Genes & Diseases

Metabolic syndrome (MS) is a cluster of metabolic abnormalities. Obesity and MS are always accompanied by elevated oxidative stress which might affect cellular bio-molecules such as DNA. The aim of the present study is to investigate DNA damage profile in obese premenopausal women and its relation to the risk of MS, polycystic ovary syndrome (PCOS) and history of recurrent pre-eclampsia. The study included 90 obese women included cases with MS (n = 30), PCOS (n = 30) and previous history of recurrent preeclampsia (n = 30) and, age-matched healthy non-obese control women (n = 50)...

Intrahepatic cholestasis of pregnancy (ICP) is related to cholestatic disorder in pregnancy. Total urinary sulfated bile acids (SBAs) were found increased in ICP. We distinguished the metabolic profiling of urinary SBAs in ICP to find potential biomarkers for the diagnosis and grading of ICP. The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze urinary SBAs profiling in mild and severe ICP cases, as well as healthy controls. 16 kinds of urinary SBAs were determined by HPLC-MS/MS...

In order to explore the molecular mechanisms behind the pathogenesis of acute liver failure (ALF) associated with hepatitis B virus (HBV) infection, the present study aimed to identify potential key genes and pathways involved using samples from patients with HBV-associated ALF. The GSE38941 array dataset was downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between 10 liver samples from 10 healthy donors and 17 liver specimens from 4 patients with HBV-associated ALF were analyzed using the Linear Models for Microarray Data package...

Alzheimer's disease (AD) is characterized by senile plaques (SP) composed of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs) composed of intracellular hyperphosphorylated tau. Recently, nuclear receptor subfamily 4 group A member 1 (NR4A1) was implicated in synaptic plasticity, long-term memory formation, suggesting that it may play a role in the pathophysiology of AD. Here, we showed that the expression of NR4A1 was significantly increased in the hippocampus of APP/PS1 transgenic mice. In addition, NR4A1 overexpression in HT22 cells up-regulated APP and BACE1 levels, down-regulated ADAM10 expression, and promoted amyloidogenesis as indicated by decreased α-CTF levels and elevated β-CTF levels...

To assess the efficacy and short-term outcomes of adherence to statin therapy among coronary heart disease (CHD) patients following their hospital discharge, we enrolled 615 CHD patients who were prescribed statins from The First Affiliated Hospital of Chongqing Medical University in China between February 1st and October 31st of 2013. Statin adherence was evaluated by identifying the proportion of patients who remained adherent or became non-adherent to statin therapy over 4-8 months post-discharge from the hospital...

Myofibrillar myopathies (MFMs) are rare genetic and slowly progressive neuromuscular disorders. Several pathogenic mutations have been reported in MFM-related genes including DES , CRYAB , MYOT , LDB3 or ZASP , FLNC , BAG3 , FHL1 and DNAJB6 . Although MFMs is commonly inherited in an autosomal dominant manner, the inheritance pattern and novel mutated genes are not thoroughly elucidated in some cases. Here, we report discovery of a novel nonsense mutation in a 29-year-old Iranian male patient with motor disorders and deformity in his lower limbs...

The in vitro organoid model is a major technological breakthrough that has been established as an important tool in many basic biological and clinical applications. This near-physiological 3D culture system accurately models various biological processes, including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutations or damage. Organoids have the potential value of being an accurate model for disease predictions or drug screening applications and to identify the ideal treatment for that patient...

Correct folding of nascent peptides occurs in the endoplasmic reticulum (ER). It is a complicate process primarily accomplished by the coordination of multiple redox proteins including members of the protein disulfide isomerase (PDI) family. As a critical member of the PDI family, thioredoxin domain containing protein 5 (TXNDC5) assists the folding of newly synthesized peptides to their mature form through series of disulfide bond exchange reactions. Interestingly, TXNDC5 is frequently found overexpressed in specimens of many human diseases including various types of cancer...

Epigenetic, along with genetic mechanisms, is essential for natural evolution and maintenance of specific patterns of gene expression in mammalians. Global epigenetic variation is inherited somatically and unlike genetic variation, it is dynamic and reversible. They are somatically associated with known genetic variations. Recent studies indicate the broad role of epigenetic mechanisms in the initiation and development of cancers, that they are including DNA methylation, histone modifications, nucleosomes changes, non-coding RNAs...

