NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke.

Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient's quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects.

Pathophysiology, diagnosis, and herbal medicine-based therapeutic implication of rheumatoid arthritis: an overview.

Rheumatoid arthritis (RA) stands as an autoimmune disorder characterized by chronic joint inflammation, resulting in profound physiological alterations within the body. Affecting approximately 0.4-1.3% of the global population, this condition poses significant challenges as current therapeutic approaches primarily offer symptomatic relief, with the prospect of complete recovery remaining elusive. This review delves into the contemporary advancements in understanding the pathophysiology, diagnosis, and the therapeutic potential of herbal medicine in managing RA. Notably, early diagnosis during the initial stages emerges as the pivotal determinant for successful recovery post-treatment. Utilizing tools such as Magnetic Resonance Imaging (MRI), anti-citrullinated peptide antibody markers, and radiography proves crucial in pinpointing the diagnosis of RA with precision. Unveiling the intricate pathophysiological mechanisms of RA has paved the way for innovative therapeutic interventions, incorporating plant extracts and isolated phytoconstituents. In the realm of pharmacological therapy for RA, specific disease-modifying antirheumatic drugs have showcased commendable efficacy. However, this conventional approach is not without its drawbacks, as it is often associated with various side effects. The integration of methodological strategies, encompassing both pharmacological and plant-based herbal therapies, presents a promising avenue for achieving substantive recovery. This integrated approach not only addresses the symptoms but also strives to tackle the underlying causes of RA, fostering a more comprehensive and sustainable path towards healing.

ddRAD sequencing-based identification of inter-genepool SNPs and association analysis in Brassica juncea.

BACKGROUND: Narrow genetic base, complex allo-tetraploid genome and presence of repetitive elements have led the discovery of single nucleotide polymorphisms (SNPs) in Brassica juncea (AABB; 2n = 4x = 36) at a slower pace. Double digest RAD (ddRAD) - a genome complexity reduction technique followed by NGS was used to generate a total of 23 million paired-end reads from three genotypes each of Indian (Pusa Tarak, RSPR-01 and Urvashi) and Exotic (Donskaja IV, Zem 1 and EC287711) genepools. RESULTS: Sequence data analysis led to the identification of 10,399 SNPs in six genotypes at a read depth of 10x coverage among the genotypes of two genepools. A total of 44 hyper-variable regions (nucleotide variation hotspots) were also found in the genome, of which 93% were found to be a part of coding genes/regions. The functionality of the identified SNPs was estimated by genotyping a subset of SNPs on MassARRAY® platform among a diverse set of B. juncea genotypes. SNP genotyping-based genetic diversity and population studies placed the genotypes into two distinct clusters based mostly on the place of origin. The genotypes were also characterized for six morphological traits, analysis of which revealed a significant difference in the mean values between Indian and Exotic genepools for six traits. The association analysis for six traits identified a total of 45 significant marker-trait associations on 11 chromosomes of A- and B- group of progenitor genomes. CONCLUSIONS: Despite narrow diversity, the ddRAD sequencing was able to identify large number of nucleotide polymorphisms between the two genepools. Association analysis led to the identification of common SNPs/genomic regions associated between flowering and maturity traits, thereby underscoring the possible role of common chromosomal regions-harboring genes controlling flowering and maturity in Brassica juncea.

Alloying-induced spin Seebeck effect and spin figure of merit in Pt-based bimetallic atomic wires of noble metals.

