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Background: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. Objective: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. Methods: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with

Dimethoate ([O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithioate]) is an organophosphate insecticide and acaricide widely used for agricultural purposes. Genotoxicity refers to the ability of a chemical agent interact directly to DNA or act indirectly leading to DNA damage by affecting spindle apparatus or enzymes involved in DNA replication, thereby causing mutations. Taking into consideration the importance of genotoxicity induced by dimethoate, the purpose of this manuscript was to provide a mini review regarding genotoxicity induced by dimethoate as a result of oxidative stress. The present study was conducted on studies available in MEDLINE, PUBMED, EMBASE, and Google scholar for all kind of articles (all publications published until May, 2020) using the following key words: dimethoate, omethoate, DNA damage, genetic damage, oxidative stress, genotoxicity, mutation, and mutagenicity. The results showed that many studies were published in the scientific literature; the approach was clearly demonstrated in multiple tissues and organs, but few papers were designed in humans. In summary, new studies within the field are important for better understanding the pathobiological events of genotoxicity on human cells, particularly to explain what cells and/or tissues are more sensitive to genotoxic insult induced by dimethoate.

The aim of this study was to evaluate cytogenotoxicity in mammalian cells induced by ingestion of superficial water from SESS. For this purpose, surface water was collected from two points of SESS: Sao Vicente Channel (SVC) and Piacaguera Channel (PIC). Four groups (n = 5) of adult male Wistar (8 weeks old) received for 5 days: (a) filtered tap water (water control), (b) tap water with 2.4% of NaCl (saline control), (c) estuarine water from PIC and (d) estuarine water from SVC. Results demonstrated that Ki67 immunoexpression was higher in hepatocytes exposed to both sampling site, while caspase-3 demonstrated downregulation in rat liver exposed to estuarine water. There was also significant increase in micronuclei frequency in bone marrow cells and hepatocytes, and DNA damage in blood and liver of rats exposed to estuarine water from SVC and PIC. In summary, studies with complex mixtures, such as contaminated estuarine water are important since this work confirmed by experiments using in vivo mammalian cells of rats that SESS water are genotoxic, mutagenic and cytotoxic, denoting concern for environmental health.

Background and aim Human gut microbiota play an important role in metabolism and host physiology. Perturbations of the gut microbial communities lead to the development of various diseases such as inflammatory bowel disease, celiac disease, allergic diseases, and metabolic diseases. Crohn's disease is a chronic inflammatory bowel disease characterized by periods of remission and relapse. Several studies suggest that intestinal inflammation arises due to an abnormal response of the intestinal immune system to the fecal microbiota. The goal of the study was to evaluate the relative amount of four bacterial groups in fecal samples of Crohn's disease patients and their relation to the inflammatory activity. Methods We studied stool samples of 105 individuals, 54 with Crohn's disease and 51 as a control group. The DNA extracted from the stool samples was subjected to real‐time polymerase chain reaction (qPCR) for quantification of the Bacteroidetes phylum, class Bacilli, and Bifidobacteriaceae and Enterobacteriaceae families. Results We found a significant increase in Bacteroidetes in Crohn's disease samples when compared to the control group (14 650 and 2060 CFU/ng DNA, respectively) (P = 0.014). On the other hand, we observed a significant reduction in Bacilli and Bifidobacteriaceae (13 and 58 CFU/ng DNA, respectively) (P, Gut microbiota is strongly associated with host physiology, and perturbations of the gut microbial communities lead to the development of various diseases. The goal of this study was to evaluate the relative amount of four bacterial groups in fecal samples of patients with Crohn's disease and their relation to the inflammatory activity. We observed that the commensal bacteria were decreased in fecal samples of participants with Crohn´s disease when compared to the control group. There was no relation between the disease localization and/or clinical condition with the microbiota.

