Autophagy related genes mediated mitophagy in yeast, mammals and higher plants.

Autophagy is classified into macro-autophagy and micro-autophagy. Two major types of autophagy in the complex eukaryotic organism are microautophagy and macroautophagy. During microautophagy, cytoplasmic components that need to be degraded are taken up by lysosomes in animals and by vacuole in yeast and plants via the invagination of tonoplast. While macroautophagy is initiated after the formation of a cup-shaped membrane structure, a phagophore develops at cargo that grows in size and is sealed by double-membrane vesicles to form autophagosome; a generalized mechanism for degradation of the organelle. Autophagic removal of damaged mitochondria is a conserved cellular process to maintain a healthy mitochondrion called Mitophagy. In plants and animals, mitophagy has crucial roles in stress responses, senescence, development, and programmed cell death. Mitophagy appears in mammals, fungi, and plants but many genes that controlled mitophagy are absent from plants. Numerous studies have been conducted by using ATG mutants for the identification of functional roles of Autophagy Related Genes (ATG) required during the autophagy process at various steps like; auto phagosome formation, ATG protein recruitment, etc. The role of more than 25 ATG genes in mitophagy has been discussed in this review paper. The main parameters, reviewed and summarized in this review paper, are the name of species, common name, function, domain, deletion, induction, and localization of these autophagy-related genes in the cell. This review will facilitate the students, researchers, and academics for their further research insights.

Promising biomarkers and therapeutic targets for the management of Parkinson's disease: recent advancements and contemporary research.

Parkinson's disease (PD) is one of the progressive neurological diseases which affect around 10 million population worldwide. The clinical manifestation of motor symptoms in PD patients appears later when most dopaminergic neurons have degenerated. Thus, for better management of PD, the development of accurate biomarkers for the early prognosis of PD is imperative. The present work will discuss the potential biomarkers from various attributes covering biochemical, microRNA, and neuroimaging aspects (α-synuclein, DJ-1, UCH-L1, ß-glucocerebrosidase, BDNF, etc.) for diagnosis, recent development in PD management, and major limitations with current and conventional anti-Parkinson therapy. This manuscript summarizes potential biomarkers and therapeutic targets, based on available preclinical and clinical evidence, for better management of PD.

Flavonoids as promising anticancer therapeutics: Contemporary research, nanoantioxidant potential, and future scope.

Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available molecules. It is widely distributed in various food products such as fruits and vegetables and beverages such as green tea, wine, and coca-based products. Many studies have reported the anticancer potential of flavonoids against different types of cancers, including solid tumors. The chemopreventive effect of flavonoids is attributed to various mechanisms, including modulation of autophagy, induction of cell cycle arrest, apoptosis, and antioxidant defense. Despite of significant anticancer activity of flavonoids, their clinical translation is limited due to their poor biopharmaceutical attributes (such as low aqueous solubility, limited permeability across the biological membranes (intestinal and blood-brain barrier), and stability issue in biological systems). A nanoparticulate system is an approach that is widely utilized to improve the biopharmaceutical performance and therapeutic efficacy of phytopharmaceuticals. The present review discusses the significant anticancer potential of promising flavonoids in different cancers and the utilization of nanoparticulate systems to improve their nanoantioxidant activity further to enhance the anticancer activity of loaded promising flavonoids. Although, various plant-derived secondary metabolites including flavonoids have been recommended for treating cancer, further vigilant research is warranted to prove their translational values.

Effectiveness of Nonfunctionalized Graphene Oxide Nanolayers as Nanomedicine against Colon, Cervical, and Breast Cancer Cells.

