Showing papers in "Frontiers in Bioscience in 2016"

The PI3K/AKT pathway in the pathogenesis of prostate cancer.

Abstract: Despite recent advances in our understanding of the biological behavior of prostate cancer (PCa), PCa is becoming the most common malignancy in men worldwide. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in prostate carcinogenesis. Inflammatory cytokines (CCR9, IL-6, and TLR3) regulate PI3K/AKT signaling during apoptosis of PCa cells, and PI3K/AKT signaling participates with androgen-, 1alpha,25(OH)2-vitamin D3-, and prostaglandin-associated mechanisms and is regulated by ErbB, EGFR, and the HER family during cell growth. During metastasis of PCa cells, the PI3K/AKT/NF-kappaB/BMP-2-Smad axis, PTEN/PI3K/AKT pathway, and PI3K/AKT/mTOR signaling regulates tumor cell metastasis and invasion. The present review focuses on the PI3K/AKT signal pathway and discusses the role of the PI3K/AKT signal pathway in PCa tumorigenesis.

Heparin and anticoagulation.

Abstract: Heparin, a sulfated polysaccharide, has been used as a clinical anticoagulant for over 90 years. Newer anticoagulants, introduced for certain specialized applications, have not significantly displaced heparin and newer heparin-based anticoagulants in most medical procedures. This chapter, while reviewing anticoagulation and these newer anticoagulants, focuses on heparin-based anticoagulants, including unfractionated heparin, low molecular weight heparins and ultra-low molecular weight heparins. Heparin's structures and its biological and therapeutic roles are discussed. Particular emphasis is placed on heparin's therapeutic application and its adverse effects. The future prospects are excellent for new heparins and new heparin-based therapeutics with improved properties.

Mitochondrial DNA damage induced autophagy, cell death, and disease.

Abstract: Mammalian mitochondria contain multiple small genomes. While these organelles have efficient base excision removal of oxidative DNA lesions and alkylation damage, many DNA repair systems that work on nuclear DNA damage are not active in mitochondria. What is the fate of DNA damage in the mitochondria that cannot be repaired or that overwhelms the repair system? Some forms of mitochondrial DNA damage can apparently trigger mitochondrial DNA destruction, either via direct degradation or through specific forms of autophagy, such as mitophagy. However, accumulation of certain types of mitochondrial damage, in the absence of DNA ligase III (Lig3) or exonuclease G (EXOG), can directly trigger cell death. This review examines the cellular effects of persistent damage to mitochondrial genomes and discusses the very different cell fates that occur in response to different kinds of damage.

Glycosaminoglycans and infection

Abstract: Glycosaminoglycans (GAGs) are complex linear polysaccharides expressed in intracellular compartments, at the cell surface, and in the extracellular environment where they interact with various molecules to regulate many cellular processes implicated in health and disease. Subversion of GAGs is a pathogenic strategy shared by a wide variety of microbial pathogens, including viruses, bacteria, parasites, and fungi. Pathogens use GAGs at virtually every major portals of entry to promote their attachment and invasion of host cells, movement from one cell to another, and to protect themselves from immune attack. Pathogens co-opt fundamental activities of GAGs to accomplish these tasks. This ingenious strategy to subvert essential activities of GAGs likely prevented host organisms from deleting or inactivating these mechanisms during their evolution. The goal of this review is to provide a mechanistic overview of our current understanding of how microbes subvert GAGs at major steps of pathogenesis, using select GAG-pathogen interactions as representative examples.

Inflammation and endometriosis.

Abstract: Endometriosis is defined by presence of endometrial glands and stroma outside the uterine cavity and it affects approximately 5%-10% of women of reproductive age. Although endometriosis is usually considered to be due to retrograde menstruation, the true pathogenesis of this disease remains poorly understood. Endometriosis is associated with an inflammatory response and this inflammation leads to endothelial dysfunction and might even lead to carcinogenesis. Here, we review our current understanding of the role of inflammatory processes in the pathogenesis of endometriosis.

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology.

Abstract: Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury.

Functional amino acids in fish nutrition, health and welfare.

Abstract: Protein is the most expensive part of fish diets and supplies amino acids (AA) for energy, growth, protein synthesis and as substrates for key metabolic pathways. Functional AA is a term used to describe AA that are involved in cellular processes apart from protein synthesis. A deficiency, or imbalance, in functional AA may impair body metabolism and homeostasis. Recent years have seen an increased interest in AA to increase disease resistance, immune response, reproduction, behavior and more. This has led to a boost of commercially available functional fish feeds that aim to optimize fish performance and quality of the product. This review aim to collect recent findings of functional AA and of how they may improve fish health and welfare. It will focus on functional properties of some of the most studied AA, namely arginine, glutamine, glutamate, tryptophan, sulfur amino acids (methionine, cysteine and taurine), histidine and branched chain amino acids. Where information is not available in fish, we will point towards functions known in animals and humans, with possible translational functions to fish.

