PHYTOCHEMICAL EVALUATION AND PHARMACOLOGICAL ACTIVITY OF SYZYGIUM AROMATICUM: A COMPREHENSIVE REVIEW

Medicinal plants are generating an ever-increasing amount of interest due to the effectiveness, low cost and minimal side-effects associated with drugs derived from them. Clove (Syzygium aromaticum (L.) (Family Myrtaceae) is one of the most important herbs in traditional medicine, having a wide spectrum of biological activity. Phytoconstituents of clove comprise of various classes and groups of chemical compounds such as monoterpenes, sesquiterpenes, phenolics and hydrocarbon compounds. The major phytochemicals found in clove oil is mainly eugenol (70-85%) followed by eugenyl acetate (15%) and β-caryophyllene (5–12%). Their derivatives result in biological benefits such as antibacterial, antifungal, insecticidal, antioxidant, anticarcinogenic capacities. In addition to clove oil's worldwide use as a food flavoring agent, it has also been employed for centuries as a topical analgesic in dentistry. This review presents an overview and details of the phytochemical and pharmacological investigations on the S. aromaticum

A Comprehensive Overview Of Biological Aspects Of Plasmodium Knowlesi

Plasmodium knowlesi, originally known to cause simian malaria, is now recognized as the fifth human malarial parasite; in addition to P. vivax, P.alciparum, P. malariae & P. ovale. It is predominant in South East (SE) Asian Countries like Malaysia, Indonesia, Thailand, Cambodia, Vietnam, Myanmar, Singapore, Brunei, and Philippines. However, until recently, its prevalence was miniscule in India. A recent report from Andaman and Nicobar Islands, India, revealed presence of P. knowlesi-specific gene sequences in 53 out of 445 cases scanned for malarial parasites. The life cycle of the parasite, like its other counterparts, requires infection of both a mosquito and a warm-blooded host. The present review provides a detailed overview of the parasite, its life cycle, prevalence and its comparisons with other Plasmodium species. In addition, a comparison is drawn at the genomic and genetic level to provide an in-depth understanding of the parasite’s unique characteristics. The cyto-adhering properties and antigenic variants of Plasmodium knowlesi are also discussed

Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk

The APOE4 allele of apolipoprotein E (apoE) is the greatest genetic risk factor for Alzheimer\u27s disease (AD) compared to APOE2 and APOE3. Amyloid-β (Aβ), particularly in a soluble oligomeric form (oAβ), is considered a proximal cause of neurodegeneration in AD. Emerging data indicate that levels of soluble oAβ are increased with APOE4, providing a potential mechanism of APOE4-induced AD risk. However, the pathway(s) by which apoE4 may increase oAβ levels are unclear and the subject of continued inquiry. In this editorial review, we present the hypothesis that apoE isoform-specific interactions with Aβ, namely apoE/Aβ complex, modulate Aβ levels. Specifically, we propose that compared to apoE3, apoE4-containing lipoproteins are less lipidated, leading to less stable apoE4/Aβ complexes, resulting in reduced apoE4/Aβ levels and increased accumulation, particularly of oAβ. Evidence that support or counter this argument, as well as the therapeutic significance of this pathway to neurodegeneration, are discussed

Soluble apoE/Aβ Complex: Mechanism and Therapeutic target for APOE4-induced AD Risk

The APOE4 allele of apolipoprotein E (apoE) is the greatest genetic risk factor for Alzheimer\u27s disease (AD) compared to APOE2 and APOE3. Amyloid-β (Aβ), particularly in a soluble oligomeric form (oAβ), is considered a proximal cause of neurodegeneration in AD. Emerging data indicate that levels of soluble oAβ are increased with APOE4, providing a potential mechanism of APOE4-induced AD risk. However, the pathway(s) by which apoE4 may increase oAβ levels are unclear and the subject of continued inquiry. In this editorial review, we present the hypothesis that apoE isoform-specific interactions with Aβ, namely apoE/Aβ complex, modulate Aβ levels. Specifically, we propose that compared to apoE3, apoE4-containing lipoproteins are less lipidated, leading to less stable apoE4/Aβ complexes, resulting in reduced apoE4/Aβ levels and increased accumulation, particularly of oAβ. Evidence that support or counter this argument, as well as the therapeutic significance of this pathway to neurodegeneration, are discussed