BACKGROUND/AIM The pesticide dimethoate (O-dimethyl-S- Nmethylcarbamoylmethyl phosphorodithioate) is able to induce severe acute toxicity in living organisms. The aim of this study was to evaluate the effects of ultraviolet radiation, alone or combined with exposure to dimethoate, on the rat skin. MATERIALS AND METHODS A total of 38 Wistar female rats (Rattus norvegicus albinus), were distributed into four groups: A (n=9) control group, B (n=10) exposed to ultraviolet-B radiation (UV-B), C (n=10) exposed to UV-B followed by application of dimethoate (UV-B+AGRO) and group D (n=9) exposed to dimethoate (AGRO). Histological examination of the tissues, as well as immunohistochemistry for cleaved caspase 3, Ki-67 and COX-2 expression were performed to all groups. RESULTS Animals submitted to UV-B exhibited hyperkeratosis with moderate cell atypia. Regarding exposure to UV-B+AGRO, the animals presented hyperkeratosis and atrophy, whereas in animals exposed to AGRO, only atrophy was noticed. The immunohistochemical results on skin revealed that UVB, AGRO and UVB+AGRO decreased cleaved caspase 3 and Ki-67 expression when compared to the control group (p

Since its discovery as an antimicrobial agent, fluoride has been used in the control of dental caries. Many studies have shown that the chronic exposure of fluoride in high concentrations causes adverse effects in multiple organs; the use of bioactive compounds present in foods as a tool to mitigate the effects of fluoride could potentially be useful for populations in different parts of the world are exposed to fluoride in a chronic and systemic way. Thus, the aim of this comprehensive review is to present and discuss the published papers that focused on the use of polyphenols and nonpolyphenols that can mitigate the harmful activities promoted by fluoride exposure. Certainly, these data will contribute toward a better understanding of the role of food compounds in the pathological outcomes induced by fluoride. The new information will be added to that already available for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

STUDY OBJECTIVES: The pathogenesis of inflammatory bowel disease (IBD) is not well understood, and sleep disorders may be potential triggers for IBD. Thus, an evaluation of the sleep characteristics, fatigue symptoms, and cytokine levels was performed in patients with IBD during periods of active disease and remission. METHODS: A total of 20 participants presenting with Crohn's disease or ulcerative colitis, with active disease (n = 7) or in remission (n = 13), underwent home polysomnography (H-PSG). Pittsburgh Sleep Quality Index (PSQI) and Modified Fatigue Impact Scale (MFIS) were applied, in addition to the evaluation of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) serum levels. Exploratory analysis, t test and Mann-Whitney U test were used. RESULTS: The mean sleep latency in patients with active disease was 133.07 minutes and 106.79 minutes in those in remission. The sleep efficiency and sleep fragmentation in patients with active disease and those in remission were 80.90% and 84.20% (median), and 76.36/min and 69.82/min (mean), respectively, although the H-PSG parameters did not differ between the groups. The PSQI scores indicated poor sleep quality (global score above 5) in all participants with IBD, and the participants with active disease presented more symptoms of fatigue (P = .032). IL-6 and TNF-α average levels were higher in the participants with disease remission, although with a larger dispersion of the data. CONCLUSIONS: No significant difference in the H-PSG characteristics was observed between the patients with IBD with active disease and those in remission; however, the perception of the participants with IBD showed significant effect on the sleep quality and fatigue symptoms. CITATION: Paixão DL, Poyares D, de Paula MS, Duarte JW, Castelo PM, Ambrogini-Júnior O, Miszputen SJ, Oshima CT, Chagas JR, Paiotti AP. Evaluation of home polysomnography findings, quality of sleep, and fatigue in inflammatory bowel disease: a case series. J Clin Sleep Med. 2019;15(1):39–45.

O tumor estromal gastrointestinal e uma neoplasia rara que afeta as celulas intersticiais cajais devido a disfuncao nos genes KIT ou PDGFRA. E considerado um tumor mesenquimal raro, mas comum no trato digestivo. O objetivo foi analisar um tratamento, epidemiologia e imunolocalizacao da proteina KIT e a atuacao do enfermeiro em relacao aos pacientes com GIST. Os criterios de inclusao foram laudos anatomopatologicos expedidos pelo servico de Anatomia Patologica da UNIFESP / EPM, a partir de 2010, com diagnostico de GIST. Vinte e uma escolhidos foram selecionados para analise imunohistoquimica do KIT. Entre as mulheres, 54,6% tinham mais de 60 anos e entre os homens 90%. A localizacao mais comum entre as mulheres foi o estomago com 63,7%, enquanto nos homens, o estomago teve a mesma porcentagem do intestino (40%). A imunohistoquimica mostrou positividade para C-KIT em 81,8% das mulheres e 90% dos homens. O tamanho medio da lesao foi de 5,58 cm e 3,8 cm nas mulheres e nos homens, respectivamente. A presenca de necrose foi verificada em 27,3% das mulheres e 30% dos homens. A morfologia mais prevalente foi uma celula fusiforme com aproximadamente 70% em mulheres e homens. Dos 21 casos, tres pacientes morreram, dois tiveram recidiva e, em cinco casos, foi realizado tratamento adjuvante com mesilato de imatinibe. Para a atuacao da enfermeira na frente do paciente com GIST, foi necessario confirmar a expressao da proteina KIT, o que permite um diagnostico diferencial. A analise da incidencia e da epidemiologia dessa populacao agregada aos enfermeiros agregar mais conhecimentos sobre esse tumor.

