Mutational and expressional association of the PIK3CA gene with the risk of breast cancer in the Pakistani population.

PI3K pathway is a very important pathway that is reported to be involved in breast cancer. Mutation of PI3K and p110 alpha-catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA) is of high predictive and prognostic values in breast cancer. The purpose of the current study was to screen the hotspot mutations of the PIK3CA gene i.e. rs2677760, rs3806685, rs121913273 & rs121913279 along with expressional analysis of PI3K and PIK3CA genes in breast cancer female patients. For mutational analysis, TaqMan assay & Sanger sequencing were performed while for expressional analysis real-time PCR was carried out. Mutant allele C of rs2677760 was observed to be high in postmenopausal patients. The frequency of mutant allele G of rs3806685 was significantly high in breast cancer patients. All diseased and control samples were of wild type for the hotspot rs121913273 and rs121913279 with allele G for rs121913273 and A for rs121913279. Expression of the PI3K was high in breast cancer tissue samples as compared to the adjacent controls. While the expression of the thePIK3CA gene was significantly high in premenopausal breast cancer patients. It was concluded that the mutant allele C of rs2677760 might have some sort of association with the menopausal status and it could be used as a diagnostic marker in post-menopausal women if studied further. Mutant allele G of rs3806685 was also found to be associated with breast cancer. While multiallelic rs121913273 and rs121913279 showed a different trend for the studied population. For expressional analysis, PI3K showed over-expression in the cases while PIK3CA gene expression was observed to be significantly associated with pre-menopausal status.

Identification of transcriptional level variations in microRNA-221 and microRNA-222 as alternate players in the thyroid cancer tumor microenvironment.

Thyroid cancer (TC) is caused by genetic factors and or their cross talk with lifestyle and environment. An important role of miRNA involvement has been identified in different human diseases alongside the cancer. The growing cloud of miRNA discoveries narrates miRNA-221 and miRNA-222 as key elements of ready arsenal in the cancer micro-niches. The aim of present study was to identify the variations of miRNA-221 and miRNA-222 expression in TC tissues and their likely association with TC. miRNA-221 and miRNA-222 were investigated for their expressional alterations in TC tissue samples and healthy thyroid tissue. Expression of miRNA-221 and -222 was analyzed through real time PCR. The relative gene expression of both the miRNA was quantified and statistically evaluated. miRNA-221 and miRNA-222 were found to be highly over expressed when compared with samples of multinodular goiter (MNG) and normal controls. Interestingly, it was also noted that miRNA-221 and miRNA-222 expression is working in a cluster in thyroid cancer patients. So, it can be concluded that the expressional alterations of miRNA-221 and -222 are playing their potential role in the development of thyroid cancer.

Linkage disequilibrium block single-nucleotide polymorphisms in FTO alpha ketoglutarate dependent dioxygenase gene inference with breast cancer and Type II diabetes in Pakistani female population.

Breast Cancer and Diabetes Mellitus are top ranked non-communicable life threatening diseases concerned in South Asia. The growing scientific clues witness the involvement of genetic variations which readily serve as risk factors for the disease onset. Comprehending the association of genetic predictors and risk factors in the conserved genome regions can help reveal underlying disease genetics and identify the sustained druggable targets. The present study aims to identify discrete inference of FTO alpha-ketoglutarate dependent dioxygenase gene linkage disequilibrium block SNPs rs9940128 and rs9939609 as prognostic genetic elements in defining the disease course either as BrC or NIDDM in Pakistani population. Clinically abreast female Breast Cancer and Type II (Non-Insulin Dependent) Diabetes Mellitus cases with the healthy controls participated in the study. The genomic study was established on the DNA of cases and controls through Tetra primers ARMS PCR and PCR-RFLP; data were analyzed statistically to reach comprehensive scientific annotation. Breast Cancer incidence was high in post menopause women. Fretful cholesterol, triglycerides, hypertension, sugar profiles and high incidence in females was evident in Type II (Non-Insulin Dependent) Diabetes Mellitus. BMI and family history were meager factor for either of the diseases. FTO gene alpha-ketoglutarate dependent dioxygenase linkage disequilibrium block Single-Nucleotide Polymorphism rs9939609 and rs9940128 threating inference was significant in the cancer and diabetes subjects correspondingly. The conclusion indicates serious clinical derailments in breast cancer and Type II (Non-Insulin Dependent) Diabetes Mellitus auxiliary to disease complication in genetically risk bearing FTO alpha-ketoglutarate dependent dioxygenase gene haplotype/linkage disequilibrium block SNPs prevailing in the affected Pakistani population. These clinical and genetic indicators could decisively be adopted in health care practice to intervene the sky rising disease incidence.

