Carbon nanospheres mediated delivery of nuclear matrix protein SMAR 1 to direct experimental autoimmune encephalomyelitis in mice

Owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR-/-). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis

Life-Detection Technologies for the Next Two Decades

Since its inception six decades ago, astrobiology has diversified immensely to encompass several scientific questions including the origin and evolution of Terran life, the organic chemical composition of extraterrestrial objects, and the concept of habitability, among others. The detection of life beyond Earth forms the main goal of astrobiology, and a significant one for space exploration in general. This goal has galvanized and connected with other critical areas of investigation such as the analysis of meteorites and early Earth geological and biological systems, materials gathered by sample-return space missions, laboratory and computer simulations of extraterrestrial and early Earth environmental chemistry, astronomical remote sensing, and in-situ space exploration missions. Lately, scattered efforts are being undertaken towards the R&D of the novel and as-yet-space-unproven life-detection technologies capable of obtaining unambiguous evidence of extraterrestrial life, even if it is significantly different from Terran life. As the suite of space-proven payloads improves in breadth and sensitivity, this is an apt time to examine the progress and future of life-detection technologies.Comment: 6 pages, the white paper was submitted to and cited by the National Academy of Sciences in support of the Astrobiology Science Strategy for the Search for Life in the Univers

Anti-diabetic activity and safety assessment of Ayurvedic medicine, <i style="mso-bidi-font-style:normal">Jasada bhasma</i> (zinc ash) in rats<span style="mso-bidi-font-weight:bold"> </span>

811-822Jasada bhasma (zinc ash) is an extensively used Ayurvedic medicine for treating diabetes mellitus. The present communication presents yet unavailable comprehensive scientific data on its physico-chemical nature vis-à-vis anti-diabetic activity and toxicity profile.Zinc ash prepared by traditional method was found to consist of 200-500 nm sized particles, predominantly zinc oxide with hexagonal wurtzite crystal structure.The effective dose range of zinc ash in oral glucose tolerance tests performed using normoglycemic Wistar rats was found to be 3-30 mg/kg. Subsequently anti-diabetic activity was assessed in streptozotocin induced type 1 and type 2 diabetic rats. Four weeks treatment with zinc ash (1, 3, 10 mg/kg) resulted in improved glucose tolerance (16-19%), lowered blood glucose levels (20-33%) and reduced serum insulin levels (27-32%). Systemic absorption was assessed by single dose pharmacokinetic study where serum zinc levels were found to be elevated (3.5 folds) after oral administration of zinc ash. Acute and sub-acute toxicity tests demonstrated safety of zinc ash up to 300 mg/kg doseie. 100 times the efficacy dose in rats.These findings, the first of their kind, provide concrete scientific evidence that justifies usage of zinc ash in diabetes treatment

Assessment of an Integrative Anticancer Treatment Using an in Vitro Perfusion-Enabled 3D Breast Tumor Model

The study presents observations on anticancer therapeutic efficacy of magnetic fluid hyperthermia and a combination of hyperthermia and chemotherapy (i.e., integrative treatment) using an in vitro perfused and non-perfused 3D breast tumor model. The 3D in vitro breast tumor models were simulated using Comsol multiphysics, fabricated using specially designed chips, and treated with doxorubicin-loaded chitosan-coated La_0.7Sr_0.3MnO₃ (DC-LSMO) nanoparticles for hyperthermia and combination therapy in both perfused and non-perfused conditions. Computation confirmed uniform heat distribution throughout the scaffold for both the models. The findings indicate that both hyperthermia and combination treatment could trigger apoptotic cell death in the perfused and non-perfused models in varying degrees. Specifically, the perfused tumors were more resistant to therapy than the non-perfused ones. The efficacy of anticancer treatment decreased with increasing physiological complexity of the tumor model. The combination (hyperthermia and chemotherapy) treatment showed enhanced efficacy over hyperthermia alone. This is a pilot study to investigate the effects of magnetic fluid hyperthermia–chemotherapy treatment using perfused and non-perfused 3D in vitro models of tumor. The feasibility of using 3D cell culture models for contributing to our understanding of cancer and its treatment was also determined as a part of this work

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

Abstract Background The adoption of Antiretroviral Therapy (ART) substantially extends the life expectancy and quality of HIV-infected patients. Yet, eliminating the latent reservoirs of HIV to achieve a cure remains an unmet need. The advent of nanomedicine has revolutionized the treatment of HIV/AIDS. The present study explores a unique combination of Tenofovir (TNF) with gold nanoparticles (AuNPs) as a potential therapeutic approach to overcome several limitations of the current ART. Results TNF-tethered AuNPs were successfully synthesized. Cell viability, genotoxicity, haemolysis, and histopathological studies confirmed the complete safety of the preparation. Most importantly, its anti-HIV1 reverse transcriptase activity was ~ 15 folds higher than the native TNF. In addition, it exhibited potent anti-HIV1 protease activity, a much sought-after target in anti-HIV1 therapeutics. Finally, the in vivo biodistribution studies validated that the AuNPs could reach many tissues/organs, serving as a secure nest for HIV and overcoming the problem of deficient drug delivery to HIV reservoirs. Conclusions We show that the combination of TNF and AuNPs exhibits multifunctional activity, viz . anti-HIV1 and anti-HIV1 protease. These findings are being reported for the first time and highlight the prospects of developing AuNP-TNF as a novel next-generation platform to treat HIV/AIDS. Graphical Abstrac

Anticancer Activity of Indian Stingless Bee Propolis: An In Vitro Study

Indian stingless bee propolis has a complex chemical nature and is reported to possess various medicinal properties. In the present study, anticancer activity of the ethanolic extract of propolis (EEP) was explored by testing the cytotoxic and apoptotic effect in four different cancer cell lines, namely, MCF-7 (human breast cancer), HT-29 (human colon adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), and B16F1 (murine melanoma), at different concentrations. Cytotoxicity was evaluated by MTT assay and Trypan blue dye exclusion assay. EEP at a concentration of 250 g/mL exhibited ≥50% mortality in all cell lines tested (i.e., IC50 value). EEP revealed a concentration and time dependent cytotoxic effect. Apoptosis was estimated by differential staining (ethidium bromide/acridine orange) and TUNEL (deoxynucleotidyl transferase-dUTP nick end labeling) assay. Light microscopy and atomic force microscopy demonstrated morphological features of apoptosis in all the cell lines after treatment with 250 g/mL EEP for 24 h. Thus, early onset of apoptosis is the reason for anticancer activity of Indian stingless bee propolis. Further, the antioxidant potential of Indian stingless bee propolis was demonstrated to substantiate its anticancer activity