Centella asiatica-Derived Endothelial Paracrine Restores Epithelial Barrier Dysfunction in Radiation-Induced Enteritis.

Radiation-induced enteritis is frequently observed following radiotherapy for cancer or occurs due to radiation exposure in a nuclear accident. The loss of the epithelial integrity leads to 'leaky gut', so recovery of damaged epithelium is an important strategy in therapeutic trials. Centella asiatica (CA), a traditional herbal medicine, is widely used for wound healing by protecting against endothelial damage. In this study, we investigated the radio-mitigating effect of CA, focusing on the crosstalk between endothelial and epithelial cells. CA treatment relieved radiation-induced endothelial dysfunction and mitigated radiation-induced enteritis. In particular, treatment of the conditioned media from CA-treated irradiated endothelial cells recovered radiation-induced epithelial barrier damage. We also determined that epidermal growth factor (EGF) is a critical factor secreted by CA-treated irradiated endothelial cells. Treatment with EGF effectively improved the radiation-induced epithelial barrier dysfunction. We also identified the therapeutic effects of CA-induced endothelial paracrine in a radiation-induced enteritis mouse model with epithelial barrier restoration. Otherwise, CA treatment did not show radioprotective effects on colorectal tumors in vivo. We showed therapeutic effects of CA on radiation-induced enteritis, with the recovery of endothelial and epithelial dysfunction. Thus, our findings suggest that CA is an effective radio-mitigator against radiation-induced enteritis.

Anti-inflammatory and anti-apoptotic effects of Shaoyao decoction on X-ray radiation-induced enteritis of C57BL/6 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: As a typical heat-clearing prescription, Shaoyao decoction (SYD) has a robust function of clearing viscera heat for the treatment of several intestinal discomfort symptoms. Clinical evidence indicated that it had the potential to cure radiation enteritis. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to probe the protective effects and the involved mechanisms of SYD on X-ray radiation-induced enteritis of C57BL/6 mice. MATERIALS AND METHODS: X-ray irradiation were used to establish the radiation enteritis model. Forty-eight male C57BL/6 mice (20 ± 2 g) were randomly divided into six groups: the control group, model group, dexamethasone group (DEX, 0.12 mg/kg) and SYD groups (0.12, 0.24 and 0.36 g/mL), respectively. All mice (except the control group) were intragastrically administrated for a continuous 7 days. H&E and Masson staining were employed to evaluate the morphological and collagen fibers changes of the colon. ELISA was performed to assess the levels of MDA, SOD, COX, LPS, IL-6, IL-1ß and TNF-α in serum. Moreover, TUNEL fluorescence, western blot and qRT-PCR were used to detect the levels of apoptosis-related proteins and genes of Dclk-1, ATM, MRE-11, Bcl-2, Bax, Caspase-3, and Cyto-c. Furthermore, immunofluorescent staining was applied to detect the protein levels of p53 and Claudin-1 in colon. RESULTS: Treatment with SYD decreased the exfoliated and necrotic epithelial cells and prevent the proliferate from damaged fibrous tissue in the crypt layer of mucos. The levels of serum peroxidation and pro-inflammatory cytokines (MDA, COX, LPS, IL-6, IL-1ß and TNF-α) were obviously inhibited, while SOD sharply increased in serum after administration. Moreover, SYD can significantly ameliorate the apoptosis of colon cells, evidenced by the reduced positive expression of TUNEL staining. Meanwhile, the results of qRT-PCR and western blot demonstrated that SYD can dramatically stimulate the expression of genes and proteins Dclk-1, ATM and MRE-11, thus promoting the expression of mitochondrial pro-apoptotic proteins Bax, Caspase-3 and Cyto-c, while increasing the level of anti-apoptotic protein Bcl-2. Furthermore, immunofluorescence revealed that SYD can notably decreased the protein level of p53 while reverse the reduction of Claudin-1. CONCLUSIONS: These results indicated that radiation enteritis in C57BL/6 mice can be ameliorated by treatment with SYD. The potential protection mechanisms may be involved in ameliorating tissue fibrosis by decreasing inflammatory and apoptotic events.

Oral administration of n-3 fatty acids positively affect the mucosal lesions after experimental ischemic enteritis in the rat.

