Recent Advances in Nanotechnology-Based Drug Delivery Approaches for Alzheimer disease.

One of the most common forms of neurodegenerative disorders, Alzheimer's disease poses a great threat to patients all over the globe with about 5.7 million cases estimated by the Alzheimer's Association Report of 2018. The disorder is a result of ß-amyloid deposition in the brain, deteriorating the cognitive ability and learning processes, commonly in geriatric patients. The review significantly elaborates the superiority of nanotechnological formulations over conventional therapeutic strategies, which exhibit numerous side effects, poor pharmacokinetic profiles and limited efficacy, as compared to the nano-medicinal approach. The review recognizes the need to establish an understanding of the transport mechanisms across the blood-brain barrier, prior to the nanoparticle studies, followed by a discussion on various nano-formulations, evidently supported by the outcome of various studies conducted to investigate the drug delivery portfolio of nanomedicines. Furthermore, the review portrays the challenges to overcome in future studies, like nanoparticle fabrication, drug loading capacity, blood residency time, toxicity regime, monitoring long term effects, in-vivo compatibility and production techniques, in order to enable the development of an optimized form of drug delivery process, which would achieve significant heights in the biomedical applications and bring about a revolution in the field of medicine and science.

Focus on Multi-targeted Role of Curcumin: a Boon in Therapeutic Paradigm.

Curcumin is a polyphenolic compound that exhibited good anticancer potential against different types of cancers through its multi-targeted effect like the termination of cell proliferation, inflammation, angiogenesis, and metastasis, thereby acting as antiproliferative and cytotoxic in nature. The present review surveys the various drug combination tried with curcumin or its synthetic analogues and also the mechanism by which curcumin potentiates the effect of almost every drug. In addition, this article also focuses on aromatherapy which is gaining much popularity in cancer patients. After thoroughly studying several articles on combination therapy of curcumin through authenticated book chapters, websites, research, and review articles available at PubMed, ScienceDirect, etc., it has been observed that multi-targeted curcumin possess enormous anticancer potential and, with whatever drug it is given in combination, has always resulted in enhanced effect with reduced dose as well as side effects. It is also capable enough in overcoming the problem of chemoresistance. Besides this, aromatherapy also proved its potency in reducing cancer-related side effects. Combining all the factors together, we can conclude that combination therapy of drugs with curcumin should be explored extensively. In addition, aromatherapy can be used as an adjuvant or supplementary therapy to reduce the cancer complications in patients.

Exploring the Various Aspects of Brain-Derived Neurotropic Factor (BDNF) in Diabetes Mellitus.

Brain-Derived Neurotrophic Factor (BDNF) serves as a modulator for neurotransmitters by participating in neuronal plasticity, essential for their growth and neuronal survival. It also shows a wide range of expression patterns in the systemic and peripheral tissues; thereby, its biological actions are not just limited to the CNS but may a vital role in peripheral disorders, such as Diabetes Mellitus (DM). Platelets serve as one of the major sources of BDNF, which regulates energy homeostasis and glucose metabolism by participating in the expression of specific pro-survival genes. It also prevents ß cell exhaustion, thus may prove to be a key factor for the management of DM. The current article reviews the intricate role of BDNF in Type 2 DM (T2DM) by involving platelet reactivity and its association with these selected inflammatory platelet activator mediators. Besides, certain adipocytokines, such as adiponectin and leptin, are also involved in the metabolism of glucose during diabetes, which has been clearly proven by recent experimental studies and thus relating BDNF with adipocytokines. It is also involved in the modulation of secretion of various neurotransmitters, peptides and hormones like gherin, leptin and insulin, suggesting its association with T2DM. Thus, based on various evidence, BDNF can be categorised as a potential biomarker in predicting the development of T2DM and may have a distinctive role in the management of this disorder.

Phytochemicals from Plant Foods as Potential Source of Antiviral Agents: An Overview.

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.

Exploring the multifocal role of phytochemicals as immunomodulators.

A well-functioning immune system of the host body plays pivotal role in the maintenance of ordinary physiological and immunological functions as well as internal environment. Balanced immunity enhances defense mechanism against infection, diseases and unwanted pathogens to avoid hypersensitivity reactions and immune related diseases. The ideal immune responses are the results of corrective interaction between the innate immune cells and acquired components of the immune system. Recently, the interest towards the immune system increased as significant target of toxicity due to exposure of chemicals, drugs and environmental pollutants. Numerous factors are involved in altering the immune responses of the host such as sex, age, stress, malnutrition, alcohol, genetic variability, life styles, environmental-pollutants and chemotherapy exposure. Immunomodulation is any modification of immune responses, often involved induction, amplification, attenuation or inhibition of immune responses. Several synthetic or traditional medicines are available in the market which promptly have many serious adverse effects and create pathogenic resistance. Phytochemicals are naturally occurring molecules, which significantly play an imperative role in modulating favorable immune responses. The present review emphasizes on the risk factors associated with alterations in immune responses, and immunomodulatory activity of phytochemicals specifically, glycosides, alkaloids, phenolic acids, flavonoids, saponins, tannins and sterols and sterolins.

Exploring the therapeutic promise of targeting HMGB1 in rheumatoid arthritis.

High mobility group box-1 (HMGB1) protein is a diverse, single polypeptide moiety, present in mammalian eukaryotic cells. In response to stimuli, this nuclear protein is actively secreted in to the extracellular compartment or passively released by the necrotic cells, in order to mediate inflammatory responses, by forming complexes with IL-1α, IL-1ß, LPS and other moieties, and binding to RAGE, TLR and other receptor ligands, initiating downstream, signaling processes. This molecule acts as a proinflammatory cytokine and contributes to the progression of diseases like, acute lung injury, autoimmune liver damage, graft rejection immune response and arthritis. Small concentrations of HMGB1 are released during apoptosis, which facilitates oxidative regulation on Cys106, and propagates immune inactivating tolerogenic signals in the body. The review portrays the role of HMGB1 in rheumatoid arthritis, evidently supported by pre-clinical and clinical investigations, demonstrating extensive HMGB1 expression in synovial tissue and fluid as well as serum, excessive expression of transduction receptor signaling molecules, bone remodeling and uncontrolled expression of bone destroying osteoclastogenesis, resulting in destruction of articular cartilage, bone deformation and synovial proliferation, alleviating the pathogenesis in RA disease. Moreover, the review highlights the therapeutic regime targeting HMGB1, facilitating inhibition of its actions and release into the extracellular compartment, to ameliorate the destructive events that prevail in rheumatoid arthritis.

Mechanistic insights into the role of pyroptosis in rheumatoid arthritis.

Cell death is ascribed as an essential biological process that is fundamental for the development of an organism along with its survival. The procedure comprises of apoptosis and pyroptosis. Pyroptosis is a programmed procedure for cell death which is inflammatory in nature and this pathway gets activated via human caspase-4, human caspase-11 and human caspase-5. The activation of this process leads to release of pro-inflammatory mediators including cytokines, alarmins, IL-18 and IL-1ß. The pro-inflammatory mediators released via interaction of intracellular kinases direct the development of Rheumatoid arthritis. Rheumatoid arthritis is characterized as disorder/disease that is auto-immune and chronic in nature. It involves erosions in marginal bone along with articular cartilage which is responsible for joint destruction. The cytokine along with its complex network is responsible for inflammation. The process of pyroptosis is linked with the destruction of plasma membrane, that releases these mediators and excessive release of these mediators is linked with rheumatoid arthritis.