Alterations in Skeletal Muscle Repair in Young Adults with Type 1 Diabetes Mellitus

Though preclinical models of type 1 diabetes (T1D) exhibit impaired muscle regeneration, this has yet to be investigated in humans with T1D. Here we investigated the impact of damaging exercise (eccentric quadriceps contractions) in eighteen physically-active young adults with and without T1D. Pre- and post-exercise (48h and 96h), participants provided blood samples, vastus lateralis biopsies and performed maximal voluntary quadriceps contractions (MVC). Skeletal muscle sarcolemmal integrity, extracellular matrix content (ECM), and satellite cell (SC) content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage. MVC was comparable between T1D and controls before exercise. Post-exercise, MVC was decreased in both groups, but T1D subjects exhibited moderately lower strength recovery at both 48h and 96h. Serum creatine kinase, an indicator of muscle damage, was moderately higher in T1D participants at rest, and exhibited a small elevation 96h post-exercise. T1D participants showed lower SC content at all timepoints and demonstrated a moderate delay in SC proliferation after exercise. A greater number of myofibers exhibited sarcolemmal damage (disrupted dystrophin) and increased ECM (laminin) content in participants with T1D despite no differences between groups in ultrastructural damage as assessed by electron microscopy. Finally, transcriptomic analyses revealed dysregulated gene networks involving RNA translation and mitochondrial respiration, providing potential explanations for previous observations of mitochondrial dysfunction in similar T1D cohorts. Our findings indicate that skeletal muscle in young adults with moderately-controlled T1D is altered after damaging exercise; suggesting that longer recovery times following intense exercise may be necessary.

Natural Bioactive as a Potential Therapeutic Approach for the Management of Cyclophosphamide-induced Cardiotoxicity

: Cyclophosphamide (CP) is an extensively used anticancer drug, but its cardiotoxic manifestation is a major concern for its widespread clinical use. The observed cardiotoxic attributes have been reported at the therapeutic dose and often result into a high mortality rate and poor clinical outcome. Fall in the level of antioxidant enzymes catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) generation of reactive oxygen species (ROS), inflammatory cytokines nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), apoptotic proteins (caspases) and direct damage to myocardial tissue (histological and ultrastructural damage) are some of the reported manifestations of cardiotoxicity. The observed clinical attributes of CP-induced cardiotoxicity are myocarditis, hemorrhage, thrombosis, myocardial infarction (MI), reduced ejection fraction, altered electrocardiogram (ECG) reading and heart failure. However, unlike Daxarazasone (an adjuvant to reduce doxorubicin-induced cardiotoxicity) no approved adjuvant is available to mitigate CP-induced cardiotoxicity. Thus, various natural bioactives have been explored for the possible cardioprotective effect against CP-induced cardiotoxicity. In the current manuscript, we have discussed the clinical and preclinical aspects of CP-induced cardiotoxicity, its various clinically used combination with other anticancer drugs, and the available therapeutic regimen to mitigate this cardiotoxicity. Further, we discussed the limitations of available synthetic drugs used as an adjuvant and discussed various natural bioactive and their experimental details. This manuscript's overall goal is to throw light on CP-induced cardiotoxicity and summarize all the experimental data so that researchers working in this field may scientifically get up-to-date information at one place.

Chemical Composition and Biological Activities of Oregano and Lavender Essential Oils

Folk medicine uses wild herbs, especially from the Lamiaceae family, such as oregano and lavender, in the treatment of many diseases. In the present study, we investigated the antibacterial activity of the essential oils of Origanum glandulosum Desf. and Lavandula dentata L. against multidrug-resistant Klebsiella pneumoniae strains. The chemical composition of essential oils and their effect on the ultrastructure of the tested bacteria and on the release of cellular components that absorb at 260 nm were studied. Furthermore, the cytotoxicity and the production of reactive oxygen species in human lymphocytes treated with essential oils were evaluated. Thymol (33.2%) was the major constituent in O. glandulosum, and β-pinene (17.3%) was the major constituent in L. dentata. We observed ultrastructural damage in bacteria and increased release of cellular material. Furthermore, ROS production in human lymphocytes treated with essential oils was lower than in untreated lymphocytes and no cytotoxicity was observed. Therefore, the essential oils of lavender and oregano could be used as a source of natural antibacterial and antioxidant agents with potential pharmacological applications.

NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1β and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1β expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.

Response of Endolithic Chroococcidiopsis Strains From the Polyextreme Atacama Desert to Light Radiation

Cyanobacteria exposed to high solar radiation make use of a series of defense mechanisms, including avoidance, antioxidant systems, and the production of photoprotective compounds such as scytonemin. Two cyanobacterial strains of the genus Chroococcidiopsis from the Atacama Desert – which has one of the highest solar radiation levels on Earth- were examined to determine their capacity to protect themselves from direct photosynthetically active (PAR) and ultraviolet radiation (UVR): the UAM813 strain, originally isolated from a cryptoendolithic microhabitat within halite (NaCl), and UAM816 strain originally isolated from a chasmoendolithic microhabitat within calcite (CaCO3). The oxidative stress induced by exposure to PAR or UVR + PAR was determined to observe their short-term response, as were the long-term scytonemin production, changes in metabolic activity and ultrastructural damage induced. Both strains showed oxidative stress to both types of light radiation. The UAM813 strain showed a lower acclimation capacity than the UAM816 strain, showing an ever-increasing accumulation of reactive oxygen species (ROS) and a smaller accumulation of scytonemin. This would appear to reflect differences in the adaptation strategies followed to meet the demands of their different microhabitats.