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.

Expatiating the molecular approaches of HMGB1 in diabetes mellitus: Highlighting signalling pathways via RAGE and TLRs.

Diabetes mellitus (DM) has become one of the major healthcare challenges worldwide in the recent times and inflammation being one of its key pathogenic process/mechanism affect several body parts including the peripheral and central nervous system. High-mobility group box 1 (HMGB1) is one of the major non-histone proteins that plays a key role in triggering the inflammatory response. Upon its release into the extracellular milieu, HMGB1 acts as an "alarmin" for the immune system to initiate tissue repair as a component of the host defense system. Furthermore, HMGB1 along with its downstream receptors like Toll-like receptors (TLRs) and receptors for advanced glycation end products (RAGE) serve as the suitable target for DM. The forthcoming research in the field of diabetes would potentially focus on the development of alternative approaches to target the centre of inflammation that is primarily mediated by HMGB1 to improve diabetic-related complications. This review covers the therapeutic actions of HMGB1 protein, which acts by activating the RAGE and TLR molecules to constitute a functional tripod system, in turn activating NF-κB pathway that contributes to the production of mediators for pro-inflammatory cytokines associated with DM. The interaction between TLR2 and TLR4 with ligands present in the host and the activation of RAGE stimulates various immune and metabolic responses that contribute to diabetes. This review emphasizes to elucidate the role of HMGB1 in the initiation and progression of DM and control over the inflammatory tripod as a promising therapeutic approach in the management of DM.

Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.

Obesity or overweight are not superficial problems, constituting a pressing issue. The obesity index has almost tripled since 1975, which is an alarming state. Most of the individuals are currently becoming overweight or have inappropriate body mass index (BMI) conditions. Obesity is characterized by increased fat accumulation and thus poses a higher health risk. There is increased size and volume of fat cells in the body, which usually accounts for obesity. Many investigations have been carried out in this area, such as behavioral improvements, dietary changes, chemical involvements, etc., but presently no such goals are established to manage these health concerns. Based on previous literature reports and our interpretation, the current review indicates the involvement of various transcriptional and transporter functions in modifying the above-mentioned health conditions. Various transcriptional factors such as Forkhead box O1 (FoxO1) impart a significant effect on the physiology and pathology of metabolic dysfunction such as obesity. FoxO1 plays a dual role whether in the progression or suppression of metabolic processes depending on its targets. Thus, in the current study, will be discussed the dual role of FoxO1 in metabolic conditions (such as obesity), also summarizing the role of various other transcriptional factors involved in obesity.

Bioinformatics Accelerates the Major Tetrad: A Real Boost for the Pharmaceutical Industry.

With advanced technology and its development, bioinformatics is one of the avant-garde fields that has managed to make amazing progress in the pharmaceutical-medical field by modeling the infrastructural dimensions of healthcare and integrating computing tools in drug innovation, facilitating prevention, detection/more accurate diagnosis, and treatment of disorders, while saving time and money. By association, bioinformatics and pharmacovigilance promoted both sample analyzes and interpretation of drug side effects, also focusing on drug discovery and development (DDD), in which systems biology, a personalized approach, and drug repositioning were considered together with translational medicine. The role of bioinformatics has been highlighted in DDD, proteomics, genetics, modeling, miRNA discovery and assessment, and clinical genome sequencing. The authors have collated significant data from the most known online databases and publishers, also narrowing the diversified applications, in order to target four major areas (tetrad): DDD, anti-microbial research, genomic sequencing, and miRNA research and its significance in the management of current pandemic context. Our analysis aims to provide optimal data in the field by stratification of the information related to the published data in key sectors and to capture the attention of researchers interested in bioinformatics, a field that has succeeded in advancing the healthcare paradigm by introducing developing techniques and multiple database platforms, addressed in the manuscript.

The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson's Disorder and Therapeutic Implications.

Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson's disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompanied by side effects and limited reliability, therefore instigating the need to develop novel optimistic treatment targets. Significant therapeutic targets have been identified, namely: chaperones, protein Abelson, glucocerebrosidase-1, calcium, neuromelanin, ubiquitin-proteasome system, neuroinflammation, mitochondrial dysfunction, and the kynurenine pathway (KP). The role of KP and its metabolites and enzymes in PD, namely quinolinic acid (QUIN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranillic acid (3-HAA), kunurenine-3-monooxygenase (KMO), etc. has been reported. The neurotoxic QUIN, N-methyl-D-aspartate (NMDA) receptor agonist, and neuroprotective KYNA-which antagonizes QUIN actions-primarily justify the Janus-faced role of KP in PD. Moreover, KP has been reported to play a biomarker role in PD detection. Therefore, the authors detail the neurotoxic, neuroprotective, and immunomodulatory neuroactive components, alongside the upstream and downstream metabolic pathways of KP, forming a basis for a therapeutic paradigm of the disease while recognizing KP as a potential biomarker in PD, thus facilitating the development of a suitable target in PD management.

