In silico Screening of Violacein as an epidermal growth factor receptor inhibitor

EGFR is a key player in the signalling cascades of various kinds of cancers and tyrosine kinase inhibitors block EGFR signalling. Natural products have long been used as candidates for therapy in the management of cancer. Violacein, a bacterial pigment, has been known for its numerous biological applications such as antimicrobial, antileishmanial, antiviral, as well as antitumoral. Computational studies have concluded that it may have activity against cancers like pancreatic cancer, thyroid cancer, colorectal cancer, and endometrial cancer indicating its potential application as a broad range of anti-cancerous drug. This study aimed to perform the molecular docking of violacein with the EGFR protein to ascertain its EGFR inhibitor property, which could lead to the development of a novel anti-cancer drug

Bio prospecting of Lapachol producing endophytic fungi

Background: The association of endophytic fungi with medicinal plants has been one of the evolving areas of research in the past few decades. The secondary metabolites produced owing to such associations have been recognised for a wide range of biological activities. Objectives: The aim of the present review is to highlight the isolation of lapachol from endophytic microorganisms with an emphasis on its biotransformation to improve its efficacy. Methodology: The researchers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Published scientific articles on endophytes, host-pathogen interaction and lapachol isolation were collected from reputed journals from 1960 to 2022 using electronic databases using the key words as stated. Following that, the authors chose the required papers based on the criteria they devised. The data was extracted using the common research elements found in the publications. Results and discussion: Lapachol is one such secondary metabolite known for potent antitumor properties. Synthesis of lapachol and its isolation from plant sources have been reported but an expensive process. Therefore, bioprospecting of this metabolite from endophytic fungi have been evaluated by a few researchers. It has been identified that A. niger and Alternaria alternata along with some of the filamentous endophytic fungi have been identified to produce lapachol. Some findings of biotransformation of lapachol to render it more potent have also been reported in the present review. Conclusion: Lapachol is one of the plant secondary metabolites that possess several therapeutic benefits. Owing to its isolation being highly expensive from plant sources, endophytes have been exploited. Furthering to the isolation, the biotrasformation of this bioactive molecule to enhance its efficiency has proven to be useful. In this regard, this review has enlightened some of the biotransformed lapachol and its derivatives with special emphasis on the endophytes that produce them. This review comprehensively highlights the various endophytic sources for lapachol production and its biotransformed derivatives

In silico examination of peptides containing selenium and ebselen Backbone To Assess Their Tumoricidal Potential

Introduction: Cancer has been one of the highest causes of morbidity and mortality in the world for decades. Owing to improved therapeutics along with detection, breast cancer mortality has been slowly reducing. The incidence of breast cancer, on the other hand, has increased gradually. More than 100 types of cancer have been identified with a wide range of treatment protocols comprising of chemotherapy, radiation therapy, hormone therapy, etc. In an attempt to curb the serious deleterious effects caused by the chemotherapeutic drugs, numerous peptide molecules are currently popular as alternatives to the standard chemotherapeutic drugs. Methods: In this study, we have carried out in silico investigations to ascertain the anti-proliferative potential of novel peptides based on selenium and ebselen, i.e. Eb-Trp-Asp, 13, Eb-Trp-Glu, 14, and Eb-Trp-Lys, 15. Analysis of protein-ligand interactions, resulting in protein-ligand complex formation, has been carried out using the AutoDockVina in PyRx aided molecular docking technique, which may be an essential indication of druggability of the test peptides. Results: The molecular docking results revealed that the screened ligands had extraordinarily strong binding interactions and affinity for the target. Conclusion: Findings suggested that novel peptide molecule Eb-Trp-Glu, 14 may be a potent anticancer agent

Volatile organic compound emissions in free-range chicken production: Impacts on environment, welfare and sustainability