Biologics and Vaccines for Nasal and Pulmonary Drug Delivery

Biologics are a rapidly emerging class of therapeutics that have succeeded clinically and commercially due to their specificity and efficacy against various diseases including cancer, inflammatory, and autoimmune diseases. Even though most biologics are administered parenterally, nasal and pulmonary delivery would be beneficial due to numerous advantages such as being patient-friendly, noninvasive, cost-effective, and less toxic. While there are currently a few nasal and inhaled biologics on the market, for example, Suprefact®, Minirin®, Miacalcin®, most of them are designed to treat ailments related to prostate carcinoma, diabetes, osteoporosis but not for respiratory diseases. Moreover, there are some marketed nasally delivered vaccines such as Flumist® and Nasovac-S® against influenza virus, inhaled vaccines that did not make it to market. Given the rise of respiratory infections such as MERS, SARS, and SARS-CoV-2, a great deal of interest exists in developing nasal and pulmonary-delivered biologics and vaccines for respiratory diseases. The objective of this chapter is to describe the potential for pulmonary and nasal delivery of biologics. Each section delves into introducing biologics and vaccines, followed by a portrayal of recent updates on nasal and pulmonary delivery of biologics and vaccines. The most promising formulation strategies for enhancing the stability and therapeutic efficacy of biologics as a part of research and development will be discussed

Anthrax-toxin-mediated delivery of a 19 kDa antigen of Mycobacterium tuberculosis into the cytosol of mammalian cells

PA63, the proteolytically activated 63 kDa fragment of protective antigen (PA, 83 kDa), mediates translocation of lethal factor (LF) and oedema factor into the cytosol. The N-terminal 254 amino acids of LF (LFn) are required for binding to PA63 and mediating translocation of active ligands fused to either the N- or C-terminus. Here we report translocation of a 19 kDa antigen of Mycobacterium tuberculosis into the cytosol of mammalian cells when fused to the C-terminus of LFn (LFn-19kDa). The fusion protein was non-toxic to J774A.1 macrophage cells in combination with PA and retained the ability to bind to PA63 when incubated with Chinese hamster ovary K1 cells. The data show the efficacy of anthrax toxin to mediate translocation of M. tuberculosis antigens into the cytosol of mammalian cells and may prove useful in delivering proteins and peptides carrying immunodominant mycobacterial antigens into the cytosol

Alanine-scanning mutations in domain 4 of anthrax toxin protective antigen reveal residues important for binding to the cellular receptor and to a neutralizing monoclonal antibody

A panel of variants with alanine substitutions in the small loop of anthrax toxin protective antigen domain 4 was created to determine individual amino acid residues critical for interactions with the cellular receptor and with a neutralizing monoclonal antibody, 14B7. Substituted protective antigen proteins were analyzed by cellular cytotoxicity assays, and their interactions with antibody were measured by plasmon surface resonance and analytical ultracentrifugation. Residue Asp683 was the most critical for cell binding and toxicity, causing an ~1000-fold reduction in toxicity, but was not a large factor for interactions with 14B7. Substitutions in residues Tyr681, Asn682, and Pro686 also reduced toxicity significantly, by 10-100-fold. Of these, only Asn682 and Pro686 were also critical for interactions with 14B7. However, residues Lys684, Leu685, Leu687, and Tyr688 were critical for 14B7 binding without greatly affecting toxicity. The K684A and L685A variants exhibited wild type levels of toxicity in cell culture assays; the L687A and Y688A variants were reduced only 1.5- and 5-fold, respectively

Effect of COVID-19 Pandemic-Induced Dietary and Lifestyle Changes and Their Associations with Perceived Health Status and Self-Reported Body Weight Changes in India: A Cross-Sectional Survey

Home confinement during the COVID-19 pandemic is accompanied by dramatic changes in lifestyle and dietary behaviors that can significantly influence health. We conducted an online cross-sectional survey to assess COVID-19 pandemic-induced dietary and lifestyle changes and their association with perceived health status and self-reported body weight changes among 1000 Indian adults in early 2021. Positive improvements in dietary habits, e.g., eating more nutritious (85% of participants) and home-cooked food (89%) and an increase in overall nutrition intake (79%), were observed. Sixty-five percent of participants self-reported increased oat consumption to support immunity. There were some negative changes, e.g., more binge eating (69%), eating more in between meals (67%), and increasing meal portion size (72%). Two-thirds of participants reported no change in lifestyles, whereas 21 and 23% reported an increase, and 13 and 10% reported a decrease in physical activity and sleep, respectively. Overall, 64 and 65% of participants reported an improvement in perceived health and an increase in body weight during the COVID-19 period compared to pre-COVID-19, respectively. The top motivations for improving dietary habits included improving physical and mental health and building immunity. In conclusion, the overall perceived health was improved and there was an increase in self-reported body weight in most participants during COVID-19. Diet emerged as the most crucial determinant for these changes