Unraveling Atopic Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives.

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD's pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis.

Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative movement disorder worldwide, which is primarily characterized by motor impairments. Even though multiple hypotheses have been proposed over the decades that explain the pathogenesis of PD, presently, there are no cures or promising preventive therapies for PD. This could be attributed to the intricate pathophysiology of PD and the poorly understood molecular mechanism. To address these challenges comprehensively, a thorough disease model is imperative for a nuanced understanding of PD's underlying pathogenic mechanisms. This review offers a detailed analysis of the current state of knowledge regarding the molecular mechanisms underlying the pathogenesis of PD, with a particular emphasis on the roles played by gene-based factors in the disease's development and progression. This study includes an extensive discussion of the proteins and mutations of primary genes that are linked to PD, including α-synuclein, GBA1, LRRK2, VPS35, PINK1, DJ-1, and Parkin. Further, this review explores plausible mechanisms for DAergic neural loss, non-motor and non-dopaminergic pathologies, and the risk factors associated with PD. The present study will encourage the related research fields to understand better and analyze the current status of the biochemical mechanisms of PD, which might contribute to the design and development of efficacious and safe treatment strategies for PD in future endeavors.

Development of a new inhaled swellable microsphere system for the dual delivery of naringenin-loaded solid lipid nanoparticles and doxofylline for the treatment of asthma.

This study developed a new dual delivery system of naringenin (NRG), a polyphenol, and doxofylline (DOX), a xanthine derivative, as an inhaled microsphere system. In this system, NRG has been first loaded into glyceryl tristearate-based solid lipid nanoparticles (NRG SLN), which were further loaded with DOX into swellable chitosan-tripolyphosphate-based microspheres (NRG SLN DOX sMS). The system was characterized based on particle size, PDI, zeta potential, surface morphology (SEM, AFM, and TEM), solid-state and chemical properties (XRD, IR, and NMR), aerodynamic parameters, drug loading, entrapment efficiency and in vitro drug release study. The optimized NRG SLN DOX sMS exhibited particle size, zeta potential, and PDI of 2.1 µm, 31.2 mV, and 0.310, respectively; a drug entrapment efficiency > 79 %; a drug loading efficiency > 13 %; cumulative drug releases of about 78 % for DOX and 72 % for NRG after 6 and 12 h, respectively; good swelling and desirable aerodynamic properties. In addition, in vivo studies conducted in mice, a murine model of asthma showed significant reductions in serum bicarbonate and eosinophil counts and improvement in respiratory flow rate, tidal volume, and bronchial wall lining compared with the asthmatic control group. Overall, this novel inhalable dual-delivery system may represent a good alternative for the effective treatment of asthma.

Green synthetic strategies and pharmaceutical applications of thiazine and its derivatives: An updated review.

Thiazines are a sizable class of organic heterocycles that are notable for their skeletal versatility and relative chemical simplicity, making them among the most flexible sources of biologically active compounds. The term "green synthesis" refers to implementing energy-efficient procedures for the nature-friendly production of materials and chemicals using green solvents, catalysts, and suitable reaction conditions.Considering the importance of green chemistry and the outstanding therapeutic profile of thiazines, the present work was designed to review the recent advances in green chemistry-based synthetic strategies of thiazine and its derivatives. The green synthetic approaches, including microwave-assisted, ultrasound-assisted, and various other synthetic methods for thiazine and its derivatives, were discussed and generalized. In addition, applications of thiazine and its derivatives in pharmaceutical sciences were explained with examples of marketed drugs.The discussed sustainable synthetic methods for thiazines and their derivatives could be useful in developing other medicinally important lead molecules. They could also aid in developing new synthetic schemes and apparatuses that may simplify chemical manufacturing processes and enable novel reactions with minimal by-products while questing for optimal, green solvents. This review can help anyone interested in this fascinating class of heterocycles to make decisions about selecting targets and tasks for future research.

Solasodine Containing Solanum torvum L. Fruit Extract Prevents Chronic Constriction Injury-Induced Neuropathic Pain in Rats: In Silico and In Vivo Evidence of TRPV1 Receptor and Cytokine Inhibition.

This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)-induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes (P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be -11.2 and -6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.