Antimicrobial peptides from frog skin: biodiversity and therapeutic promises.

Abstract: More than a thousand antimicrobial peptides (AMPs) have been reported in the last decades arising from the skin secretion of amphibian species. Generally, each frog species can express its own repertoire of AMPs (typically, 10-20 peptides) with differing sequences, sizes, and spectrum of action, which implies very rapid divergence, even between closely related species. Frog skin AMPs are highly potent against antibiotic-resistant bacteria, protozoa, yeasts, and fungi by permeating and destroying their plasma membrane and/or inactivating intracellular targets. These peptides have attracted considerable interest as a therapeutic alternative to conventional anti-infective agents. However, efforts to obtain a new generation of drugs using these peptides are still challenging because of high associated R&D costs due to their large size (up to 46 residues) and cytotoxicity. This review deals with the biodiversity of frog skin AMPs and assesses the therapeutic possibilities of temporins, the shortest AMPs found in the frog skin, with 8-17 residues. Such short sequences are easily amenable to optimization of the structure and to solution-phase synthesis that offer reduced costs over solid-phase chemistry.

SOCS2: physiological and pathological functions.

Abstract: Suppressors of cytokine signalling (SOCS) proteins are modulators of cytokine and growth factor signalling whose aberrant regulation has been linked to a variety of inflammatory and neoplastic diseases. SOCS proteins are able to act as substrate-recruiting component of E3-ubiquitin ligase complexes and target interacting proteins for degradation. At least some of the family members can also directly inhibit tyrosine kinases such as Janus Kinases (JAK). The most studied family members, CIS, SOCS1, SOCS2 and SOCS3 are important regulators of the JAK-STAT pathway. Here, we focus on SOCS2 and review its biological function as well as its implication in pathological processes. Furthermore, we take advantage of the known crystal structures of SOCS2 to discuss the potential effects of a selection of SOCS2 mutations that were identified in tumour tissues.

Lysophospholipids and their G protein-coupled receptors in atherosclerosis.

Abstract: Lysophospholipids (LPLs) are bioactive lipid-derived signaling molecules generated by the enzymatic and chemical processes of regiospecific phospholipases on substrates such as membrane phospholipids (PLs) and sphingolipids (SLs). They play a major role as extracellular mediators by activating G-protein coupled receptors (GPCRs) and stimulating diverse cellular responses from their signaling pathways. LPLs are involved in various pathologies of the vasculature system including coronary heart disease and hypertension. Many studies suggest the importance of LPLs in their association with the development of atherosclerosis, a chronic and severe vascular disease. This paper focuses on the pathophysiological effects of different lysophospholipids on atherosclerosis, which may promote the pathogenesis of myocardial infarction and strokes. Their atherogenic biological activities take place in vascular endothelial cells, vascular smooth muscle cells, fibroblasts, monocytes and macrophages, dendritic cells, T-lymphocytes, platelets, etc.

Regulation and involvement of matrix metalloproteinases in vascular diseases.

Abstract: Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases whose main function is to degrade and deposit structural proteins within the extracellular matrix (ECM). A dysregulation of MMPs is linked to vascular diseases. MMPs are classified into collagenases, gelatinases, membrane-type, metalloelastase, stromelysins, matrilysins, enamelysins, and unclassified subgroups. The production of MMPs is stimulated by factors such as oxidative stress, growth factors and inflammation which lead to its up- or down-regulation with subsequent ECM remodeling. Normally, excess activation of MMPs is controlled by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). An imbalance of MMPs and TIMPs has been implicated in hypertension, atherosclerotic plaque formation and instability, aortic aneurysms and varicose vein wall remodeling. Also, recent evidence suggests epigenetic regulation of some MMPs in angiogenesis and atherosclerosis. Over the years, pharmacological inhibitors of MMPs have been used to modify or prevent the development of the disease with some success. In this review, we discuss recent advances in MMP biology, and their involvement in the manifestation of vascular disease.

Role of mitochondria, ROS, and DNA damage in arsenic induced carcinogenesis.

