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This current in vitro, ex vivo, and in vivo research aims to evaluate and analyze the linalool-zinc oxide nanocomposite (Lin-ZNP) for treating cystic echinococcosis. Lin-ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The protoscolicidal effects of Lin-ZNP were tested on hydatid cyst protoscoleces (PTS) in both in vitro and ex vivo by eosin exclusion test. The study also examined the impact on caspase-3 gene expression and the external structure of PTS. The in vivo effect was measured by examining hydatid cysts' quantity, dimensions, and weight in mice intraperitoneally infected with 0.5 mL of PTS solution containing 1,000 PTS. The antioxidant and inflammatory cytokine gene expression levels were examined using real-time PCR. Lin-ZNP significantly (P < 0.001) killed the PTS in both in vitro and ex vivo in a dose- and time-dependent manner. The treated PTS exhibited creases and protrusions as a result of bleb formation and upregulation in the gene expression of caspase-3. Upon treatment with Lin-ZNP, there was a significant (P < 0.001) reduction in the number, diameter, and weight of the hydatid cysts. Treatment with Lin-ZNP nanocomposite led to a significant increase in the expression of antioxidant genes and a notable decrease in oxidative stress markers, and the expression levels of IL-4 and IL-10. Lin-ZNP has the potential to act as a scolicidal agent and demonstrates promise in controlling hydatid cysts in a mouse model, attributed to its antioxidant and anti-inflammatory properties. However, additional studies in clinical trials are needed to confirm the use of Lin-ZNP for treating hydatidosis.
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The present in vitro and in vivo study aimed to fabricate and characterize linalool-zinc oxide nanoparticles (Lin-ZNP) and evaluate their effectiveness against Toxoplasma gondii infection in terms of inflammation, oxidative stress, and pathogenicity. Lin-ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The anti-Toxoplasma and cytotoxicity activities of Lin-ZNP were investigated, along with its effects on nitric oxide (NO) production, caspase-3 activity, and pro-inflammatory genes. After treating T. gondii-infected mice with Lin-ZNP for 14 days, the number and size of tissue cysts, antioxidant potential, pro-inflammatory cytokines, and T. gondii pathogenicity-related genes were evaluated by real-time polymerase chain reaction and Western blot analysis. The Lin-ZNP composite showed a reduced tendency with an average size of 105 nm. Lin-ZNP significantly reduced the viability of tachyzoites. The obtained selectivity index higher than 10, indicating high specificity for parasites with low cytotoxicity to normal cells. The Lin-ZNP significantly (p < 0.05) increased the production of NO, caspase-3 activity, and the expression levels of pro-inflammatory genes. Lin-ZNP significantly (p < 0.001) decreased the size and number of tissue cysts and caused a significant reduction in the level of malondialdehyde and a considerable increase (p < 0.001) in antioxidant enzymes and their expression genes. Lin-ZNP significantly downregulated both mRNA and protein expression of the inflammation-related markers associated with the TLRs/NF-κB pathway. The expression levels of the T. gondii pathogenicity-related genes were significantly downregulated (p < 0.05). The recent survey indicated that Lin-ZNP manages T. gondii infection by its antioxidant activity and inhibiting the TLRs/NF-κB pathway without toxicity in mice.
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Monoterpenos Acíclicos , Inflamação , Nanocompostos , Óxido Nítrico , Estresse Oxidativo , Toxoplasma , Óxido de Zinco , Animais , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Toxoplasma/efeitos dos fármacos , Toxoplasma/patogenicidade , Inflamação/tratamento farmacológico , Monoterpenos Acíclicos/farmacologia , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Óxido Nítrico/metabolismo , Nanocompostos/química , Antioxidantes/farmacologia , Citocinas/metabolismo , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Caspase 3/metabolismo , Caspase 3/genética , FemininoRESUMO
Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy.
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Catequina , Mangifera , Camundongos , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/química , Mangifera/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Simulação de Acoplamento Molecular , Catequina/análise , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Sementes/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêuticoRESUMO
Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.
