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The change in composition and pressure, both of which lead to new desired properties by altering the structure, is particularly important for improving device performance. Given this, we focused here on the mechanical, elastic, and optoelectronic characteristics of the Cd0.75Zn0.25Se alloy using density functional theory at various pressures from 0 GPa to 20 GPa. It is found that the bulk modulus of the material rises with increasing pressure and exhibits mechanical stability as well as cubic symmetry. In addition, the increased pressure leads to a rise in the direct bandgap energy of the material from 2.03 eV to 2.48 eV. The absorption coefficient of the alloy also increases as the pressure increases, where the effective range of absorption covers the broad spectrum of light in the visible range from orange to cyan. This is due to the electronic transitions caused by the altered pressure. The optical parameters, including optical conductivity, extinction coefficient, reflection, and refractive index, are also analyzed under the influence of pressure. Based on this research, effective applications of the Cd substituted Zn-chalcogenides (CdZnSe) alloys in the fields of optoelectronics and photovoltaics are outlined, especially concerning fabricating solar cells, photonic devices, and pressure sensors for space technology.
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This study uses the aerial parts of Panicum maximum total extract (PMTE) to synthesize silver nanoparticles (AgNPs) in an environmentally friendly manner. TEM, SEM, FTIR, X-ray powder diffraction (XRD), Zeta potential, UV, and FTIR were used to characterize the green silver nanoparticles (PM-AgNPs). PM-AgNPs were evaluated as anticancer agents compared to (PMTE) against breast (MCF-7), lung (A549), and ovary adenocarcinoma (SKOV3) human tumour cells. The antibacterial activity of AgNPs was assessed against Staphylococcus aureus isolates. The PM-AgNPs had an absorbance of 418 nm, particle size of 15.18 nm, and zeta potential of -22.4 mV, ensuring the nanosilver's stability. XRD evaluated the crystallography nature of the formed PM-AgNPs. The cytotoxic properties of PM-AgNPs on MCF-7 and SKOV 3 were the strongest, with IC50s of 0.13 ± 0.015 and 3.5 ± 0.5 g/ml, respectively, as compared to A549 (13 ± 3.2 µg/mL). The increase in the apoptotic cells was 97.79 ± 1.61 and 96.6 ± 1.91% for MCF-7 and SKOV3 cell lines, respectively. PM-AgNPs were found to affect the membrane integrity and membrane permeability of 50 and 43.75% of the tested isolates, respectively. Also, PM-AgNPs have recorded a reduction in the biofilm formation of S. aurues. These results suggest using PM-AgNPs to treat breast and ovarian cancers.
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Antibacterianos , Química Verde , Nanopartículas Metálicas , Simulação de Acoplamento Molecular , Prata , Prata/química , Prata/farmacologia , Humanos , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Linhagem Celular Tumoral , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Técnicas de Química Sintética , Células MCF-7RESUMO
BACKGROUND: Despite cisplatin's long history as a cornerstone in cancer therapy, both acquired chemoresistance and significant impacts on healthy tissues limit its use. Hepatotoxicity is one of its side effects. Adjunct therapies have shown promise in not only attenuating liver damage caused by cisplatin but also in enhancing the efficacy of chemotherapy. In this context, a new quaternary ammonium chitosan Schiff base (QACSB) was synthesized and applied as an encapsulating agent for the in-situ synthesis of QACSB-ZnO nanocomposite. MATERIAL AND METHODS: Thirty male albino rats were classified into Group 1 (control) distilled water, Group 2 (Cisplatin-treated) (12 mg/kg, i.p), and Group 3 (QACSB-ZnO NCs/cisplatin-treated) (150 mg/kg/day QACSB-ZnO NCs, i.p) for 14 days + a single dose of cisplatin. Liver functions, tissue TNF-α, MDA, and GSH were measured as well as histopathological and immunohistochemical studies were performed. RESULTS: The QACSB-ZnO NCs significantly restore liver functions, tissue TNF-α, MDA, and GSH levels (p < 0.001). Histopathological examination showed patchy necrosis in the cisplatin-treated group versus other groups. The QACSB-ZnO NCs showed a weak TGF-ß1 (score = 4) and a moderate Bcl-2 immunohistochemistry expression (score = 6) versus the CP group. CONCLUSIONS: QACSB-ZnO NCs have been shown to protect the liver from cisplatin-induced hepatotoxicity.