We have investigated using first principles the occurrence and tunability of the spin Seebeck effect in Pt-based bimetallic wires of noble metals (viz. XPt, X = Cu, Ag, and Au) modelled in linear, ladder, and double zigzag (DZZ) topologies. The spin figure of merit ZsT and its charge counterpart ZcT are calculated by considering both electronic and phononic contributions to the thermal conductance. For this endeavour, we have employed the Landauer-Büttiker approach, with the requisite electron τel(E) and phonon τph(E) transmission functions obtained using the non-equilibrium Green's function approach, based on density functional theory and the general utility lattice program, respectively. We find that alloying and/or topological tailoring bring in quantitative as well as qualitative changes in the transport properties. Unlike the pristine wires, τel(E) now depends (except for the CuPt wire in the ladder topology) markedly on spin, thus resulting in an unequal current in the two spin channels and hence a non-zero spin Seebeck coefficient Ss. Remarkably, the AgPt wire in the linear topology and all wires in the DZZ1 and DZZ3 configurations of the DZZ topology exhibit half-metallic conduction, with a sizable gap in the density of ↑-spin states at the Fermi level. Alloying also introduces energy gap(s) in the phonon density of states. Consequently, we find a significant reduction in the electronic and phononic thermal conductance. Interestingly, Ss is of the same order as its charge counterpart Sc, and both can be tuned via the topology and chemical potential µ of the electrodes. This together with the reduced thermal conductance results in a significantly high room-temperature ZcT (∼33) and ZsT (∼25) at µ ∼ 0.24 eV in the AgPt wire in the DZZ3 topology, with about a ten-fold increase in ZcT as compared to the pristine wires. Furthermore, there exists a characteristic µ in some bimetallic wires for which Sc approaches zero, but Ss remains quite appreciable. This result arises due to the emergence of bipolar thermal conduction, which under criticality makes S↑ + S↓ = 0. Importantly, such a situation may be exploited to generate a pure thermal spin voltage. Our results can be explicated on the basis of changes in the electronic band structure and phononic spectra due to alloying and topological effects.

Systematic Study on TiO2 Crystallization via Hydrothermal Synthesis in the Presence of Different Ferrite Nanoparticles as Nucleation Seeds.

In the present work, the crystallization of anatase TiO2 nanoparticles (NPs), using different ferrite nanoparticles with different chemical composition, dimensions and shape as nucleation seeds, was investigated. In particular, CoFe2O4, NiFe2O4 and Fe3O4 NPs with a volume ratio equal to 1:1000 with respect of TiO2 amount, were used in order to investigate the synthesis of nanocrystalline tetragonal anatase TiO2 by a hydrothermal synthesis. In addition, Lu2O3 nanoparticles were also used to detect the effect of a non-magnetic nanoparticle on the synthesis and nanocrystallization of titania. For each sample, a deep physical characterization was performed by XRD (with a Rietveld refinement of the structural data), FE-SEM, STEM, HRTEM, DSC analysis and BET surface area measurement. Furthermore, for some samples, the photocatalytic activity was investigated by degradation of methylene blue in aqueous medium, in the framework of a standard ISO 10678:2010 protocol. The hydrothermal synthesis was performed with a 3 hours' thermal treatment, at a pressure of approximatively 9 bar and a temperature significantly lower (Tmax═150 °C) than the usual temperature necessary to obtain crystalline anatase TiO2 (Tcryst═350 °C). The results give evidence that the mere presence of a nucleation seeds in the hydrothermal reactor, without any particular need for the composition and morphology, leads to crystalline anatase TiO2 nanoparticles with high photocatalytic performances.

Optimization of Three-Dimensional (3D) Chemical Imaging by Soft X-Ray Spectro-Tomography Using a Compressed Sensing Algorithm.

Soft X-ray spectro-tomography provides three-dimensional (3D) chemical mapping based on natural X-ray absorption properties. Since radiation damage is intrinsic to X-ray absorption, it is important to find ways to maximize signal within a given dose. For tomography, using the smallest number of tilt series images that gives a faithful reconstruction is one such method. Compressed sensing (CS) methods have relatively recently been applied to tomographic reconstruction algorithms, providing faithful 3D reconstructions with a much smaller number of projection images than when conventional reconstruction methods are used. Here, CS is applied in the context of scanning transmission X-ray microscopy tomography. Reconstructions by weighted back-projection, the simultaneous iterative reconstruction technique, and CS are compared. The effects of varying tilt angle increment and angular range for the tomographic reconstructions are examined. Optimization of the regularization parameter in the CS reconstruction is explored and discussed. The comparisons show that CS can provide improved reconstruction fidelity relative to weighted back-projection and simultaneous iterative reconstruction techniques, with increasingly pronounced advantages as the angular sampling is reduced. In particular, missing wedge artifacts are significantly reduced and there is enhanced recovery of sharp edges. Examples of using CS for low-dose scanning transmission X-ray microscopy spectroscopic tomography are presented.

