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42 result(s) for "Mukherjee, Tapan Kumar"
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Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment
Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with consequent invasion and metastasis. Treatment with CDs is indeed well-versed but it is badly curtailed with accompanying side effects and inadequacies of site-specific drug delivery. As a result, drug carriers ensuring stealth delivery and sustained drug release with improved pharmacokinetics and biodistribution are urgently needed. Core–shell mesoporous silica nanoparticles (MSNPs) have recently been a cornerstone in this context, attributed to their high surface area, low density, robust functionalization, high drug loading capacity, size–shape-controlled functioning, and homogeneous shell architecture, enabling stealth drug delivery. Recent interest in using MSNPs as drug delivery vehicles has been due to their functionalization and size–shape-driven versatilities. With such insights, this article focuses on the preparation methods and drug delivery mechanisms of MSNPs, before discussing their emerging utility in BC treatment. The information compiled herein could consolidate the database for using inorganic nanoparticles (NPs) as BC drug delivery vehicles in terms of design, application and resolving post-therapy complications.
Exogenous Estrogens as Breast Cancer Risk Factors: A Perspective
Background: The human body’s exposure to high levels of endogenous estrogens and their metabolites, such as estradiol, estriol, 2-hydroxyestradiol, and 4-hydroxyestradiol, is implicated in the development and complications of breast cancers (BCs). Besides endogenous estrogen production, the human body is also exposed to environmental sources of estrogen and estrogen-like compounds, which include pharmaceutical estrogens, xenoestrogens, and phytoestrogens. Females consume pharmaceutical estrogens as a constituent of postmenopausal hormone replacement therapy (HRT) and oral contraceptive pills, either alone or in combination with progestins. Additionally, humans, including females, are exposed to estrogen-resembling non-native compounds called xenoestrogens, prevailing in pesticides, plastics, and personal care items via inhalation, dermal contact, and oral consumption. Several phytoestrogens, such as isoflavones and lignans, are consumed by humans as food ingredients. Methods and Results: Emerging cellular and molecular experimental evidence indicates that when binding to estrogen receptors (ERs), various pharmaceutical estrogens, including equine/synthetic forms, progestin combinations, and xenoestrogens, promote BC development and complications by triggering survival, proliferation, angiogenesis, and invasion of these cells. Conversely, other experimental observations reveal the protective and beneficial effects of phytoestrogens like genistein from soy products on BC development and complications. Conclusions: This comprehensive review article describes the implications of exposure to exogenous estrogens, such as pharmaceutical estrogens, xenoestrogens, and phytoestrogens, as risk factors in the prevention or development of BC and its complications.
Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective
Non-small cell lung cancers (NSCLCs) account for ~85% of lung cancer cases worldwide. Mammalian lungs are exposed to both endogenous and exogenous estrogens. The expression of estrogen receptors (ERs) in lung cancer cells has evoked the necessity to evaluate the role of estrogens in the disease progression. Estrogens, specifically 17β-estradiol, promote maturation of several tissue types including lungs. Recent epidemiologic data indicate that women have a higher risk of lung adenocarcinoma, a type of NSCLC, when compared to men, independent of smoking status. Besides ERs, pulmonary tissues both in healthy physiology and in NSCLCs also express G-protein-coupled ERs (GPERs), epidermal growth factor receptor (EGFRs), estrogen-related receptors (ERRs) and orphan nuclear receptors. Premenopausal females between the ages of 15 and 50 years synthesize a large contingent of estrogens and are at a greater risk of developing NSCLCs. Estrogen—ER/GPER/EGFR/ERR—mediated activation of various cell signaling molecules regulates NSCLC cell proliferation, survival and apoptosis. This article sheds light on the most recent achievements in the elucidation of sequential biochemical events in estrogen-activated cell signaling pathways involved in NSCLC severity with insight into the mechanism of regulation by ERs/GPERs/EGFRs/ERRs. It further discusses the success of anti-estrogen therapies against NSCLCs.
Applications of CRISPR/Cas technology against drug-resistant lung cancers: an update
Out of all the cancer types, the most prevalent one is lung cancer. Multiple genes and signaling pathways play role in the progression of lung cancer. Considering the wider prevalence and fatality of lung cancer it has become the focus of current cancer research. Though currently used approaches have shown positive results against lung cancer but success against non-small cell lung cancer (NSCLC) still looms as an enigma for the entire research fraternity. The development of resistance against inhibitors within a short span is one of the reasons responsible for the failure and relapse of lung cancer. Under these prevailing conditions genome/gene-editing technology using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR associated proteins (Cas), popularly known as CRISPR/Cas technology offers a convenient and flexible method for inducing precise changes within the lung cancer cell. Additionally, CRISPR-barcoding and CRISPR knockout screens at the genome-wide level can help in the functional investigation of specific mutations and identification of novel cancer drivers respectively. Several variants of the CRISPR/Cas system are being developed to limit off-targeting with enhanced precision. The present review article updates the usefulness of CRISPR/Cas technology against various types of lung cancers.
CRISPR/Cas technology for improving nutritional values in the agricultural sector: an update
Background The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system was initially identified in bacteria and archaea as a defense mechanism to confer immunity against phages. Later on, it was developed as a gene editing tool for both prokaryotic and eukaryotic cells including plant cells. Methods and Results CRISPR/Cas9 approach has wider applications in reverse genetics as well as in crop improvement. Various characters involved in enhancing economic value and crop sustainability against biotic/abiotic stresses can be targeted through this tool. Currently, CRISPR/Cas9 gene editing mechanism has been applied on around 20 crop species for improvement in several traits including yield enhancement and resistance against biotic and abiotic stresses. In the last five years, maximum genome editing research has been validated in rice, wheat, maize and soybean. Genes targeted in these plants has been involved in causing male sterility, conferring resistance against pathogens or having certain nutritional value. Conclusions Current review summarizes various applications of CRISPR/Cas system and its future prospects in plant biotechnology targeting crop improvement with higher yield, disease tolerance and enhanced nutritional value.