AIM: The purpose of the study was to evaluate the effect of oral administration of n-3 polyunsaturated fatty acids in experimental ischemic enteritis in rats. METHODS: Forty Wistar rats were submitted to control narrowing of the superior mesenteric artery and were divided in two groups: N3 polyunsaturated fatty acids, which received a high-molecular polymer solution of artificial total enteral nutrition enriched with n-3 fatty acids and CONTROL which received a high-molecular polymer solution of artificial total enteral nutrition. RESULTS: Reduction of the animals' body weight was observed in both groups, but there was no difference between the two groups. Regarding the level of cytokines interleukin (IL)-1b, IL-6, and tumor necrosis factor a (TNF-a) there was no statistically significant difference between the two groups. Ischemic lesions to the small bowel mucosa were observed in both groups. A statistically significant difference in the extent of intestinal lesions was observed between the two groups with the animals that received enteral nutrition enriched with n-3 fatty acid developing fewer lesions. CONCLUSION: Enteral nutrition enriched with n-3 polyunsaturated fatty acids reduces the mucosal lesions caused by mesenteric ischemia compared to standard enteral nutrition, by modifying the local, but not the systemic, immune, and inflammatory response.

OBJETIVO: El propósito del estudio fue evaluar el efecto de la administración oral de ácidos grasos poliinsaturados n-3 en enteritis isquémica experimental en ratas. MÉTODOS: 40 ratas Wistar fueron sometidas a un estrechamiento controlado de la arteria mesentérica superior y se dividieron en dos grupos: N3PUFA, que recibieron una solución de polímero de alto peso molecular de nutrición enteral total artificial enriquecida con ácidos grasos n-3 y CONTROL que recibió un alto -Solución de polímero molecular de nutrición enteral total artificial. RESULTADOS: Se observó una reducción del peso corporal de los animales en ambos grupos, pero no hubo diferencias entre los dos grupos. Con respecto al nivel de citocinas IL-1b, IL-6 y TNF-a, no hubo diferencia estadísticamente significativa entre los dos grupos. Se observaron lesiones isquémicas de la mucosa del intestino delgado en ambos grupos. Se observó una diferencia estadísticamente significativa en la extensión de las lesiones intestinales entre los dos grupos y los animales que recibieron nutrición enteral enriquecida con ácido graso n-3 desarrollaron menos lesiones. CONCLUSIÓN: La nutrición enteral enriquecida con ácidos grasos poliinsaturados n-3 reduce las lesiones mucosas causadas por isquemia mesentérica en comparación con la nutrición enteral estándar, al modificar la respuesta local, pero no sistémica, inmunitaria e inflamatoria.

External treatment of traditional Chinese medicine for radiation enteritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Radiation enteritis (RE) is a common complication that often occurs after radiotherapy for abdominal and pelvic malignancies. RE could influence patients' quality of life seriously and it is difficult to cure by conventional treatments. A lot of studies have revealed that the external treatment of traditional Chinese medicine (TCM) for RE is a safe and economical approach, but there is no relevant systematic review. The present study performed a systematic review and meta-analysis to compare TCM external treatment and conventional treatment for RE to evaluate the effectiveness and safety of external treatment of traditional Chinese medicine in the treatment of RE. METHODS: Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wan-Fang database, VIP Chinese Science and Technique Journals Database, and the Chinese Biomedical Literature Database (CBM) were searched. The time of publication was limited from inception to April, 2021. Two reviewers independently searched for the selected articles and extract the data. The RevMan V.5.3 statistical software (Cochrane Collaboration) and Stata V.16.0 software were used to conduct the meta-analysis. RESULTS: We will show the results of this study in a peer-reviewed journal. CONCLUSION: This meta-analysis will provide reliable evidence for external treatment of TCM in the treatment of RE. INPLASY REGISTRATION NUMBER: INPLASY202140120.

Efficacy of Compound Herbal Medicine Tong-Xie-Yao-Fang for Acute Radiation Enteritis and Its Potential Mechanisms: Evidence from Transcriptome Analysis.

