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Aim: The study was designed to develop and analyze curcumin nanoparticles. Methods: Curcumin nanoparticles were formulated and evaluated. Their efficacy in protecting against brain damage was investigated in a rat model of ischemic stroke, considering motor function, muscle strength and antioxidant enzyme activity. Results: Curcumin nanoparticles displayed a zeta potential of -55 ± 13.5 mV and an average particle size of 51.40 ± 21.70 nm. In ischemic stroke rat models, curcumin nanoparticle treatment significantly improved motor functions, and muscle strength and increased the activities of antioxidant enzymes like glutathione peroxidase, glutathione, glutathione S-transferase, superoxide dismutase and catalase, reducing oxidative stress and inflammation. Conclusion: Curcumin nanoparticles showed significant neuroprotective effects in ischemic stroke models.
[Box: see text].
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Antioxidantes , Curcumina , Modelos Animales de Enfermedad , Inflamación , Accidente Cerebrovascular Isquémico , Estrés Oxidativo , Animales , Curcumina/farmacología , Curcumina/química , Estrés Oxidativo/efectos de los fármacos , Ratas , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Masculino , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Tamaño de la Partícula , Nanogeles/química , Fármacos Neuroprotectores/farmacología , Superóxido Dismutasa/metabolismo , Ratas Wistar , Polietilenglicoles/química , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismoRESUMEN
PURPOSE: Coronal shear fractures of the distal humerus involving the capitellum and trochlea are rare injuries. Internal fixation with headless compression screws provides a stable construct facilitating early mobilisation. Our study aimed to identify the key determinants of both radiological and functional outcomes of patients with distal humerus coronal shear fractures treated with internal fixation. METHODS: A retrospective analysis of 61 patients with distal humerus coronal shear fractures who were treated surgically was done. Demographics, fracture morphology, time to surgery, operative details such as surgical approach and implant used, quality of reduction, time to union, and associated complications from hospital records. Radiological outcomes were assessed using plain radiographs, and the functional outcomes were by Oxford Elbow Score (OES) and Mayo Elbow Performance Index (MEPI). RESULTS: Patients with anatomical reduction of the fracture had better functional outcomes and range of motion. The presence of posterior comminution of capitellum resulted in poorer outcomes (p = 0.03). Delayed presentation did not alter the outcome when the anatomical reduction was achieved. Myositis ossificans was noted in nine patients and non-union in five patients. Two patients developed avascular necrosis of the capitellum and arthritis of the elbow joint. CONCLUSION: Anatomical reduction and posterior comminution are the two key determinants of the functional outcome in these coronal shear fractures of the distal humerus. Early mobilisation following a stable fixation is crucial in achieving a good outcome.
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Articulación del Codo , Fracturas Conminutas , Fracturas del Húmero , Humanos , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Estudios Retrospectivos , Fracturas del Húmero/diagnóstico por imagen , Fracturas del Húmero/cirugía , Húmero , Radiografía , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Fracturas Conminutas/cirugía , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by the inclusion of adjuvants, which are substances that potentiate and modulate the immune response. This review is based on extensive searches in reputable databases such as Web of Science, PubMed, EMBASE, Scopus, and Google Scholar. The goal of this review is to provide a thorough analysis of the advances in the field of adjuvant research, to trace the evolution, and to understand the effects of the various adjuvants. Historically, alum was the pioneer in the field of adjuvants because it was the first to be approved for use in humans. It served as the foundation for subsequent research and innovation in the field. As science progressed, research shifted to identifying and exploiting the potential of newer adjuvants. One important area of interest is nano formulations. These advanced adjuvants have special properties that can be tailored to enhance the immune response to vaccines. The transition from traditional alum-based adjuvants to nano formulations is indicative of the dynamism and potential of vaccine research. Innovations in adjuvant research, particularly the development of nano formulations, are a promising step toward improving vaccine efficacy and safety. These advances have the potential to redefine the boundaries of vaccination and potentially expand the range of diseases that can be addressed with this approach. There is an optimistic view of the future in which improved vaccine formulations will contribute significantly to improving global health outcomes.
