Impact of diet and physical activity on reproductive profile: A comparison of middle-aged and elderly men.

Age is a known determinant of reproductive health and fertility in both genders. The present work aims to assess the reproductive hormone profile of a middle-aged and elderly man. For this descriptive cross-sectional study, healthy male subjects (n=77) were recruited from the valley. Any individual suffering from any acute or chronic diseases and on drugs was ruled out from the study. Group A consisted of 40 elderly men between 60-70 years of age, and Group B comprised 37 men between 35-46 years of age. Blood samples were taken to estimate the reproductive hormone profile. Level of oxidant and antioxidant: Malondialdehyde and Glutathione. The demographic variables, which included retrospective and prospective questions, helped to assess the physical activity and diet intake behaviour of all inducted individuals. The analysis of the reproductive profile of both groups was similar and within the normal range of standards. However, the median level of LH was higher in group A than in group B: 6.7 mIU/ml versus 3.4 mIU/ml, respectively, and p<0.003. Both groups showed predominantly involvement in physical activity, >90%. The correlation of biochemical variables gives an insight into the fact that the Mediterranean diet and physical activity help to maintain a normal BMI. These implicate the normal secretion of various hormones, leading to intact spermatogenesis. We can safely deduce from this study that physically active lifestyles and a healthy diet are crucial factors in maintaining an endocrine profile.

L'âge est un déterminant connu de la santé reproductive et de la fécondité chez les deux sexes. Le présent travail vise à évaluer le profil hormonal de la reproduction d'un homme d'âge moyen et âgé. Pour cette étude transversale descriptive, des sujets masculins en bonne santé (n = 77) ont été recrutés dans la vallée. Toute personne souffrant de maladies aiguës ou chroniques et prenant des médicaments a été exclue de l'étude. Le groupe A était composé de 40 hommes âgés de 60 à 70 ans et le groupe B de 37 hommes âgés de 35 à 46 ans. Des échantillons de sang ont été prélevés pour estimer le profil des hormones reproductives. Niveau d'oxydant et d'antioxydant : Malondialdéhyde et Glutathion. Les variables démographiques, qui comprenaient des questions rétrospectives et prospectives, ont permis d'évaluer l'activité physique et le comportement alimentaire de tous les individus intronisés. L'analyse du profil reproducteur des deux groupes était similaire et se situait dans la fourchette normale des normes. Cependant, le taux médian de LH était plus élevé dans le groupe A que dans le groupe B : respectivement 6,7 mUI/ml versus 3,4 mUI/ml et p<0,003. Les deux groupes présentaient une participation prédominante à l'activité physique, > 90 %. La corrélation des variables biochimiques donne un aperçu du fait que le régime méditerranéen et l'activité physique contribuent à maintenir un IMC normal. Celles-ci impliquent la sécrétion normale de diverses hormones, conduisant à une spermatogenèse intacte. Nous pouvons déduire de cette étude qu'un mode de vie physiquement actif et une alimentation saine sont des facteurs cruciaux pour maintenir un profil endocrinien.

Cellular preconditioning and mesenchymal stem cell ferroptosis.

In this editorial, we comment on the article published in the recent issue of the World Journal of Stem Cells. They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionine γ-lyase/hydrogen sulfide (H2S) pathway as a novel approach to treat vascular disorders, particularly pulmonary hypertension. Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh, unfavorable microenvironment of the injured tissue. They also secrete various paracrine factors against apoptosis, necrosis, and ferroptosis to enhance cell survival. Ferroptosis, a regulated form of cell death characterized by iron accumulation and oxidative stress, has been implicated in various pathologies encompassing degenerative disorders to cancer. The lipid peroxidation cascade initiates and sustains ferroptosis, generating many reactive oxygen species that attack and damage multiple cellular structures. Understanding these intertwined mechanisms provides significant insights into developing therapeutic modalities for ferroptosis-related diseases. This editorial primarily discusses stem cell preconditioning in modulating ferroptosis, focusing on the cystathionase gamma/H2S ferroptosis pathway. Ferroptosis presents a significant challenge in mesenchymal stem cell (MSC)-based therapies; hence, the emerging role of H2S/cystathionase gamma/H2S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention. Further research into understanding the precise mechanisms of H2S-mediated cytoprotection against ferroptosis is warranted to enhance the therapeutic potential of MSCs in clinical settings, particularly vascular disorders.

Essential role of CD38 in platelet aggregation through the PKC-mediated internalization and activation.

Introduction: CD38 is a multifunctional enzyme with a potent Ca2+ mobilizing effect, cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). Here, we aimed to demonstrate the role of CD38 in platelets via protein kinase C (PKC)-mediated internalization and activation. Methods: Mouse platelets were used in this study. Thrombin, an agonist of platelet function, provoked a prompt and long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i), resulting from an interplay of multifold Ca2+ mobilizing messengers.The signaling pathway was delineated using different inhibitors and techniques such as platelet aggregation assay, intracellular calcium measurements, immunoprecipitation, immunoblotting, and flow cytometry. Results: We observed a sequential formation of cADPR and NAADP through CD38 activation by PKC of non-muscle myosin heavy chain IIA (MHCIIA), resulting in phospholipase C (PLC) activation in the thrombin-stimulated platelets. These findings reveal that PKC is fundamental in activating CD38 and elicits a physiological response in the murine platelets. Conclusion: PKC is involved in many signaling pathways. Specifically, PKC is involved in the internalization of CD38 via MHCIIA in CD38+/+ wild-type (WT) and CD38-/- knockout mice (KO). CD38 generates calcium-mobilizing agents that act on specific receptors of the calcium stores. Calcium triggered platelet aggregation while serving as a secondary messenger.

