Phytoestrogens: Chemistry, potential health benefits, and their medicinal importance.

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.

CAR T-Cell therapy for the management of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma (NHL) of mature B-cells characterized by translocation, which is typically due to excess expression of Cyclin D1. Although with the progress in our knowledge of the causes for MCL and available treatments for MCL, this cancer is still incurable. Age, male gender, rapid advancement, significant nodal involvement, elevated serum lactate dehydrogenase level, and prognostic indications including increased expression of Ki-67 and presence of TP53 mutation, are symbols of poor outcome. Advanced immunotherapy using chimeric antigen receptor (CAR)-T cells is advantageous for patients suffering from B-cell malignancies and MCL. Targeting B-cell antigens on the cell surface is a feasible approach in re-occurring (R/R) MCL because of significant responses obtained in other B-cell cancers. USFDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19), a novel CAR T-cell therapy to be used in patients with MCL who have not responded to previous treatments or have relapsed. The FDA approved this new treatment depending on the outcomes of the ZUMA-2 clinical trial. Serious adverse reactions, moderate anti-tumor activity, allergen withdrawal, antigen escape, limited tumor infiltration, and trafficking are major barriers to successful CAR T-cell therapy. This review is a brief synopsis of the development of CAR T-cell therapy for MCL.

Rosacea Topical Treatment and Care: From Traditional to New Drug Delivery Systems.

Rosacea is a multifactorial chronic inflammatory dermatosis characterized by flushing, nontransient erythema, papules and pustules, telangiectasia, and phymatous alterations accompanied by itching, burning, or stinging, the pathophysiology of which is not yet fully understood. Conventional topical treatments usually show limited efficacy due to the physical barrier property of the skin that hinders skin penetration of the active ingredients, thereby hampering proper drug skin delivery and the respective therapeutic or cosmetic effects. New advances regarding the physiopathological understanding of the disease and the underlying mechanisms suggest the potential of new active ingredients as promising therapeutic and cosmetic approaches to this dermatosis. Additionally, the development of new drug delivery systems for skin delivery, particularly the potential of nanoparticles for the topical treatment and care of rosacea, has been described. Emphasis has been placed on their reduced nanometric size, which contributes to a significant improvement in the attainment of targeted skin drug delivery. In addition to the exposition of the known pathophysiology, epidemiology, diagnosis, and preventive measures, this Review covers the topical approaches used in the control of rosacea, including skin care, cosmetics, and topical therapies, as well as the future perspectives on these strategies.

Antibody-Biopolymer Conjugates in Oncology: A Review.

Cancer is one of the most prevalent diseases and affects a large proportion of the population worldwide. Conventional treatments in the management include chemotherapy, radiotherapy, and surgery. Although being well-accepted, they have many lacunas in the form of severe side effect resulting from lack of targeted delivery. Antibody biopolymer conjugates are a novel method which is an add-on to older methods of immunization. It is used in various diseases and disorders. It ensures the targeted delivery of molecules to increase its efficacy and reduce unwanted effects of the molecule/drug to normal cells. It shows miraculous results in the treatment and management of several cancers even in advanced stages. Herein, we present the chemistry between biopolymer and antibody, their effects on cancer as well as the basic differences between antibody-drug conjugates and antibody-biopolymer conjugates.

Potential Anti-SARS-CoV-2 Prodrugs Activated by Phosphorylation and Their Role in the Aged Population.

The COVID-19 pandemic has flared across every part of the globe and affected populations from different age groups differently. People aged from 40 to 80 years or older are at an increased risk of morbidity and mortality due to COVID-19. Therefore, there is an urgent requirement to develop therapeutics to decrease the risk of the disease in the aged population. Over the last few years, several prodrugs have demonstrated significant anti-SARS-CoV-2 effects in in vitro assays, animal models, and medical practice. Prodrugs are used to enhance drug delivery by improving pharmacokinetic parameters, decreasing toxicity, and attaining site specificity. This article discusses recently explored prodrugs such as remdesivir, molnupiravir, favipiravir, and 2-deoxy-D-glucose (2-DG) and their implications in the aged population, as well as investigating recent clinical trials.

SARS-CoV-2 variants and vulnerability at the global level.

Numerous variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have evolved. Viral variants may evolve with harmful susceptibility to the immunity established with the existing COVID-19 vaccination. These variants are more transmissible, induce relatively extreme illness, have evasive immunological features, decrease neutralization using antibodies from vaccinated persons, and are more susceptible to re-infection. The Centers for Disease Control and Prevention (CDC) has categorized SARS-CoV-2 mutations as variants of interest (VOI), variants of concern (VOC), and variants of high consequence (VOHC). At the moment, four VOC and many variants of interest have been defined and require constant observation. This review article summarizes various variants of SARS-CoV-2 surfaced with special emphasis on VOCs that are spreading across the world, as well as several viral mutational impacts and how these modifications alter the properties of the virus.

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review.

The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a 'twincretin', is a 'first-in-class' and the only dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by more than 20% and improving lipid metabolism. This novel anti-diabetic drug is a synthetic peptide analog of the human GIP hormone with a C20 fatty-diacid portion attached which, via acylation technology, can bind to albumin in order to provide a dose of the drug, by means of subcutaneous injection, once a week, which is appropriate to its a half-life of about five days. Tirzepatide, developed by Eli Lilly, was approved, under the brand name Mounjaro, by the United States Food and Drug Administration in May 2022. This started the 'twincretin' era of enormously important and appealing dual therapeutic options for diabetes and obesity, as well as advanced management of closely related cardiometabolic settings, which constitute the leading cause of morbidity, disability, and mortality worldwide. Herein, we present the key characteristics of tirzepatide in terms of synthesis, structure, and activity, bearing in mind its advantages and shortcomings. Furthermore, we briefly trace the evolution of this kind of medical agent and discuss the development of clinical studies.