Recent studies in nanomedicine have intensively explored the prospective applications of surface-tailored graphene oxide (GO) as anticancer entity. However, the efficacy of nonfunctionalized graphene oxide nanolayers (GRO-NLs) as an anticancer agent is less explored. In this study, we report the synthesis of GRO-NLs and their in vitro anticancer potential in breast (MCF-7), colon (HT-29), and cervical (HeLa) cancer cells. GRO-NLs-treated HT-29, HeLa, and MCF-7 cells showed cytotoxicity in the MTT and NRU assays via defects in mitochondrial functions and lysosomal activity. HT-29, HeLa, and MCF-7 cells treated with GRO-NLs exhibited substantial elevations in ROS, disturbances of the mitochondrial membrane potential, an influx of Ca2+, and apoptosis. The qPCR quantification showed the upregulation of caspase 3, caspase 9, bax, and SOD1 genes in GRO-NLs-treated cells. Western blotting showed the depletion of P21, P53, and CDC25C proteins in the above cancer cell lines after GRO-NLs treatment, indicating its function as a mutagen to induce mutation in the P53 gene, thereby affecting P53 protein and downstream effectors P21 and CDC25C. In addition, there may be a mechanism other than P53 mutation that controls P53 dysfunction. We conclude that nonfunctionalized GRO-NLs exhibit prospective biomedical application as a putative anticancer entity against colon, cervical, and breast cancers.

Enhanced In Vivo Wound Healing Efficacy of a Novel Piperine-Containing Bioactive Hydrogel in Excision Wound Rat Model.

These days an extensive amount of the attention of researchers is focused towards exploring bioactive compounds of natural or herbal origin for therapeutic intervention in different ailments of significant importance. One such novel bioactive compound that has a variety of biological properties, including anti-inflammatory and antioxidant activities, is piperine. However, until today, piperine has not been explored for its potential to improve inflammation and enhance healing in acute and chronic wounds. Therefore, the present study aimed to investigate the wound healing potential of piperine hydrogel formulation after topical application. Hydrogels fit the need for a depot system at the wound bed, where they ensure a consistent supply of therapeutic agents enclosed in their cross-linked network matrices. In the present study, piperine-containing carbopol 934 hydrogels mixed with Aloe vera gels of different gel strengths were prepared and characterized for rheological behavior, spreadability, extrudability, and percent (%) content uniformity. Furthermore, the wound healing potential of the developed formulation system was explored utilizing the excision wound healing model. The results of an in vivo study and histopathological examination revealed early and intrinsic healing of wounds with the piperine-containing bioactive hydrogel system compared to the bioactive hydrogel system without piperine. Therefore, the study's findings establish that the piperine-containing bioactive hydrogel system is a promising therapeutic approach for wound healing application that should be diligently considered for clinical transferability.

Marine Natural Compound (Neviotin A) Displays Anticancer Efficacy by Triggering Transcriptomic Alterations and Cell Death in MCF-7 Cells.

We investigated the anticancer mechanism of a chloroform extract of marine sponge (Haliclona fascigera) (sample C) in human breast adenocarcinoma (MCF-7) cells. Viability analysis using MTT and neutral red uptake (NRU) assays showed that sample C exposure decreased the proliferation of cells. Flow cytometric data exhibited reactive oxygen species (ROS), nitric oxide (NO), dysfunction of mitochondrial potential, and apoptosis in sample C-treated MCF-7 cells. A qPCR array of sample C-treated MCF-7 cells showed crosstalk between different pathways of apoptosis, especially BIRC5, BCL2L2, and TNFRSF1A genes. Immunofluorescence analysis affirmed the localization of p53, bax, bcl2, MAPKPK2, PARP-1, and caspase-3 proteins in exposed cells. Bioassay-guided fractionation of sample C revealed Neviotin A as the most active compound triggering maximum cell death in MCF-7, indicating its pharmacological potency for the development of a drug for the treatment of human breast cancer.

Trigonella foenum-graecum (fenugreek) differentially regulates antioxidant potential, photosynthetic, and metabolic activities under arsenic stress.

Arsenic (As) contamination is continuously increasing in the groundwaters and soils around the world causing toxicity in the plants with a detrimental effect on physiology, growth, and yield. In a hydroponic system, thirty-day-old plants of Trigonella foenum-graecum were subjected to 0, 50, or 100 µM NaHAsO40.7 H2O for 10 days. The magnitude of oxidative stress increased, whereas growth indices and photosynthetic parameters decreased in a dose-dependent manner. The efficiency of photosystem II in terms of Hill reaction activity (HRA) or chlorophyll-a was adversely affected by As stress. The antioxidant potential of plants regarding ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays was enhanced, indicating the augmented resistance mechanism in plants to counter As stress. The metabolite analysis of leaf extracts revealed many As responsive metabolites including amino acids, organic acids, sugars/polyols, and others. Phenylalanine and citrulline were highly accumulated at 50 or 100 µM As, salicylic acid accumulated more at 50 µM of As while ascorbic acid notably increased at 100 µM of As. At 50 or 100 µM As, the glucose and fructose contents increased while the sucrose content decreased. At both As doses, tagatose and glucitol contents were 13 times higher than controls. Varied accumulation of metabolites could be associated with the different As doses that represent the range of tolerance in T. foenum-graecum towards As toxicity. Pathway analysis of metabolites revealed that amino acid and carbohydrate metabolism and the citrate cycle play important roles under As stress. This study helps in a better metabolomic understanding of the dose-dependent toxicity and response of As in T. foenum-graecum.