L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles.

Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn(2+) and L-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested.

Study of Molecular Conformation and Activity-Related Properties of Lipase Immobilized onto Core-Shell Structured Polyacrylic Acid-Coated Magnetic Silica Nanocomposite Particles.

A facile approach for the preparation of core-shell structured poly(acrylic acid) (PAA)-coated Fe3O4 cluster@SiO2 nanocomposite particles as the support materials for the lipase immobilization is reported. Low- or high-molecular-weight (1800 and 100,000, respectively) PAA molecules were covalently attached onto the surface of amine-functionalized magnetic silica nanoacomposite particles. The successful preparation of particles were verified by scanning transmission electron microscopy (STEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), zeta potential measurement, and Fourier-transform infrared (FTIR) techniques. Once lipase is covalently immobilized onto the particles with an average diameter of 210 ± 50 nm, resulting from high binding sites concentrations on the low- and high-molecular-weight PAA-coated particles, high lipase immobilization efficiencies (86.2% and 89.9%, respectively), and loading capacities (786 and 816 mg g(-1), respectively) are obtained. Results from circular dichroism (CD) analysis and catalytic activity tests reveal an increase in the ß-sheet content of lipase molecules upon immobilization, along with an enhancement in their activities and stabilities. The lipases immobilized onto the low- and high-molecular-weight PAA-coated particles show maximum activities at 55 and 50 °C, respectively, which are ∼28% and ∼15% higher than that of the free lipase at its own optimum temperature (40 °C), respectively. The immobilized lipases exhibit excellent performance at broader temperature and pH ranges and high thermal and storage stabilities, as well as superior reusability. These prepared magnetic nanocomposite particles can be offered as suitable support materials for efficient immobilization of enzymes and improvement of the immobilized enzymes properties.

Colloid-probe AFM studies of the interaction forces of proteins adsorbed on colloidal crystals.

In recent years, colloid-probe AFM has been used to measure the direct interaction forces between colloidal particles of different size or surface functionality in aqueous media, as one can study different forces in symmerical systems (i.e., sphere-sphere geometry). The present study investigates the interaction between protein coatings on colloid probes and hydrophilic surfaces decorated with hexagonally close packed single particle layers that are either uncoated or coated with proteins. Controlled solvent evaporation from aqueous suspensions of colloidal particles (coated with or without lysozyme and albumin) produces single layers of close-packed colloidal crystals over large areas on a solid support. The measurements have been carried out in an aqueous medium at different salt concentrations and pH values. The results show changes in the interaction forces as the surface charge of the unmodified or modified particles, and ionic strength or pH of the solution is altered. At high ionic strength or pH, electrostatic interactions are screened, and a strong repulsive force at short separation below 5 nm dominates, suggesting structural changes in the absorbed protein layer on the particles. We also study the force of adhesion, which decreases with an increment in the salt concentration, and the interaction between two different proteins indicating a repulsive interaction on approach and adhesion on retraction.

Size-dependent surface effects in maghemite nanoparticles and its impact on interparticle interactions in dense assemblies.

The question of the dominant interparticle magnetic interaction type in random closely packed assemblies of different diameter (6.2-11.5 nm) bare maghemite nanoparticles (NPs) is addressed. Single-particle magnetic properties such as particle anisotropy and exchange bias field are first of all studied in dilute (reference) systems of these same NPs, where interparticle interactions are neglible. Substantial surface spin disorder is revealed in all particles except the smallest, viz. for diameters d = 8-11.5 nm but not for d = 6.2-6.3 nm. X-ray diffraction analysis points to a crystallographic origin of this effect. The study of closely packed assemblies of the d ≥ 8 nm particles observes collective (superspin) freezing that clearly appears to be governed by interparticle dipole interactions. However, the dense assemblies of the smallest particles exhibit freezing temperatures that are higher than expected from a simple (dipole) extrapolation of the corresponding temperatures found in the d ≥ 8 nm assemblies. It is suggested that the nature of the dominant interparticle interaction in these smaller particle assemblies is superexchange, whereby the lack of significant surface spin disorder allows this mechanism to become important at the level of interacting superspins.