TRAIL mediated apoptosis ruling and anticancer trigger by fine-tuned nano spheres of Fagonia cretica methanolic extracts as novel cancer regime.

Fagonia cretica L. is a tropical plant of family Zygophyllaceae with wide range of medicinally important secondary metabolites. The low cellular uptake of the polar compounds in the extract of the plant limits its biological application. In present study efficacy of F. cretica modified bioactive nano-formulations for in vitro modulation of TRAIL mediated extrinsic apoptotic pathway as cancer therapy was investigated. F. cretica methanolic extracts were formulated at nano-scale for green synthesis of silver nanoparticles, albumin conjugation and liposomes encapsulation to enhance targeted bioactivity against cancer. Physical characterization of the synthesized nanoparticles was done by SEM, EDX and Zeta potential analyzer. In vitro cell viability assay MTT was done for MCF-7, Hep-2, HUH-7 and HCEC cell lines. Relative expression variation of the apoptotic pathway-associated genes was done by qRT-PCR. SEM revealed spherical shape of 56.62 ± 8.04, 143 ± 11.54 and 83.36 ± 38.73 nm size and zeta potential - 18.6, - 15.5 and - 18.3 mV for liposomes, silver and albumin nanoparticles. Silver nanoparticles showed highest anticancer activity in vitro than albumin and liposomes nanoparticles with IC50 0.101 ± 0.004, 0.177 ± 0.03 and 0.434 ± 0.022 mg/mL in MCF-7, Hep-2 and HUH-7 respectively. F. cretica albumin and silver nanoparticles upregulated the in vitro TRAIL, DR4, DR5 and FADD gene expression at statistically significant levels in Hep-2 cell lines. Nano-formulations of F. cretica proved therapeutically important biomolecules in vitro. The hypothesized modulation of extrinsic apoptosis pathway genes through the plant nanoparticles proved novel medicinal options for effective treatment of cancer and enhancing the bioavailability of the active plant metabolites.

Analysis of Rare Alleles of miRNA-146a (rs2910164) and miRNA-34b/c (rs4938723) as a Prognostic Marker in Thyroid Cancer in Pakistani Population.

Background: Rationale: The miRNAs are short non-coding functional RNAs that are involved in the regulation of transcriptomes. It was found that human miRNA-146a and miRNA34b/c are important microRNAs and are functioning either as onco-miRNAs, or acting as tumor suppressors, in different conditions. To date, no study has been performed to evaluate the alterations of miRNA-146ars2910164 and miRNA34b/crs4938723 polymorphism as a risk factor in the development of thyroid cancer in the Pakistani population. Mutational analysis of rs2910164 and rs4938723 of miRNA-146a and miRNA-34b/c was carried out to check their association with the development of thyroid carcinogenesis. Material and Methods: Papillary thyroid cancer (PTC) patients with age and gender-matched controls were recruited for the present study. DNA extraction, genotyping of rs2910164 and rs4938723 was carried out by ARMS-PCR. Statistical analyses were carried out using SPSS software (version 20). Results: The odds ratio for risk allele C of rs2910164 for patients and controls was 23.0168 (3.0321−174.7208) with a p-value of <0.0001, showing that the frequency of the major allele G was lower in patients while the frequency of minor allele C was higher in patients. Similarly, the odds ratio for risk allele C of rs4938723 was 1.8621 (1.0321−3.3596) with a p-value of <0.03788 showing significant association with the development of thyroid cancer. Conclusions: The study highlights the significant association of miRNAs SNPs as one of the genetic risk factor for PTC. It was concluded that miRNA-146a (rs2910164) showed higher frequency of minor allele C in patients. Similarly in miRNA-34b/c gene SNP rs4938723 was observed to have a strong association with the development of thyroid cancer as the frequency of rare allele C was higher in patients.

