Hydroxychloroquine interaction with phosphoinositide 3-kinase modulates prostate cancer growth in bone microenvironment: In vitro and molecular dynamics based approach.

Patients with advanced prostate cancer (PCa) are more likely to develop bone metastases. Tumor cells thrive in the bone microenvironment, interacting with osteoblasts and osteoclasts. Given the PI3K/AKT pathway's metastatic potential and signal integration's ability to modulate cell fates in PCa development, drugs targeting this system have great therapeutic promise. Hydroxychloroquine (HCQ) is an anti-malarial medication commonly used to treat clinical conditions such as rheumatology and infectious disorders. We explored the anti-neoplastic effect of HCQ on PC3 and C4-2B cell lines in the bone microenvironment. Interestingly, HCQ treatment substantially decreases the viability, proliferation, and migration potential of PCa cells in the bone microenvironment. HCQ induces apoptosis and cell cycle arrest, even in the presence of osteoblast-secreted factors. Mechanistically, HCQ inhibited the activity of the PI3K/AKT signaling pathway, which ultimately regulates the proliferation and migration of PCa cells in the bone. The binding energy for docking HCQ with PI3K was -6.7 kcal/mol, and the complex was stabilized by hydrogen bonds, hydrophobic forces, and van der Waals forces. Molecular simulations further validated the structural integrity of the HCQ-PI3K complex without altering PI3K's secondary structure. Our findings underscore the efficacy of HCQ as a potential therapeutic agent in treating PCa.

Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights.

Copper, a vital trace element, orchestrates diverse cellular processes ranging from energy production to antioxidant defense and angiogenesis. Copper metabolism and cuproptosis are closely linked in the context of human diseases, with a particular focus on cancer. Cuproptosis refers to a specific type of copper-mediated cell death or copper toxicity triggered by disruptions in copper metabolism within the cells. This phenomenon encompasses a spectrum of mechanisms, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and perturbations in metal ion equilibrium. Mechanistically, cuproptosis is driven by copper binding to the lipoylated enzymes within the tricarboxylic acid (TCA) cycle. This interaction participates in protein aggregation and proteotoxic stress, ultimately culminating in cell death. Targeting copper metabolism and its associated pathways in cancer cells hold therapeutic potential by selectively targeting and eliminating cancerous cells. Strategies to modulate copper levels, enhance copper excretion, or interfere with cuproptotic pathways are being explored to identify novel therapeutic targets for cancer therapy and improve patient outcomes. Understanding the relationship between cuproptosis and copper metabolism in human malignancies remains an active area of research. This review provides a comprehensive overview of the association among copper metabolism, copper homeostasis, and carcinogenesis, explicitly emphasizing the cuproptosis mechanism and its implications for cancer pathogenesis. Additionally, we emphasize the therapeutic aspects of targeting copper and cuproptosis for cancer treatment.

From orphan to oncogene: The role of GPR35 in cancer and immune modulation.

G protein-coupled receptors (GPCRs) are well-studied and the most traceable cell surface receptors for drug discovery. One of the intriguing members of this family is G protein-coupled receptors 35 (GPR35), which belongs to the class A rhodopsin-like family of GPCRs identified over two decades ago. GPR35 presents interesting features such as ubiquitous expression and distinct isoforms. Moreover, functional and genome-wide association studies on its widespread expression have linked GPR35 with pathophysiological disease progression. Various pieces of evidence have been accumulated regarding the independent or endogenous ligand-dependent role of GPR35 in cancer progression and metastasis. In the current scenario, the relationship of this versatile receptor and its putative endogenous ligands for the activation of oncogenic signal transduction pathways at the cellular level is an active area of research. These intriguing features offered by GPR35 make it an oncological target, justifying its uniqueness at the physiological and pathophysiological levels concerning other GPCRs. For pharmacologically targeting receptor-induced signaling, few potential competitive antagonists have been discovered that offer high selectivity at a human level. In addition to its fascinating features, targeting GPR35 at rodent and human orthologue levels is distinct, thus contributing to the sub-species selectivity. Strategies to modulate these issues will help us understand and truly target GPR35 at the therapeutic level. In this article, we have provided prospects on each topic mentioned above and suggestions to overcome the challenges. This review discusses the molecular mechanism and signal transduction pathways activated by endogenous ligands or spontaneous auto-activation of GPR35 that contributes towards disease progression. Furthermore, we have highlighted the GPR35 structure, ubiquitous expression, its role in immunomodulation, and at the pathophysiological level, especially in cancer, indicating its status as a versatile receptor. Subsequently, we discussed the various proposed ligands and their mechanism of interaction with GPR35. Additionally, we have summarized the GPR35 antagonist that provides insights into the opportunities for therapeutically targeting this receptor.

