Systemic lupus erythematosus, a disease conditioned by the environment / Lupus eritematoso sistémico, una enfermedad condicionada por el medio ambiente

ABSTRACT Systemic lupus erythematosus is an autoimmune disease that involves several systems, affects mainly young adult women, and causes a significant deterioration in quality of life. Different environmental aspects are known to facilitate the development of lupus in predisposed individuals. For several years it has been known that factors such as exposure to UV rays are related to the development of lupus; however, due to factors inherent to globalization, life-style changes, improved knowledge of cell signaling pathways as well as a better understanding of metabolomics, proteomics an genomics, it has been possible to better understand the relationship between cells and their environment. This study based on a narrative review, compiles the existing evidence on different risk factors and the development of lupus, including aspects typical of the Colombian population.

RESUMEN El lupus eritematoso sistémico es una enfermedad autoinmune que compromete diferentes sistemas, afecta principalmente a mujeres adultas jóvenes y genera un deterioro significativo de la calidad de vida. Es bien conocido que diferentes aspectos relacionados con la calidad de vida facilitan el desarrollo del lupus en individuos predispuestos. Desde hace varios años se sabe que factores tales como la exposición a los rayos ultravioleta se relacionan con el desarrollo de lupus; sin embargo, debido a factores inherentes a la globalización, a los cambios en los hábitos, a un mayor conocimiento de las vías de señalización celular, así como a una mayor comprensión de la metabolómica, la proteómica y la genómica, ha sido posible entender mejor la relación entre las células y su medio ambiente. En el presente estudio reunimos, a través de una revisión narrativa, la evidencia actual sobre diferentes factores de riesgo y el desarrollo del lupus, incluyendo aspectos típicos de la población colombiana.

Innate immune responses in RNA viral infection / 医学前沿

RNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

Progress in arsenic carcinogenesis / 中华地方病学杂志

Arsenic is one of the chemical pollutants,which is widely distributed in natural environment.International agency for research on cancer (IARC) has made it clear that arsenic and its compounds are carcinogens;endemic arseniasis has become a public health problem that seriously endangers human health.However,the arsenic metabolic and toxic effects of the species vary widely,failure to replicate a suitable carcinogenic model on animals,and there is no recognized carcinogenic mechanism.The author provide a brief review of arsenic metabolism,arsenic genotoxicity,arsenic-induced epigenetic changes,arsenic-induced changes in cell signaling pathways,arsenic and estrogen receptor expression,and arsenic immunotoxicity,to provide a reference for control and prevention of endemic arseniasis.

Thyroid Tumorigenesis / 대한내분비외과학회지

Thyroid tumors display an intriguing biological diversity from benign follicular adenomas to lethal anaplastic carcinomas. Thyroid tumorigenesis is becoming better understood. Benign follicular adenomas are frequently associated with mutation of the thyrotrophin receptor, G alpha s or RAS. Although confirmatory studies are necessary, the present knowledge concerning the similarity in gene expression profiling between follicular adenomas and follicular carcinomas supports the progression of adenoma to carcinoma sequence. Four major genetic aberrations in follicular cellderived thyroid carcinomas such as papillary, follicular, and Hurthle cell carcinomas include mutations of BRAF or RAS, and chromosomal rearrangement of RET/papillary thyroid tumor or PAX8/peroxisome proliferator-activated receptor gamma. Differentiated thyroid carcinomas of follicular cell origin dedifferentate to poorly differentiated or anaplastic thyroid carcinomas through mutation of p53 and CTNNB1. Familial nonmedullary thyroid carcinomas are heterogenous in genetic profiling, but some genes have been investigated as candidates for causative genetic aberration. Ret mutations can cause medullary thyroid carcinomas. A genotype- phenotype relationship helps to decide prophylactic thyroidectomiesin family members of hereditary medullary carcinomas such as MENIIa or MENIIb. Primary thyroid lymphomasare closely related with Hashimoto's thyroiditis. Recent novel and promising findings include additional abnormalities in the regulation of microRNA expression, polymorphisms associated with thyroid cancer susceptibility and epigenetic changes. A newly proposed fetal cell carcinogenesis hypothesis explains more about thyroid tumorigenesis than classical multi-step carcinogenesis model, but is not yet firmly supported by evidence. Future studies need to uncover new molecular mechanisms in thyroid tumorigenesis and to provide novel therapeutic targets for thyroid carcinomas.

Epigenetic Changes (Aberrant DNA Methylation) in Colorectal Neoplasia

Both genetic and epigenetic events have been implicated in the stepwise histological progression involving adenoma-carcinoma and hyperplastic polyp/serrated adenoma-carcinoma sequences in the development of colorectal cancer. Genetic changes have been observed at each step in the initiation and progression of polyps to adenocarcinomas. Epigenetic changes also occur at each step in the pathogenesis of colorectal cancers and include CpG island DNA hypermethylation in the promoter region of genes resulting in transcriptional silencing through associated changes in chromatin structure and effects on binding of transcription factors, and DNA global hypomethylation which leads to chromosomal instability. Recent studies on MLH1 and APC genes indicate that epigenetic and genetic changes cooperate to facilitate tumor initiation and progression. Since aberrant CGI DNA promoter hypermethylation can be detected not only in colorectal polyps and cancers, but also in sera and stool, hypermethylated genes may serve as molecular markers for early detection, risk assessment and diagnosis. In addition, silenced genes caused by CGI DNA promoter hypermethylation can be reactivated by demethylating agents and also by both the inhibitors of DNA methyltransferases and histone deacetylases. Therefore, these epigenetically acting drugs should be evaluated for their chemopreventive and therapeutic potential for colorectal cancers.

The hypermethylation of CpG island in promoter regions and protein expression of O~6-methylguanine-DNA methyltransferase gene in colorectal tumor / 中华消化杂志

Objective To investigate the effect of promoter hypermethylation of O 6 methylguanine DNA methyltransferase (MGMT) gene on colorectal tumorigenesis and progression. Methods The promoter hypermethylation of O 6 methylguanine DNA methyltransferase gene was assayed in 27 sporadic colorectal adenomas, 62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation specific PCR. At the same time, the expression of MGMT protein was studied in the same samples using immunohistochemistry. Results None of the normal colorectal mucosa tissues showed methylated bands. Promoter hypermethylation was detected in 40.7%(11/27) of adenomas and 43.5% (27/62) of carcinomas, respectively. MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues. Loss of MGMT expression was found in 22.2% (6/27) of adenomas and 45.2% (28/62) of carcinomas, respectively. There were significant difference among them ( P =0.041). Methylation was detected in 5 of the 6 adenomas( P =0.027) and 24 of the 28 carcinomas( P