Potencial quimiopreventivo de lipídios estruturados obtidos da Tributirina e Tricaprilina na fase de promoção da hepatocarcinogênese experimental / Chemopreventive potential of structured lipids obtained from Tributyrin and Tricaprylin in the promotion phase of experimental hepatocarcinogenesis

A quimioprevenção do câncer refere-se ao uso de compostos naturais ou sintéticos para prevenir o desenvolvimento das neoplasias antes do estabelecimento da malignidade. O ácido butirico (AB) atua como um potente quimiopreventivo na hepatocarcinogênese, reduzindo o número e o tamanho de lesões pré neoplásicas persistentes (pLPN), induzindo a apoptose e modulando mecanismos epigenéticos. Já o ácido caprílico (AC), além da sua atuação como potencializador de absorção, vem sendo investigado na área da prevenção do câncer. Neste cenário, o objetivo do trabalho visa avaliar a atividade quimiopreventiva de lipídios estruturados (EST) obtidos por interesterificação enzimática da tributirina com a tricaprilina, na fase de promoção da hepatocarcinogênese experimental. Após o processo de interesterificação, o produto final apresentou novos triacilgliceróis com composição de duas moléculas de ácido butírico para uma de ácido caprilíco. Ratos machos isogênicos da linhagem Fischer 344 foram submetidos ao modelo do hepatócito resistente, sendo distribuídos em dois grupos e tratados diariamente por via intragástrica com lipídios estruturados (EST) ou com o seu controle isocalórico, a maltodextrina (MD), durante a fase de promoção. Como esperado, não houve diferença estatística (p>0,05) em relação ao peso inicial e final dos animais dos grupos MD e EST, o que indica ausência de toxicidade dos compostos administrados. Na análise macroscópica do fígado, foi observada uma redução de 33,3% no grupo EST em relação ao número médio de nódulos macroscópicos em comparação ao grupo MD, porém essa redução não atingiu diferença estatística (p>0,05). Para a avaliação das lesões pré neoplásicas (LPN) foi utilizada a marcação imunoistoquímica para glutationa-S-transferase (GST-P). O grupo EST apresentou uma redução no número de lesões em remodelação e total GSTP-P+, quando comparado com o grupo MD (p<0,05). Quando avaliada a % de corpúsculos apoptóticos e índice de proliferação celular, não houve diferença estatística entre os grupos (p>0,05). Animais tratados com lipídios estruturados apresentaram maiores (p<0,05) concentrações de AC e AB por grama de tecido hepático em relação ao tratamento com maltodextrina. Em relação aos danos no DNA, o grupo EST resultou em cometas de comprimentos menores (p<0,05), menores níveis de γ-H2AX (p<0,05) e maiores concentrações de p53 nuclear, quando comparados aos animais que receberam maltodextrina, sugerindo uma proteção contra danos no DNA no grupo tratado com EST. Os resultados mostraram que o tratamento com EST resultou em ações efetivas na fase de promoção da hepatocarcinogênese experimental

Cancer chemoprevention refers to the use of natural or synthetic compounds to prevent the development of neoplasms before the establishment of malignancy. Butyric acid (AB) acts as a potent chemopreventive in hepatocarcinogenesis, reducing the number and size of persistent preneoplastic lesions (pLPN), inducing apoptosis and modulating epigenetic mechanisms. Caprylic acid (CA), in addition to its role as an absorption enhancer, has been investigated in the area of cancer prevention. In this scenario, the objective of this work was to evaluate the chemopreventive activity of structured lipids (EST) obtained by enzymatic interesterification of tributyrin with tricaprylin, in the phase of promotion experimental hepatocarcinogenesis. After the interesterification process, the final product presented new triacylglycerols with a composition of two molecules of butyric acid to one of caprylic acid. Isogenic male Fischer 344 rats were submitted to the resistant hepatocyte model, divided into two groups and treated daily intragastrically with structured lipids (EST) or with its isocaloric control, maltodextrin (MD), during the promotion phase. As expected, there was no statistical difference (p>0.05) in relation to the initial and final weight of the animals in the MD and EST groups, which indicates the absence of toxicity of the administered compounds. In the macroscopic analysis of the liver, a reduction of 33.3% was observed in the EST group in relation to the mean number of macroscopic nodules compared to the MD group, but this reduction did not reach a statistical difference (p>0.05). For the evaluation of pre-neoplastic lesions (PNL) immunohistochemical staining for glutathione-Stransferase (GST-P) was used. The EST group showed a reduction in the number of remodeling lesions and total GSTP-P+, when compared to the MD group (p<0.05). Animals treated with structured lipids had higher (p<0.05) concentrations of AC and AB per gram of liver tissue compared to treatment with maltodextrin. Regarding DNA damage, the EST group resulted in comets of shorter lengths (p<0.05), lower levels of γ-H2AX (p<0.05) and high concentration of nuclear p53, when compared to animals that received maltodextrin, suggesting protection against DNA damage in the EST treated group. The results showed that EST treatment resulted in effective actions in the promotion phase of experimental hepatocarcinogenesis

Incidencia de cáncer de mama a 5 años en mujeres con lesiones premalignas / Incidence of breast cancer at 5 years in women with premalignant lesions

