Cardiovascular diseases (CVDs) represent the primary cause of mortality globally, accounting for around 17.9 million fatalities annually. These conditions frequently arise from structural and functional injuries in heart, including cardiac hypertrophy, vascular stiffening and impaired muscle contraction. A major contributor to many forms of CVD is dysregulation of calcium-dependent cardiomyocyte contraction. The entry of calcium ions (Ca2+) via L-type voltage-dependent calcium channels (L-VDCCs) is essential for contraction of cardiac and smooth muscle cells. These channels are on plasma membrane and T-tubules in cardiomyocytes, along with trafficking and scaffold proteins. A range of transmitters and hormones are known for regulating Cav1.2 and have been linked to CVDs, many of which also involve protein kinase C (PKC). Activation of Gq-coupled receptors and subsequent activation of protein lipase C (PLC) are among the most common mechanisms of PKC activation in cardiac and smooth muscle cells. Both in vitro and in vivo, Cav1.2 found to be regulated, phosphorylated, and linked with PKC. In addition to PKC-mediated regulation, β-adrenergic receptors are stimulated, and adenylate cyclase produces more cyclic adenosine monophosphate, which activates protein kinase A (PKA) and phosphorylates L-VDCC. This review highlights functional significance of L-VDCCs in cardiac physiology and examines therapeutic potential of calcium channel blockers (CCBs) in clinical trials.
Breast cancer continues to be a significant global health issue, prompting the continuous pursuit of innovative therapeutic and adjunctive approaches. This review offers an extensive examination of the existing scientific evidence regarding the anti-cancer efficacy of plant-derived oils in relation to breast cancer pathogenesis, with a specific emphasis on differentiating their two primary categories: fixed oils (vegetable oils) and essential oils. Fixed oils, such as extra-virgin olive oil and flaxseed oil, mainly exert their effects by their fatty acid compositions and non-volatile phenolic compounds, demonstrating mechanisms such as estrogen receptor modulation and HER2 inhibition. Plant-derived essential oils, which are rich in volatile terpenes and phenols, such as frankincense and Zataria multiflora, primarily provoke apoptosis by oxidative stress and mitochondrial dysfunction. We conduct a systematic analysis of the in vitro and in vivo evidence that substantiates their anti-proliferative and pro-apoptotic effects across diverse breast cancer subtypes. This review essentially focuses on the significant gap between actual in vitro concentrations and doses that can be reached in vivo. We underscore the necessity for subsequent research to transcend descriptive studies and address critical issues in bioavailability, standardized efficacy, and the advancement of sophisticated delivery systems. The review seeks to elucidate this intricate domain, repositioning plant-derived oils from simple alternative medications to a significant repository of bioactive compounds, pioneering pharmaceutical strategies and requiring rigorous scientific validation for their oncology integration.
There are two key proteins, A0A844SEK3_9BRAD and A0A6P1CI42_RHITR, from Bradyrhizobium yuanmingense and Rhizobium tropici strain CIAT 899, respectively that are known to play an important role in symbiotic relationships with legumes and nitrogen fixation. Studying these proteins mechanism is essential for advancing agricultural practices. This study aims to provide insights into their structural features. The analysis of the physicochemical properties of the proteins revealed their molecular weights, theoretical isoelectric points, and amino acid compositions. Secondary structure analysis predicted the presence of alpha helices, extended strands, and random coils in both proteins, indicating diverse structural compositions that contribute to their overall architecture and potential functions. Tertiary structure prediction provided insights into the three-dimensional arrangement of the proteins, with models exhibiting moderate to good quality and high structural similarity to the templates. Domain analysis identified distinct domains within the proteins, and Nif-specific regulatory protein domains, which shed light on their functional characteristics. The presence of specific domains in the proteins suggests their involvement in ATP binding, signal transduction, DNA binding, and transcriptional regulation. The structural and functional characteristics of A0A844SEK3_9BRAD and A0A6P1CI42_RHITR are thoroughly understood in this study, which advances our understanding of nitrogen fixation and plant-microbe relationships. The results have implications for optimizing agricultural practices.
