Safety assessment of rat embryonic fraction for in vivo regenerative therapy.

Regenerative therapy is considered a novel option for treating various diseases, whereas a developing embryo is a prime source of molecules that help repair diseased tissue and organs. Organoid culture studies also confirmed the inherent biological functions of several embryonic factors. However, the in vivo safety and efficacy of embryonic protein fraction (EPF) were not validated. In this study, we investigated the effectiveness of EPF on healthy adult rats. We obtained embryos from SD female rats of E14, E16, and E19 embryonic days and collected protein lysate. This lysate was administered intravenously into adult Sprague-Dawley rats on sequential days. We collected blood and performed hematological and biochemical parameters of rats that received EPF. C-reactive protein levels, interleukin-6, blood glucose levels, serum creatinine, blood urea, total leucocyte counts, and % of neutrophils and lymphocytes were comparable between rats receiving EPF and saline. Histological examination of rats' tissues administered with EPF is devoid of abnormalities. Our study revealed that intravenous administration of EPF to healthy adult rats showed that EPF is non-immunogenic, non-inflammatory, non-tumorigenic and safe for in vivo applications. Our analysis suggests that EPF or its components could be recommended for validating its therapeutic abilities in organ regenerative therapy.

Effect of Second and Third Molar Eruption Stages on First Molar and Maxillary Arch Distalization With Modified Palatal Anchorage Plate and Beneslider: A 3D Finite Element Analysis.

AIM: To analyze the effects of the maxillary second molar and third molar eruption stages on the distalization of first molars with a modified palatal anchorage plate (MPAP) and Beneslider using three-dimensional (3D) finite element analysis. MATERIALS AND METHOD: Six finite element models (FEMs) of individual maxillary molar distalization and six FEM models of en-masse maxillary arch distalization (EMAD) at different stages of the maxillary molar eruption were created from cone-beam computed tomography (CBCT) images of the maxillary complex, and 3D displacements of the maxillary first and second molars were evaluated with MPAP and Beneslider. RESULTS: On individual molar distalization, Beneslider showed first molar distal translation during the second and third molar follicular stages, while MPAP showed distal tipping of the first molar. With EMAD, either of the appliances showed distal tipping of the first molars. There was palatal rolling and extrusion of the first molars. The second molar showed buccal drifting with intrusion, and the incisors showed palatal displacement along with extrusion. CONCLUSIONS: Second and third molar eruption stages had no adverse influence on first molar and en-masse maxillary arch distalization. Beneslider showed distal translation of the first molar, while distal tipping was seen with MPAP.

Determination of the time of refractive stability after uneventful phacoemulsification in Indian eyes.

BACKGROUND: Knowledge about refractive stabilization and the accuracy of postoperative refractive error measurements are crucial for improved patient outcomes after phacoemulsification. Existing guidelines typically recommend waiting 4-6 wk before prescribing corrective lenses. Our research focused on identifying factors that influence refractive errors in the early stages of post-cataract surgery, thus contributing to the existing literature on this topic. AIM: To investigate the time required for refraction stability after uneventful phacoemulsification surgery. METHODS: We compared the variation and statistical significance of the difference in spherical, cylindrical components, and the spherical equivalent between the 1- and 6-wk follow-up period in a group of 257 eyes that underwent uneventful phacoemulsification with foldable intraocular lens implantation, all performed by a single experienced surgeon. The Wilcoxon-Signed Rank Test was utilized to assess the magnitude of the change and determine its statistical significance. The refractive stability was defined as the point at which the change in spherical equivalent was within ± 0.5 dioptres for two consecutive visits. RESULTS: The average age of the patients was 64.9 ± 8.9 yr. The differences observed in both the visits in spherical power (0.1 ± 0.2), cylinder power (0.3 ± 0.4), and spherical equivalent (0.2 ± 0.2) were minimal and not statistically significant. The majority of eyes (93.4%) achieved refractive stability within 6 wk after the surgery. The cylindrical power differed between age groups at the 6th wk post-operative and the difference was statistically significant (P value 0.013). There were no significant differences in refractive stability when considering sex and axial length. CONCLUSION: Phacoemulsification with foldable intraocular lens implantation results in no significant changes in refraction for the majority of cases during the 6-wk follow-up period. Therefore, a spectacle prescription can be given at the completion of 1 wk.