Resumen OBJETIVO: Determinar la incidencia acumulada de cáncer de mama a cinco años de seguimiento en pacientes con lesiones preinvasoras o premalignas de la glándula mamaria en un centro de referencia y establecer los factores de riesgo asociados. MATERIALES Y MÉTODOS: Estudio de cohorte retrospectiva efectuado en pacientes atendidas en el Hospital Ángeles Lomas entre los años 2012 a 2016 con diagnóstico, durante su tamizaje mastográfico, de alguna lesión precursora o preinvasora de cáncer de mama. El seguimiento fue a cinco años para determinar la incidencia. Las variables categóricas se expresan en frecuencias y porcentajes. Se utilizó la prueba de χ2 para diferencia de proporciones entre grupos. RESULTADOS: Se obtuvieron 3360 pacientes que acudieron al servicio de Mastología durante el tiempo establecido. Se obtuvieron 245 pacientes con lesiones premalignas pero 30 de ellas no cumplieron con el seguimiento a cinco años y se perdieron en ese tiempo estipulado de vigilancia. Al final quedaron 215 pacientes que cumplieron todos los criterios de inclusión establecidos. La incidencia acumulada global de cáncer de mama invasivo fue que a 5 años el 14.9% de las pacientes con lesiones premalignas tendrá cáncer de mama. El carcinoma lobulillar in situ fue el de mayor incidencia o progresión de cáncer invasor, con un 32.1% a los cinco años, seguido de las lesiones mucocele-like, carcinoma ductal in situ y papiloma intraductal con un 23.1, 21.1 y 17.1%, respectivamente. CONCLUSIONES: El cáncer de mama sigue siendo un problema de salud pública en México y en todo el mundo. Si bien cada vez se dispone de más y mejores programas de tamizaje, ello ha traído consigo otras problemáticas, como las lesiones premalignas o de alto riesgo de carcinogénesis, que han aumentado su incidencia.

Abstract OBJECTIVE: To determine the cumulative incidence of breast cancer at five years of follow-up in patients with preinvasive or premalignant lesions of the mammary gland in a referral canter and to establish the associated risk factors. MATERIALS AND METHODS: Retrospective cohort study carried out in patients seen at Hospital Ángeles Lomas between 2012 and 2016 with a diagnosis, during their mastographic screening, of a precursor or pre-invasive lesion of breast cancer. Categorical variables are expressed in frequencies and percentages. The χ2 test was used for difference of proportions between groups. RESULTS: We obtained 3360 patients who attended the mastology service during the established time. We obtained 245 patients with premalignant lesions but 30 of them did not comply with the five-year follow-up and were lost within the stipulated surveillance period. This left 215 patients who met all the inclusion criteria. The overall cumulative incidence of invasive breast cancer was that at 5 years 14.9% of patients with premalignant lesions will have breast cancer. Lobular carcinoma in situ had the highest incidence or progression of invasive cancer, with 32.1% at 5 years, followed by mucocele-like lesions, ductal carcinoma in situ and intraductal papilloma with 23.1, 21.1 and 17.1%, respectively. CONCLUSIONS: Breast cancer remains a public health problem in Mexico and worldwide. Although more and better screening programmes are becoming available, this has brought with it other problems, such as premalignant or high-risk carcinogenic lesions, which have increased in incidence.

Chemopreventive agents on a mouse skin carcinogenesis model: an integrative review / Agentes quimiopreventivos em um modelo de carcinogênese de pele em camundongos: uma revisão integrativa / Agentes quimiopreventivos en un modelo de carcinogénesis cutánea en ratón: una revisión integradora

Squamous cell carcinoma (SCC) is a non-melanoma skin cancer, with chronic sun exposure as the main risk factor. Excisional surgery is the most indicated treatment; however, patients can suffer functional, aesthetic, and psychological damage depending on the lesion site. Topical administration of 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-Tetradecanoylphorbol-13- acetate (TPA) induce to the appearance of benign skin tumors in mice, some of which develop into SCC. This protocol has been used to analyze the effects of many chemopreventive agents that may block or inhibit the mechanisms of action of chemical carcinogenesis. We compared the effects of chemopreventive agents in an induced skin carcinogenesis animal model. In the Scopus, PubMed, and EMBASE databases, we searched for manuscripts published between June 16, 2011, and June 16, 2021. We excluded studies conducted in vitro or on transgenic mice; in addition, studies without drug dosage, route of administration, or tumor incidence were excluded. We selected 26 studies and analyzed their main characteristics and the outcomes of tumorigenesis analysis. Most chemopreventive agents have shown excellent potential to inhibit the development of skin tumors. This review also discusses the standardization of studies in animal models to ensure better responses and future randomized clinical trials for cancer treatment and prevention.

O carcinoma espinocelular cutâneo (CEC) é um câncer de pele não melanoma, com a exposição solar crônica como o principal fator de risco. A cirurgia excisional é o tratamento mais indicado; entretanto, os pacientes podem sofrer danos funcionais, estéticos e psicológicos dependendo do local da lesão. A administração tópica de 7,12-dimetilbenz[a]antraceno (DMBA) e 12-O- Tetradecanoilforbol-13-acetato (TPA) induz ao aparecimento de tumores cutâneos benignos em camundongos, alguns dos quais evoluíram para CEC. Este protocolo tem sido utilizado para analisar os efeitos de muitos agentes quimiopreventivos que podem bloquear ou inibir os mecanismos de ação da carcinogênese química. Comparamos os efeitos de agentes quimiopreventivos em um modelo animal que foi induzido à carcinogênese de pele. Nas bases de dados Scopus, PubMed e EMBASE, buscamos manuscritos publicados entre 16 de junho de 2011 e 16 de junho de 2021. Excluímos estudos realizados in vitro ou em camundongos transgênicos; além disso, estudos sem dosagem de drogas, via de administração ou incidência de tumores foram excluídos. Selecionamos 26 estudos e analisamos suas principais características e os resultados da análise da tumorigênese. A maioria dos agentes quimiopreventivos tem demonstrado excelente potencial para inibir o desenvolvimento de tumores cutâneos. Esta revisão também discute a padronização de estudos em modelos animais para garantir melhores respostas e futuros ensaios clínicos randomizados para tratamento e prevenção do câncer.