Long-Term Use of Metformin and Vitamin B12 Deficiency in Diabetes.

This extensive review delves into the complex relationship between prolonged use of metformin and the possible emergence of vitamin B12 deficiency (VB12D) in diabetic patients. Metformin, a pivotal element in diabetes management, is constantly linked with decreased absorption of vitamin B12, prompting concerns about the enduring consequences of this interaction. The review systematically amalgamates current evidence, elucidating the prevalence, mechanisms, and clinical ramifications of VB12D induced by consistent consumption of metformin. Exploring the different pathways through which metformin might disrupt the absorption of Vitamin B12, the review encompasses interference with the calcium-dependent membrane activity and alterations of the microbiota present in the gut. A meticulous analysis of experimental studies and human trials is undertaken, accentuating the prevalence of variable VB12D among individuals on long-duration treatment of metformin across diverse populations and age groups. Clinical indications of cobalamin deficiency, spanning haematological abnormalities to neurological complications, are systematically examined. Furthermore, the review delves into the potential implications of cobalamin deficiency associated with metformin on diabetes-related complications and overall patient health. This review offers a comprehensive overview of the intricate interplay between the use of metformin and deficiency of vitamin B12 in diabetic patients, emphasizing the importance that lies in routine monitoring, early detection, and personalized interventions to optimize the long-period safety and efficiency of metformin in the treatment of diabetes. It also proposes future research directions to refine clinical guidelines and enhance the understanding regarding the correlation between diabetes, metformin, and vitamin B12.

Intravitreal therapeutic nanoparticles for age-related macular degeneration: Design principles, progress and opportunities.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. The current standard treatment for AMD involves frequent intravitreal administrations of therapeutic agents. While effective, this approach presents challenges, including patient discomfort, inconvenience, and the risk of adverse complications. Nanoparticle-based intravitreal drug delivery platforms offer a promising solution to overcome these limitations. These platforms are engineered to target the retina specifically and control drug release, which enhances drug retention, improves drug concentration and bioavailability at the retinal site, and reduces the frequency of injections. This review aims to uncover the design principles guiding the development of highly effective nanoparticle-based intravitreal drug delivery platforms for AMD treatment. By gaining a deeper understanding of the physiology of ocular barriers and the physicochemical properties of nanoparticles, we establish a basis for designing intravitreal nanoparticles to optimize drug delivery and drug retention in the retina. Furthermore, we review recent nanoparticle-based intravitreal therapeutic strategies to highlight their potential in improving AMD treatment efficiency. Lastly, we address the challenges and opportunities in this field, providing insights into the future of nanoparticle-based drug delivery to improve therapeutic outcomes for AMD patients.

Role of Mean Platelet Volume (MPV) as a Prognostic Marker in Patients with Acute Kidney Injury.

This study aimed to investigate the prognostic significance of mean platelet volume (MPV) in 50 AKI patients. Blood samples were collected according to KDIGO guidelines, and complete blood counts, including MPV, were analyzed. Significant differences in MPV were observed among patients who recovered with or without dialysis and those who expired. A statistically significant difference was present in between the mean platelet count of patients recovered without dialysis, recovered with dialysis, and the expired patients. The Area Under Curve (AUC) for MPV scores was as high as 0.842. Indicating that in up to 84% of the pairs (death-survival) the models correctly estimated that the probability of survival was higher than that of death. MPV had an optimum cutoff point of score value <9.60 with a sensitivity of 80% and specificity of 91.11%. These findings suggested that MPV could serve as a cost-effective and superior tool to creatinine in early AKI detection.

A Comparative Study on Levels of hs-CRP and Lipid Profile in Prediabetic and Normal Population.