Assessment of Bone Thickness at the Infra Zygomatic Crest Region for Various Orthodontic Miniscrew Implant (OMSI) Insertion Angles: A Cone-Beam Computed Tomographic Study.

Objective: To evaluate the infrazygomatic crest (IZC) bone and develop guidelines for the optimum placement of orthodontic miniscrew implants (OMSIs) along the distobuccal root of the permanent maxillary first molar. Methods: Bone thickness of the IZC region of 50 young adults (25 males and 25 females) aged 18-30 years were evaluated using cone-beam computed tomography images. The infrazygomatic bone thickness along the distobuccal root of the permanent maxillary first molar was assessed at various insertion angles (40° to 75° i.r.t the maxillary occlusal plane) with an increment of 5°. Student's t-test was used to compare the IZC bone thickness and height at the orthodontic miniscrew insertion site for males and females on the right and left sides. Results: The bone thickness of the IZC region above the distobuccal root of the permanent maxillary first molar was estimated between 4.39±0.25 mm and 9.03±0.45 mm for insertion angles from 40° to 75° to the maxillary occlusal plane. The corresponding OMSI insertion heights were 17.71±0.61 mm to 13.69±0.75 mm, respectively, above the maxillary occlusal plane. There were statistically significant gender and side-wise variations in bone thickness at the IZC area and insertion height. Conclusion: The safe position for OMSI placement at the IZC was 13.69-16 mm from the maxillary occlusal plane with an insertion angle between 55° and 75°. These parameters provide the optimum placement of OMSIs along the distobuccal root of the permanent maxillary first molar.

Forecasting deep learning-based risk assessment of vector-borne diseases using hybrid methodology.

BACKGROUND: Dengue fever is rapidly becoming Malaysia's most pressing health concern, as the reported cases have nearly doubled over the past decade. Without efficacious antiviral medications, vector control remains the primary strategy for battling dengue, while the recently introduced tetravalent immunization is being evaluated. The most significant and dangerous risk increasing recently is vector-borne illnesses. These illnesses induce significant human sickness and are transmitted by blood-feeding arthropods such as fleas, parasites, and mosquitos. A thorough grasp of various factors is necessary to improve prediction accuracy and typically generate inaccurate and unstable predictions, as well as machine learning (ML) models, weather-driven mechanisms, and numerical time series. OBJECTIVE: In this research, we propose a novel method for forecasting vector-borne disease risk using Radial Basis Function Networks (RBFNs) and the Darts Game Optimizer (DGO) algorithm. METHODS: The proposed approach entails training the RBFNs with historical disease data and enhancing their parameters with the DGO algorithm. To prepare the RBFNs, we used a massive dataset of vector-borne disease incidences, climate variables, and geographical data. The DGO algorithm proficiently searches the RBFN parameter space, fine-tuning the model's architecture to increase forecast accuracy. RESULTS: RBFN-DGO provides a potential method for predicting vector-borne disease risk. This study advances predictive demonstrating in public health by shedding light on effectively controlling vector-borne diseases to protect human populations. We conducted extensive testing to evaluate the performance of the proposed method to standard optimization methods and alternative forecasting methods. CONCLUSION: According to the findings, the RBFN-DGO model beats others in terms of accuracy and robustness in predicting the likelihood of vector-borne illness occurrences.

Beneficial Effect of Synbiotic Combination of Limosilactobacillus fermentum FS-10, Lactiplantibacillus plantarum Lp1-IC and Short-Chain Fructooligosaccharides in Colitis Murine Model.