El carcinoma de células escamosas (CCE) es un cáncer de piel no melanoma, cuyo principal factor de riesgo es la exposición crónica al sol. La cirugía de escisión es el tratamiento más indicado; sin embargo, los pacientes pueden sufrir daños funcionales, estéticos y psicológicos dependiendo de la localización de la lesión. La administración tópica de 7,12-dimetilbenz[a]antraceno (DMBA) y 12-O-Tetradecanoilforbol-13-acetato (TPA) inducen a la aparición de tumores cutáneos benignos en ratones, algunos de los cuales se convierten en CCE. Este protocolo se ha utilizado para analizar los efectos de muchos agentes quimiopreventivos que pueden bloquear o inhibir los mecanismos de acción de la carcinogénesis química. Comparamos los efectos de los agentes quimiopreventivos en un modelo animal de carcinogénesis cutánea inducida. En las bases de datos Scopus, PubMed y EMBASE, se buscaron los manuscritos publicados entre el 16 de junio de 2011 y el 16 de junio de 2021. Se excluyeron los estudios realizados in vitro o en ratones transgénicos; además, se excluyeron los estudios sin dosis de fármacos, vía de administración o incidencia tumoral. Se seleccionaron 26 estudios y se analizaron sus características principales y los resultados del análisis de la tumorigénesis. La mayoría de los agentes quimiopreventivos han mostrado un excelente potencial para inhibir el desarrollo de tumores cutáneos. Esta revisión también analiza la estandarización de los estudios en modelos animales para garantizar mejores respuestas y futuros ensayos clínicos aleatorios para el tratamiento y la prevención del cáncer.

Experimental carcinogenesis with 7, 12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates / Carcinogénesis experimental con 7, 12-dimetilbenzantraceno (DMBA) y su inhibición con isitiocianatos

Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC). Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40). Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas). Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).

Introducción: El DMBA es un carcinógeno químico que induce carcinomas a las pocas semanas de su aplicación. Desarrollamos un modelo experimental de carcinogénesis inducida por DMBA disuelto en aceite de parafina al 0,5% (DMBA-Ap) comprobando el efecto inhibidor de la carcinogénesis de los isotiocianatos fenil (PhITC), fenetil (PhnITC) y bencil isotiocianato (BITC). Material y Métodos: Para ello, se distribuyeron 88 hámsteres en 3 grupos: uno expuesto al DMBA-Ap (Grupo 1, n=12), tres subgrupos (n=12) expuestos a PhITC, PhnITC, BITC y DMBA-Ap (Grupo 2, n=36) y cuatro subgrupos controles (n=10), no expuestos al carcinógeno en el que se aplicaron Ap e isotiocianatos (Grupo 3, n=40). Resultados:El experimento tuvo una duración de 20 semanas, al final de la cual se establece de forma comparativa el efecto inhibidor comparando las lesiones desarrolladas en los grupos que recibieron isotiocianatos con respecto al grupo tratado sólo con DMBA-Ap. El efecto carcinógeno del DMBA-Ap es del 100% (35 carcinomas) y el efecto inhibidor 0, mientras que en presencia de isotiocianatos el efecto carcinógeno disminuye, con un efecto inhibidor del 86% para BITC (5 carcinomas) y del 74% para el PhITC (9 carcinomas). Conclusión:El efecto inhibidor del PhnITC es del 80% en relación con el COCE invasivo (1 carcinoma).

Phytochemicals targeting NF-κB signaling:Potential anti-cancer interventions / 药物分析学报

Nuclear factor κB(NF-κB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-κB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells.NF-κB is the only signaling molecule that governs both pro-and anti-apoptotic,and pro-and anti-inflammatory responses.This is due to the canonical and non-canonical components of the NF-κB signaling pathway.Together,these pathways orchestrate cancer-related inflammation,hyperplasia,neoplasia,and metastasis.Non-canonical NF-κB pathways are particularly involved in the chemoresistance of cancer cells.In view of its pivotal role in cancer progression,NF-κB represents a potentially significant therapeutic target for modifying tumor cell behavior.Several phy-tochemicals are known to modulate NF-κB pathways through the stabilization of its inhibitor,IKB,by inhibiting phosphorylation and ubiquitination thereof.Several natural pharmacophores are known to inhibit the nuclear translocation of NF-κB and associated pro-inflammatory responses and cell survival pathways.In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-κB component,we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-κB signaling pathways for controlling the fate of tumor cells for cancer-directed interventions.

Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

The use of chemoprophylaxis or not for dvt in spine surgery: a systematic review / O uso da quimioprofilaxia ou não para tvp em cirurgia de coluna: revisão sistemática / El uso de quimioprofilaxis o no para la tvp en la cirugía de columna vertebral: revisión sistemática

ABSTRACT Objective: To compare pharmacological and non-pharmacological prophylaxis in elective spine surgery to determine the risks of DVT, PTE, and epidural hematoma (EH) in both groups, as well as their respective treatment effectiveness. Methods: Systematic review and meta-analysis based on systematically searched articles, using combinations of MeSH terms related to chemoprophylaxis and non-chemoprophylaxis for prevention of deep vein thrombosis and pulmonary embolism in elective spine surgery. Adult patients were eligible for inclusion in the study, except for those with trauma, spinal cord injury, neoplasms, or those using vena cava filters. Results: Five studies were selected for this systematic review and meta-analysis: 3 retrospective studies, 1 prospective study, and 1 case series. Data analysis showed that 4.64% of patients treated with chemoprophylaxis had an unfavorable outcome regarding DVT, while this outcome occurred in 1.14% of patients not treated with chemoprophylaxis (p=0.001). Among patients using chemoprophylaxis, only 0.1% developed epidural hematoma and 0.38% developed PTE. Among those on non-pharmaceutical prophylaxis, 0.04% had EH (p=0.11) and 0.42% had PTE (p=0.45). Conclusions: No benefits were found for chemoprophylaxis as compared to non-chemoprophylaxis in preventing DVT in elective spine surgery, nor was there an increased risk of epidural hematoma or fatal thromboembolic events. Level of evidence III; Therapeutic studies; Investigation of treatment results.

RESUMO Objetivo: Comparar profilaxia farmacológica e não farmacológica em cirurgia eletiva da coluna vertebral, a fim de determinar os riscos de TVP, TEP e hematoma epidural (HE) em ambos os grupos, bem como a respectiva eficácia do tratamento. Métodos: Revisão sistemática e metanálise com base em artigos sistematicamente pesquisados, usando combinações de termos MESH relacionados à quimioprofilaxia e à não quimioprofilaxia para prevenção de trombose venosa profunda e embolia pulmonar em cirurgia eletiva da coluna vertebral. Pacientes adultos foram elegíveis para inclusão no estudo, exceto aqueles com trauma, lesão medular, neoplasias e aqueles que usavam filtros de veia cava. Resultados: Cinco estudos foram incluídos para fazer parte desta revisão sistemática e metanálise: três estudos retrospectivos, um prospectivo e um série de casos. A análise dos dados mostrou que 4,64% dos pacientes tratados com quimioprofilaxia tiveram um resultado desfavorável em relação à TVP, enquanto esse resultado ocorreu em 1,14% dos pacientes não tratados com quimioprofilaxia (p = 0,001). Entre os pacientes em uso de quimioprofilaxia, apenas 0,1% desenvolveram hematoma epidural (HE) e 0,38% desenvolveram TEP. Entre aqueles em profilaxia não medicamentosa, 0,04% apresentaram HE (p = 0,11) e 0,42% tiveram TEP (p = 0,45). Conclusões: Não foram encontrados benefícios para a quimioprofilaxia quando comparada à não quimioprofilaxia na prevenção da TVP em cirurgia eletiva da coluna vertebral, assim como não foi verificado aumento do risco de hematoma epidural ou eventos tromboembólicos fatais. Nível de evidência III; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Objetivo: Comparar la profilaxis farmacológica y no farmacológica en la cirugía de columna electiva para determinar los riesgos de TVP, TEP y hematoma epidural (HE) en ambos grupos, así como la respectiva eficacia del tratamiento. Métodos: Revisión sistemática y metanálisis basados en artículos buscados sistemáticamente, utilizando combinaciones de términos MESH relacionados con quimioprofilaxis y no quimioprofilaxis para la prevención de trombosis venosa profunda y embolia pulmonar en cirugía electiva de columna. Se eligieron pacientes adultos para su inclusión en el estudio, excepto aquellos con traumatismos, lesión medular, neoplasias y aquellos que usan filtros de vena cava. Resultados: Se incluyeron cinco estudios para formar parte de esta revisión sistemática y metanálisis: 3 estudios retrospectivos, 1 prospectivo y 1 serie de casos. El análisis de los datos reveló que el 4,64% de los pacientes tratados con quimioprofilaxis tuvieron un resultado desfavorable con respecto a la TVP, mientras que este resultado se produjo en el 1,14% de los pacientes no tratados con quimioprofilaxis (p = 0,001). Entre los pacientes que recibieron quimioprofilaxis, sólo el 0,1% desarrolló hematoma epidural (HE) y el 0,38% desarrolló TEP. Entre los que recibieron profilaxis no farmacológica, el 0,04% desarrolló HE (p = 0,11) y el 0,42% desarrolló TEP (p = 0,45). Conclusiones: No se encontraron beneficios para la quimioprofilaxis en comparación con la no quimioprofilaxis para prevenir la TVP en la cirugía de columna electiva, así como tampoco un mayor riesgo de hematoma epidural o eventos tromboembólicos fatales. Nivel de evidencia - III; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Seasonal malaria chemoprevention coverage in Burkina Faso in 2018: Descriptive analysis of mothers' knowledge and attitude during cross sectional survey