Abstract: The International Agency for Research on Cancer (IARC) declared arsenic a class I carcinogen. Arsenic exposure induces several forms of human cancers, including cancers of skin, lung, liver, and urinary bladder. The majority of the arsenic-induced cancers occur in skin. Among these, the most common is Bowen's disease, characterized by epidermal hyperplasia, full layer epidermal dysplasia, leading to intraepidermal carcinoma as well as apoptosis, and moderate dermal infiltrates, which require the participation of mitochondria. The exact mechanism underlying arsenic induced carcinogenesis remains unclear, although increased reactive oxidative stresses, leading to chromosome abnormalities and uncontrolled growth, and aberrant immune regulations might be involved. Here, we highlight how increased mitochondrial biogenesis and oxidative stress lead to mitochondrial DNA damage and mutation in arsenic induced cancers. We also provide therapeutic rationale for targeting mitochondria in the treatment of arsenic induced cancers.

Pathophysiology of neutrophil-mediated extracellular redox reactions.

Abstract: Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

The neurobiology of acetyl-L-carnitine.

Abstract: A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system. Here, we review the current state of knowledge on effects of ALC in the nervous system.

Molecular mechanisms in differentiated thyroid cancer.

Abstract: Thyroid cancer is a common endocrine malignancy. The tumorigenesis of thyroid tumours has been identified in recent years, including numerous genetic alterations and several major signalling pathways. However, the molecular mechanisms involved in thyroid cancer metastasis remain controversial. Studies in thyroid cancer metastasis suggested that reactivation of several pathways, including epithelial to mesenchymal transition and microenvironment change, may be involved in thyroid cancer migration. The previously identified thyroid oncogenes, BRAF, RET/PTC and Ras, play important roles in regulating the metastatic process. Here, we review the recent knowledge eon molecular mechanisms involved in thyroid cancer metastasis.

Potential benefits of colostrum in gastrointestinal diseases.

Abstract: This paper reviews the composition of colostrum and the potential preventive and therapeutic use of this "first milk" for treating various gastrointestinal disorders in humans. Colostrum is a complex biological liquid that is richer in antimicrobial peptides, immune-regulating compounds and growth factors than the subsequent mature milk. The main functions of colostrum are to provide essential nutritional components, strengthen the natural defense system, modulate immune response, balance intestinal microbiota and enhance the growth and repair of several tissues. Several studies and clinical trials carried out both in vitro and in vivo on humans and animals suggest the clinical benefits of bovine colostrum (BC) supplementation in gastro-intestinal diseases. Despite the encouraging results, further well-designed studies are required in order to confirm these effects, the dose and duration of treatment. Colostrum is safe since there are no contraindications regarding high dose levels and few side effects of clinical relevance have been reported. In conclusion, in the near future, colostrum-based supplements may play a complementary role to synthetic drugs in the prevention and treatment of various gastrointestinal disorders.

EGFR and HER2 signaling in breast cancer brain metastasis.

Abstract: Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis.

Exosomes mediate embryo and maternal interactions at implantation and during pregnancy.

Abstract: Shedding of exosomes and microvesicles is now a well-recognized, important method of cell-cell communication in a number of different cell types. However, their importance in the female reproductive tract and in mediating embryo-maternal interactions during pregnancy has only recently been recognized. Here we review the current literature as to release of extracellular vesicles by uterine cells, the embryo,, and placental trophoblast cells; how release is regulated; and the different types of signaling molecules and genetic information contained within such vesicles. We also discuss the role of these exosomes and microvesicles in regulating critical processes during implantation and pregnancy such as angiogenesis, matrix remodeling, alterations in immune function and pathological effects in gestational diseases. A better understanding of the role of exosomes and microvesicles in reproduction may lead to the development of new therapeutic approaches for treatment of infertility and pregnancy complications.

Epididymosomes: Role of extracellular microvesicles in sperm maturation.

Abstract: The spermatozoa of vertebrate species that practice internal fertilization have to transit along the epididymis after leaving the testis. This epididymis is a single, long convoluted tubule that links the testis to the vas deferens (1). During this transit, the male gametes acquire their fertilizing ability and their forward motility properties. Collectively, these modifications known as sperm maturation depend on a series of well-orchestrated biochemical modifications imposed upon the transiting male gamete (2). These modifications are in part regulated by extracellular microvesicles called epididymosomes that are found in the intraluminal epididymal compartment (3, 4). In this review, the biochemical composition of epididymosomes, their mode of secretion, the mechanisms underlying their interactions with the male gamete, and how they are involved in sperm maturation will be described.

Paradoxical impact of cholesterol on lipid packing and cell stiffness.