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BACKGROUND: Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting. METHODS: We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated. RESULTS: A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma. CONCLUSIONS: To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development.
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Neoplasias Glandulares y Epiteliales , Timoma , Neoplasias del Timo , Humanos , Timoma/genética , Timoma/patología , Neoplasias del Timo/genética , Neoplasias del Timo/patología , Neoplasias Glandulares y Epiteliales/genética , GenómicaRESUMEN
The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensive investigation, including physicochemical characterization, in vivo assessment of biomarkers, and an examination of immune response through cytokine modulation. The zeta potential of LLDDNP was - 24.5 ± 12 mV, while their average particle size was 334.9 z.d.nm. The particles exhibited a conductivity of 2.10 mS/cm, while their mobility in the injectable dosage form was measured at - 3.65 µm cm/Vs. The scanning electron microscopy investigation, the lyophilization processes resulted in discrete particles forming particle aggregations. However, transmission electron microscopy analysis revealed that LLDDNP is spherical and smooth. The thermogram showed that about 95% of LLDDNP's weight was lost at 270 °C, indicating that the particles are extremely thermal stable. The XRD analysis of LLDDNP exhibited clear and distinctive peaks at 2θ angles, specifically at 9.6°, 20.3°, 21.1°, 22°, 24.6°, 25.2°, 36°, and 44.08°, providing compelling evidence of the crystalline nature of the particles. According to proton NMR studies, the proton dimension fingerprint region of LLDDNP ranges from 1.00 to 1.03 ppm. The in vitro release of LTF from LLDDNP was found to follow zero-order kinetics, with a commendable R2 value of 0.942, indicating a consistent and predictable release pattern over time. The in vivo investigation revealed a significant impact of hepatotoxicity on the elevation of various cytokines, including IL-1ß, IL-6, IL-8R, TNF-α, IL-2, IL-4, IL-10, and IFN-γ. Additionally, the presence of hepatotoxicity led to an increase in apoptosis markers, namely caspase 3 and caspase 9, as well as elevated levels of liver biomarkers such as CRP, ALP, ALT, and AST. In contrast, the treatment with LLDDNP modulated the levels of all biomarkers, including cytokines level in the treatment group extremely high significant at p < 0.001.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Lactoferrina , Humanos , Ácidos Docosahexaenoicos , Dextranos , Protones , CitocinasRESUMEN
In recent years, nucleic-acid amplification tests (NAATs), which are highly specific and sensitive, have helped to transform the TB diagnostic landscape. According to the WHO 2021 Guidelines on Diagnostics, the NAATs used in TB diagnosis at the point of care (POC) include Xpert MTB/RIF a cartridge-based test manufactured by Cepheid, and Truenat a chip-based test manufactured by Molbio. Other POC tests that are expected to be implemented in near future include Xpert Omni and Xpert MTB/XDR. The use of line probe assay is involved at the level of reference labs for the detection of MTB and its resistance to first-line (Isoniazid and Rifampicin) and second-line (fluoroquinolones and second-line injectables) drugs. When the currently available NAATs detect mutations for drug resistance at a particular region of MTB sequence, the Whole genome sequencing (WGS) platform demonstrates the exceptional potential for reliable and comprehensive resistance prediction for MTB isolates, by multiple gene regions or whole genome sequence analysis allowing for accurate clinical decisions.