Characterization and quantitative assessment of lactic acid bacteria in fermented finger millet (Eleusine coracana) Variety-ML365
Finger millet (Eleusine coracana), a nutrient-rich cereal, is traditionally consumed in India and Africa, particularly among low-income populations. It is a great source of proteins, fibres, carbohydrates, and minerals, including calcium, making it a viable substrate for the development of functional meals. The aim was to separate and molecularly characterize lactic acid bacteria (LAB) from the fermented flour of the Indian finger millet variety ML365. Twelve bacterial isolates were isolated on MRS (de Man Rogosa and Sharpe) agar after fermentation. Based on morphological, biochemical, and preliminary probiotic screening tests, five isolates (EC01–EC05) were selected for detailed study. Biochemical characterization revealed traits typical of LAB, including positive lactose utilization, starch hydrolysis, and negative catalase and oxidase activities. For molecular identification, the 16S rRNA gene was amplified and sequenced. Sequence analysis using BLAST revealed that the isolates were similar to species belonging to the Bacillus and Brevibacterium genera. In particular, isolates closely resembled Brevibacterium sp., Bacillus cereus, Bacillus subtilis, Bacillus amyloliquefaciens, and Bacillus pumilus. Their genetic ties were further validated by phylogenetic analysis. The accession numbers for the nucleotide sequences that were put into the GenBank database were PQ606366.1, PQ606365.1, PQ606371.1, PQ606367.1, and PQ606372.1. The study found that fermented finger millet flour is a good source of LAB and may possess probiotic qualities. Isolates like these may be utilized in the development of innovative probiotic formulations and functional foods. It is recommended that further in vivo research be conducted to investigate their safety profiles, potential technical applications in the food industry, and health-promoting properties.  
Short peptide based nanotubes capable of effective curcumin delivery for treating drug resistant malaria
Background Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm’s bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine–α,β-dehydrophenylalanine (FΔF), arginine-α,β-dehydrophenylalanine (RΔF), valine-α,β-dehydrophenylalanine (VΔF) and methonine-α,β-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. Results FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC 50 , 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC 50 , 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nanoparticles were highly biocompatible and didn’t show any toxic effect on mammalian cell lines and normal blood cells. Conclusion This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an enhancement in its efficacy as an antimalarial agent.
Molecular dynamics simulation as a tool for assessment of drug binding property of human serum albumin
Human serum albumin (HSA) is a major plasma protein and binding of drugs with this plasma protein has a great importance. It possess esterase activity which can cleave the drugs containing ester bond and thus, can regulate the effect of drugs. Till date no systematic study has been done to analyse binding of such drugs and to compare the results with the drugs which do not have ester bond. Therefore, in the present study two different categories—ester and non-ester drugs have been considered to analyse their interaction with HSA at two principle drug binding sites using molecular modelling tools. It is observed that the drugs irrespective of ester or non-ester nature prefer either Sudlow site I or II by hydrogen bond and hydrophobic interactions. The information obtained from the study can assist to study pharmacokinetics of the drugs and that in turn will help in noval drug discoveries.
Evaluation of Boerhavia diffusa and Eichhornia crassipes plant extracts in vitro as potential antifungal agents against human pathogenic fungi Candida albician and Candida tropicalis : A comparative study
Plant extracts are used to make herbal remedies with no side effects and little expense. During the COVID-19 pandemic, fungal species responsible for mucormycosis were found resistant to a variety of antifungals, including flucytosine, ketoconazole, fluconazole, voriconazole, itraconazole and echinocandins, due to their variable susceptibility. Amphotericin B is widely used as an antifungal agent due to its high inhibition capacity against various fungi. The present study aimed to compare the antifungal potential of Amphotericin B and herbal extract in vitro. The experiment was designed to measure zones of inhibition with the help of well-diffusion method. Four solvents, viz. methanol, chloroform, hexane and distilled water, were used to extract plant extract. The efficiency of plant extracts was found to be low compared to Amphotericin B (1.4mm). Chloroform extract of Boerhavia diffusa was found antifungal against Candida albician and C. tropicalis (0.45mm). Methanol and hexane extract of Eichhornia crassipes showed higher antifungal activity (1.35mm) and (1.75mm), respectively. The plant extracts also showed significant antifungal activity against C. tropicalis, revealing its potential to be used as a natural antifungal agent (1.1mm). Additionally, the findings showed that the chloroform and methanol extracts of B. diffusa and E. crassipes were also efficient against C. albician and C. tropicalis. The findings provide important insights about using plant extracts as a potential alternative to conventional antifungal agents.  
Immunogenic decapeptide in melanoma immunotherapy
Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells. Immunogenicity of the oligopeptide can be further intensified by its simultaneous binding to the programmed death receptor of the T lymphocytes. We have used the molecular dynamics (MD) simulation approach to reveal the dynamics of the decapeptide and its consequences to immunogenic effects. The dynamics have ensembled various conformations of the peptide which have been clustered in their representative conformers. During the dynamics, the peptide was found to fold to its conformation with a minimum free energy. Moreover, multiple analysis of the MD trajectory has provided many physiochemical features involved in the biological activity to improve the immunogenicity of this antigenic peptide. The manuscript concludes by proposing this decapeptide as a potential vaccine for the melanoma cancer.