Genetic analysis of failed male puberty using whole exome sequencing.

OBJECTIVES: Although at least 598 genes are involved in the development of the hypothalamo-pituitary-testicular (HPT) axis, mutations in only 75 genes have so far been shown to cause delayed puberty. METHODS: Six male patients with failed puberty, manifested as absence of pubertal changes by 18 years of age, underwent whole exome sequencing of genomic DNA with subsequent bioinformatics analysis and confirmation of selected variants by Sanger sequencing. Genes having plausibly pathogenic non-synonymous variants were characterized as group A (previously reported to cause delayed puberty), group B (expressed in the HPT-axis but no mutations therein were reported to cause delayed puberty) or group C (not reported previously to be connected with HPT-axis). RESULTS: We identified variants in genes involved in GnRH neuron differentiation (2 in group A, 1 in group C), GnRH neuron migration (2 each in groups A and C), development of GnRH neural connections with supra-hypothalamic and hypothalamic neurons (2 each in groups A and C), neuron homeostasis (1 in group C), molecules regulating GnRH neuron activity (2 each in groups B and C), receptors/proteins expressed on GnRH neurons (1 in group B), signaling molecules (3 in group C), GnRH synthesis (1 in group B), gonadotropins production and release (1 each in groups A, B, and C) and action of the steroid hormone (1 in group A). CONCLUSIONS: Non-synonymous variants were identified in 16 genes of the HPT-axis, which comprised 4 in group A that contains genes previously reported to cause delayed puberty, 4 in group B that are expressed along HPT-axis but no mutations therein were reported previously to cause delayed puberty and 8 in group C that contains novel candidate genes, suggesting wider genetic causes of failed male puberty.

Role of lidocaine and its effect on postoperative outcomes in abdominal cholecystectomy.

OBJECTIVE: To investigate the role of pre- and intra-operative lidocaine infusion on post-operative pain management. METHODS: The interventional, prospective study was conducted from September 2019 to June 2020 at the Pakistan Ordnance Factories Hospital, Wah Cantt, Pakistan, and comprised patients aged 18-60 years undergoing elective cholecystectomy who were randomised into intervention group A and control group B. Group A was given a bolus dose of lidocaine hydrochloride 2 mg/kg in addition to the standard anaesthesia protocol, while group B was given continuous intravenous infusion of 0.9% normal saline along with the standard protocol. Blood samples for interleukins 6 and 8 were taken at baseline, and then at 2, 6 and 8 hours Post-operatively. Data was analysed using SPSS 23. RESULTS: Of the 40 patients, 20(50%) were in each of the two groups. There was a marked decrease in interleukins 6 and 8 levels group A compared to group B (p<0.05). Interleukin 8 level showed a marked decline compared to that of interleukin 6 (p<0.05). CONCLUSIONS: A decrease in interleukins 6 and 8 levels highlighted the anti-inflammatory role of lidocaine and resulted in a decrease in post-operative opioid consumption.

Natural plant extracts mediated expression regulation of TGF-ß receptors and SMAD genes in human cancer cell lines.

