The evolution of lipid nanoparticles (LNPs) has been remarkably interesting and in beneficent directions for food and health industries working towards human well being. Since the discovery of the first-generation lipid based self-assembled nanostructures, i.e., liposomes in the 1960s, it has witnessed significant advances in their development and distinctive potential in different application domains. Based on the composition and structure, these lipid based structures have varied from liposome to lipid nanoparticles such as nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLN) to overcome certain limitation pertaining to their use in different fields. The outstanding application of LNPs as therapeutic delivery systems has made them key players to treat different human disorders including the fatal cancers. Their life-saving global contribution has recently been witnessed in the form of mRNA vaccines against deadly COVID-19. They have also significantly served purpose in other domains such as biomedical imaging, cosmetics, nutrition, and agriculture. Their prominent role is in the area of anticancer therapy as delivery vectors for nucleic acids and drugs. Some issues with respect to the cellular delivery of drugs and genes, such as circulation time and stability have been somewhat resolved, but the unmet goal of site-specific substantial delivery remains the main focus in LNPs development research. Despite the promise shown by LNPs in animal studies and the fact that technological advances in LNPs research have made the approval possible of a few formulations, therapeutic outcomes in human are not satisfactory. The LNPs technology has managed to survive due to possible tailoring of their properties by virtue of the possibility of altering the composition and modifying the surface. Therefore, enormous scientific endeavours are on the rise to transform lipid structures, composition along with tinkering with surface of LNPs. The alternative methods to guide LNPs coupled with advances in small molecule nucleic acid therapeutics and drug development technology to make the entry possible to specific cells may be effective in cancer therapy. The development is very promising; however enduring efforts are required till the goal is reached.
Gut microbiota broadly impacts human health, but urinary microbial metabolites remain largely undefined. The concentration of microbial metabolites can be directly correlated with microbial populations in the human gut to define disease states. Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms is being used for ages in the Indian ayurvedic system of medicine and it has hypolipidemic and hypoglycaemic activity. Present study investigate the MS-based metabolomics variations of possible gut microbiota associated metabolites in hyperlipidemia (HPL) and HPL treated with Tinospora cordifolia extract (TCE) (TRT). Twenty-four HPL male patients and 10 age-matched controls (HLT) were enrolled. Early morning fasting blood and urine samples were collected on days 0 and 14th of TCE treatment and subjected to lipid profiling and Q-TOF-MS analysis. Multivariate analysis showed urinary levels of urocanic acid, hydroxyphenylacetate, linolenic acid, phenylpropionate, hypoxanthine, and indole acetate produced by Peptostreptococcs asaccharolyticus, Clostridium difficile, Faecalibacterium prausnitzii, Bifidobacterium, Subdoligranulum, Lactobacillus, Clostridium sporogenes, E. coli were depleted in HPL patients as compared to healthy controls. In contrast, levels of serotonin, acetylleucine, hippuric acid, and arabinitol were found to be increased (>2.0 fold, p<0.005). However, TCE treatment reverted the levels of these metabolites and therefore, gut microflora. Also, Cloacibacterium haliotis, Lactobacillus, Clostridium, and Bifidobacterium population decreased in HPL patients. Increased secretion of yeast or Candida albicans associated metabolites was because of their increased population. Hence, TCE treatment enhanced the growth of useful gut microbiota in hyperlipidemia patients.
The origin of COVID-19 pandemic, caused by SARS-CoV-2, was traced to Wuhan, China. Thereafter, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved into various variants owing to genome-wide mutations, causing emergence of multiple variants, including Variant of Interest and Variant of Concern. Here, we discuss genomic architecture of SARS-CoV-2, as well as its multiple variants- alpha, beta, gamma, and delta, along with their biological properties, such as transmissibility, reduction in antibody-mediated neutralization, virulence, disease severity, vaccine effectiveness, and the prevalence across the India vis-à-vis world. Our data on VOC, pooled from the Global Initiative on Sharing All Influenza Data up to 31 October 2021, shows around 89% prevalence of delta VOC across various Indian States. Whereas alpha, beta, and gamma variants show 10.44%, 0.57%, and 0.11% prevalence, respectively. Compared with global scale, the reported Indian prevalence of alpha, beta, gamma, and delta are 0.40%, 0.63%, 0.04%, and 1.7%, respectively. Furthermore, prevalent vaccines of various natures show significantly reduced effectiveness against these VOCs, necessitating urgent need for development of effective prophylactic vaccines and potential therapy to contain the pandemic.
In the dire need of novel inhibitors of enzymes, computational approaches have significantly expedited the drug discovery process. Aspartic protease enzymes of Plasmodium falciparum such as plasmepsin II (PfPlm II) and plasmepsin IV (PfPlm IV) have been recognized as an attractive drug target for antimalarial drug discovery. In line with this, we performed high-throughput screening of 316 novel compounds based on validated pharmacophore i.e., hydroxyethylamine (HEA) and piperazine against both PfPlm II and PfPlm IV. The obtained hit compound-protein complexes were subjected for molecular dynamics (MD) simulations at 200ns and found stable. Thermodynamic energy calculated for the complexes also supported compound’s stability within the binding pocket of plasmepsins. The results of our study strongly support an immediate validation of the virtually screened hits in biological systems.
Plants and their extracts have been extensively studied for their efficacy in therapeutic applications. Their Essential Oils (EOs) are responsible for the majority of biological properties such as anticancer, antibacterial and antimicrobial, antioxidant, anti-inflammatory, and cardio-protective. The utilization of natural compounds is gaining a lot of attention these days. These oils act as natural alternatives to the modern medical system to cure the illness that occurs in the biological system. This review provides an overview of the impact of the two most important plant-based oils: Mustard oil and Olive oil, the role of their components in different biological activities leading to their therapeutic applications. Their intake provides health benefits by controlling the symptoms of the diseases that involve cancer, bacterial infections, inflammation, cardiovascular, and some other common diseases. Most of the results come from in vitro and in vivo studies. However, their use in clinical studies is very little known.
COVID-19, a perilous disease caused by SARS-CoV-2, has brought a massive damage to humankind, and turned into a global catastrophe. It was first reported in Wuhan, China in December 2019 and since then has been a constant source of worry for the scientists and the medical world, due to the carnage it has caused globally. Extensive clinical studies are being carried to explore drug therapy and prophylaxis to combat this pestilence. It is still an excessively big challenge for the scientists and pharmacological industry to develop potential drugs for the treatment of this deadly virus. At present though no specific drug has been identified as a perfect cure for this zoonotic disease, medical practitioners are using the therapy of repurposing of drugs for the treatment. Systemic research was carried out through e-resources to identify drugs for the treatment of COVID-19. A recent proposal of 2-DG drug as a cure for COVID-19 has also been discussed in this review.
Tuberculosis is a leading cause of death from infectious diseases worldwide with more than 1.5 million deaths occurring annually. Males have been known to be more susceptible to tuberculosis than females. Sex hormones could be an important factor governing this gender bias. Here, we discuss the evidence that testosterone may be a crucial factor in male susceptibility to tuberculosis considering that testosterone impairs important factors which have a significant bearing on the outcome of tuberculosis. We also discuss possible underlying mechanisms through which testosterone modulates the immune response that is necessary for host resistance to tuberculosis. We discuss various models that have helped to uncover the role of testosterone in the outcome of infection by M. tuberculosis. Studying the role of testosterone on the various components that constitute the immune response to the disease have provided valuable insights into the sexual dichotomy observed in male bias in tuberculosis morbidity.
COVID-19, caused by the novel coronavirus SARS-CoV-2, has put most of the world under lockdown. Despite approved vaccines, COVID-19 cases, hospitalizations, and deaths have remained on the rise. Rapid diagnosis and necessary public health measures are still key parts to contain the pandemic. Here, the colorimetric isothermal nucleic acid amplification tests (iNAATs) for SARS-CoV-2 detection based on loop-mediated isothermal amplification (LAMP), cross-priming amplification (CPA), and polymerase spiral reaction (PSR) were designed and compared in performance for the first time. The findings showed that, for the detection of SARS-CoV-2 genomic-RNA, LAMP outperformed both CPA and PSR, exhibiting the limit of detection (LOD) of roughly 43.14 copies/reaction. The results can be read with the naked eye within 45 minutes, without cross-reactivity to closely related coronaviruses. The direct detection of SARS-CoV-2 RNA in simulated specimens by iNAATs was also successful. Additionally, the lyophilized reagents for LAMP reactions maintained the sensitivity and LOD of the liquid assays. The colorimetric LAMP assay was validated using clinical samples, showing 98.1% sensitivity and 100% specificity upon using extracted samples and 82.4% sensitivity and 86.2% specificity upon using unextracted specimens. The results indicate that the direct colorimetric LAMP assay developed is highly suitable for detecting SARS-CoV-2 at point-of-care.
Human reproductive system involve a number of intricate complex interconnected physiological metabolic pathways and metabolites with involvement of overall health of different body organs. Overall health alterations mediated physiological conditions such as obesity, diabetes etc. bring about additional variations in expression and presence of metabolic constituents including kinases, hormones, proteins, peptides. The detailed analysis of various molecules like endocrine hormones, neuropeptides, immunity and inflammation associated kinases and proteins that have an end effect in cells and tissues, and might be playing a role in impacting male reproduction have been deliberated here. A deliberative collection of obesity and infertility related molecules including endocrine hormones, cytokines, adipokines, adiponectin, resistin, visfatin, ghrelin, orexins, leptin, adropin, chemerin, along with diabetes and age related physiological impact analysis on male reproductive system have been included in this selective compilation. An in-depth understanding of changes and introduction of new intermediate molecules for regulation of physiological phenomena like energy homeostasis in obesity regulation and their interlinked associated impact on the male fertility potential would provide a reflection for possible development of new therapeutics.
Adipokines, mostly produced by white adipose tissues, have been established to be endocrine factors which are also essential in energy homeostasis. More recently, their contribution in fertility regulation has been recommended. Resistin as well as visfatin are unique adipocyte-derived signaling chemicals whose expressions enhance in advanced obesity and are implicated in insulin resistance as well as type-2 diabetes. They are also found to be immune modulators and may participate in aggravating inflammatory responses which may partly explain obesity-mediated systemic inflammation. They are yet much less explored adipokines with potential to regulate metabolic rate, immune homeostasis as well as fertility. These adipokines are shown to be expressed in the hypothalamus in an area in charge of energy balance. Evidence suggest that they can potentially affect the hypothalamo-pituitary-gonadal (HPG) axis thereby modulating reproductive functions. They are also found to be expressed highly by the testes. In rodents, resistin and visfatin may positively modulate Leydig cell number and steroidogenesis. Additionally, visfatin exists in the human spermatozoa and may play role in the sperm maturation. However, reports on the impact of resistin and visfatin on human male fertility are inconsistent. In this article, we review the available literature on the role resistin and visfatin on male reproduction and integrate the mechanisms to discuss if they act as sensor for body energy dyshomeostatis and modulate male reproductive functions as per the metabolic status.