Acute radiation enteritis (ARE) is a common complication with radiotherapy for pelvic and abdominal malignancy. This research is designed to investigate the efficacy of Tong-Xie-Yao-Fang (TXYF) on ARE and to explore the underlying mechanisms by microarray analysis. The ARE rat model was established by a single abdominal irradiation with a gamma-ray dose of 10 Gy. Next, the ARE rats were treated with distilled water, TXYF, and glutamine by gavage for 7 consecutive days according to the scheduled groups. For each group, the jejunal tissue was taken at 6 h after gastric lavage. The morphology of intestinal tissue was observed by hematoxylin and eosin (H&E) stain under a light microscope. The height of the villus and the thickness of the whole layer of the TXYF-treated groups were significantly ameliorative than that of the model control group. The transcriptome analysis was produced using the Agilent SurePrint G3 Rat GE V2.0 microarray. A total of 90 differentially expressed genes (DEGs), including 48 upregulated genes and 42 downregulated genes, were identified by microarray and bioinformatics analysis. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to explore the possible mechanisms of DEGs taking part in the TXYF-mediated therapeutic process for ARE. In conclusion, we reveal that TXYF has a protective effect on the intestinal tissue of rats with ARE and summarize several DEGs, suggesting the possible mechanisms of TXYF-mediated efficacy for ARE.

Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease.

The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn's disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.

Dietary intake from complementary feeding is associated with intestinal barrier function and environmental enteropathy in Brazilian children from the MAL-ED cohort study.

A child's diet contains nutrients and other substances that influence intestinal health. The present study aimed to evaluate the relations between complementary feeding, intestinal barrier function and environmental enteropathy (EE) in infants. Data from 233 children were obtained from the Brazilian site of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project cohort study. Habitual dietary intake from complementary feeding was estimated using seven 24-h dietary recalls, from 9 to 15 months of age. Intestinal barrier function was assessed using the lactulose-mannitol test (L-M), and EE was determined as a composite measure using faecal biomarkers concentrations - α-1-antitrypsin, myeloperoxidase (MPO) and neopterin (NEO) at 15 months of age. The nutrient adequacies explored the associations between dietary intake and the intestinal biomarkers. Children showed adequate nutrient intakes (with the exception of fibre), impaired intestinal barrier function and intestinal inflammation. There was a negative correlation between energy adequacy and L-M (ρ = -0·19, P < 0·05) and between folate adequacy and NEO concentrations (ρ = -0·21, P < 0·01). In addition, there was a positive correlation between thiamine adequacy and MPO concentration (ρ = 0·22, P < 0·01) and between Ca adequacy and NEO concentration (ρ = 0·23; P < 0·01). Multiple linear regression models showed that energy intakes were inversely associated with intestinal barrier function (ß = -0·19, P = 0·02), and fibre intake was inversely associated with the EE scores (ß = -0·20, P = 0·04). Findings suggest that dietary intake from complementary feeding is associated with decreased intestinal barrier function and EE in children.

Efficacy of herbal medicine TJ-14 for acute radiation-induced enteritis: a multi-institutional prospective Phase II trial.

The purpose of this multi-institutional Phase II trial study was to prospectively investigate the efficacy of the herbal medicine TJ-14 for acute radiation-induced enteritis (ARE). TJ-14 was administered orally as a first-line treatment for ARE. The primary end point was efficacy at 1 week. The secondary end points were: (i) the efficacy of TJ-14 at 2 and 3 weeks after its administration, (ii) the quality of life score (FACT-G) at 1, 2 and 3 weeks after its administration, and (iii) adverse events. If the efficacy of TJ-14 was observed in eight patients or fewer, its efficacy was rejected. Results: Forty patients receiving pelvic radiotherapy were enrolled. Of these, 22 developed ARE and received TJ-14. Among these, 19 had cervical cancer and 9 received chemoradiotherapy. TJ-14 efficacy was shown in 19 out of the 22 patients (86%). Stool frequency per day at 1 week significantly decreased (mean ± SD: 4.9 ± 2.1 vs 3.7 ± 1.9, P = 0.02). This effect continued at 2 (2.2 ± 1.4, P = 0.004) and 3 weeks (2.1 ± 0.9, P = 0.05). Thirteen out of the 22 patients (59%) continued TJ-14 until the end of radiotherapy. FACT-G score deterioration was not observed after the administration of TJ-14. Grade 1 hypokalemia was observed in 4 patients, and Grade 1 constipation in 3. We concluded that TJ-14 is sufficiently promising to be examined in a Phase III trial. A randomized controlled trial is currently being planned.