α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation.

Prostate cancer (PCa) progression leads to bone modulation in approximately 70% of affected men. A nutraceutical, namely, α-lipoic acid (α-LA), is known for its potent anti-cancer properties towards various cancers and has been implicated in treating and promoting bone health. Our study aimed to explore the molecular mechanism behind the role of α-LA as therapeutics in preventing PCa and its associated bone modulation. Notably, α-LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose-dependent manner. In addition, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway. Flow cytometry data revealed the arrest of the cell cycle in the S-phase, which has led to apoptosis of PCa cells. Furthermore, the results of ALP (Alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) staining signifies that α-LA supplementation diminished the PCa-mediated differentiation of osteoblasts and osteoclasts, respectively, in the MC3T3-E1 and bone marrow macrophages (BMMs) cells. In summary, α-LA supplementation enhanced cellular apoptosis via increased ROS levels, HIF-1α expression, and JNK/caspase-3 signaling pathway in advanced human PCa cell lines. Also, the treatment of α-LA improved bone health by reducing PCa-mediated bone cell modulation.

Pt-doped Ru nanoparticles loaded on 'black gold' plasmonic nanoreactors as air stable reduction catalysts.

This study introduces a plasmonic reduction catalyst, stable only in the presence of air, achieved by integrating Pt-doped Ru nanoparticles on black gold. This innovative black gold/RuPt catalyst showcases good efficiency in acetylene semi-hydrogenation, attaining over 90% selectivity with an ethene production rate of 320 mmol g-1 h-1. Its stability, evident in 100 h of operation with continuous air flow, is attributed to the synergy of co-existing metal oxide and metal phases. The catalyst's stability is further enhanced by plasmon-mediated concurrent reduction and oxidation of the active sites. Finite-difference time-domain simulations reveal a five-fold electric field intensification near the RuPt nanoparticles, crucial for activating acetylene and hydrogen. Kinetic isotope effect analysis indicates the contribution from the plasmonic non-thermal effects along with the photothermal. Spectroscopic and in-situ Fourier transform infrared studies, combined with quantum chemical calculations, elucidate the molecular reaction mechanism, emphasizing the cooperative interaction between Ru and Pt in optimizing ethene production and selectivity.

Ionic Liquid-Induced Assembly of DNA at Air-Water Interface.

DNA nanotechnology is the future of many products in the pharmaceutical and cosmetic industries. Self-assembly of this negatively charged biopolymer at surfaces and interfaces is an essential step to elaborate its field of applications. In this study, the ionic liquid (IL) monolayer-assisted self-assembly of DNA macromolecules at the air-water interface has been closely monitored by employing various quantitative techniques, namely, surface pressure-area (π-A) isotherms, surface potential, interfacial rheology, and X-ray reflectivity (XRR). The π-A isotherms reveal that the IL 1,3-didecyl 3-methyl imidazolium chloride induces DNA self-assembly at the interface, leading to a thick viscoelastic film. The interfacial rheology exhibits a notable rise in the viscoelastic modulus as the surface pressure increases. The values of storage and loss moduli measured as a function of strain frequency suggest a relaxation frequency that depends on the length of the macromolecule. The XRR measurements indicate a considerable increase in DNA layer thickness at the elevated surface pressures depending on the number of base pairs of the DNA. The results are considered in terms of the electrostatic and hydrophobic interactions, allowing a quantitative conclusion about the arrangement of DNA strands underneath the monolayer of the ILs at the air-water interface.