The increasing demand for free-range poultry products has led to a surge in their availability in the market, prompting a potential decline in premium prices associated with these products. This shift places considerable pressure on upstream costs in chicken production. A comprehensive under-standing of its impact on the environment is essential to ensure the success of commercial and industrial free-range chicken production. However, there exists a significant knowledge gap concerning the emission and concentrations of volatile organic compounds (VOCs) from organic-free range chicken, and their environmental implications have yet to be understood. We aim to address this critical knowledge gap by elucidating the role of VOC emissions in chicken production and assessing their impact on human and animal health, as well as environmental challenges. Understanding the implications of VOC emissions is essential for promoting sustainable and responsible free-range chicken farming practices. By identifying the sources of VOC emissions and their impacts, stakeholders can implement appropriate measures to optimize air quality and enhance the well-being of chickens and workers. Ultimately, this review highlights the role of VOCs in animal production, providing valuable insights for improving the efficiency, environmental sustainability and welfare aspects of free-range chicken farming

Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR

Research Article A new Informatics Framework for Evaluating the Codon Usage Metrics, Evolutionary Models and Phylogeographic reconstruction of Tomato yellow leaf curl virus (TYLCV) in different regions of Asian countries

Tomato yellow leaf curl virus (TYLCV) is a major devastating viral disease, majorly affecting the tomato production globally. The disease is majorly transmitted by the Whitefly. The Begomovirus (TYLCV) having a six major protein coding genes, among them the C1/AC1 is evidently associated with viral replication. Owing to immense role of C1/AC1 gene, the present study is an initial effort to elucidate the factors shaping the codon usage bias and evolutionary pattern of TYLCV-C1/AC1 gene in five major Asian countries. Based on publically available nucleotide sequence data the Codon usage pattern, Evolutionary and Phylogeographic reconstruction was carried out. The study revealed the presence of significant variation between the codon bias indices in all the selected regions. Implying that the codon usage pattern indices (eNC, CAI, RCDI, GRAVY, Aromo) are seriously affected by selection and mutational pressure, taking a supremacy in shaping the codon usage bias of viral gene. Further, the tMRCA age was 1853, 1939, 1855, 1944, 1828 for China, India, Iran, Oman and South Korea, respectively for TYLCV-C1/AC1 gene. The integrated analysis of Codon usage bias, Evolutionary rate and Phylogeography analysis in viruses signifies the positive role of selection and mutational pressure among the selected regions for TYLCV (C1/AC1) gene

The first study on analysis of the codon usage bias and evolutionary analysis of the glycoprotein envelope E2 gene of seven Pestiviruses

Background and Aim: Pestivirus, a genus of the Flaviviridae family, comprises viruses that affect bovines, sheep, and pigs. Symptoms, including hemorrhagic syndromes, abortion, respiratory complications, and deadly mucosal diseases, are produced in infected animals, which cause huge economic losses to the farmers. Bovine viral diarrhea virus-1, bovine viral diarrhea virus-2, classical swine fever virus, border disease virus, Bungowannah, Hobi-like, and atypical porcine pestivirus belonging to the Pestivirus genus were selected for the study. This study aimed to estimate the codon usage bias and the rate of evolution using the glycoprotein E2 gene. Furthermore, codon usage bias analysis was performed using publicly available nucleotide sequences of the E2 gene of all seven Pestiviruses. These nucleotide sequences might elucidate the disease epidemiology and facilitate the development of designing better vaccines. Materials and Methods: Coding sequences of the E2 gene of Pestiviruses A (n = 89), B (n = 60), C (n = 75), D (n = 10), F (n = 07), H (n = 52), and K (n = 85) were included in this study. They were analyzed using different methods to estimate the codon usage bias and evolution. In addition, the maximum likelihood and Bayesian methodologies were employed to analyze a molecular dataset of seven Pestiviruses using a complete E2 gene region. Results: The combined analysis of codon usage bias and evolutionary rate analysis revealed that the Pestiviruses A, B, C, D, F, H, and K have a codon usage bias in which mutation and natural selection have played vital roles. Furthermore, while the effective number of codons values revealed a moderate bias, neutrality plots indicated the natural selection in A, B, F, and H Pestiviruses and mutational pressure in C, D, and K Pestiviruses. The correspondence analysis revealed that axis-1 significantly contributes to the synonymous codon usage pattern. In this study, the evolutionary rate of Pestiviruses B, H, and K was very high. The most recent common ancestors of all Pestivirus lineages are 1997, 1975, 1946, 1990, 2004, 1990, and 1990 for Pestiviruses A, B, C, D, F, H, and K, respectively. This study confirms that both mutational pressure and natural selection have played a significant role in codon usage bias and evolutionary studies. Conclusion: This study provides insight into the codon usage bias and evolutionary lineages of pestiviruses. It is arguably the first report of such kind. The information provided by the study can be further used to elucidate the respective host adaptation strategies of the viruses. In turn, this information helps study the epidemiology and control methods of pestiviruses

