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The protein, N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, is significantly decreased or absent in many types of cancer. There is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion, in different cancers. In contrast, the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation, growth, adhesion and migration of many types of cancer cells. The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells. We hypothesize that the delivery of the mRNA of the NDRG2 protein, encapsulated by lipid nanoparticles, could represent a potential treatment of metastatic and drug-resistant cancers. This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase, obtained from an in vitrotranscribed (IVT) mRNA. The IVT mRNA would be encapsulated in a lipid nanoformulation. The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive, nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells, would be treated with the nano- formulation and monitored for efficacy and adverse effects. If the appropriate preclinical studies indicate this formulation is efficacious and safe, it is possible it could be evaluated in clinical trials.
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The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak, which causes COVID-19, had a devastating impact on both people's lives and the global economy. During the course of the pandemic, the lack of specific drugs or treatments tailored for COVID-19 led to extensive repurposing of existing drugs in the pursuit of effective treatments. Some drug molecules demonstrated efficacy, while others proved ineffective. In this context, the approach of drug repurposing emerged as a novel strategy for combating COVID-19. Repurposed drugs and biologics have shown effectiveness, leading to improved clinical outcomes among patients with COVID-19. Similarly, It is equally important to assess the risk-benefit ratio associated with drugs and biologics adapted for COVID-19 treatment. Herein, we primarily focus on evaluating adverse drug events linked to repurposed COVID-19 medications, repurposed biologics, and COVID-specific drug molecules.
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Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state-of-the-art in cancer nanovaccine development, elucidating innovative strategies and technologies employed in their design. It explores both preclinical and clinical advancements, emphasizing key studies demonstrating their potential to elicit robust anti-tumor immune responses. The study encompasses various facets, including integrating biomaterial-based nanocarriers for antigen delivery, adjuvant selection, and the impact of nanoscale properties on vaccine performance. Detailed insights into the complex interplay between the tumor microenvironment and nanovaccine responses are provided, highlighting challenges and opportunities in optimizing therapeutic outcomes. Additionally, the study presents a thorough analysis of ongoing clinical trials, presenting a snapshot of the current clinical landscape. By curating the latest scientific findings and clinical developments, this study aims to serve as a comprehensive resource for researchers and clinicians engaged in advancing cancer immunotherapy. Integrating nanotechnology into vaccine design holds immense promise for revolutionizing cancer treatment paradigms, and this review provides a timely update on the evolving landscape of cancer nanovaccines.
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Traditionally known for managing blood sugar, GLP-1, a gut hormone, is emerging as a potential key to both lengthening lifespan and combating age-related ailments. While widely recognized for its role in blood sugar control, GLP-1 is increasingly recognized for its diverse effects on various biological pathways beyond glucose metabolism. Research across organisms and humans suggests that activating GLP-1 receptors significantly impacts cellular processes linked to aging. Its ability to boost mitochondrial function, enhance cellular stress resistance, and quell inflammation hints at its wider influence on aging mechanisms. This intricate interplay between GLP-1 and longevity appears to act through multiple pathways. One key effect is its ability to modulate insulin sensitivity, potentially curbing age-related metabolic issues like type 2 diabetes. Its neuroprotective properties also make it a promising candidate for addressing age-related cognitive decline and neurodegenerative diseases. Furthermore, preclinical studies using GLP-1 analogs or agonists have shown promising results in extending lifespan and improving healthspan in various model organisms. These findings provide a compelling rationale for exploring GLP-1-based interventions in humans to extend healthy aging. However, despite the exciting therapeutic prospects of GLP-1 in promoting longevity, challenges remain. Determining optimal dosages, establishing long-term safety profiles, and investigating potential adverse effects require comprehensive clinical investigations before we can confidently translate these findings to humans. This article emphasises the wide applicability of GLP-1.