An Intelligent Attention-Based Transfer Learning Model for Accurate Differentiation of Bone Marrow Stains to Diagnose Hematological Disorder.

Bone marrow (BM) is an essential part of the hematopoietic system, which generates all of the body's blood cells and maintains the body's overall health and immune system. The classification of bone marrow cells is pivotal in both clinical and research settings because many hematological diseases, such as leukemia, myelodysplastic syndromes, and anemias, are diagnosed based on specific abnormalities in the number, type, or morphology of bone marrow cells. There is a requirement for developing a robust deep-learning algorithm to diagnose bone marrow cells to keep a close check on them. This study proposes a framework for categorizing bone marrow cells into seven classes. In the proposed framework, five transfer learning models-DenseNet121, EfficientNetB5, ResNet50, Xception, and MobileNetV2-are implemented into the bone marrow dataset to classify them into seven classes. The best-performing DenseNet121 model was fine-tuned by adding one batch-normalization layer, one dropout layer, and two dense layers. The proposed fine-tuned DenseNet121 model was optimized using several optimizers, such as AdaGrad, AdaDelta, Adamax, RMSprop, and SGD, along with different batch sizes of 16, 32, 64, and 128. The fine-tuned DenseNet121 model was integrated with an attention mechanism to improve its performance by allowing the model to focus on the most relevant features or regions of the image, which can be particularly beneficial in medical imaging, where certain regions might have critical diagnostic information. The proposed fine-tuned and integrated DenseNet121 achieved the highest accuracy, with a training success rate of 99.97% and a testing success rate of 97.01%. The key hyperparameters, such as batch size, number of epochs, and different optimizers, were all considered for optimizing these pre-trained models to select the best model. This study will help in medical research to effectively classify the BM cells to prevent diseases like leukemia.

RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy, with ETV6::RUNX1 being the most prevalent translocation whose exact pathogenesis remains unclear. IGF2BP1 (Insulin-like Growth Factor 2 Binding Protein 1) is an oncofetal RNA binding protein seen to be specifically overexpressed in ETV6::RUNX1 positive B-ALL. In this study, we have studied the mechanistic role of IGF2BP1 in leukemogenesis and its synergism with the ETV6::RUNX1 fusion protein. METHODS: Gene expression was analyzed from patient bone marrow RNA using Real Time RT-qPCR. Knockout cell lines were created using CRISPR-Cas9 based lentiviral vectors. RNA-Seq and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed using the Illumina platform. Mouse experiments were done by retroviral overexpression of donor HSCs followed by lethal irradiation of recipients using a bone marrow transplant model. RESULTS: We observed specific overexpression of IGF2BP1 in ETV6::RUNX1 positive patients in an Indian cohort of pediatric ALL (n=167) with a positive correlation with prednisolone resistance. IGF2BP1 expression was essential for tumor cell survival in multiple ETV6::RUNX1 positive B-ALL cell lines. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RIP-Seq after IGF2BP1 pulldown in Reh cell line revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including TNFα/NFκB and PI3K-Akt pathways. These pathways were also dysregulated in primary ETV6::RUNX1 positive B-ALL patient samples from our center as well as in public B-ALL patient datasets. IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript itself. This positive feedback loop led to constitutive dysregulation of several oncogenic pathways. Enforced co-expression of ETV6::RUNX1 and IGF2BP1 in mouse bone marrow resulted in marrow hypercellularity which was characterized by multi-lineage progenitor expansion and strong Ki67 positivity. This pre-leukemic phenotype confirmed their synergism in-vivo. Clonal expansion of cells overexpressing both ETV6::RUNX1 and IGF2BP1 was clearly observed. These mice also developed splenomegaly indicating extramedullary hematopoiesis. CONCLUSION: Our data suggest a combined impact of the ETV6::RUNX1 fusion protein and RNA binding protein, IGF2BP1 in activating multiple oncogenic pathways in B-ALL which makes IGF2BP1 and these pathways as attractive therapeutic targets and biomarkers.