Phytochemical fractions from Annona muricata seeds and fruit pulp inhibited the growth of breast cancer cells through cell cycle arrest at G(0)/G(1) phase

Introduction: Annona muricata (L.) (AM), commonly known as Soursop and Lakshmanaphala/Hanumaphala in India, has been extensively used in ethnomedicine for treating tuberculosis, urinary tract infections (UTIs) and cancers. The fruit is a rich source of antioxidants and antitumor agents. Methods: In this study, we have extracted phytochemicals that exhibited anti-cancer property from the (a) fruit pulp using methanol (AMPM) and water (AMPW); and (b) seeds using methanol (AMSM). Qualitative phytochemical analysis showed the presence of phenolics, tannins, alkaloids, flavonoids, sterols, terpenoids, carbohydrates and proteins in AMPM and AMPW. All three extracts were first checked for in vitro antioxidant and anti-inflammatory properties and then tested for efficacy against MCF-7 and MDA-MB-231. Results: Among these three extracts, AMSM showed the highest antioxidant power as well as similar to 80% inhibition at 320 mu g/ml concentration in both cell lines upon treatment for 24h. However, only about 40% inhibition was observed with 320 mu g/ml AMPM treatment, despite its highest anti-inflammatory potential. Water extract AMPW exhibited about 80% growth inhibition at 50% dilution. Since fruit pulp is the one consumed, the extracts AMPM and AMPW were further tested for apoptosis induction and cell cycle arrest. Analysis of the data showed increased apoptosis and G0/G1 cell cycle arrest upon exposure to AMPM and AMPW

Virtual Screening and Quantitative Structure–Activity Relationship of Moringa oleifera with Melanoma Antigen A (MAGE-A) Genes against the Therapeutics of Non-Small Cell Lung Cancers (NSCLCs)

In the last decade, there have been significant advancements in the treatment of non-small cell lung cancer, including remarkable gains in detection, diagnosis, and therapy. The emergence of molecular targeted therapies, immunotherapeutic inhibitors, and antiangiogenesis medicines has largely fueled improvements in combination therapy and systemic treatments, all of which have dramatically ameliorated patient outcomes. The Moringa oleifera bioactive compounds have been effective in the suppression of cancers, making them the therapeutic agents of choice for the current investigation to treat MAGE-A presented in NSCLC. The ligand entrants were screened for their pharmacological properties, and 2,2-diphenyl-1,3-benzodioxole was stipulated as the lead candidate. 2,2-Diphenyl-1,3-benzodioxole exhibited better pharmacological properties and superior binding with branched-chain amino acids, making it an ideal candidate to address MAGE-A. The study concluded that addressing MAGE-A to impede their activity and antigenicity can be exploited as immunotarget(s)

Antitumor Potential of Green Synthesized ZnONPs Using Root Extract of Withania somnifera against Human Breast Cancer Cell Line

Herein we report the synthesis of zinc oxide nanoparticles (ZnONPs) using Withania somnifera root extract (WSE) as an effective chelating agent. The microscopic techniques viz., X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED) were employed to analyze the as-obtained ZnONPs. The crystalline planes observed from the XRD pattern agrees with the hexagonal wurtzite structure of the as-prepared ZnONPs. The aggregations and agglomerations observed in the SEM images indicated that the size of the as-prepared ZnONPs was between 30 and 43 nm. The interplanar distance between the lattice fringes observed in the HRTEM image was found to be 0.253 nm, which is in good agreement with the (100) plane obtained in the XRD pattern. Furthermore, the anti-breast cancer cytotoxic evaluation was carried out using the MCF-7 cell line, and the results showed significant cytotoxic effects in a dose-dependent manner