Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic ...factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
Genetics of COPD Silverman, Edwin K
Annual review of physiology,
02/2020, Letnik:
82, Številka:
1
Journal Article
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Although chronic obstructive pulmonary disease (COPD) risk is strongly influenced by cigarette smoking, genetic factors are also important determinants of COPD. In addition to Mendelian syndromes ...such as alpha-1 antitrypsin deficiency, many genomic regions that influence COPD susceptibility have been identified in genome-wide association studies. Similarly, multiple genomic regions associated with COPD-related phenotypes, such as quantitative emphysema measures, have been found. Identifying the functional variants and key genes within these association regions remains a major challenge. However, newly identified COPD susceptibility genes are already providing novel insights into COPD pathogenesis. Network-based approaches that leverage these genetic discoveries have the potential to assist in decoding the complex genetic architecture of COPD.
Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol’s actions in the brain that explain (1) ...acute ethanol-related behavioral changes, such as stimulant followed by depressant effects, and (2) chronic changes in behavior, including escalated use, tolerance, compulsive seeking, and dependence. Our knowledge of ethanol use and abuse thus relies on understanding its effects on the brain. Scientists have employed both bottom-up and top-down approaches, building from molecular targets to behavioral analyses and vice versa, respectively. This review highlights current progress in the field, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors. The focus of the field is now on pinpointing which molecular effects in specific neurons within a brain region contribute to behavioral changes across the course of acute and chronic ethanol exposure.
The effects of alcohol on the brain are often misunderstood to be nonspecific. Abrahao et al. review the most recent literature arguing against this common misconception and synthesize a broader and more cohesive perspective of alcohol’s effects on brain circuits and behavior.
The incidence of type 2 diabetes (T2D) has rapidly increased over recent decades, and T2D has become a leading public health challenge in China. Compared with European descents, Chinese patients with ...T2D are diagnosed at a relatively young age and low BMI. A better understanding of the factors contributing to the diabetes epidemic is crucial for determining future prevention and intervention programs. In addition to environmental factors, genetic factors contribute substantially to the development of T2D. To date, more than 100 susceptibility loci for T2D have been identified. Individually, most T2D genetic variants have a small effect size (10-20% increased risk for T2D per risk allele); however, a genetic risk score that combines multiple T2D loci could be used to predict the risk of T2D and to identify individuals who are at a high risk. Furthermore, individualized antidiabetes treatment should be a top priority to prevent complications and mortality. In this article, we review the epidemiological trends and recent progress in the understanding of T2D genetic etiology and further discuss personalized medicine involved in the treatment of T2D.
Endometriosis represents a debilitating disease affecting women at fertile age which is associated with severe symptoms such as chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. The ...pathogenesis of this disease is not fully understood so far, multiple theories being proposed. However, more recently, attention was focused on identifying the role of genetic factors in endometriosis development. In the current paper we aimed to review the most important theories regarding pathogenesis. Furthermore we discuss the genetic factors regarding this illness as well as other genes that are suspected to be culprits in leading to this pathology.
Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population. This disease has been proved to be the major cause of death in both the developed and ...developing countries. Lifestyle, environmental factors, and genetic factors pose as risk factors for the development of cardiovascular disease. The prevalence of risk factors among healthy individuals elucidates the probable occurrence of CAD in near future. Genome‐wide association studies have suggested the association of chromosome 9p21.3 in the premature onset of CAD. The risk factors of CAD include diabetes mellitus, hypertension, smoking, hyperlipidemia, obesity, homocystinuria, and psychosocial stress. The eradication and management of CAD has been established through extensive studies and trials. Antiplatelet agents, nitrates, β‐blockers, calcium antagonists, and ranolazine are some of the few therapeutic agents used for the relief of symptomatic angina associated with CAD.
Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population. This disease has been proved to be the major cause of death in both the developed and developing countries. Lifestyle, environmental factors, and genetic factors pose as risk factors for the development of cardiovascular disease. The prevalence of risk factors among healthy individuals elucidates the probable occurrence of CAD in near future. Genome‐wide association studies have suggested the association of chromosome 9p21.3 in the premature onset of CAD. The risk factors of CAD include diabetes mellitus, hypertension, smoking, hyperlipidemia, obesity, homocystinuria, and psychosocial stress. The eradication and management of CAD has been established through extensive studies and trials. Antiplatelet agents, nitrates, β‐blockers, calcium antagonists, and ranolazine are some of the few therapeutic agents used for the relief of symptomatic angina associated with CAD.