No abstract text is available yet for this article.

Traditional thiazolidinediones (TZDs), such as rosiglitazone, are peroxisome proliferator-activated receptor γ (PPARγ) potent agonists that can be used to treat type 2 diabetes but carry unwanted effects, including increased risk for fracture. The present work aimed to compare the insulin-sensitizing efficacies and bone-loss side effects of CMHX008, a novel TZDs-like PPARγ partial agonist, with those of rosiglitazone. A TR-FRET PPARγ competitive binding assay was used to compare the binding affinity between CMHX008 and rosiglitazone...

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in developing nations like India. RHD commonly affects the mitral valve which is lined by a single layer of endothelial cells (ECs). The role of ECs in mitral valve damage during RHD is not well elucidated. In here, anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs (HUVECs and HMVECs). ECs proinflammatory phenotype with increased expression of TNFα, IL-6, IL-8, IFNγ, IL-1β, ICAM1, VCAM1, E-selectin, laminin B, and vimentin was documented in both ECs...

Di-(2-ethylhexyl) phthalate (DEHP), is known to impair testicular functions and reproduction. However, its effects on immature testis Blood-testis barrier (BTB) and the underlying mechanisms remain obscure. We constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by DEHP. Sprague-Dawley rats were developmentally exposed to 0, 250 and 500 mg/kg DEHP via intragastric administration from postnatal day (PND) 1 to PND 35. Testicular morphology, expressions of BTB junction proteins and autophagy related proteins were detected...

Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and -318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology...

Ischemic stroke is a common disease with high mortality and morbidity worldwide. One of the important pathophysiological effects of ischemic stroke is apoptosis. A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra. Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR. Therefore, this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra...

Preeclampsia is characterized by new onset of hypertension and proteinuria after 20 weeks' gestation and is a leading cause of maternal and neonatal morbidity and mortality. The pathogenesis of preeclampsia is often associated with aberrant trophoblast function that leads to shallow placental implantation. However, the exact underlying mechanisms remain unclear. Placental LncZBTB39-1:2 expression level was investigated in 20 healthy placentae and 20 placentae with preeclampsia using qRT-PCR, and the metabolic profile of trophoblasts overexpressing LncZBTB39-1:2 in vitro was analysed using gas chromatography-mass spectrometry (GC-MS)...

Inflammation is indispensable for host defense, whereas excessive inflammation often develop inflammatory diseases. Autophagy is thought to be engaged in many extracellular stress responses, such as starvation and innate immunity. Thus, autophagy plays an important role in maintaining homeostasis. The purpose of this study was to elucidate the function of BRF1 in the regulation of inflammation and autophagy response in macrophages. We found that BRF1 inhibited the LPS-induced inflammatory factors expression and the autophagy flux in macrophage...

Fish oil is a natural product that has shown efficacy for managing inflammatory conditions with few side effects. There is emerging evidence that crosstalks between gut epithelial cells and immune cells contribute to chronic infectious diseases. HIV-infected (HIV+) older adults show age-related co-morbidities at a younger age than their uninfected counterparts. Persistent inflammation related to the chronic viral infection and its sequelae is thought to contribute to this disparity. However, little is known about whether fish oil reduces intestinal inflammation in HIV + patients...

The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest, apoptosis, senescence, and DNA repair. The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability. MDM2, p53, and the p53-MDM2 pathway represent well-documented targets for preventing and/or treating cancer. Natural products, especially those from medicinal and food plants, are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers...

Emerging evidence suggests that the clinical success of conventional chemotherapy is not solely attributed to tumor cell toxicity, but also results from the restoration of immunosurveillance, which has been largely neglected in the past preclinical and clinical research. Antitumor immune response can be primed by immunogenic cell death (ICD), a type of cell death characterized by cell-surface translocation of calreticulin (CRT), extracellular release of ATP and high mobility group box 1 (HMGB1), and stimulation of type I interferon (IFN) responses...