Future therapies for eosinophilic gastrointestinal disorders.

OBJECTIVE: To review novel therapeutics in development for treatment of eosinophilic gastrointestinal disorders (EGIDs). DATA SOURCES: Clinical trial data (clinicaltrials.gov) and literature search on PubMed. STUDY SELECTIONS: Studies on treatment and clinical trials in EGIDs were included in this review. RESULTS: During the past decade, significant progress has been made in understanding disease mechanisms in EGIDs. As a result, a variety of novel therapeutics have been developed for treatment of these disorders. Several monoclonal antibodies against targets, including interleukin (IL) 4, IL-5, IL-13, integrins, and siglec-8, have shown promise in early trials. Novel formulations of corticosteroids are also in development. CONCLUSION: The field of EGID research has advanced rapidly, and disease-modifying therapeutics are closer to clinical application.

Sini San ameliorates duodenal mucosal barrier injury and low­grade inflammation via the CRF pathway in a rat model of functional dyspepsia.

The gut­brain interaction is associated with impaired duodenal mucosal integrity and low­grade inflammation, which have been proven to be important pathological mechanisms of functional dyspepsia (FD). Sini San (SNS) is a classical Chinese medicine used to treat FD, but its underlying mechanisms are poorly understood. The aim of the present study was to evaluate the effects of SNS on duodenal mucosal barrier injury and low­grade inflammation with FD, and to assess its potential molecular mechanisms on the brain­gut axis. FD rats were established using the iodoacetamide and tail­squeezed methods. The expression of corticotropin­releasing factor (CRF), CRF receptor 1 (CRF­R1) and CRF­R2, were determined by western blot analysis and/or immunohistochemistry (IHC). In addition, mast cell (MC) migration was assessed by IHC with an anti­tryptase antibody, and histamine concentration was quantified using ELISA. The mRNA expression levels of tryptase and protease­activated receptor 2 (PAR­2) were quantified using reverse transcription­quantitative PCR, and the protein expression levels of zona occludens protein 1 (ZO­1), junctional adhesion molecule 1 (JAM­1), ß­catenin and E­cadherin were determined via western blot analysis. It was demonstrated that the expression level of CRF was downregulated in the central nervous system and duodenum following SNS treatment, and that SNS modulated the expression of both CRF­R1 and CRF­R2. In addition, SNS suppressed MC infiltration and the activity of the tryptase/PAR­2 pathway in the duodenum. Furthermore, treatment with SNS restored the normal expression levels of ZO­1, JAM­1 and ß­catenin in FD rats. These findings suggested that the therapeutic effects of SNS on FD were achieved by restoring mucosal barrier integrity and suppressing low­grade inflammation in the duodenum, which was at least partially mediated via the CRF signaling pathway.

Corn gluten meal induces enteritis and decreases intestinal immunity and antioxidant capacity in turbot (Scophthalmus maximus) at high supplementation levels.

Corn gluten meal (CGM) is an important alternative protein source in aquafeed production. However, in turbot (Scophthalmus maximus), CGM could not be effectively utilized because of its low digestibility, the reason for which is still unclear. The purpose of the present study was to investigate and elucidate the cause for the poor utilization of CGM by turbot from the view of gut health. An 8-week feeding trial was conducted with turbot individuals (initial body weight 11.4 ± 0.2 g), which were fed with one of four isonitrogenous and isolipidic diets formulated to include 0%, 21.2%, 31.8%, and 42.6% CGM to progressively replace 0%, 33%, 50%, and 67% fish meal (FM) protein in a FM-based diet, respectively. The results showed that CGM caused dose-dependent decreases in (1) growth performance, nutrient digestibility, and feed utilization; (2) activities of brush-border membrane enzymes; (3) intestinal antioxidant indices of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activities, and reduced glutathione level; (4) intestinal immune parameters of acid phosphatase activity, complement 3, complement 4, and IgM concentrations. Dose-dependent increases in the severity of the inflammation, with concomitant alterations on microvilli structure and increasing expression of inflammatory cytokine genes of Il-1ß, Il-8, and Tnf-α were observed but without a change in the intracellular junctions and the epithelial permeability established by the plasma diamine oxidase activity and D-lactate level examinations. In conclusion, the present work proved that CGM negatively affected the gut health of turbot by inducing enteritis and by decreasing intestinal immunity and antioxidant capacity, which could be one of the reasons for the reduced utilization of CGM by turbot.

