Insights into association between urolithiasis and prostate cancer

Background and objective: Urolithiasis or renal stones form a major urinary tract infection with formation of calcifications in the bladder and uterus. With the lifestyle diseases burgeoning, the renal stones have become a common cause with an approximate 1 in 1000 people affected all over the world with a risk ratio of 3 : 1 in men and women. On the other hand, prostate or genitourinary cancers are well documented to be associated with urolithiasis. Methods: A gene list was prepared from the published NCBI dataset, comprising all the genes related to urolithiasis primarily with mutations (both pathogenic and likely pathogenic Single nucleotide polymorphisms, SNP’s) for every particular gene screened later from the published datasets. To see the interactions among all the potential genetic factors, PPI based tools were used and an interaction map was prepared. For the characterization of mutations, we have used gnomAD for verifying all the SNPs whether they are synonymous or nonsynonymous mutations. Results: We outlined the list of genes and discussed the systems bioinformatics integrated approach associated with it. Conclusion: We found a large number of genes common to them and their association is subtly known for immunomodulatory response

Nanophytosome formulation of β-1,3-glucan and Euglena gracilis extract for drug delivery applications

Euglena gracilis (EG) is a unicellular freshwater alga known for its high β-1,3-glucan (BG) content with well-known biological properties and immune response. The high molecular weight structure of BG traditionally poses a challenge in terms of its size and absorption. Therefore, the aim of this study was to develop a novel drug delivery mechanism of BG and EG to nanophytosomes (NPs) by converting the heavy molecular weight of BG and EG into lipid phosphatidylcholine (PC), which plays an important role in improving their bioavailability and entrapment in captivity. The BG and EG NPs were developed by the solvent evaporation method while varying time and temperature to optimize their drug delivery ability. The size of BG-PC and EG-PC obtained by the Dynamic Light Scattering (DLS) method was 134.62 and 158.38 nm, respectively. Chemical (Fourier Transform Infra-Red) and structural (X-Ray Diffraction) characterization of NPs improved the binding capacity and the amorphous nature of both NPs. The shape of the NPs by Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) revealed their spherical, vesicular nature. The encapsulation efficiency of BG-PC and EG-PC was 82 ± 1.62 % and 87 ± 3.22 %, respectively, which improves the bioavailability. The developed methodology has thus proven effective in synthesizing BG-PC and EG-PC, which may be useful as NP drug delivery carriers. Future research could demonstrate the safety and effectiveness of long-term storage conditions for medical and pharmaceutical applications. • Nanophytosomes are tailored in size, shape and composition to optimize the delivery of phytochemicals/phytocompounds through nanoscale size and surface modification for better physiological absorption. • Nanophytosomes increase the stability of phytochemicals/phytocompounds and protect them from degradation due to heat or chemical reactions, leading to longer shelf life and improved therapeutic efficacy. • In this method, optimal conditions were created for the formation of β-1,3-glucan and Euglena gracilis extract nanophytosomes for successful development of drug delivery system that can effectively deliver bioactive compounds

Characterisation, development and validation of UV Spectrophotometric technique for determining Diosmetin in bulk and nanoformulations

Background: From ancient times, India and many other countries have utilised natural products to manage various illnesses. Because they are abundantly available and have fewer adverse effects than synthetic medications, flavonoids are secondary metabolites with diverse biological activities. But till now, no formulations are developed by utilizing Diosmetin and no technique was formulated by utilizing self-biosynthesized Diosmetin (pure). It is a flavone (subclass of flavonoids) isolated from multiple medicinal plants but, in large amounts, is found in citrus plants. They have a variety of biological and pharmacological properties. They also improve lymphatic drainage by raising the duration and severity of lymphatic compression and the exact number of fully operational lymphatic capillaries. Methodology: We have procured Diosmetin from Otto Kemi Pvt. Ltd. and other chemicals from SIGMA chemicals. Furthermore, the characterisation of selected flavone has been performed through solubility studies and method development for development and validation by the UV method for nano-formulation. Result: Diosmetin is pure and soluble in various solvents and has a melting point between 259.14 and 261.84°Celsius, and is more soluble in Acetone, Chloroform, and DMSO, but we have utilised Diosmetin for Cancer studies, so we have taken it in 5% DMSO for further studies. Diosmetin is stable in DMSO till 20 mg/ml at room temperature