Passer domesticus is an avian which is believed to be under extinction. In India, many Passerines existed, but urban life paving the way for, and the rural habitation dwindling, there is a threat for these birds to go under extinction. In recent years, electromagnetic radiation (EMR) from mobile communication infrastructure and power systems has also been hypothesized as a contributing stressor, with reported associations between high EMR exposure and altered avian behaviour, reproductive success, and embryonic development in birds. This review integrates ecological, physiological, and genomic perspectives to evaluate potential mechanisms underlying Passer domesticus population decline. Particular emphasis is placed on urban ecological disruption, chronoecological mismatches affecting breeding cycles, and the Allee effect in small or fragmented populations. Overall, Passer domesticus emerges as both a sensitive bioindicator of urban environmental change and a valuable model for studying human-driven ecological and genomic impacts. The synthesis underscores the need for integrative conservation approaches combining ecological monitoring, reproductive biology, and genomic tools to better understand and mitigate ongoing population declines in urban avifauna.
Microbial phytase enhances food quality by hydrolysing phytate into simpler derivatives and releasing elements that serve as macroelements. Fungi were isolated from the pulp and seeds of jackfruit on potato dextrose agar. The fungi were screened for phytase production, and the best phytase producer was selected and identified molecularly using the ITS region. Phytase production by the selected fungus was optimised. The effects of temperature, pH, and cations on the produced phytase were determined. Jackfruit was treated with the selected fungus, and proximate analyses of both treated and untreated jackfruits were carried out. The top phytase producer, with a hydrolytic index of 2.67, was identified as Aspergillus aculeatus JF3, with accession number OQ992634. Maximum phytase production was recorded in a medium containing Na+, sucrose, peptone, and Triton X-100. Phytase activity of Aspergillus aculeatus JF3 was relatively stable between 35 and 85℃ and from pH 3 to 9. Iron II positively influenced the phytase activity of Aspergillus aculeatus JF3. The phytic acid content of jackfruit treated with Aspergillus aculeatus JF3 decreased by 18% compared to the untreated samples. The phytase-producing Aspergillus aculeatus JF3 isolated from Artocarpus heterophyllus exhibited stability across different temperatures and pH levels, enhancing nutrient bioavailability in Artocarpus heterophyllus.
Current PCOS treatments may cause adverse effects and inadequately address endocrine and metabolic disturbances, warranting safer multitarget phytochemicals. This study evaluated the therapeutic potential of sesamol and daidzein in a letrozole-induced PCOS model in female Wistar rats. Acute oral toxicity studies were conducted in accordance with OECD guideline 425, based on which treatment doses were selected. PCOS was induced through a 21-day administration of letrozole (1 mg/kg body weight), followed by 14 days of treatment with sesamol (10 and 50 mg/kg) and daidzein (10 and 50 mg/kg), administered orally. Therapeutic potency was estimated through analysis of oestrous cycle regulation, fasting blood glucose, serum hormone concentrations, lipid profiles and histopathological examination of ovarian tissues. 1593 mg/kg was estimated as the LD₅₀ of sesamol. Within the 14-day treatment period, sesamol and daidzein reduced elevated testosterone levels, improved oestrous cyclicity, and decreased ovarian cyst formation. At lower doses, oestrogen levels improved more noticeably, whereas changes in fasting blood glucose and lipid profile remained modest and inconsistent. Daidzein and sesamol especially revived hormonal balance and ovarian function, with limited impacts on metabolic parameters.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline, often linked to the dysfunction of acetylcholinesterase (AChE). In this study, anthranilic acid-based alkaloids isolated from Persicaria tinctoria were virtually screened for their inhibitory potential against AChE using molecular docking and molecular dynamics simulations. Docking analysis revealed that several compounds exhibited strong binding affinities, interacting with key residues at the catalytic active site, peripheral anionic site, and choline-binding site. Among them, Compound 13 demonstrated the highest binding affinity (–9.01 kcal/mol) and a favorable inhibition constant (253.32 nM), forming stable interactions with critical residues including TRP86, TYR124, TYR341, and PHE295. Molecular dynamics simulations confirmed the structural stability and flexibility of the AChE–Compound 13 complex, further supporting its potential as a lead candidate. Other compounds also showed varied inhibitory profiles, targeting peripheral and allosteric sites of the enzyme. These findings suggest that alkaloids from P. tinctoria may serve as promising natural scaffolds for developing novel AChE inhibitors for AD therapy.