Protective Effect of Aplysin Supplementation on Intestinal Permeability and Microbiota in Rats Treated with Ethanol and Iron.

Aplysin, a kind of phytochemicals or phytonutrients, is purified from red alga Laurencia tristicha. The present study aims to investigate the influence of aplysin on changes of intestinal permeability and microbiota induced by excessive ethanol and iron. Thirty male rats were randomly divided into three groups (10/group): control group (normal saline); ethanol + iron group as EI treated with ethanol (8⁻12 mL/kg/day) and iron (1000 mg/kg) in diet; EI supplemented with aplysin (150 mg/kg/day) group as AEI; the trial lasts for 12 weeks. The result showed that levels of plasma endotoxin, fatty acid-binding protein 2, D-lactic acid, diamine oxidase were increased in rats in the EI group; and significantly decreased by 14%, 17%, 26%, 16%, respectively (p < 0.05) in the AEI group after the 12-week aplysin treatment. Moreover, in the AEI group the amount of Escherichia coli and Bacteroides fragilis were higher, while the amount of Lactobacillus, Bifidobacterium and Clostridium were lower than those in the EI group. The expressions of iron transporters divalent-metal transporter 1(DMT1) and ferroportin 1(FPN1) were significantly upregulated in the EI group compared to those in the control group. In conclusion, aplysin could effectively improve intestinal permeability and intestinal flora disorder induced with excessive ethanol and iron.

Lactoferrin Decreases the Intestinal Inflammation Triggered by a Soybean Meal-Based Diet in Zebrafish.

Intestinal inflammation is a harmful condition in fish that can be triggered by the ingestion of soybean meal. Due to the positive costs-benefits ratio of including soybean meal in farmed fish diets, identifying additives with intestinal anti-inflammatory effects could contribute to solving the issues caused by this plant protein. This study evaluated the effect of incorporating lactoferrin (LF) into a soybean meal-based diet on intestinal inflammation in zebrafish. Larvae were fed with diets containing 50% soybean meal (50SBM) or 50SBM supplemented with LF to 0.5, 1, 1.5 g/kg (50SBM+LF0.5; 50SBM+LF1.0; 50SBM+LF1.5). The 50SBM+LF1.5 diet was the most efficient and larvae had a reduced number of neutrophils in the intestine compared with 50SBM larvae and an indistinguishable number compared with control larvae. Likewise, the transcription of genes involved in neutrophil migration and intestinal mucosal barrier functions (mmp9, muc2.2, and ß-def-1) were increased in 50SBM larvae but were normally expressed in 50SBM+LF1.5 larvae. To determine the influence of intestinal inflammation on the general immune response, larvae were challenged with Edwardsiella tarda. Larvae with intestinal inflammation had increased mortality rate compared to control larvae. Importantly, 50SBM+LF1.5 larvae had a mortality rate lower than control larvae. These results demonstrate that LF displays a dual effect in zebrafish, acting as an intestinal anti-inflammatory agent and improving performance against bacterial infection.

[Hyperbaric oxygen and radiotherapy: From myth to reality]. / Oxygénothérapie hyperbare et radiothérapie : entre mythe et réalité.

Worldwide, more than a million people receive each year a curative radiotherapy. While local control and overall survival are steadily increasing, 5 to 15% of patients still develop above grade 2 late toxicities. Late toxicities treatments are complex. Hyperbaric oxygenation was shown to induce revascularization and healing of injured tissues, but indications are still debated. Through a literature review, we summarized the hyperbaric oxygenation indications in radiation-induced late toxicities. We also studied the knowledge and practice of French local radiation therapists. It seems that hyperbaric oxygen therapy can be a conservative treatment of haemorrhagic cystitis and radiation-induced pain, in case of drug therapies failure. Often associated with a significant morbidity and mortality, surgery could be avoided. The risk of complications in case of tooth extraction in irradiated tissues is also reduced. However, the role of hyperbaric oxygenation for mandibular osteoradionecrosis, radiation-induced proctitis, enteritis, lymphoedema, brachial plexopathy, skin and neurological sequelae seems more questionable since studies results are conflicting. Future outcomes of phase III studies are expected to clarify the role of hyperbaric oxygenation in the management of radio-induced toxicities, including for head and necks complications.

Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones.

BACKGROUND: Capsaicin, which is the major pungent principle in chili peppers, is able to induce satiety and reduce caloric intake. The exact mechanism behind this satiating effect is still unknown. We hypothesized that capsaicin induces satiety through the release of gastrointestinal peptides, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), from enteroendocrine cells in the small intestine. OBJECTIVE: We investigate the effects of an intraduodenal capsaicin infusion (1.5 mg pure capsaicin) in healthy volunteers on hunger, satiety, and gastrointestinal symptoms and the release of GLP-1 and PYY. DESIGN: Thirteen participants (7 women) [mean ± SEM age: 21.5 ± 0.6 y; body mass index (in kg/m(2)): 22.8 ± 0.6] participated in this single-blind, randomized, placebo-controlled crossover study with 2 different treatments. During test days, an intraduodenal infusion of either capsaicin or a placebo (physiologic saline) was performed with the use of a nasoduodenal catheter over a period of 30 min. Visual analog scale scores were used to measure hunger, satiety, and gastrointestinal symptoms. Blood samples were drawn at regular intervals for GLP-1 and PYY. Gallbladder volumes were measured with the use of real-time ultrasonography. RESULTS: The intraduodenal capsaicin infusion significantly increased satiety (P-treatment effect < 0.05) but also resulted in an increase in the gastrointestinal symptoms pain (P-treatment × time interaction < 0.0005), burning sensation (P-treatment × time interaction < 0.0001), nausea (P-treatment × time interaction < 0.05), and bloating (P-treatment × time interaction < 0.001) compared with the effects of the placebo infusion. Satiety scores had a positive correlation with all gastrointestinal symptoms. No differences in GLP-1 and PYY concentrations and gallbladder volumes were observed after the capsaicin infusion compared with after the placebo infusion. CONCLUSIONS: An intraduodenal infusion of capsaicin significantly increases satiety but does not affect plasma concentrations of GLP-1 and PYY. Rather, the effect on satiety seems related to gastrointestinal stress as shown by the associations with pain, burning sensation, nausea, and bloating scores. This trial was registered at clinicaltrials.gov as NCT01667523.

[NUTRIENTS AND RADIOTHERAPY; REVIEW OF THE LITERATURE]. / NUTRIENTES Y RADIOTERAPIA; REVISIÓN DE LA LITERATURA.

INTRODUCTION: nutrition is an important influence on treatments and quality of life of cancer patients. The relationship between different nutritional components and radiotherapy is today a topic of growing interest. OBJECTIVE: to evaluate the influence of macro and micronutrients on tolerance and effectiveness of radiotherapy and their role in modulating chronic toxicity. MATERIALS AND METHODS: we performed a research of the published literature by consulting the MEDLINE database and Cochrane Library online between 1995 and 2015, relevant publications based on impact factor were selected. Data from the analyzed studies were exposed in sections by type of nutrient. RESULTS: most of the studies showed common features: small sample sizes, high heterogeneity, underpowered results and few prospective randomized studies. In the section of fiber, its use in prophylaxis and treatment of radiation enteritis has been successfully evaluated in some studies, although evidence of its recommendation is still weak. Omega 3 and omega 6 fatty acids have a high metabolic potential, however the evidence regarding this benefit is limited to observational studies in certain tumors. Among the amino acids, glutamine is the most studied, and controversial results of its effect on mucositis, esophagitis and radiation enteritis were found. Vitamins and minerals are a heterogeneous group of substances that showed potential benefit due to their antioxidant activity and their supposed protector effect against toxicity secondary to radiotherapy. Ketogenic diets are beginning to be clinically studied after promising preclinical results. CONCLUSIONS: the analyzed studies show controversial or inconclusive results regarding the influence of nutrients in the radiotherapy. It has been not found Sorong evidence about their role in patients receiving ionizing radiation. Well-designed, prospective and randomized studies are needed to establish recommendations.