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Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Longevidade , Humanos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Animais , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Envelhecimento/fisiologia , Resistência à Insulina/fisiologia , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
INTRODUCTION: The emergence of SARS-CoV-2 triggered a global health emergency, causing > 7 million deaths thus far. Limited early knowledge spurred swift research, treatment, and vaccine developments. Implementation of public health measures such as, lockdowns and social distancing, disrupted economies and strained healthcare. Viral mutations highlighted the need for flexible strategies and strong public health infrastructure, with global collaboration crucial for pandemic control. AREAS COVERED: (i) Revisiting diagnostic strategies, (ii) adapting to the evolving challenge of the virus, (iii) vaccines against new variants, (iv) vaccine hesitancy in the light of the evolving disease, (v) treatment strategies, (vi) hospital preparedness for changing clinical needs, (vii) global cooperation and data sharing, (viii) economic implications, and (ix) education and awareness- keeping communities informed. EXPERT OPINION: The COVID-19 crisis forced unprecedented adaptation, emphasizing public health readiness, global unity, and scientific advancement. Key lessons highlight the importance of adaptability and resilience against uncertainties. As the pandemic evolves into a 'new normal,' ongoing vigilance, improved understanding, and available vaccines and treatments equip us for future challenges. Priorities now include proactive pandemic strategies, early warnings, supported healthcare, public education, and addressing societal disparities for better health resilience and sustainability.
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Vacinas contra COVID-19 , COVID-19 , Saúde Global , Saúde Pública , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Desenvolvimento de Vacinas , Pandemias/prevenção & controleRESUMO
Phytoestrogens, also known as xenoestrogens, are secondary metabolites derived from plants that have similar structures and biological effects as human estrogens. These compounds do not directly affect biological functions but can act as agonists or antagonists depending on the level of endogenous estrogen in the body. Phytoestrogens may have an epigenetic mechanism of action independent of estrogen receptors. These compounds are found in more than 300 plant species and are synthesized through the phenylpropanoid pathway, with specific enzymes leading to various chemical structures. Phytoestrogens, primarily phenolic compounds, include isoflavonoids, flavonoids, stilbenes, and lignans. Extensive research in animals and humans has demonstrated the protective effects of phytoestrogens on estrogen-dependent diseases. Clinical trials have also shown their potential benefits in conditions such as osteoporosis, Parkinson's disease, and certain types of cancer. This review provides a concise overview of phytoestrogen classification, chemical diversity, and biosynthesis and discusses the potential therapeutic effects of phytoestrogens, as well as their preclinical and clinical development.
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Fitoestrógenos , Fitoestrógenos/farmacologia , Fitoestrógenos/química , Humanos , Animais , Osteoporose/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/química , Neoplasias/tratamento farmacológico , Isoflavonas/farmacologia , Isoflavonas/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Aromatherapy, a holistic healing practice utilizing the aromatic essences of plant-derived essential oils, has gained significant attention for its therapeutic potential in promoting overall well-being. Use of phytoconstituent based essential oil has played a significant role in the evolving therapeutic avenue of aromatherapy as a complementary system of medicine. AIM OF THE STUDY: This comprehensive review article aims to explore the usage of essential oils for aromatherapy, shedding light on their diverse applications, scientific evidence, and safety considerations. Furthermore, the growing interest in using essential oils as complementary therapies in conjunction with conventional medicine is explored, underscoring the significance of collaborative healthcare approaches. MATERIALS AND METHODS: Literature search was performed from databases like PubMed, ScienceDirect, Scopus, and Bentham using keywords like Aromatherapy, Aromatic Plants, Essential oils, Phytotherapy, and complementary medicine. The keywords were used to identify literature with therapeutic and mechanistic details of herbal agents with desired action. RESULTS: The integration of traditional knowledge with modern scientific research has led to a renewed interest in essential oils as valuable tools in contemporary healthcare. Various extraction methods used to obtain essential oils are presented, emphasizing their impact on the oil's chemical composition and therapeutic properties. Additionally, the article scrutinizes the factors influencing the quality and purity of essential oils, elucidating the significance of standardization and certification for safe usage. A comprehensive assessment of the therapeutic effects of essential oils is provided, encompassing their potential as antimicrobial, analgesic, anxiolytic, and anti-inflammatory agents, among others. Clinical trials and preclinical studies are discussed to consolidate the existing evidence on their efficacy in treating diverse health conditions, both physical and psychological. Safety considerations are of paramount importance when employing essential oils, and this review addresses potential adverse effects, contraindications, and best practices to ensure responsible usage. CONCLUSIONS: This comprehensive review provides valuable insights into the exploration of essential oils for aromatherapy, emphasizing their potential as natural and potent remedies for a wide range of ailments. By amalgamating traditional wisdom and modern research, this article aims to encourage further investigation into the therapeutic benefits of essential oils while advocating for their responsible and evidence-based incorporation into healthcare practices.
