Novel Insights Into the Architecture of Macro and Microstructures in Cattle Ossa Cordis.

Ossa cordis, bones located within the heart trigones, are often classified as heterotopic or ectopic bones. Despite their high prevalence in cattle and some other bovids, little is known about their structure or development. Scanning electron microscopy, X-ray microtomography, gross dissections, and measurements showed the anatomical locations, prevalence, shapes, and measurements of the cardiac bones in both Egyptian Baladi cattle and Holstein-Friesians. All cattle (n = 12) had an Ossa cordis dextrum (average = 50.70 × 20.91 × 5.40 mm). Additionally, 80% Egyptian Baladi and 57% Holstein-Friesian had a smaller Ossa cordis sinistrum (average = 24.94 × 12.75 × 4.12 mm). Egyptian Baladi Ossa cordis were smaller than observed in Holstein-Friesians. Energy-dispersive X-ray analysis showed the elemental constitution (carbon, oxygen, calcium, nitrogen, phosphorus, sodium, and magnesium) of Ossa cordis and Cartilago cordis. These imaging techniques, plus four histological stains (hematoxylin and eosin, Crossman's trichrome, Alcian blue with Van Gieson, and Sirius Red) and microscopy, demonstrated osteoblasts, osteocytes, osteoclasts, astrocytes, blood vessels, bone marrow, lamellar and woven bone, cortical bone, trabeculations with pores and canaliculi, and fibrous components including collagen in the Ossa cordis dextrum and sinistrum. Hyaline cartilage and fibrocartilage (chondrocytes and cartilage matrix) were found within and surrounding the Ossa cordis. These findings were additionally compared against other cattle breeds and species.

Dermatological Manifestation of SLE Patients, Living in Aseer Region.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects both men and women differently and has a variety of multisystemic symptoms. One of the diseases most often affected target organs is the skin. Different ethnic and racial groupings may display variations in disease incidence, clinical heterogeneity, and severity depending on environmental, cultural, or genetic factors. This study is conducted to determine the prevalence of SLE's cutaneous symptoms and their relationship to organ involvement. Materials and Methods: Data were gathered for this study from the patient chart, the study design was the retrospective chart review after the consent of the patients and obtaining an ethical approval, The study was carried out in Aseer Central Hospital, Abha Saudi Arabia. Results: Out of a total of 100 patients 92% were females while 8% were males. The mean (SD) of the age of the respondent was 38.3 (8.5). 89.2 of the respondents had skin manifestations. Conclusion: A thorough understanding of SLE skin lesions will aid in the accurate identification of the condition and in the effective therapy of lupus patients. In order to more accurately diagnose cutaneous lesions in SLE patients, we need more dermatology and rheumatology clinics that combine expertise together.

Urinary Bladder Carcinosarcoma (Sarcomatoid Carcinoma) With Long Survival After Transurethral Resection: A Case Report.

Carcinosarcoma or sarcomatoid carcinoma of the urinary bladder is a rare but aggressive bladder cancer characterized by malignant epithelial and mesenchymal components, with only a few cases reported in the literature so far. In this report, we discuss a case of a 74-year-old female nonsmoker who presented with intermittent hematuria and passage of clots in the last four months. Radiographic images showed an irregular mass lesion (6.2 x 6 cm) in the left lateral wall of the urinary bladder near to left vesicoureteral junction. The mass was completely removed with transurethral resection of the bladder tumor (TUR-BT). Histopathological study revealed high-grade carcinosarcoma, and immunohistochemistry showed diffuse positivity for vimentin, pan-cytokeratin (CK) and CK7, epithelial membrane antigen (EMA), and CK5/6. The patient declined radical cystectomy and only agreed to receive intravesical chemotherapy (gemcitabine), and she remains alive after more than four years of follow-up. Carcinosarcoma of the urinary bladder is a rare tumor primarily affecting older people, and it is most commonly treated with radical cystectomy and different combination treatments such as chemotherapy and radiation. However, tumor resection followed by intravesical chemotherapy may be an alternative option in the early stages of bladder carcinosarcoma for some patients, thereby avoiding the need for aggressive treatments, especially for elderly patients who decline to undergo radical surgery.

Electrospun Polymeric Nanofibers: Current Trends in Synthesis, Surface Modification, and Biomedical Applications.