Acetylene Semi-Hydrogenation at Room Temperature over Pd-Zn Nanocatalyst.

A reaction of fundamental and commercial importance is acetylene semi-hydrogenation. Acetylene impurity in the ethylene feedstock used in the polyethylene industry poisons the Ziegler-Natta catalyst which adversely affects the polymer quality. Pd based catalysts are most often employed for converting acetylene into the main reactant, ethylene, however, it often involves a tradeoff between the conversion and the selectivity and generally requires high temperatures. In this work, bimetallic Pd-Zn nanoparticles capped by hexadecylamine (HDA) have been synthesized by co-digestive ripening of Pd and Zn nanoparticles and studied for semi-hydrogenation of acetylene. The catalyst showed a high selectivity of ~85 % towards ethylene with a high ethylene productivity to the tune of ~4341 µmol g-1 min-1 , at room temperature and atmospheric pressure. It also exhibited excellent stability with ethylene selectivity remaining greater than 85 % even after 70 h on stream. To the best of the authors' knowledge, this is the first report of room temperature acetylene semi-hydrogenation, with the catalyst effecting high amount of acetylene conversion to ethylene retaining excellent selectivity and stability among all the reported catalysts thus far. DFT calculations show that the disordered Pd-Zn nanocatalyst prepared by a low temperature route exhibits a change in the d-band center of Pd and Zn which in turn enhances the selectivity towards ethylene. TPD, XPS and a range of catalysis experiments provided in-depth insights into the reaction mechanism, indicating the key role of particle size, surface area, Pd-Zn interactions, and the capping agent.

ERFVII action and modulation through oxygen-sensing in Arabidopsis thaliana.

Oxygen is a key signalling component of plant biology, and whilst an oxygen-sensing mechanism was previously described in Arabidopsis thaliana, key features of the associated PLANT CYSTEINE OXIDASE (PCO) N-degron pathway and Group VII ETHYLENE RESPONSE FACTOR (ERFVII) transcription factor substrates remain untested or unknown. We demonstrate that ERFVIIs show non-autonomous activation of root hypoxia tolerance and are essential for root development and survival under oxygen limiting conditions in soil. We determine the combined effects of ERFVIIs in controlling gene expression and define genetic and environmental components required for proteasome-dependent oxygen-regulated stability of ERFVIIs through the PCO N-degron pathway. Using a plant extract, unexpected amino-terminal cysteine sulphonic acid oxidation level of ERFVIIs was observed, suggesting a requirement for additional enzymatic activity within the pathway. Our results provide a holistic understanding of the properties, functions and readouts of this oxygen-sensing mechanism defined through its role in modulating ERFVII stability.

Prognostic relevance of surface expression of cytokine receptor-like factor 2 in pediatric B-lineage acute lymphoblastic leukemia.

Overexpression of cytokine receptor-like factor 2 (CRLF2) resulting from its genomic rearrangement is the most frequent genetic alteration found in Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL), a high-risk leukemia. Detection of CRLF2 expression by multiparameter flow cytometry has been proposed as a screening tool for the identification of Ph-like B-ALL. However, the prognostic relevance of flow cytometric expression of CRLF2 in pediatric B-ALL is not very clear. Additionally, its association with common copy number alterations (CNA) has not been studied in detail. Hence, in this study, we prospectively evaluated the flow cytometric expression of CRLF2 in 256 pediatric B-ALL patients and determined its association with molecular features such as common CNAs detected using Multiplex ligation-dependent probe amplification and mutations in CRLF2, JAK2 and IL7RA genes. Further, its association with clinicopathological features including patient outcome was assessed. We found that 8.59% (22/256) pediatric B-ALL patients were CRLF2-positive at diagnosis. Among CNAs, CRLF2 positivity was associated with presence of PAX5 alteration (P=0.041). JAK2 and IL-7R mutations were found in 9% and 13.6% CRLF2-positive patients, respectively. IGH::CRLF2 or P2RY8::CRLF2 fusions were each found in 1/22 individuals. CRLF2-positive patients were found to have inferior overall (hazard ratio (HR) =4.39, P=0.006) and event free survival (HR=2.62, P=0.045), independent to other clinical features. Furthermore, concomitant CNA of IKZF1 in CRLF2 positive patients was associated with a greater hazard for poor overall and event free survival, compared to patients without these alterations or presence of any one of them. Our findings demonstrate that the surface CRLF2 expression in association with IKZF1 copy number alteration can be used to risk stratify pediatric B-ALL patients.