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Quitosana , Cisplatino , Nanocompostos , Compostos de Amônio Quaternário , Bases de Schiff , Óxido de Zinco , Animais , Cisplatino/efeitos adversos , Bases de Schiff/química , Bases de Schiff/farmacologia , Quitosana/química , Quitosana/farmacologia , Ratos , Nanocompostos/química , Masculino , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glutationa/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Fator de Necrose Tumoral alfa/metabolismo , Malondialdeído/metabolismoRESUMO
BACKGROUND: Plant-derived products or extracts are widely used in folk/traditional medicine to treat several infections, ailments, or disorders. A well-known medicinal herb, Myrtus communis is an evergreen fragrant plant native to the Mediterranean region that has been used for ages in traditional medicine around the world. MATERIALS AND METHODS: The microplate alamarBlue assay and the well diffusion method were used to evaluate the zone of inhibition and MIC, respectively. The double-disc diffusion method was used to investigate the synergy between antibiotics and the extract. The crystal violet method was used to investigate biofilm development. The SulphoRhodamine-B assay and DNA flow cytometry were used to investigate the proliferation and subsequent distribution of cells among different phases of the cell cycle. The apoptotic and necrotic phases of the cancer cells were examined using flow cytometry in conjunction with Annexin V-FITC/PI labeling. Using the IBM SPSS statistical program, a one-way ANOVA with Tukey's post hoc test was employed for statistical analysis. RESULTS: The ethanolic leaf extract of M. communis showed a strong growth inhibition effect (zone of inhibition: 20.3 ± 1.1-26.3 ± 2.5 mm, MIC: 4.88-312.5 µg/mL, and MBC: 39.07-1250 µg/mL) against several rapidly growing and slow-growing mycobacterial strains in a dose-dependent manner. Damage to the cell wall of bacterial cells was determined to be the cause of the antimycobacterial action. The extract inhibited biofilm formation (MBIC of 9.7 µg/mL) and eradicated already-formed mature and ultra-mature biofilms of M. smegmatis, with MBEC values of 78 µg/mL and 156 µg/mL, respectively. Additionally, the extract exhibited potent anticancer effects against diverse cancer cell lines of the breast (MCF-7), liver (HepG2), cervix (HeLa), and colon (HCT116) (IC50 for HCT116: 83 ± 2.5, HepG2: 53.3 ± 0.6, MCF-7: 41.5 ± 0.6, and HeLa: 33.3 ± 3.6) by apoptosis after arresting the cells in the G1 phase of the cell cycle. CONCLUSIONS: These results suggest that M. communis leaf extract is a potential source of secondary metabolites that could be further developed as potential anticancer and antimycobacterial agents to treat diverse types of cancers and mycobacterial infections.
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A series of novel coumarin-thiazoles was designed and synthesized as a possible CDK2 inhibitor with anticancer activity with low toxicity. The design relied on having hydrazine thiazole or its open-form thioamide to form H-bonds with the ATP binding site while coumarin maintained the crucial hydrophobic interactions for proper fitting. The biological evaluation revealed that the hydroxycoumarin-thiazole derivative 6c demonstrated the best inhibition with HepG2 and HCT116 IC50 2.6 and 3.5 µM, respectively. Similarly, its open thioamide chain congener 5c exhibited potent inhibition on MCF-7 and HepG2 with IC50 of 4.5 and 5.4 µM, respectively. Molecular docking simulations supported the assumption of inhibiting CDK2 by preserving the crucial interaction pattern with the hinge ATP site and the surrounding hydrophobic (HPO) side chains. Furthermore, molecular dynamics simulations of 5c and 6c established satisfactory stability and affinity within the CDK2 active site.
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The present study was focused on exploring the efficient inhibitors of closed state (form) of type III effector Xanthomonas outer protein Q (XopQ) (PDB: 4P5F) from the 44 phytochemicals of Picrasma quassioides using cutting-edge computational analysis. Among them, Kumudine B showed excellent binding energy (-11.0 kcal/mol), followed by Picrasamide A, Quassidine I and Quassidine J with the targeted closed state of XopQ protein compared to the reference standard drug (Streptomycin). The molecular dynamics (MD) simulations performed at 300 ns validated the stability of top lead ligands (Kumudine B, Picrasamide A, and Quassidine I)-bound XopQ protein complex with slightly lower fluctuation than Streptomycin. The MM-PBSA calculation confirmed the strong interactions of top lead ligands (Kumudine B and QuassidineI) with XopQ protein, as they offered the least binding energy. The results of absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed that Quassidine I, Kumudine B and Picrasamide A were found to qualify most of the drug-likeness rules with excellent bioavailability scores compared to Streptomycin. Results of the computational studies suggested that Kumudine B, Picrasamide A, and Quassidine I could be considered potential compounds to design novel antibacterial drugs against X. oryzae infection. Further in vitro and in vivo antibacterial activities of Kumudine B, Picrasamide A, and Quassidine I are required to confirm their therapeutic potentiality in controlling the X. oryzae infection.