Electrospun polymeric nanofibers are essential in various fields for various applications because of their unique properties. Their features are similar to extracellular matrices, which suggests them for applications in healthcare fields, such as antimicrobials, tissue engineering, drug delivery, wound healing, bone regeneration, and biosensors. This review focuses on the synthesis of electrospun polymeric nanofibers, their surface modification, and their biomedical applications. Nanofibers can be fabricated from both natural and synthetic polymers and their composites. Even though they mimic extracellular matrices, their surface features (physicochemical characteristics) are not always capable of fulfilling the purpose of the target application. Therefore, they need to be improved via surface modification techniques. Both needle-based and needleless electrospinning are thoroughly discussed. Various techniques and setups employed in each method are also reviewed. Furthermore, pre- and postspinning modification approaches for electrospun nanofibers, including instrument design and the modification features for targeted biomedical applications, are also extensively discussed. In this way, the remarkable potential of electrospun polymeric nanofibers can be highlighted to reveal future research directions in this dynamic field.

RefAI: a GPT-powered retrieval-augmented generative tool for biomedical literature recommendation and summarization.

OBJECTIVES: Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes-real-time search and pretrained model utilization-it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. MATERIALS AND METHODS: RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics ("cancer immunotherapy and target therapy" and "LLMs in medicine") were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. RESULTS: The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions-relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). DISCUSSION: RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. CONCLUSION: By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.

Copper/Tin Nanocomposites-Loaded Exosomes Induce Apoptosis and Cell Cycle Arrest at G0/G1 Phase in Skin Cancer Cell Line.

This study aims to explore the efficacy of Copper/Tin (CuS/SnS) nanocomposites loaded into exosomes against skin cancer A431 cell line. CuS/SnS nanocomposites (S1, S2, S3) were synthesized and characterized, then loaded into exosomes (Exo) (S1-Exo, S2-Exo and S3-Exo) and characterized. After that, the loaded samples were investigated in vitro against A431 using cytotoxicity, apoptosis, and cell cycle assays. CuS/SnS nanocomposites were indexed to hexagonal CuS structure and orthorhombic α-SnS phase and showed nano-rode shape. The exosomes loaded with nanocomposites were regular and rounded within the size of 120 nm, with no signs of broken exosomes or leakage of their contents. The cytotoxicity assay indicated the enhanced cytotoxic of S1-Exo versus the free nano-form S1 on A431. Interestingly, S1-Exo recorded 1.109 times more than DOX in its anti-skin cancer capacity. Moreover, S1-Exo recorded 40.2% for early apoptosis and 22.1% for late apoptosis. Furthermore, it displayed impact in arresting the cancer cell cycle at G0/G1 phase and reducing G2/M phase. Noteworthy, loaded nanocomposites were safe against normal HSF skin cells. In conclusion, the loaded CuS/SnS nanocomposites into the exosomes could be of great potential as anti-skin cancer candidates through induction of apoptosis and promotion of the cell cycle arrest at G0/G1 phase.

Exploring the synthesis, characterization, and corrosion inhibition of new tris-thiosemicarbazone derivatives for acidic steel settings using computational and experimental studies.

A novel two tri-thiosemicarbazones derivatives, namely 2,2',2''-((2-Hydroxybenzene-1,3,5-triyl)tris(methanylylidene))tris(N-benzylhydrazine-1-carbothioamide) (HBC) and 2,2',2''-((2-hydroxybenzene-1,3,5-triyl) tris (methanylylidene)) tris (N-allylhydrazine-1-carbothioamide) (HAC), have been synthesized and their chemical structures were determined using different spectroscopic and analytical approaches. Then, utilizing methods including open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy, the inhibitory effect of the synthesized thiosemicarbazones on mild steel (MS) in an acidic environment (0.5 M H2SO4) was thoroughly investigated. Remarkably, raising the concentration of our recently synthesized tri-thiosemicarbazones HBC and HAC increased the inhibitory efficiency values. The η values of the two investigated tri-thiosemicarbazones derivatives (HAC and HBC), at each concentration are extremely high, and the maximum values of the efficiencies are 98.5% with HAC and 98.8% with HBC at the 800 ppm. The inhibitors adsorbed on the mild steel surface and generated a charge and mass movement barrier that protected the metal from hostile ions. According to polarization curves, HBC and HAC act as mixed-type inhibitors. Electrochemical impedance testing revealed a notable rise in charge transfer resistance (Rct) readings to 4930-Ω cm2, alongside a reduction in the Constant Phase Element (CPE) value to 5.81 µF, suggesting increased effectiveness in preventing corrosion. Also, density functional theory (DFT) was applied to investigate the assembled tri-thiosemicarbazones HBC and HAC. Moreover, the adsorption mechanism of HBC and HAC on the mild steel surface was explored using Monte Carlo simulation. Finally, the theoretical outputs were discovered to support the practical outcomes.

