"Cutting the Mustard" with Induced Pluripotent Stem Cells: An Overview and Applications in Healthcare Paradigm.

Treatment of numerous ailments has been made accessible by the advent of genetic engineering, where the self-renewal property has unfolded the mysteries of regeneration, i.e., stem cells. This is narrowed down to pluripotency, the cell property of differentiating into other adult cells. The generation of induced pluripotent stem cells (iPSCs) was a major breakthrough in 2006, which was generated by a cocktail of 4 Yamanaka Factors, following which significant advancements have been reported in medical science and therapeutics. The iPSCs are reprogrammed from somatic cells, and the fascinating results focused on developing authentic techniques for their generation via molecular reprogramming mechanisms, with a plethora of molecules, like NANOG, miRNAs, and DNA modifying agents, etc. The iPSCs have exhibited reliable results in assessing the etiology and molecular mechanisms of diseases, followed by the development of possible treatments and the elimination of risks of immune rejection. The authors formulate a comprehensive review to develop a clear understanding of iPSC generation, their advantages and limitations, with potential challenges associated with their medical utility. In addition, a wide compendium of applications of iPSCs in regenerative medicine and disease modeling has been discussed, alongside bioengineering technologies for iPSC reprogramming, expansion, isolation, and differentiation. The manuscript aims to provide a holistic picture of the booming advancement of iPSC therapy, to attract the attention of global researchers, to investigate this versatile approach in treatment of multiple disorders, subsequently overcoming the challenges, in order to effectively expand its therapeutic window.

There is nothing exempt from the peril of mutation - The Omicron spike.

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets - kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways - on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.

Connecting the dots between mitochondrial dysfunction and Parkinson's disorder: focus mitochondria-targeting therapeutic paradigm in mitigating the disease severity.

Mitochondria are unique cell organelles, which exhibit multifactorial roles in numerous cell physiological processes, significantly preserving the integrity of neural synaptic interconnections, mediating ATP production, and regulating apoptotic signaling pathways and calcium homeostasis. Multiple neurological disorders occur as a consequence of impaired mitochondrial functioning, with greater sensitivity of dopaminergic (DA) neurons to mitochondrial dysfunction, due to oxidative nature and low mitochondrial mass, thus supporting the contribution of mitochondrial impairment in Parkinson's disorder (neuronal damage due to curbed dopamine levels). The pathophysiology of the second most common disorder, PD, is potentiated by various mitochondrial homeostasis regulating genes, as discussed in the review. The PD symptoms are known to be aggravated by multiple mitochondria-linked alterations, like reactive oxygen species (ROS) production, Ca2+ buffering, imbalanced mitochondrial dynamics (fission, fusion, mitophagy), biogenetic dysfunctions, disrupted mitochondrial membrane potential (MMP), protein aggregation, neurotoxins, and genetic mutations, which manifest the central involvement of unhealthy mitochondria in neurodegeneration, resulting in retarded DA neurons in region of substantia nigra pars compacta (SNpc), causing PD. Furthermore, the review tends to target altered mitochondrial components, like oxidative stress, inflammation, biogenetic alterations, impaired dynamics, uncontrolled homeostasis, and genetic mutations, to provide a sustainable and reliable alternative in PD therapeutics and to overcome the pitfalls of conventional therapeutic agents. Therefore, the authors elaborate the relationship between PD pathogenesis and mitochondrial dysfunctions, followed by a suitable mitochondria-targeting therapeutic portfolio, as well as future considerations, aiding the researchers to investigate novel strategies to mitigate the severity of the disease.

Unfolding Nrf2 in diabetes mellitus.

In spite of much awareness, diabetes mellitus continues to remain one of major reasons for mortality and morbidity rate all over the globe. Free radicals cause oxidative stress which is responsible for causing diabetes. The recent advancements in elucidation of ARE/keap1/Nrf2 pathway can help in better understanding of diabetes mellitus. Various clinical trials and animal studies have shown the promising effect of Nrf2 pathway in reversing diabetes by counteracting with the oxidative stress produced. The gene is known to dissociate from Keap1 on coming in contact with such stresses to show preventive and prognosis effect. The Nrf2 gene has been marked as a molecular player in dealing with wide intracellular as well as extracellular cellular interactions in different diseases. The regulation of this gene gives some transcription factor that contain antioxidant response elements (ARE) in their promoter region and thus are responsible for encoding certain proteins involved in regulation of metabolic and detoxifying enzymes.