BACKGROUND: Transforming growth factor beta (TGF-ß) superfamily has key role in cell proliferation which leads to tumor promoting activities at metastatic stage of cancer. Inhibition of transforming growth factor beta receptor (TGFßR) signaling pathway can provide better therapeutic strategy to control cancer. Natural products are best known for their safety, less toxic nature, antioxidant characteristics making them a promising candidate to inhibit TGFßR signaling pathway. METHODS AND RESULTS: Crude methanolic extracts (CMEs) of 16 selected plants were prepared by using maceration method and subjected to phytochemical assays for identification of major phytometabolites particularly cancer chemopreventive antioxidant constituents. Total flavonoid content of all plants CME was > 0.6 mg/ml exhibiting the Cichorium intybus contains comparatively highest amount of total flavonoid content (0.53 mg/ml). Scanvenging activity of all plants was determined having IC50 ranges between 2 and 88 (µg/ml) while Moringa oleifera revealed the maximum scavenging activity (IC50 2.03 µg/ml). Comparative cytotoxicity of plant extracts was evaluated in HUH and MCF-7 cell lines using 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) colorimetric assay. The nine active plant extracts i.e. Fagonia cretica, Argemone Mexicana, Rubus fruticosus, M. oleifera, Punica granatum, Cichorium intybus, Xanthium strumarium, Carissa opaca, Cyperus rotundus were identified based on their high antiproliferative activity > 50% against cancer cell lines and subjected to relative expression studies. Modulation of TGFß signaling molecules (i.e.TGFßR1, 2 & 3, SMAD3, SMAD5) and ubiquitous proteins i.e. SMURF1 and SMURF2 genetic expression by potent extracts was determined by RT-PCR using GAPDH (housekeeping gene) as gene of reference. CONCLUSIONS: This present study revealed that CME of Fagonia cretica and Argemone mexicana significantly inhibit TGF beta mediated signaling cascade by downregulating the gene expression fold change > 1 of TGFßR 1, 2 & 3 and receptor associated complex protein SMAD3 as compared to control.

Graphene nanoplatelets/CeO2 nanotiles nanocomposites as effective antibacterial material for multiple drug-resistant bacteria.

Antibacterial agents with low toxicity to normal cells, redox activity and free radical scavenging property are urgently needed to address the global health crisis. The phenomenal conducting nature of graphene is a best fit to enhance the antibacterial properties of metal oxides. In this work, CeO2 nanotiles and graphene nanoplatelets/CeO2 nanotiles nanocomposites (G/CeO2) have been synthesized by a solvothermal method. The prepared materials have been characterized using XRD, FE-SEM, EDX, and UV-visible spectroscopy techniques to investigate their crystallinity, morphology, composition, and optical bandgap energies. The CeO2 and G/CeO2 nanocomposites have also been tested for antibacterial applications. The neat CeO 2 nanotiles sample inhibits the bacterial growth of Pseudomonas aeruginosa and Staphylococcus aureus up to 14.21% and 39.53% respectively. The antibacterial activity was tremendously enhanced using 25% graphene-loaded sample (G/CeO2-II) i.e., approximately 83% loss of P. aeruginosa and 89% in case of S. aureus has been observed. This can be attributed to the unique nano-architecture, oxidative stress due to the excellent ability of reversible conversion between the two electronic states of CeO2 and the stress exerted by the planar graphene and CeO2 nanotiles. Therefore, the G/CeO2 nanocomposites can find potential application as nano-antibiotics for controlling pathogens.

Genetic predisposition of SNPs in miRNA-149 (rs2292832) and FOXE1 (rs3758249) in thyroid Cancer.

BACKGROUND: Many efforts have been made in recent years to investigate the alterations in protein-coding genes as well as non-coding RNAs that are playing an emerging role in the development and progression of cancers. These miRNAs are short non-coding functional RNAs that are involved in the regulation of transcriptome. In different studies, it was found that human miRNA-149 is an important microRNA that is functioning either as onco-miRNAs or acting as tumor suppressors, in different conditions. RATIONALE: Many of the miRNAs are regulating different SNPs of FOXE1 in different studies which are causing low-to-moderate penetrance of genes that initiates the development of thyroid cancer. The involvement of SNPs in miRNA-149 gene rs2292832 and FOXE1 rs3758249 with PTC for better disease prognosis and management was determined in this study and the relation between these SNPs at the genotypic level was also evaluated. MATERIALS AND METHODS: PTC patients with age and gender-matched controls were recruited in the present study. Blood samples were collected in EDTA vacutainer followed by DNA extraction by the organic method. Genotyping of rs2292832 and rs3758249 was done by ARMS-PCR and PCR- RFLP respectively. Statistical analyses were carried out by using SPSS software (version 20). RESULTS: The mutation T>C in miRNA-149 rs2292832 was significantly associated with thyroid cancer (p-value 0.0004, < 0.05) while rs3758249 G>C did not show significant association with the disease (p-value 0.124244, > 0.05). Moreover, no correlation of rs2292832 at the genotype level was observed with rs3758249. CONCLUSIONS: miRNA-149 gene SNP rs2292832 was observed in strong association with thyroid cancer. Lack of genetic association of rs3758249 of FOXE1 gene has been ruled for the disease. The statistically significant association of rs2292832 with thyroid cancer depicts its mechanistic involvement at the cellular level in Papillary Thyroid Carcinoma.