Bioactive injectable mucoadhesive thermosensitive natural polymeric hydrogels for oral bone and periodontal regeneration.

Periodontitis is an inflammation-related condition, caused by an infectious microbiome and host defense that causes damage to periodontium. The natural processes of the mouth, like saliva production and eating, significantly diminish therapeutic medication residency in the region of periodontal disease. Furthermore, the complexity and diversity of pathological mechanisms make successful periodontitis treatment challenging. As a result, developing enhanced local drug delivery technologies and logical therapy procedures provides the foundation for effective periodontitis treatment. Being biocompatible, biodegradable, and easily administered to the periodontal tissues, hydrogels have sparked substantial an intense curiosity in the discipline of periodontal therapy. The primary objective of hydrogel research has changed in recent years to intelligent thermosensitive hydrogels, that involve local adjustable sol-gel transformations and regulate medication release in reaction to temperature, we present a thorough introduction to the creation and efficient construction of new intelligent thermosensitive hydrogels for periodontal regeneration. We also address cutting-edge smart hydrogel treatment options based on periodontitis pathophysiology. Furthermore, the problems and prospective study objectives are reviewed, with a focus on establishing effective hydrogel delivery methods and prospective clinical applications.

Design, synthesis, antineoplastic activity of new pyrazolo[3,4-d]pyrimidine derivatives as dual CDK2/GSK3ß kinase inhibitors; molecular docking study, and ADME prediction.

In the current study, novel pyrazolo[3,4-d]pyrimidine derivatives 5a-h were designed and synthesized as targeted anti-cancer agents through dual CDK2/GSK-3ß inhibition. The designed compounds demonstrated moderate to potent activity on the evaluated cancer cell lines (MCF-7 and T-47D). Compounds 5c and 5 g showed the most promising cytotoxic activity against the tested cell lines surpassing that of the used reference standard; staurosporine. On the other hand, both compounds showed good safety and tolerability on normal fibroblast cell line (MCR5). The final compounds 5c and 5 g showed a promising dual CDK2/GSK-3ß inhibitory activity with IC50 of 0.244 and 0.128 µM, respectively, against CDK2, and IC50 of 0.317 and 0.160 µM, respectively, against GSK-3ß. Investigating the effect of compounds 5c and 5 g on CDK2 and GSK-3ß downstream cascades showed that they reduced the relative cellular content of phosphorylated RB1 and ß-catenin compared to that in the untreated MCF-7 cells. Moreover, compounds 5c and 5 g showed a reasonable selective inhibition against the target kinases CDK2/GSK-3ß in comparison to a set of seven off-target kinases. Furthermore, the most potent compound 5 g caused cell cycle arrest at the S phase in MCF-7 cells preventing the cells' progression to G2/M phase inducing cell apoptosis. Molecular docking studies showed that the final pyrazolo[3,4-d]pyrimidine derivatives have analogous binding modes in the target kinases interacting with the hinge region key amino acids. Molecular dynamics simulations confirmed the predicted binding mode by molecular docking. Moreover, in silico predictions indicated their favorable physicochemical and pharmacokinetic properties in addition to their promising cytotoxic activity.

Unveiling dynamics of nitrogen content and selected nitrogen heterocycles in thrombin inhibitors: a ceteris paribus approach.

BACKGROUND: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors. RESEARCH DESIGN AND METHODS: A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed. RESULTS: The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors. CONCLUSIONS: The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.

Estimating the energy consumption for residential buildings in semiarid and arid desert climate using artificial intelligence.

This research aims to develop predictive models to estimate building energy accurately. Three commonly used artificial intelligence techniques were chosen to develop a new building energy estimation model. The chosen techniques are Genetic Programming (GP), Artificial Neural Network (ANN), and Evolutionary Polynomial Regression (EPR). Sixteen energy efficiency measures were collected and used in designing and evaluating the proposed models, which include building dimensions, orientation, envelope construction materials properties, window-to-wall ratio, heating and cooling set points, and glass properties. The performance of the developed models was evaluated in terms of the RMS, R2, and MAPE. The results showed that the EPR model is the most accurate and practical model with an error percent of 2%. Additionally, the energy consumption was found to be mainly governed by three factors which dominate 87% of the impact; which are building size, Solar Heating Glass Coefficient (SHGC), and the target inside temperature in summer.

Ultrafast Events of Photoexcited Iron(III) Chloride for Activation of Benzylic C-H Bonds.

