Metal-based nanomaterials and nanocomposites as promising frontier in cancer chemotherapy.

Cancer is a disease associated with complex pathology and one of the most prevalent and leading reasons for mortality in the world. Current chemotherapy has challenges with cytotoxicity, selectivity, multidrug resistance, and the formation of stemlike cells. Nanomaterials (NMs) have unique properties that make them useful for various diagnostic and therapeutic purposes in cancer research. NMs can be engineered to target cancer cells for early detection and can deliver drugs directly to cancer cells, reducing side effects and improving treatment efficacy. Several of NMs can also be used for photothermal therapy to destroy cancer cells or enhance immune response to cancer by delivering immune-stimulating molecules to immune cells or modulating the tumor microenvironment. NMs are being modified to overcome issues, such as toxicity, lack of selectivity, increase drug capacity, and bioavailability, for a wide spectrum of cancer therapies. To improve targeted drug delivery using nano-carriers, noteworthy research is required. Several metal-based NMs have been studied with the expectation of finding a cure for cancer treatment. In this review, the current development and the potential of plant and metal-based NMs with their effects on size and shape have been discussed along with their more effective usage in cancer diagnosis and treatment.

Recent Trends in Rationally Designed Molecules as Kinase Inhibitors.

Protein kinases modulate the structure and function of proteins by adding phosphate groups to threonine, tyrosine, and serine residues. The phosphorylation process mediated by the kinases regulates several physiological processes, while their overexpression results in the development of chronic diseases, including cancer. Targeting of receptor tyrosine kinase pathways results in the inhibition of angiogenesis and cell proliferation that validates kinases as a key target in the management of aggressive cancers. As such, the identification of protein kinase inhibitors revolutionized the contemporary anticancer therapy by inducing a paradigm shift in the management of disease pathogenesis. Contemporary drug design programs focus on a broad range of kinase targets for the development of novel pharmacophores to manage the overexpression of kinases and their pathophysiology in cancer pathogenesis. In this review, we present the emerging trends in the development of rationally designed molecular inhibitors of kinases over the last five years (2016-2021) and their incipient role in the development of impending anticancer pharmaceuticals.

Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

Molecular aspects of Omicron, vaccine development, and recombinant strain XE: A review.

The global pandemic of COVID-19 began in December 2019 and is still continuing. The past 2 years have seen the emergence of several variants that were more vicious than each other. The emergence of Omicron (B.1.1.529) proved to be a huge epidemiological concern as the rate of infection of this particular strain was enormous. The strain was identified in South Africa on November 24, 2021 and was classified as a "Variant of Concern" on November 26, 2021. The Omicron variant possessed mutations in the key RBD region, the S region, thereby increasing the affinity of ACE2 for better transmission of the virus. Antibody resistance was found in this variant and it was able to reduce vaccine efficiency of vaccines. The need for a booster vaccine was brought forth due to the prevalence of the Omicron variant and, subsequently, this led to targeted research and development of variant-specific vaccines and booster dosage. This review discusses broadly the genomic characters and features of Omicron along with its specific mutations, evolution, antibody resistance, and evasion, utilization of CRISPR-Cas12a assay for Omicron detection, T-cell immunity elicited by vaccines against Omicron, and strategies to decrease Omicron infection along with COVID-19 and it also discusses on XE recombinant variant and on infectivity of BA.2 subvariant of Omicron.

Managing Apoptosis in Lung Diseases using Nano-assisted Drug Delivery System.

Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer.

Genetic associated complications of type 2 diabetes mellitus.

According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with diabetes mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DM complications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, diabetic foot ulcer (DFU) and Alzheimer's disease (AD). According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are adiponectin gene (ACRP30) and apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and mitochondria superoxide dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, janus kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with monocyte chemoattractant protein-1 (MCP-1) and insulin-like growth factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. DFU is manifested by slowing in re-epithelialization of keratinocyte, persistence wound inflammation and healing impairment. Re-epithelialization disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T2DM and AD. The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.

The viral capsid as novel nanomaterials for drug delivery.

The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging.

Perfluorocarbons Therapeutics in Modern Cancer Nanotechnology for Hypoxiainduced Anti-tumor Therapy.

With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.

An Appraisal of the Current Scenario in Vaccine Research for COVID-19.

The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2.

Interleukin-13: A pivotal target against influenza-induced exacerbation of chronic lung diseases.

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.

Targeting LIN28: a new hope in prostate cancer theranostics.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

Overview of key molecular and pharmacological targets for diabetes and associated diseases.

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.

An overview of vaccine development for COVID-19.

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.

Hypoxia-Inducible Factor (HIF): Fuel for Cancer Progression.

Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1ß (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.

Pharmaceutical Aspects of Green Synthesized Silver Nanoparticles: A Boon to Cancer Treatment.

BACKGROUND: Silver nanoparticles (AgNPs) are among the most investigated nanostructures in recent years, which exhibit more challenging and promising qualities in different biomedical applications. The AgNPs synthesized by the green approach provide potential healthcare benefits over chemical approaches, including improvement of tissue restoration, drug delivery, diagnosis, being environmentally friendly, and a boon to cancer treatment. OBJECTIVE: In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians. METHODS: Google, Web of Science, and PubMed portals have been searched for potentially relevant literature to get the latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications, especially in the treatment of different types of cancers. RESULTS: The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment-friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues. CONCLUSION: With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs need greater attention as unanticipated toxic effects must be ruled out for their diversified applications.

Targeting Cancer using Curcumin Encapsulated Vesicular Drug Delivery Systems.

Curcumin is a major curcuminoid present in turmeric. The compound is attributed to various therapeutic properties, which include anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcumin has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as nanoparticle-based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary of nanoparticle-based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as for biotechnology, nutraceutical, and functional food industries.

Nanosuspensions - An Update on Recent Patents, Methods of Preparation, and Evaluation Parameters.

BACKGROUND: Nanosuspensions are colloidal systems consisting of pure drug and stabilizers, without matrix or lyophilized into a solid matrix. Nanosuspensions improve the solubility of the drug both in the aqueous and organic phases. Nanosuspensions are also known as brick dust molecules, as they increase the dissolution of a system and improve absorption. METHODS: Extensive information related to nanosuspensions and its associated patents were collected using Pub Med and Google Scholar. RESULTS: Over the last decade nanosuspensions have attracted tremendous interest in pharmaceutical research. It provides unique features including, improved solubility, high drug loading capacity, and passive targeting. These particles are cost-effective, simple, and have lesser side effects with minimal dose requirements. However, the stability of nanosuspensions still warrants attention. CONCLUSION: Nanosuspensions play a vital role in handling the numerous drug entities with difficult physico-chemical characteristics such as solubility and can further aid with a range of routes that include nasal, transdermal, ocular, parenteral, pulmonary etc. This review highlights the relevance of nanosuspensions in achieving safe, effective and targeted drug delivery.