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.

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.

Lyotropic liquid crystalline phases: Drug delivery and biomedical applications.

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.

Conjugated Nanoparticles for Solid Tumor Theranostics: Unraveling the Interplay of Known and Unknown Factors.

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.

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.

Convalescent plasma (hyperimmune immunoglobulin) for COVID-19 management: An update.

The pandemic COVID-19 has spread widely throughout the globe and has been responsible for millions of deaths worldwide. Recently, it has been identified that there is no specific and 100% effective treatment available to manage the infection especially for the severe cases. A significant amount of research efforts and clinical trials have been undertaken globally and many more are underway to find the potential treatment option. Earlier, convalescent plasma or hyperimmune immunoglobulin was effectively used in the treatment of many endemic or epidemic viral infections as a part of passive immunization. In this article, we have touched upon the immunopathology of COVID-19 infection, a basic understanding of convalescent plasma, it's manufacturing as well as evaluation, and have reviewed the scientific developments focussing on the potential of convalescent plasma vis-à-vis other modalities for the management of COVID-19. The article also covers various research approaches, clinical trials conducted globally, and the clinical trials which are at various stages for exploring the efficacy and safety of the convalescent plasma therapy (CPT) to predict its future perspective to manage COVID-19.

Adenoviral Vector-Based Vaccine Platform for COVID-19: Current Status.

The coronavirus disease (COVID-19) breakout had an unimaginable worldwide effect in the 21st century, claiming millions of lives and putting a huge burden on the global economy. The potential developments in vaccine technologies following the determination of the genetic sequence of SARS-CoV-2 and the increasing global efforts to bring potential vaccines and therapeutics into the market for emergency use have provided a small bright spot to this tragic event. Several intriguing vaccine candidates have been developed using recombinant technology, genetic engineering, and other vaccine development technologies. In the last decade, a vast amount of the vaccine development process has diversified towards the usage of viral vector-based vaccines. The immune response elicited by such vaccines is comparatively higher than other approved vaccine candidates that require a booster dose to provide sufficient immune protection. The non-replicating adenoviral vectors are promising vaccine carriers for infectious diseases due to better yield, cGMP-friendly manufacturing processes, safety, better efficacy, manageable shipping, and storage procedures. As of April 2022, the WHO has approved a total of 10 vaccines around the world for COVID-19 (33 vaccines approved by at least one country), among which three candidates are adenoviral vector-based vaccines. This review sheds light on the developmental summary of all the adenoviral vector-based vaccines that are under emergency use authorization (EUA) or in the different stages of development for COVID-19 management.

Advanced Phytochemical-Based Nanocarrier Systems for the Treatment of Breast Cancer.

As the world's most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of treatment to eradicate invasive disease, the current chemotherapy regimen faces significant challenges associated with chemotherapy-induced side effects and the development of drug resistance. Therefore, serious concerns regarding current chemotherapeutics are pressuring researchers to develop alternative therapeutics with better efficacy and safety. Due to their extremely biocompatible nature and efficient destruction of cancer cells via numerous mechanisms, phytochemicals have emerged as one of the attractive alternative therapies for chemotherapeutics to treat breast cancer. Additionally, phytofabricated nanocarriers, whether used alone or in conjunction with other loaded phytotherapeutics or chemotherapeutics, showed promising results in treating breast cancer. In the current review, we emphasize the anticancer activity of phytochemical-instigated nanocarriers and phytochemical-loaded nanocarriers against breast cancer both in vitro and in vivo. Since diverse mechanisms are implicated in the anticancer activity of phytochemicals, a strong emphasis is placed on the anticancer pathways underlying their action. Furthermore, we discuss the selective targeted delivery of phytofabricated nanocarriers to cancer cells and consider research gaps, recent developments, and the druggability of phytoceuticals. Combining phytochemical and chemotherapeutic agents with nanotechnology might have far-reaching impacts in the future.

The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far.

The world has not yet completely overcome the fear of the havoc brought by SARS-CoV-2. The virus has undergone several mutations since its initial appearance in China in December 2019. Several variations (i.e., B.1.616.1 (Kappa variant), B.1.617.2 (Delta variant), B.1.617.3, and BA.2.75 (Omicron variant)) have emerged throughout the pandemic, altering the virus's capacity to spread, risk profile, and even symptoms. Humanity faces a serious threat as long as the virus keeps adapting and changing its fundamental function to evade the immune system. The Delta variant has two escape alterations, E484Q and L452R, as well as other mutations; the most notable of these is P681R, which is expected to boost infectivity, whereas the Omicron has about 60 mutations with certain deletions and insertions. The Delta variant is 40-60% more contagious in comparison to the Alpha variant. Additionally, the AY.1 lineage, also known as the "Delta plus" variant, surfaced as a result of a mutation in the Delta variant, which was one of the causes of the life-threatening second wave of coronavirus disease 2019 (COVID-19). Nevertheless, the recent Omicron variants represent a reminder that the COVID-19 epidemic is far from ending. The wave has sparked a fervor of investigation on why the variant initially appeared to propagate so much more rapidly than the other three variants of concerns (VOCs), whether it is more threatening in those other ways, and how its type of mutations, which induce minor changes in its proteins, can wreck trouble. This review sheds light on the pathogenicity, mutations, treatments, and impact on the vaccine efficacy of the Delta and Omicron variants of SARS-CoV-2.