An Insight into Cellular and Molecular Mechanisms Underlying the Pathogenesis of Neurodegeneration in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prominent neurodegenerative disorder in the aging population. It is characterized by cognitive decline, gradual neurodegeneration, and the development of amyloid-ß (Aß)-plaques and neurofibrillary tangles, which constitute hyperphosphorylated tau. The early stages of neurodegeneration in AD include the loss of neurons, followed by synaptic impairment. Since the discovery of AD, substantial factual research has surfaced that outlines the disease's causes, molecular mechanisms, and prospective therapeutics, but a successful cure for the disease has not yet been discovered. This may be attributed to the complicated pathogenesis of AD, the absence of a well-defined molecular mechanism, and the constrained diagnostic resources and treatment options. To address the aforementioned challenges, extensive disease modeling is essential to fully comprehend the underlying mechanisms of AD, making it easier to design and develop effective treatment strategies. Emerging evidence over the past few decades supports the critical role of Aß and tau in AD pathogenesis and the participation of glial cells in different molecular and cellular pathways. This review extensively discusses the current understanding concerning Aß- and tau-associated molecular mechanisms and glial dysfunction in AD. Moreover, the critical risk factors associated with AD including genetics, aging, environmental variables, lifestyle habits, medical conditions, viral/bacterial infections, and psychiatric factors have been summarized. The present study will entice researchers to more thoroughly comprehend and explore the current status of the molecular mechanism of AD, which may assist in AD drug development in the forthcoming era.

Promising Repurposed Antiviral Molecules to Combat SARS-CoV-2: A Review.

COVID-19, an extremely transmissible and pathogenic viral disease, triggered a global pandemic that claimed lives worldwide. To date, there is no clear and fully effective treatment for COVID-19 disease. Nevertheless, the urgency to discover treatments that can turn the tide has led to the development of a variety of preclinical drugs that are potential candidates for probative results. Although most of these supplementary drugs are constantly being tested in clinical trials against COVID-19, recognized organizations have aimed to outline the prospects in which their use could be considered. A narrative assessment of current articles on COVID-19 disease and its therapeutic regulation was performed. This review outlines the use of various potential treatments against SARS-CoV-2, categorized as fusion inhibitors, protease inhibitors, and RNA-dependent RNA polymerase inhibitors, which include antiviral drugs such as Umifenovir, Baricitinib, Camostatmesylate, Nafamostatmesylate, Kaletra, Paxlovide, Darunavir, Atazanavir, Remdesivir, Molnupiravir, Favipiravir, and Ribavirin. To understand the virology of SARS-CoV-2, potential therapeutic approaches for the treatment of COVID-19 disease, synthetic methods of potent drug candidates, and their mechanisms of action have been addressed in this review. It intends to help readers approach the accessible statistics on the helpful treatment strategies for COVID-19 disease and to serve as a valuable resource for future research in this area.

Moringa oleifera: An Updated Comprehensive Review of Its Pharmacological Activities, Ethnomedicinal, Phytopharmaceutical Formulation, Clinical, Phytochemical, and Toxicological Aspects.

Moringa oleifera, also known as the "tree of life" or "miracle tree," is classified as an important herbal plant due to its immense medicinal and non-medicinal benefits. Traditionally, the plant is used to cure wounds, pain, ulcers, liver disease, heart disease, cancer, and inflammation. This review aims to compile an analysis of worldwide research, pharmacological activities, phytochemical, toxicological, and ethnomedicinal updates of Moringa oleifera and also provide insight into its commercial and phytopharmaceutical applications with a motive to help further research. The scientific information on this plant was obtained from various sites and search engines such as Scopus, Pub Med, Science Direct, BMC, Google Scholar, and other scientific databases. Articles available in the English language have only been referred for review. The pharmacological studies confirm the hepatoprotective, cardioprotective, and anti-inflammatory potential of the extracts from the various plant parts. It was found that bioactive constituents are present in every part of the plant. So far, more than one hundred compounds from different parts of Moringa oleifera have been characterized, including alkaloids, flavonoids, anthraquinones, vitamins, glycosides, and terpenes. In addition, novel isolates such as muramoside A&B and niazimin A&B have been identified in the plant and have potent antioxidant, anticancer, antihypertensive, hepatoprotective, and nutritional effects. The traditional and nontraditional use of Moringa, its pharmacological effects and their phytopharmaceutical formulations, clinical studies, toxicity profile, and various other uses are recognized in the present review. However, several traditional uses have yet to be scientifically explored. Therefore, further studies are proposed to explore the mechanistic approach of the plant to identify and isolate active or synergistic compounds behind its therapeutic potential.

Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

OBJECTIVE: This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. MATERIALS AND METHODS: TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. RESULTS: TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. CONCLUSIONS: Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.