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Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Farmacorresistencia Bacteriana/genética , Rifampin/farmacología , Isoniazida/farmacología , Sensibilidad y Especificidad , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antibióticos Antituberculosos/farmacologíaRESUMEN
The proposed research outlines a facile method to synthesize Silver Chromate/reduced graphene oxide nanocomposites (Ag2CrO4/rGO NCs) with a narrow dissemination size for the ecological treatment of hazardous organic dyes. The photodegradation performance toward the decontamination of model artificial methylene blue dye was assessed under solar light irradiation. The crystallinity, particle size, recombination of photogenerated charge carriers, energy gap and surface morphologies of synthesized nanocomposites were determined. The experiment objective is to use rGO nanocomposites to increase Ag2CrO4 photocatalytic efficiency in the solar spectrum. Tauc plots of ultraviolet-visible (UV-vis) spectrum were used to calculate the optical bandgap energy of the produced nanocomposites â¼1.52 eV, which resulted in a good photodegradation percentage of â¼92 % after 60 min irradiation of Solar light. At the same time, pure Ag2CrO4 and rGO nanomaterials showed â¼46 % and â¼ 30 %, respectively. The ideal circumstances were discovered by investigating the effects of several parameters, including catalyst loading and different pH levels, on the degradation of dyes. However, the final composites maintain their ability to degrade for up to five cycles. According to the investigations, Ag2CrO4/rGO NCs are an effective photocatalyst and can be used as the ideal material to prevent water pollution. Furthermore, antibacterial efficacy for the hydrothermally synthesized nanocomposite was tested against gram-positive (+ve) bacteria viz. Staphylococcus aureus and gram-negative (-ve) bacteria viz. Escherichia coli. The maximum zone of inhibition for S. aureus and E. coli were 18.5 and 17 mm, respectively.
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Antibacterianos , Nanocompuestos , Antibacterianos/farmacología , Antibacterianos/química , Aguas del Alcantarillado , Escherichia coli , Staphylococcus aureus , Nanocompuestos/químicaRESUMEN
BACKGROUND: The quantitative measure of dopamine transporter (DaT) in the human midbrain is generally used as a biomarker for analyzing Parkinson's disease (PD). INTRODUCTION: DaT scan images or Single- photon emission computed tomography (SPECT) images are utilized to capture the dopamine content more accurately. METHODS: Only sixteen slices out of ninety-one of SPECT images were chosen on the basis of the high amount of dopamine content and were named Volume rendering image slices (VRIS). This paper proposes a novel Convolutional Neural Network (CNN) called JAN Net which particularly treats the VRIS for identifying PD. The JAN Net preserves the edges and spatial features of the striatum by using a modified exigent feature (M-ExFeat) block, that contains convolutional and additive layer. The different-sized convolutional layer extracts both low- and high-level features of Striatum. The additive layer adds up all the features of different filter sized convolutional layers like 1x1, 3x3, and 5x5. The added output features are used to improve the learnability of neurons in the hidden layer. The network performance is tested for stride 1 and stride 2. RESULTS: The results are validated using the dataset taken from the Parkinson's Progression Markers Initiative (PPMI) database. The JAN Net ensures improved performance in terms of accuracy. The training and validation accuracy for stride 2 is 100% with minimum losses. The outcome has been compared with different deep learning architectures and the machine learning techniques like Extreme Learning Machines (ELM), and Artificial Neural Networks (ANN) to highlight the efficacy of the proposed architecture. CONCLUSION: Hence, the present work could be of great aid to the experts in neurology to protect the neurons from impairment.
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The study aimed to develop cisplatin-loaded PEGylated chitosan nanoparticles. The optimal batch of cisplatin-loaded PEGylated chitosan nanoparticles had a + 49.9 mV zeta potential, PDI of 0.347, and % PDI of 58.9. Nanoparticle zeta size was 741.4 z. d.nm, the size in diameter was 866.7 ± 470.5 nm, and nanoparticle conductivity in colloidal solution was 0.739 mS/cm. Differential scanning calorimetry (DSC) revealed that cisplatin-loaded PEGylated chitosan nanoparticles had sharp endothermic peaks at temperatures at 168.6 °C. The thermogravimetric analysis (TGA) showed the weight loss of cisplatin-loaded PEGylated chitosan nanoparticles, which was observed as 95% at 262.76 °C. XRD investigation on cisplatin-loaded PEGylated chitosan nanoparticles exhibited distinct peaks at 2θ as 9.7°, 20.4°, 22.1°, 25.3°, 36.1°, 38.1°, 39.5°, 44.3°, and 64.5°, confirming crystalline structure. The 1H NMR analysis showed the fingerprint region of cisplatin-loaded PEGylated chitosan nanoparticles as 0.85, 1.73, and 1.00 ppm in the proton dimension and de-shielded proton peaks appeared at 3.57, 3.58, 3.58, 3.59, 3.65, 3.67, 3,67, 3,67, 3.70, 3.71, 3.77, 3.78 and 4.71 ppm. The 13C NMR spectrum showed specified peaks at 63.18, 69.20, and 70.77 ppm. The FT-IR spectra of cisplatin loaded PEGylated nanoparticles show the existence of many fingerprint regions at 3186.52, 2931.68, 1453.19, 1333.98, 1253.71, 1085.19, 1019.60, 969.98, 929.53, 888.80, 706.13, and 623.67 cm-1. The drug release kinetics of cisplatin loaded PEGylated chitosan nanoparticles showed zero order kinetics with 48% of drug release linearity fashion which has R2 value of 0.9778. Studies on the MCF-7 ATCC human breast cancer cell line in vitro revealed that the IC50 value 82.08 µg /mL. Injectable nanoparticles had good physicochemical and cytotoxic properties. This method is novel since the application of the PEGylation processes leads to an increased solubility of chitosan nanoparticles at near neutral pH.
