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Recent Advances in Inflammation & Allergy Drug Discovery - Online First
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Unlocking Toll-Like Receptors: Targeting Therapeutics for Respiratory Tract Infections and Inflammatory Disorders
Authors: Vishal Pandey, Debasis Sen, Sunny Rathee, Sakshi Soni, Shashank Mishra, Sanjay K. Jain and Umesh K. PatilAvailable online: 08 October 2024More LessThe Toll-like Receptors (TLRs) family has significantly enhanced the understanding of innate immune responses by identifying and responding to various microbes or host-derived organisms. TLRs contribute to these responses by increasing the levels of cytokines, interleukins, and other inflammatory mediators through multiple pathways. Located both intracellularly and on the surface of various cells and tissues, including vascular smooth muscles (VSMs) and myocardium cells, TLRs play distinct roles in innate immune activation, such as recognizing pathogen-associated molecular patterns (PAMPs) and activating downstream signaling pathways. In the context of COVID-19, TLRs are critically involved in the pathophysiology by mediating excessive inflammatory responses that exacerbate disease severity, influencing both the acute phase and long-term outcomes. It has been observed that inflammatory diseases such as atherosclerosis, viral myocarditis, and other comorbidities associated with the spread of COVID-19 have increased, although the exact mechanisms remain not fully understood. Nonetheless, there is evidence of TLR-mediated increased pro-inflammatory signaling by different mechanisms in these diseases. This review explains the role of TLRs in various inflammatory diseases related to COVID-19, including viral myocarditis, acute lung infections, and atherosclerosis. Furthermore, the review discusses various herbal drugs, such as Platycodon grandiflorum, Acanthopanax senticosus, Scutellaria baicalensis Georgi, and Engelhardia roxburghiana, and their mechanisms of action on TLRs, including NF-κB, MyD88-dependent, MyD88-independent pathways, and Plasmacytoid DCs. Enhanced clarity on TLRs' specific contributions to COVID-19 pathophysiology and stronger evidence supporting herbal interventions targeting TLRs could improve the impact and applicability of these findings in clinical settings.
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Cyclooxygenases: From Prostaglandin Synthesis to Innovative Therapies for Inflammation
Authors: Sumeet Sharma, Prerna Sharma and Nidhi RaniAvailable online: 03 October 2024More LessCyclooxygenases are enzymes involved in prostaglandin synthesis, a part of the inflammatory process. The most frequently applied anti-inflammatory drugs are NSAIDs; however, these medications exhibit very serious side effects, and often, reduce production or are withdrawn from the market. Recently, researchers were focused on finding new, safe, selective COX-2 inhibitors with safety features. This paper reviews cyclooxygenase enzyme malfunction-related diseases, current therapies and new drug discovery opportunities. Prostaglandin-endoperoxide synthases are enzymes involved in the synthesis of prostanoid peptides through the oxidation of nitric oxide and pyruvate phosphate. They are participating factors for various physiological and pathological processes, which include disorders of the oral tissues such as periodontitis, pulpitis, and oral cancer. This paper is a review of some pharmaceutical products in terms of history, efficiency, and possible side effects as inhibitors of the Cyclooxygenase enzyme. The analysis concludes that more recent Cox inhibitors, such as dietary modifications and natural supplements, hold promise for safer and more efficient treatment of diseases involving Cox enzyme function.
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A Comprehensive Review of Acanthosis Nigricans: Pathogenesis, Clinical manifestation and Management
Authors: Shiana, Shivika Parmar, Priyanka guleria, Shammy Jindal, M.S Ashawat and Pravin KumarAvailable online: 03 October 2024More LessBackgroundAcanthosis Nigricans is a dermatological condition characterized by hyperpigmented velvet plaques that can be observed in flexural areas such as the neck, axilla, and groin. AN is frequently associated with insulin resistance and obesity, however, it can also appear in non-obese people and as a paraneoplastic disease. Its prevalence varies across different populations, with higher rates observed in individuals with obesity, diabetes, and certain genetic syndromes. Classification of AN can be based on underlying etiology, distinguishing primary and secondary forms. Pathogenesis is the complex interplay of genetic, hormonal, and environmental factors, with insulin resistance playing a central role. Diagnosis relies on clinical evaluation of characteristics of skin changes, often requiring further investigation for underlying systemic disease. Topical therapies involve keratolytic agents, retinoids, and alpha hydroxyl acids to improve the cosmesis and reduce the plaque's thickness. Treatment strategies address underlying conditions by emphasizing lifestyle modifications and in some cases, pharmacological interventions.
ObjectiveThis review aims to comprehensively examine the pathogenesis, clinical manifestation, and management of acanthosis nigricans.
DiscussionAN is closely linked to insulin resistance, characterized by impaired cellular response to insulin, leading to compensatory hyperinsulinemia. Recognizing AN’s clinical presentation is paramount for early diagnosis and appropriate management.
ConclusionAcanthosis Nigricans is a skin condition characterized by dark, thickened patches of skin, typically occurring in skin folds and creases. It can be a sign of an underlying health issue such as insulin resistance, obesity, hormonal disorders, or certain medications. Proper diagnosis and management of the underlying conditions are crucial. Treatment may involve addressing the underlying causes, lifestyle changes, and topical medications to improve the appearance of the skin. Regular monitoring and follow-up with a health care professional are essential for optimal management and to prevent complications.
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