The accelerating thermal demands of contemporary energy, electronic and biomedical systems have rendered conventional working fluids inadequate for high‐flux heat dissipation. Mono‐ and binary‐hybrid nanofluids partially address this deficit, yet the synergistic potential of three dissimilar nanoparticles dispersed in a single base fluid remains insufficiently characterised, particularly under the simultaneous action of rotation, temperature‐dependent viscosity and nonlinear thermal radiation. The present investigation is motivated by this gap and seeks to quantify how a water‐based ternary nanofluid composed of copper, alumina and silver (Cu–Al2O3–Ag/H2O) responds, in a rotating frame, to the coupled influence of partial velocity slip, Arrhenius activation energy, Newtonian cooling and nonlinear thermal radiation. The governing partial differential equations are reduced to a set of nonlinear, coupled ordinary differential equations through suitable similarity transformations and are integrated numerically by employing a fifth‐order Runge–Kutta–Fehlberg algorithm coupled with the shooting technique. Rigorous validation against previously reported limiting‐case solutions establishes the fidelity of the present scheme. The hydrodynamic, thermal and concentration fields are interrogated systematically with respect to all pertinent physical parameters, and the engineering quantities of interest; skin friction coefficient, local nusselt number and local sherwood number are tabulated. The numerical experiments reveal that the axial velocity is attenuated by augmentation of the slip parameter, the viscosity parameter and the nonlinear radiation parameter, whereas it is amplified by the Newtonian cooling parameter. The thermal field is enhanced by viscous dissipation, Brownian diffusion and thermophoresis, and the ternary suspension consistently outperforms its binary‐hybrid counterpart in terms of heat transport efficiency. The findings furnish quantitative guidance for the design of advanced thermal‐management devices that exploit multi‐component nanofluids.
Systemic inflammation is increasingly linked to Major Depressive Disorder (MDD), and its expression may vary across populations. This study evaluates serum high sensitive C-reactive protein (hs-CRP) and Interleukin-1β (IL-1β) levels in MDD patients (n-40) and healthy controls (n=40) to understand the biological basis of depression within the unique ethnic and environmental context of Sikkim. Females were the majority in both MDD (67.5%) and control (70%) groups. Most participants had a normal BMI (MDD: 62.5%, Control: 67.5%), with few cases of obesity or underweight. Nepali ethnicity was predominant in both MDD: 80% and,Control: 77.5% followed by Bhutias and others however statistically insignificant. hs-CRP differed significantly between MDD (3335.7 pg/L) and controls (3164.7 pg/L) P< 0.05, though it did not vary by depression severity. hs-CRP showed fair diagnostic ability (AUC = 0.746, 95% CI: 0.638–0.854, P< 0.01; sensitivity 65%, specificity 77.5%), whereas IL-1β demonstrated poor performance. hs–CRP shows potential as an adjunct inflammatory marker in assessing depression. Future studies should explore composite biomarker approach combined with clinical tools to enhance diagnostic and treatment strategies.