This study aimed to compare high-sensitivity C-reactive protein (hs-CRP) and lipid profile levels between prediabetic and normal populations and explore correlations between hs-CRP and lipid profile in prediabetic individuals. The study was conducted among Group A comprising 75 prediabetic individuals, and Group B, which included 75 non-diabetic controls from the general population. Results showed that the mean hs-CRP level in Group A (1.717) significantly exceeded that of Group B (0.917) (p = 0.001). Pearson correlation analysis revealed significant positive linear relationships between hs-CRP and lipid profile parameters, indicating that as total cholesterol, triglycerides (TGs), high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL) increased, hs-CRP also increased. A significant negative linear relationship was observed between hs-CRP and HDL. Moreover, a positive linear relationship existed between hs-CRP and glycemic parameters (fasting blood sugar (FBS), postprandial blood sugar (PPBS), and Glycated haemoglobin (HbA1c)). It is concluded that elevated hs-CRP, an inflammatory marker, correlated with dysregulated lipid profiles, and glycemic parameters, indicating its potential role in assessing inflammation in prediabetic individuals and its association with dyslipidemia and glucose metabolism.

Research on psychotherapy in India: A systematic review.

We systematically reviewed empirical studies of psychotherapy with Indian clients. We defined psychotherapy as an intervention aimed at treating mental disorders using "talk," which, in a professional medical setting, along with the therapeutic relationship, acquires medicinal value. Besides manual searches in three leading Indian psychiatry journals, we conducted digital searches in PubMed, Google Scholar, and Scopus databases. We found that the commonly practiced evidence-based psychotherapy in India follows the cognitive-behavioral model. Our findings suggest several replication studies which claimed to have used the well-established western models of cognitive behavioural paradigm but have mostly focused on basic behavioural techniques in their protocol. A few innovations were observed, and several essential errors were noted. Innovations include contextual modifications to address the difficulties and challenges faced in service delivery, while errors include deviations from protocol without adequate rationale.

Advancements in Combating Fungal Infections: A Comprehensive Review on the Development of Azole Hybrid Antifungals.

OBJECTIVE: In this review, we have summarized antifungal agents containing potent azole analogues. DATA ACQUISITION: The provided literature is related to the development and application of azole derivatives and has been accessed from electronic data bases such as Science direct, Google Scholar, and Pubmed using keywords such as "design, synthesis and evaluation", "azole hybrids", "diazole hybrids", "indazole derivatives", "imidazole derivatives", "triazole derivatives", "tetrazole derivatives" and related combinations. RESULT: From this review, it was identified that azole derivatives with promising antifungal activity play a vital role in drug discovery and development. The literature revealed that azole derivatives can effectively fight several types of microorganisms, such as Candida albicans, Aspergillus niger, and others. The rational design and structure‒activity relationship of these compounds are discussed in this paper, highlighting their potential as effective therapeutic options against various fungal pathogens. Moreover, this work addresses the challenges and future directions in the development of azole hybrids. The results of docking studies of several of the hybrids that the researchers provided are also summarized. CONCLUSION: The current work attempts to review such innovations, which may lead to the preparation of novel therapeutics. More research is required to confirm their safety and effectiveness in clinical practices.

Artificial viruses: A nanotechnology based approach.

OBJECTIVES: The main objective of this work was to review and summarise the detailed literature available on viral nanoparticle and the strategies utilised for their manufacture along with their applications as therapeutic agents. DATA ACQUISITION: The reported literature related to development and application of virus nanoparticles have been collected from electronic data bases like ScienceDirect, google scholar, PubMed by using key words like "viral nanoparticles", "targeted drug delivery" and "vaccines" and related combinations. RESULT: From the detailed literature survey, virus nanoparticles were identified as carriers for the targeted delivery. Due to the presence of nanostructures in virus nanoparticles, these protect the drugs from the degradation in the gastrointestinal tract and in case of the delivery of gene medicine, they carry the nucleic acids to the target/susceptible host cells. Thus, artificial viruses are utilised for targeted delivery to specific organ in biomedical and biotechnological areas. CONCLUSION: Thus, virus nanoparticles can be considered as viable option as drug/gene carrier in various healthcare sectors especially drug delivery and vaccine and can be explored further in future for the development of better drug delivery techniques.

Synthesis, in silico screening, and biological evaluation of novel pyridine congeners as anti-epileptic agents targeting AMPA (α-amino-3-hydroxy-5-methylisoxazole) receptors.

