accumulates and inhibits procarcinogenic HDACs. In addition, recent studies suggest that butyrate may improve the healing of colonic tissue after surgery in animal models, specifically at the site of reconnection of colonic ends, anastomosis, after surgical resection. Here, we review current evidence on the impact of butyrate on epithelial integrity and colorectal cancer and present current knowledge on data that support its potential applications in surgical practice.

Cluster of factors associated with physical frailty in community-dwelling elderly people / Agregamento de fatores associados à fragilidade física em idosos residentes na comunidade

Abstract Frailty is characterized as a set of factors related to the body structure that lead the subject to a process of physical vulnerability, increasing their dependence. The study aims to investigate the aggregation of factors related to physical frailty (PF) in elderly residents of a city with a low Human Development Index (HDI). This is a cross-sectional study carried out in the city of Ibicuí, state of Bahia, Brazil, and including a random 270 elderly people aged ≥ 60 years. The physical frailty condition was identified according to the criteria proposed by Fried and collaborators. In the data analysis, descriptive statistics, cluster analysis, and multinominal logistic regression procedures were used. The highest prevalence of aggregation was identified when the four risk factors were combined: weight loss, strength, walking speed and physical activity levels (O/E = 4.36; CI = 4.04 - 4.68). It was identified that older people (80 years old or more) with a lower level of education (unlettered) were more likely to have three or more risk factors for physical frailty (p <0.05). As for sociodemographic variables, those who were older and had lower levels of education were more likely to have three or more risk factors. The development of actions that encourage a healthier lifestyle to favor the prevention and treatment of physical frailty, as well as to increase health literacy and knowledge, may reduce the problems related to this condition in older adults, mainly thinking about the next generations.

Resumo A fragilidade é caracterizada como um conjunto de fatores relacionados à estrutura corporal que levam o sujeito a um processo de vulnerabilidade física, aumentando sua dependência. O estudo tem como objetivo investigar a agregação de fatores relacionados à fragilidade física (FP) em idosos residentes em um município com baixo Índice de Desenvolvimento Humano (IDH). Trata-se de um estudo transversal realizado na cidade de Ibicuí, estado da Bahia, Brasil, e incluiu aleatoriamente 270 idosos com idade ≥ 60 anos. A condição de fragilidade física foi identificada de acordo com os critérios propostos por Fried e colaboradores. Na análise dos dados, foram utilizadas estatísticas descritivas, análise de cluster e procedimentos de regressão logística multinominal. A maior prevalência de agregação foi identificada quando os quatro fatores de risco foram combinados: perda de peso, força, velocidade de caminhada e níveis de atividade física (O/E = 4,36; IC = 4,04 - 4,68). Identificou-se que idosos (80 anos ou mais) com menor escolaridade (analfabetos) apresentaram maior probabilidade de apresentar três ou mais fatores de risco para fragilidade física (p <0,05). Quanto às variáveis ​​sociodemográficas, aqueles que eram mais velhos e com menor escolaridade tinham maior chance de apresentar três ou mais fatores de risco. O desenvolvimento de ações que estimulem um estilo de vida mais saudável para favorecer a prevenção e o tratamento da fragilidade física, bem como aumentar a alfabetização e o conhecimento em saúde, pode reduzir os problemas relacionados a essa condição nos idosos, principalmente pensando nas próximas gerações.

Acute invariant NKT cell activation triggers an immune response that drives prominent changes in iron homeostasis.

Iron homeostasis is an essential biological process that ensures the tissue distribution of iron for various cellular processes. As the major producer of hepcidin, the liver is central to the regulation of iron metabolism. The liver is also home to many immune cells, which upon activation may greatly impact iron metabolism. Here, we focus on the role of invariant natural killer T (iNKT) cells, a subset of T lymphocytes that, in mice, is most abundant in the liver. Activation of iNKT cells with the prototypical glycosphingolipid antigen, α-galactosylceramide, resulted in immune cell proliferation and biphasic changes in iron metabolism. This involved an early phase characterized by hypoferremia, hepcidin induction and ferroportin suppression, and a second phase associated with strong suppression of hepcidin despite elevated levels of circulating and tissue iron. We further show that these changes in iron metabolism are fully dependent on iNKT cell activation. Finally, we demonstrate that the biphasic regulation of hepcidin is independent of NK and Kupffer cells, and is initially driven by the STAT3 inflammatory pathway, whereas the second phase is regulated by repression of the BMP/SMAD signaling pathway. These findings indicate that iNKT activation and the resulting cell proliferation influence iron homeostasis.

Current evidence on the relation between gut microbiota and intestinal anastomotic leak in colorectal surgery.

BACKGROUND: Anastomotic leak (AL) is a major complication in colorectal surgery. It worsens morbidity, mortality and oncological outcomes in colorectal cancer. Some evidence suggests a potential effect of the intestinal microbiome on wound healing. This review aims to provide a comprehensive review on historical and current evidence regarding the relation between the gastrointestinal microbiota and AL in colorectal surgery, and the potential microbiota-modifying effect of some perioperative commonly used measures. DATA SOURCES: A comprehensive search was conducted in Pubmed, Medline and Embase for historical and current clinical and animal studies addressing perioperative intestinal microbiota evaluation, intestinal healing and AL. CONCLUSIONS: Evidence on microbes' role in AL is mainly derived from animal experiments. The microbiota's composition and implications are poorly understood in surgical patients. Elaborate microbiota sequencing is required in colorectal surgery to identify potentially beneficial microbial profiles that could lead to specific perioperative microbiome-altering measures and improve surgical and oncological outcomes.

Curcumin induces mild anemia in a DSS-induced colitis mouse model maintained on an iron-sufficient diet.

Anemia is frequently encountered in patients with inflammatory bowel disease (IBD), decreasing the quality of life and significantly worsening the prognosis of the disease. The pathogenesis of anemia in IBD is multifactorial and results mainly from intestinal blood loss in inflamed mucosa and impaired dietary iron absorption. Multiple studies have proposed the use of the polyphenolic compound curcumin to counteract IBD pathogenesis since it has significant preventive and therapeutic properties as an anti-inflammatory agent and very low toxicity, even at high dosages. However, curcumin has been shown to possess properties consistent with those of an iron-chelator, such as the ability to modulate proteins of iron metabolism and decrease spleen and liver iron content. Thus, this property may further contribute to the development and severity of anemia of inflammation and iron deficiency in IBD. Herein, we evaluate the effects of curcumin on systemic iron balance in the dextran sodium sulfate (DSS) model of colitis in C57Bl/6 and BALB/c mouse strains that were fed an iron-sufficient diet. In these conditions, curcumin supplementation caused mild anemia, lowered iron stores, worsened colitis and significantly decreased overall survival, independent of the mouse strain. These findings suggest that curcumin usage as an anti-inflammatory supplement should be accompanied by monitoring of erythroid parameters to avoid exacerbation of iron deficiency anemia in IBD.