Electromagnetic fields promote severe and unique vascular calcification in an animal model of ectopic calcification

BackgroundThe effects of electromagnetic fields (EMFs) on cardiovascular calcification is unknown. We sought to evaluate the effects of EMF on vascular calcification in normal rats and in rats with chronic kidney disease (CKD) – a condition which promotes calcification.MethodsWe used four groups of rats: group 1 – exposed to EMF, group 2 – not exposed to EMF, group 3 – rats with CKD exposed to EMF, group 4 – rats with CKD not exposed to EMF. In order to induce CKD, groups 3 and 4 rats were fed with a uremia-inducing diet. Groups 1 and 3 rats were continuously exposed to EMF using a system similar to an electrical transformer, which consists of a primary coil, a ferrite ring, and a secondary coil. The system transmitter emitted a series of exponentially decaying electromagnetic sine waves (continuous exposure with pulsed peaks) in randomly selected frequencies between 150 and 155 kHz, with random exposure intensities between 4 and 7 mG. Clinical investigations included multislice computed tomography of the aortic roots. Pathological examinations of the aortas included histological characterization, and antigen expression analyses.ResultsNo calcification was found in either group of rats with normal kidney function. Aortic root calcification was significantly higher in rats exposed to EMF (group 3) compared with group 4 rats – with a mean Agatston score of 138±25 vs. 80±20 respectively (p < 0.05). Pathological examination showed massive aortic calcification in group 3 rats. The calcification pattern was unique as it formed circular rings along the length of the aortic media.Although increased calcification was noticed in group 3 rats, antigen expression of osteoblast markers was significantly decreased in group 3 compared with group 4.ConclusionsEMF exposure may have potential harmful effects on the cardiovascular system, as it promotes severe vascular calcification in CKD miliue.     

Emerging and Established Therapeutic Approaches for Nonalcoholic Fatty Liver Disease

PurposeNonalcoholic fatty liver disease (NAFLD), more recently referred to as metabolic-associated fatty liver disease, refers to a disease spectrum ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis, associated with hepatic complications (including liver fibrosis, cirrhosis, and hepatocellular carcinoma) and extrahepatic complications (particularly cardiometabolic complications, including type 2 diabetes and cardiovascular disease). Treatment options include lifestyle interventions (dietary modification and physical activity programs) and pharmacologic interventions. Treatment aims should be broad, with a hepatic focus (to improve/reverse hepatic inflammation, fibrosis, and steatohepatitis), ideally with additional extrahepatic effects affecting metabolic co-morbidities (eg, insulin resistance, glucose dysregulation, dyslipidemia), causing weight loss and affording cardiovascular protection. NASH and fibrosis represent the main histopathological features that warrant treatment to prevent disease progression. Despite a paucity of established treatments, the array of potential molecular targets, pathways, and potential treatments is continually evolving. The goal of this article was to provide a narrative review summarizing the emerging and more established therapeutic options considering the complex pathophysiology of NAFLD and the important long-term sequelae of this condition.MethodsThe literature was reviewed by using PubMed, conference abstracts, and press releases from early-phase clinical studies to provide an overview of the evidence.FindingsAs understanding of the pathophysiology of NASH/NAFLD evolves, drugs with different mechanisms of action, targeting different molecular targets and aberrant pathways that mediate hepatic steatosis, inflammation, and fibrosis, have been developed and are being tested in clinical trials. Pharmacologic therapies fall into 4 main categories according to the molecular targets/pathways they disrupt: (1) meta-bolic targets, targeting insulin resistance, hepatic de novo lipogenesis, or substrate utilization; (2) inflam-matory pathways, inhibiting inflammatory cell recruitment/signaling, reduce oxidative/endoplasmic reticulum stress or are antiapoptotic; (3) the liver–gut axis, which modulates bile acid enterohepatic circulation/signaling or alters gut microbiota; and (4) antifibrotic targets, targeting hepatic stellate cells, decrease collagen deposition or increase fibrinolysis.ImplicationsLifestyle modification must remain the cornerstone of treatment. Pharmacologic treatment is reserved for NASH or fibrosis, the presence of which requires histopathological confirmation. The disease complexity provides a strong rationale for combination therapies targeting multiple pathways simultaneously.     

Dexmedetomidine alleviates LPS-induced apoptosis and inflammation in macrophages by eliminating damaged mitochondria via PINK1 mediated mitophagy

The macrophage is an innate immune response cell that plays an important role in the development of sepsis. Dexmedetomidine (DEX) is a sedation drug, which have anti-oxidative, anti-inflammatory and anti-apoptosis effects and can be used on sepsis patients in the ICU. However, its mechanisms of action remain poorly understood. PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threonine protein kinase that recognizes damaged mitochondria and leads to mitophagy. This study investigated the effects of DEX on Lipopolysaccharides(LPS)-induced macrophage injury and explained the underlying mechanisms. The results showed that LPS treatment caused mitochondrial damage, mitochondria-dependent apoptosis and PINK1-mediated mitophagy; at the same time, PINK1 has a protective effect on LPS-induced macrophage apoptosis and inflammation by mitophagy that eliminates dysfunctional mitochondria. DEX could promote the clearance of damaged mitochondria characterized by low Mitochondrial membrane potential (MMP) and high reactive oxygen species(ROS), thus exerting a protective effect in LPS treated macrophages, and PINK1 mediated mitophagy is required for this protective effect.     

Hereditary glaucoma associated with oculodentodigital dysplasia

CASE REPORT: A newborn evaluated at 20 days old due to occasional nystagmus. Her mother had presented with oculodentodigital dysplasia (ODDD) and glaucoma. The physical examination revealed opaque micro-corneas, and horizontal nystagmus. The tonometry showed 35 mm Hg in OD and 40 mm Hg in OS and the fundus examination was normal. She had a narrow nasal bridge with narrow nostrils, and fourth and fifth finger syndactylyl in both hands. A bilateral trabeculectomy was performed with a good response. DISCUSSION: ODDD is a rare autosomal dominant disease with heterogeneous phenotype manifestations. The most frequent cause of loss of visual acuity is the glaucoma, requiring long-term follow up with periodical control of the intraocular pressure (IOP).     

Lack of association between lymphotoxin-α, galectin-2 polymorphisms and coronary artery disease: A meta-analysis

ObjectivePrevious case–control studies suggested the single nucleotide polymorphisms of lymphotoxin-α (LTA) gene and galectin-2 (LGASL2) gene are associated with coronary artery disease and myocardial infarction. However, other studies did not confirm this relationship. The objective was to assess the relationship of LTA gene, LGALS2 gene and coronary artery disease, using a meta-analysis.MethodsDatabases, including PubMed, EMbase, CBM and CNKI, were searched to get the genetic association studies. Data were extracted by two authors and pooled odds ratio (OR) and 95% confidence interval (CI) were calculated.ResultThe meta-analysis included 20640 (LTA-A252G) and 10552 (LGALS2-C3279T) cases, 15388 (A252G) and 10545 (C3279T) controls. The pooled OR of 252G was 1.02 (95%CI: 0.97–1.07) compared to wild type allele in dominant model, and was 1.00 (95%CI: 0.94–1.07) in recessive model. The pooled OR of 3279T was 0.95 (95%CI: 0.89–1.01) compared to wild type allele in dominant model, and was 0.89 (95%CI: 0.78–1.00) in recessive model. None of the polymorphisms was found to associate with coronary artery disease.ConclusionIn present study, the LTA gene and LGALS2-C3279T are not associated with coronary artery disease.