Combinatorial treatment with Gefitinib and Bay11-7085 sensitizes primary Gefitinib-resistant OSCC cells by influencing the EGFR- NFκB signaling axis.

EGFR-targeted therapies are reported to yield modest effect in OSCC. Activation of NFκB signaling is considered as molecular driver of EGFR inhibitor resistance in various cancers. In this scenario, present study focused on the molecular crosstalk between EGFR and NFκB signaling pathways and its therapeutic importance in OSCC. The EGFR- NFκB p65 co-expressed human OSCC cell lines UPCI:SCC066, UPCI:SCC040 and UM-SCC083B were used for in vitro studies. Recombinant human EGF, siRNAs, Western blot and qRT-PCR were used to dissect the molecular crosstalk between EGFR-NFκB signaling pathways in OSCCs. The effect of NFκB p65 knockdown on cancer hallmarks was studied by respective functional assays and RNA-Seq analysis was performed to identify the differentially expressed genes upon NFκB p65 knockdown. Gefitinib and Bay 11-7085 combination treatment was done to study the chemotherapeutic potential of EGFR- NFκB axis. Significant positive correlation between EGFR and NFκB p65 expression was observed in Head and Neck TCGA data set. EGFR induction or knockdown respectively stimulate or impair the NFκB signaling in EGFR- NFκB p65 co-expressed OSCC cell lines. NFκB p65 knockdown causes apoptosis and suppresses the viability, colony formation, migration, invasion, and spheroid formation. Using RNA-seq analysis, we identified PIK3CD as the NFκB target gene, which is commonly involved in these functions. Gefitinib and Bay 11-7085 combination treatment was found to be useful in chemosensitizing the Gefitinib-resistant OSCC cells by capitulating the EGFR- NFκB signaling axis. Combination treatment using Gefitinib and Bay 11-7085 enhanced the apoptosis and reduced cell viability and colony formation in a synergistic way. Our data demonstrated that EGFR-NFκB signaling axis plays a key role in the pathogenesis of OSCCs. Therefore, simultaneous therapeutic intervention of these pathways may be a good alternative approach for the management of OSCCs.

Spiritual Care: Define and Redefine Self.

Spiritual care is deep rooted in the traditional ancient system of medicine. However, due to lack of high grade evidences, practitioners of modern system of medicine are hesitant to inculcate spirituality in their clinical practice. This paper is an attempt to basic understanding of spiritual care therapy, current evidences for it and the challenges for incorporation in the allopathic system of medicine.

Purification, crystallization and anticancer activity evaluation of the compound alternariol methyl ether from endophytic fungi Alternaria alternata.

AIMS: Medicinal plant-associated endophytic fungi are important sources of precious bioactive compounds, contributing more than 80% of the natural drugs for various ailments. The present study was aimed at evaluating the anticancer activity of the crystallized compound alternariol methyl ether (AME) against hepatocellular carcinoma (HCC) both in vitro and in vivo from an endophytic fungus residing in the medicinal plant Vitex negundo. METHODS AND RESULTS: The secondary metabolites from the endophytic fungus Alternaria alternata MGTMMP031 were isolated. Purification and characterization of the compound was performed and the potential compound was identified as AME. The crystal structure of AME was unambiguously confirmed by X-ray analysis. AME has been checked for its antibacterial and anticancer properties which showed its effectiveness against various bacteria and demonstrated marked anti-proliferative activity against the human HCC cells (HUH-7) both in vitro and in vivo. Mode of actions included cell cycle arrest, reducing the level of markers enzymes of liver cancer and preventing tumour growth. CONCLUSIONS: Alternariol methyl ether acts as a potential therapeutic target against HCC. The compound was isolated and the crystal structure was obtained for the first time from the endophytic fungus A. alternata MGTMMP031. In the present study, the crystallized structure of AME was obtained by slow evaporation technique. It can be concluded that AME acts as a potential therapeutic target against HCC. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi residing in the medicinal plants have strong biological significance and bioactive compounds from these fungi provide better therapeutic targets against diseases.

Structure, luminescence, mechanical and in vitro behavior of zirconia toughened alumina due to terbium substitutions.

