SRF: a seriously responsible factor in cardiac development and disease.

The molecular mechanisms that regulate embryogenesis and cardiac development are calibrated by multiple signal transduction pathways within or between different cell lineages via autocrine or paracrine mechanisms of action. The heart is the first functional organ to form during development, which highlights the importance of this organ in later stages of growth. Knowledge of the regulatory mechanisms underlying cardiac development and adult cardiac homeostasis paves the way for discovering therapeutic possibilities for cardiac disease treatment. Serum response factor (SRF) is a major transcription factor that controls both embryonic and adult cardiac development. SRF expression is needed through the duration of development, from the first mesodermal cell in a developing embryo to the last cell damaged by infarction in the myocardium. Precise regulation of SRF expression is critical for mesoderm formation and cardiac crescent formation in the embryo, and altered SRF levels lead to cardiomyopathies in the adult heart, suggesting the vital role played by SRF in cardiac development and disease. This review provides a detailed overview of SRF and its partners in their various functions and discusses the future scope and possible therapeutic potential of SRF in the cardiovascular system.

SUMO proteins in the cardiovascular system: friend or foe?

Post-translational modifications (PTMs) are crucial for the adaptation of various signalling pathways to ensure cellular homeostasis and proper adaptation to stress. PTM is a covalent addition of a small chemical functional group such as a phosphate group (phosphorylation), methyl group (methylation), or acetyl group (acetylation); lipids like hydrophobic isoprene polymers (isoprenylation); sugars such as a glycosyl group (glycosylation); or even small peptides such as ubiquitin (ubiquitination), SUMO (SUMOylation), NEDD8 (neddylation), etc. SUMO modification changes the function and/or fate of the protein especially under stress conditions, and the consequences of this conjugation can be appreciated from development to diverse disease processes. The impact of SUMOylation in disease has not been monotonous, rather SUMO is found playing a role on both sides of the coin either facilitating or impeding disease progression. Several recent studies have implicated SUMO proteins as key regulators in various cardiovascular disorders. The focus of this review is thus to summarize the current knowledge on the role of the SUMO family in the pathophysiology of cardiovascular diseases.

In vitro and in vivo effects of two coconut oils in comparison to monolaurin on Staphylococcus aureus: rodent studies.

Since monolaurin, a monoglyceride formed in the human body in small quantities, has proven effective both in vitro and in vivo against certain strains of Staphylococcus aureus, an important question arises whether consuming a substance high in lauric acid content, such as coconut oil could increase intrinsic monolaurin production to levels that would be successful in overcoming staphylococcal and other microbial invaders. Both a cup plate method and a microdilution broth culture system were employed to test bacteriostatic and bactericidal effects of the test agents in vitro. To test effectiveness in vivo, female C3H/he mice (10-12 per group) were orally administered sterile saline (regular control), vancomycin (positive control), aqueous monolaurin, or two varieties of coconut oil (refined, bleached, deodorized coconut oil and virgin coconut oil) for 1 week before bacterial challenge and 30 days after. A final group received both monolaurin and vancomycin. In contrast to monolaurin, the coconut oils did not show bactericidal activity in vitro. In vivo, the groups receiving vancomycin, monolaurin, or the combination showed some protection--50-70% survival, whereas the protection from the coconut oils were virtually the same as control--0-16% survival. Although we did not find that the two coconut oils are helpful to overcome S. aureus infections, we corroborated earlier studies showing the ability of monolaurin to do such.

Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice.

New Zealand black (NZB) mice with autoimmune and B lymphoproliferative disease (B-LPD) are a model for human chronic lymphocytic leukemia (CLL). A genomewide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content, and microsatellite polymorphisms, 74 had disease. The CD5(+), IgM(+), B220(dim), hyperdiploid LPD was linked to 3 loci on chromosomes 14, 18, and 19 that are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs mir-15a16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3' flanking sequence of the identical microRNA, mir-16-1, and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cell-cycle alterations and increased apoptosis. Linkage of the mir-15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the mir-15a/16-1 is the molecular lesion in CLL.

Effects of Essential Oils and Monolaurin on Staphylococcus aureus: In Vitro and In Vivo Studies.

The antimicrobial properties of volatile aromatic oils and medium-chain fatty acids derived from edible plants have been recognized since antiquity. To give examples, Origanum oil, used as a food-flavoring agent, possesses a broad spectrum of antimicrobial activity due, at least in part, to its high content of phenolic derivatives such as carvacrol and thymol. Similarly, lauric acid, present in heavy concentrations in coconuts, forms monolaurin in the body that can inhibit the growth of pathogenic microbes. Using Staphylococcus aureus in broth cultures and a microdilution method, comparative efficacy of Origanum oil, and a constituent carvacrol, other essential oils and monolaurin were examined. Origanum oil was the most potent of the essential oils tested and proved bactericidal in culture to two strains of Staphylococcus aureus (ATCC #14154 and #14775) at 0.25 mg/mL. In vitro, monolaurin's effects mirrored Origanum oil. The combination of both was bactericidal at the 0.125 mg/mL concentration of each. In two separate In vivo experiments, injected Staphylococcus aureus (ATCC #14775) killed all 14 untreated mice within a 1-week period. In treated mice, over one third survived for 30 days when given oral Origanum oil daily for 30 days (6/14). Fifty percent of the mice survived for 30 days when receiving daily vancomycin (7/14) and monolaurin (4/8). Over 60% of mice survived when receiving a daily combination of Origanum oil and monolaurin (5/8). Origanum oil and/or monolaurin may prove to be useful antimicrobial agents for prevention and therapy of Staphylococcus aureus infections.