mRNA-based vaccines - global approach, challenges, and could be a promising wayout for future pandemics.

mRNA-based vaccines are assured to significantly boost biopharmaceuticals since outbreak of coronavirus disease- 2019. Respiratory infections, such as influenza, SARS, MERS, COVID-19, and respiratory syncytial virus, often have high transmission rates due to their airborne spread. Respiratory infections can lead to severe illness and death. These outbreaks can cause substantial economic and social disruption, as seen with the COVID-19 pandemic. In our interconnected world, respiratory diseases can spread rapidly across borders. mRNA-based vaccines (e.g. mRNA-1283) can reduce the transmission by creating immunity in the population, thus lowering the incidence and spread of these diseases. Vaccines are crucial for global health security, helping to prevent local outbreaks from becoming global pandemics. Nevertheless, various concerns remain such as intracellular delivery, susceptibility to degradation by catalytic hydrolysis, and instability due to several physiological conditions. Therefore, an hour needed to address these challenges and opportunities for attaining high-quality and stable mRNA-based vaccines with novel drug delivery systems. The authors contributed an extensive review of the mRNA-based clinical development, progress in stability, and delivery challenges to mitigate market needs. In addition, the authors discuss crucial advances in the growth of mRNA-based vaccines to date; which dominate an extensive scope of therapeutic implementation. Finally, recent mRNA-based vaccines in clinical trials, adjuvant benefits, and prospects are discussed.

Evaluating the Synergistic Potency of Essential Oils and Antibiotics Against Klebsiella pneumoniae BLSE Strains.

Klebsiella pneumoniae producing extended-spectrum ß-lactamases (ESBL) continues to pose huge therapeutic challenges in the treatment of infections, primarily urinary infections, due to its multidrug resistance to antibiotics. Therefore, there is a need for research on this topic to investigate ways to reduce the spread of antibiotic resistance, identify novel therapeutic approaches to treat these infections and gain a better understanding of the mechanisms of resistance. In this context, this study aimed to analyze the chemical composition of essential oils (EOs) of Thymus algeriensis, Syzygium aromaticum, and Eucalyptus globulus and assess their activity against K. pneumoniae ESBL strains, as well as the interaction type between these EOs and antibiotics used for the treatment of K. pneumoniae ESBL infections. The composition of the EOs was determined by gas chromatography-mass spectrometry (GC-MS). The activity of EOs was tested using the disc diffusion and liquid microdilution methods. The type of interaction between EOs and antibiotics was studied using the agar disk diffusion and chessboard methods. The analysis of the EO of T. algeriensis showed that the main compounds were thymol (23.14%), linalool (18.44%), and p-cymene (16.17%). The main constituents of EO of E. globulus were eucalyptol (54.29%), α-pinene (17.32%), aromadendrene (7.02%), and pinocarveol (6.32%). As for the EO of S. aromaticum, the major constituents were eugenol (80.46%) and eugenol acetate (16.23%). Results of the activity tests showed that all three EOs were active against the tested strains, with inhibition diameters ranging from 7.39±0.44mm to 32.4±1.05mm and minimum inhibitory concentrations (MICs) varying from 2 to 441.5±5.66 mg/ml. A synergistic interaction was obtained between amoxicillin-clavulanic acid and T. algeriensis EO against two strains of K. pneumoniae ESBL. These results demonstrate the potential of our EOs to inhibit multi-resistant pathogenic ESBL strains, as well as their synergistic interaction with antibiotics used in therapy, which could be an alternative to the use of antibiotics alone in treatment to fight against these multi-resistant pathogenic bacteria.

Physicochemical, pharmacokinetics, and histological evaluation of new naproxen-quercetin co-lyophilizate to diminish drug-induced gastric irritations in rats.

Quercetin (QUE) is a flavonoid found in several plants and commonly distributed in edible vegetables and fruits. To evaluate the effect of co-lyophilization of naproxen (NPX) with QUE at different weight ratios on physicochemical characteristics induced gastric irritation, and drug pharmacokinetics. NPX binary systems with QUE in different weight ratios were prepared by freeze-drying alkalinized solutions, and were characterized in terms of physicochemical properties as well as NPX dissolution rate in acidic pH. NPX-induced gastric inflammation studies were carried out in rats for 7 days. The pharmacokinetics of the two formulations were assessed to evaluate the bioavailability of NPX-QUE 1:2 co-lyophilizate. Westar rats were administered oral doses equivalent to 40 mg kg-1 of NPX and blood samples were taken from the retro-orbital vein of rats at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 12.0, and 24.0 h post dosing. Co-lyophilization of NPX with QUE enhanced drug dissolution rate in the acidic medium, which was correlated with an increased QUE weight ratio in the co-lyophilizates. Rat stomachs from group V (NPX-QUE 1:2 co-lyophilizate) showed non-significant changes, and biopsies from this group showed no significant leukocyte infiltration and edema in the mucosa. The bioavailability of NPX-QUE 1: 2 co-lyophilizate was similar to the control sample. NPX-QUE 1: 2 co-lyophilizate could be an alternative to NPX in the treatment of arthritis as it minimizes the potential for gastric irritation and enhances safety while retaining the same efficacy and bioavailability.