Seasonal malaria chemoprevention (SMC) is effective to prevent malaria in children 3 to 59 months in the Sahel region. Mother's seasonal malaria chemoprevention related knowledge and attitudes and the coverage of the strategy among targeted children were assessed. A cross-sectional survey was conducted in 1828 children aged 3 to 59 months from November 7 to 18, 2018 in eight health regions of Burkina Faso where SMC was implemented with Malaria Consortium supported fund. Data were collected using structured questionnaire and direct inspection of SMC card. MAGPI software was used for data collection and STATA 12.0 was used for the analysis. A total of 1828 children 3 to 59 months were enrolled and 951 mothers interviewed on different aspects of SMC. Overall, the SMC coverage was high for single cycle or for cumulative coverage basis. Single cycle coverage increased over rounds, from mother and tutor's interview (from 87.09% (1592/1828) to 91.19% (1667/1828); p=0.001). Over 91.18% (869/951) knew that SMC objective was to prevent malaria. Overall SMC was well tolerated and most 95.2% (296/320) of mothers and tutors surveyed owned treated bed nets. Despite combining high coverage and treated bed-net use, at least 16.19% remained rapid diagnosis test positives during the survey. SMS coverage was high in the current survey and most mothers knew the relevance of SMC administration with high bed-net coverage.

Advances in mechanisms for inflammation-associated colon carcinogenesis and chemoprevention / 药学学报

Colorectal cancer is a common malignant tumor of digestive tract, and the risk of inflammatory bowel disease developing into colorectal cancer is significantly increased. Immune signaling pathways NF-κB, IL-6/STAT3, COX-2/PGE2, IL-23/Th17 and TLRs have been confirmed to promote the transformation from colitis to colorectal cancer. NOD2 and intestinal microbes also participate in the regulation of inflammation mediated carcinogenesis. Chronic inflammation is a potential risk for colorectal cancer, and anti-inflammatory drugs may play a chemical preventive role. In this review, we summarize the signaling pathways involved in inflammation-associated colon carcinogenesis and evaluate the chemoprophylaxis of colon cancer.

Advances in drug prophylaxis against bronchopulmonary dysplasia / 中华围产医学杂志

Bronchopulmonary dysplasia (BPD) is a common respiratory complication after preterm birth that severely affects the prognosis and quality of life in preterm infants. In recent years, significant progress has been made in neonatal care, but the incidence of BPD remains high. After long-term exploration and application, some medications such as exogenous pulmonary surfactants, glucocorticoids and caffeine have been widely used for the prevention and treatment of BPD. However, some medications including diuretics, inhaled nitric oxide and bronchodilators have not been proved to be effective and safe. This review summarizes the present drugs for the prevention of BPD in publications.

Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation / 中国天然药物

Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.

Eficacia y seguridad del concentrado liofilizado de Zea mays morado en la prevención de formación de pólipos colónicos / Efficacy and safety of lyophilized concentrate purple corn (Zea mays L.) in preventing the formation of colonic polyps

RESUMEN Introducción : El cáncer colorrectal (CCR) es un problema mundial de salud pública y se origina principalmente a partir de pólipos. Hace 25 años se ha considerado una estrategia denominada quimioprevención que consiste en el consumo de alimentos como maíz morado y cúrcuma o sustancias químicas como ácido acetilsalicílico (AAS) y anti inflamatorios no esteroideos (AINEs) que previenen la carcinogénesis efectivamente al reducir el riesgo de desarrollo de pólipos. Objetivo : Determinar la eficacia y seguridad del concentrado liofilizado Zea mays morado 200 mg en la prevención de formación de pólipos colónicos en la práctica gastroenterológica privada. Material y métodos : aleatorizamos 112 pacientes (casos) para recibir este producto y 112 pacientes (controles) para recibir placebo, durante 3 años. Ambos grupos de similares características demográficas, clínicas y antecedentes patológicos. Resultados : Hallamos que los casos al final del estudio desarrollaron 83% menos pólipos que los controles (p<0,001). Los casos que desarrollaron pólipos fueron menores en número, tamaño e histología que al inicio del ensayo. Los eventos adversos que presentaron los casos fueron 4,5% similar a los controles, principalmente petequias. Conclusiones : Concluimos que el concentrado liofilizado de Zea mays morado 200 mg es eficaz y seguro en la prevención del desarrollo de pólipos colónicos.

ABSTRACT Introduction : Colorectal cancer (CRC) is a worldwide problem of public health and arises mainly from polyps. In last 25 years, a strategy called chemoprevention that consists of food intake like purple corn and turmeric or chemical substances like acetyl salicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) that prevent effectively carcinogenesis reducing the risk of polyp development. Objective : To determine the efficacy and safety of lyophilized concentrate of purple corn (Zea mays L.) 200 mg in the prevention of colonic polyps development in private gastroenterological practice Methods : we randomly assigned 112 patients (cases) to receive this product and 112 patients (controls) to receive placebo, during 3 years. Both groups had similar demographic, clinical and medical history characteristics. Results : we found that cases developed 83% less polyps than controls (p<0.001). The cases that developed polyps were smaller in number, size and histology than at the beginning of the trial. The adverse events that cases presented were 4.5% similar to controls, mainly petechiae. Conclusion : We conclude that the lyophilized concentrate of purple corn (Zea mays L.) 200 mg was effective and safe in preventing the development of colonic polyps.