Worldwide, digestive diseases are now a prevalent issue that cause a considerable amount of illness. The available treatments for digestive issues frequently have drawbacks and adverse consequences. The major limitations are rebound effect, addressing the root cause, dependence, addiction, etc. These issues motivate research into traditional herbal treatments as a possible medicinal solution is gaining momentum. Herbs such as betel leaf, liquorice, saunth, cinnamon, fennel, cardamom, marica, pipali, and caraway, have long been used to treat digestive problems. Their combined effects on the modulation of digestive enzymes, however, have not been well investigated. Considering fewer Ayurvedic digestive formulations and formulation available in market a new poly herbal churna formulation was prepared for this investigation. Using lipase, amylase, and protease assays, the formulation was evaluated in vitro. The formulation's impact on digestive enzyme activity was compared to standard. The prepared formulation exhibited significant amylase and lipase inhibitory activities, comparable to standard inhibitors. The formulation's digestive enzyme modulation properties were attributed to the synergistic effects of its constituent herbs. A network pharmacology study of the churna's phytoconstituents targeting digestive function and related diseases identified top 10 genes (STAT3, HIF1A, IL6, JUN, TNF, MTOR, SRC, MMP9, ESR1, and NFKB1). KEGG pathway analysis revealed involvement of these genes in pathways related to insulin resistance, inflammatory bowel disease, cancer, pancreatic cancer, and hepatitis. The formulation may be used therapeutically to treat digestive problems because of its capacity to alter the activity of digestive enzymes. To better understand the formulation's mechanisms of action and investigate its potential therapeutic uses, more in vivo studies are necessary.
Cancer, particularly acute myeloid leukemia, remains a critical global health challenge, necessitating innovative therapeutic strategies. In Chinese traditional medicine, the resin of Dracaena draco L. has been used for promoting blood circulation and alleviating stasis, and steroidal saponins isolated from this plant have shown cytotoxic potential against acute myeloid leukemia cells. However, their molecular mechanisms remain insufficiently defined. Given the pivotal role of BCL-2 mediated apoptosis regulation in acute myeloid leukemia pathogenesis, this study evaluated the anti-leukemic properties of selected steroidal saponins using computational approaches. Molecular docking demonstrated CPD1's superior binding affinity (-10.93 kcal/mol) and favorable positioning within the 6GL8 binding pocket compared to venetoclax (-8.65 kcal/mol). Molecular dynamics simulations over 100 ns confirmed stable interactions underscoring CPD1's capacity to modulate BCL-2 effectively. MMGBSA analysis revealed a more favorable binding free energy for CPD1-6GL8 (-56.13 kcal/mol) than venetoclax-6GL8 (-30.29 kcal/mol). ADMET profiling indicated CPD1's non-genotoxicity, minimal hepatotoxicity, and balanced clearance, despite moderate intestinal absorption (55.034%) relative to venetoclax (100%). DFT analysis highlighted CPD1's enhanced reactivity (Delta E = 2.8949 eV) compared to venetoclax (Delta E = 4.8522 eV), reflecting greater electrophilicity (13.8734 eV vs. 9.0166 eV). These results position CPD1 as a promising candidate for acute myeloid leukemia therapy through BCL-2-mediated anti-apoptosis.
Conventional anti-inflammatory therapies provide symptomatic relief but are often constrained by adverse effects and reduced long-term efficacy. As a result, there is a growing interest towards the development of natural compounds as safer alternatives. Marine-derived polysaccharides are known for the biocompatibility, low toxicity and immunomodulatory properties. Our earlier study evaluated the anti-inflammatory potential of the polysaccharide fractions extracted from the marine bivalves. The fractions were isolated from Saccostrea cucullata (SCP), Perna viridis (PVP), Perna indica (PIP) and Geloina erosa (GEP). All of them exhibited potent anti-inflammatory activity in formalin induced paw oedema model in mice. In the present study, the underlying molecular mechanisms of these polysaccharides were investigated using RTqPCR analysis. The reference drug used was indomethacin at the dose of 10 mg/kg. Formalin induction led to pronounced upregulation of pro-inflammatory mediators. Among the four polysaccharides, GEP markedly downregulated NF-kappa B along with its downstream mediators TNF-alpha, IL-6, iNOS, and COX-2. PVP, PIP, and SCP also demonstrated dose-dependent inhibitory effects, although their activities were comparatively less pronounced. Taken together, these findings suggest that the polysaccharide derived from marine bivalves have potent anti-inflammatory efficacy mediated through modulation of multiple molecular targets within the canonical NF-kappa B signalling pathway.