Green Synthesis of Titanium Dioxide Nanoparticles Using Ocimum sanctum Leaf Extract: In Vitro Characterization and Its Healing Efficacy in Diabetic Wounds.

Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an Ocimum sanctum leaf extract-mediated green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO2 NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO2 nanoparticles. XRD analysis indicated the crystallinity of TiO2 NPs in anatase form. Microscopic investigation revealed that TiO2 NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO2 NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO2 NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO2 NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO2 NPs containing CS gel in diabetic rats.

Strain tuning of the Curie temperature and valley polarization in two dimensional ferromagnetic WSe2/CrSnSe3heterostructure.

Magnetic proximity effect can be used to tailor the magnetic ground state and valley polarization in the monolayer of transition metal dichalcogenides. Thus, we explore the effect of biaxial tensile and compressive strain on valley polarization in the WSe2/CrSnSe3heterostructures with different stacking orders systematically. The indirect band gaps in the two most stable stackings; hollow (0.27 eV) and top (0.33 eV) were further enhanced to 0.35 eV under tensile strain while suppressed to almost 0.13 eV under compressive strain. The heterostructures had a FM ground state with a total magnetic moment per unit cell of 6µBin pristine as well as strained structures. In hollow stacking and compressively strained structures, we obtained a perpendicular magnetocrystalline anisotropy, while the top stacking and tensile strain structures had small in-plane anisotropy. An enhancement was found in Curie temperature from 73 K in pristine to 128 K in a 6% tensile strained structure. The valley splittings found in pristine hollow (4 meV) and top (9 meV) stacked heterostructures were further enhanced to 29 meV and 22 meV at 5% compressive strain respectively. This enhancement was attributed to the increased spatial dependence of the charge density along K+and K-directions of the Brillouin zone, which give rise to the different local dipolar fields at these valleys. Our results suggest that strain could be an effective way to control or tune the valley splitting in WSe2/CrSnSe3heterostructures.

Development and Evaluation of Repurposed Etoricoxib Loaded Nanoemulsion for Improving Anticancer Activities against Lung Cancer Cells.

In the present work, novel modality for lung cancer intervention has been explored. Primary literature has established the potential role of cyclooxygenase-2 (COX-2) inhibitor in regression of multiple forms of carcinomas. To overcome its poor water solubility and boost anticancer activity, etoricoxib (ETO) was chosen as a therapeutic candidate for repurposing and formulated into a nanoemulsion (NE). The prepared ETO loaded NE was characterized for the surface charge, droplet size, surface morphology, and in vitro release. The optimized ETO loaded NE was then investigated for its anticancer potential employing A549 lung cancer cell line via cytotoxicity, apoptotic activity, mitochondrial membrane potential activity, cell migration assay, cell cycle analysis, Caspase-3, 9, and p53 activity by ELISA and molecular biomarker analysis through RT-PCR test. The developed ETO-NE formulation showed adequate homogeneity in the droplet size distribution with polydispersity index (PDI) of (0.2 ± 0.03) and had the lowest possible droplet size (124 ± 2.91 nm) and optimal negative surface charge (-8.19 ± 1.51 mV) indicative of colloidal stability. The MTT assay results demonstrated that ETO-NE exhibited substantial anticancer activity compared to the free drug. The ETO-NE showed a substantially potent cytotoxic effect against lung cancer cells, as was evident from the commencement of apoptosis/necrotic cell death and S-phase cell cycle arrests in A549 cells. The study on these molecules through RT-PCR confirmed that ETO-NE is significantly efficacious in mitigating the abundance of IL-B, IL-6, TNF, COX-2, and NF-kB as compared to the free ETO and control group. The current study demonstrates that ETO-NE represents a feasible approach that could provide clinical benefits for lung cancer patients in the future.

