MicroRNAs in Cardiac Hypertrophy

Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy. - 2019 by the authors. Licensee MDPI, Basel, Switzerland

Asymmetry and structural system analysis of the proximal femur meta-epiphysis: osteoarticular anatomical pathology

<p>Abstract</p> <p>Background</p> <p>The human femur is commonly considered as a subsystem of the locomotor apparatus with four conspicuous levels of organization. This phenomenon is the result of the evolution of the locomotor apparatus, which encompasses both constitutional and individual variability. The work therein reported, therefore, underlies the significance of observing anatomical system analysis of the proximal femur meta-epiphysis in normal conditions, according to the anatomic positioning with respect to the right or left side of the body, and the presence of system asymmetry in the meta-epiphysis structure, thus indicating structural and functional asymmetry.</p> <p>Methods</p> <p>A total of 160 femur bones of both sexes were compiled and a morphological study of 15 linear and angulated parameters of proximal femur epiphysis was produced, thus defining the linear/angulated size of tubular bones. The parameters were divided into linear and angulated groups, while maintaining the motion of the hip joint and transmission of stress to the unwanted parts of the limb. Furthermore, the straight and vertical diameters of the femoral head and the length of the femoral neck were also studied. The angle between the neck and diaphysis, the neck antiversion and angle of rotation of the femoral neck were subsequently measured. Finally, the condylo-diaphyseal angle with respect to the axis of extremity was determined. To visualize the force of intersystem ties, we have used the method of correlation galaxy construction.</p> <p>Results</p> <p>The absolute numeral values of each linear parameter were transformed to relative values. The values of superfluity coefficient for each parameter in the right and left femoral bone groups were estimated and Pearson's correlation coefficient has been calculated (> 0.60). Retrospectively, the observed results have confirmed the presence of functional asymmetry in the proximal femur meta-epiphysis. On the basis of compliance or insignificant difference in the confidence interval of the linear parameters, we have revealed, therefore, a discrepancy in values between the neck and the diaphysis angle and the angle of femoral neck rotation (range displacement of confident interval to a greater degree to the right).</p> <p>Conclusion</p> <p>This study assessed the observations of a systemic anatomical study encompassing the proximal femur meta-epiphysis behavior in normal condition. This work has significance in medical practice as the theoretical basis is also required in knowing the decreased frequency and degree of severity of osteoarthritic pathologies in the dominant lower extremity.</p

Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits. Hence, the development of novel approaches is greatly needed. Methods In this study, we found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-34, is very effective in activating S/G2M cell cycle checkpoints, resulting in permanent cell cycle arrest and reactivation of p53 transcription functions and caspase-3-dependent apoptosis of HTLV-I-transformed and patient-derived ATLL tumor cells. We also found that HTLV-I-transformed MT-2 cells are resistant to PJ-34 therapy associated with reduced cleaved caspase-3 activation and increased expression of RelA/p65. Conclusion Since PJ-34 has been tested in clinical trials for the treatment of solid tumors, our results suggest that some ATLL patients may be good candidates to benefit from PJ-34 therapy

Mechanisms of HTLV-1 persistence and transformation

Adult T-cell leukaemia (ATL) is caused by the human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 has elaborated strategies to persist and replicate in the presence of a strong immune response. In this review, we summarise these mechanisms and their contribution to T-cell transformation and ATL development

Supplementing essential amino acids with the nitric oxide precursor, l-arginine, enhances skeletal muscle perfusion without impacting anabolism in older men

Postprandial limb blood flow and skeletal muscle microvascular perfusion reduce with aging. Here we tested the impact of providing bolus essential amino acids (EAA) in the presence and absence of the nitric oxide precursor, l-Arginine (ARG), upon skeletal muscle blood flow and anabolism in older men. Healthy young (YOUNG: 19.7 ± 0.5 y, N = 8) and older men (OLD, 70 ± 0.8 y, N = 8) received 15 g EAA or (older only) 15 g EAA +3 g ARG (OLD-ARG, 69.2 ± 1.2 y, N = 8). We quantified responses in muscle protein synthesis (MPS; incorporation of 13C phenylalanine into myofibrillar proteins), leg and muscle microvascular blood flow (Doppler/contrast enhanced ultrasound (CEUS)) and insulin/EAA in response to EEA ± ARG. Plasma EAA increased similarly across groups but argininemia was evident solely in OLD-ARG (∼320 mmol, 65 min post feed); increases in plasma insulin (to ∼13 IU ml−1) were similar across groups. Increases in femoral flow were evident in YOUNG >2 h after feeding; these effects were blunted in OLD and OLD-ARG. Increases in microvascular blood volume (MBV) occurred only in YOUNG and these effects were isolated to the early postprandial phase (+45% at ∼45 min after feeding) coinciding with detectable arterio-venous differences in EAA reflecting net uptake by muscle. Increases in microvascular flow velocity (MFV) and tissue perfusion (MBV × MFV) occurred (∼2 h) in YOUNG and OLD-ARG, but not OLD. Postprandial protein accretion was greater in YOUNG than OLD or OLD-ARG; the latter two groups being indistinguishable. Therefore, ARG rescues aspects of muscle perfusion in OLD without impacting anabolic blunting, perhaps due to the “rescue” being beyond the period of active EAA-uptake