SnO2nanorods/graphene nanoplatelets nanocomposites: towards fast removal of malachite green and pathogen control.

The world is facing alarming challenges of environmental pollution due to uncontrolled water contamination and multiple drug resistance of pathogens. However, these challenges can be addressed by using novel nanocomposites materials such as, SnO2/graphene nanopaletelets (GNPs) nanocomposites remarkably. In this work, we have prepared SnO2nanorods and SnO2/GNPs nanocomposites (GS-I and GS-II) with size of 25 ± 6 nm in length and 4 ± 2 nm in diameter. The optical bandgap energies change from 3.14 eV to 2.80 eV in SnO2and SnO2/GNPs nanocomposite. We found that SnO2/GNPs nanocomposite (GS-II) completely removes (99.11%) malachite green in 12 min, under UV light exposure, while under same conditions, SnO2nanorods removes only 37% dye. Moreover, visible light exposure resulted in 99.01% removal of malachite green in 15 min by GSII as compared to 24.7% removal by SnO2. In addition, GS-II nanocomposite inhibits 79.57% and 78.51% growth ofP. aeruginosaandS. aureusrespectively. A synchronized contribution of SnO2and GNPs makes SnO2/GNPs nanocomposites (GS-II) an innovative multifunctional material for simultaneous fast and complete removal of malachite green and inhibition of drug resistant pathogens.

Manganese-doped cerium oxide nanocomposite as a therapeutic agent for MCF-7 adenocarcinoma cell line.

The preparation of a manganese-doped cerium oxide (Mn:CeO2) nanocomposite via hydrothermal route is described. Cubic fluorite structure of single phase was exhibited by studying structural analysis through x-ray diffraction (XRD) technique and morphological analysis was conducted by scanning electron microscope. Surface analytic technique of energy dispersive x-ray spectroscopy (EDX) was conducted to analyze the relative amount of any impurity and doping. Structural changes due to manganese doping such as increment in production of vacancies of oxygen within crystal of cerium oxide, and reduction in size of crystallite and constant of lattice was observed in our research study. Moreover, the Mn:CeO2 nanocomposite demonstrates differential cytotoxicity against MCF-7 adenocarcinoma cell line, which renders it a promising candidate for targeted cancer therapy. The anti-tumorous activity of the cerium oxide nanocomposite was significantly enhanced with doping of manganese, which is directly linked with the generation of highly reactive oxygen facets. The experimental results are supported by a mathematical model that confirms a confidence level of 95%. This research has paved the way for many utilities in therapeutics and magnetic resonance imaging diagnostics through new observations, and hence verified their math model.

Potential risk assessment of miR-143 gene polymorphisms rs41291957 and rs353292 in colorectal cancer.

