Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are non-receptor protein tyrosine kinases that are involved in cell proliferation, migration and survival. Current research of FAK and Pyk2 is greatly focused in cancer biology and several small molecule inhibitors are being tested under clinical development. Like cancer, certain chronic diseases such as cardiovascular disease, bone disease, fibrosis, rheumatoid arthritis, and neurological disorders, share malignant characteristics of cancer. Accumulating evidence has demonstrated that FAK and Pyk2 contribute to other proliferative and degenerative diseases. Thus, the goal of this review is to briefly highlight studies that have implicated FAK and Pyk2 as players in disease progression.

The MLL/SET family of histone H3 lysine 4 methyltransferases form enzyme complexes with core subunits ASH2L, WDR5, RbBP5, and DPY-30 (often abbreviated WRAD), and are responsible for global histone H3 lysine 4 methylation, a hallmark of actively transcribed chromatin in mammalian cells. Accordingly, the function of these proteins is required for a wide variety of processes including stem cell differentiation, cell growth and division, body segmentation, and hematopoiesis. While most work on MLL-WRAD has focused on the function this core complex in histone methylation, recent studies indicate that MLL-WRAD proteins interact with a variety of other proteins and lncRNAs and can localize to cellular organelles beyond the nucleus. In this review, we focus on the recently described activities and interacting partners of MLL-WRAD both inside and outside the nucleus.

Polyhydroxyalkanoates (PHAs) are a class of biopolyesters that are synthesized intracellularly by microorganisms, mainly by different genera of eubacteria. These biopolymers have diverse physical and chemical properties that also classify them as biodegradable in nature and make them compatible to living systems. In the last two decades or so, PHAs have emerged as potential useful materials in the medical field for different applications owing to their unique properties. The lower acidity and bioactivity of PHAs confer them with minimal risk compared to other biopolymers such as poly-lactic acid (PLA) and poly-glycolic acid (PGA). Therefore, the versatility of PHAs in terms of their non-toxic degradation products, biocompatibility, desired surface modifications, wide range of physical and chemical properties, cellular growth support, and attachment without carcinogenic effects have enabled their use as in vivo implants such as sutures, adhesion barriers, and valves to guide tissue repair and in regeneration devices such as cardiovascular patches, articular cartilage repair scaffolds, bone graft substitutes, and nerve guides. Here, we briefly describe some of the most recent innovative research involving the use of PHAs in medical applications. Microbial production of PHAs also provides the opportunity to develop PHAs with more unique monomer compositions economically through metabolic engineering approaches. At present, it is generally established that the PHA monomer composition and surface modifications influence cell responses.PHA synthesis by bacteria does not require the use of a catalyst (used in the synthesis of other polymers), which further promotes the biocompatibility of PHA-derived polymers.

The purpose of this study was a comparative investigation of activity of aldehyde scavenger enzymes in mitochondrial fraction of a thigh muscle in intact and immobilized rats of different ages. It has been shown that 12-month-old (adult) rats have high basal levels of aldehyde dehydrogenase, aldehyde reductase and glutathione transferase activity in mitochondrial fraction of thigh muscle. Aldehyde dehydrogenase activity increases during immobilization stress in adult rats. This change promote to enhance the effectiveness of utilization of carbonyl products of free radical oxidation in mitochondria of skeletal muscle of 12-month-old rats during stress. Immobilization of old and pubertal rats is accompanied by metabolic preconditions leading to accumulation of endogenous aldehydes in mitochondria, and, as a result, to the injury of muscular fibers and intensification of sarcopenia manifestations.