Thymoquinone Loaded Topical Nanoemulgel for Wound Healing: Formulation Design and In-Vivo Evaluation.

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to <100 nm through ultrasonication. The influence of formulation composition, and the ultrasonication process conditions, were investigated on the mean globule size and polydispersity index of the generated nanoemulsion. Irrespective of surfactant/co-surfactant ratio and % concentration of surfactant/co-surfactant mixture, the ultrasonication time had a significant (p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.

Cytotoxicity and cell death induced by engineered nanostructures (quantum dots and nanoparticles) in human cell lines.

In recent years, the industrial use of ZnO quantum dots (QDs) and nanoparticles (NPs) has risen and there is a high chance of these nanoparticles affecting human health. In this study, different sizes of ZnO-NPs (6-100 nm) were prepared and characterized. The generation of reactive oxygen species (ROS) and its involvement in apoptosis when HepG2 cells were exposed to QDs (6 nm) and NPs of different sizes (15-20, 50, and 100 nm) was also investigated. At a concentration of 25-200 µg/mL, NPs induced dose-dependent cytotoxicity in HepG2 cells. The engineered NPs increased oxidative stress in a dose- and size-dependent manner, as seen by an increase in ROS production, lipid peroxidation, and glutathione reduction. Furthermore, cell-cycle analysis of HepG2 cells treated with different sizes of NPs showed an increase in the apoptotic peak after a 24-h exposure period. Quantitative real-time PCR data showed that the mRNA levels of apoptotic marker genes such as p53, bax, and caspase-3 were upregulated, whereas bcl-2, an anti-apoptotic gene, was downregulated; therefore, apoptosis was mediated through the p53, bax, caspase-3, and bcl-2 pathways, suggesting a possible mechanism by which QDs and NPs of ZnO mediate their toxicity.Graphic abstract.

One-Pot Hydrothermal Synthesis of Ternary 1T-MoS2 /Hexa-WO3 /Graphene Composites for High-Performance Supercapacitors.

A new ternary composite of 1T-molybdenum disulfide, hexagonal tungsten trioxide, and reduced graphene oxide (M-W-rGO) is synthesized by using a one-pot hydrothermal process. The synergetic effect of 1T-MoS2 and hexa-WO3 nanoflowers improves the electrochemical performance for supercapacitors by inducing additional active sites and hexagonal tunnels, respectively, which lead to high storage capacity and easy transfer of electrolyte ions. The ternary M-W-rGO composite has a high specific capacitance of 836 F g-1 at 1 A g-1 , which is nearly twice that of binary composites of M-rGO and W-rGO with high capacitance retention of 86.35 % after 3000 cycles at a high current density of 5 A g-1 . This study provides a new ternary composite that can be used as an electrode material for high-performance supercapacitors.

Survival of probiotic bacteria in the presence of food grade nanoparticles from chocolates: an in vitro and in vivo study.

The use of probiotics to treat gastrointestinal diseases such as diarrhea especially in children is becoming increasingly popular. Besides, the use of nanomaterials in food products is increasing rapidly especially in candies and chocolates. How these nanomaterials influence probiotic bacteria and their activity remains unexplored. Therefore, nanomaterials from commercial chocolate were purified and characterized by using SEM-EDS and XRD. The tested chocolate contained nano-TiO2 with an average size of ~ 40 nm. The influence of the extracted TiO2 on a commercial probiotic formulation usually used to treat diarrhea in children was studied. The probiotic formulation contained Bacillus coagulans, Enterococcus faecalis, and Enterococcus faecium as evident from 16S rRNA gene sequences and polyphasic characterization. Isolated bacteria exhibited known probiotic activities like biofilm formation, acid production, growth at 6% salt, and antibiotic resistance. TiO2 from chocolates inhibited the growth and activity of the probiotic formulation over a concentration range of 125-500µg/ml in vitro. Based on results, it is estimated that 20 g of such chocolate contains enough TiO2 to disturb the gut microbial community of children aged 2-8 years with a stomach capacity of ~ 0.5-0.9 l. The in vivo study on white albino mice shows the same response but with a higher dose. The results obtained by plate counts, MTT assay, live/dead staining, and qPCR suggest that TiO2 from chocolates inhibits the growth and viability of probiotic bacteria in mice gut even at a concentration of 50-100 µg/day/mice. Therefore, TiO2 in chocolate discourages survival of probiotic bacteria in the human gut.

Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome.

Olive (Olea europaea Linn., Fam. Oleaceae) is commonly known as Zaytoon in Mediterranean region. Its fruits and oil are essential components of Mediterranean diets. Olive tree is a prevalent plant species and one of the important cultivated crops of Mediterranean region. Oleuropein is a phenolic constituents of olive, which, along with its related compounds, has been indicated to be majorly responsible for its beneficial effects. Oleuropein is a secoiridoid type of phenolic compound and consists of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule. It is also reported to be the chemotaxonomic marker of olive. The oleuropein is reported to possess a number of biological activities including action against dyslipidemia, antiobesity, antidiabetic, antioxidant, antiatherogenic, antihypertensive, antiinflammatory, and hepatoprotective actions. The scientific evidence supports the role of oleuropein as a potential agent against metabolic syndrome. The present review discusses chemistry of oleuropein along with potential role of oleuropein with reference to pathophysiology of metabolic syndrome.

Proteomic and ecophysiological responses of soybean (Glycine max L.) root nodules to Pb and hg stress.

BACKGROUND: Lead (Pb) and mercury (Hg) are persistent hazardous metals in industrially polluted soils which can be toxic in low quantities. Metal toxicity can cause changes at cellular and molecular level which should be studied for better understanding of tolerance mechanism in plants. Soybean (Glycine max L.) is an important oilseed crop of the world including India. Indian soils growing soybean are often contaminated by Pb and Hg. The aim of this study was to explore how soybean root nodule responds to Pb and Hg through proteomic and ecophysiological alterations in order to enhance tolerance to metal stress. RESULTS: Soybean plants were exposed to Pb (30 ppm PbCl2) and Hg (0.5 ppm HgCl2) to study histological, histochemical, biochemical and molecular response of N2-fixing symbiotic nodules. Both Pb and Hg treatment increased the level of oxidative stress in leaves and nodules. Chlorosis in leaves and morphological/anatomical changes in nodules were observed. Activities of ascorbate peroxidase, glutathione reductase and catalase were also modulated. Significant changes were observed in abundance of 76 proteins by Pb and Hg. Pb and Hg influenced abundance of 33 proteins (17 up and 16 down) and 43 proteins (33 up and 10 down), respectively. MS/MS ion search identified 55 proteins which were functionally associated with numerous cellular functions. Six crucial proteins namely catalase (CAT), allene oxide synthase (AOS), glutathione S-transferase (GST), calcineurin B like (CBL), calmodulin like (CML) and rapid alkalinisation factor (RAF) were selected for transcript abundance estimation. The qRT-PCR based real time expression exhibited a positive correlation with proteomics expression except for GST and RAF. CONCLUSION: Soybean root nodule responds to metal stress by increased abundance of defence, development and repair related proteins. An efficient proteomic modulation might lead to metal-induced stress tolerance in N2-fixing nodules. Although concentrations of Pb and Hg used in the study cannot be considered equimolar, yet Hg seems to induce more changes in nodule proteomic profile, and higher damage to both bacteroides and root anatomy.

Application of advanced oxidation processes and toxicity assessment of transformation products.

