An Innovative Approach in Nanotechnology-based Delivery System for the Effective Management of Psoriasis.

INTRODUCTION: Psoriasis is an incurable, non-contagious inflammatory autoimmune skin disease characterised by abnormal skin redness and flaky patches on the body surface. It is caused by negative signals produced by the immune system, leading to excessive growth and differentiation of keratinocytes and other inflammatory reactions on the skin. The topical route is primarily preferred in treating skin disorders due to the smaller size of the drug molecule, which allows them to cross the outer layer of the skin, i.e., stratum corneum, and permeate into the deep layer, unlike transdermal and other routes. The conventional topical treatments used in the past, such as coal tar and dithranol, lead to meager patient compliance due to decreased potency and imperfect aesthetic. In contrast, systemic therapy such as methotrexate, cyclosporine, and acitretin produce related side effects. At present, various novel carriers like liposomes, ethosomes, niosomes, nanostructured lipid carriers, etc., have shown promising results in the treatment of psoriasis. Therefore, this review primarily concentrates on the current advancements in novel carriers for various drugs to treat psoriasis topically. DISCUSSION: The goal of this review is to provide a comprehensive overview of the pathophysiology, epidemiology, types, causes, diagnosis, and topical treatment options for psoriasis, as well as the role of nanotechnology- based delivery systems in psoriasis management.

Natural Bioactives as Potential Therapeutic Modalities Against NeuroAIDS.

With the introduction of antiretroviral therapy, the worldwide AIDS-related deaths have decreased, and life expectancy has increased, including the prevalence of AIDS-related neurological disorders or neuroAIDS. HIV-associated neurocognitive disorders such as mild neurocognitive disorder and asymptomatic neurocognitive impairment have largely remained stable or increased among the HIV-infected individuals in the combination antiretroviral therapy era. The emerging evidence that antiretrovirals with high CNS penetration effectiveness score contribute to the neurotoxicity and HIV-associated neurocognitive disorders has ushered the search for natural, nontoxic bioactive constituents having pre-established neuroprotective, anti-inflammatory, and restorative neurocognitive activity. In this review, we have highlighted the probable mechanism of neuroAIDS infection, the problem with the existing antiretroviral therapy, along with various bioactive constituents with in vivo, in vitro, or ex vivo evidence of their neuroprotective activity that can be used as an adjuvant with the current combination antiretroviral therapy regimen or can even serve as an alternate to the antiretrovirals for treatment of HIV associated neurocognitive disorder.

Natural Products, a Potential Therapeutic Modality in Management and Treatment of nCoV-19 Infection: Preclinical and Clinical Based Evidence.

A recent outbreak of novel coronavirus (nCoV-19) has put an enormous burden on global public health. Millions of people were affected by this pandemic, and as of now, no effective antiviral drug has been found for the management of this situation. Cytokine storm, acute respiratory distress, hypoxia and multi-organ failure are hallmark clinical conditions of this disease. Trials for several investigational and repurposed drugs are being conducted, but none of them were found to be safe and effective. However, for the critically ill patient, plasma therapy, dexamethasone, and remdesivir are included in the treatment protocol. For a long time, various natural drugs have been used as antiviral agents in Indian and Chinese traditional medicines, which can be explored as a potential therapeutic option in such situation. It is, therefore, speculated that the proper screening and standardization of these medicines can be a breakthrough in the management and treatment of nCoV-19 infection. As natural products possess antioxidant, anti-inflammatory, anti-apoptotic, immunomodulatory properties and also specifically act on various viral enzymatic machinery and affect their replication process, thus they may be useful as alternatives in relieving symptoms and treatment of nCoV-19 infection. However, only on the basis of their traditional value, discrimination and off-label use of these natural drugs must be prevented, and robust preclinical and clinical data along with appropriate guidelines are needed for them to enter into clinical practice.

Polyphenols as Potential Therapeutics for Pain and Inflammation in Spinal Cord Injury.

Spinal cord injury (SCI) and associated pain and inflammation caused by trauma or infection are serious health care issues world-wide. The various inflammatory, redox-sensitive and apoptotic events are contributing factors, but altered neuronal function, axonal degeneration, activated microglia, endothelial cells, astrocytes, fibroblasts, pericytes, Schwann cells, and meningeal cells are major players in its pathogenesis. Further, monocytes and neutrophil infiltration get recruited and facilitate the release of chemokines, cytokines, and other mediators of inflammation. This event leads to the production of different amino acids, neuropeptides kinin, prostaglandins, prostacyclin, thromboxane, leukotrienes, bradykinin, histamine, matrix metal proteinases, and serotonin that stimulate nerve endings and manifest the inflammation and pain processes, etc. Arachidonic acid (AA), NF-kB, NLRP3 inflammasome, and nitric oxide pathways along with P2X7 receptor and ion channel transient receptor potential (TRP) vanilloid are some of the recently explored targets for modulation of pain and inflammation in SCI. Till now, NSAIDs, opioids, antidepressants, anticonvulsants, NMDA antagonists, α2-adrenergic agonists, and GABA-receptor agonists are used for the management of these pathological conditions. However, these drugs are associated with various side effects. Additionally, the number of available animal models for SCI has enhanced the understanding of the complex pathological mechanisms involved in the generation of chronic inflammatory pain in SCI. These findings enable us to identify and validate several potent natural analgesic-anti-inflammatory drug candidates with minimal side effects. However, these compounds have been studied in preclinical models and shown promising results, but no clinical studies have been performed. Therefore, a detailed exploration of these natural compounds is important for bringing them from bench to bedside.