Abstract: Cell stiffness or deformability is a fundamental property that is expected to play a major role in multiple cellular functions. It is well known that cell stiffness is dominated by the intracellular cytoskeleton that, together with the plasma membrane, forms a membrane-cytoskeleton envelope. However, our understanding of how lipid composition of plasma membrane regulates physical properties of the underlying cytoskeleton is only starting to emerge. In this review, we first briefly describe the impact of cholesterol on the physical properties of lipid bilayers in model membranes and in living cells, with the dominant effect of increasing the order of membrane lipids and decreasing membrane fluidity. Then, we discuss accumulating evidence that removal of cholesterol, paradoxically, decreases the mobility of membrane proteins and increases cellular stiffness, with both effects being dependent on the integrity of the cytoskeleton. Finally, we discuss emerging evidence that oxidized modifications of low-density lipoproteins (oxLDL) have the same effects on endothelial biomechanical properties as cholesterol depletion, an effect that is mediated by the incorporation of oxysterols into the membrane.

Regeneration in the nervous system with erythropoietin

Abstract: Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system.

Hypoxia increases Nrf2-induced HO-1 expression via the PI3K/Akt pathway.

Abstract: Accumulating evidence indicates that transient hypoxic preconditioning improves resistance to severe hypoxia and enhances the therapeutic potential of endothelial progenitor cells (EPCs) in cell-based therapies for vascular repair and ischemic disease; however, the mechanisms underlying this process remain unclear. This study aimed to test the hypothesis that hypoxic preconditioning activates nuclear factor E2-related factor 2 (Nrf2) and expression of its target genes, resulting in improved biological function and resistance to hypoxia. Exposure to hypoxia following small interfering RNA (siRNA)-mediated knockdown of Nrf2 resulted in increased apoptosis and impaired proliferation and angiogenesis in vitro as a result of activation of nuclear translocation of Nrf2 by the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and subsequent increase in expression of the Nrf2 target gene, heme oxygenase 1 (HO-1). Moreover, the hypoxia-induced secretion of hypoxia-inducible factor 1-alpha (HIF-1 alpha) in EPCs was inhibited by Nrf2 siRNA. In conclusion, the increased resistance to hypoxia and improved therapeutic potential of EPCs as a result of hypoxia preconditioning is mediated via the PI3K/Akt-Nrf2-HO-1 signaling pathway, and the secretion of HIF-1 alpha followed by Nrf2 activation.

Caspase-1 Mediates Hyperlipidemia-Weakened Progenitor Cell Vessel Repair

Abstract: Caspase-1 activation senses metabolic danger-associated molecular patterns (DAMPs) and mediates the initiation of inflammation in endothelial cells. Here, we examined whether the caspase-1 pathway is responsible for sensing hyperlipidemia as a DAMP in bone marrow (BM)-derived Stem cell antigen-1 positive (Sca-(1+)) stem/progenitor cells and weakening their angiogenic ability. Using biochemical methods, gene knockout, cell therapy and myocardial infarction (MI) models, we had the following findings: 1) Hyperlipidemia induces caspase-1 activity in mouse Sca-(1+) progenitor cells in vivo; 2) Caspase-1 contributes to hyperlipidemia-induced modulation of vascular cell death-related gene expression in vivo; 3) Injection of Sca-1+ progenitor cells from caspase-1(-/-) mice improves endothelial capillary density in heart and decreases cardiomyocyte death in a mouse model of MI; and 4) Caspase-1(-/-) Sca-(1+) progenitor cell therapy improves mouse cardiac function after MI. Our results provide insight on how hyperlipidemia activates caspase-1 in Sca-(1+) progenitor cells, which subsequently weakens Sca-(1+) progenitor cell repair of vasculature injury. These results demonstrate the therapeutic potential of caspase-1 inhibition in improving progenitor cell therapy for MI.

Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms.

Abstract: Electrophilic nitro-fatty acids (NO2-FAs) are endogenously formed by redox reactions of nitric oxide (()NO)- and nitrite (()NO2)- derived nitrogen dioxide with unsaturated fatty acids Nitration preferentially occurs on polyunsaturated fatty acids with conjugated dienes under physiological or pathophysiological conditions such as during digestion, metabolism and as adaptive inflammatory processes Nitro-fatty acids are present in free and esterified forms achieving broad biodistribution in humans and experimental models Structural, functional and biological characterization of NO2-FAs has revealed clinically relevant protection from inflammatory injury in a number of cardiovascular, renal and metabolic experimental models NO2-FAs are engaged in posttranslational modifications (PTMs) of a selective redox sensitive pool of proteins and regulate key adaptive signaling pathways involved in cellular homeostasis and inflammatory response Here, we review and update the biosynthesis, metabolism and signaling actions of NO2-FAs, highlighting their diverse protective roles relevant to the cardiovascular system

Genes associated with T helper 17 cell differentiation and function.