The paper is an attempt to model the Dynamic Cognitive System (DCS) in order to describe the interaction between the brain and the all-pervasive cosmic field, which is equated with the zero-point Field (ZPF) of physics, theorized within the framework of stochastic electrodynamics. The interaction has been modelled in terms of the DCS, of which the all-pervasive cosmic field is considered to be an integral component. The modelling of the DCS, inspired by some recent works, aims at addressing the hard problem of consciousness and further exploring some novel features of the brain corresponding to the different states of consciousness. The model is a scientific conceptualization informed by some philosophical insights. The empirical ideas are scientifically characterized and mapped on to the framework of stochastic electrodynamics. The problem thus has been reduced to the dynamics of a harmonic oscillator dipped in the classical vacuum, which is characterized by the ZPF. The differential equation with a noise term becomes the representative model for the DCS, opening up an enormous scope for interpretation in regard to the physics of the cognitive response of the brain and also that of the qualia. The model is expected to have a bearing on the neural correlates on consciousness.
Efficient and controlled gene delivery remains a critical requirement in biomedical research, particularly for applications in tissue engineering, gene therapy and cell-based assays. Conventional non-viral gene delivery methods often face limitations such as low transfection efficiency, lack of spatial control and cytotoxicity. Hence there is need for innovative platforms that enable precise, efficient and localized gene transfer. In this study, in-house developed Poly(N-isopropylacrylamide)-Co-Glycidyl Metharylate (NGMA) polymer has been evaluated as a non-viral gene transfer platform by transferring plasmid DNA encoded with Green Fluorescent Protein (GFP). The NGMA-plasmid complexes were coated onto tissue culture polystyrene surfaces and L-929 cells were cultured on these surfaces. Gene transfer was induced through temperature modulation in the presence of a transfection reagent, enabling intracellular uptake and functional expression of GFP. The delivery of plasmids into the cell monolayer was evaluated in different conditions. Results demonstrated rapid and efficient cellular internalization of plasmid DNA, with distinct GFP expression observed only on polymer-coated regions, confirming the spatial and temporal control of this solid-state gene delivery system. This novel approach merges non-viral gene delivery with substrate-associated cell culture, providing a versatile platform for generating genetically modified cell monolayers.
Vincristine sulfate, a naturally occurring vinca alkaloid from Catharanthus roseus, remains a crucial component of polychemotherapeutic regimens for a wide range of haematological malignancies, including acute lymphoblastic leukemia (ALL), Hodgkin's lymphoma, and non-Hodgkin's lymphomas. Vinca alkaloid relies on its antineoplastic property to interfere with the microtubule’s dynamics, thereby, it stops mitosis, inducing apoptotic cascades in rapidly dividing cells. Vincristine is being utilised in chemotherapy formulation due to its high-affinity binding to tubulin dimers, which inhibits microtubule assembly and induces mitotic arrest and apoptosis during the mitotic M-phase of the cell cycle. Since lymphoid and myeloid neoplasms proliferate quickly, vincristine offers a targeted cytotoxic advantage with a distinct, bone-marrow-sparing toxicity profile. As vincristine does not significantly impair myelosuppression, it can be incorporated into dose-intensive, multi-drug regimens that have greatly increased survival rates in both adult and paediatric populations. However, its clinical utility is often challenged by dose-limiting peripheral neurotoxicity and emerging resistance mechanisms. There is a substantial gap in standardised vincristine toxicity assessment, pharmacogenomic prediction, and targeted drug delivery systems, highlighting the need for continued investigation. This review investigates current pharmacological aspects and clinical outcomes, vincristine’s status as a therapeutic agent in curative-intent regimens while evaluating recent innovations, like liposomal formulation and structural modifications, designed to enhance delivery and mitigate adverse effects like toxicity and other oncologic factors, including its clinical uses and limitations.