Selenium supplementation prevents DNA damage in ram spermatozoa / Suplementação com selênio previne danos ao DNA espermático de ovinos

ABSTRACT: In the present study, we aimed to evaluate the effects of different concentrations of selenium (Se) ovine nutritional supplementation on spermatozoa DNA integrity. Thirty male ovines (age: 10 months) were used. They were fed with hay and ram food in an intensive system, which was divided into stalls (5 m long and 3 m wide) with feeding troughs, and had ad libitum access to food and water. Ovines in group 1 (G1, the negative control) received mineral salt supplementation without Se; ovines in G2 received the same mineral salt mixed with 5 mg Se (as sodium selenite)/kg mineral supplement;ovines in G3 received 10 mg Se/kg mineral supplement; ovines in G4 received 15 mg Se/kg mineral supplement; and ovines in G5 received 20 mg Se/kg mineral supplement. Ovines in all groups remained untreated for 14 days, followed by a treatment period of 56 days. Semen samples were obtained by electroejaculation. The DNA damage in semen samples was evaluated using the comet assay. The experimental design was implemented using a 5 × 5 Latin Square, i.e., five treatments and five experimental periods. The mean differences were compared using Tukey's test at a significance level of 5%. The control group (G1) showed a high percentage of DNA damage compared to the Se-treated groups (G2-G5). Therefore, Se supplementation could decrease the basal level of DNA damage in sperm cells, suggesting that Se might exert protective effects on sperm DNA.

RESUMO: O presente estudo teve por objetivo avaliar os efeitos da suplementação mineral com diferentes concentrações de selênio (Se) sobre a integridade de DNA espermático de ovinos. Utilizaram-se 30 machos, com 10 meses de idade. Eles foram mantidos em sistema intensivo, sendo alimentados com feno e ração própria para ovinos, divididos em baias (5 m x 3 m), com cochos e água ad libitum. Os ovinos do grupo 1 (G1=controle negativo) receberam suplementação de sal mineral sem a adição de Se, os animais do G2 receberam a mesma mistura mineral, porém com 5 mg de Se (selenito de sódio)/kg mistura mineral, os ovinos do G3 receberam 10 mg Se/kg mistura, os animais do G4 receberam 15 mg Se/kg mistura, os do G5 receberam 20 mg Se/kg mistura. Os ovinos de todos os grupos passaram por um período de adaptação de 14 dias, seguido por um período de tratamento de 56 dias. O sêmen foi colhido por meio de eletroejaculação. A integridade do DNA espermático foi avaliada por meio do teste de cometa. O modelo experimental utilizado foi Quadrado Latino 5 x 5, com cinco grupos e cinco períodos experimentais. A diferença entre as médias foi analisada pelo teste de Tukey, com 5% de nível de significância. O grupo controle (G1) apresentou elevada porcentagem de danos quando comparada aos demais grupos de tratamentos (G2 a G5). Portanto, a suplementação de Se diminui o nível de danos ao DNA espermáticos, sugerindo que o Se pode exercer efeitos protetores sobre o DNA dos espermatozoides de ovinos.

Mechanism of tanshinone IIA to prevent spontaneous breast cancer in mice / 药学学报

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg-1·day-1), and high-dose TanIIA treatment group (60 mg·kg-1·day-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg-1·day-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

Research progress of the chemoprevention agents for breast cancer / 国际外科学杂志

As one of the most common malignant tumors in women,breast cancer has the characteristics of high inc idence,strong invasion,easy recurrence and metastasis.Although the mortality of breast cancer has decreased in recent years,its incidence has not been effectively controlled.Chemoprevention is a kind of preventive measure to reduce the incidence of disease by using natural or synthetic chemical drugs to prevent the asymptomatic high-risk population.At present,only estrogen receptor modulators and aromatase inhibitors are allowed to be used in clinical chemoprevention of breast cancer.Therefore,researcher should actively take measures to find new highefficient,low-toxic chemoprevention agents that take into account the majority of the population.The main purpose of this review is to summarize the mechanisms and related experimental studies of six chemoprevention agents for breast cancer including estrogen receptor modulators,include aromatase inhibitors,aspirin,metformin,flavones and poly(ADP-ribose) polymerases inhibitors.

Research progress of the chemoprevention agents for breast cancer / 国际外科学杂志

As one of the most common malignant tumors in women, breast cancer has the characteristics of high incidence, strong invasion, easy recurrence and metastasis. Although the mortality of breast cancer has decreased in recent years, its incidence has not been effectively controlled. Chemoprevention is a kind of preventive measure to reduce the incidence of disease by using natural or synthetic chemical drugs to prevent the asymptomatic high-risk population. At present, only estrogen receptor modulators and aromatase inhibitors are allowed to be used in clinical chemoprevention of breast cancer. Therefore, researcher should actively take measures to find new high-efficient, low-toxic chemoprevention agents that take into account the majority of the population. The main purpose of this review is to summarize the mechanisms and related experimental studies of six chemoprevention agents for breast cancer including estrogen receptor modulators, include aromatase inhibitors, aspirin, metformin, flavones and poly(ADP-ribose) polymerases inhibitors.