Abstract: Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFalpha. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.

The sarcoglycan complex in skeletal muscle.

Abstract: In skeletal muscle, the dystrophin-associated glycoprotein complex forms a link between the actin cytoskeleton and the extracellular matrix that is critical for muscle integrity. Within this complex resides the sarcoglycan subcomplex, which consists of four transmembrane glycoproteins (alpha-, beta-, gamma-, and delta-sarcoglycan). During assembly, beta-sarcoglycan tightly associates with delta-sarcoglycan to form a functional core that then recruits gamma- and alpha-sarcoglycan to form the sarcoglycan complex. Together with sarcospan, the sarcoglycan complex binds other components of the dystrophin-associated glycoprotein complex and integrates into the myofibre's membrane. Once integrated, the sarcoglycan complex plays a pivotal role in mechanically stabilising the sarcolemma as well as the dystrophin-associated glycoprotein complex. Additionally, the sarcoglycan complex undergoes chemical modifications in response to muscle contractions, thereby transducing mechanical information into a cellular signal. Mutations in the sarcoglycans induce limb girdle muscular dystrophy, and several animal models have been established to study the molecular biology and function of the sarcoglycan complex. This review discusses the role of the sarcoglycan complex in skeletal muscle and describes the functional deficiencies that lead to muscular dystrophies.

Mesenchymal stem cells and their relationship to pericytes.

Abstract: Our body contains cells that can be propagated in vitro and give rise to cells with mature mesenchymal phenotypes. These cells are interesting not only because of their differentiation capability, which could be used for tissue engineering, but also because they secrete molecules which have trophic, chemoattractant, and immunomodulatory properties. Along decades of study, these cells have been referred to as fibroblastic cells, stromal cells, or mesenchymal stem cells. There is evidence that pericytes, cells that wrap endothelial cells in blood vessels, behave as stem cells in the tissues, and give rise to these progenitor cells when removed from the body and expanded in culture - a process that may reflect changes that occur in vivo under injury conditions. Here, we discuss the evidence that favors this thesis, and discuss culture methods, clinical and preclinical applications of mesenchymal stem cells under this perspective.

DEAD box RNA helicases: crucial regulators of gene expression and oncogenesis.

Abstract: DEAD box protein family of RNA helicases are vital players of RNA metabolism, and constitute the largest family of RNA helicases. Members of this family share nine conserved motifs including an Asp-Glu-Ala-Asp motif, giving this family its characteristic name as DEAD box RNA helicases. These conserved motifs confer RNA binding and RNA unwinding properties. Besides functioning in RNA metabolism, emerging evidences suggests several DEAD box RNA helicases to possess potential roles in regulating gene expression by acting as a transcriptional co-activator. Many of them are deregulated in cancers, and are implicated in possessing oncogenic potential. On the contrary, each of them also possesses tumor suppressive property in a context dependent manner. In this review, we discuss the mechanistic insights of gene regulation by DEAD box RNA helicases, and their significance in cancers.

Chemical immobilization of antimicrobial peptides on biomaterial surfaces.

Abstract: The hospital infections associated with surgical procedures and implants still represents a severe problem to modern society. Therefore, new strategies to combat bacterial infections mainly caused by microorganisms resistant to conventional antibiotics are extremely necessary. In this context, antimicrobial peptides have gained prominence due their biocompatibility, low toxicity and effectiveness. The immobilization of antimicrobial peptides (AMPs) onto a biomaterial surface is an excellent alternative to the development of new biodevices with microbicide properties. Herein, we describe reports related to physical-chemical characterization, in vitro/in vivo studies and clinical applicability. In this review, we focused on the AMPs mechanisms of action, different peptide immobilization strategies on solid surface and their microbicide effectiveness.

Implication of sphingosin-1-phosphate in cardiovascular regulation

Abstract: Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite generated by phosphorylation of sphingosine catalyzed by sphingosine kinase. S1P acts mainly through its high affinity G-protein-coupled receptors and participates in the regulation of multiple systems, including cardiovascular system. It has been shown that S1P signaling is involved in the regulation of cardiac chronotropy and inotropy and contributes to cardioprotection as well as cardiac remodeling; S1P signaling regulates vascular function, such as vascular tone and endothelial barrier, and possesses an anti-atherosclerotic effect; S1P signaling is also implicated in the regulation of blood pressure. Therefore, manipulation of S1P signaling may offer novel therapeutic approaches to cardiovascular diseases. As several S1P receptor modulators and sphingosine kinase inhibitors have been approved or under clinical trials for the treatment of other diseases, it may expedite the test and implementation of these S1P-based drugs in cardiovascular diseases.