Advanced Oxidation Processes (AOPs) are the techniques employed for oxidation of various organic contaminants in polluted water with the objective of making it suitable for human consumption like household and drinking purpose. AOPs use potent chemical oxidants to bring down the contaminant level in the water. In addition to this function, these processes are also capable to kills microbes (as disinfectant) and remove odor as well as improve taste of the drinking water. The non-photochemical AOPs methods include generation of hydroxyl radical in absence of light either by ozonation or through Fenton reaction. The photochemical AOPs methods use UV light along with H2O2, O3 and/or Fe+2 to generate reactive hydroxyl radical. Non-photochemical method is the commonly used whereas, photochemical method is used when conventional O3 and H2O2 cannot completely oxidize organic pollutants. However, the choice of AOPs methods is depended upon the type of contaminant to be removed. AOPs cause loss of biological activity of the pollutant present in drinking water without generation of any toxicity. Conventional ozonation and AOPs can inactivate estrogenic compounds, antiviral compounds, antibiotics, and herbicides. However, the study of different AOPs methods for the treatment of drinking water has shown that oxidation of parent compound can also lead to the generation of a degradation/transformation product having biological activity/chemical toxicity similar to or different from the parent compound. Furthermore, an increased toxicity can also occur in AOPs treated drinking water. This review discusses various methods of AOPs, their merits, its application in drinking water treatment, the related issue of the evolution of toxicity in AOPs treated drinking water, biocatalyst, and analytical methods for identification of pollutants /transformed products and provides future directions to address such an issue.

Nickel Oxide Nanoparticles Induced Transcriptomic Alterations in HEPG2 Cells.

Nickel oxide nanoparticles (NiO-NPs) are increasingly used and concerns have been raised on its toxicity. Although a few studies have reported the toxicity of NiO-NPs, a comprehensive understanding of NiO-NPs toxicity in human cells is still lagging. In this study, we integrated transcriptomic approach and genotoxic evidence to depict the mechanism of NiO-NPs toxicity in human hepatocellular carcinoma (HepG2) cells. DNA damage analysis was done using comet assay, which showed 26-fold greater tail moment in HepG2 cells at the highest concentration of 100 µg/ml. Flow cytometric analysis showed concentration dependent enhancement in intracellular reactive oxygen species (ROS). Real-time PCR analysis of apoptotic (p53, bax, bcl2) and oxidative stress (SOD1) genes showed transcriptional upregulation. Transcriptome analysis using qPCR array showed over expression of mRNA transcripts related to six different cellular pathways. Our data unequivocally suggests that NiO-NPs induces oxidative stress, DNA damage, apoptosis and transcriptome alterations in HepG2 cells.

Odyssey of an accidently ingested sewing needle from mouth to mesentery of small bowel in a young female - Case Report.

Foreign body (FB) ingestion is one of the most common complaint in the emergency room and, extra-intestinal migration of penetrating sharp FBs is one of the most overlooked aspect of medical research. We report a case of accidental ingestion of a sewing needle which was recovered from the mesentery. The 28-year-old female presented to our hospital with abdominal pain and one-month's history of needle ingestion. Initially laparoscopy was performed, which was inconclusive. Afterward, through laparotomy, the needle was successfully removed from the mesentery of small bowel.

Zinc oxide and titanium dioxide nanoparticles induce oxidative stress, inhibit growth, and attenuate biofilm formation activity of Streptococcus mitis.

Streptococcus mitis from the oral cavity causes endocarditis and other systemic infections. Rising resistance against traditional antibiotics amongst oral bacteria further aggravates the problem. Therefore, antimicrobial and antibiofilm activities of zinc oxide and titanium dioxide nanoparticles (NPs) synthesized and characterized during this study against S. mitis ATCC 6249 and Ora-20 were evaluated in search of alternative antimicrobial agents. ZnO and TiO2-NPs exhibited an average size of 35 and 13 nm, respectively. The IC50 values of ZnO and TiO2-NPs against S. mitis ATCC 6249 were 37 and 77 µg ml(-1), respectively, while the IC50 values against S. mitis Ora-20 isolate were 31 and 53 µg ml(-1), respectively. Live and dead staining, biofilm formation on the surface of polystyrene plates, and extracellular polysaccharide production show the same pattern. Exposure to these nanoparticles also shows an increase (26-83 %) in super oxide dismutase (SOD) activity. Three genes, namely bapA1, sodA, and gtfB like genes from these bacteria were identified and sequenced for quantitative real-time PCR analysis. An increase in sodA gene (1.4- to 2.4-folds) levels and a decrease in gtfB gene (0.5- to 0.9-folds) levels in both bacteria following exposure to ZnO and TiO2-NPs were observed. Results presented in this study verify that ZnO-NPs and TiO2-NPs can control the growth and biofilm formation activities of these strains at very low concentration and hence can be used as alternative antimicrobial agents for oral hygiene.