Genotoxicity is the ability of an agent to produce damage on the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, to elucidate the putative mechanisms of genotoxicity induced by fluoride are important to measure the degree of risk involved to human populations. The purpose of this article is to provide a comprehensive review on genotoxicity induced by fluoride on the basis of its mechanisms of action. In the last 10 years, all published data showed some evidence related to genotoxicity, which is due to mitochondrial disruption, oxidative stress, and cell cycle disturbances. However, this is an area that still requires a lot of investigation since the published data are not sufficient for clarifying the genotoxicity induced by fluoride. Certainly, the new information will be added to those already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

The aim of this study was to evaluate the protective effect of grape skin or purple carrot extracts against cadmium-induced intoxication in rats’ kidneys. For this purpose, 30 male Wistar rats were distributed into six groups (n = 5), as follows: control group; cadmium group and groups treated with grape skin at 175 or 350 mg / L doses; or purple carrot extract at 400 mg / L or 800 mg / L doses, by drinking water. In the group exposed to cadmium, histopathological analysis revealed severe tissue injury as a result of coagulation necrosis, congested vessels and inflammatory infiltrate. Animals treated with grape skin or purple carrot extracts improved the histopathological changes induced by cadmium. 8-OHdG immunoexpression and catalase gene expression decreased in rats treated with purple carrot or grape skin extracts. Grape skin extract was able to increase SOD-CuZn gene expression as well. Toll-like signaling pathway (TLR2, PIKK and TRAF6) and cytochrome c expressions were not altered after the treatment with grape skin or purple carrot extracts. Taken together, we conclude that grape skin and purple carrot extracts had a protective effect on the rats’ kidneys after cadmium intoxication, by means of tissue regenerating tissue regeneration and antioxidant properties, grape skin extract being more effective for this purpose.

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

AIM To evaluate the technical application of fluorescence in situ hybridization (FISH) as a support to classical cytogenetic in numerical chromosomal aneuploidies studies in samples of amniotic fluid, chorionic villus, and fetal loss. MATERIALS AND METHODS The authois performed cytogenetic analyses in 1,409 patients (678 amniocentesis, 512 chorionic villus samples, and 219 spontaneous abortions) during one year. FISH molecular study aided traditional cytogenetic in 90 cases. These cases were indicated based on the diagnostic hypothesis of each patient or when no cellular growth was obtained. The authors standardized the FISH in discoloured slides. RESULTS They had 85% positive FISH in amniotic fluid, 70% in chorionic villus, and 90% in abortion material using 13, 18, 21 X and Y centromeric probes. It showed 12% of altered FISH in amniotic fluid (100% trisomies), 10% in chorionic'villus (50% trisomy and 50% X - monosomy), and 22% in abortion material (50% trisomy, 25% X-monosomy, and 25% triploidy). FISH and cytogenetic analysis confirmed the results. CONCLUSION This technique revolutionized clinical and research applications of cytogenetics. In this particular paper, FISH was a valuable and reliable technique to promptly identify rapid detection of aneuploidies in interphase cells, metaphase spread and paraffin-embedded samples. It is hoped that, in the future, the economic viability of array CGH and FISH, with the decreasing cost of testing and their genomics advantages can be incorporated as routine and customized in the approach of prenatal diagnosis.

The aim of this study was to investigate if purple carrot extract is able to protect against the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis, genotoxicity and oxidative status were investigated in this setting. A total of twenty Wistar rats weighing 250g on the average, and 8 weeks age were distributed into four groups (n=5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and Purple carrot extract groups at 400mg/L or 800mg/L. Histopathological analysis revealed that liver from animals treated with purple carrot extract improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as depicted by comet and micronucleus assays in animals treated with purple carrot extract. SOD-CuZn and cytocrome C gene expression increased in groups treated with purple carrot extract. Purple carrot extract also reduced the 8OHdG levels in liver cells when compared to cadmium group. Taken together, our results demonstrate that purple carrot extract is able to protect against cadmium intoxication by means of reducing tissue regeneration, genotoxicity and oxidative stress in multiple organs of Wistar rats.

Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.

The aim of this study was to evaluate the health benefits associated with apple consumption following cadmium exposure. A total of 15 Wistar rats were distributed into three groups (n=5), as follows: control group (non-treated group, CTRL); cadmium group (Cd) and apple juice group (Cd+AJ). The results showed a decrease in the frequency micronucleated cells in bone marrow and hepatocytes in the group exposed to cadmium and treated with apple juice. Apple juice was also able to reduce the 8OHdG levels and to decrease genetic damage in liver and peripheral blood cells. Catalase (CAT) was decreased following apple juice intake. Taken together, our results demonstrate that apple juice seems to be able to prevent genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.

Several studies have shown that apple (Malus sp.) has many components able to exert chemopreventive activity. The aim of this study was to evaluate the chemopreventive potential of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO) by means of histopathological analysis and gene expression of antioxidant enzymes, such as CuZnSOD, MnSOD and catalase. A total of 30 male Wistar rats were distributed into five groups, as follows (n = 6 per group): Group 1 - negative control group (non-treated group); Group 2 - received 4NQO during 8 weeks in drinking water and treated with apple extract by gavage between the 1st and 4th weeks daily (initiation phase); Group 3 - received 4NQO for 8 weeks in drinking water and treated with apple extract by gavage between the 5th and 8th weeks daily (promotion phase); Group 4 - received apple extract by gavage for eight consecutive weeks only; and Group 5 - received 4NQO for 8 weeks in drinking water daily. Histopathological analysis revealed that apple extract protect oral lesions induced by 4NQO at initiation or promotion phase. Higher gene expression of CuZnSOD and MnSOD enzymes were noticed in groups treated with apple extract as well. Taken together, our results demonstrate that the apple extract is able to modulate medium-term oral carcinogenesis assay as a result of antioxidant activity.

The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis.For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate.The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p 0.05) among groups.In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.

The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 – Sham group:; G2 – TNBS group; G3, G4 –colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 – colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

The aim of this study was to evaluate the toll like signaling pathway and atrophy after sleep deprivation (SD) in rat masticatory muscles: masseter and temporal. A total of twenty-four animals was distributed into three groups: Control group (CTL, n = 8), subjected to SD for 96 hours (SD96, n = 8) and subjected to SD for 96 hours more 96 hours of sleep recovery (SD96 + R, n = 8). Histopathological analysis revealed the presence of acute inflammatory cells, congested vessels, fibrosis and high cellularity in the skeletal muscle fibers from masseter and temporal submitted to SD. These morphological alterations were not observed in the control group since neither inflammatory cells nor congested vessels were observed to this group. In the group SD96 + R, the absence of inflammation was noticed to the masseter only. In this group, COX-2 and TNF-alpha downregulation were detected when comparing to control group. MyD88 and pIKK decreased in SD96 and SD96+ R groups being pNFKBp50 downregulatated in SD96 + R. MyD88 expression increased in rats submitted to SD96 and SD96 + R in temporal when compared to control group. On the other hand, pIKK decreased the protein expression in groups SD96 and SD96 + R while pNFKBp50 showed a decreased protein expression in group SD96 only. The activation of atrophy by means of MAFbx upregulation was detected in temporal muscle in SD96 and SD96 + R when compared to control. In summary, our results show that SD is able to induce morphological alterations in rat masticatory muscles. Toll like signaling pathway and atrophy play important roles in ethiopathogenesis induced by SD, being dependent of skeletal muscle type. This article is protected by copyright. All rights reserved

Dental X-rays are widely used in clinical practice, since the technique is an important approach for diagnosing diseases in dental and periodontal tissues. However, it is widely known that radiation is capable of causing damage to cellular systems, such as genotoxicity or cytotoxicity. Thus, the aim of this review was to present a critical analysis regarding the studies published on genotoxicity and cytotoxicity induced by dental X-rays in oral mucosa cells. Such studies have revealed that some oral cell types are more sensitive than others following exposure to dental X-rays. Certainly, this review will contribute to a better understanding of this matter as well as to highlighting perspectives for further studies. Ultimately, such data will promote better safety for both patients and dental professionals.

