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Background: To examine the effect of anastomosis on experimental carcinogenesis in the colon of rats.Methods: Forty-three 10-week-old male and female Sprague-Dawley rats were operated on by performing an end-to-side ileorectostomy. Group A:16 rats received no treatment. Group B: 27 rats received 18 subcutaneous injections weekly at a dose of 21 mg/kg wt of 1-2 dimethylhydrazine (DMH), from the eighth day after the intervention. Animals were sacrificed between 25-27 weeks. The number of tumours, their localization, size and microscopic characteristics were recorded. A paired chi-squared analysis was performed comparing tumoral induction in the perianastomotic zone with the rest of colon with faeces.Results: No tumours appeared in the dimethylhydrazine-free group. The percentage tumoral area was greater in the perianastomotic zone compared to tumours which had developed in the rest of colon with faeces (p = 0.014).Conclusion: We found a cocarcinogenic effect due to the creation of an anastomosis, when using an experimental model of colonic carcinogenesis induced by DMH in rats. [ABSTRACT FROM AUTHOR]

The paper shows how PM speciation studies allow the evaluation of the strategies to be followed to diminish PM pollution in highly industrialized areas with a large number of potential pollution sources. Evolution of levels and speciation of PM10 in the ceramic producing area of Castelló (East Spain) was studied from April 2002 until December 2005. PM10 levels were measured at one rural (Borriana-rural), two suburban (Almassora and Onda) and three urban (Borriana-urban, L''Alcora and Vila-real) sites, all influenced by the ceramics industry. Average PM10 levels varied between 27 and 36 μg/m3 for the study period. Evaluation of 1996–2005 PM data from Onda shows a clear decrease of PM levels since the beginning of 2002. Summer peak levels and winter minima occurred at both rural and suburban sites, whereas urban sites had no clear seasonal trend, with high PM10 episodes being due variously to local, regional, and African dust intrusion events. PM10 chemical analysis at four of the sites showed the dominant constituent to be mineral matter, exceeding by 5–12 μg/m3 the usual ranges of annual mineral loadings in PM10 at comparable Spanish urban or regional background sites with no industrial influence. Given current PM10 loadings, we recommend a lowering target of 3–5 μg/m3 of the annual mean at the urban sites, which should be achievable given available emission abatement techniques. [Copyright &y& Elsevier]

Purpose of Review: The aim of this systematic review was to investigate the effects of whole grain Avena sativa and Hordeum vulgare L., or their isolated fractions, on immune and inflammatory functions, as well as their influence on gut microbiota. A structured literature search was undertaken in line with PRISMA guidelines. Randomized controlled trials (RCTs) that investigated the effects of oats or barley consumption in adults and reported ≥ 1 of the following: C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-2, IL-8, IL-18, lipopolysacharide binding protein (LBP) or gut microbiota-related outcomes, were included., Recent Findings: A total of 16 RCTs were included, among which 6 studies recruited metabolically at-risk population, including individuals with overweight and obesity, metabolic syndrome or hypercholesterolemia. Additionally, 3 trials involved young healthy population, 5 trials targeted older individuals (aged over 50 years), and 2 studies encompassed populations with other disease states. A total of 1091 individuals were included in the evaluation of short-term (up to 14 days) and long-term (beyond 14 days, up to 90 days) supplementation with oats or barley-based products. 9 studies measured inflammatory biomarkers and 5 of them reported significant reductions, specifically in long-term studies. Notably, no evidence of anti-inflammatory benefits was found in healthy individuals, whereas studies involving metabolically at-risk populations showed promising reductions in inflammation. 13 studies measured the impact on gut microbiota, and collectively suggest that oats and barley food products can influence the composition of gut microbiota, associated in some cases with metabolic improvements. Oats and barley consumption may confer anti-inflammatory effects in metabolically at-risk populations and influence gut microbiota outcomes. However, no anti-inflammatory benefits were observed in healthy individuals. Results from this systematic review suggests caution in interpreting findings due to limited trials and variations in interventions and health conditions., (© 2024. The Author(s).)