<i style="mso-bidi-font-style:normal"><span style="font-size:11.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-bidi-font-family:Mangal;mso-ansi-language:EN-GB; mso-fareast-language:EN-US;mso-bidi-language:HI" lang="EN-GB">NRAS</span></i><span style="font-size:11.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-bidi-font-family:Mangal;mso-ansi-language:EN-GB; mso-fareast-language:EN-US;mso-bidi-language:HI" lang="EN-GB"> Mutations in <i style="mso-bidi-font-style:normal">de novo</i> acute leukemia: Prevalence and clinical significance</span>

207-210The activating mutations of the Ras gene or other abnormalities in Ras signaling pathway lead to uncontrolled growth factor-independent proliferation of hematopoietic progenitors. Oncogenic mutations in NRAS gene have been observed with variable prevalence in hematopoietic malignancies. In the present study, NRAS mutations were detected using bidirectional sequencing in 264 acute leukemia cases — 129 acute lymphocytic leukemia (ALL) and 135 acute myeloid leukemia (AML) and 245 age- and gender-matched controls. Missense mutation was observed only in the 12th codon of NRAS gene in 4.7% of AML and 3.16% of ALL cases. The presence of NRAS mutation did not significantly influence blast % and lactate dehydrogenase (LDH) levels in AML patients. When the data were analyzed with respect to clinical variables, the total leukocyte count was elevated for mutation positive group, compared to negative group. In AML patients with NRAS mutations, 60% failed to achieve complete remission (CR), as compared to 34.8% in mutation negative group. These results indicated that NRAS mutations might confer poor drug response. In AML, disease free survival (DFS) in NRAS mutation positive group was lesser, compared to mutation negative group (9.5 months <i style="mso-bidi-font-style: normal">vs. 11.68 months). In ALL patients, DFS of <i style="mso-bidi-font-style: normal">NRAS mutation positive group was lesser than mutation negative group (9.2 months vs. 27.5 months). The CR rate was also lower for mutation-positive patients group, compared to mutation-negative group. In conclusion, these results suggested that presence of NRAS mutation at 12th codon was associated with poor response and poorer DFS in both ALL and AML

Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort

Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with genetics, genomics, and the environmental influence in the causality of PCa, not many studies employing the Next Generation Sequencing (NGS) approaches of PCa have been carried out. In our previous study, we identified some causal genes and mutations specific to Indian PCa using Whole Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify differentially expressed genes (DEGs) including long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using the RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened six patients who underwent prostatectomy; we performed whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz., GeneMANIA, Stringdb, Cytoscape-Cytohubba, and cbioportal, to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa, such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, and HN1L, and some other important genes known to be involved in different cancer pathways, such as COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1, etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, ENSG00000287903, and ENST00000647843.1 that need to be characterized further. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which perhaps have not been reported. This has set a precedent for us to validate candidates further experimentally, and we firmly believe this will pave a way toward the discovery of biomarkers and the development of novel therapies

Optimization and Characterization of a Novel Exopolysaccharide from Bacillus haynesii CamB6 for Food Applications

Extremophilic microorganisms often produce novel bioactive compounds to survive under harsh environmental conditions. Exopolysaccharides (EPSs), a constitutive part of bacterial biofilm, are functional biopolymers that act as a protecting sheath to the extremophilic bacteria and are of high industrial value. In this study, we elucidate a new EPS produced by thermophilic Bacillus haynesii CamB6 from a slightly acidic (pH 5.82) Campanario hot spring (56.4 &deg;C) located in the Central Andean Mountains of Chile. Physicochemical properties of the EPS were characterized by different techniques: Scanning electron microscopy- energy dispersive X-ray spectroscopy (SEM-EDS), Atomic Force Microscopy (AFM), High-Performance Liquid Chromatography (HPLC), Gel permeation chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), 1D and 2D Nuclear Magnetic Resonance (NMR), and Thermogravimetric analysis (TGA). The EPS demonstrated amorphous surface roughness composed of evenly distributed macromolecular lumps. GPC and HPLC analysis showed that the EPS is a low molecular weight heteropolymer composed of mannose (66%), glucose (20%), and galactose (14%). FTIR analysis demonstrated the polysaccharide nature (&ndash;OH groups, Acetyl groups, and pyranosic ring structure) and the presence of different glycosidic linkages among sugar residues, which was further confirmed by NMR spectroscopic analyses. Moreover, D-mannose &alpha;-(1&rarr;2) and &alpha;-(1&rarr;4) linkages prevail in the CamB6 EPS structure. TGA revealed the high thermal stability (240 &deg;C) of the polysaccharide. The functional properties of the EPS were evaluated for food industry applications, specifically as an antioxidant and for its emulsification, water-holding (WHC), oil-holding (OHC), and flocculation capacities. The results suggest that the study EPS can be a useful additive for the food-processing industry