The significance of Tb3+ inclusions at the zirconia toughened alumina (ZTA) structure was explored. The influence of Tb3+ content at the crystal structures of ZrO2 and Al2O3 and the resultant optical, mechanical, magnetic and cytotoxicity properties were deliberated. The critical role of Tb3+ to attain a structurally stable ZTA until 1500 °C is ensured. Depending on the Tb3+ content, either tetragonal zirconia (t-ZrO2) or cubic zirconia (c-ZrO2) structures were stabilized while the propensity of Tb3+ reaction with Al2O3 to yield TbAlO3 is transpired only after exceeding the occupancy limit in ZrO2. The green emission and paramagnetic features are imparted by the Tb3+ inclusions at the ZTA structure. Dense and pore free microstructures with a direct impact on the improved mechanical features of ZTA is empowered by the presence of Tb3+. Further, the results from MTT assay and live/dead cell staining ensured the negligence of Tb3+ contained ZTA systems to induce toxicity.

Phytosynthesis of silver nanoparticles using Mangifera indica flower extract as bioreductant and their broad-spectrum antibacterial activity.

The present study focused on the evaluation of antibacterial property of silver nanoparticles (AgNPs) synthesized using mango flower extract. The morphology of the synthesized AgNPs was observed under transmission electron microscopy and the particles have shown spherical shape in the range of 10-20 nm. X-ray powder diffraction analysis confirmed the crystalline nature of the AgNPs. The atomic percentage of the Ag element in the nanoparticles was about 7.58% which is greater than the other elements present in the sample. The AgNPs showed extensive lethal effect on both Gram-positive (Staphylococcus sp.) and Gram-negative (Klebsiella sp., Pantoea agglomerans, and Rahnella sp.) bacteria. The extensive lethal effect of AgNPs against clinically important pathogens demonstrated that the mango flower mediated AgNPs could be applied as potential antibacterial agent to control the bacterial population in the respective industries.

Structural and bio-mineralization features of alumina zirconia composite influenced by the combined Ca2+ and PO43- additions.

The structural and bioactivity features of alumina zirconia composite (AZC) due to Ca2+ and PO43- additions are demonstrated. An in situ synthetic approach, starting from the solution precursors is devised for the powder synthesis in which the assorted range of Ca2+ and PO43- additions were done to the equimolar concentrations of Al3+ and Zr4+ precursors. The results witnessed the unique crystallization of tetragonal zirconia (t-ZrO2) at 1100 °C while Ca2+, PO43- and Al2O3 remained in their amorphous state in the system. On further heat treatment, α-Al2O3 crystallized at 1200 °C, which enforced t- → m-ZrO2 transformation while Ca2+ and PO43- still retained their amorphous state. The immersion tests in simulated body fluid (SBF) solution validated the enhanced bio-mineralization activity of AZC due to Ca2+ and PO43- additions. The results from the indentation tests demonstrated good uniformity in the elastic modulus and hardness data of the investigated specimens. Further, in vitro cell culture tests ascertained the bioactivity of all the AZC compositions.

Hyperthermia effect and antibacterial efficacy of Fe3+ /Co2+ co-substitutions in ß-Ca3 (PO4 )2 for bone cancer and defect therapy.

The combined effect of cobalt and iron substitutions in ß-Ca3 (PO4 )2 as a potent material for application in hyperthermia and as a bone substitute is presented. Structural analysis reveals the preferential accommodation of Co2+ and Fe3+ at the Ca2+ (5) sites of ß-Ca3 (PO4 )2 until the limit of ∼10 mol % and, thereafter, prefer Ca2+ (4) lattice sites. Occupancy of both the Co2+ and Fe3+ ions induces a significant contraction of the ß-Ca3 (PO4 )2 unit cell. The Co2+ /Fe3+ co-substitutions in ß-Ca3 (PO4 )2 display magnetic characteristics that enhances hyperthermia effect. In addition, the presence of Co2+ in ß-Ca3 (PO4 )2 enunciates pronounced antibacterial efficacy against tested microorganisms. Nevertheless, the enhanced level of Co2+ in ß-Ca3 (PO4 )2 results to induce significant toxicity. The biocompatibility of the synthesized thermoseeds is verified from the hemolytic tests and cytotoxicity test performed on human sarcoma cell line MG-63. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1317-1328, 2018.