The present study attempted for the first time to investigate the metabolic fate of (poly)phenolic compounds provided by a hull-less and purple grain barley genotype biofortified in anthocyanins. Balb/c mice were supplemented either with standard purified diet (SD) or whole-grain barley supplemented diet (WGB) for six weeks. Subsequently, (poly)phenolic metabolites were determined in urine samples by UPLC-MS/MS, and the principal metabolic pathways were elucidated. Thirty-nine (poly)phenolics compounds were identified in WGB which were distributed between the free (58%) and bound (42%) fractions, encompassing anthocyanins, phenolic acids, flavan-3-ols and flavones. Upon WGB intake, forty-two (poly)phenolic metabolites were identified, predominantly comprising phase-II sulphate, glucuronide, and/or methylated conjugates, along with colonic catabolites. Noteworthy metabolites included peonidin-3- O -glucuronide, peonidin-3- O -6''- O -malonylglucoside, and peonidin-3- O -glucoside among anthocyanins; hydroxyphenylpropanoic acid- O -sulphate among phenolic acids; and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone- O -sulphate among flavan-3-ols. Metabolites like phenylpropionic, phenylacetic, hydroxybenzoic, and hippuric acids were found in both WGB and SD groups, with higher levels after barley consumption, indicating both endogenous and polyphenolic metabolism origins. Overall, this study offers valuable insights into the metabolism of (poly)phenols in purple barley, setting the stage for future investigations into the health benefits linked to the consumption of purple grain barley.

The present review has analyzed the scientific literature, available in the PubMed and Scopus databases, in order to summarize the current state of diet anthocyanin research in breast cancer (BC) and colorectal cancer (CRC) animal models but also for up-to-date human studies. For CRC, 28 preclinical and 9 clinical studies were selected in line with our search query in science databases. In relation to BC, 14 preclinical and 5 clinical studies were selected. Remarkably, all the preclinical studies, to a greater or lesser degree, suggested a chemoprevention effect of anthocyanin in BC/CRC rodent models. These encouraging results from animal models are not extrapolated to the same degree to human studies where, from the similar theoretical daily doses of anthocyanins in these studies, the opposite results were reported. Nevertheless, it is worth mentioning that the anthocyanin doses in the human studies carried out recently are low if we consider the estimated exposure to anthocyanins issued by the European Food Safety Agency (EFSA) or extremely low if we consider with caution the human equivalent dose based on body surface area from the preclinical dosage regimes used. Therefore, although some clinical data has demonstrated an inverse relation between anthocyanin consumption and BC/CRC, this could, in fact, be more relevant if we increase the daily human anthocyanin dose (as observed in animal model dose-effect studies) while new toxicological data for this flavonoid subtype are brought to light., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats., (© 2021 Wiley-VCH GmbH.)