Peptide-Drug Conjugates: A New Hope for Cancer Management.

Cancer remains the leading cause of death worldwide despite advances in treatment options for patients. As such, safe and effective therapeutics are required. Short peptides provide advantages to be used in cancer management due to their unique properties, amazing versatility, and progress in biotechnology to overcome peptide limitations. Several appealing peptide-based therapeutic strategies have been developed. Here, we provide an overview of peptide conjugates, the better equivalents of antibody-drug conjugates, as the next generation of drugs for required precise targeting, enhanced cellular permeability, improved drug selectivity, and reduced toxicity for the efficient treatment of cancers. We discuss the basic components of drug conjugates and their release action, including the release of cytotoxins from the linker. We also present peptide-drug conjugates under different stages of clinical development as well as regulatory and other challenges.

A new era of immune therapeutics for pancreatic cancer: Monoclonal antibodies paving the way.

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.

How do we change our approach to COVID with the changing face of disease?

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.

Unlocking longevity with GLP-1: A key to turn back the clock?

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.

Self-assembled peptide hydrogels for the treatment of diabetes and associated complications.

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.

Unveiling the promise: Exosomes as game-changers in anti-infective therapy.

Extracellular vesicles (EVs)-based intercellular communication (through exosomes, microvesicles, and apoptotic bodies) is conserved across all kingdoms of life. In recent years, exosomes have gained much attention for targeted pharmaceutical administration due to their unique features, nanoscale size, and capacity to significantly contribute to cellular communication. As drug delivery vehicles, exosomes have several advantages over alternative nanoparticulate drug delivery technologies. A key advantage lies in their comparable makeup to the body's cells, which makes them non-immunogenic. However, exosomes vesicles face several challenges, including a lack of an effective and standard production technique, decreased drug loading capacity, limited characterization techniques, and underdeveloped isolation and purification procedures. Exosomes are well known for their long-term safety and natural ability to transport intercellular nucleic acids and medicinal compounds across the blood-brain-barrier (BBB). Therefore, in addition to revealing new insights into exosomes' distinctiveness, the growing availability of new analytical tools may drive the development of next-generation synthetic systems. Herein, light is shed on exosomes as drug delivery vehicles in anti-infective therapy by reviewing the literature on primary articles published between 2002 and 2023. Additionally, the benefits and limitations of employing exosomes as vehicles for therapeutic drug delivery are also discussed.

Propolis in the management of cardiovascular disease.

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.

Essential oils for clinical aromatherapy: A comprehensive review.

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.

Combatting infectious diarrhea: innovations in treatment and vaccination strategies.

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.

Plant-derived exosomes in therapeutic nanomedicine, paving the path toward precision medicine.

BACKGROUND: Plant-derived exosomes (PDEs), are nanoscale vesicles secreted by multivesicular bodies, play pivotal roles in critical biological processes, including gene regulation, cell communication, and immune defense against pathogens. Recognized for their potential health-promoting properties, PDEs are emerging as innovative components in functional nutrition, poised to enhance dietary health benefits. PURPOSE: To describe the efficacy of PDEs in nanoform and their application as precision therapy in many disorders. STUDY DESIGN: The design of this review was carried out in PICO format using randomized clinical trials and research articles based on in vivo and in vitro studies. METHODS: All the relevant clinical and research studies conducted on plant-derived nanovesicle application and efficacy were included, as retrieved from PubMed and Cochrane, after using specific search terms. This review was performed to determine PDEs' efficacy as nanomedicine and precision therapy. Sub-group analysis and primary data were included to determine the relationship with PDEs. RESULT: PDEs are extracted from plant materials using sophisticated techniques like precipitation, size exclusion, immunoaffinity capture, and ultracentrifugation, encapsulating vital molecules such as lipids, proteins, and predominantly microRNAs. Although their nutritional impact may be minimal in small quantities, the broader application of PDEs in biomedicine, particularly as vehicles for drug delivery, underscores their significance. They offer a promising strategy to improve the bioavailability and efficacy of therapeutic agents carrying nano-bioactive substances that exhibit anti-inflammatory, antioxidant, cardioprotective, and anti-cancer activities. CONCLUSION: PDEs enhance the therapeutic potency of plant-derived phytochemicals, supporting their use in disease prevention and therapy. This comprehensive review explores the multifaceted aspects of PDEs, including their isolation methods, biochemical composition, health implications, and potential to advance medical and nutritional interventions.

Nanoemulsions: Summary of a Decade of Research and Recent Advances.

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.

Protein subunit vaccines: Promising frontiers against COVID-19.

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.

Nanotheranostics-based Management of Head and Neck Cancer.

Head and neck cancer is affecting a large sort of population. Many treatments are available on a regular base, but they have their limitations. Diagnosis in the early stage is essential to cope with the disease which is a limitation in the majority of present diagnostic tools. Many of them are invasive methods that lead to patient discomfort. Interventional nanothernostics is an emerging field in the management of Head and Neck cancer. It facilitates both diagnostic and therapeutic approaches. It also helps with the overall management of the disease. This method allows the early and accurate detection of the disease which improvises the chances of recovery. Additionally, it makes sure that the medicine is delivered specifically to increase clinical outcomes and reduce side effects. The use of radiation in addition to the medicine supplied can produce a synergistic effect. It contains several nanoparticles, including silicon and gold nanoparticles. This review paper focuses on the shortcomings of existing therapeutic techniques and how nanotheranostics fills the void.