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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.
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COVID-19 , COVID-19/prevención & control , Humanos , Pandemias , SARS-CoV-2/genética , Desarrollo de VacunasRESUMEN
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.
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Antibacterianos , Esteroides , Corticoesteroides/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinflamatorios , Citocinas , Esteroides/uso terapéuticoRESUMEN
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.
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Terapia Molecular Dirigida , Medicina de Precisión , Neoplasias de la Próstata/terapia , Proteínas de Unión al ARN/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.
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Alérgenos/inmunología , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Asma/genética , Asma/inmunología , Sistemas de Liberación de Medicamentos , Humanos , Cumplimiento de la Medicación , MicroARNs/genéticaRESUMEN
The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and ß and three distinct subtypes of ß receptor: ß1-, ß2-, and ß3-adrenoceptors. The ß adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi ßγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.
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Insuficiencia Cardíaca/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Insuficiencia Cardíaca/complicaciones , Fosforilación , Transducción de SeñalRESUMEN
Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
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Sistemas de Liberación de Medicamentos , Neutrófilos/metabolismo , Enfermedades Respiratorias/tratamiento farmacológico , Animales , Enfermedad Crónica , Humanos , Sistema Inmunológico/inmunología , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Neutrófilos/inmunología , Estrés Oxidativo/efectos de los fármacos , Enfermedades Respiratorias/inmunología , Enfermedades Respiratorias/fisiopatologíaRESUMEN
Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients.
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Inflamación/metabolismo , Inflamación/patología , Enfermedades Respiratorias/metabolismo , Enfermedades Respiratorias/patología , Transducción de Señal/fisiología , Animales , Enfermedad Crónica , HumanosAsunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/metabolismo , Humanos , Neumonía Viral/epidemiología , Neumonía Viral/metabolismo , Factores de Riesgo , SARS-CoV-2RESUMEN
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.
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Neoplasias , Humanos , Neoplasias/patología , Proteínas Tirosina Quinasas Receptoras , Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , FosforilaciónRESUMEN
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.
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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 T
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Pie Diabético , Nefropatías Diabéticas , Neuropatías Diabéticas , Retinopatía Diabética , Adulto , Enfermedades Cardiovasculares/complicaciones , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Pie Diabético/complicaciones , Pie Diabético/diagnóstico , Pie Diabético/genética , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/genética , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inflamación , Interleucina-6/genética , Canal de Sodio Activado por Voltaje NAV1.7/genética , Polimorfismo de Nucleótido SimpleRESUMEN
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.
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Neoplasias Pulmonares , Nanopartículas , Humanos , Nanopartículas/uso terapéutico , Sistema de Administración de Fármacos con Nanopartículas , Sistemas de Liberación de Medicamentos/métodos , Nanotecnología , Apoptosis , Neoplasias Pulmonares/tratamiento farmacológico , Portadores de FármacosRESUMEN
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.
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Antineoplásicos/farmacología , Tecnología Química Verde , Nanopartículas del Metal/química , Neoplasias/tratamiento farmacológico , Plata/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/patología , Plata/químicaRESUMEN
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.
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Curcumina , Neoplasias , Curcumina/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Liposomas/uso terapéutico , Neoplasias/tratamiento farmacológico , SolubilidadRESUMEN
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.
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Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/virología , Humanos , Inmunidad , Inmunidad Colectiva , SARS-CoV-2/aislamiento & purificación , VacunaciónRESUMEN
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.
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Gripe Humana/inmunología , Interleucina-13/inmunología , Enfermedades Pulmonares/inmunología , Enfermedad Crónica , Humanos , Inflamación/inmunología , Inflamación/patología , Gripe Humana/patología , Enfermedades Pulmonares/patología , Moco/inmunologíaRESUMEN
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.