Actividad antimutagénica e identificación de compuestos antioxidantes en la planta Poincianella bracteosa (Fabaceae)

Introducción: Poincianella bracteosa (Tul.) L.P. Queiroz. (Fabaceae), conocida como catingueira, es tradicionalmente utilizada en la medicina para tratar diarrea, hepatitis y anemia. Sin embargo, no hay estudios sobre los efectos tóxico genéticos de la P. bracteosa. Objetivo: En el presente estudio se tuvo como objetivo investigar el perfil fitoquímico y el potencial mutagénico y antimutagénico del extracto acuoso de la cáscara de P. bracteosa en Allium cepa y Mus musculus. Métodos: El extracto de la cáscara fue diluido en agua destilada para fornecer las cuatro concentraciones (2, 4, 8 y 16 mg/ml) utilizadas en el bioensayo A. cepa y las tres dosis (10, 20 y 40 mg / Kg) fueron administradas a los ratones (5 animales por grupo). El perfil fito-químico fue realizado por el test colorimétrico para identificar los principales metabólitos secundarios en el extracto de la cáscara. Tras el tratamiento, 5 000 células meristemáticas fueron analizadas para determinar el índice mitótico, el promedio de alteraciones cromosómicas y el porcentaje de reducción de daños. Para ratones, tras 24, 48 y 72 h, la sangre de la cola de cada animal fue recolectado para la preparación de dos láminas por animal. Para cada animal, 2 000 eritrocitos normocromáticos por ratón fueron evaluados para establecer el número de micronúcleos y el efecto protector. Se analizaron los dados por el test de Kruskal-Wallis (P < 0.05). El estudio fito-químico del extracto detectó azúcares reductores y taninos. Resultados: Ninguna de las concentraciones del extracto fue citotóxica y en todos los tratamientos (pre, simultáneo y después) fue observado el efecto citoprotetor en A. cepa. El promedio total de las alteraciones cromosómicas en todas las concentraciones apuntó actividad no mutagénica de la cáscara. El porcentaje de reducción del daño fue observada en los tratamientos pre (de 77.6 al 90.5 %), simultáneo (del 95.6 al 114.7 %) y tras (de 84.8 al 117.7 %). En los ratones, ninguna de las dosis del extracto presentó efecto mutagénico y el porcentaje de reducción del daño osciló de -21.2 al 78.6 % (pre); de 27.5 al 101.3 % (simultánea) y de 85.5 al 120.6 % (tras-tratamiento). Probablemente, los fito-químicos presentes en el extracto no interfirieron en el ciclo celular (A. cepa), tampoco causaron daños al DNA (A. cepa y ratones) y presentaron efecto protector en las dos especies estudiadas. Los datos observados apuntan la importancia del extracto de la cáscara de P. bracteosa para inhibición del daño y quimio prevención. Sin embargo, más estudios deben ser realizados para garantizar su efecto protector sobre el material genético.

Introduction: Poincianella bracteosa (Tul.) L.P. Queiroz. (Fabaceae), known as catingueira, is traditionally used in medicine to treat diarrhea, hepatitis and anemia. However, there are no studies on their toxicogenetic effects. Objective: The present study aimed to investigate the phytochemical profile as well as the mutagenic and antimutagenic potential of P. bracteosa aqueous bark extract in Allium cepa and Mus musculus. Methods: The extract from barks was diluted in distilled water to yield the four concentrations (2, 4, 8 and 16 mg/ml) used in the A. cepa bioassay and the three doses (10, 20 and 40 mg/Kg) administered to the mice (five animals per group). The phytochemical profile was performed by the colorimetric test to identify the main secondary metabolites in the bark extract. After treatment, five-thousand meristematic cells were analyzed to determine the mitotic index, the mean number of chromosome alterations and the percentage of damage reduction. For mice, after 24, 48 and 72 h, tail blood was collected from each animal for the preparation of two slides per animal. For each animal, 2 000 normochromatic erythrocytes per mice were evaluated to establish the number of micronuclei and the protective effect. Data were analyzed by Kruskal-Wallis test (P < 0.05). Results: The phytochemical analysis of the extract detected reducing sugars and tannins. None of the concentrations of extract was cytotoxic and the cytoprotective effect was observed in A. cepa for all treatments (pre-, simultaneous and post-). The total mean of chromosome alterations in all concentrations indicated a non-mutagenic activity of the bark. The percentage of damage reduction was observed in the pre- (77.6 to 90.5 %), simultaneous (95.6 to 114.7 %) and post- (84.8 to 117.7 %) treatments. In mice, none of the dosages of extract presented mutagenic effect and the percentage of damage reduction varied from -21.16 to 78.63 % (pre-); from 27.51 to 101.28 % (simultaneous) and from 85.47 to 120.63 % (post-treatment). Conclusions: Probably, the phytochemicals in the extract did not interfere with the cell cycle (A. cepa) nor caused damage to the DNA (A. cepa and mice), and exhibited protective effect in both studied species. The observed data indicate the importance of P. bracteosa bark extract for the inhibition of damage and chemoprevention. However, more studies should be carried out to ensure its protective effect on the genetic material.

Evaluation of antimutagenic and cytotoxic activity of skin secretion extract of Rhinella marina and Rhaebo guttatus (Anura, Bufonidae) / Avaliação da atividade antimutagênica e citotóxica da secreção cutânea de Rhinella marina e Rhaebo guttatus (Anura, Bufonidae)

The skin secretion from toads of the Bufonidae family has great potential in the search for new active compounds to be used as drug candidates in treating some diseases, among them cancer. In this context, this study aimed to evaluate the cytotoxic and antimutagenic activity of the parotoid gland secretion extracts of Rhinella marina and Rhaebo guttatus, as well as biochemically analyze transaminases and serum creatinine for liver and renal damage, respectively. Cytotoxicity was performed by the colorimetric method based on MTT (3- [4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide) with different concentrations of the extracts in Walker or splenic tumor cell cultures from rats and mice. The micronucleus test was performed with male Swiss mice treated orally with the extracts for 15 days, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg kg-1). Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. The extracts showed cytotoxic activity in the evaluated cells. There was a significant reduction in the frequency of MNPCE (R. marina = 56% and R. guttatus = 75%, p < 0.001), indicating antimutagenic potential of the extracts. The groups treated only with extract showed an increase in MNPCE frequency, evidencing mutagenic potential. Biochemical analyzes showed no significant difference between treatments. Thus, under our experimental conditions, the extracts of R. marina and R. guttatus skin secretions presented chemopreventive potential for cancer. (AU)