Exploring the molecular approach of COX and LOX in Alzheimer's and Parkinson's disorder.

Neuroinflammation is well established biomarker for the major neurodegenerative like Alzheimer's disease (AD) and Parkinson's disease (PD). Cytokines/chemokines excite phospholipase A2 and cyclooxygenases (COX), facilitating the release of arachidonic acid (AA) and docosahexaenoic acid (DHA) from membrane glycerophospholipids, in which the former is oxidized to produce pro-inflammatory eicosanoids (prostaglandins, leukotrienes and thromboxane's), which intensify the neuroinflammatory events in the brain. Similarly, resolvins and neuroprotectins are the metabolized products of docosahexaenoic acid, which exert an inhibitory effect on the production of eicosanoids. Furthermore, an oxidized product of arachidonic acid, lipoxin, is generated via 5-lipoxygenase (5-LOX) pathway, and contributes to the resolution of inflammation, along with anti-inflammatory actions. Moreover, DHA and its lipid mediators inhibit neuroinflammatory responses by blocking NF-κB, inhibiting eicosanoid production, preventing cytokine secretion and regulating leukocyte trafficking. Various epidemiological studies reported, elevated levels of COX-2 enzyme in patients with AD and PD, indicating its role in progression of the disease. Similarly, enhanced levels of 5-LOX and 12/15-LOX in PD models represent their role brain disorders, where the former is expressed in AD patients and the latter exhibits it involvement in PD. The present review elaborates the role of AA, DHA, eicosanoids and docosanoids, along with COX and LOX pathway which provides an opportunity to the researchers to understand the role of these lipid mediators in neurological disorders (AD and PD). The information gathered from the review will aid in facilitating the development of appropriate therapeutic options targeting COX and LOX pathway.

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-ß Cascade in Alzheimer's Disease.

One of the most commonly occurring neurodegenerative disorders, Alzheimer's disease (AD), encompasses the loss of cognitive and memory potential, impaired learning, dementia and behavioral defects, and has been prevalent since the 1900s. The accelerating occurrence of AD is expected to reach 65.7 million by 2030. The disease results in neural atrophy and disrupted inter-neuronal connections. Amongst multiple AD pathogenesis hypotheses, the amyloid beta (Aß) cascade is the most relevant and accepted form of the hypothesis, which suggests that Aß monomers are formed as a result of the cleavage of amyloid precursor protein (APP), followed by the conversion of these monomers to toxic oligomers, which in turn develop ß-sheets, fibrils and plaques. The review targets the events in the amyloid hypothesis and elaborates suitable therapeutic agents that function by hindering the steps of plaque formation and lowering Aß levels in the brain. The authors discuss treatment possibilities, including the inhibition of ß- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aß aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aß circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aß aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aß peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients.

While the most common manifestations associated with rheumatoid arthritis (RA) are synovial damage and inflammation, the systemic effects of this autoimmune disorder are life-threatening, and are prevalent in 0.5-1% of the population, mainly associated with cardiovascular disorders (CVDs). Such effects have been instigated by an altered lipid profile in RA patients, which has been reported to correlate with CV risks. Altered lipid paradox is related to inflammatory burden in RA patients. The review highlights general lipid pathways (exogenous and endogenous), along with the changes in different forms of lipids and lipoproteins in RA conditions, which further contribute to elevated risks of CVDs like ischemic heart disease, atherosclerosis, myocardial infarction etc. The authors provide a deep insight on altered levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in RA patients and their consequence on the cardiovascular health of the patient. This is followed by a detailed description of the impact of anti-rheumatoid therapy on the lipid profile in RA patients, comprising DMARDs, corticosteroids, anti-TNF agents, anti-IL-6 agents, JAK inhibitors and statins. Furthermore, this review elaborates on the prospects to be considered to optimize future investigation on management of RA and treatment therapies targeting altered lipid paradigms in patients.

The Link Between Alzheimer's Disease and Stroke: A Detrimental Synergism.

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-ß plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.

Unlocking the potential of oncology biomarkers: advancements in clinical theranostics.

INTRODUCTION: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment. CONTENT: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack. SUMMARY AND OUTLOOK: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.

A propitious role of marine sourced polysaccharides: Drug delivery and biomedical applications.