Apples and their derivatives are rich in phytochemicals, including flavonoids (catechins, flavonols, quercetin) and phenolic acids (quercetin glycosides, catechin, epicatechin, procyanidins), vitamins, and fibers, that confer an important antioxidant property. Chemoprevention is defined by the use of natural or synthetic agents to interfere with the progression, reverse, or inhibit carcinogenesis, thereby reducing the risk of developing clinically invasive disease. The aim of this article is to present data generated from the use of apples as a chemopreventive agent in carcinogenesis using in-vivo and in-vitro test systems. Apple and its bioactive compounds can exert chemopreventive properties as a result of antioxidant activity and cell cycle control. However, future focus of research on apple such as identifying the specific phytochemical responsible for the anticarcinogenic effect, timing of consumption, and adequate amount of apples to achieve the best preventive effect using human large randomized-controlled trials is needed. Furthermore, animal studies are also relevant for better understanding the role of this fruit in human health as well as modulation of degenerative diseases such as cancer. Therefore, this area warrants further investigation as a new way of thinking, which would apply not only to apples but also to other fruit used as promising therapeutic agents against human diseases.

1 Pathology, 2 Psichobiology, 3 ABSTRACT Background: The aim of this study was to evaluate whether paradoxical sleep deprivation could affects the mechanisms and pathways essentials for cancer cells in tongue cancer induced by 4‑nitroquinole 1‑oxide in Wistar rats. Materials and Methods: For this purpose, the animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to paradoxical sleep deprivation (PSD) for 72 h using the modified multiple platform method, which consisted of placing 5 mice in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl‑2 proteins related to apoptosis and its pathways. Results: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre‑neoplasic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53 and for bcl‑2 and for all immunomarkers after 12 weeks of 4NQO administration. Conclusion: Our results reveal that sleep deprivation exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis. AQ1

The aim of this study was to evaluate the antimutagenic and antigenotoxic potential of grape juice concentrate in rodent organs exposed to cadmium chloride intoxication. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (CTRL; nontreated group), cadmium group (Cd), and cadmium-grape juice group (Cd + GJ). Exposed animals received intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) diluted in water and, after 15 days, Cd + GJ group received grape juice concentrate for 15 days, by gavage (0.8 mL, 1.18 mg of polyphenols kg(-1) day(-1)). Grape juice concentrate was able to decrease genotoxic effects induced by cadmium in peripheral blood and liver cells as depicted by single cell gel (comet) and micronucleus assays. A decrease for anti-8-hydroxy-20-deoxyguanosine (8OHdG) expression in hepatocytes of animals exposed to cadmium and treated with grape juice concentrate was also detected. Higher CuZn-SOD activity was observed in liver cells of the Cd + GJ group. No remarkable differences were seen regarding Mn-SOD activity among groups. Taken together, our results demonstrate that grape juice concentrate was able to exert antimutagenic and antigenotoxic activities in blood and liver cells of rats exposed to cadmium.

Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Flavonoids exert several biological activities, which are mainly related to their ability to inhibit inflammatory process and/or to their antioxidant properties, and are able to regulate the immune response. The aim of this study was to evaluate whether phenolic compounds present in grape juice could reduce the inflammatory effects induced by experimental colitis. A total of 41 male Wistar rats were randomized into seven groups, as follows: G1--Sham group: sham induced-colitis rats; G2--(2,4,6-rinitrobenzenesulfonic acid) TNBS group: nontreated induced-colitis; G3--2% grape juice control group; G4--1% grape juice 24h after TNBS colitis induction; G5--1% grape juice on day 7 after colitis induction; G6--2% grape juice 24h after colitis induction; G7--2% grape juice on day 7 after colitis induction. Genotoxicity was evaluated by comet assay. Immunohistochemistry was determined using the streptavidin-biotin-peroxidase method being analyzed in control (normal tissue) and "hot spot" areas i.e., presenting inflammatory process being graded as 1 (weak), 2 (moderate), or 3 (strong). Both parameters were evaluated in the cytoplasm of epithelial or inflammatory cells. TNF-immunoexpression and iNOS were reduced after drinking grape juice 24 h or after 7 days for all doses tested. COX-2 was reduced in the groups exposed to 1% grape juice 24 h or 7 days of exposure. The grape juice at 1% dose in the last 7 days of treatment as well as grape juice at 2% dose decreased the peripheral blood genotoxicity. Taken together, the grape juice mainly at 1% dose exerts anti-inflammatory effects in chronic colitis caused by TNBS as a result of down regulation in the expression of pro-inflammatory cytokines and reduction of genotoxicity in peripheral blood cells.

