The role of DNA methylation detection in the early diagnosis and prognosis of lung cancer / 中华检验医学杂志

Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.

Effects of valproic acid on wound healing of the abdominal wall musculoaponeurotic layer: an experimental study in rats / Os efeitos do ácido valpróico na cicatrização do plano músculoaponeurótico da parede abdominal: estudo experimental em ratos

ABSTRACT Introduction: valproic acid (VPA), an epigenetic drug, has potential for the treatment of neoplasms. Its effects on the healing of the peritoneal-musculo-aponeurotic plane (PMA) of the abdominal wall are studied. Method: sixty Wistar rats were allocated into two groups: experimental (VPA) and control (0.9% sodium chloride), treated daily, starting three days before the intervention and until euthanasia. Under anesthesia, a median laparotomy was performed and repaired with two synthetic layers. Assessments took place 3, 7 and 14 days after surgery. The integrity of the wounds, the quality of the inflammatory reaction, the intensity of the leukocyte infiltrate, collagen synthesis, the intensity of angiogenesis and the presence of myofibroblasts were studied. Results: there was dehiscence of the PMA plane in 11 of the 30 animals (p=0.001) in the experimental group. There was no difference in the quality and intensity of the inflammatory reaction. Immunohistochemistry revealed, in the experimental group, less collagen I (p3=0.003, p7=0.013 and p14=0.001) and more collagen III (p3=0.003, p7=0.013 and p14= 0.001). Collagen evaluated by Sirus Supra Red F3BA showed, in the experimental group, less collagen at all three times (p<0.001) with less collagen I and collagen III (p<0.001). A lower number of vessels was found on the 3rd day (p<0.001) and on the 7th day (p=0.001) and did not affect the number of myofibroblasts. Conclusion: VPA showed dehiscence of the PMA plane, with less deposition of total collagen and collagen I, less angiogenic activity, without interfering with the number of myofibroblasts.

RESUMO Introdução: o ácido valpróico (VPA), droga epigenética, apresenta-se com potencial para o tratamento de neoplasias. Estudam-se seus efeitos sobre a cicatrização do plano peritônio-músculo-aponeurótico (PMA) da parede abdominal. Método: sessenta ratos Wistar, foram alocados em dois grupos: o experimental (VPA) e o controle (cloreto de sódio 0,9%), tratados diariamente, iniciando três dias antes da intervenção e até a eutanásia. Sob anestesia, fez-se uma laparotomia mediana que foi reparada com dois planos de síntese. As avaliações aconteceram 3, 7 e 14 dias após a cirurgia. Estudou-se a integridade das feridas, a qualidade da reação inflamatória, a intensidade do infiltrado de leucócitos, a síntese do colágeno, a intensidade da angiogênese e a presença de miofibroblastos. Resultados: o plano PMA mostrou-se deiscente em 11 dos 30 animais (p=0,001) do grupo experimento. Não houve diferença na qualidade da reação inflamatória e nem no infiltrado de leucócitos. A imuno-histoquímica revelou, no grupo experimento, menos colágeno I (p3=0,003, p7=0,013 e p14=0,001) e mais colágeno III (p3=0,003, p7=0,013 e p14= 0,001). Colágeno avaliado pelo Sirus Supra Red F3BA mostrou, no grupo experimento,menos colágeno nos três tempo (p<0,001) com menos colágeno I e colágeno III (p<0,001). Constatou-se menor número de vasos no 3º dia (p<0,001) e no 7º dia (p=0,001) e não afetou a quantidade de miofibroblastos. Conclusão: o VPA mostrou deiscências do plano PMA, com reação inflamatória semelhante.ao controle, menor deposição de colágeno total e de colágeno I, menor atividade angiogênica, sem interferir na quantidade de miofibroblastos.