Nanoparticle-Based Delivery Systems for Vaccines.

Vaccination is still the most cost-effective way to combat infectious illnesses. Conventional vaccinations may have low immunogenicity and, in most situations, only provide partial protection. A new class of nanoparticle-based vaccinations has shown considerable promise in addressing the majority of the shortcomings of traditional and subunit vaccines. This is due to recent breakthroughs in chemical and biological engineering, which allow for the exact regulation of nanoparticle size, shape, functionality, and surface characteristics, resulting in improved antigen presentation and robust immunogenicity. A blend of physicochemical, immunological, and toxicological experiments can be used to accurately characterize nanovaccines. This narrative review will provide an overview of the current scenario of the nanovaccine.

Variant influenza: connecting the missing dots.

BACKGROUND: In June 2009, the World Health Organization declared a new pandemic, the 2009 swine influenza pandemic (swine flu). The symptoms of the swine flu pandemic causing strain were comparable to most of the symptoms noted by seasonal influenza. AREA COVERED: Zoonotic viruses that caused the swine flu pandemic and its preventive measures. EXPERT OPINION: As per Centers for Disease Control and Prevention (CDC), the clinical manifestations in humans produced by the 2009 H1N1 'swine flu' virus were equivalent to the manifestations caused by related flu strains. The H1N1 vaccination was the most successful prophylactic measure since it prevented the virus from spreading and reduced the intensity and consequences of the pandemic. Despite the availability of therapeutics, the ongoing evolution and appearance of new strains have made it difficult to develop effective vaccines and therapies. Currently, the CDC recommends yearly flu immunization for those aged 6 months and above. The lessons learned from the A/2009/H1N1 pandemic in 2009 indicated that readiness of mankind toward new illnesses caused by mutant viral subtypes that leap from animals to people must be maintained.

Fast-track development of vaccines for SARS-CoV-2: The shots that saved the world.

In December 2019, an outbreak emerged of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which leads to coronavirus disease 2019 (COVID-19). The World Health Organisation announced the outbreak a global health emergency on 30 January 2020 and by 11 March 2020 it was declared a pandemic. The spread and severity of the outbreak took a heavy toll and overburdening of the global health system, particularly since there were no available drugs against SARS-CoV-2. With an immediate worldwide effort, communication, and sharing of data, large amounts of funding, researchers and pharmaceutical companies immediately fast-tracked vaccine development in order to prevent severe disease, hospitalizations and death. A number of vaccines were quickly approved for emergency use, and worldwide vaccination rollouts were immediately put in place. However, due to several individuals being hesitant to vaccinations and many poorer countries not having access to vaccines, multiple SARS-CoV-2 variants quickly emerged that were distinct from the original variant. Uncertainties related to the effectiveness of the various vaccines against the new variants as well as vaccine specific-side effects have remained a concern. Despite these uncertainties, fast-track vaccine approval, manufacturing at large scale, and the effective distribution of COVID-19 vaccines remain the topmost priorities around the world. Unprecedented efforts made by vaccine developers/researchers as well as healthcare staff, played a major role in distributing vaccine shots that provided protection and/or reduced disease severity, and deaths, even with the delta and omicron variants. Fortunately, even for those who become infected, vaccination appears to protect against major disease, hospitalisation, and fatality from COVID-19. Herein, we analyse ongoing vaccination studies and vaccine platforms that have saved many deaths from the pandemic.

Therapeutic drug repositioning with special emphasis on neurodegenerative diseases: Threats and issues.

Drug repositioning or repurposing is the process of discovering leading-edge indications for authorized or declined/abandoned molecules for use in different diseases. This approach revitalizes the traditional drug discovery method by revealing new therapeutic applications for existing drugs. There are numerous studies available that highlight the triumph of several drugs as repurposed therapeutics. For example, sildenafil to aspirin, thalidomide to adalimumab, and so on. Millions of people worldwide are affected by neurodegenerative diseases. According to a 2021 report, the Alzheimer's disease Association estimates that 6.2 million Americans are detected with Alzheimer's disease. By 2030, approximately 1.2 million people in the United States possibly acquire Parkinson's disease. Drugs that act on a single molecular target benefit people suffering from neurodegenerative diseases. Current pharmacological approaches, on the other hand, are constrained in their capacity to unquestionably alter the course of the disease and provide patients with inadequate and momentary benefits. Drug repositioning-based approaches appear to be very pertinent, expense- and time-reducing strategies for the enhancement of medicinal opportunities for such diseases in the current era. Kinase inhibitors, for example, which were developed for various oncology indications, demonstrated significant neuroprotective effects in neurodegenerative diseases. This review expounds on the classical and recent examples of drug repositioning at various stages of drug development, with a special focus on neurodegenerative disorders and the aspects of threats and issues viz. the regulatory, scientific, and economic aspects.