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Amikacin sulfate-loaded dextran sulfate sodium nanoparticles were formulated, lyophilized (LADNP), and then analyzed. The LADNP had a -20.9 ± 8.35 mV zeta potential, PDI of 0.256, and % PDI of 67.7. The zeta average nano size of LADNP was 317.9 z. d.nm, while the dimension of an individual particle was 259.3 ± 73.52 nm, and nanoparticle conductivity in colloidal solution was 2.36 mS/cm. LADNP has distinct endothermic peaks at temperatures at 165.77 °C, according to differential scanning calorimetry (DSC). The thermogravimetric analysis (TGA) showed the weight loss of LADNP, which was observed as 95% at 210.78 °C. XRD investigation on LADNP exhibited distinct peaks at 2θ as 9.6°, 10.4°, 11.4°, 18.9°, 20.3°, 24.4°, 28.2°, 33.2°, 38.9°, and 40.4° confirming crystalline structure. The amikacin release kinetics from LADNP revealed zero order kinetics with a linear release showed zero order kinetics with 37% of drug release in 7 h and had an R2 value of 0.99. The antibacterial effect of LADNP showed broad-spectrum activity against tested human pathogenic bacteria. The preset study demonstrated that LADNP is a promising antibacterial agent.
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Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1ß, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.
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The present study focused on demonstrating the induction of humoral and cell-mediated immunity through the establishment of a cytokine network. We hypothesized the anti-inflammatory, pro-inflammatory, and IgE antibody levels after vaccination with lyophilized recombinant HBsAg-loaded docosahexaenoic acid nanovesicles (LRPDNV), and the efficacy compared well with standard commercial recombinant hepatitis B vaccine. The cytokine network was efficiently regulated by striking a balance between pro-inflammatory cytokines IL-6, IL-8R, and IL-12 and anti-inflammatory cytokines such as IL-2, IL-4, IL-10, and IFN-γ immune response on the 14th and 30th day after primary and booster immunization. The acute phase protein CRP level was increased due to IL-6 after immunizing with LRPDNV. On the other hand, the IgE level was not significantly increased to induce any allergic reactions after immunization with LRPDNV. The study concluded that after immunizing with LRPDNV, a significant immunological response was established, implying that DHA nanovesicles have significant potential as an adjuvant method for delivering recombinant HBsAg protein. On the other hand, following immunization with LRPDNV, the IgE level was not noticeably elevated enough to cause any adverse reactions. The study concludes that a robust immune response was developed after immunizing with LRPDNV and suggests that DHA nanovesicles have much potential to deliver recombinant HBsAg protein.