Valproic acid and bladder healing: an experimental study in rats / Ácido valpróico e cicatrização em bexiga: estudo experimental em ratos

ABSTRACT Purpose: to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats. Method: twenty male Wistar rats were divided in two groups: experimental (A), treated with VPA (150mg/Kg/day), and control (B) with 0.9% sodium chloridrate. Healing was analyzed on the third and seventh days, evaluating the inflammatory reaction, collagen synthesis and angiogenesis. Results: inflammatory reaction on the third day was minimal and acute in both groups. On the seventh day, it was subacute in both groups, moderate intensity in group A and minimal in group B (p=0.0476). Collagen III intensity, marked by immunohistochemistry, was similar in both groups. Collagen I intensity on the third day was similar in both groups, but on the seventh day it was higher in experimental than control (p=0.0476). Collagen evaluation by picrosiriusred allowed to verify that the presence of collagen III was similar in both groups (p=0.3312) on the third day, and it was higher in control on the seventh day (p=0.0015). Collagen I showed similarity on the third day (p=0.3100), and it was higher in control on the seventh day (p=0.0015). Vessel marked with anti-SMA counting showed fewer vessels on the third (p=0.0034) and seventh day (p=0.0087) in experimental group. The lower intensity of angiogenesis was confirmed with anti-CD34, on the third day (p=0,0006) and on the seventh day (p=0,0072). Conclusion: VPA determined alterations in the bladder healing process, in rats, with lower collagen density and less angiogenic activity, but without compromising the integrity of the organ.

RESUMO Objetivo: reconhecer os efeitos do ácido valpróico (VPA), uma droga epigenética, no processo de cicatrização da bexiga, em ratos. Método: vinte ratos Wistar machos foram divididos em dois grupos: experimental (A), utilizando VPA (150mg/Kg/dia), e controle (B), tratados com cloreto de sódio 0,9% por gavagem. A cicatrização da bexiga foi analisada no terceiro e sétimo dia, estudando-se a reação inflamatória, síntese de colágeno, reepitelização e angiogênese. Resultados: a reação inflamatória no terceiro dia foi mínima e aguda em ambos os grupos. No sétimo dia, foi subaguda em ambos os grupos com intensidade moderada no grupo A e mínima no grupo B (p=0,0476). A intensidade do colágeno III, marcada pela imuno-histoquímica, foi semelhante nos dois grupos, nos dois tempos estudados. A intensidade de colágeno I no terceiro dia foi semelhante nos dois grupos, e maior no sétimo dia no grupo experimental (p=0,0476). A avaliação do colágeno pelo picrosiriusred mostrou que a presença de colágeno III foi semelhante em ambos os grupos (p=0,3312) no terceiro dia, e maior no controle no sétimo dia (p=0,0015). O colágeno I foi semelhante no terceiro dia (p=0,3100), e maior no controle no sétimo dia (p=0,0015). A contagem de vasos marcados pelo anti-SMA mostrou menos vasos no terceiro (p=0,0034) e sétimo dia (p=0,0087) no grupo experimental, confirmado pelo anti-CD34, no terceiro (p=00006) e no sétimo dia (p=0,0072). Conclusão: o VPA determinou alterações no processo de cicatrização da bexiga, em ratos, com menor densidade de colágeno e menor atividade angiogênica, mas sem comprometer a integridade do órgão.

Validación de cuestionario sobre interacción de factores genéticos y ambientales en la aparición del asma bronquial / Validation of a questionnaire on the interaction of genetic and environmental factors in the development of bronchial asthma