Since December 2019, a new form of severe acute respiratory syndrome (SARS) from a novel strain of coronavirus (SARS coronavirus 2 SARS‐CoV‐2) has been spreading worldwide. The disease caused by ...SARS‐CoV‐2 was named Covid‐19 and declared as a pandemic by the World Health Organization in March 2020. Clinical symptoms of Covid‐19 range from common cold to more severe disease defined as pneumonia, hypoxia, and severe respiratory distress. In the next stage, disease can become more critical with respiratory failure, sepsis, septic shock, and/or multiorgan failure. Outcomes of Covid‐19 indicate large gaps between the male–female and the young–elder groups. Several theories have been proposed to explain variations, such as gender, age, comorbidity, and genetic factors. It is likely that mixture of genetic and nongenetic factors interplays between virus and host genetics and determines the severity of disease outcome. In this review, we aimed to summarize current literature in terms of potential host genetic and epigenetic factors that associated with increased severity of Covid‐19. Several studies indicated that the genetic variants of the SARS‐CoV‐2 entry mechanism‐related (angiotensin‐converting enzymes, transmembrane serine protease‐2, furin) and host innate immune response‐related genes (interferons IFNs, interleukins, toll‐like receptors), and human leukocyte antigen, ABO, 3p21.31, and 9q34.2 loci are critical host determinants related to Covid‐19 severity. Epigenetic mechanisms also affect Covid‐19 outcomes by regulating IFN signaling, angiotensin‐converting enzyme‐2, and immunity‐related genes that particularly escape from X chromosome inactivation. Enhanced understanding of host genetic and epigenetic factors and viral interactions of SARS‐CoV‐2 is critical for improved prognostic tools and innovative therapeutics.
Idiopathic pulmonary fibrosis Richeldi, Luca, Prof; Collard, Harold R, MD; Jones, Mark G, PhD
The Lancet,
05/2017, Letnik:
389, Številka:
10082
Journal Article
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Summary Idiopathic pulmonary fibrosis is a prototype of chronic, progressive, and fibrotic lung disease. Healthy tissue is replaced by altered extracellular matrix and alveolar architecture is ...destroyed, which leads to decreased lung compliance, disrupted gas exchange, and ultimately respiratory failure and death. In less than a decade, understanding of the pathogenesis and management of this disease has been transformed, and two disease-modifying therapies have been approved, worldwide. In this Seminar, we summarise the presentation, pathophysiology, diagnosis, and treatment options available for patients with idiopathic pulmonary fibrosis. This disease has improved understanding of the mechanisms of lung fibrosis, and offers hope that similar approaches will transform the management of patients with other progressive fibrotic lung diseases.
Colorectal cancer (CRC) ranks among the world’s most prevalent cancers, annually claiming tens of thousands of lives. Early detection of tumor DNA in serum/plasma before metastasis can significantly ...enhance patient outcomes post-tumor removal. Recent advances in detecting tumor DNA in serum/plasma have catalyzed many new research directions and opportunities for molecular diagnostics. This article synthesizes data from approximately 45 research and review papers, representing the latest findings in this field. Specifically, 30 research articles from databases such as PubMed, Web of Science, Scopus, and Google Scholar were reviewed to investigate the diagnostic significance of Oct-4 in CRC. These articles focused on tissue samples from CRC and adjacent non-tumor tissues.Oct-4, an octamer-binding transcription factor, is crucial for developing embryonic stem and germ cells. Moreover, it plays a vital role in preserving cancer stem-like characteristics in specific tumor types, making it a pivotal biomarker for cancer stem cells. Our study indicates a strong association between Oct-4 expression and CRC. Primary CRC tissues, matched non-tumor tissues, and benign polyp tissues, each representing different carcinogenesis stages, were analyzed to substantiate this claim. Oct-4 expression was quantified through reverse transcription polymerase chain reaction, flow cytometry, and immunohistochemistry analyses.Furthermore, medical records of CRC patients were examined, and clinical pathology analyses were conducted to assess the correlation between Oct-4 expression and specific clinical pathology features. Findings reveal a progressive increase in Oct- 4 transcription and translation from non-tumor tissues to benign polyp tissues and from benign polyps to CRC tissues. These observations suggest that aberrant Oct-4 expression may significantly contribute to the development of CRC.
Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating ...that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (r
= 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
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