The Multicellular Effects of VDAC1 N-Terminal-Derived Peptide

The mitochondrial voltage-dependent anion channel-1 (VDAC1) protein functions in a variety of mitochondria-linked physiological and pathological processes, including metabolism and cell signaling, as well as in mitochondria-mediated apoptosis. VDAC1 interacts with about 150 proteins to regulate the integration of mitochondrial functions with other cellular activities. Recently, we developed VDAC1-based peptides that have multiple effects on cancer cells and tumors including apoptosis induction. Here, we designed several cell-penetrating VDAC1 N-terminal-derived peptides with the goal of identifying the shortest peptide with improved cellular stability and activity. We identified the D-Δ(1-18)N-Ter-Antp comprising the VDAC1 N-terminal region (19-26 amino acids) fused to the Antp, a cell-penetrating peptide. We demonstrated that this peptide induced apoptosis, autophagy, senescence, cell volume enlargement, and the refusion of divided daughter cells into a single cell, it was responsible for reorganization of actin and tubulin filaments, and increased cell adhesion. In addition, the peptide induced alterations in the expression of proteins associated with cell metabolism, signaling, and division, such as enhancing the expression of nuclear factor kappa B and decreasing the expression of the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha. These cellular effects may result from the peptide interfering with VDAC1 interaction with its interacting proteins, thereby blocking multiple mitochondrial/VDAC1 pathways associated with cell functions. The results of this study further support the role of VDAC1 as a mitochondrial gatekeeper protein in controlling a variety of cell functions via interaction with associated proteins

Molecular docking studies on potent adsorbed receptor of Thrh protein: A new target for biodegradation of indigo dye

Vat dyes are aromatic compounds widely used for denim textile industries, this result in a great wastewater problem from this industry due to recalcitrant nature of these dyes. The active protein (ThrH) was purified from Pseudomonas aeruginosa by DEAE-Sepharose A-50 column chromatography and this 3D crystal structure was reported recently. The present study aimed to demonstrate the binding energy between 3D crystal structures of indigo dye and ThrH. We have calculated the gliding score as well as gliding energy based on the hydrophobic interactions between targeted sites (amino acid and dye residue) and the main think is binding energy which was observed maximum level because of the presence of magnesium ions along with catalytic molecules located at the binding sites. The dye degraded mineralized compound was predicted by mass spectrum and infrared spectroscopy

Effect of maghemite nanoparticles in the induction of apoptosis on human hepatocellular carcinoma (Hep G2) cell line

176-181The present study focuses on the effect ofmaghemite nanoparticle in the induction of apoptosis in human hepatocellular carcinoma (Hep G2) cells. The antiproliferative effect of maghemite nanoparticle was analysed by cell viability assay and results showed less cytotoxicity at 50 to 250 µg/mL concentration. However, further increase in particle concentration exhibited higher cytotoxicity. Dysfunction of cell was noted by shrinking and small size of the cells in morphological analysis. The induction of apoptosis was revealed with live/dead assay and DNA fragmentation assay results by noticing increasing apoptotic fluorescent cells and fragmented DNA pattern, respectively. The cell cycle analysis of Hep G2 cells illustrated that they were arrested at G2/M phase transition and favoured induction of apoptosis. The expression of inflammatory cytokines interferon-γ (IFN-γ) and interleukin-12 (IL-12) were analysed by semi quantitative polymerase chain reaction that showed altered expression compared to the control. Thus the present study shows that maghemite nanoparticles induced apoptosis in Hep G2 cells through arresting the cell cycle at G2/M phase transition mediated by IFN-γ pathway

Supercritical Fluid Facilitated Disintegration of Hexagonal Boron Nitride Nanosheets to Quantum Dots and Its Application in Cells Imaging

Preparation of quantum dots (QDs) and exfoliation of two-dimensional layered materials have gathered significant attention in recent days. Though, there are number of attempts have been reported, facile and efficient methodology is yet to be explored. Here, we demonstrate supercritical fluid processing approach for rapid and facile synthesis of blue luminescent BN QDs from layered bulk material via in situ exfoliation followed by disintegration. The microscopic and AFM analysis confirmed the few layer BN QDs formation. The strong luminescent behavior of BN QDs is utilized to stain Gram-negative bacterial cells specifically in the presence of Gram-positive bacterial cells

Molecular prevalence and characterization of Hepatozoon ursi infection in Indian sloth bears (Melursus ursinus)

Hepatozoon species are parasites that infect a wide variety of domestic and wild animals. The objective of the study was to detect the occurrence of Hepatozoon ursi in Indian sloth bears and to characterize the parasite based on phylogenetic analysis of the partial 18S rRNA gene sequence. Hepatozoon infection could be detected in 38 (70%) out of fifty-four blood samples of Indian sloth bears (captive and wild), suggestive of high prevalence of Hepatozoon infection in Indian sloth bears. Sequencing of partial 18S rRNA gene of the positive samples and BLAST analysis indicated that the nearest phylogenetic neighbour was H. ursi with which they exhibited 99-100% similarity. Additionally, Hepatozoon sp. isolated from wild sloth bears of India were identical to those in captive sloth bears and phylogenetically related to H. ursi reported from Japanese black bears from Japan. To our knowledge, this is the first report on the molecular characterization of H. ursi infection in Indian sloth bears

Silencing VDAC1 to Treat Mesothelioma Cancer: Tumor Reprograming and Altering Tumor Hallmarks

Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their growth and motility. Here, we examined the effects of silencing the expression of the voltage-dependent anion channel 1 (VDAC1), controlling the metabolic and energetic crosstalk between mitochondria and the rest of the cell. We demonstrate that VDAC1 is overexpressed in mesothelioma patients; its levels increase with disease stage and are associated with low survival rates. Silencing VDAC1 expression using a specific siRNA identifying both mouse and human VDAC1 (si-m/hVDAC1-B) inhibits cell proliferation of mesothelioma cancer cells. Treatment of xenografts of human-derived H226 cells or mouse-derived AB1 cells with si-m/hVDAC1-B inhibited tumor growth and caused metabolism reprogramming, as reflected in the decreased expression of metabolism-related proteins, including glycolytic and tricarboxylic acid (-)cycle enzymes and the ATP-synthesizing enzyme. In addition, tumors depleted of VDAC1 showed altered microenvironments and inflammation, both associated with cancer progression. Finally, tumor VDAC1 silencing also eliminated cancer stem cells and induced cell differentiation to normal-like cells. The results show that silencing VDAC1 expression leads to reprogrammed metabolism and to multiple effects from tumor growth inhibition to modulation of the tumor microenvironment and inflammation, inducing differentiation of malignant cells. Thus, silencing VDAC1 is a potential therapeutic approach to treating mesothelioma