Exploring Anthocyanins: Unveiling Sources, Analytical Techniques, and Biological Activities.

Anthocyanins (ANCs) are obtained from pigmented foods like blueberry, strawberry, and red cabbage and are phenolic compounds belonging to the flavonoids family. ANCs have garnered significant attention in recent years due to their diverse biological activities and potential health benefits. This comprehensive review presents a holistic exploration of anthocyanins, spanning from their chemical structure and biosynthesis pathways to the myriad analytical techniques employed for their identification and quantification. Furthermore, the rich tapestry of plant sources yields anthocyanins is delved into, highlighting their incorporation into various pharmaceutical formulations. This review aims to provide a comprehensive synthesis of current knowledge on anthocyanins, spanning from their origins in nature to their multifaceted pharmacological activities and innovative pharmaceutical applications.

Formulation and application of poly lactic acid, gum, and cellulose-based ternary bioplastic for smart food packaging: A review.

In future, global demand for low-cost-sustainable materials possessing good strength is going to increase tremendously, to replace synthetic plastic materials, thus motivating scientists towards green composites. The PLA has been the most promising sustainable bio composites, due to its inherent antibacterial property, biodegradability, eco-friendliness, and good thermal and mechanical characteristics. However, PLA has certain demerits such as poor water and gas barrier properties, and low glass transition temperature, which restricts its use in food packaging applications. To overcome this, PLA is blended with polysaccharides such as gum and cellulose to enhance the water barrier, thermal, crystallization, degradability, and mechanical properties. Moreover, the addition of these polysaccharides not only reduces the production cost but also helps in manufacturing packaging material with superior quality. Hence this review focuses on various fabrication techniques, degradation of the ternary composite, and its application in the food sector. Moreover, this review discusses the enhanced barrier and mechanical properties of the ternary blend packaging material. Incorporation of gum enhanced flexibility, while the reinforcement of cellulose improved the structural integrity of the ternary composite. The unique properties of this ternary composite make it suitable for extending the shelf life of food packaging, specifically for fruits, vegetables, and fried products. Future studies must be conducted to investigate the optimization of formulations for specific food types, explore scalability for industrial applications, and integrate these composites with emerging technologies (3D/4D printing).

Integrating Nanotechnological Advancements of Disease-Modifying Anti-Rheumatic Drugs into Rheumatoid Arthritis Management.

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.

The Link Between Alzheimer's Disease and Stroke: A Detrimental Synergism.

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-ß plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.

Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications.

Prostate cancer is one of the most life-threatening disorders that occur in males. It has now become the third most common disease all over the world, and emerging cases and spiking mortality rates are becoming more challenging day by day. Several approaches have been used to treat prostate cancer, including surgery, radiation therapy, chemotherapy, etc. These are painful and invasive ways of treatment. Primarily, chemotherapy has been associated with numerous drawbacks restricting its further application. The majority of prostate cancers have the potential to become castration-resistant. Prostate cancer cells exhibit resistance to chemotherapy, resistance to radiation, ADT (androgen-deprivation therapy) resistance, and immune stiffness as a result of activating tumor-promoting signaling pathways and developing resistance to various treatment modalities. Nanomedicines such as liposomes, nanoparticles, branched dendrimers, carbon nanotubes, and quantum dots are promising disease management techniques in this context. Nanomedicines can target the drugs to the target site and enhance the drug's action for a prolonged period. They may also increase the solubility and bioavailability of poorly soluble drugs. This review summarizes the current data on nanomedicines for the prevention and treatment of prostate cancer. Thus, nanomedicine is pioneering in disease management.

In-silico and in-vitro evaluation of antifungal bioactive compounds from Streptomyces sp. strain 130 against Aspergillus flavus.

