Dose response of transcranial near infrared light stimulation on brain functional connectivity and cognition in older adults-A randomized comparison.

Photobiomodulation, also called low-level light therapy, has been reported in animal studies to have an effect on brain activity and cognition. However, studies in humans regarding its effect on cognition and brain functional connectivity, and the required dose threshold for achieving the same have been very limited. We compared the effects of different doses of photobiomodulation (PBM) on cognition and resting state brain functional connectivity in 25 cognitively normal adults aged 55-70 years. They were randomized to a single session of the sham group, "low-dose" and "high-dose" groups receiving NIR light with transcranial fluence of 26 and 52 J/cm2 respectively, and intranasal fluence of 9 and 18 J/cm2 respectively. There was a significant increase in resting state functional connectivity of the left superior frontal gyrus (SFG) with the left planum temporale (PT), p = 0.0016, and with the left inferior frontal gyrus, pars triangularis, p = 0.0235 in the "high-dose" group only compared to the "sham" group. There was also a significant improvement in visual search and processing speed (p = 0.012) in the "high-dose" group. Replication of these findings in an adequately powered randomized sham-controlled study in healthy older adults can pave the way for clinical application of NIRL as a therapeutic modality in patients with Alzheimer's disease.

Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) and Zinc Sulfate (ZnSO4). Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death. Therefore, cellular zinc homeostasis in Leishmania can be explored for new drug targets and chemotherapeutics to control Leishmanial growth and disease progression.