Therapies targeting gut microbiota are being extensively researched for colitis patients. In this study, we have tested the efficacy of indigenously isolated strains Lactiplantibacillus plantarum Lp1-IC and Limosilactobacillus fermentum FS-10 and their combination with short-chain fructooligosaccharides (sc-FOS) in mice models of DSS-induced colitis. For a desired efficacy, a synbiotic should be very meticulously formulated with the right choice of prebiotic and probiotic. Therefore, the ability of lactobacilli to utilize scFOS for growth was first tested by culturing the strains in a specially designed minimal media supplemented with scFOS as carbon source. The bacteria utilized scFOS and produced metabolites such as acetate and lactate. Thereafter, the in vitro anti-inflammatory effect was tested on markers such as TNF-alpha (TNF-α), nitric oxide and IL-10 in human monocyte (THP-1) and mouse macrophage (Raw 264.7) cell lines. The in vivo efficacy was studied in mice model of DSS-induced colitis, and the effect on the systemic and localized inflammatory markers was assessed in serum and colon tissue samples respectively. Administration of DSS elicited predominant clinical signs of weight loss, diarrhoea, faecal occult blood, increase in inflammatory markers and extensive damage of colon tissue. These symptoms were significantly reversed in all the treatment groups; however, the combination of lactobacilli and scFOS performed better than the individual ingredients. The study highlights the potential of the indigenous lactobacilli strains, scFOS and their combination for management of gut inflammation in colitis patients.

Tricompartmental Microcarriers with Controlled Release for Efficient Management of Parkinson's Disease.

Parkinson's is a progressive neurodegenerative disease of the nervous system. It has no cure, but its symptoms can be managed by supplying dopamine artificially to the brain.This work aims to engineer tricompartmental polymeric microcarriers by electrohydrodynamic cojetting technique to encapsulate three PD (Parkinson's disease) drugs incorporated with high encapsulation efficiency (∼100%) in a single carrier at a fixed drug ratio of 4:1:8 (Levodopa (LD): Carbidopa(CD): Entacapone (ENT)). Upon oral administration, the drug ratio needs to be maintained during subsequent release from microparticles to enhance the bioavailability of primary drug LD. This presents a notable challenge, as the three drugs vary in their aqueous solubility (LD > CD > ENT). The equilibrium of therapeutic release was achieved using a combination of FDA-approved polymers (PLA, PLGA, PCL, and PEG) and the disc shape of particles. In vitro studies demonstrated the simultaneous release of all the three therapeutics in a sustained and controlled manner. Additionally, pharmacodynamics and pharmacokinetics studies in Parkinson's disease rats induced by rotenone showed a remarkable improvement in PD conditions for the microparticles-fed rats, thereby showing a great promise toward efficient management of PD.

Assessment of prevalence of elevated blood lead levels and risk factors among children and pregnant women in Bihar, India.

BACKGROUND: While modeled estimates and studies in contaminated areas indicate high lead exposure among children in Bihar, India, local data on lead exposure in the child population is limited. OBJECTIVES: To characterize lead exposure, and assess potential sources of lead exposure among a state-representative sample of children and their pregnant mothers residing in Bihar. METHODS: Blood samples were collected from 697 children under five and 55 pregnant women from eight districts in Bihar. Blood lead levels were determined using capillary blood and a portable lead analyzer. Household demographics, home environment, behavior, and nutrition information were collected through computer-assisted personal interviews with primary caregivers. Logistic regression was used to assess associations between potential risk factors and elevated blood lead levels. RESULTS: More than 90% of children and 80% of pregnant women reported blood lead levels ≥5 µg/dL. Living near a lead-related industry and pica behavior of eating soil were significantly associated with increased odds of having elevated blood lead levels. Additional risk factors for having a blood level ≥5 µg/dL included the use of skin lightning cream (aOR = 5.11, 95%CI: 1.62, 16.16) and the use of eyeliners (aOR = 2.81, 95%CI: 1.14, 6.93). Having blood lead levels ≥10 µg/dL was also significantly associated with the household member who had an occupation or hobby involving the use of lead (aOR = 1.75, 95%CI: 1.13, 2.72). DISCUSSION: Elevated blood lead levels were prevalent among children and pregnant women in Bihar, indicating the urgent need for a comprehensive lead poisoning prevention strategy.

Fabrication and characterization of cocoa butter-based caffeine fast-melting tablets.