Numerous compounds, with extensive applications in biomedical and biotechnological fields, are present in the oceans, which serve as a prime renewable source of natural substances, further promoting the development of novel medical systems and devices. Polysaccharides are present in the marine ecosystem in abundance, promoting minimal extraction costs, in addition to their solubility in extraction media, and an aqueous solvent, along with their interactions with biological compounds. Certain algae-derived polysaccharides include fucoidan, alginate, and carrageenan, while animal-derived polysaccharides comprise hyaluronan, chitosan and many others. Furthermore, these compounds can be modified to facilitate their processing into multiple shapes and sizes, as well as exhibit response dependence to external conditions like temperature and pH. All these properties have promoted the use of these biomaterials as raw materials for the development of drug delivery carrier systems (hydrogels, particles, capsules). The present review enlightens marine polysaccharides providing its sources, structures, biological properties, and its biomedical applications. In addition to this, their role as nanomaterials is also portrayed by the authors, along with the methods employed to develop them and associated biological and physicochemical properties designed to develop suitable drug delivery systems.

AChE as a spark in the Alzheimer's blaze - Antagonizing effect of a cyclized variant.

The amyloid precursor protein (APP), presenilin 1 (PS1), amyloid beta (Aß), and GSK3 are the effectors, which are significantly associated with progression of Alzheimer's Disease (AD) and its symptoms. A significant protein, acetylcholinesterase (AChE) becomes dysfunctional as a result of cholinergic neuronal loss in AD pathology. However, certain associated peptides potentiate the release of primary neuropathological hallmarks, i.e., senile plaque and neurofibrillary tangles (NFTs), by modulating the alpha 7 acetylcholinesterase receptor (α7nAChR). The AChE variants, T30 and T14 have also been found to be elevated in AD patients and mimic the toxic actions of pathological events in patients. The manuscript discusses the significance of AChE inhibitors in AD therapeutics, by indicating the disastrous role of molecular alterations and elevation of AChE, accompanied with the downstream effects instigated by the peptide, supported by clinical evidence and investigations. The cyclized variant of AChE peptide, NBP14 has been identified as a novel candidate that reverses the harmful effects of T30, T14 and Aß, mainly calcium influx, cell viability and AChE release. The review aims to grab the attention of neuro-researchers towards the significance of triggering effectors in propagating AD and role of AChE in regulating them, which can potentially ace the development of reliable therapeutic candidates, similar to NBP14, to mitigate neurodegeneration.

Chrysin restores the cardioprotective effect of ischemic preconditioning in diabetes-challenged rat heart.

Background: Ischemic preconditioning (IPC) is the utmost capable design to achieve protection over ischemia-reperfusion injury (I/R), but this phenomenon gets attenuated during various pathological conditions like diabetes. Chrysin exhibits cardioprotection in various experiments however, its therapeutic potential on IPC-mediated cardioprotection via PI3K-Akt-eNOS pathway in streptozotocin (STZ) triggered diabetes-challenged rat heart is yet to be assessed. For that reason, the experiment has been planned to investigate chrysin's effect on the cardioprotective action of IPC involving the PI3K-Akt-eNOS cascade in rat hearts challenged to diabetes. Methods: The project was accomplished through means of absorbance studies for biochemical parameters, infarct size measurement (TTC stain) and coronary flow. Results: The findings of the present study revealed that STZ drastically augmented the serum glucose level and the chrysin significantly reversed the IPC-stimulated increased coronary flow, nitrite release, and reduced LDH (lactate dehydrogenase), CK-MB (creatine kinase) activities as well as infarct size in diabetes-induced rat heart. Furthermore, chrysin also reversed the IPC-induced reduction in oxidative stress in an isolated Langendorff's perfused diabetic rat heart. Moreover, four episodes of preconditioning by either PI3K or eNOS inhibitor in chrysin-pretreated diabetic rat hearts significantly abolished the protective effect of chrysin. Conclusion: Consequently, these observations suggested that chrysin increases the therapeutic efficiency of IPC in mitigating I/R injury via PI3K-Akt-eNOS signalling in diabetes-challenged rat hearts. Hence, chrysin could be a potential alternative option to IPC in diabetic rat hearts.

BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aß) and tau accumulation. Aß accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aß accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aß pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.

The Locus Coeruleus - Noradrenaline system: Looking into Alzheimer's therapeutics with rose coloured glasses.