Colorectal cancer is a life-threatening and therapeutically challenging disease. Increasingly it is being deciphered that genetic and epigenetic mutations play a central role in cancer onset and progression. Excitingly, discovery of non-coding RNAs is considered to be a milestone in molecular oncology and emerging evidence is deepening our understanding about pivotal role of miRNAs in carcinogenesis. miR-143 has been experimentally verified to play an instrumental role as tumor suppressor. Recent studies suggest that single nucleotide polymorphisms rs41291957 and rs353292 in miR-143 may associate with the progression and or development of colorectal cancer. In present study 400 Pakistani subjects participated including 200 colorectal cancer patients and 200 age and gender matched healthy individuals. Blood samples and clinical information of the confirmed patients was collected from cancer diagnosis and treatment hospitals in Pakistan. The polymorphisms rs41291957 and rs353292 were genotyped in patients and controls by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were validated by Sanger sequencing. The association of the SNPs within the study group was analyzed by χ² test with p value < 0.05 as significant. Odds ratio was calculated with 95% confidence interval.Genetic predisposition to cancer was observed in presence of characteristic rs45291957 polymorphism. χ² test results show strongly significant association mi-RNA rs45291957 SNP with colorectal cancer p value 0.0111 (<0.05) along with the statistically significant correlation tested by odds ratio with 95% confidence interval. However, no significant correlation (p value 0.6683) could be found for the association of rs353292 with colorectal cancer in Pakistani population. The present study for the first time gave evidence of miR-143 rs41291957 involvement in colorectal cancer patients of Pakistani population. This target can be a useful molecular tool for the prognosis and treatment targets for colorectal cancer in Pakistani population. rs353292 genetic association can be explored for different cancers in Pakistan to completely rule out its role in cancer.

Synthesis of Functional Silver Nanoparticles and Microparticles with Modifiers and Evaluation of Their Antimicrobial, Anticancer, and Antioxidant Activity.

An accumulating body of evidence reports the synthesis and biomedical applications of silver nanoparticles. However, the studies regarding the use of maleic acid and citric acid in the synthesis of nano-sized silver particles (AgNPs) and micro-sized silver particles (AgMPs) as well as their antibacterial, antifungal, and anticancer activities have not been reported. In the current study, we synthesized AgNPs and AgMPs using maleic acid and citric acid as capping agents and have characterized them by UV-Vis, energy-dispersive X-Ray spectroscopy (EDS), X-Ray diffraction (XRD), and scanning electron microscope (SEM) analysis. The capped silver particles were examined for their antimicrobial activity and cytotoxicity against bacteria, fungi, and brine shrimp. Additionally, the anticancer activity of these particles was tested against human breast and liver cancer cell lines. The free radical scavenging activity of capped silver particles was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. SEM analysis revealed a round plate-like morphology of maleic acid capped particles with an average size of 39 ± 4 nm, whereas citric acid capped particles display flower-shaped morphology with rough surfaces and an average size of 250 ± 5 nm. The uncapped AgMPs were hexagonal with 500 ± 4 nm size. EDS and XRD analysis confirmed the presence of Ag and face-centered cubic crystalline nature, respectively. Functionally, capped silver particles exhibited antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus) and Gram-negative bacteria (Salmonella setubal, Enterobacter aerogenes, and Agrobacterium tumefaciens). The bactericidal activity was more active against Gram-negative bacteria with minimum inhibitory concentration (MIC) as low as 5 ppm as compared to 25 ppm for Gram-positive. Similarly, the silver particles demonstrated antifungal activity by inhibiting the growth of five fungal strains (Mucor species, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, and Fusarium solani) up to 50% at the concentration of 500 ppm. Additionally, these particles showed substantial toxicity against brine shrimp and also significantly inhibited the proliferation of breast cancer (MCF7) and liver cancer (HePG2) cell lines (IC50 8.9-18.56 µM). Uncapped AgMPs were less effective, inhibiting only the proliferation of MCF7 cells with IC50 46.54 µM. Besides cytotoxicity, these particles acted as potential antioxidants, showing free radical scavenging up to 74.4% in a concentration-dependent manner. Taken together, our results showed that the modifiers affect the shape and size of silver particles and may, in part, contribute to the antimicrobial and antioxidant activity of silver particles. However, the contribution of maleic acid and citric acid in enhancing the antimicrobial, anticancer, and antioxidant potential independent of silver nano and microparticles needs to be studied further. In vivo experiments may determine the therapeutic effectiveness of silver particles capped with these modifiers.

Manganese-Doped Cerium Oxide Nanocomposite Induced Photodynamic Therapy in MCF-7 Cancer Cells and Antibacterial Activity.