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OBJECTIVE: The treatment of tuberculosis with isoniazid and rifampin is associated with hepatocellular damage. Therefore, the study was designed to evaluate the hepatoprotective potential of diosmin against hepatotoxic effect of isoniazid and rifampin in Wistar rats. METHODS: Hepatotoxicity was induced by administering isoniazid and rifampin (100 mg/kg), whereas diosmin was given as treatment control. Markers of liver function (ALT, AST, ALP and bilirubin), inflammatory cytokines (TNFα, IL-6 and IL-1ß), apoptosis (caspase-3), oxidative stress parameters (LPO, GSH, CAT and SOD) and histological changes in liver were assessed in normal, hepatotoxic control and treatment groups. RESULTS: The administration of isoniazid and rifampin significantly increased markers of liver dysfunction (ALT, AST, ALP and bilirubin), cytokines (TNFα, IL-6 and IL-1ß) and apoptosis (caspase-3). However, daily dosing of diosmin significantly reduced these markers of liver dysfunction, inflammatory cytokines and apoptosis to near normal levels. Additionally, markers of hepatocellular oxidative stress parameters were significantly altered as evident from increased LPO level and decreased endogenous antioxidants such as GSH, SOD and CAT in isoniazid-and rifampin-treated hepatotoxic group. It was observed that diosmin treatment reduced high levels of LPO and demonstrated significant improvement in antioxidant levels. Histological studies of liver also supported our biochemical findings, which are also manifested as diosmin treatment exhibited protection against hepatocellular degeneration and inflammation. CONCLUSION: Results of the present study demonstrate hepatoprotective potential of diosmin against isoniazid-and rifampin-treated hepatotoxicity. Thus, we conclude that diosmin may be used along with anti-tubercular drugs (isoniazid and rifampin) in tuberculosis patients to overcome their hepatotoxic adverse effect.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Diosmina , Ratas , Animales , Isoniazida/toxicidad , Ratas Wistar , Rifampin/toxicidad , Factor de Necrosis Tumoral alfa , Diosmina/farmacología , Diosmina/uso terapéutico , Caspasa 3 , Interleucina-6 , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Hígado , Bilirrubina/farmacología , Superóxido DismutasaRESUMEN
Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1ß, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies.
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Cardiotoxicidad , Citocinas , Animales , Ratas , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Citocinas/farmacología , Ratas Wistar , Estrés Oxidativo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Glutatión/metabolismoRESUMEN
The objective of this study was to characterize the bioactive ingredients and antiulcer effects of Lactuca sativa leaves. Several bioactive chemicals were found in the cold methanolic extract of Lactuca sativa leaves after gas chromatography-mass spectrometry (GC-MS) research: 9,12-octadecadienoic acid (Z,Z)-, cyclononasiloxane, octadecamethyl-, n-hexadecanoic acid, Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl, octadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, 9-octadecenamide, (Z)-, hexadecanoic acid, stigmasterol, benzothiazole, ethyl iso-allocholate, and octacosane. Distinct fingerprint regions in GCMS indicated the existence of bioactive compounds. The leaf powder of Lactuca sativa (LPL) demonstrated substantial antiulcer properties at 400 mg/kg, which was almost equivalent to the standard drug at 20 mg/kg. The cytokine network was efficiently regulated by reducing the production of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-α. The levels of caspase-3 and caspase-9 were also considerably lowered at p < 0.05 significant level.
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Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1ß and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.
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Antineoplásicos , Insuficiencia Renal , Animales , Antineoplásicos/farmacología , Antioxidantes/farmacología , Apoptosis , Caspasa 3/metabolismo , Creatinina/metabolismo , Ciclofosfamida/toxicidad , Citocinas/metabolismo , Dioxoles , Riñón/metabolismo , Lignanos , Malondialdehído/metabolismo , Estrés Oxidativo , Ratas , Insuficiencia Renal/metabolismo , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ácido Úrico/metabolismoRESUMEN
BACKGROUND: Standardization of cell culture medium plays a vital role in the development of primary or continuous cell line. Apart from the basal media, supplements in the medium and various physical factors promote the cell growth. With this context, the study was carried out to optimize the culture medium using various supplements and physical factors for the growth of hemocytes culture from Penaeus vannamei. METHODS: Various concentrations of Fetal Bovine Serum (FBS; 1-25%), Shrimp Muscle Extract (SME; 1-25%) and basic Fibroblast Growth Factor (bFGF; 0.5-5 ng mL -1) were attempted to optimize the cell culture media for the development of primary hemocytes culture of P. vannamei. Various pH, temperature and osmolality was also screened to optimize the medium. RESULTS: 15% FBS was ideal for the healthy morphology of cells with rapid replication. SME supplementation at 5-20% supported the cell growth for 24 h but only 30% of cell viability was observed after 48 h. bFGF (0.5-5 ng mL-1) enhanced cell growth in the medium with 15% FBS; The ideal pH level was examined by preparing the HBSCM-5 medium at pH between 6.8-8.0. Osmolality of 730 ± 20, pH of 7.2 and temperature of 28 °C resulted in the healthy cells with good morphology. NSW supplement supported the cell growth at low concentrations of salt; however, more than 2% salt concentrations cells did not form fibroblast-like morphology and instead a crystal-like morphology was observed. CONCLUSION: The hemocytes culture were optimized for use as an in vitro cell culture system by testing cell growth on HBSCM-5 medium with various supplements, growth factors and physical parameters.