Aim: The objective of this study was to develop and characterize the physical properties of fast-melting tablets (FMTs) using cocoa butter as the base and caffeine as the model drug. Method: The simple refrigerator freezing method was employed to prepare caffeine-loaded, FMTs from cocoa butter bases. Results: The F3 chosen formulation achieved a disintegration time of 1.20 min ± 0.035, which falls within the specified limit set by the European Pharmacopoeia. The cumulative drug release data of F3, was 88.52 and 94.08% within 60 and 75 min, respectively (NLT 85% as per US FDA requirement). All the other physical test standards for FMTs met the pharmacopeial specifications. Conclusion: Based on the findings, the simple refrigerator freezing method could be used to formulate FMTs.

Patient-friendly natural caffeine-loaded cocoa butter-based fast-melting tablets with rapid disintegration, affordability, safety and biocompatibility are an efficient base for drug delivery.

Effect of Yoga-Based Cardiac Rehabilitation Program on Endothelial Function, Oxidative Stress, and Inflammatory Markers in Acute Myocardial Infarction: A Randomized Controlled Trial.

Aims: The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI). Methods: A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation. Results: Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups. Conclusion: Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity.

Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis.

BACKGROUND: Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far. METHODS: The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia). RESULTS: The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan. CONCLUSION: The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.

Nickel-Catalyzed Alkene Isomerization to Access Bench-Stable Enamines and Their [3 + 2] Annulation.

Enamines are difficult to prepare on the bench due to their instability, which results in side reactions, decompositions, poor yields, etc. Herein, we developed a simple and effective method for making bench-stable enamines using a very low amount of nickel catalyst loading. The deuterium exchange, competitive reaction, and radical clock experiment have all been found to favor the ionic mechanism of this alkene isomerization. Scale-up and [3 + 2] annulation reaction of enamines with activated cyclopropane to deliver cyclopentane derivatives have shown the value of this method in organic synthesis.

A chemical modification of a peroxisome proliferator-activated receptor pan agonist produced a shift to a new dual alpha/gamma partial agonist endowed with mitochondrial pyruvate carrier inhibition and antidiabetic properties.

New analogs of the PPAR pan agonist AL29-26 encompassed ligand (S)-7 showing potent activation of PPARα and -γ subtypes as a partial agonist. In vitro experiments and docking studies in the presence of PPAR antagonists were performed to help interpretation of biological data and investigate the main interactions at the binding sites. Further in vitro experiments showed that (S)-7 induced anti-steatotic effects and enhancement of the glucose uptake. This latter effect could be partially ascribed to a significant inhibition of the mitochondrial pyruvate carrier demonstrating that (S)-7 also acted through insulin-independent mechanisms. In vivo experiments showed that this compound reduced blood glucose and lipid levels in a diabetic mice model displaying no toxicity on bone, kidney, and liver. To our knowledge, this is the first example of dual PPARα/γ partial agonist showing these combined effects representing, therefore, the potential lead of new drugs for treatment of dyslipidemic type 2 diabetes.

Adequate Levels of Zinc and Copper on Turkey Poult Performance, Immunological Response, and Skeletal Health.