In this experimental approach, we explored the structures, morphologies, phototoxicities, and antibacterial activities of undoped and Mn-doped ceria nanocomposite materials, Mn x Ce1-x O2. The Mn x Ce1-x O2 nanocomposites were synthesized by employing a soft chemical route. Our prime focus was on the influence of different factors, both physical and chemical, i.e., the concentration of manganese in the product, size of the nanocomposite, drug dose, and incubation time, on the bacterial strains. Different bacterial strains were selected as experimental biological models of the antibacterial activity of the manganese-doped cerium oxide nanocomposite. In addition to the photodynamic response, the adenocarcinoma cell line (MCF-7) was also studied. Based on cell viability losses and bacterial inhibition analyses, the precise mechanisms of apoptosis or necrosis of 5-ALA/PpIX-exposed MCF-7 cells under 630 nm red lights and under dark conditions were elucidated. It was observed that the undoped nanocomposites had lower cytotoxicities and inhibitions compared with those of the doped nanocomposites towards pathogens. The antibacterial activity and effectiveness for photodynamic therapy were enhanced in the presence of the manganese-doped ceria nanocomposite, which could be attributed to the correlation of the maximum reactive oxygen species generation for targeted toxicity and maximum antioxidant property in bacteria growth inhibition. The optimized cell viability dose and doping concentration will be beneficial for treating cancer and bacterial infections in the future.

Superior antibacterial activity of ZnO-CuO nanocomposite synthesized by a chemical Co-precipitation approach.

Synthesis of highly efficient antibacterial agents has become highly important due to emergence of antibiotic resistance. Herein, Pristine ZnO and ZnO-CuO nanocomposite has been synthesized by simple chemical co-precipitation method and characterized by X-ray diffraction (XRD), microscopic and spectroscopic techniques. The prepared ZnO-CuO nanocomposite is composed of two dimensional nanosheets consisting of hexagonal ZnO and monoclinic CuO crystal phases present in coexistence. Moreover, a minute presence of Cu5Zn8 cubic phase has been evident in the XRD pattern of ZnO-CuO nanocomposite. Fourier Transform Infrared Spectroscopy (FTIR) spectrum of the prepared nanocomposite has revealed the presence of vibrational modes related to both Zn-O and Cu-O. Photoluminescence (PL) investigations depicted the formation of huge amounts of surface defects in ZnO-CuO nanocomposite as compared to pristine ZnO nanostructures. The prepared ZnO-CuO nanocomposite has efficiently killed Methicillin resistant Staphylococus aureus (s. aureus) bacterium by producing 24 mm of zone of inhibition (ZOI) comparing to 8 mm ZOI produced by pristine ZnO. The superior antibacterial activity of ZnO-CuO nanocomposite has been attributed to oxidative stress generated by electron transfer pathway and reactive oxygen species (ROS) generation.

Formulation of active packaging system using Artemisia scoparia for enhancing shelf life of fresh fruits.

An improved active packaging system was developed for fresh fruits using silver nanoparticles (AgNPs) coupled with calcium alginate (Ca-ALG). For the synthesis of AgNPs aqueous, ethanol and methanol extracts of Artemisia scoparia (AS) were used. These AgNP's were characterized using UV-Vis, SEM, EDS, AFM, FTIR and gel electrophoresis. Ethanol extract of AS (ASE) produced AgNPs with smallest size in comparison to aqueous AS (ASA) and methanol extract of AS (ASM). AgNPs synthesized from ASE had a size range of 12.0-23.3 nm and were tested on Human Corneal Epithelial Cells to evaluate their cytotoxicity. At 0.05 ng/mL of AgNP's concentration, no toxic effects were observed on the evaluated cell line. Therefore, 0.05 ng/mL of AgNPs mixed with edible coating of Ca-ALG were applied on strawberries and loquats as active coating to increase their shelf life. Significant improvement was observed in the quality parameters of strawberries and loquats such as microbial analysis, acidity loss, soluble solid content loss, weight loss and quality decay. Ca-ALG coating incorporated with AgNPs enhanced the shelf life of strawberries and loquats in comparison to no treatment and simple Ca-ALG coatings. This study provides an insight to food industry to extend the shelf life of fresh fruits using AgNP's formulated coatings.

