Atorvastatin preserves the integrity of endothelial adherens junctions by inhibiting vascular endothelial cadherin tyrosine phosphorylation

Vascular endothelial cadherin (VE-cad) tyrosine (Tyr) phosphorylation has been implicated in the disruption of adherens junctions (AJs) induced by inflammatory reactions. The impacts of statins on integrity of AJs and VE-cad Tyr phosphorylation have not been explored. The effects of atorvastatin on IL-1β and monocyte-induced VE-cad Tyr phosphorylation in human umbilical vein endothelial cells (ECs) were studied. In ECs treated with interleukin (IL)-1β for 30 min, VE-cad Tyr phosphorylation, dissociation of the VE-cad/β-catenin complex and transendothelial migration (TEM) of monocytes were increased. These processes were mediated by activation of HRas and RhoA that leads to phosphorylation of myosin light chain (MLC). Atorvastatin inhibited IL-1β-induced Tyr phosphorylation of VE-cad by inhibiting RhoA and by dephosphorylating MLC. The attenuating effect of atorvastatin on VE-cad Tyr phosphorylation was reversed when RhoA was activated or MLC phosphatase was inhibited. Furthermore, inhibiting farnesyl transferase or geranylgeranyl transferase reproduced the inhibitory effects of atorvastatin on VE-cad Tyr phosphorylation. In addition, atorvastatin inhibited monocyte-induced VE-cad Tyr phosphorylation in ECs and attenuated IL-1β-induced TEM of monocytes. Our study introduces a novel pleiotropic effect of atorvastatin and suggests that statins protect the integrity of AJs in ECs by inhibiting RhoA-mediated Tyr phosphorylation of VE-cad.     

Epigenetics in osteoarthritis: Novel spotlight

Osteoarthritis (OA) is the most common type of arthritis and no longer is considered as an absolute consequence of joint mechanical use (wear and tear); rather recent data demonstrate the pivotal role of inflammatory mediators in the development and progression of this disease. This multifactorial disease results from several environmental and inherited factors. Genetic cannot solely explain all the contribution share of inheritance and, this way, it is speculated that epigenetics can play a role, too. Moreover, environmental factors can induce local epigenetic changes. The epigenetic contribution to OA pathogenesis occurs at all of its levels, DNA methylation, histone modification, microRNA, and long noncoding RNA. In fact, during early phases of OA pathogenesis, environmental factors employ epigenetic mechanisms to provide a positive feedback for the OA-related pathogenic mechanisms and pathways with an ultimate outcome of a well-established clinical OA. These epigenetic changes stay during clinical disease and prevent the body natural healing and regenerative processes to work properly, resulting in an incurable disease condition. In this review article, we aimed to have an overview on the studies performed with regard to understanding the role of epigenetics in the etiopathogenesis of OA and highlighted the importance of such kind of regulatory mechanisms within this context.     

Implications of the noncoding RNAs in rheumatoid arthritis pathogenesis

Epigenetics refers to a set of regulatory mechanisms that affect gene expression, while the original sequence of the DNA remains unchanged. Because the advance of noncoding RNAs (ncRNAs), the role of microRNAs (miRNAs) has been gradually highlighted in the regulation of numerous cellular processes. A bulk of studies has identified that ncRNAs might be divided into several subtypes. On the one hand, investigations have disclosed the role of these molecules in normal physiological conditions of the cells. On the other hand, there is sufficient evidence that ncRNAs participate in the pathogenesis of diseases. Through this review article, we attempted to gain a comprehensive understanding of the role of ncRNAs, long ncRNAs, miRNAs, and other subtypes in pathogenesis, diagnosis, and treatment of rheumatoid arthritis (RA). Research demonstrated aberrant expression of several miRNAs in various cell and tissue types of patients with RA in comparison to the healthy individuals as well as in animal studies. Furthermore, plausible molecular mechanisms of alterations in ncRNAs expression has been discussed in causing the disease state. These alterations seem promising to be used as biomarkers in RA diagnosis. Alternately, they might be targeted by drugs to interrupt inflammation and other disease complications to treat patients with RA.     

Meiosis and beyond – understanding the mechanistic and evolutionary processes shaping the germline genome

The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.     

Effect of environmental factors on seed germination and emergence of Lepidium vesicarium

Lepidium vesicarium is a weed species with a wide distribution in the rangelands and dry‐land farming in East Azarbaijan, Iran. The experiments were undertaken to assay the effects of light, temperature, pH, osmotic potential, NaCl concentration and burial depth on seed germination and emergence of L. vesicarium. Germination was maintained at high levels (> 80%) over a wide day/night temperature range (10/5 to 30/20°C), but a severe reduction in the germination rate of L. vesicarium was found below 20/10°C. Germination of L. vesicarium was influenced by different light/dark regimes, as the germination rate was highest at 16 h light for the all treatments (0, 8, 12, 16 and 24 h light). Germination was 92–95% over a wide range of pH (2‐10). Germination was >50% at a water potential of ?0.7 MPa and salinity of 21 dS/m, indicating that drought and salt conditions have a minimal impact on seed germination. With increasing burial depth from 0 to 2 cm, the number of days required for 50% emergence increased and no germination was observed at burial depths deeper than 3 cm. This suggests that L. vesicarium would become troublesome in the rangelands and for growers in reduced‐tillage cropping systems. The ability to emerge from shallow depths, coupled with tolerance of a wide pH range, drought and salinity at germination, should be taken into account when managing this weed species.     

The Combination of TGF-β3 and BMP-6 Synergistically Promotes the Chondrogenic Differentiation of Equine Bone Marrow-Derived Mesenchymal Stem Cells

International Journal of Peptide Research and Therapeutics - Stem cell therapy is a new approach in veterinary medicine for the treatment of complicated disorders such as articular...