Colorectal cancer (CRC) is the fourth cancer with the most new cases reported in 2018 worldwide. Consumption of fruit and vegetables is a protective factor against the risk of CRC. Beyond this, flavonoids could orchestrate these healthy effects. Apart from containing the typical apple flavonoids, red-fleshed apples also contain anthocyanins, mainly cyanidin-3-O-galactoside (Cy3Gal). Through an azoxymethane rat carcinogenesis model, a study was carried out in order to assess the possible protective effects of apple polyphenols, with special attention to anthocyanins. In addition, apart from negative and positive controls, a group with chemotherapy with 5-fluorouracil (5FU) was included to compare their performance against the output collected from the animal treatments with white-fleshed apple (WF), red-fleshed apple (RF) and Cy3Gal (AE). Although the 5FU group presented the best performance towards aberrant crypt foci (ACF) inhibition (70.1%), rats fed with white-fleshed apples ('Golden Smoothee') were able to achieve 41.3% ACF inhibition, while none of the challenged treatments (WF, RF and AE) suffered mucin depletion in their colonocytes. Expression changes of 17 genes related to CRC were assessed. In detail, the ACF inhibition phenotype detected in 5FU and WF groups could be explained through the expression changes detected in the apoptosis-related genes of Aurka, p53 and Cox2. Moreover, in the apple consumption groups (WF and RF), a reduced protein expression of matrix metalloproteinases with gelatinase activity (MMP-2 and 9) was detected. Overall, our study suggests an effect of apple polyphenols and apple anthocyanin Cy3Gal against colon carcinogenesis, retarding/diminishing the appearance of the precancerous markers studied., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Chronic infection with hepatitis C virus is a risk factor for developing atheromatous plaques, although the possible effect of virus clearance is unknown. Our aim was to determine whether or not subclinical atheromatosis improved and there was any modification in the composition of the plaques 12 months after eradication of hepatitis C virus by direct-acting antiviral agents., Materials and Methods: Prospective study that included 85 patients with chronic hepatitis C virus infection in different stages of fibrosis who were on direct-acting antiviral agents. Patients with a cardiovascular history, diabetes and kidney disease were excluded. An arterial ultrasound (carotid and femoral) was performed to diagnose atheromatous plaques (defined as intima-media thickness ≥1.5mm) and the composition (percentage of lipids, fibrosis and calcium with HEMODYN4 software) was analysed at the beginning of the study and 12 months after stopping the therapy., Results: After follow-up no changes were detected in the intima-media thickness (0.65mm vs. 0.63mm, P=.240) or in the presence of plaques (65.9% vs 71.8%, P=.063). There was also no significant change in their composition or affected vascular territory, with an increase in blood lipid profile (P<.001) after 12 months of treatment. These results were confirmed in subgroups by severity of liver disease., Discussion: The eradication of hepatitis C virus by direct-acting antiviral agents does not improve the atheroma plaques and nor does it vary their composition, regardless of liver fibrosis. More prospective studies are needed to evaluate residual cardiovascular risk after virus eradication., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Colorectal cancer (CRC), also known as colon cancer, is the third most common form of cancer worldwide in men and the second in women and is characterized by several genetic alterations, among them the expression of several genes. 1,2-dimethylhydrazine (DMH) and its metabolite azoxymethane (AOM) are procarcinogens commonly used to induce colon cancer in rats (DMH/AOM rat model). This rat model has been used to study changes in mRNA expression in genes involved in this pathological condition. However, a lack of proper detailed PCR primer design in the literature limits the reproducibility of the published data. The present study aims to design, optimize and validate the qPCR, in accordance with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines, for seventeen genes commonly used in the DMH/AOM rat model of CRC ( Apc, Aurka, Bax, Bcl2, β -catenin, Ccnd1, Cdkn1a, Cox2, Gsk3beta, IL-33, iNOs, Nrf2, p53, RelA, Smad4, Tnfα and Vegfa ) and two reference genes ( Actb or β - actin and B2m ). The specificity of all primer pairs was empirically validated on agarose gel, and furthermore, the melting curve inspection was checked as was their efficiency (%) ranging from 90 to 110 with a correlation coefficient of r 2  > 0.980. Finally, a pilot study was performed to compare the robustness of two candidate reference genes., Competing Interests: The authors declare there are no competing interests.

Background: Telomere length (TL) shortened occurs in colorectal carcinogenetic process. Our objective is to determine if it is only a local fact or there are alterations in normal colon cells and in other body cells., Methods: TL of tumoral and normal mucosa and leukocytes of 40 patients operated of colorectal cancer (CRC) and 40 control patients with normal colonoscopy were measured by Southern-blot. Groups were matched by the same localization as tumors, sex, and age., Results: In CRC patients, TRFL (Telomere Repeat Factor Length) leukocytes mean was 8.84 kpb, normal colonic mucosa 7.97 kpb, and tumoral mucosa 7.33 kpb (P < 0.001). In the 40 normal control patients, mean TRFL of colonic mucosa was 7.76 kpb, while in blood cells was 7.01 kpb (P < 0.001). We observed an inverse correlation between leukocytes TRFL and age (r(2)  = 0.17, P = 0.008). Mucosa TRFL correlates significantly with patient's age (r(2)  = 0.138, P = 0.018). TRFL of controls colonic mucosa correlates with TRFL of their blood cells (r(2)  = 0.354, P < 0.001)., Conclusions: Normal colonic mucosa and leukocytes in CCR patients presents telomere altered in respect to normal patients. Telomere length in normal leukocytes could be an initial marker for colorectal cancer., (© 2015 Wiley Periodicals, Inc.)