Vaccination efforts for Buruli ulcer.

BACKGROUND: Buruli ulcer is one of the most common mycobacterial diseases usually affecting poorer populations in tropical and subtropical environments. This disease, caused by M. ulcerans infection, has devastating effects for patients, with significant health and economic burden. Antibiotics are often used to treat affected individuals, but in most cases, surgery is necessary. AREA COVERED: We present progress on Buruli ulcer vaccines and identify knowledge gaps in this neglected tropical disease. EXPERT OPINION: The lack of appropriate infrastructure in endemic areas, as well as the severity of symptoms and lack of noninvasive treatment options, highlights the need for an effective vaccine to combat this disease. In terms of humoral immunity, it is vital to consider its significance and the magnitude to which it inhibits or slows down the progression of the disease. Only by answering these key questions will it be possible to tailor more appropriate vaccination and preventative provisions.

COVID-19 and vaccination: myths vs science.

INTRODUCTION: Several vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed since the inception of the coronavirus disease 2019 (COVID-19) in December 2019, at unprecedented speed. However, these rapidly developed vaccines raised many questions related to the efficacy and safety of vaccines in different communities across the globe. Various hypotheses regarding COVID-19 and its vaccines were generated, and many of them have also been answered with scientific evidence. Still, there are many myths/misinformation related to COVID-19 and its vaccines, which create hesitancy for COVID-19 vaccination, and must be addressed critically to achieve success in the battle against the pandemic. AREA COVERED: The development of anti-SARS-CoV-2 vaccines against COVID-19, their safety and efficacy, and myths/misinformation relating to COVID-19 and vaccines are presented. EXPERT OPINION: In this pandemic, we have seen a global collaborative effort of researchers, governments, and industry, supported by billions of dollars in funding, have allowed the development of vaccines far more quickly than in the past. Vaccines go through rigorous testing, analysis, and evaluations in clinical settings prior to their approval, even if they are approved for emergency use. Despite the myths, vaccination represents an important strategy to get back to normality.

An Ayurgenomics Approach: Prakriti-Based Drug Discovery and Development for Personalized Care.

Originating in ancient India, Ayurveda is an alternative medicinal approach that provides substantial evidence for a theoretical-level analysis of all aspects of life. Unlike modern medicine, Ayurveda is based upon tridoshas (Vata, pitta, and Kapha) and Prakriti. On the other hand, the research of all the genes involved at the proteomics, metabolomics, and transcriptome levels are referred to as genomics. Geoclimatic regions (deshanupatini), familial characteristics (kulanupatini), and ethnicity (jatiprasakta) have all been shown to affect phenotypic variability. The combination of genomics with Ayurveda known as ayurgenomics provided new insights into tridosha that may pave the way for precision medicine (personalized medicine). Through successful coordination of "omics," Prakriti-based treatments can help change the existing situation in health care. Prakriti refers to an individual's behavioral trait, which is established at the moment of birth and cannot be fully altered during one's existence. Ayurvedic methodologies are based on three Prakriti aspects: aushadhi (medication), vihara (lifestyle), and ahara (diet). A foundation of Prakriti-based medicine, preventative medicine, and improvement of life quality with longevity can be accomplished through these ayurvedic characteristics. In this perspective, we try to understand prakriti's use in personalized medicine, and how to integrate it with programs for drug development and discovery.

Replicating Viral Vector-Based Vaccines for COVID-19: Potential Avenue in Vaccination Arena.

The "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" is the third member of human coronavirus (CoV) that is held accountable for the current "coronavirus disease 2019 (COVID-19)" pandemic. In the past two decades, the world has witnessed the emergence of two other similar CoVs, namely SARS-CoV in 2002 and MERS-CoV in 2013. The extent of spread of these earlier versions was relatively low in comparison to SARS-CoV-2. Despite having numerous reports inclined towards the zoonotic origin of the virus, one cannot simply sideline the fact that no animal originated CoV is thus far identified that is considered similar to the initial edition of SARS-CoV-2; however, under-sampling of the diverse variety of coronaviruses remains a concern. Vaccines are proved to be an effective tool for bringing the end to such a devastating pandemic. Many vaccine platforms are explored for the same but in this review paper, we will discuss the potential of replicating viral vectors as vaccine carriers for SARS-CoV-2.

Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19.

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19.