The research involves the synthesis of a series of new pyridine analogs 5(i-x) and their evaluation for anti-epileptic potential using in silico and in vivo models. Synthesis of the compounds was accomplished by using the Vilsmeier-Haack reaction principle. AutoDock 4.2 was used for their in silico screening against AMPA (-amino-3-hydroxy-5-methylisoxazole) receptor (PDB ID:3m3f). For in vivo testing, the maximal electroshock seizure (MES) model was used. The physicochemical, pharmacokinetic, drug-like, and drug-score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. The in silico results showed that all the synthesized compounds 5(i-x) had 1-3 interactions and affinities ranging from -6.5 to -8.0 kJ/mol with the targeted receptor compared to the binding affinities of the standard drug phenytoin and the original ligand of the target (P99), which were -7.6 and -6.8 kJ/mol, respectively. In vivo study results showed that the compound 5-Carbamoyl-2-formyl-1-[2-(4-nitrophenyl)-2-oxo-ethyl]-pyridinium gave 60% protection against epileptic seizures compared to 59% protection afforded by regular phenytoin. All of them met Lipinski's rule of five and had drug-likeness and drug score values of 0.55 and 0.8, respectively, making them chemically and functionally like phenytoin. According to the findings of the studies, the synthesized derivatives have the potential to be employed as a stepping stone in the development of novel anti-epileptic drugs.

Understanding CFTR Functionality: A Comprehensive Review of Tests and Modulator Therapy in Cystic Fibrosis.

Cystic fibrosis is a genetic disorder inherited in an autosomal recessive manner. It is caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene on chromosome 7, which leads to abnormal regulation of chloride and bicarbonate ions in cells that line organs like the lungs and pancreas. The CFTR protein plays a crucial role in regulating chloride ion flow, and its absence or malfunction causes the production of thick mucus that affects several organs. There are more than 2000 identified mutations that are classified into seven categories based on their dysfunction mechanisms. In this article, we have conducted a thorough examination and consolidation of the diverse array of tests essential for the quantification of CFTR functionality. Furthermore, we have engaged in a comprehensive discourse regarding the recent advancements in CFTR modulator therapy, a pivotal approach utilized for the management of cystic fibrosis, alongside its concomitant relevance in evaluating CFTR functionality.

Effect of Vitamin D on Retinoblastoma Protein in Prediabetic Individuals.

About 50.8 million people were diagnosed with diabetes in 2011; the count has increased by 10 million in the last five years. Type-1 diabetes could occur at any age, but predominantly in children and young adults. The risk of developing type II diabetes mellitus in the offspring of parents with DM II is 40% if one parent has DM II and approaches 70% if both parents have DM II. The process of developing diabetes from normal glucose tolerance is continuous, with insulin resistance being the first stage. As prediabetes progresses slowly to DM II, it may take approximately 15-20 years for an individual to become diabetic. This progression can be prevented or delayed by taking some precautions and making some lifestyle amendments, e.g., reducing weight by 5-7% of total body weight if obese, etc. Retinoblastoma protein is one of the pocket proteins that act as crucial gatekeepers during the G1/S transition in the cell cycle. A loss or defect in single- cell cycle activators (especially CDK4 and CDK6) leads to cell failure. In diabetic or stress conditions, p53 becomes a transcription factor, resulting in the transactivation of CKIs, which leads to cell cycle arrest, cell senescence, or cell apoptosis. Vitamin D affects insulin sensitivity by increasing insulin receptors or the sensitivity of insulin receptors to insulin. It also affects peroxisome proliferator-activated receptors (PPAR) and extracellular calcium. These influence both insulin resistance and secretion mechanisms, undertaking the pathogenesis of type II diabetes. The study confines a marked decrement in the levels of random and fasting blood glucose levels upon regular vitamin D intake, along with a significant elevation of retinoblastoma protein levels in the circulatory system. The most critical risk factor for the occurrence of the condition came out to be family history, showing that patients with first-degree relatives with diabetes are more susceptible. Factors such as physical inactivity or comorbid conditions further aggravate the risk of developing the disease. The increase in pRB levels caused by vitamin D therapy in prediabetic patients directly influences blood glucose levels. pRB is supposed to play a role in maintaining blood sugar levels. The results of this study could be used for further studies to evaluate the role of vitamin D and pRB in regeneration therapy for beta cells in prediabetics.