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Antibacterianos , Simulação de Dinâmica Molecular , Xanthomonas , Antibacterianos/farmacologia , Antibacterianos/química , Xanthomonas/efeitos dos fármacos , Quimioinformática/métodos , Simulação de Acoplamento Molecular , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/químicaRESUMO
[This retracts the article DOI: 10.1007/s13205-020-2077-x.].
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Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.
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Melanoma , Nanopartículas Metálicas , Neoplasias Cutâneas , Óxido de Zinco , Animais , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Espectroscopia de Infravermelho com Transformada de Fourier , Melanoma/tratamento farmacológico , Soroalbumina Bovina/química , Neoplasias Cutâneas/tratamento farmacológico , Estresse Oxidativo , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/químicaRESUMO
The article discusses the removal of methylene blue (MB) dye, a common cationic dye used in the textile industry, from aqueous solutions through an adsorption process. The use of porous components as adsorbents are shown to facilitate complete separation after the process is completed. The substrate was synthesized by connecting zinc copper ferrite (ZnCuFe2O4), polyethyleneimine (PEI), and Graphene Oxide (GO) sheets to MCM-48, which is a mesoporous material. The surface of MCM-48 was modified using CPTMS, which created an O-Si-Cl bridge, thereby improving the adsorption rate. The substrate was shown to have suitable sites for electrostatic interactions and creating hydrogen bonds with MB. The adsorption process from the Freundlich isotherm (R2 = 0.9224) and the pseudo-second-order diagram (R2 = 0.9927) demonstrates the adsorption of several layers of dye on the heterogeneous surface of the substrate. The synthesized substrate was also shown to have good bactericidal activity against E. coli and S. aureus bacterial strain. Furthermore, the substrate maintained its initial ability to adsorb MB dye for four consecutive cycles. The research resulted that ZnCuFe2O4@MCM-48/PEI-GO substrate has the potential for efficient and economical removal of MB dye from aqueous solutions (R = 88.82%) (qmax = 294.1176 mg. g-1), making it a promising solution for the disposal of harmful industrial waste.
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Compostos Férricos , Grafite , Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Dióxido de Silício , Polietilenoimina , Cobre , Zinco , Escherichia coli , Porosidade , Staphylococcus aureus , Antibacterianos/farmacologia , Azul de Metileno/química , Purificação da Água/métodos , Adsorção , Cinética , Poluentes Químicos da Água/análise , Concentração de Íons de HidrogênioRESUMO
The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.
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BACKGROUND: The emergence of carbon dots (CDs) as anticancer agents had sparked a transformation in cancer research and treatment strategies. These fluorescent CDs, initially introduced in the early 2000 s, possess exceptional biocompatibility, tunable fluorescence, and surface modification capabilities, positioning them as promising tools in biomedical applications. AIM OF REVIEW: The review encapsulates the transformative trajectory of green CDs as future anticancer nanomedicine, poised to redefine the strategies employed in the ongoing fight against cancer. KEY SCIENTIFIC CONCEPTS OF REVIEW: The versatility of CDs was rooted in their various synthesis approaches and sustainable strategies, enabling their adaptability for diverse therapeutic uses. In vitro studies had showcased CDs' selective cytotoxicity against cancer cells while sparing healthy counterparts, forming the basis for targeted therapeutic potential. This selectivity had been attributed to the reactive oxygen species (ROS) generation, which opened avenues for targeted interventions. The role of CDs in combination therapies, synergizing with chemotherapy, radiotherapy, and targeted approaches was then investigated to heighten their anticancer efficacy. Notably, in vivo studies highlight CDs' remarkable biocompatibility and minimal side effects, endorsing their translational promise. Integration with conventional cancer treatments such as chemotherapy, radiotherapy, and immunotherapy amplified the versatility and effectiveness of CDs. The exploration of CDs' applications in photo-induced treatments further solidified their significance, positioning them as photosensitizers (PS) in photodynamic therapy (PDT) and photothermal agents (PA) in photothermal therapy (PTT). In PDT, CDs triggered the generation of ROS upon light exposure, facilitating cancer cell elimination, while in PTT, they induced localized hyperthermia within cancer cells, enhancing therapeutic outcomes. In vitro and in vivo investigations validated CDs' efficacy in PDT and PTT, affirming their potential for integration into combination therapies. Looking ahead, the future of CDs in anticancer treatment encompasses bioavailability, biocompatibility, synergistic treatments, tumor targeting, artificial intelligence (AI) and robotics integration, personalized medicine, and clinical translation. This transformative odyssey of CDs as future anticancer agents is poised to redefine the paradigm of cancer treatment strategies.