Clinical trials in allied medical fields: A cross-sectional analysis of World Health Organization International Clinical Trial Registry Platform.

BACKGROUND: Clinical trials are mandatory for evidence-based practice. Hardly, any data are available regarding the number of clinical trials and their methodological quality that are conducted in allied fields of medicine. OBJECTIVE: The present study was envisaged to assess methodological quality of trials in allied medical fields. MATERIALS AND METHODS: Registered clinical trials in World Health Organization International Clinical Trials Registry Platform (http://apps.who.int/trialsearch/AdvSearch.aspx) in the following fields were extracted: Acupuncture; Ayurveda; biofeedback; complementary and alternate medicine; herbal; homeopathy; massage; naturopathy; Reiki; Siddha; Unani; and yoga. The eligible studies were assessed for the following key details: Type of sponsors; health condition in which the trial has been conducted; recruitment status; study design; if randomization was present, method of randomization and allocation concealment; single or multi-centric; retrospective or prospective registration; and publication status in case of completed studies. RESULTS: A total of 276 clinical trials were registered majority of which have been proposed to be conducted in the field of oncology and psychiatry. Most of the clinical trials were done in single centers (87.75%), and almost all the clinical trials were investigator-initiated with pharmaceutical company sponsored studies contributing to a maximum extent of 24.5%. A large majority of the study designs were interventional where almost 85% of the studies were randomized controlled trials. However, an appropriate method of randomization was mentioned only in 27.4%, and the rate of allocation concealment was found to be just 5.5%. Only 1-2% of the completed studies were published, and the average rate of retrospective registration was found to be 23.6% in various fields. CONCLUSION: The number of clinical trials done in allied fields of medicine other than the allopathic system has lowered down, and furthermore focus is required regarding the methodological quality of these trials and more support from various organizations.

Deposition, structure, physical and invitro characteristics of Ag-doped ß-Ca3(PO4)2/chitosan hybrid composite coatings on Titanium metal.

Pure and five silver-doped (0-5Ag) ß-tricalcium phosphate [ß-TCP, ß-Ca3(PO4)2]/chitosan composite coatings were deposited on Titanium (Ti) substrates and their properties that are relevant for applications in hard tissue replacements were assessed. Silver, ß-TCP and chitosan were combined to profit from their salient and complementary antibacterial and biocompatible features.The ß-Ca3(PO4)2 powders were synthesized by co-precipitation. The characterization results confirmed the Ag(+) occupancy at the crystal lattice of ß-Ca3(PO4)2. The Ag-dopedß-Ca3(PO4)2/chitosan composite coatings deposited by electrophoresis showed good antibacterial activity and exhibited negative cytotoxic effects towards the human osteosarcoma cell line MG-63. The morphology of the coatings was observed by SEM and their efficiency against corrosion of metallic substrates was determined through potentiodynamic polarization tests.

Transesterification of edible, non-edible and used cooking oils for biodiesel production using calcined layered double hydroxides as reusable base catalysts.

Fatty acid methyl esters (FAME) were produced from edible, non-edible and used cooking oils with different fatty acid contents by transesterification with methanol using calcined layered double hydroxides (LDHs) as solid base catalysts. Among the catalysts, calcined CaAl2-LDH (hydrocalumite) showed the highest activity with >90% yield of FAME using low methanol:oil molar ratio (<6:1) at 65 °C in 5 h. The activity of the catalyst was attributed to its high basicity as supported by Hammett studies and CO(2)-TPD measurements. The catalyst was successfully reused in up to four cycles. Some of the properties such as density, viscosity, neutralization number and glycerol content of the obtained biodiesel matched well with the standard DIN values. It is concluded that a scalable heterogeneously catalyzed process for production of biodiesel in high yields from a wide variety of triglyceride oils including used oils is possible using optimized conditions.

Antifeedant activity of Momordica dioica fruit pulp extracts on Spodoptera litura.