Current Quest in Natural Bioactive Compounds for Alzheimer's Disease: Multi-Targeted-Designed-Ligand Based Approach with Preclinical and Clinical Based Evidence.

Alzheimer's disease is a common and most chronic neurological disorder (NDs) associated with cognitive dysfunction. Pathologically, Alzheimer's disease (AD) is characterized by the presence of ß-amyloid (Aß) plaques, hyper-phosphorylated tau proteins, and neurofibrillary tangles, however, persistence oxidative-nitrative stress, endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory cytokines, pro-apoptotic proteins along with altered neurotransmitters level are common etiological attributes in its pathogenesis. Rivastigmine, memantine, galantamine, and donepezil are FDA approved drugs for symptomatic management of AD, whereas tacrine has been withdrawn because of hepatotoxic profile. These approved drugs only exert symptomatic relief and exhibit poor patient compliance. In the current scenario, the number of published evidence shows the neuroprotective potential of naturally occurring bioactive molecules via their antioxidant, anti-inflammatory, antiapoptotic and neurotransmitter modulatory properties. Despite their potent therapeutic implications, concerns have arisen in context to their efficacy and probable clinical outcome. Thus, to overcome these glitches, many heterocyclic and cyclic hydrocarbon compounds inspired by natural sources have been synthesized and showed improved therapeutic activity. Computational studies (molecular docking) have been used to predict the binding affinity of these natural bioactive as well as synthetic compounds derived from natural sources for the acetylcholine esterase, α/ß secretase Nuclear Factor kappa- light-chain-enhancer of activated B cells (NF-kB), Nuclear factor erythroid 2-related factor 2(Nrf2) and other neurological targets. Thus, in this review, we have discussed the molecular etiology of AD, focused on the pharmacotherapeutics of natural products, chemical and pharmacological aspects and multi-targeted designed ligands (MTDLs) of synthetic and semisynthetic molecules derived from the natural sources along with some important on-going clinical trials.

Environmental neurotoxic pollutants: review.

Environmental pollutants are recognized as one of the major concerns for public health and responsible for various forms of neurological disorders. Some of the common sources of environmental pollutants related to neurotoxic manifestations are industrial waste, pesticides, automobile exhaust, laboratory waste, and burning of terrestrial waste. Among various environmental pollutants, particulate matter, ultrafine particulate matter, nanoparticles, and lipophilic vaporized toxicant (acrolein) easily cross the blood-brain barrier, activate innate immune responses in the astrocytes, microglia, and neurons, and exert neurotoxicity. Growing shreds of evidence from human epidemiological studies have correlated the environmental pollutants with neuroinflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, myelin sheath disruption, and alterations in the blood-brain barrier anatomy leading to cognitive dysfunction and poor quality of life. These environmental pollutants also considerably cause developmental neurotoxicity, exhibit teratogenic effect and mental growth retardance, and reduce IQ level. Until now, the exact mechanism of pollutant-induced neurotoxicity is not known, but studies have shown interference of pollutants with the endogenous antioxidant defense system, inflammatory pathway (Nrf2/NF-kB, MAPKs/PI3K, and Akt/GSK3ß), modulation of neurotransmitters, and reduction in long-term potentiation. In the current review, various sources of pollutants and exposure to the human population, developmental neurotoxicity, and molecular mechanism of different pollutants involved in the pathogenesis of different neurological disorders have been discussed.

Redactable and auditable data access for bioinformatics research.

Presently, the process of extraction and dissemination of data subsets for research from clinical data warehouses is cumbersome and error prone. Furthermore, large-scale research projects often involve multiple users of the same data extract; each of these users may be authorized to access different data elements and specific subsets of the data extract. Once initial data extraction has been done for a research project, capability to transform the data for individual users and track which data are being accessed by which users in a secure environment is lacking in existing systems. This paper describes several methods that the authors are integrating into a system designed to provide secure, flexible, and auditable support for supplying users with data subsets. The methods implement secure, redactable, and auditable mechanisms for data extraction and dissemination. This paper describes the architecture along with an initial proof-of-concept implementation. Preliminary performance measurements show that the approach manages clinical data in redactable and auditable form with reasonable overheads.