Owing to the challenging ethos of global healthcare system, the Alzheimer's Disease (AD) researchers are consistently striving for a suitable target for disease amelioration. Besides the neurotransmitter release by neurons, the cells release tau proteins and amyloid peptides, within the extracellular vacancies, aggregating into tangles and plaques (AD pathological hallmarks). During neuro-stimulation, release of neuromodulator noradrenaline (NA), contained in the locus coeruleus (LC), exerts a significant impact on the neurons and microglia. The production of amyloid-ß (Aß) and hyperphosphorylation of tau proteins are affected by the α2A and ß adrenoreceptors, parallel to influencing their clearance. The manuscript entails a detailed understanding of the LC-NA system, as a possible avenue in AD management. The authors provide a comprehensive data on AD pathology and its link with LC neuroanatomical projections, followed by the pathogenic implications of LC-NA system in AD. The data also integrates numerous studies from online databases, evidently supporting the loss of the system integrity in AD patients, and the impact of the sympathetic system on specific AD hallmarks. Thus, the objective of this review is to compile a wide compendium of studies, for the convenience of the neuro-researchers, aiding in the establishment of a suitable therapeutic regimen for AD treatment.

The road to precision medicine: Eliminating the "One Size Fits All" approach in Alzheimer's disease.

The expeditious advancement of Alzheimer's Disease (AD) is a threat to the global healthcare system, that is further supplemented by therapeutic failure. The prevalence of this disorder has been expected to quadrupole by 2050, thereby exerting a tremendous economic pressure on medical sector, worldwide. Thus, there is a dire need of a change in conventional approaches and adopt a novel methodology of disease prevention, treatment and diagnosis. Precision medicine offers a personalized approach to disease management, It is dependent upon genetic, environmental and lifestyle factors associated with the individual, aiding to develop tailored therapeutics. Precision Medicine Initiatives are launched, worldwide, to facilitate the integration of personalized models and clinical medicine. The review aims to provide a comprehensive understanding of the neuroinflammatory processes causing AD, giving a brief overview of the disease interventions. This is further followed by the role of precision medicine in AD, constituting the genetic perspectives, operation of personalized form of medicine and optimization of clinical trials with the 3 R's, showcasing an in-depth understanding of this novel approach in varying aspects of the healthcare industry, to provide an opportunity to the global AD researchers to elucidate suitable therapeutic regimens in clinically and pathologically complex diseases, like AD.

CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target.

The combat against the Corona virus disease of 2019 (COVID-19), has created a chaos among the healthcare institutions and researchers, in turn accelerating the dire need to curtail the infection spread. The already established entry mechanism, via ACE2 has not yet successfully aided in the development of a suitable and reliable therapy. Taking in account the constant progression and deterioration of the cases worldwide, a different perspective and mechanistic approach is required, which has thrown light onto the cluster of differentiation 147 (CD147) transmembrane protein, as a novel route for SARS-CoV-2 entry. Despite lesser affinity towards COVID-19 virus, as compared to ACE2, this receptor provides a suitable justification behind elevated blood glucose levels in infected patients, retarded COVID-19 risk in women, enhanced susceptibility in geriatrics, greater infection susceptibility of T cells, infection prevalence in non-susceptible human cardiac pericytes and so on. The manuscript invokes the title role and distribution of CD147 in COVID-19 as an entry receptor and mediator of endocytosis-promoted entry of the virus, along with the "catch and clump" hypothesis, thereby presenting its Fundamental significance as a therapeutic target for potential candidates, such as Azithromycin, melatonin, statins, beta adrenergic blockers, ivermectin, Meplazumab etc. Thus, the authors provide a comprehensive review of a different perspective in COVID-19 infection, aiming to aid the researchers and virologists in considering all aspects of viral entry, in order to develop a sustainable and potential cure for the 2019 COVID-19 disease.

The dichotomy of nanotechnology as the cutting edge of agriculture: Nano-farming as an asset versus nanotoxicity.

The unprecedented setbacks and environmental complications, faced by global agro-farming industry, have led to the advent of nanotechnology in agriculture, which has been recognized as a novel and innovative approach in development of sustainable farming practices. The agricultural regimen is the "head honcho" of the world, however presently certain approaches have been imposing grave danger to the environment and human civilization. The nano-farming paradigm has successfully elevated the growth and development of plants, parallel to the production, quality, germination/transpiration index, photosynthetic machinery, genetic progression, and so on. This has optimized the traditional farming into precision farming, utilising nano-based sensors and nanobionics, smart delivery tools, nanotech facets in plant disease management, nanofertilizers, enhancement of plant adaptive potential to external stress, role in bioenergy conservation and so on. These applications portray nanorevolution as "the big cheese" of global agriculture, mitigating the bottlenecks of conventional practices. Besides the applications of nanotechnology, the review identifies the limitations, like possible harmful impact on environment, mankind and plants, as the "Achilles heel" in agro-industry, aiming to establish its defined role in agriculture, while simultaneously considering the risks, in order to resolve them, thus abiding by "technology-yes, but safety-must". The authors aim to provide a significant opportunity to the nanotech researchers, Botanists and environmentalists, to promote judicial use of nanoparticles and establish a secure and safe environment.

"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.