The hexane extract and ethyl acetate soluble fraction of methanolic extract of the fruit pulp of Momordica dioica exhibited moderate and concentration dependent antifeedant activity against Spodoptera litura.

Insect antifeedant and growth regulating activities of salannobutyrolactone and desacetylsalannobutyrolactone.

Salannobutyrolactone and its deacetylderivative were tested for insect antifeedant and growth regulatory activities against the tobacco cutworm, Spodoptera litura. Salannobutyrolactone was the most effective antifeedant. Desacetylsalannobutyrolactone increased larval duration and larval mortality.

ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase.

We have identified a novel basic leucine zipper (bZIP) protein, designated ATF-7, that physically interacts with the PRL-1 protein-tyrosine phosphatase (PTPase). PRL-1 is a predominantly nuclear, farnesylated PTPase that has been linked to the control of cellular growth and differentiation. This interaction was initially found using the yeast two-hybrid system. ATF-7 is most closely related to members of the ATF/CREB family of bZIP proteins, with highest homology to ATF-4. ATF-7 homodimers can bind specifically to CRE elements. ATF-7 is expressed in a number of different tissues and is expressed in association with differentiation in the Caco-2 cell model of intestinal differentiation. We have confirmed the PRL-1.ATF-7 interaction and mapped the regions of ATF-7 and PRL-1 important for interaction to ATF-7's bZIP region and PRL-1's phosphatase domain. Finally, we have determined that PRL-1 is able to dephosphorylate ATF-7 in vitro. Further insight into ATF-7's precise cellular roles, transcriptional function, and downstream targets are likely be of importance in understanding the mechanisms underlying the complex processes of maintenance, differentiation, and turnover of epithelial tissues.

Infant feeding practices of Anglo American and Asian Indian American mothers.

OBJECTIVE: To compare infant feeding practices of Anglo-American (AA) (n = 25) and Asian-Indian American (AIA) mothers (n = 25) residing in the southeastern United States. METHODS: Feeding practices (breast-feeding, formula-feeding, introduction of solid foods) were assessed at infant ages one, three, six, nine and twelve months for a total of 250 interviews conducted in the home. Mothers' sources of information about infant feeding practices and dietary intakes of their infants were collected (24-hour recalls). RESULTS: Compared to their AIA counterparts, AA mothers breast-fed for significantly longer durations and introduced formula and solid foods into the infants' diet at a later age (p<0.05). Throughout the first year, AA mothers relied primarily upon health professionals for infant feeding information compared to AIA mothers, who sought information primarily from the family network during the first six months and relied more on health professionals during the second six months of the infant's life. Throughout the first twelve months, infants of both groups exceeded 100% of the RDA for energy, protein, calcium, iron, vitamin A, and vitamin C. CONCLUSION: Health professionals, including nutrition educators, should educate AIA mothers about and encourage AA mothers to follow current feeding recommendations and guidelines about breast-feeding, formula-feeding and introducing solid foods.

Expression of galactoside-specific endogenous lectins and their ligands in human oral squamous cell carcinoma.

Human endogenous lectins have a wide spectrum of biological functions. The present study analyses the expression of beta-galactoside specific and N-acetyl-D-galactosamine specific endogenous lectins in oral squamous cell carcinomas using biotinylated neoglycoproteins. The expression pattern of beta-galactosyl-containing glycoconjugates or ligands of beta-galactoside specific lectins in these tissues was also studied using an endogenous biotinylated lectin, the human 14-kDa lectin. For comparison a galactoside specific plant lectin from mistletoe, Viscum album was also employed. The results demonstrate that oral squamous cell carcinomas mainly express accessible binding sites for lactosylated neoglycoprotein (90%) while few carcinomas expressed mild amount of N-acetyl-D-galactosamine specific binding sites (40%). There was no difference in the binding patterns of these probes between well and less differentiated carcinomas. Expression of these neoglycoprotein binding sites were mostly concentrated in immature basaloid cells, indicating a possible association with cell proliferation. The binding pattern of D-galactosyl specific lectins (human 14-kDa and mistletoe lectins) showed conspicuous differences. This feature emphasizes the caution that needs to be exercised in interpreting the biological significance of results attained using plant lectins on human tissue.