Marinobacterium lacunae sp. nov. isolated from estuarine sediment.

A novel motile bacterium was isolated from a sediment sample collected in Kochi backwaters, Kerala, India. This bacterium is Gram negative, rod shaped, 1.0-1.5 µm wide, and 2.0-3.0 µm long. It was designated as strain AK27T. Colonies were grown on marine agar displayed circular, off-white, shiny, moist, translucent, flat, margin entire, 1-2 mm in diameter. The major fatty acids identified in this strain were C18:1 ω7c, C16:0, and summed in feature 3. The composition of polar lipids in the strain AK27T included phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unidentified amino lipid, two unidentified aminophospholipids, two unidentified phospholipids, and six unidentified lipids. The genomic DNA of strain AK27T exhibited a G+C content of 56.4 mol%. Based on the analysis of 16S rRNA gene sequence, strain AK27T showed sequence similarity to M. ramblicola D7T and M. zhoushanense WM3T as 98.99% and 98.58%, respectively. Compared to other type strains of the Marinobacterium genus, strain AK27T exhibited sequence similarities ranging from 91.7% to 96.4%. When compared to Marinobacterium zhoushanense WM3T and Marinobacterium ramblicola D7T, strain AK27T exhibited average nucleotide identity values of 80.25% and 79.97%, and dDDH values of 22.9% and 22.6%, respectively. The genome size of the strain AK27T was 4.55 Mb, with 4,229 coding sequences. Based on the observed phenotypic and chemotaxonomic features, and the results of phylogenetic and phylogenomic analysis, this study proposes the classification of strain AK27T as a novel species within the genus Marinobacterium. The proposed name for this novel species is Marinobacterium lacunae sp. nov.

Distinct oncogenic phenotypes in hematopoietic specific deletions of Trp53.

Loss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. In order to dissect the role of P53 in the hematopoietic system, we generated and analyzed two different mouse models deficient for P53. A pan-hematopoietic P53 deletion mouse was created using Vav1-Cre based deletion; and a B-cell-specific deletion mouse was created using a CD19-Cre based deletion. The Vav1-P53CKO mice predominantly developed T-cell malignancies in younger mice, and myeloid malignancies in older mice. In T-cell malignancies, there was accelerated thymic cell maturation with overexpression of Notch1 and its downstream effectors. CD19-P53CKO mice developed marginal zone expansion in the spleen, followed by marginal zone lymphoma, some of which progressed to diffuse large B-cell lymphomas. Interestingly, marginal zone and diffuse large B-cell lymphomas had a unique gene expression signature characterized by activation of the PI3K pathway, compared with wild type marginal zone or follicular cells of the spleen. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.

Surfactant gel-based method: A universal soft method for the exfoliation of 2D materials.

HYPOTHESIS: Fluidic micelles and reverse micelles have served as exfoliation mediums. However, an additional force, such as extended sonication, is required. Gelatinous cylindrical micelles that are formed once desired conditions are achieved can be an ideal medium for the quick exfoliation of 2D materials without the need for any external force. The quick formation of gelatinous cylindrical micelles can rip off layers from the 2D materials suspended in the mixture leading to the quick exfoliation of 2D materials. EXPERIMENTS: Herein, we introduce a quick universal method capable of delivering high-quality exfoliated 2D materials cost-effectively using CTAB-based gelatinous micelles as an exfoliation medium. The approach is devoid of harsh treatment, such as prolonged sonication and heating, and a quick exfoliation of 2D materials is completed using this approach. FINDINGS: We successfully exfoliated four 2D materials (MoS2, Graphene, WS2, and BN) and investigated their morphology, chemical, and crystal structure along with optical and electrochemical properties to probe the quality of the exfoliated product. Results revealed that the proposed method is highly efficient in exfoliating 2D materials in a quick time without causing any significant damage to the mechanical integrity of the exfoliated materials.