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In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1.13 µM. Structure-activity relationship (SAR) analysis revealed that N-substituted derivatives generally enhanced the cytotoxic effect, particularly with aliphatic side chains that facilitated favorable target interactions. We also investigated apoptosis, DNA fragmentation, invasion assay, and anti-migration effects, and discussed their underlying molecular mechanisms for the most active compound 7c. We demonstrated that 7c N-propyl analogue could inhibit MDA-MB-231 TNBC cell proliferation by inducing apoptosis through the regulation of vital proteins, namely c-Src, p53, and Bax. In addition, our results also revealed the potential of these compounds against tumor metastasis by downregulating the invasion and migration modes. Moreover, the in vitro inhibitory effect of active analogs against c-Src kinase was studied and proved that might be the main cause of their antiproliferative effect. Overall, these compelling results point towards the therapeutic potential of these derivatives, particularly those with N-substitution as promising candidates for the treatment of TNBC type of breast cancer.
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Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteína Tirosina Quinase CSK/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Quinases da Família src , Relação Estrutura-Atividade , Pirimidinas/química , Pirimidinas/farmacologia , Pirazóis/química , Pirazóis/farmacologiaRESUMO
The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabolites screened, three metabolites such as Harzianelactone A, Pretrichodermamide G and Aspochalasin M, potentially bound with the active binding site of EGFR tyrosine kinase domain(PDB ID: 1M17) with a threshold docking score of ≤- 9.0 kcal/mol when compared with the standard EGFR inhibitor (Erlotinib). The MD simulation was run to investigate the potential for stable complex formation in EGFR tyrosine kinase domain-unbound/lead metabolite (Aspochalasin M)-bound/standard inhibitor (Erlotinib)-bound complex. The MD simulation analysis at 100 ns revealed that Aspochalasin M formed the stable complex with EGFR. Besides, the in silico predication of pharmacokinetic properties further confirmed that Aspochalasin M qualified the drug-likeness rules with no harmful side effects (viz., hERG toxicity, hepatotoxicity and skin sensitization), non-mutagenicity and favourable logBB value. Moreover, the BOILED-Egg model predicted that Aspochalasin M showed a higher gastrointestinal absorption with improved bioavailability when administered orally and removed from the central nervous system (CNS). The results of the computational studies concluded that Aspochalasin M possessed significant efficacy in binding EGFR's active sites compared to the known standard inhibitor (Erlotinib). Therefore, Aspochalasin M can be used as a possible anticancer drug candidate and further in vitro and in vivo experimental validation of Aspochalasin M of Trichoderma spp. are required to determine its anticancer potential.
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Trichoderma , Cloridrato de Erlotinib , Simulação de Acoplamento Molecular , Receptores ErbBRESUMO
As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.