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Aromaterapia , Óleos Voláteis , Óleos Voláteis/uso terapêutico , Aromaterapia/métodos , Humanos , AnimaisRESUMO
BACKGROUND: Propolis is a resinous compound that is obtained from honey bees. It consists of numerous chemical constituents that impart different therapeutic action. The heart is the core of the body and cardiovascular disease (CVD) is a burden for the human being. This article emphasizes how propolis is fruitful in the management of various CVDs. SCOPE AND APPROACH: This review focuses on how various constituents of the propolis (such as terpenes, flavonoids, phenolics, etc.) impart cardio protective actions. KEY FINDING AND CONCLUSION: With the support of various clinical trials and research outcomes, it was concluded that propolis owns niche cardio protective properties that can be a boon for various cardiac problems (both in preventive and therapeutic action) such as atherosclerosis, excessive angiogenesis, hypertension, and many more.
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Doenças Cardiovasculares , Própole , Animais , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Flavonoides/uso terapêutico , Flavonoides/química , Flavonoides/farmacologia , Própole/química , Própole/uso terapêuticoRESUMO
INTRODUCTION: The escalating prevalence of infectious diseases is an important cause of concern in society. Particularly in several developing countries, infectious diarrhea poses a major problem, with a high fatality rate, especially among young children. The condition is divided into four classes, namely, acute diarrhea, invasive diarrhea, acute bloody diarrhea, and chronic diarrhea. Various pathogenic agents, such as bacteria, viruses, protozoans, and helminths, contribute to the onset of this condition. AREAS COVERED: The review discusses the scenario of infectious diarrhea, the prevalent types, as well as approaches to management including preventive, therapeutic, and vaccination strategies. The vaccination techniques are extensively discussed including the available vaccines, their advantages as well as limitations. EXPERT OPINION: There are several approaches available to develop new-improved vaccines. In addition, route of immunization is important and aerosols/nasal sprays, oral route, skin patches, powders, and liquid jets to minimize needles can be used. Plant-based vaccines, such as rice, might save packing and refrigeration costs by being long-lasting, non-refrigerable, and immunogenic. Future research should utilize predetermined PCR testing intervals and symptom monitoring to identify persistent pathogens after therapy and symptom remission.
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Diarreia , Vacinas , Criança , Humanos , Pré-Escolar , Diarreia/prevenção & controle , Diarreia/epidemiologia , Vacinação , Imunização , Custos e Análise de CustoRESUMO
Pancreatic cancer, particularly pancreatic ductal adenocarcinoma, remains a devastating disease with a dismal prognosis and limited survival rates. Despite various drug treatments and regimens showing promise in managing the disease, the clinical outcomes have not significantly improved. Immunotherapy however, has become a forefront area in pancreatic cancer treatment. This approach comprises a range of agents, including small molecule drugs, antibodies, combination therapies, and vaccines. In the last 5-8 years, there has been an upsurge of research into the use of monoclonal antibodies to block receptors on cancer or immune cells, revolutionising cancer treatment and management. Several targets have been identified and studied, with the most encouraging noted in relation to checkpoint markers, namely, antibodies targeting anti-programmed cell death 1 (PD-1) and its receptor PD-L1. Herein, we present the clinical developments in immunotherapy in the last 5 years especially those which have been tested in humans against pancreatic cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Anticorpos Monoclonais/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Terapia Combinada , ImunoterapiaRESUMO
The emergence of COVID-19 has posed an unprecedented global health crisis, challenging the healthcare systems worldwide. Amidst the rapid development of several vaccine formulations, protein subunit vaccines have emerged as a promising approach. This article provides an in-depth evaluation of the role of protein subunit vaccines in the management of COVID-19. Leveraging viral protein fragments, particularly the spike protein from SARS-CoV-2, these vaccines elicit a targeted immune response without the risk of inducing disease. Notably, the robust safety profile of protein subunit vaccines makes them a compelling candidate in the management of COVID-19. Various innovative approaches, including reverse vaccinology, virus like particles, and recombinant modifications are incorporated to develop protein subunit vaccines. In addition, the utilization of advanced manufacturing techniques facilitates large-scale production, ensuring widespread distribution. Despite these advancements, challenges persist, such as the requirement for cold-chain storage and the necessity for booster doses. This article evaluates the formulation and applications of protein subunit vaccines, providing a comprehensive overview of their clinical development and approvals in the context of COVID-19. By addressing the current status and challenges, this review aims to contribute to the ongoing discourse on optimizing protein subunit vaccines for effective pandemic control.