RESUMEN Introducción: el asma bronquial es la clásica enfermedad dentro de las afecciones alérgicas, y tiene gran impacto en la salud mundial. Es una enfermedad compleja tanto genética como fenotípicamente, y las interacciones genética-ambientales la complejizan aún más. Objetivo: validar un cuestionario para el estudio de los factores genéticos y su interacción con factores ambientales en la aparición de los trastornos inmunitarios por asma bronquial. Métodos: el estudio se generó en el departamento de Inmunología del Hospital Pediátrico Provincial Docente Pepe Portilla de la provincia Pinar del Río. Se seleccionó el grupo coordinador de la técnica a realizar. Se utilizó la Metodología Delphi, en sus cuatro fases: definición del tema, selección de expertos, ejecución de rondas de consultas y evaluación de los resultados. Para determinar las similitudes y concordancias de las respuestas, se calculó el coeficiente de concordancia de Kendall y Friedman. Resultados: se seleccionaron 21 expertos con altos niveles de competencia de acuerdo al cálculo de los coeficientes de conocimiento y argumentación. En la tercera versión del cuestionario existió similitud en las respuestas de los expertos a favor de la categoría superior de Muy imprescindible, así como concordancia en el nivel de respuesta. Conclusiones: el cuestionario diseñado alcanza niveles óptimos de validez de contenido y factibilidad para determinar la contribución de los factores genéticos y su interacción con factores ambientales en la aparición de los trastornos inmunitarios por asma bronquial.

ABSTRACT Introduction: bronchial asthma is the classic disease among allergic conditions, and has great impact on health worldwide. It is a complex disease both genetically and phenotypically, and genetic-environmental interactions make it even more complex. Objective: to validate a questionnaire for the study of the involvement of genetic factors and their interaction with environmental factors in the onset of immune disorders due to bronchial asthma. Methods: the study was developed in the Department of Immunology at Pepe Portilla Provincial Pediatric Teaching Hospital in Pinar del Río province. The coordinating group of the technique to be carried out was selected and comprised three professionals responsible for the proposed research. The Delphi Methodology was used, completing its four phases: definition of the topic, selection of experts, implementation of consultation rounds and assessment of results. To determine the agreement or similarities of the responses of the evaluators respectively, the Kendall and Friedman concordance coefficient was calculated. Results: twenty-one (21) experts with high levels of competence were selected according to the calculation of the coefficients of knowledge and argumentation. In the third version of the questionnaire, there was similarity in the responses of the experts in favor of the higher category of Very Essential, as well as agreement in the level of response of the experts. Conclusions: the designed questionnaire reaches optimal levels of content validity and feasibility to determine the contribution of genetic factors and their interaction with environmental factors on the onset of immune disorders due to bronchial asthma.

Chinese herbal medicines for prevention and treatment of colorectal cancer: From molecular mechanisms to potential clinical applications / 中西医结合学报

Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.

Chinese herbal medicines for prevention and treatment of colorectal cancer: From molecular mechanisms to potential clinical applications / 中西医结合学报

Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.

The advances of epigenetics in diabetic retinopathy / 中华眼底病杂志

Epigenetics refers to the changes in gene expression level and function caused by non-genetic sequence changes.It can provide the time,location and mode of the genetic information for the execution of DNA sequences,including DNA methylation,histone modification,non-coding RNA and chromatin remodeling.Studies had shown that epigenetics plays an important role in the development of diabetic retinopathy (DR),and it had been found that epigenetic-related treatment regimens had a certain effect on the treatment of DR through animal experiments and in vitro experiments.It was benefit to regulate the development of diabetes and its complications by depth study of DNA methylation,histone modification,miRNA and metabolic memory.An understanding of changes in gene transcriptional mechanisms at the epigenetic level could help us to further study the prevention and control of diabetes and its complications,and to provide new ideas for treatment.

Long-term effects of early life stress on neurodevelopment / 中华围产医学杂志

Early life stress can have long-term effects on human health.Both prenatal and postnatal stress exposure affect offspring's neurodevelopment,and increase the risk of emotional disorders and cognitive and behavioral abnormalities.However,these effects are gender and species specific and individualized with intergenerational influence.Many factors,including neurobiological responses,such as glucocorticoid,brainderived neurotrophic factors,glutamate and gamma-aminobutyric acid,neuroimmune network function as well as epigenetic regulation of key functional genes in stress response,play important roles in the long-term effects of early life stress on neurodevelopment.Various postnatal environment can alleviate the neurological and behavioral abnormalities induced by stress.Therefore,the risk of long-term effects may be reduced along with environment optimization.