A secreção cutânea de anuros da família Bufonidae tem grande potencial na busca de novos compostos ativos para utilização como fármacos candidatos no tratamento de algumas doenças, entre elas o câncer. Neste contexto, este estudo teve como objetivo avaliar a atividade citotóxica e antimutagênica dos extratos da secreção da glândula parótida de Rhinella marina e Rhaebo guttatus, bem como a análise bioquímica de transaminases e creatinina séricas, para avaliar dano hepático e renal, respectivamente. A avaliação de citotoxicidade foi realizada pelo método colorimétrico baseado no MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide), com diferentes concentrações dos extratos em culturas de células do Tumor de Walker ou células esplênicas de rato e camundongo. O teste do micronúcleo foi realizado com camundongos Swiss machos que receberam tratamento oral com os extratos durante 15 dias, seguido de tratamento intraperitoneal com N-etil-N-nitrosuréia (50 mg kg-1). A frequência de eritrócitos policromáticos micronucleados (PCEMN) foi determinada em medula óssea. Os extratos apresentaram ação citotóxica nas células avaliadas. Houve uma redução significativa na frequência de PCEMN (R. marina = 56% e R. guttatus = 75%, p < 0,001), observando-se um potencial antimutagênico dos extratos. Os grupos tratados somente com os extratos apresentaram um aumento na frequência de PCEMNs, evidenciando um potencial mutagênico. As análises bioquímicas não apresentaram diferença significativa entre os tratamentos. Assim, nas condições experimentais testadas, as secreções cutâneas de R. marina e R. guttatus apresentaram potencial quimiopreventivo para câncer.(AU)

Anti-Cancer Potential Of Polysaccharide Isolated From Methanolic Extract Of Tinospora Cordifolia Stem Bark

Objective: The exploration of the anticancer potential of polysaccharide isolated from the methanolic extract of Tinospora cordifolia (T. cordifolia) stem bark against breast cancer in DMBA-induced female albino Wistar rat models were examined by various hematological parameters. Methods: Analysis of Red blood cell (RBC), White blood cell (WBC) and platelet level, Tumor markers Carcino Embryonic Antigen (CEA) and Cancer Antigen 15.3 (CA 15.3) in the serum, was done in the normal, cancer and compound treated rats using specific kits. Histological studies were performed to examine the changes in the tissue morphology and cell patterns in breast tissue. Results: The decreased levels of RBC, WBC and platelets in 7,12-Dimethylbenz [a] anthracene (DMBA)-induced breast cancer (Group III) animals were revived to the normal conditions in polysaccharide treated breast cancer (Group IV) animals as that of normal (Group I). The level of tumor markers CEA and CA 15.3, was found elevated in serum of DMBA-induced breast cancer groups (Group III) when compared to their levels in the normal groups (Group I) whereas polysaccharide treatment (Group IV) prevented this rise in the levels of tumor markers. The histological studies on the breast tissue samples of all the groups showed the appropriate features where the normal (Group I) animals were characterized with normal cells uniformly arranged without any change in orientation and morphology, DMBA-induced cancer (Group III) animals showed an improper orientation of cells arranged as glandular structures, as nest, or cords of various sizes or as solid sheets foci of necrosis in some areas with margins infiltrating, pushing, circumcised or mixed and the polysaccharide treated (Group IV) animals showed results resembling that of the normal (Group I) animals. Conclusion: Thus, polysaccharide is proved as an effective chemo preventive agent against breast cancer.

Factores influyentes en la adherencia y abandono en la terapia preventiva para la infección por tuberculosis latente en pacientes con VIH / Influential factors in the adherence and abandonment of preventive therapy for latent tuberculosis infection in patients with HIV

Objetivo: describir los factores que influyen en la falta de adherencia al tratamiento de la infección tuberculosa latente. Materiales y métodos: estudio retrospectivo y descriptivo, en pacientes infectados con el Virus de la Inmunodeficiencia Humana atendidos en una institución prestadora de salud de Medellín, Colombia. Resultados: el 45% de los pacientes presentaron problemas de adherencia como interrupciones menores a 30 días o pérdida del seguimiento, la significación estadística (p<0,05) se presento en las variables efectos adversos y adherencia a la terapia antirretroviral. Conclusión: los efectos adversos presentados y la adherencia a la terapia antirretroviral se asocian a los problemas de adherencia al tratamiento preventivo de la Infección Tuberculosa Latente..(AU)

Objective: to describe the factors that influence the lack of adherence to the treatment of the latent tuberculosis infection. Materials and methods: retrospective and descriptive study in people living with the human immunodeficiency virus treated in a health institution of Medellin, Colombia. Results:45% of patients presented adherence problems such as interruptions less than 30 days or loss of follow-up, the statistical significance (p <0.05) was presented in the variables of adverse effects and adherence to antiretroviral treatment. Conclusion: adverse effects to treatment and adherence to antiretroviral therapy are associated with problems of adherence to preventive treatment of latent tuberculosis infection..(AU)