Pharmacophore modeling for identification of anti-IGF-1R drugs and in-vitro validation of fulvestrant as a potential inhibitor.

Insulin-like growth factor 1 receptor (IGF-1R) is an important therapeutic target for breast cancer treatment. The alteration in the IGF-1R associated signaling network due to various genetic and environmental factors leads the system towards metastasis. The pharmacophore modeling and logical approaches have been applied to analyze the behaviour of complex regulatory network involved in breast cancer. A total of 23 inhibitors were selected to generate ligand based pharmacophore using the tool, Molecular Operating Environment (MOE). The best model consisted of three pharmacophore features: aromatic hydrophobic (HyD/Aro), hydrophobic (HyD) and hydrogen bond acceptor (HBA). This model was validated against World drug bank (WDB) database screening to identify 189 hits with the required pharmacophore features and was further screened by using Lipinski positive compounds. Finally, the most effective drug, fulvestrant, was selected. Fulvestrant is a selective estrogen receptor down regulator (SERD). This inhibitor was further studied by using both in-silico and in-vitro approaches that showed the targeted effect of fulvestrant in ER+ MCF-7 cells. Results suggested that fulvestrant has selective cytotoxic effect and a dose dependent response on IRS-1, IGF-1R, PDZK1 and ER-α in MCF-7 cells. PDZK1 can be an important inhibitory target using fulvestrant because it directly regulates IGF-1R.

MicroRNA Regulation of Telomerase Reverse Transcriptase (TERT): Micro Machines Pull Strings of Papier-Mâché Puppets.

Substantial fraction of high-quality information is continuously being added into the existing pool of knowledge related to the biology of telomeres. Based on the insights gleaned from decades of research, it is clear that chromosomal stability needs a highly controlled and dynamic balance of DNA gain and loss in each terminal tract of telomeric repeats. Telomeres are formed by tandem repeats of TTAGGG sequences, which are gradually lost with each round of division of the cells. Targeted inhibition of telomerase to effectively induce apoptosis in cancer cells has attracted tremendous attention and overwhelmingly increasingly list of telomerase inhibitors truthfully advocates pharmacological significance of telomerase. Telomerase reverse transcriptase (TERT) is a multi-talented and catalytically active component of the telomerase-associated protein machinery. Different proteins of telomerase-associated machinery work in a synchronized and orchestrated manner to ensure proper maintenance of telomeric length of chromosomes. Rapidly emerging scientific findings about regulation of TERT by microRNAs has revolutionized our understanding related to the biology of telomeres and telomerase. In this review, we have comprehensively discussed how different miRNAs regulate TERT in different cancers. Use of miRNA-based therapeutics against TERT in different cancers needs detailed research in preclinical models for effective translation of laboratory findings to clinically effective therapeutics.

Molecular characterization of autosomal recessive non syndromic hearing loss in selected families from District Mardan, Pakistan.

Deafness is the most common sensory disorder, which affects 1/1000 neonates globally. Genetic factors are major contributors for hearing impairment. This study was conducted to explore the linkage of DFNB loci and their mutations with NSHL in selected Pakistani families. We included 10 families with history of deafness from district Mardan, Pakistan. Blood sample (5ml) along with personal and clinical information was collected from the available family members including both diseased and un-affected individuals. Genomic DNA was amplified using loci specific STR markers to investigate the linkage of DFNB loci. Family found linked with DFNB4 locus was screened for SLC26A4 mutations. One out of the ten explored families was found linked with DFNB4 locus which was further investigated for SLC26A4 gene mutation through direct DNA sequencing. Two novel mutations were observed in the studied family, one at splice donor site (164+2T>G) and the other at position 164+5C>G only in the affected members of the linked family. DFNB4 locus was found linked in the present study which harbors SLC26A4 gene. The novel mutation of SLC26A4 gene at the splice donor site results in skipping of the first coding exon and thus can lead to loss of expression of SLC26A4 product in the inner ear.