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Diarileptanoides , Doença de Parkinson , Ratos , Animais , Diarileptanoides/uso terapêutico , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Acetilcolinesterase , Modelos Animais de Doenças , Doença de Parkinson/tratamento farmacológicoRESUMO
Quercetin (QtN) displays low systemic bioavailability caused by poor water solubility and instability. Consequently, it exerts limited anticancer action in vivo. One solution to increase the anticancer efficacy of QtN is the use of appropriate functionalized nanocarriers that preferentially target and deliver the drug to the tumor location. Herein, a direct advanced method was designed to develop water-soluble hyaluronic acid (HA)-QtN-conjugated silver nanoparticles (AgNPs). HA-QtN reduced silver nitrate (AgNO3) while acting as a stabilizing agent to produce AgNPs. Further, HA-QtN#AgNPs served as an anchor for folate/folic acid (FA) conjugated with polyethylene glycol (PEG). The resulting PEG-FA-HA-QtN#AgNPs (further abbreviated as PF/HA-QtN#AgNPs) were characterized both in vitro and ex vivo. Physical characterizations included UV-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), particle size (PS) and zeta potential (ZP) measurements, and biopharmaceutical evaluations. The biopharmaceutical evaluations included analyses of the cytotoxic effects on the HeLa and Caco-2 cancer cell lines using the MTT assay; cellular drug intake into cancer cells using flow cytometry and confocal microscopy; and blood compatibility using an automatic hematology analyzer, a diode array spectrophotometer, and an enzyme-linked immunosorbent assay (ELISA). The prepared hybrid delivery nanosystem was hemocompatible and more oncocytotoxic than the free, pure QtN. Therefore, PF/HA-QtN#AgNPs represent a smart nano-based drug delivery system (NDDS) and could be a promising oncotherapeutic option if the data are validated in vivo.
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Produtos Biológicos , Nanopartículas Metálicas , Neoplasias , Humanos , Ácido Hialurônico/química , Quercetina/farmacologia , Nanopartículas Metálicas/química , Células CACO-2 , Prata , Polietilenoglicóis/química , Água , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Marine algae are rich in bioactive nutraceuticals (e.g., carbohydrates, proteins, minerals, fatty acids, antioxidants, and pigments). Biotic (e.g., plants, microorganisms) and abiotic factors (e.g., temperature, pH, salinity, light intensity) contribute to the production of primary and secondary metabolites by algae. Easy, profitable, and sustainable recovery methods include novel solid-liquid and liquid-liquid extraction techniques (e.g., supercritical, high pressure, microwave, ultrasound, enzymatic). The spectacular findings of algal-mediated synthesis of nanotheranostics has attracted further interest because of the availability of microalgae-based natural bioactive therapeutic compounds and the cost-effective commercialization of stable microalgal drugs. Algal extracts can serve as stabilizing/capping and reducing agents for the synthesis of thermodynamically stable nanoparticles (NPs). Different types of nanotherapeutics have been synthesized using physical, chemical, and biological methods. Marine algae are a fascinating source of lead theranostics compounds, and the development of nanotheranostics has been linked to enhanced drug efficacy and safety. Indeed, algae are remarkable nanobiofactories, and their pragmatic properties reside in their (i) ease of handling; (ii) capacity to absorb/accumulate inorganic metallic ions; (iii) cost-effectiveness; and (iv) capacity of eco-friendly, rapid, and healthier synthesis of NPs. Preclinical and clinical trials shall enable to really define effective algal-based nanotherapies. This review aims to provide an overview of the main algal compounds that are nutraceuticals and that can be extracted and purified for nanotheranostic purposes.
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Produtos Biológicos/metabolismo , Clorófitas/metabolismo , Phaeophyceae/metabolismo , Rodófitas/metabolismo , Alga Marinha/metabolismo , Animais , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Humanos , NanomedicinaRESUMO
Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Ehrlich , Ácidos Graxos Monoinsaturados/farmacologia , Proteínas de Neoplasias/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/química , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Ciclofosfamida/química , Ciclofosfamida/farmacologia , Relação Dose-Resposta a Droga , Ácidos Graxos/química , Ácidos Graxos Monoinsaturados/química , Feminino , CamundongosRESUMO
Acrylamide (ACR) is a water-soluble chemical used widely in industry, which can be formed in tobacco smoke and in starchy foods cooked at high temperatures. ACR is considered to be a neurotoxin, genotoxin and carcinotoxin. Previous studies reported that ACR-exposed workers and experimental animals exhibited visual function defects, although the underlying mechanisms have not been elucidated. In this study, we found that zebrafish embryos exposed to 1â¯mM and 2â¯mM ACR showed significantly increased reactive oxygen species (ROS), decreased expression of the antioxidant genes Sod1, Sod2, Catalase, Gpx1 and Nrf2, reduced activity of superoxide dismutase (SOD) and catalase, and elevated malondialdehyde (MDA), compared with control embryos. ACR exposure caused loss of both rod and cone photoreceptor cells through Caspase-3-dependent apoptotis. When embryos were simultaneously exposed to ACR and the natural antioxidative substance carnosic acid (CA), the presence of the latter (10⯵M) markedly counteracted the above ACR-induced toxic effects. Our data suggest that CA can protect photoreceptor cells against ACR-induced oxidative damage and has a potential for neuroprotection of visual function in humans exposed to ACR.