In this study, the impact of varying dietary zinc (Zn) and copper (Cu) levels on the growth, immunological response, and skeletal health of developing turkey poults was investigated. For 0-4 and 5-8 weeks of age, respectively, three Zn levels of 50, 70, and 90 mg/kg and 45, 65, and 85 mg/kg were employed. Three Cu levels, namely 8, 12, and 16 mg/kg for 0-8 weeks of age, were also utilized. There were 288 (9 × 4 × 8) day-old turkey poults with equal body weight that were randomly assigned to 9 treatments, each consisting of 4 replicates and 8 poults per replicate. In comparison to other dietary combinations, there was a significant (P ≤ 0.05) increase in body weight gain observed in the 90 and 85 mg Zn/kg with 16 mg Cu/kg diet during 0-4 and 0-8 weeks of age, respectively, and the 70 and 65 mg Zn with 16 mg Cu /kg diet during 0-4 and 0-8 weeks of age, respectively. When compared to low levels of zinc in the diet at 5-8 and 0-8 weeks of age, respectively, feed conversion ratio was shown to be significantly (P ≤ 0.01) better with 90 and 85 mg Zn/kg diet. In a similar pattern, feed utilization efficiency was considerably (P ≤ 0.01) higher at 16 mg Cu/kg diet than it was at lower Cu levels in the diets given to the animals over the 0-4 week period. Compared to other dietary combinations, there was a substantial (P ≤ 0.01) improvement in cell-mediated immune response (foot web index to PHAP) and humoral immune response (HA titer to SRBC) when 85 mg zinc and 16 mg copper/kg diet was consumed at 0-4 and 5-8 weeks of age. At greater dietary Zn and Cu levels than its lower values, the weight of the spleen and thymus was considerably (P ≤ 0.05) higher. In a dietary combination of 90 mg Zn with 16 mg Cu/kg during 0-4 and 85 mg Zn with 16 mg Cu/kg diet during 5-8 weeks of age, respectively, there were significantly (P ≤ 0.05) greater bone width (proximal and distal), tibia bone ash, calcium, and phosphorus detected respectively. Significantly (P ≤ 0.01) greater Zn and Fe contents were found in the tibia bone at 90 and 85 mg Zn/kg diet, respectively, compared to values obtained at other Zn levels in the diet throughout 0-4 and 5-8 weeks of age. During the first 8 weeks of life, a diet containing 12 mg of copper per kilogram was shown to have a significantly (P ≤ 0.05) increased Zn and Fe content in the tibia bone compared to other levels. It is possible to draw the conclusion from the data that, for growing turkey poults, dietary combinations of 90 mg Zn/kg with 16 mg Cu/kg diet and 85 mg Zn with 16 mg Cu/kg diet between 0 and 4 and 5-8 weeks of age, respectively, were sufficient for optimum development, immunity, and skeletal health indices.

Engineered inulin-based hybrid biomaterials for augmented immunomodulatory responses.

Modified biopolymers that are based on prebiotics have been found to significantly contribute to immunomodulatory events. In recent years, there has been a growing use of modified biomaterials and polymer-functionalized nanomaterials in the treatment of various tumors by activating immune cells. However, the effectiveness of immune cells against tumors is hindered by several biological barriers, which highlights the importance of harnessing prebiotic-based biopolymers to enhance host defenses against cancer, thus advancing cancer prevention strategies. Inulin, in particular, plays a crucial role in activating immune cells and promoting the secretion of cytokines. Therefore, this mini-review aims to emphasize the importance of inulin in immunomodulatory responses, the development of inulin-based hybrid biopolymers, and the role of inulin in enhancing immunity and modifying cell surfaces. Furthermore, we discuss the various approaches of chemical modification for inulin and their potential use in cancer treatment, particularly in the field of cancer immunotherapy.

Investigating the impact of alumina nanoparticles in coconut oil distillate biodiesel to lessen emissions in direct injection diesel engine.

Petroleum fuels are commonly used for automobiles. However, the continuous depletion and exhaust gas emission causes serious problems. So, there is a need for an alternative eco-friendly fuel. Biodiesel is a type of fuel manufactured through a process called transesterification, which involves converting vegetable oils into a usable form. The process parameters of the transesterification process were optimized using the Taguchi method to achieve maximum biodiesel yield. However, the main problem of biodiesel is its high cost which could be reduced by using low-cost feedstock. To address this challenge, biodiesel (BCFAD) is derived from coconut fatty acid distillate (CFAD), a by-product obtained from refining coconut oil. This work uses BCFAD and BCFAD with Alumina nanoparticles as fuels. Alumina nanoparticles in the mass fraction of 25 ppm, 50 ppm, and 100 ppm are dispersed in BCFAD. The investigation results reveal an increase of 6.5% in brake thermal efficiency for BCFAD with 100 ppm nanoparticles when compared to BCFAD. There is a reduction of 29.29% of hydrocarbon and 34% of Carbon monoxide emissions with BCFAD100 in comparison with diesel. However, there is a marginal increase in NOx emission with the increase in nanoparticles. The heat release rate and cylinder pressure of BCFAD100 are comparable to diesel fuel. It was concluded that the utilization of BCFAD with a nanoparticle dispersion of 100 ppm is suitable for direct use as fuel in diesel engines.