Shear-induced phase transition in the aqueous solution of an imidazolium-based ionic liquid.

An ionic liquid (IL) is a salt in the liquid state that consists of a cation and an anion, one of which possesses an organic component. Because of their non-volatile property, these solvents have a high recovery rate, and, hence, they are considered as environment-friendly green solvents. It is necessary to study the detailed physicochemical properties of these liquids for designing and processing techniques and find suitable operating conditions for IL-based systems. In the present work, the flow behavior of aqueous solutions of an imidazolium-based IL, 1-methyl-3-octylimidazolium chloride, is investigated, where the dynamic viscosity measurements indicate non-Newtonian shear thickening behavior in the solutions. Polarizing optical microscopy shows that the pristine samples are isotropic and transform into anisotropic after shear. These shear thickened liquid crystalline samples change into an isotropic phase upon heating, which is quantified by the differential scanning calorimetry. The small angle x-ray scattering study revealed that the pristine isotropic cubic phase of spherical micelles distort into non-spherical micelles. This has provided the detailed structural evolution of mesoscopic aggregates of the IL in an aqueous solution and the corresponding viscoelastic property of the solution.

Molecular Tools for Early Detection of Invasive Malaria Vector Anopheles stephensi Mosquitoes.

Reports of the expansion of the Asia malaria vector Anopheles stephensi mosquito into new geographic areas are increasing, which poses a threat to the elimination of urban malaria. Efficient surveillance of this vector in affected areas and early detection in new geographic areas is key to containing and controlling this species. To overcome the practical difficulties associated with the morphological identification of immature stages and adults of An. stephensi mosquitoes, we developed a species-specific PCR and a real-time PCR targeting a unique segment of the second internal transcribed spacer lacking homology to any other organism. Both PCRs can be used to identify An. stephensi mosquitoes individually or in pooled samples of mixed species, including when present in extremely low proportions (1:500). This study also reports a method for selective amplification and sequencing of partial ribosomal DNA from An. stephensi mosquitoes for their confirmation in pooled samples of mixed species.

Preliminary investigation on impact of intergenerational treatment of resveratrol endorses the development of 'super-pups'.

BACKGROUND: Redox biology balances free radical generation and scavenging systems, whereas an imbalanced cellular redox can hasten the onset of various diseases and be regarded as a Pandora's box of ailments. The current study aims to assess the pathophysiological impact of intergenerational resveratrol treatment on diabetes-related cognitive and cardio-renal disorders. MATERIAL AND METHOD: Diabetic rats of the first, second, and third generations were subjected to an intergenerational treatment of resveratrol (20 mg/kg/p.o./day) for 5 months. During this period, the second generation of animals (pups of the first generation) was produced. After the adulthood of second-generation rats, they used to produce third-generation rats. The rats of each generation were evaluated for physiological parameters (BMI, litter size, and life expectancy) and the pathological impact of streptozotocin (55 mg/kg/i.p.), cognitive dysfunctions, and cardio-renal injury. RESULTS: The intergenerational treatment of resveratrol significantly reduced litter size and improved anthropometric parameters, life expectancy, and blood glucose levels in diabetic animals. Resveratrol treatment ameliorates oxidative stress as measured by increased serum nitrite/nitrate concentrations, SOD activity, reduced glutathione concentrations, total serum antioxidant capacity, and diminished serum TBARS level in diabetic animals. Furthermore, diabetic rats receiving intergenerational resveratrol treatment showed improved cognitive behaviour and cardio-renal functionality when compared to the disease control group. CONCLUSION: The intergenerational treatment of resveratrol improved the physiological traits and vital abilities of the heart, kidney, and brain, which endorse its antioxidant potential. Surprisingly, resveratrol treatment increases the second and third generations' resistance to neurobehavioral changes, diabetes, and -associated cardio-renal dysfunction, implying that these generations are "super-pups."