The phosphatase and tensin homolog (PTEN) gene plays a crucial role in signal transduction by negatively regulating the PI3K signaling pathway. It is the most frequent mutated gene in many human-related cancers. Considering its critical role, a functional analysis of missense mutations of PTEN gene was undertaken in this study. Thirty five nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of the PTEN gene were selected for our in silico investigation, and five nsSNPs (G129E, C124R, D252G, H61D, and R130G) were found to be deleterious based on combinatorial predictions of different computational tools. Moreover, molecular dynamics (MD) simulation was performed to investigate the conformational variation between native and all the five mutant PTEN proteins having predicted deleterious nsSNPs. The results of MD simulation of all mutant models illustrated variation in structural attributes such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and total energy; which depicts the structural stability of PTEN protein. Furthermore, mutant PTEN protein structures also showed a significant variation in the solvent accessible surface area and hydrogen bond frequencies from the native PTEN structure. In conclusion, results of this study have established the deleterious effect of the all the five predicted nsSNPs on the PTEN protein structure. Thus, results of the current study can pave a new platform to sort out nsSNPs that can be undertaken for the confirmation of their phenotype and their correlation with diseased status in case of control studies.
In this work the survival of Lactobacillus plantarum in guava juice upon spray‐drying process using maltodextrin (MD) and inulin (INU) as drying carriers was evaluated. The microbial viability, color, water activity (Aw), and rehydration time in spray‐dried lacto‐fermented guava juice powder were evaluated at room temperature (25°C) and refrigerated conditions (4°C) for 45 days. Spray drying was done at inlet temperature of drying air 120°C, feed flow rate 5 ml/min, hot air flow 3.0 m3/min, pressurized air flow 30 L/min, and outlet temperature at 75°C. Results indicated that the highest survival rates of 80% for 45 days and 85% up to 15 days were observed at 4°C and 25°C, respectively, for powders obtained using 10% MD + 10% INU blend. Highest yield and lowest rehydration time were obtained by 20% MD. Aw was maintained low and no color difference in the product was seen in any of the formulations. Practical Applications The practical applications of this research will help in catering the growing demand for functional foods with nondairy food matrix containing both prebiotics and probiotics (known as synbiotic). In the present work a source of prebiotic‐guava and lactobacillus strain as a probiotic was used to formulate a, synbiotic beverage which was then spray dried in optimized method. Such unique combinations improve the nutritional attributes and bring forth health benefits of fruit juices, and delivers health potential from both sources (fruit juices and probiotics). This spray‐dried synbiotic powder will be a preferred choice for lactose‐intolerant people. The synbiotic not only help in immunomodulatory functions but also help in efficient functioning of gut microbiota which is scientifically related to many body vitals. The most critical practical challenge of preserving the needed microbial viability over shelf life is also dealt with in the present work. This consumer friendly form not only offers an ease of commercial transport but a closely packed form of deliverables for combating micronutrient deficiency.
Hepatitis C virus (HCV) is the most prevalent viral pathogen that infects more than 185 million people worldwide. HCV infection leads to chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma. Direct-acting antivirals (DAAs) are the recent combination therapy for HCV infection with reduced side effects than prior therapies. Sustained virological response (SVR) acts as a gold standard marker to monitor the success of antiviral treatment.Older treatment therapies attain 50-55% of SVR compared with DAAs which attain around 90-95%. The current review emphasizes the recent chemogenomic updates that have been unfolded through structure-based drug design of HCV drug target proteins (NS3/4A, NS5A, and NS5B) and ligand-based drug design of DAAs in achieving a stable HCV viral treatment strategies.
Oncogenesis involves continuous genetic alterations that lead to compromised cellular integrity and immortal cell fate. The cells remain under excessive stress due to endo‐ and exogenous influences. Human Satellite III long noncoding RNA (SatIII lncRNA) is a key regulator of the global cellular stress response, although its function is poorly explained in cancers. The principal regulator of cancer meshwork is tumor protein p53, which if altered may result in chemoresistance. The heat shock factor 1 (HSF1) being a common molecule between the oncogenic control and global cellular stress acts as an oncogene as well as transcribes SatIII upon heat shock. This prompted us to determine the structure of SatIII RNA and establish the association between SatIII‐HSF1‐p53. We determined the most stable structure of SatIII RNA with the least energy of − 115.7 kcal/mol. Also, we observed a possible interaction of p53 with SatIII and HSF1 using support vector machine (SVM) algorithm for predicting RNA‐protein interaction (RPI). Further, we employ the STRING database to understand if p53 is an interacting component of the nuclear stress bodies (nSBs). A precise inference was drawn from molecular docking which confirmed the interaction of SatIII‐HSF1‐p53, where a mutated p53 resulted in an altered DNA‐binding property with the SatIII molecule. This study being first of its kind infers p53 to be a possible integral component of the nSBs, which may regulate cellular stress response during cancer progression in the presence of HSF1 and SatIII. An extended research on the regulations of SatIII and p53 may open new avenues in the field of apoptosis in cancer and the early approach of molecular targeting.
Hepatitis C virus infection causes chronic liver disease that leads to cancer-related mortality. Presently around 30% of the HCV (infected) affected population get rid of the infection through spontaneous disease clearance. This phenomenon is conducted by a set of reported immune candidate genes. Hence, this study focuses only on these immune-response related genes with aid of network approach, where the idea is to disseminate the network for better understanding of key functional genes and their transcription control activity. Based on the network analysis the IFNG, TNF, IFNB1, STAT1, NFKB1, STAT3, SOCS1, and MYD88 genes are prioritized as hub genes along with their common transcription factors (TFs), IRF9, NFKB1, and STAT1. The dinucleotide frequency of TF binding elements indicated GG-rich motifs in these regulatory elements. On the other hand, gene enrichment report suggests the regulation of response to interferon gamma signaling pathway, which plays central role in the spontaneous HCV clearance. Therefore, our study tends to prioritize the genes, TFs, and their regulatory pathway towards HCV clearance. Even so, the resultant hub genes and their TFs and TF binding elements could be crucial in underscoring the clearance activity in specific populations.
Hepatitis C virus (HCV) infection is among the leading causes of hepatocellular carcinoma and liver cirrhosis globally, with a high economic burden. The disease progression is well established, but less is known about the spontaneous HCV infection clearance. This study tries to establish the relationship between codon biasness and expression of HCV clearance candidate genes in normal and HCV infected liver tissues. A total of 112 coding sequences comprising 151 679 codons were subjected to the computation of codon indices, namely relative synonymous codon usage, an effective number of codon (Nc), frequency of optimal codon, codon adaptation index, codon bias index, and base compositions. Codon indices report of GC3s, GC12, hydropathicity, and aromaticity implicates both mutational and translational selection in the candidate gene set. This was further correlated with the differentially expressed genes among the selected genes using BioGPS. A significant correlation is observed between the gene expression of normal liver and cancerous liver tissues with codon bias (Nc). Gene expression is also correlated with relative codon bias values, indicating that CCL5, APOA2, CD28, IFITM1, and TNFSF4 genes have higher expression. These results are quite encouraging in selecting the high responsive genes in HCV clearance. However, there could be additional genes which could also orchestrate the clearance role with the above mentioned first line of defensive genes.
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