The aim of this study was to evaluate the anti-tumor activity of grape juice concentrate following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO). A total of 30 male Wistar rats were distributed into five groups, as follows (n = 6 per group): Group 1 - negative control group (non-treated group); Group 2 - received grape juice concentrate at 1% dose by gavage for eight consecutive weeks; Group 3 - received 4NQO for 8 weeks at 20 ppm dose in drinking water daily; Group 4 - received 4NQO at 20 ppm dose during 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage for first 4 weeks after 4-NQO administration; Group 5 - received 4NQO at 20 ppm dose for 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage between the 5th and 8th weeks daily. Histopathological analysis revealed a decrease in hyperplasic and dysplastic lesions in Group 4. Groups 4 and 5 showed decreased COX-2 and TNF-alpha and eNOS gene expression. Grape juice concentrate also increased SOD Cu/Zn and catalase expression. However, Ki-67 immunoexpression was reduced at the promotion step of oral carcinogenesis (G5). Taken together, our results demonstrate that grape juice concentrate modulates rat tongue carcinogenesis as a result of anti-inflammatory activity, antioxidant activity and down-regulation of oral cells proliferation.

Background: Gastric cancer is the fifth most frequent cancer and the third most common cause of cancer-related deaths worldwide.It has been reported that Wnt/ betacatenin pathway is activated in 30-50% of these tumors. However,the deregulation of this pathway has not been fully elucidated. Aim: To determine the expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins in gastric adenocarcinoma tissues and correlate with clinical and pathological parameters. Method: Seventy-one patients with gastric adenocarcinoma undergoing gastrectomy were enrolled. The expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins was detected by immunohistochemistryand related to the clinical and pathological parameters. Results: The expression rates of E-cadherin in the membrane was 3%; betacatenin in the cytoplasm and nucleus were 23,4% and 3,1% respectively; APC in the cytoplasm was 94,6%; TCF-4 in the nucleus was 19,4%; and survivin in the nucleus 93,9%. The expression rate of E-cadherin was correlated with older patients (p=0,007), while betacatenin with tumors

Heat shock proteins are molecular chaperones that may be constitutively present in cells protecting them from various stresses, such as extreme temperature, anoxia or chemical agents. Cervical cancer is the second most prevalent malignancy of women. In this study, we analyzed the expression of Hsp27 by immunohistochemistry in cervical intraepithelial lesions of Brazilian women, along with samples from non neoplasic lesions (NN). Cervical intraepithelial neoplasia I (CIN I), II (CIN II) and III (CIN III)/in situ carcinoma and squamous cell carcinoma (SCC) were included. Immunostaining was observed in 30 (100%) samples of NN, 46 (92%) in CIN I, 50 (100%) in CIN II, 52 (98.11%) in CIN III/CIS, and 46 (98.11%) in SCC. In group NN Hsp27 immunostaining was heterogeneous, more intense in basal and parabasal layers of the epithelium and less or absent in the intermediate and superficial layer. The majority of the samples of CIS and SCC presented strong staining in allepithelial layers. Metaplasic cells, when present, were strongly stained. In this study, Hsp27 protein was found to be commonly expressed in cervical epithelial cells.