Mesenchymal stem cells' "garbage bags" at work: Treating radial nerve injury with mesenchymal stem cell-derived exosomes.

Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular and molecular processes. The contemporary treatment options are limited, with surgical intervention as the gold-standard method; however, each treatment option has its associated limitations, especially when the injury is severe with a large gap. Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI. The recent pilot study is a leap forward in the field, which is expected to pave the way for more enormous, systematic, and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach, in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

Critical role for CD38-mediated Ca2+ signaling in thrombin-induced procoagulant activity of mouse platelets and hemostasis.

CD38, a multifunctional enzyme that catalyzes the synthesis of intracellular Ca(2+) messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), is known to be expressed on platelets. However, the role of CD38 in platelets remains unclear. Our present results show that treatment of platelets with thrombin results in a rapid and sustained Ca(2+) signal, resulting from a coordinated interplay of Ca(2+)-mobilizing messengers, inositol 1,4,5-trisphosphate, cADPR, and NAADP. By dissecting the signaling pathway using various agents, we delineated that cADPR and NAADP are sequentially produced through CD38 internalization by protein kinase C via myosin heavy chain IIA following phospholipase C activation in thrombin-induced platelets. An inositol 1,4,5-trisphosphate receptor antagonist blocked the thrombin-induced formation of cADPR and NAADP as well as Ca(2+) signals. An indispensable response of platelets relying on cytosolic calcium is the surface exposure of phosphatidylserine (PS), which implicates platelet procoagulant activity. Scrutinizing this parameter reveals that CD38(+/+) platelets fully express PS on the surface when stimulated with thrombin, whereas this response was decreased on CD38(-/-) platelets. Similarly, PS exposure and Ca(2+) signals were attenuated when platelets were incubated with 8-bromo-cADPR, bafilomycin A1, and a PKC inhibitor. Furthermore, in vivo, CD38-deficient mice exhibited longer bleeding times and unstable formation of thrombus than wild type mice. These results demonstrate that CD38 plays an essential role in thrombin-induced procoagulant activity of platelets and hemostasis via Ca(2+) signaling mediated by its products, cADPR and NAADP.

Generation of cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate by CD38 for Ca2+ signaling in interleukin-8-treated lymphokine-activated killer cells.

We have previously demonstrated that cyclic ADP-ribose (cADPR) is a calcium signaling messenger in interleukin 8 (IL-8)-induced lymphokine-activated killer (LAK) cells. In this study we examined the possibility that IL-8 activates CD38 to produce another messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), in LAK cells, and we showed that IL-8 induced NAADP formation after cADPR production. These calcium signaling messengers were not produced when LAK cells prepared from CD38 knock-out mice were treated with IL-8, indicating that the synthesis of both NAADP and cADPR is catalyzed by CD38 in LAK cells. Application of cADPR to LAK cells induced NAADP production, whereas NAADP failed to increase intracellular cADPR levels, confirming that the production of cADPR precedes that of NAADP in IL-8-treated LAK cells. Moreover, NAADP increased intracellular Ca(2+) signaling as well as cell migration, which was completely blocked by bafilomycin A1, suggesting that NAADP is generated in lysosome-related organelles after cADPR production. IL-8 or exogenous cADPR, but not NAADP, increased intracellular cAMP levels. cGMP analog, 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate, increased both cADPR and NAADP production, whereas the cAMP analog, 8-(4-chlorophenylthio)-cAMP, increased only NAADP production, suggesting that cAMP is essential for IL-8-induced NAADP formation. Furthermore, activation of Rap1, a downstream molecule of Epac, was required for IL-8-induced NAADP formation in LAK cells. Taken together, our data suggest that IL-8-induced NAADP production is mediated by CD38 activation through the actions of cAMP/Epac/protein kinase A/Rap1 in LAK cells and that NAADP plays a key role in Ca(2+) signaling of IL-8-induced LAK cell migration.

Hyperglycemia associated blood viscosity can be a nexus stimuli.

BACKGROUND: The viscosity of a fluid is a measure of its resistance. It is the thickness and stickiness of blood, and a direct measure of the resistance of blood to flow through the vessels. Various factors in the blood have direct or indirect impact on blood viscosity. These hemorheological factors play an important role in the pathogenesis of many diseases. Glucose is one such factor, which, when increased in the blood, causes resistance in the blood flow. OBJECTIVE: The present study is aimed to assess the changes in blood viscosity associated with hyperglycemia in rodents. METHODS: Diabetic patients were grouped, depending on the duration of their diabetic status assessed by their increased HbA1c. Similarly rodents were subjected to acute or chronic hyperglycemic conditions in various experiments. In vivo, perfusion study was performed using micro probe in diabetic mice. Flow cytometry was used to assess the expression of VCAM-1 on endothelial surface. RESULTS: An approximate 40% increase in blood viscosity is observed in individual who were diabetic for the past 15 years than those who were diagnosed just one year back. Similarly such increase in blood viscosity was evident in different experiments of rodents. Our in vivo perfusion study did not showed conclusive finding however long term hyperglycemia can have deleterious effect on flow rate. Vascular pathology which was evident from the data of flow cytometry, where increase in VCAM-1 expression on the endothelial surface was observed in response to glucose and in diabetic mice. CONCLUSIONS: Hyperglycemia implicates the blood viscosity which in turn can have tedious effect on metabolic syndromes thus causing the serious effect in the tissue perfusion of an organs.