Potential toxicity of transition metals like Hg, Cu and Cd are well known and their affinity toward proteins is of great concern. This work explores the selective nature of interactions of Cu²⁺, Hg²⁺ and Cd²⁺ with the heme proteins leghemoglobin, myoglobin and cytochrome C. The binding profiles were analyzed using absorbance spectrum and steady-state fluorescence spectroscopy. Thermodynamic parameters like enthalpy, entropy and free energy changes were derived by isothermal calorimetry and consequent binding parameters were compared for these heme proteins. Free energy (DG) values revealed Cu²⁺ binding toward myoglobin and leghemoglobin to be specific and facile in contrast to weak binding for Hg²⁺ or Cd²⁺ . Time correlated single photon counting indicated significant alteration in excited state lifetimes for metal complexed myoglobin and leghemoglobin suggesting bimolecular collisions to be involved. Interestingly, none of these cations showed significant affinity for cytochrome c pointing that, presence of conserved sequences or heme group is not the only criteria for cation binding toward heme proteins, but the microenvironment of the residues or a specific folding pattern may be responsible for these differential conjugation profile. Binding of these cations may modulate the conformation and functions of these biologically important proteins.

Fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability and a cause for autism. FXS females report milder phenotypes and a lower rate of cognitive problems compared to males. This is most likely because most females are heterozygous, while males are hemizygous for the disease. Thus, most preclinical studies have been completed in males. As there is major interest in testing experimental drugs for FXS, it is imperative to determine whether females in animal models used for research, present behavioral alterations that might translate to humans in order to confirm that experimental drugs have an effect on both genders. In our study we describe behavioral phenotypes in homozygous FXS female mice developed on the FVB.129 background. We focused on detection of hippocampal-mediated cognitive abilities and other behaviors described for FXS. Our research shows that, while female FVB.129-Fmr1 knockout mice present normal learning, they have impaired memory, as well as susceptibility to audiogenic seizures. In agreement with previous reports in rodents and humans, significant levels of the small GTPase Rac1 were found in FXS female mice. Because Rac1 is involved in neuronal development, plasticity and behavior, we additionally aimed to pharmacologically inhibit Rac1 and determine whether observed phenotypes are rescued. Treatment of female FVB.129-Fmr1 knockout with a Rac1 inhibitor abolished behavioral deficits, bringing phenotypes to control levels. Our results suggest that female FVB.129-Fmr1 knockout mice display behavioral impairments that resemble FXS in humans. Moreover, those behavioral shortfalls might be associated with alteration of plasticity involving excessive Rac1 function, since pharmacological reduction of Rac1 normalizes previously altered phenotypes to control levels.

MicroRNAs (miRNAs) play an essential role in the development and progression of acute lymphoblastic leukemia (ALL), and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lymphoid differentiation has been here with discussed. However, the role of this miRNA in the outcome of ALL is not well understood. Peripheral blood of 48 patients with ALL and 20 age- and sex-matched healthy control subjects was used to accurately evaluate the expression of miR-146a by stem-loop Real time PCR. No statistically significant difference was found between patients and controls in total miR-146a expression. The expression of miR-146a was high (18.75%), low (27.08%) and not different (54.17%) in ALL patients. Our analysis indicated no association between the expression of miR-146a and any prognostic factors such as WBC/PLT counts, Hb, fusion genes (P190 and some translocations) with ALL type. This study revealed that miR-146a cannot be an independent factor for predicting the outcome of ALL patients. We suggest a multi-parameter analysis including miRNAs, transcription factors and critical genes to achieve a precise clinical panel for prognostic values.

With increasing industrialization, numerous air pollutants are generated. This research aimed to investigate the effects of inhalation of oxidative pollutants. H₂O₂ was used to simulate oxidative air pollutants, and glutathione, a reducing agent that is widely distributed in organisms, was used as an antagonist, to protect cells from oxidative stress. H₂O₂ was diluted using two gradients (0.05 mM, 0.20 mM, 0.80 mM, 3.20 mM and 0.05 mM, 0.10 mM, 0.15 mM, 0.20 mM) and GSH was dissolved at 20 μM. MTT, MDA, ROS, GSH, and TSLP were used as biomarkers to evaluate oxidative stress and possible resulting molecular events. A dose–response relationship was observed between H₂O₂ concentrations and the above-mentioned biomarkers. Glutathione significantly reduced levels of oxidative stress.