Background: activation of the Wnt pathway by mutated APC gene is considered the initial event in colorectal carcinogenesis. The identification of these mutations can improve the specific treatment of the adenocarcinoma. Objective: detect and evaluate wild-type APC protein in tissue from colorectal adenoma, adenocarcinoma and adjacent mucosa. Methods: 42 patients that underwent surgery for adenocarcinoma and 53 patients with resected adenomas were studied. Tissue samples from the adenocarcinoma were obtained from the tumor and from adjacent non-neoplastic mucosa located 10 cm from the proximal margin of the tumor. Adenoma tissue was obtained from representative areas. Blocks of tissue microarray (TMA) were submitted to immunohistochemistry with anti-APC, with readings of positivity and intensity of immunostaining and the score of immune expression of APC protein was obtained. Results: the APC protein immune expression score showed a significantly lower expression of APC protein in the adenoma when compared with the adenocarcinoma (p < 0.0001) and adjacent mucosa (p < 0.0001). The APC protein immune expression score in the colorectal mucosa and adjacent to the adenocarcinoma showed no significant difference (p = 0.24). Conclusions: the finding of decreased expression of APC protein in adenoma tissue may indicate that the mutated APC gene may contribute to the changes in the adenoma-carcinoma process of carcinogenesis sequence. The strong expression of protein APC in tissues from the carcinoma and adjacent mucosa suggests that in most patients in this series, the mutation of the APC gene did not participate in the oncogenesis mechanism. Resumo: Racional: a ativação da via Wnt pelo gene APC mutado é considerado evento inicial da carcinogênese colorretal. A identificação dessas mutações pode tornar o tratamento do adenocarcinoma mais específico. Objetivo: detectar e avaliar a proteína APC não mutada em tecidos de adenoma, adenocarcinoma e mucosa adjacente. Método: estudados 42 doentes operados de adenocarcinoma e 53 com adenomas ressecados. Tecidos de adenocarcinoma foram obtidas da neoplasia e da mucosa adjacente não neoplásica situadas a 10 cm da margem proximal do tumor. Tecidos do adenoma foram obtidas de área representativa. Blocos de tissue microarray (TMA) foram submetidos a imuno-histoquímica com anticorpo anti-APC. Avaliadas a positividade e intensidade da expressão e obtidos escores da imunoexpressão da proteína APC. Resultados: o escore da imunoexpressão da proteína APC no adenoma foi significantemente menor do que no adenocarcinoma (p < 0,0001) e na mucosa adjacente (p < 0,0001). O escore da imunoexpressão da proteína APC na mucosa adjacente e no adenocarcinoma não mostraram diferença significante (p = 0,24). Conclusões: a menor expressão da proteína APC no adenoma pode indicar que o gene APC mutado participa das alterações do processo adenoma-carcinoma. A forte expressão da proteína APC no CCR e na mucosa adjacente sugerem que a mutação do gene APC não participou da oncogênese. Keywords: Colorectal neoplasms Carcinoma, Adenoma APC Gene, Immunohistochemistry Biological tumor markers, Palavras-chave: Neoplasias colorretais Carcinoma, Adenoma Gene APC, Imunoistoquímica, Marcadores biológicos de tumor

Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Our goal in this study was to detect c-myc, p21WAF/CIP1, p53, C-erbB-2 and COX-2 immuno-expression in ESCC. Archival formalin-fixed, paraffin-embedded tissues of 18 cases of ESCC (13 biopsies and 5 surgical specimens) were studied, retrospectively, by immunohistochemistry. p53 protein was observed in 50% of the cases, while c-myc was found in 6 of 18 samples (33.33%). All samples (100%) were negative for p21WAF/CIP1. C-erbB-2 oncoprotein and the COX-2 protein were detected in 5.5% (1/18) and 16.66% (3/18) of the cases, respectively. Taken together, our results suggest that c-myc, p53, C-erbB-2 and COX-2 proteins do not correlate with cancer stage or follow-up in ESCC as revealed by immunohistochemistry.

Waste collectors collect, transport, and process the garbage produced by people living in the city. Nowadays, this activity requires special attention due to the environmental impact of garbage and its potential consequences on human health. The aim of this study was to evaluate potential cytotoxic and mutagenic effects of garbage collection on waste collectors. For this purpose, a total of 47 male waste collectors aged from 24 to 53 years were included in the experimental group. A total of 30 men matched by age were used as the control group. Cytotoxicity and mutagenicity were analyzed by micronucleus test in buccal mucosaI cells. No statistically significant difference (p>0.05) in the frequency of micronuclei was detected in the waste collectors when compared to controls. Nevertheless, higher frequencies of karyolysis and pyknosis (p

Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1–Sham/saline solution, G2–CAE/control, G3–acetic acid/control, G4–curative- CAE treatment and G5–preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma.Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used.In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p0.001 and p0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma.These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted.Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina.Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada.No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p0,001 e p0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma.Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma colorretal, o aumento das expressões da betacatenina, GSK3β, 1 axina, e ubiquitina indicaram que o complexo de destruição de betacatenina estava alterado.