Water stress is a significant global issue that severely limits crop production worldwide, and recent changes in the global climate have exacerbated the problem. Wheat crops are especially vulnerable to water shortages, which result in decreased yield and production. Mutation breeding offers a potential alternative approach for developing crops that are important for agriculture. It can enhance specific traits without altering entire genotype. In this study, ISSR markers were employed to evaluate genetic variation and diversity at the molecular level among selected M3 mutant lines and wild-type wheat genotypes after chemical mutagenesis in response to moisture stress during 2022-2023 rabi season at SVPUA&T, Meerut, India. Out of 15 ISSR primers, 12 showed successful amplification across both genotypes. In HD-3226, 50 alleles and 585 amplified bands were recorded across 13 ISSR loci. PIC values ranged from 0.21 to 0.81, with an average of 0.47 for EMS and 0.39 for SA. The resolving power ranged between 2.33 and 9.56, while the marker index ranged from 0.59 to 3.95. Nine primers exhibited 100% polymorphism, and genetic similarity ranged from 0.40 to 0.88. UPGMA clustering grouped mutant lines into five clusters with genetic distances ranges from 0.54 to 1.00. The greatest dissimilarity (0.404) was observed between mutant 0.5% EMS (15% PEG, P-41) and 0.75% EMS (15% PEG, P-63) whereas the highest similarity (0.880) was between 0.04% SA (15% PEG, P-36) and 0.25% EMS (15% PEG, P-19). In HI-1620, 41 alleles and 273 amplified bands were produced. PIC values ranged from 0.00 to 0.89, with averages of 0.35 (EMS) and 0.42 (SA). Resolving power varied from 1.40 to 7.00, and marker index from 0.30 to 2.75. Eight primers showed 100% polymorphism. Genetic similarity ranged from 0.411 to 0.823. UPGMA dendrogram formed four clusters with genetic distances between 0.50 and 0.97. M3 mutant lines 0.02% SA (15% PEG, P-28) and 0.25% EMS (15% PEG, P-4) were found to closely dissimilar (0.411) to each other while highest genetic similarity (0.823) was detected between mutant lines 0.02% SA (15% PEG, P-4) and 0.25% EMS (15% PEG, P-4). Our study found that ISSR markers, with their high PIC and resolving power, are highly effective at distinguishing closely related wheat mutant lines. Furthermore, identified M3 mutants represent promising resources for reverse genetics and functional genomics approaches to improve drought tolerance in wheat.
The global popularity of traditional herbal medicine is on the rise, despite facing disparagement for lack of scientific validation. Many traditional herbal preparations are endorsed for their anti-inflammatory properties. Cytokines, as key regulators of the immune system, can significantly impact immune status. Given the limited understanding of molecular targets and mechanisms, there is a crucial need to scientifically validate the potential of anti-inflammatory herbs at the molecular level. In view of this, Aegle marmelos (L.) Correa, commonly known as ‘Bael’, was investigated for its antioxidative and anti-inflammatory properties using chicken lymphocytes culture system. The study utilized aqueous extract of Aegle marmelos leaves (AME) to assess antioxidative potential through various assays. The calculated maximum non-cytotoxic dose of AME was used for treatment in chicken lymphocytes in vitro, allowing for the examination of transcriptional modulation of selected genes via qRT-PCR. Results showed significant in vitro antioxidant properties of AME across multiple assays. Gene expression analysis revealed notable alterations due to AME exposure, with pro-inflammatory genes being down-regulated and anti-inflammatory genes up-regulated. The study concluded that AME exhibits potent anti-oxidative and anti-inflammatory potential, warranting further exploration through appropriate in vivo experiments due to its strong anti-inflammatory activity.