The usage of rare-earth-metal catalysts in the synthesis of organic compounds is widespread in chemical industries but is limited owing to its environmental and economic costs. However, recent studies indicate that abundant-earth metals like iron(III) chloride can photocatalyze diverse organic transformations using blue-light LEDs. Still, the underlying mechanism behind such activity is debatable and controversial, especially in the absence of ultrafast spectroscopic results. To address this urgent challenge, we performed femtosecond time-resolved electronic absorption spectroscopy experiments of iron(III) chloride in selected organic solvents relevant to its photocatalytic applications. Our results show that the long-lived species [Fe(II) ← Cl•]* is primarily responsible for both oxidizing the organic substrate and reducing molecular oxygen through the diffusion process, leading to the final product and regenerating the photocatalyst rather than the most widely proposed free chloride radical (Cl•). Our study will guide the rational design of efficient earth-abundant photocatalysts.

Effect of thermomechanical ageing on force transmission by orthodontic aligners made of different thermoformed materials: An experimental study.

OBJECTIVES: Investigating the impact of thermal and mechanical loading on the force generation of orthodontic aligners made from various thermoplastic materials and different compositions. MATERIALS AND METHODS: Five distinct materials were utilized including, three multi-layer (Zendura FLX, Zendura VIVA, CA Pro) and two single-layer (Zendura A and Duran). A total of 50 thermoformed aligners (n = 10) underwent a 48-hour ageing protocol, which involved mechanical loading resulting from a 0.2 mm facial malalignment of the upper right central incisor (Tooth 11) and thermal ageing through storage in warm distilled water at 37°C. The force exerted on Tooth 11 of a resin model was measured both before and after ageing using pressure-sensitive films and a biomechanical setup. RESULTS: Before ageing, pressure-sensitive films recorded normal contact forces ranging from 83.1 to 149.7 N, while the biomechanical setup measured resultant forces ranging from 0.1 to 0.5 N, with lingual forces exceeding facial forces. Multi-layer materials exhibited lower force magnitudes compared to single-layer materials. After ageing, a significant reduction in force was observed, with some materials experiencing up to a 50% decrease. Notably, multi-layer materials, especially Zendura VIVA, exhibited lower force decay. CONCLUSIONS: The force generated by aligners is influenced by both the aligner material and the direction of movement. Multi-layer materials exhibit superior performance compared to single-layer materials, primarily because of their lower initial force, which enhances patient comfort, and their capability to maintain consistent force application even after undergoing ageing.

Reduced levels of MRE11 cause disease phenotypes distinct from ataxia telangiectasia-like disorder.

The MRE11/RAD50/NBS1 (MRN) complex plays critical roles in cellular responses to DNA double-strand breaks. MRN is involved in end binding and processing, and it also induces cell cycle checkpoints by activating the ataxia-telangiectasia mutated (ATM) protein kinase. Hypomorphic pathogenic variants in the MRE11, RAD50, or NBS1 genes cause autosomal recessive genome instability syndromes featuring variable degrees of dwarfism, neurological defects, anemia, and cancer predisposition. Disease-associated MRN alleles include missense and nonsense variants, and many cause reduced protein levels of the entire MRN complex. However, the dramatic variability in the disease manifestation of MRN pathogenic variants is not understood. We sought to determine if low protein levels are a significant contributor to disease sequelae and therefore generated a transgenic murine model expressing MRE11 at low levels. These mice display dramatic phenotypes including small body size, severe anemia, and impaired DNA repair. We demonstrate that, distinct from ataxia telangiectasia-like disorder caused by MRE11 pathogenic missense or nonsense variants, mice and cultured cells expressing low MRE11 levels do not display the anticipated defects in ATM activation. Our findings indicate that ATM signaling can be supported by very low levels of the MRN complex and imply that defective ATM activation results from perturbation of MRN function caused by specific hypomorphic disease mutations. These distinct phenotypic outcomes underline the importance of understanding the impact of specific pathogenic MRE11 variants, which may help direct appropriate early surveillance for patients with these complicated disorders in a clinical setting.

Comparative metabolomics study on the secondary metabolites of the red alga, Corallina officinalis and its associated endosymbiotic fungi.

Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).

Insights into the photoactivatable CO releasing properties of dicarbonyl Ru(II) complex with 8-amino quinoline ligand: Experimental and theoretical studies.

Reaction between the polymeric [RuCl2(CO)2]n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl2(CO)2Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells.