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COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinas de Subunidades Proteicas , Criopreservação , PandemiasRESUMO
Nanoemulsions consist of a combination of several components such as oil, water, emulsifiers, surfactants and cosurfactants. Various techniques for producing nanoemulsions include high-energy and low-energy approaches such as high-pressure homogenization, microfluidization, jet disperser and phase inversion methods. The properties of a formulation can be influenced by elements such as the composition, concentration, size and charge of droplets, which in turn can affect the technique of manufacture. Characterization is conducted by the assessment of several factors such as physical properties, pH analysis, viscosity measurement and refractive index determination. This article offers a thorough examination of the latest developments in nanoemulsion technology, with a focus on their wide-ranging applications and promising future possibilities. It also discusses the administration of nanoemulsions through several methods.
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Diabetes is a widespread epidemic that includes a number of comorbid conditions that greatly increase the chance of acquiring other chronic illnesses. Every year, there are significantly more people with diabetes because of the rise in type-2 diabetes prevalence. The primary causes of illness and mortality worldwide are, among these, hyperglycemia and its comorbidities. There has been a lot of interest in the creation of peptide-based hydrogels as a potentially effective platform for the treatment of diabetes and its consequences. Here, we emphasize the use of self-assembled hydrogel formulations and their unique potential for the treatment/management of type-2 diabetes and its consequences. (i.e., wounds). Key aspects covered include the characteristics of self-assembled peptide hydrogels, methods for their preparation, and their pre-clinical and clinical applications in addressing metabolic disorders such as type-2 diabetes.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Humanos , Cicatrização , Hidrogéis/uso terapêutico , Peptídeos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológicoRESUMO
Cancer diagnoses have been increasing worldwide, and solid tumors are among the leading contributors to patient mortality, creating an enormous burden on the global healthcare system. Cancer is responsible for around 10.3 million deaths worldwide. Solid tumors are one of the most prevalent cancers observed in recent times. On the other hand, early diagnosis is a significant challenge that could save a person's life. Treatment with existing methods has pitfalls that limit the successful elimination of the disorder. Though nanoparticle-based imaging and therapeutics have shown a significant impact in healthcare, current methodologies for solid tumor treatment are insufficient. There are multiple complications associated with the diagnosis and management of solid tumors as well. Recently, surface-conjugated nanoparticles such as lipid nanoparticles, metallic nanoparticles, and quantum dots have shown positive results in solid tumor diagnostics and therapeutics in preclinical models. Other nanotheranostic material platforms such as plasmonic theranostics, magnetotheranostics, hybrid nanotheranostics, and graphene theranostics have also been explored. These nanoparticle theranostics ensure the appropriate targeting of tumors along with selective delivery of cargos (both imaging and therapeutic probes) without affecting the surrounding healthy tissues. Though they have multiple applications, nanoparticles still possess numerous limitations that need to be addressed in order to be fully utilized in the clinic. In this review, we outline the importance of materials and design strategies used to engineer nanoparticles in the treatment and diagnosis of solid tumors and how effectively each method overcomes the drawbacks of the current techniques. We also highlight the gaps in each material platform and how design considerations can address their limitations in future research directions.
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Liquid crystal (LC)-based nanoformulations may efficiently deliver drugs and therapeutics to targeted biological sites. Lyotropic liquid crystalline phases (LLCPs) have received much interest in recent years due to their unique structural characteristics of both isotropic liquids and crystalline solids. These LLCPs can be utilized as promising drug delivery systems to deliver drugs, proteins, peptides and vaccines because of their improved drug loading, stabilization, and controlled drug release. The effects of molecule shape, microsegregation, and chirality are very important in the formation of liquid crystalline phases (LCPs). Homogenization of self-assembled amphiphilic lipids, water and stabilizers produces LLCPs with different types of mesophases, bicontinuous cubic (cubosomes) and inverse hexagonal (hexosomes). Moreover, many studies have also shown higher bioadhesivity and biocompatibility of LCs due to their structural resemblance to biological membranes, thus making them more efficient for targeted drug delivery. In this review, an outline of the engineering aspects of LLCPs and polymer-based LLCPs is summarized. Moreover, it covers parenteral, oral, transdermal delivery and medical imaging of LC in targeting various tissues and is discussed with a scope to design more efficient next-generation novel nanosystems. In addition, a detailed overview of advanced liquid crystal-based drug delivery for vaccines and biomedical applications is reviewed.