The cryopreserved semen is used in assisted reproductive technologies. There is a continued oxidative stress during cryopreservation, causing oxidative damage to spermatozoa. The isoAsp formation during oxidative stress results in the loss of protein function. The protein L-isoaspartate-O-methyltransferase (PIMT) repairs back the isoAsp residues to L-aspartyl, restoring the lost functionality of the affected proteins. The quality of cryopreserved semen could be improved by using PIMT as a supplement to semen extender. The objective of the study was to express biologically active buffalo recombinant PIMT (rPIMT). The similar to 650 bp PCR-amplified PIMT was cloned and sequenced. The protein was consistently expressed as inclusion bodies in E. coli T7 Express lysS cells and then bulk-purified under denaturing conditions. The protein sequence showed 96.55% identity with the bovine PIMT protein. The purified rPIMT showed a single protein band corresponding to 31 kDa on SDS-PAGE and Western blot. A synthetic isoaspartate-containing peptide served as the substrate to assess enzymatic activity. The effective methylation of iso-aspartate residues in the synthetic peptide substrate served as evidence of PIMT enzyme activity. Thus, the bioactive rPIMT could potentially be added to buffalo semen extender to repair the oxidatively damaged seminal plasma proteins that arise during cryopreservation.
Insulin resistance (IR) is a significant risk factor for cardiovascular disease, which is the leading cause of death worldwide. A straightforward and reasonably priced surrogate indicator for IR and cardiovascular risk is the triglycerideglucose (TyG) index. The purpose of this study was to assess the TyG index's correlation and diagnostic value in patients with confirmed coronary artery disease (CAD). 75 CAD patients and 75 healthy controls were compared in this hospitalbased cross sectional study. The TyG index was evaluated as an independent predictor using logistic regression, which was adjusted for age, sex, and BMI. The ideal cutoff and diagnostic accuracy were determined by ROC curve analysis. The mean TyG index was significantly higher in the CAD group (4.94 +/- 0.34) versus Controls (4.56 +/- 0.21) (P< 0.001). Multivariate analysis confirmed the TyG index as an independent predictor of CAD (OR: 18.49, 95% CI: 3.57-95.82, P=0.001). ROC analysis yielded an AUC of 0.818. The optimal cutoff was 4.71, achieving 77%sensitivity and 80% specificity. The TyG index is a robust, independent predictor of CAD with high diagnostic utility, supporting its integration into routine clinical practice for early risk stratification.
Possible therapeutic interventions of acetylcholinesterase induction were studied. Inhibition of AChE might be helpful in treating the neuro-muscular diseases. Over-expressions of acetylcholinesterase (AChE), a key regulation of the neurotransmitter acetylcholine influences some neurodegenerative/neuro-muscular disorders. Present study evaluated the effect of black-tea components on AChE-activity in in vitro, and in vivo i.e. arsenic-intoxicated (0.6ppm/day/4-weeks) rat brain-AChE inhibition. Inhibitory-effects and enzyme kinetics on purified-AChE were screened from ten pure teaphytochemicals. In vivo experiment and bioinformatics studies were also performed. Pure theaflavin-digallate and theaflavin-monogallate showed promising AChE inhibitory effects/kinetics in dose-dependent/mixed-type manner with IC50 values, 1.6 & micro;M and 3.3 & micro;M, respectively. Tea galloyl-ester catechins compounds inhibited AChE with IC50 values of 41-67 & micro;M. Arsenic exposure increased AChE activity in rat cerebellum which was significantly restored by black-tea paralleling with our in vitro results. Molecular-docking and MD-simulation (GROMACS2021.2 server) of AChE (PDB Id:4M0E) and the experimental compounds suggests that theaflavin-digallate showed the lowest Atomic-Contact-Energy-369.87 kcal/mol and hampers the enzyme catalytic-hydrolytic-action and nucleophilic attack by SER203 supporting the in vitro and animal experimental results. Compared to other flavonoid or positive-control inhibitor eserine sulfate, TFDG and TFMG demonstrated significant inhibition of AChE. In conclusion, current MD-simulation, in vitro, and in vivo data may help treat certain cholinergic diseases. Further studies are suggested.