Streptomyces spp. are considered excellent reservoirs of natural bioactive compounds. The study evaluated the bioactive potential of secondary metabolites from Streptomyces sp. strain 130 through PKS-I and NRPS gene-clusters screening. GC-MS analysis was done for metabolic profiling of bioactive compounds from strain 130 in the next set of experiments. Identified antifungal compounds underwent ADMET analyses to screen their toxicity. All compounds' molecular docking was done with the structural gene products of the aflatoxin biosynthetic pathway of Aspergillus flavus. MD simulations were utilized to evaluate the stability of protein-ligand complexes under physiological conditions. Based on the in-silico studies, compound 2,4-di-tert butyl-phenol (DTBP) was selected for in-vitro studies against Aspergillus flavus. Simultaneously, bioactive compounds were extracted from strain 130 in two different solvents (ethyl-acetate and methanol) and used for similar assays. The MIC value of DTBP was found to be 314 µg/mL, whereas in ethyl-acetate extract and methanol-extract, it was 250 and 350 µg/mL, respectively. A mycelium growth assay was done to analyze the effect of compounds/extracts on the mycelium formation of Aspergillus flavus. In agar diffusion assay, zone of inhibitions in DTBP, ethyl-acetate extract, and methanol extract were observed with diameters of 11.3, 13.3, and 7.6 mm, respectively. In the growth curve assay, treated samples have delayed the growth of fungi, which signified that the compounds have a fungistatic nature. Spot assay has determined the fungal sensitivity to a sub-minimum inhibitory concentration of antifungal compounds. The study's results suggested that DTBP can be exploited for antifungal-drug development.Communicated by Ramaswamy H. Sarma.

Mechanistic QSAR modeling derived virtual screening, drug repurposing, ADMET and in-vitro evaluation to identify anticancer lead as lysine-specific demethylase 5a inhibitor.

A lysine-specific demethylase is an enzyme that selectively eliminates methyl groups from lysine residues. KDM5A, also known as JARID1A or RBP2, belongs to the KDM5 Jumonji histone demethylase subfamily. To identify novel molecules that interact with the LSD5A receptor, we created a quantitative structure-activity relationship (QSAR) model. A group of 435 compounds was used in a study of the quantitative relationship between structure and activity to guess the IC50 values for blocking LASD5A. We used a genetic algorithm-multilinear regression-based quantitative structure-activity connection model to forecast the bioactivity (PIC50) of 1615 food and drug administration pharmaceuticals from the zinc database with the goal of repurposing clinically used medications. We used molecular docking, molecular dynamic simulation modelling, and molecular mechanics generalised surface area analysis to investigate the molecule's binding mechanism. A genetic algorithm and multi-linear regression method were used to make six variable-based quantitative structure-activity relationship models that worked well (R2 = 0.8521, Q2LOO = 0.8438, and Q2LMO = 0.8414). ZINC000000538621 was found to be a new hit against LSD5A after a quantitative structure-activity relationship-based virtual screening of 1615 zinc food and drug administration compounds. The docking analysis revealed that the hit molecule 11 in the KDM5A binding pocket adopted a conformation similar to the pdb-6bh1 ligand (docking score: -8.61 kcal/mol). The results from molecular docking and the quantitative structure-activity relationship were complementary and consistent. The most active lead molecule 11, which has shown encouraging results, has good absorption, distribution, metabolism, and excretion (ADME) properties, and its toxicity has been shown to be minimal. In addition, the MTT assay of ZINC000000538621 with MCF-7 cell lines backs up the in silico studies. We used molecular mechanics generalise borne surface area analysis and a 200-ns molecular dynamics simulation to find structural motifs for KDM5A enzyme interactions. Thus, our strategy will likely expand food and drug administration molecule repurposing research to find better anticancer drugs and therapies.Communicated by Ramaswamy H. Sarma.

Computational exploration of Picrasma quassioides compounds as CviR-mediated quorum sensing inhibitors against Chromobacterium violaceum.

Chromobacterium violaceum an opportunistic human pathogenic bacterium, exhibits resistance to conventional antibiotics by exploiting its quorum sensing mechanism to regulate virulence factor expression. In light of this, disrupting the quorum sensing mechanism presents a promising avenue for treating infections caused by this pathogen. The study focused on using the cytoplasmic quorum sensing receptor CviR from C. violaceum as a model target to identify novel quorum sensing inhibitors from P. quassioides through in silico computational approaches. Molecular docking analyses unveiled that several phytochemicals derived from Picrasma quassioides exhibit the potential to inhibit quorum sensing by binding to CviR protein. Notably, the compounds such as Quassidine I (- 8.8 kcal/mol), Quassidine J (- 8.8 kcal/mol), Kumudine B (- 9.1 kcal/mol) and Picrasamide A (- 8.9 kcal/mol) exhibited high docking scores, indicating strong binding affinity to the CviR protein. The native ligand C6-HSL (N-hexanoyl-L-homoserine lactone) as a positive control/co-crystal inhibitor also demonstrated a significant binding energy of-7.7 kcal/mol. The molecular dynamics simulation for 200 ns showed the thermodynamic stability and binding affinity refinement of the top-ranked CviR inhibitor (Kumudine B) with its stable binding and minor fluctuations compared to positive control (C6-HSL). Pharmacokinetic predictions indicated that Kumudine B possesses favourable drug-like properties, which suggest its potential as a drug candidate. The study highlight Kumudine B as a potential agent for inhibiting the CviR protein in C. violaceum. The comprehensive evaluation of Kumudine B provides valuable insights into its pharmacological profiles, facilitating its assessment for diverse therapeutic applications and guiding future research activities, particularly as antibacterial agents for clinical drug development.

NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer's Disease.

The nuclear factor kappa B (NF-κB) pathway has emerged as a pivotal player in the pathogenesis of various diseases, including neurodegenerative illnesses like Alzheimer's disease (AD). The involvement of the NF-κB pathway in immune system responses, inflammation, oxidative stress, and neuronal survival highlights its significance in AD progression. We discuss the advantages of NF-κB pathway inhibition, including the potential to mitigate neuroinflammation, modulate amyloid beta (Aß) production, and promote neuronal survival. However, we also acknowledge the limitations and challenges associated with this approach. Balancing the fine line between dampening inflammation and preserving physiological immune responses is critical to avoid unintended consequences. This review combines current knowledge on the NF-κB pathway's intricate involvement in AD pathogenesis, emphasizing its potential as a therapeutic target. By evaluating both advantages and limitations, we provide a holistic view of the feasibility and challenges of NF-κB pathway modulation in AD treatment. As the quest for effective AD therapies continues, an in-depth understanding of the NF-κB pathway's multifaceted roles will guide the development of targeted interventions with the potential to improve AD management.

Mesoporous Silica Nanoparticles: Types, Synthesis, Role in the Treatment of Alzheimer's Disease, and Other Applications.

Globally, many individuals struggle with Alzheimer's disease (AD), an unrelenting and incapacitating neurodegenerative condition. Despite notable research endeavors, effective remedies for AD remain constrained, prompting the exploration of innovative therapeutic avenues. Within this context, silica-based nanoplatforms have emerged with pronounced potential due to their unique attributes like expansive surface area, customizable pore dimensions, and compatibility with living systems. These nanoplatforms hold promise as prospective interventions for AD. This assessment provides a comprehensive overview encompassing various forms of mesoporous silica nanoparticles (MSNs), techniques for formulation, and their applications in biomedicine. A significant feature lies in their ability to precisely guide and control the transport of therapeutic agents to the brain, facilitated by the adaptability of these nanoplatforms as drug carriers. Their utility as tools for early detection and monitoring of AD is investigated. Challenges and prospects associated with harnessing MSNs are studied, underscoring the imperative of stringent safety evaluations and optimization of how they interact with the body. Additionally, the incorporation of multifunctional attributes like imaging and targeting components is emphasized to enhance their efficacy within the intricate milieu of AD. As the battle against the profound repercussions of AD persists, MSNs emerge as a promising avenue with the potential to propel the development of viable therapeutic interventions.

Zingerone (4-(four-hydroxy-3-methylphenyl) butane-two-1) modulates adjuvant-induced rheumatoid arthritis by regulating inflammatory cytokines and antioxidants.

OBJECTIVE: Ginger (Zingiber officinale Roscoe) is considered to be one of the most commonly consumed dietary condiments of the world. The present study was designed to explicate the protective role of zingerone; an active ingredient of ginger in complete Freund's adjuvant (FCA)-immunized arthritic rats. METHODS: 24 Wistar rats were divided into 4 groups with 6 rats each. Group I as control followed by group II, III and IV were treated with single intradermal injection of FCA (0.1 ml = 100 µg) to induce rheumatoid arthritis. Group III and IV were also administered with zingerone orally at 25 mg/kg b.w for 3 weeks at two different time points. RESULTS: Adjuvant-treated rats exhibited a significant increase in lipid peroxidation and a reduction in the enzymatic antioxidants such as SOD, catalase and GPx, in the liver and joint tissues. Moreover, FCA inoculation resulted in the increase in levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and a decrease in IL-10 levels. Zingerone significantly reduced the levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and markedly increased IL-10 levels. Levels of antioxidant enzymes were also restored by zingerone treatment. DISCUSSION: Oral administration of zingerone ameliorated inflammatory outburst and decreased oxidative stress, suggesting its role in the prevention of rheumatoid arthritis. Further mechanistic insights are necessary to study the exact mechanism involved.