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Nanopartículas Metálicas , Extratos Vegetais , Humanos , Extratos Vegetais/química , Química Verde , Plantas , Medicina Tradicional , Nanopartículas Metálicas/química , Atenção à SaúdeRESUMO
Gastric ulcers are worrying, and their worsening conditions may result in bleeding in the internal lining of the stomach. The problem is annoying, and both patients and professionals are still not satisfied with the available treatment options. Hesperidin, a flavonoid molecule with potent anti-inflammatory and antioxidant effects, can work like witchcraft to repair gastric ulcers and preserve the stomach lining. Here, we employed a strategy that involved covering the surface of the nano-lipid carriers (NLCs) with sericin before encasing the hesperidin within (Se-He-NLC). Sericin, a biodegradable polymer increases the muco-adhesion with stomach lining and deployment of hesperidin in controlled manner. Se-He-NLCs were physico-chemically characterized for drug loading, encapsulation, particle size, morphology, drug release, chemical stability, and chemical bonding. The nanocarriers showed first order drug release in a controlled manner. Se-He-NLCs showed better in vitro permeation and ex vivo mucoadhesion, thereby by promoting the in vivo bioavailability. Se-He-NLCs also promoted the reduced glutathione (GSH) and glutathione-S-transferase (GST) levels by 2.24- and 1.61-folds, respectively in the stomach lining, and also the regulation of superoxide dismutase (SOD) and catalase (CAT) activities parallel to the control group. In addition, tissues lipid hydroperoxides (LOOH) and myeloperoxidase (MPO) activity were reduced significantly with Se-He-NLCs administration. Se-He-NLC therapy of stomach ulcers in vivo demonstrated better binding ratio and ulcer healing potential. This approach reveals huge capacity for delivering therapies to treat gastric ulcers based on the clinical significance of sericin coated hesperidin nanocarriers in gastric ulcer treatment.
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Hesperidina , Nanopartículas , Sericinas , Úlcera Gástrica , Humanos , Ratos , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Hesperidina/farmacologia , Ratos Wistar , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismoRESUMO
In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.
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Cisplatino , Rim , Polietilenoglicóis , Polietilenoimina , Ratos , Masculino , Animais , Cisplatino/farmacologia , Sulfatos de Condroitina/farmacologia , Nanogéis , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Doxorrubicina/farmacologia , Estresse Oxidativo , Creatinina/metabolismoRESUMO
Background: Exogenous administration of acylated ghrelin (AG) afforded reproductive protective effect in several animal models but not in those treated with doxorubicin (DOX). This study evaluated the protective effect of AG against DOX-induced testicular damage and impairment in sperm parameters in rats and examined the potential mechanisms of action. Materials and Methods: Adult male rats were divided into five groups (n = 8/each) as control, control + AG (40 nmol/kg/day; subcutaneous), DOX (10 mg/kg/day 1; intraperitoneal [i.p.]), DOX + AG, and DOX + AG + brusatol (an Nrf2 inhibitor) (2 mg/kg/every 3 days; i.p.). The treatment regimen continued for 65 days. Results: AG prevented testicular damage and apoptosis; increased sperm count, motility, and viability; and reduced the number of abnormal sperms. It also increased their circulatory levels of AG, des-acylated ghrelin (DAG), and AG/DAG ratio and the testicular mRNA levels of ghrelin and growth hormone secretagogue receptor 1a Concomitantly, AG increased serum and testicular testosterone levels, reduced serum levels of the follicle-stimulating hormone and luteinizing hormone, and upregulated the testicular protein levels of the steroidogenic acute regulatory protein and 3ß-hydroxysteroid dehydrogenase in DOX-treated rats. In the testes of the control and DOX-treated rats, AG increased the phosphorylation of mammalian target of rapamycin and stimulated the levels of glutathione and superoxide dismutase, as well as the nuclear activation of Nrf2. All these effects were completely prevented by co-treatment with brusatol. Conclusion: AG replacement therapy could be a novel strategy to prevent reproductive toxicity in cancer patients.