We have previously demonstrated that the non-digestible fraction (NDF) from common cooked beans (P. vulgaris L., cv Negro 8025) inhibits azoxymethane (AOM)-induced colon cancer and influences the expression of genes involved in the induction of apoptosis and cell cycle arrest through the action of butyrate. The objective of this study was to identify cell cycle alterations and morphological changes induced by treatment with AOM and to examine the formation of colonic aberrant crypt foci (ACF) in male Sprague Dawley rats fed with these beans. Rats were fed control diets upon arrival and were randomly placed into four groups after one week of acclimatization: control, NDF (intragastric administration), NDF + AOM and AOM. Rats treated with NDF + AOM exhibited a significantly lower number of total colonic ACF with a notable increase in the number of cells present in the G1 phase (83.14%); a decreased proliferation index was observed in the NDF + AOM group when compared to AOM group. NDF + AOM also displayed a higher number of apoptotic cells compared to AOM group. NDF of cooked common beans inhibited colon carcinogenesis at an early stage by inducing cell cycle arrest of colon cells and morphological changes linked to apoptosis, thus confirming previous results obtained with gene expression studies.

Background: colorectal cancer is the third cancer cause of death in Spain. It is important to investigate new tumoral markers for early diagnosis, disease monitoring and prevention strategies. Telomeres protect the chromosome from degradation by nucleases and endto-end fusion. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1) is a protein that binds at telomere ends., Purpose: to measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa., Method: from normal and tumoral samples of 83 patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration by Western Blot, telomerase activity, by the fluorescent-telomeric repeat amplification protocol assay and telomere length by Southern Blot., Results: high levels of TRF1 were observed in 68.7% of tumor samples, while the majority of normal samples (59%) showed negative or weak TRF1 concentrations. Among the tumor samples, telomere length was significantly associated with TRF1 protein levels (p = 0.023)., Conclusions: a relationship was found between telomere length and TRF1 abundance protein in tumor samples, which means that TRF1 is an important factor in the tumor progression and maybe a diagnostic factor.

Colorectal cancers exhibit a high telomerase activity, usually correlated with the hypermethylation of the promoter of its hTERT catalytic subunit. Although telomerase is not expressed in normal tissue, certain proliferative somatic cells such as intestinal crypt cells have demonstrated telomerase activity. The aim of this study was to determine whether a correlation exists between telomerase activity, levels of hTERT methylation and telomere length in tumoral and normal colorectal tissues. Tumor, transitional and normal tissues were obtained from 11 patients with a colorectal cancer. After bisulfite modification of genomic DNA, hTERT promoter methylation was analyzed by methylation-sensitive single-strand conformation analysis (MS-SSCA). Telomerase activity and telomere length were measured by a fluorescent-telomeric repeat amplification protocol assay and by Southern blotting, respectively. A significant increase of hTERT methylation and telomerase activity, and a reduction of the mean telomere length were observed in the tumor tissues compared to the transitional and normal mucosa. In the transitional and normal mucosa, telomerase activity was significantly lower than that in tumor tissues, even with high levels of hTERT methylation. Nevertheless, hTERT promoter methylation was not linearly correlated to telomerase activity. These data indicate that hTERT promoter methylation is a necessary event for hTERT expression, as is telomerase activity. However, methylation is not sufficient for hTERT activation, particularly in normal colorectal cells.

