Implications of siRNA Therapy in Bone Health: Silencing Communicates.

The global statistics of bone disorders, skeletal defects, and fractures are frightening. Several therapeutic strategies are being used to fix them; however, RNAi-based siRNA therapy is starting to prove to be a promising approach for the prevention of bone disorders because of its advanced capabilities to deliver siRNA or siRNA drug conjugate to the target tissue. Despite its 'bench-to-bedside' usefulness and approval by food and drug administration for five siRNA-based therapeutic medicines: Patisiran, Vutrisiran, Inclisiran, Lumasiran, and Givosiran, its use for the other diseases still remains to be resolved. By correcting the complications and complexities involved in siRNA delivery for its sustained release, better absorption, and toxicity-free activity, siRNA therapy can be harnessed as an experimental tool for the prevention of complex and undruggable diseases with a personalized medicine approach. The present review summarizes the findings of notable research to address the implications of siRNA in bone health for the restoration of bone mass, recovery of bone loss, and recuperation of bone fractures.

A Molecular Troika of Angiogenesis, Coagulopathy and Endothelial Dysfunction in the Pathology of Avascular Necrosis of Femoral Head: A Comprehensive Review.

Avascular necrosis of the femoral head (ANFH) is a painful disorder characterized by the cessation of blood supply to the femoral head, leading to its death and subsequent joint collapse. Influenced by several risk factors, including corticosteroid use, excessive alcohol intake, hypercholesterolemia, smoking and some inflammatory disorders, along with cancer, its clinical consequences are thrombus formation due to underlying inflammation and endothelial dysfunction, which collaborates with coagulopathy and impaired angiogenesis. Nonetheless, angiogenesis resolves the obstructed free flow of the blood by providing alternative routes. Clinical manifestations of early stage of ANFH mimic cysts or lesions in subchondral bone, vasculitis and transient osteoporosis of the hip, rendering it difficult to diagnose, complex to understand and complicated to cure. To date, the treatment methods for ANFH are controversial as no foolproof curative strategy is available, and these depend upon different severity levels of the ANFH. From an in-depth understanding of the pathological determinants of ANFH, it is clear that impaired angiogenesis, coagulopathy and endothelial dysfunction contribute significantly. The present review has set two aims, firstly to examine the role and relevance of this molecular triad (impaired angiogenesis, coagulopathy and endothelial dysfunction) in ANFH pathology and secondly to propose some putative therapeutic strategies, delineating the fact that, for the better management of ANFH, a combined strategy to curtail this molecular triangle must be composed rather than focusing on individual contributions.

Neutrophil Extracellular Traps and NLRP3 Inflammasome: A Disturbing Duo in Atherosclerosis, Inflammation and Atherothrombosis.

Atherosclerosis is the formation of plaque within arteries due to overt assemblage of fats, cholesterol and fibrous material causing a blockage of the free flow of blood leading to ischemia. It is harshly impinging on health statistics worldwide because of being principal cause of high morbidity and mortality for several diseases including rheumatological, heart and brain disorders. Atherosclerosis is perpetuated by pro-inflammatory and exacerbated by pro-coagulatory mediators. Besides several other pathways, the formation of neutrophil extracellular traps (NETs) and the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contribute significantly to the initiation and propagation of atherosclerotic plaque for its worst outcomes. The present review highlights the contribution of these two disturbing processes in atherosclerosis, inflammation and atherothrombosis in their individual as well as collaborative manner.