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Penaeidae , Animales , Suplementos Dietéticos , Factor 2 de Crecimiento de Fibroblastos , Hemocitos , Albúmina Sérica BovinaRESUMEN
Recombinant HBsAg-loaded docosahexaenoic acid nanovesicles were successfully developed, lyophilized (LRPDNV) and characterized for their physico-chemical properties. The zetapotential (ZP) of LRPDNV was -60.4 ± 10.4 mV, and its polydispersity (PDI) was 0.201, with a % PDI of 74.8. The particle sizes of LRPDNV were 361.4 ± 48.24 z. d.nm and 298.8 ± 13.4 r.nm. The % mass (r.nm) of LRPDNV in a colloidal injectable system was 50, its mobility value was -3.417 µm cm/Vs, while the conductivity of the particles was 0.728 (mS/cm). Transmission electron microscopic (TEM) analysis showed smooth morphological characteristics of discrete spherical LRPDNV. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of LRPDNV revealed that LRPDNV is thermostable. The X-ray diffraction (XRD) studies showed a discrete crystalline structure of LRPDNV at 2θ. Nuclear magnet resonance (NMR) studies (1H-NMR and 13C-NMR spectrum showed the discrete structure of LRPDNV. The immunogenicity study was performed by antibody induction technique. The anti-HBs IgG levels were elevated in Wistar rats; the antibody induction was observed more in the product (LRPDNV) treatment group when compared to the standard vaccine group. The level of antibodies on the 14th and 30th day was 6.3 ± 0.78 U/mL and 9.24 ± 1.76 U/mL in the treatment and standard vaccine groups, respectively. Furthermore, the antibody level on the 30th day in the treatment group was 26.66 ± 0.77 U/mL, and in the standard vaccine group, the antibody level was 23.94 ± 1.62 U/mL. The LRPDNV vaccine delivery method released HBsAg sustainably from the 14th to the 30th day. The results of this study indicate the successful formulation of DHA nanovesicles which have great potential as an adjuvant system for the delivery of recombinant HBsAg protein.
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In this work, copper (Cu) matrix composite reinforced with titanium carbide (TiC) was fabricated by powder metallurgy (PM) method with the varying TiC content from 0% to 12% by weight in the step of 4%. The required weight percentage of powders was milled in an indigenously developed ball milling setup. Green compacts were made using a computer-controlled hydraulic press (400 kN) and sintered in a muffle furnace at a temperature of 950°C. Scanning electron microscope (SEM) was used to analyze the distribution of TiC particles in Cu matrix in as-sintered conditions. X-ray diffraction (XRD) analysis resulted in the existence of respective phases in the produced composites. The structural characteristics such as stress, strain, dislocation density, and grain size of the milled composites were evaluated. Cold upsetting was conducted for the sintered composites at room temperature to evaluate the axial (σ z ), hoop (σ Ó© ), hydrostatic (σ m ), and effective (σ eff ) true stresses. These stresses were analyzed against true axial strain (ε z ). Results showed that the increase in the inclusion of weight percentage of TiC into the Cu matrix increases density, hardness, (σ z ), (σ Ó© ), (σ m ), (σ eff ), and stress ratio parameters such as (σ z /σ eff ), (σ θ /σ eff ), (σ m /σ eff ), and (σ z /σ θ ) of the composites.
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The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ. Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R2 = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R2 = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.