Comparative analysis of patient demographics, perioperative outcomes, and adverse events after lumbar spinal fusion between urban and rural hospitals: an analysis of the National Inpatient Sample (NIS) database.

OBJECTIVE: Rural location of a patient's primary residence has been associated with worse clinical and surgical outcomes due to limited resource availability in these parts of the US. However, there is a paucity of literature investigating the effect that a rural hospital location may have on these outcomes specific to lumbar spine fusions. METHODS: Using the National Inpatient Sample (NIS) database, we identified all patients who underwent primary lumbar spinal fusion in the years between 2009 and 2020. Patients were separated according to whether the operative hospital was considered rural or urban. Univariable and multivariable regression models were used for data analysis. RESULTS: Of 2,863,816 patients identified, 120,298 (4.2 %) had their operation at a rural hospital, with the remaining in an urban hospital. Patients in the urban cohort were younger (P < .001), more likely to have private insurance (39.81 % vs 31.95 %, P < .001), and fewer of them were in the first (22.52 % vs 43.00 %, P < .001) and second (25.96 % vs 38.90 %, P < .001) quartiles of median household income compared to the rural cohort. The urban cohort had significantly increased rates of respiratory (4.49 % vs 3.37 %), urinary (5.25 % vs 4.15 %), infectious (0.49 % vs 0.32 %), venous thrombotic (0.57 % vs 0.24 %, P < .001), and neurological (0.79 % vs 0.36 %) (all P < .001) perioperative complications. On multivariable analysis, the urban cohort had significantly increased odds of the same perioperative complications: respiratory (odds ratio[OR] = 1.48; 95 % confidence interval [CI], 1.26-1.74), urinary (OR = 1.34; 95 %CI, 1.20-1.50), infection (OR = 1.63; 95 %CI, 1.23-2.17), venous thrombotic (OR = 1.79; 95 %CI, 1.32-2.41), neurological injury (OR = 1.92; 95 %CI, 1.46-2.53), and localized infection (OR = 1.65; 95 %CI, 1.25-2.17) (all P < .001). CONCLUSIONS: Patients undergoing lumbar fusions experience significantly different outcomes based on the rural or urban location of the operative hospital.

Piracetam mitigates nephrotoxicity induced by cisplatin via the AMPK-mediated PI3K/Akt and MAPK/JNK/ERK signaling pathways.

AIMS: Cisplatin (CDDP) is commonly employed as an antineoplastic agent, but its use is significantly limited by the occurrence of dose-dependent nephrotoxicity, the detailed mechanisms of which remain unclear. This research is aimed to explore the molecular mechanisms of Piracetam (PIR)'s protective effects on nephrotoxicity resulting from CDDP exposure and to elucidate the mechanisms responsible for these effects. MAIN METHODS: PIR was given in dosages of 100 and 300 mg/kg body weight for a duration of 15 days; concurrently, on the last day, a single 10 mg/kg dose of CDDP was delivered via intraperitoneal injection. Forty-eight hours post-CDDP injection, the animals were sacrificed to assess nephrotoxicity. Blood samples and renal tissues were taken for biochemical and histopathological investigations. Serum creatinine and blood urea nitrogen (BUN) were measured. AMP-activated protein kinase (AMPK), caspase-9 and nuclear factor kappa b p65 (NF-κB p65) were assessed by immunohistochemistry method. Enzyme-linked immunosorbent assay (ELISA) analysis was employed to determine cytochrome c (Cyt. c), Bcl-2-associated X-protein (BAX), caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), and interleukin-1ß (IL-1ß) levels in renal tissue homogenates. The mRNA levels of tumor protein P53 (TP53), phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK) were tested by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, histopathological evaluations of the renal tissues and the binding affinity of PIR to AMPK by molecular docking were also performed. KEY FINDINGS: Pre-treatment with PIR enhanced renal function markers such as urea and creatinine, mitigated histological damage, and diminished inflammatory cell presence in renal tubules. PIR demonstrated antioxidant effects by reestablishing the equilibrium between pro-oxidants and antioxidants such as MPO, HO-1, Nrf2, as well as SOD. Furthermore, PIR inhibited the inflammatory pathways through the MAPK/NF-κB pathway. Additionally, PIR counteracted the CDDP-induced decline in PI3K/Akt activity and hindered caspase-dependent apoptotic processes. SIGNIFICANCE: In summary, PIR appears to be an effective therapeutic strategy for reducing CDDP-induced nephrotoxicity, attributed to its antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Consequently, PIR may serve as a complementary treatment alongside CDDP to alleviate nephrotoxicity associated with CDDP.