A high expression of vitamin D receptor (VDR) in colorectal cancer (CRC) tumoral tissue has been related to a good prognosis and it has been proposed that it could be a good biological marker of CRC progression. Nevertheless, there are no previous studies that compare the VDR expression in tumoral towards normal tissue of the same CRC patient in relation to VDR BsmI genotype. We collected normal and tumoral tissue samples, as well as blood samples, from CRC patients (n=170) and controls (n=122). VDR genotyping was performed and BsmI homozygous patients were selected (CRC=50, Cont=32). VDR mRNA and protein levels were analyzed. We also measured 25-Hydroxyvitamin D serum levels. We found no differences in the polymorphism distribution in tumoral versus normal tissue (control: BB=15.7%, bb=41.3%, Bb=43%; CRC: BB=14.2%, bb=41.9%, Bb=43.9%). Furthermore, VDR levels decreased in colonic cancer tissue (mean: 3.03) versus normal mucosa (11.62) from the same patient (p<0.001), but this decrease was similar in both genotypes. There were differences in 25-Hydroxyvitamin D(3) levels between the CRC and the control group (CRC=8.65 ng/ml, Cont=18.15 ng/ml). In conclusion, we found a decrease in VDR levels in tumoral compared with normal mucosa from the same patient. This difference is independent of the BsmI polymorphism.

Aims: The present study was designed to examine the effect of ursodeoxycholic acid as chemoprotective agent in experimental colon carcinogenesis in rats., Material and Methods: One hundred and ten 10-week-old, Sprague-Dawley rats were divided into five groups: group A (20), no treatment. Group B (20), receiving daily both ursodeoxycholic acid (UDCA) 4 mg/kg of body weight and ethanol 1.23 g/kg of body weight added to the drinking water from the beginning of the study through 24 weeks. Group C (30), receiving 18 weekly doses of dimethylhydrazine (DMH) 21 mg/kg of body weight subcutaneously from the beginning of the study, with the same doses of UDCA and ethanol as in group B. Group D (20), ethylen-diamin-tetracetic acid solution alone for 18 weeks. Group E (20), receiving the same doses of ethanol plus DMH injections as in group C. All experimental animals were sacrificed after 25-27 weeks., Results: No tumors developed in dimethylhydrazine-free groups. No significant differences in number of tumor-free animals, number of tumors per rat, and macro-microscopic tumor findings were seen between animals in group C and animals in group E., Conclusions: We concluded that such an ursodeoxycholic acid supplementation did not modify colorectal carcinogenesis using a dynamic DMH-induced model in rats.

Background and Objective: The most effective currently available therapy for chronic hepatitis C virus infection is the combination of interferon alpha-2b plus ribavirin both, in patients with human immunodeficiency virus (HIV) coinfection and in patients without coinfection. In an attempt to avoid morbidity and health costs we searched for an indicator of early virologic response (EVR). We evaluated the EVR efficiency at 4 and 12-weeks after the initiation of antiviral combination therapy., Patients and Method: A total of consecutive 127 patients with chronic hepatitis C virus infection treated with combination therapy for 12 months in genotypes 1 and 4 and for 6 months in genotypes 2 and 3, were studied, 62 HIV-coinfected and 65 non-coinfected. They were evaluated for sustained virologic response and EVR at 4 and 12-weeks to initial therapy., Results: Sustained virologic response was greater in the non-coinfected group than coinfected group; these differences were significant for genotypes 1 and 4. In both groups EVR had a 100% predictive negative value at 12-weeks after the initiation of therapy in genotypes 1 and 4, however came down in 79% at 4-weeks., Conclusions: The EVR at 12-weeks after the initiation of therapy has a 100% predictive negative value in coinfected and non-coinfected patients. Patient adherence to prescribed antiviral therapy is a predictive value of response.

Objective: To investigate the effect of repetitive mucosal trauma, anastomosis and intestinal content on experimental colonic carcinogenesis as there is the possibility than non-specific colon lesions can promote cancer., Material and Method: We performed to sixty female Sprague-Dawley rats a 4 cm colon loop defunctionalization with double colostomy (traumatic site). Intestinal continuity was restored with an end-to-end colo-colic silk anastomosis. The surviving 47 rats were divided in 3 groups: Group A: 27 rats treated with DMH. Group B: 10 rats treated with EDTA and Group C: Control of 10 rats. Animals were sacrificed 31-32 weeks after surgery for macro and micropathological studies., Results: In group A appeared 60 tumours: 44 in the functional colon, 20 of them in the anastomotic site; 8 in the non traumatised defunctionalized segment and 18 in the traumatised segment (p < 0.05)., Conclusions: a) Continuous microtraumas on colonic mucosa in rats are cancer promotional factors; b) silk suture in anastomosis promotes cancer.