Introducción: la nutrición ejerce una importante influencia sobre los tratamientos y la calidad de vida del paciente oncológico. En la actualidad, la relación de los distintos componentes nutricionales con el tratamiento radioterápico es un tema de creciente interés. Objetivos: evaluar la posible influencia de los macro y micronutrientes sobre la tolerancia y eficacia del tratamiento radioterápico, así como su papel en la modulación de la toxicidad crónica. Material y métodos: se ha realizado una revisión bibliográfica consultando las bases de datos MEDLINE y Biblioteca Cochrane online entre los años 2000 y 2015, seleccionando los trabajos más relevantes según factor de impacto. Los datos obtenidos de los estudios analizados se han expuesto por apartados según el tipo de nutriente. Resultados: la mayoría de los estudios analizados presentan características comunes: pequeños tamaños muestrales, alta heterogeneidad en estudios de un mismo tema, escaso poder estadístico, pocos estudios prospectivos y aleatorizados. En el apartado de la fibra, su empleo como profilaxis y tratamiento de la enteritis rádica ha sido evaluado con resultados satisfactorios en algunos estudios, aunque la evidencia de su recomendación es todavía débil. Los ácidos grasos omega­3 y omega­6 tienen una gran potencialidad metabólica, aunque la evidencia de su beneficio se limita a estudios observacionales en determinados tumores. Entre los aminoácidos, la glutamina es el más estudiado, con resultados contradictorios en el aporte de beneficio en la mucositis oral, la esofagitis y la enteritis rádica. Las vitaminas y minerales constituyen un grupo heterogéneo de sustancias con beneficio potencial por su actividad antioxidante y su posible efecto protector, disminuyendo la toxicidad producida por la radioterapia. Las dietas cetogénicas están comenzando a estudiarse clínicamente después de los prometedores resultados preclínicos. Conclusiones: los estudios analizados muestran resultados contradictorios o poco concluyentes respecto a la influencia de los nutrientes en el tratamiento radioterápico. No se pueden establecer en la actualidadrecomen daciones claras sobre su papel. Son necesarios estudios prospectivos y aleatorizados, bien diseñados, para poder establecer recomendaciones.

A comparative study of intensity-modulated radiotherapy and standard radiation field with concurrent chemotherapy for local advanced cervical cancer.

OBJECTIVE: This study aimed to compare three-dimensional conformal radiotherapy (3D CRT) and intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy for cervical cancer. MATERIALS AND METHODS: A total of 72 patients with Grades IIa-IIIb cervical cancer were randomly divided into two groups, namely, the IMRT group for IMRT plan (primary lesion, 45 Gy/22; the pelvic wall lymphatic drainage area, 50 Gy/22), and the 3D CRT group (conformal pelvic radiotherapy, 45 Gy/22; subsequent supplement of pelvic wall, 6.0 Gy/3). Both groups received concurrent chemotherapy of nedaplatin 30 mg/m2 weekly for six cycles, with an after-loading therapy of 6 Gy/6 each time. RESULTS: In the IMRT group, the grade III diarrhea rate was 5.6% and the rate in the 3D CRT group was 30.6%; both groups significantly differed. No significant difference was observed between the overall survival and disease-free survival in first, second, and third years in both groups. CONCLUSION: Cervical cancer IMRT can significantly reduce the incidence of acute enteritis. For standard 3D CRT, no significant difference was observed in overall survival and disease-free survival.

Preterm Birth Reduces Nutrient Absorption With Limited Effect on Immune Gene Expression and Gut Colonization in Pigs.

OBJECTIVES: The primary risk factors for necrotizing enterocolitis (NEC) are preterm birth, enteral feeding, and gut colonization. It is unclear whether feeding and colonization induce excessive expression of immune genes that lead to NEC. Using a pig model, we hypothesized that reduced gestational age would upregulate immune-related genes and cause bacterial imbalance after birth. METHODS: Preterm (85%-92% gestation, n = 53) and near-term (95%-99% gestation, n = 69) pigs were delivered by cesarean section and euthanized at birth or after 2 days of infant formula or bovine colostrum feeding. RESULTS: At birth, preterm delivery reduced 5 of 30 intestinal genes related to nutrient absorption and innate immunity, relative to near-term pigs, whereas 2 genes were upregulated. Preterm birth also reduced ex vivo intestinal glucose and leucine uptake (40%-50%), but failed to increase cytokine secretions from intestinal explants relative to near-term birth. After 2 days of formula feeding, NEC incidence was increased in preterm versus near-term pigs (47% vs 0%-13%). A total of 6 of the 30 genes related to immunity (TLR2, IL1B, and IL8), permeability (CLDN3, and OCLN), and absorption (SGLT) decreased in preterm pigs without affecting Gram-negative bacteria-related responses (TLR4, IKBA, NFkB1, TNFAIP3, and PAFA). Bacterial abundance tended to be higher in preterm versus near-term pigs (P = 0.09), whereas the composition was unaffected. CONCLUSIONS: Preterm birth predisposes to NEC and reduces nutrient absorption but does not induce upregulation of immune-related genes or cause bacterial dyscolonization in the neonatal period. Excessive inflammation and bacterial overgrowth may occur relatively late in NEC progression in preterm neonates.

Nasal carriage of mecA-positive methicillin-resistant Staphylococcus aureus in pigs exhibits dose-response to zinc supplementation.

Zinc (Zn) is often supplemented at elevated concentrations in swine diets, particularly in piglets, to prevent enteric infections and promote growth. Previous studies from Denmark have suggested a genetic linkage and a phenotypic association between Zn resistance, encoded by czrC, and methicillin-resistance conferred by mecA in Staphylococcus aureus. Such an association has not been reported in the U.S. swine population. We conducted an analysis of the effects of Zn, supplemented as zinc oxide (ZnO), on the nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) in nursery (n=40) and finisher pigs (n=40) enrolled in a nutritional study. Nasal swabs, collected from nursery and finisher pigs, were inoculated onto MRSA CHROMagar and presumptive MRSA colonies were tested for the presence of mecA and czrC genes by polymerase chain reaction. Zinc susceptibility was determined by the agar dilution method. The prevalence of mecA-positive MRSA was 10% (4/40) and 20% (8/40) among nursery and finisher pigs, respectively. Of the 12 mecA-positive S. aureus isolates, 7 had the czrC gene (58.3%) compared to none among the 68 mecA-negative isolates. The presence of both mecA (p=0.002) and czrC (p=0.006) genes were positively associated with higher levels of Zn supplementation. The median minimum inhibitory concentrations of Zn for czrC-positive and czrC-negative isolates were 12 and 2 mM, respectively (p<0.0001). The link between czrC and mecA genes suggests the importance of elevated Zn supplementation in the co-selection and propagation of methicillin resistance among S. aureus in pigs.

Protective effects of L-alpha-glycerylphosphorylcholine on ischaemia-reperfusion-induced inflammatory reactions.

PURPOSE: Choline-containing dietary phospholipids, including phosphatidylcholine (PC), may function as anti-inflammatory substances, but the mechanism remains largely unknown. We investigated the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated PC derivative, in a rodent model of small intestinal ischaemia-reperfusion (IR) injury. METHODS: Anaesthetized Sprague-Dawley rats were divided into control, mesenteric IR (45 min mesenteric artery occlusion, followed by 180 min reperfusion), IR with GPC pretreatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to ischaemia) or IR with GPC post-treatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to reperfusion) groups. Macrohaemodynamics and microhaemodynamic parameters were measured; intestinal inflammatory markers (xanthine oxidoreductase activity, superoxide and nitrotyrosine levels) and liver ATP contents were determined. RESULTS: The IR challenge reduced the intestinal intramural red blood cell velocity, increased the mesenteric vascular resistance, the tissue xanthine oxidoreductase activity, the superoxide production, and the nitrotyrosine levels, and the ATP content of the liver was decreased. Exogenous GPC attenuated the macro- and microcirculatory dysfunction and provided significant protection against the radical production resulting from the IR stress. The GPC pretreatment alleviated the hepatic ATP depletion, the reductions in the mean arterial pressure and superior mesenteric artery flow, and similarly to the post-treatments with GPC, also decreased the xanthine oxidoreductase activity, the intestinal superoxide production, the nitrotyrosine level, and normalized the microcirculatory dysfunction. CONCLUSIONS: These data demonstrate the effectiveness of GPC therapies and provide indirect evidence that the anti-inflammatory effects of PC could be linked to a reaction involving the polar part of the molecule.