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Fator 2 Relacionado a NF-E2 , Testículo , Humanos , Ratos , Masculino , Animais , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Sirolimo/farmacologia , Grelina/farmacologia , Ratos Wistar , Sêmen/metabolismo , Espermatozoides/metabolismo , Doxorrubicina/toxicidade , Serina-Treonina Quinases TOR/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Mamíferos/metabolismoRESUMO
SUMMARY: The livers of reptiles are being studied as a model for the link between the environment and hepatic tissue. There have been few investigations on the histology of reptile livers, and very few or no studies have examined the histology of liver of veiled chameleon (Chamaeleo calyptratus). This paper describes the histomorphological, histochemical and ultrastructural characterization of the liver of veiled chameleons in southern Saudi Arabia. Seven Chamaeleo calyptratus were captured in the summer season in Abha City, Aseer region, southern Saudi Arabia. Chamaeleon liver samples were processed for histomorphology, histochemistry and ultrastructure analyses. Morphologically liver of Chamaeleo calyptratus was observed as a large dark brown organ with lighter speckles, which represent melanin deposits. It located at the ventral part of abdominal cavity forward of the stomach. Its dimensions approximately were 3.7 x 2 cm. The liver was a bilobed organ divided into two lobes, right and left lobes. The right one was bigger than the others. The gallbladder was well developed and had an elongated shape, situated between the two lobes and contained the bile for the digestion. Microscopically, the liver was found to be covered by a thick layer of connective tissue, which formed the hepatic capsule. Hepatic parenchyma probably appeared in cross sections as hepatic glandular-like alveoli "acini" or follicular structures with various diameters, each acinus contains approximately four to six hepatocytes, surrounded by sinusoidal capillaries filled with abundant melanomacrophages, which are absent in birds and mammals. Melanomacrophages are common in the hepatic parenchyma's perisinusoidal areas, particularly near portal spaces. Hepatocytes are polyhedral or pyramidal with and mostly contained large, rounded nuclei mostly peripherally located, with prominent dark oval nucleoli. Some of nuclei are eccentric or central position. The cytoplasm appeared spongy or vacuolated and more eosinophilic when stained by hematoxylin-eosin and strongly reactive to PAS staining technique, indicating abundant glycogen content. The reticular fibers that surround hepatocytes, blood arteries, and sinusoids supported the hepatic parenchyma. The blood sinusoids are seen interspersed among hepatocytes of varying sizes. The sinusoidal lumen was bordered by flattened endothelial cells and includes elliptical nucleated erythrocytes and liver macrophages as phagocytes, which are also known as Kupffer cells. Branches of the portal vein, hepatic artery, small bile duct, and lymph vessels were detected in the hepatic portal area "tract" or triad which made up of connective. Hematopoietic tissue was observed in subcapsular region and portal triads. Ultrastructurally, the hepatocyte appeared polyhedric containing a single large rounded basal or eccentric vesicular nucleus with prominent nucleolus. Extensive network of rough endoplasmic reticulum (RER) often arranged in an array parallel to the nuclear membrane with many mitochondria, and Golgi apparatus were described. The cytoplasm contained glycogen granules, vesicles or vacuoles scattered throughout the cytoplasm especially at the apical region were reported. The bile canaliculi and the hepatic "Kupffer" cells were also discussed. This is the first study on the histological characterization of the healthy liver of Yemen veiled chameleon in southern Saudi Arabia. The findings reported here should be used as a reference to compare with the pathological abnormalities of the liver in this animal.
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Assuntos
Animais , Fígado/anatomia & histologia , Lagartos/anatomia & histologia , Fotomicrografia , Hepatócitos , Microscopia Eletrônica de Transmissão , Fígado/ultraestruturaRESUMO
Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula, a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients.
RESUMO
An opportunistic human pathogenic bacterium, Chromobacterium violaceum resists the potency of most antibiotics by exploiting the quorum sensing system within their community to control virulence factor expression. Therefore, blocking the quorum sensing mechanism could help to treat several infectious caused by this organism. The quorum sensing receptor (CviR) of C. violaceum was used as a model target in the current investigation to identify potentially novel quorum sensing inhibitors from Cladosporium spp. through in silico computational approaches. The molecular docking results confirmed the anti-quorum sensing potential of bioactive compounds from Cladosporium spp. through binding to CviR with varying docking scores between - 5.2 and - 9.5 kcal/mol. Relative to the positive control [Azithromycin (- 7.4 kcal/mol)], the top six metabolites of Cladosporium spp. had higher docking scores and were generally greater than - 8.5 kcal/mol. The thermodynamic stability and binding affinity refinement of top-ranked CviR inhibitors were further studied through a 160 ns molecular dynamic (MD) simulation. The Post-MD simulation analysis confirmed the top-ranked compounds' affinity, stability, and biomolecular interactions with CviR at 50 ns, 100 ns, and 160 ns with Coniochaetone K of the Cladosporium spp. having the highest binding free energy (- 30.87 kcal/mol) and best interactions (two consistent hydrogen bond contact) following the 160 ns simulation. The predicted pharmacokinetics properties of top selected compounds point to their drug likeliness, potentiating their chance as a possible drug candidate. Overall, the top-ranked compounds from Cladosporium spp., especially Coniochaetone K, could be identified as potential C. violaceum CviR inhibitors. The development of these compounds as broad-spectrum antibacterial medicines is thus possible in the future following the completion of further preclinical and clinical research.