Cardiovascular Autonomic Deficits in Different Types of Achalasia.

Background and objective Achalasia cardia is a primary esophageal motility disorder, and the etiopathology of this disease's progression is not known. Moreover, autonomic dysfunction has not been studied in different types of achalasia. In light of this, we aimed to address this lack of data in this study. Methods The diagnosis of achalasia was done using high-resolution esophageal manometry (HRM)-based Chicago classification v4.0. Autonomic function tests (AFT) such as the head-up tilt test, deep breathing test (DBT), Valsalva maneuver (VM), handgrip test (HGT), and cold pressor test (CPT), as well as the heart rate variability (HRV) test, were performed among the cohort and the results were compared with those of 39 age- and sex-matched healthy controls. Results AFT and HRV tests were done on 62 patients (30 achalasia type I, 28 type II, and 4 type III) and compared with 39 age- and sex-matched healthy controls. The mean duration of symptoms, high Eckardt score, and dysphagia were most common in type I achalasia, followed by type II and III. The results of AFT showed a generalized loss of parasympathetic and baroreflex-independent sympathetic reactivity in all types of achalasia. However, baroreflex-dependent cardiovascular adrenergic reactivity was normal. Regarding cardiac autonomic tone, there was a loss of parasympathetic and sympathetic influence, but sympathovagal balance was maintained. The severity of the loss of autonomic functions was higher in type I, followed by type II. Conclusions In all types of achalasia, parasympathetic reactivity, baroreflex-independent sympathetic reactivity, and cardiac autonomic tone were lower compared to healthy controls, and the severity of dysfunction increased during the progression of the disease from type II to type I.

Insight in Quinazoline-based HDAC Inhibitors as Anti-cancer Agents.

Cancer remains a primary cause of death globally, and effective treatments are still limited. While chemotherapy has notably enhanced survival rates, it brings about numerous side effects. Consequently, the ongoing challenge persists in developing potent anti-cancer agents with minimal toxicity. The versatile nature of the quinazoline moiety has positioned it as a pivotal component in the development of various antitumor agents, showcasing its promising role in innovative cancer therapeutics. This concise review aims to reveal the potential of quinazolines in creating anticancer medications that target histone deacetylases (HDACs).

Metabolomics in Depression: What We Learn from Preclinical and Clinical Evidences.

Depression is one of the predominant common mental illnesses that affects millions of people of all ages worldwide. Random mood changes, loss of interest in routine activities, and prevalent unpleasant senses often characterize this common depreciated mental illness. Subjects with depressive disorders have a likelihood of developing cardiovascular complications, diabesity, and stroke. The exact genesis and pathogenesis of this disease are still questionable. A significant proportion of subjects with clinical depression display inadequate response to antidepressant therapies. Hence, clinicians often face challenges in predicting the treatment response. Emerging reports have indicated the association of depression with metabolic alterations. Metabolomics is one of the promising approaches that can offer fresh perspectives into the diagnosis, treatment, and prognosis of depression at the metabolic level. Despite numerous studies exploring metabolite profiles post-pharmacological interventions, a quantitative understanding of consistently altered metabolites is not yet established. The article gives a brief discussion on different biomarkers in depression and the degree to which biomarkers can improve treatment outcomes. In this review article, we have systemically reviewed the role of metabolomics in depression along with current challenges and future perspectives.

Glutaminase - A potential target for cancer treatment.

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of glutaminase aggravates oxidative stress by reducing glutathione level, thus leading to apoptotic-mediated cell death in cancer cells Therefore, inhibiting the glutaminase activity using glutaminase inhibitors such as BPTES, DON, JHU-083, CB-839, compound 968, etc. may answer many intriguing questions behind the uncontrolled proliferation of cancer cells and serve as a prophylactic treatment for cancer. Earlier reports neither discuss nor provide perspectives on exact signaling gene or pathway. Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment.