A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.

Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by a gradual destruction of insulin-producing ß-cells in the endocrine pancreas due to innate and specific immune responses, leading to impaired glucose homeostasis. T1D patients usually require regular insulin injections after meals to maintain normal serum glucose levels. In severe cases, pancreas or Langerhans islet transplantation can assist in reaching a sufficient ß-mass to normalize glucose homeostasis. The latter procedure is limited because of low donor availability, high islet loss, and immune rejection. There is still a need to develop new technologies to improve islet survival and implantation and to keep the islets functional. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells with high plasticity that can support human pancreatic islet function both in vitro and in vivo and islet co-transplantation with MSCs is more effective than islet transplantation alone in attenuating diabetes progression. The beneficial effect of MSCs on islet function is due to a combined effect on angiogenesis, suppression of immune responses, and secretion of growth factors essential for islet survival and function. In this review, various aspects of MSCs related to islet function and diabetes are described.

Healthy lifestyles in pre-service teachers in Israel: the impact of academic institutions.

Purpose: This study examines the impact of academic institutions on changes to students' awareness and habits regarding a healthy lifestyle, specifically through nutrition and physical exercise, following the Covid-19 pandemic. Design and subjects: In May 2020, quantitative online questionnaires were completed by 266 pre-service teachers (83.5% female), aged 19-63, who were studying at an academic institution in Israel. Setting: The questionnaire, which included health-related 15 items, as well as a number of demographic questions, was distributed via social media, academic mailing lists, and the researchers' colleagues. Methods: The respondents were asked to provide socio-demographic data and information regarding their health-related habits, such as smoking and exercising, at two timepoints: prior to the Covid-19 pandemic and during the first lockdown in Israel (March-May 2020). Analysis: Statistical analysis included paired t-tests, Wilcoxon and McNemar tests, Pearsons's correlations, and hierarchical regressions. Results: The academic institution's promoting of a healthy lifestyle, as perceived by students, was found to contribute to the explained variance (EPV) of their maintaining a healthy lifestyle, prior to and during the Covid-19 pandemic (R2 = 9.4%, p < .001and R2 = 2.4%, p = 0.009, respectively), beyond the respondents' demographic characteristics. Moreover, correlations were found between the institution's promoting of a healthy lifestyle at both timepoints. Respondents who perceived their institution as promoting a healthy lifestyle prior to the pandemic maintained healthier lifestyles than their peers; healthier lifestyles were also maintained by respondents who were unmarried, non-smokers, more educated, and watched less television. Finally, the institution's promoting of a healthy lifestyle prior to the pandemic significantly contributed to the students' maintaining a healthy lifestyle and healthy nutrition during the pandemic. Conclusion: The findings of this study highlight the impact of academic institutions on maintaining healthy lifestyles, even in times of crises and emergencies, thereby contributing to public health.

sFasL-The Key to a Riddle: Immune Responses in Aging Lung and Disease.

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.

ATP dependence of the non-specific ion channel in Torpedo synaptic vesicles.

Synaptic vesicles of Torpedo electromotor neurons contain a high amount of ATP. The concentration of total ATP is around 120 mM, whereas the free [ATP] is about 5-6 mM. We examined the effect of intravesicular ATP on the non-specific ion channel in Torpedo-fused synaptic vesicles. It was found that this channel is closed when the ATP concentration is above 2 mM, but it is very frequently open at lower ATP concentrations. Unmasking this ion channel at a low ATP concentration may be significant for post-fusion control of transmitter release by the 'kiss and run' mechanism in normal conditions, while during metabolic stress it may underlie dissipation of important gradients across the vesicle membrane.

Hydrogen ions control synaptic vesicle ion channel activity in Torpedo electromotor neurones.

During exocytosis the synaptic vesicle fuses with the surface membrane and undergoes a pH jump. When the synaptic vesicle is inside the presynaptic nerve terminal its internal pH is about 5.5 and after fusion, the inside of the vesicle comes in contact with the extracellular medium with a pH of about 7.25. We examined the effect of such pH jump on the opening of the non-specific ion channel in the synaptic vesicle membrane, in the context of the post-fusion hypothesis of transmitter release control. The vesicles were isolated from Torpedo ocellata electromotor neurones. The pH dependence of the opening of the non-specific ion channel was examined using the fused vesicle-attached configuration of the patch clamp technique. The rate of opening depends on both pH and voltage. Increasing the pH from 5.5 to 7.25 activated dramatically the non-specific ion channel of the vesicle membrane. The single channel conductance did not change significantly with the alteration in the pH, and neither did the mean channel open time. These results support the hypothesis that during partial fusion of the vesicle with the surface membrane, ion channels in the vesicle membrane open, admit ions and thus help in the ion exchange process mechanism, leading to the release of the transmitter from the intravesicular ion exchange matrix. This process may have also a pathophysiological significance in conditions of altered pH.