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Abietanos/farmacologia , Acrilamida/toxicidade , Antioxidantes/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Catalase/metabolismo , Sobrevivência Celular/fisiologia , Embrião não Mamífero/metabolismo , Glutationa Peroxidase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Glutationa Peroxidase GPX1RESUMO
This study aimed to produce linalool loaded zinc oxide nanocomposite (LZNPs) and assess its in vitro and in vivo antileishmanial effects against Leishmania major. LZNPs was produced through the synthesis of an ethanolic solution containing polyvinyl alcohol. The average size of LZNPs was determined to be 105 nm. The findings indicated that LZNPs displayed significant (p < 0.01) antileishmanial effects on promastigotes and amastigotes. Following exposure of promastigotes to LZNPs, there was a notable rise in the percentage of early and late apoptotic cells from 9.0 to 57.2 %. The gene expression levels of iNOS, IFN-γ, and TNF-α in macrophages were upregulated in a dose-dependent approach following exposure to LZNPs. LZNPs alone and in conjunction with glucantime (Glu) resulted in a reduction in the diameter and parasite load of CL lesions in infected mice. Treatment of the CL-infected mice with LZNPs at 25 and 50 mg/kg mainly in combination with Glu-reduced the tissue level of malondialdehyde (MDA), increased both gene and protein expression of the antioxidant enzymes as well as raised the expression level of IFN-γ and IL-12 cytokines, whereas caused a significant reduction in the expression level of IL-4. The present study shows that LZNPs has potent antileishmanial effects and controls CL in a mice model through its antioxidant and immunomodulatory properties. Further investigation, especially in clinical trials, could explore the potential use of this nanocomposite in managing and treating CL.
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Monoterpenos Acíclicos , Antiprotozoários , Cicloexanóis , Compostos de Tritil , Óxido de Zinco , Animais , Camundongos , Óxido de Zinco/farmacologia , Antioxidantes/farmacologia , Zinco , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Antimoniato de Meglumina , Camundongos Endogâmicos BALB CRESUMO
This research aimed to produce and analyze zinc oxide nanoparticles (ZNPs) loaded with linalool (LZNPs), and to evaluate their in vitro and in vivo efficacy through targeting the inflammation and oxidative stress. LZNPs were synthesized using an ethanolic solution of polyvinyl alcohol. The Malstat technique was used to evaluate the effectiveness of LZNPs against both sensitive and resistant strains of Plasmosium falciparum. In vivo effects of ZNPs and LZNPs on parasite growth suppression, survival rate, oxidative stress markers, antioxidant genes, and gene and protein levels of inflammatory cytokines were evaluated by Real-time PCR and Western blot techniques. The results indicated that LZNPs demonstrated noteworthy (P < 0.001) antiplasmodial activity against both susceptible and resistant strains of P. falciparum. P. berghei NK65 strain-infected mice treated with the ZNPs and LZNPs at doses of 5-15 mg/kg notably (p < 0.001) increased the survival rates and parasite growth suppression. LZNPs at 5-15 mg/kg demonstrated a significant (p < 0.001) decrease in oxidative stress markers, increased the expression level of antioxidant genes, and reduced the gene and protein expression level of inflammatory cytokines. The current experimental study demonstrated the potent in vitro antiplasmodial activity of LZNPs against chloroquine-resistant and sensitive strains of P. falciparum compared to ZNPs alone. Additionally, the study identified the potential benefits of this nanocomposite in suppressing the parasite and extending the survival rate in mice infected with P. berghei by targeting inflammation and oxidative stress. It also showed minimal toxicity in liver and kidney function in healthy mice. Nevertheless, further research is essential to elucidate the comprehensive mechanisms and practical effectiveness of LZNPs.
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Monoterpenos Acíclicos , Antimaláricos , Monoterpenos , Nanopartículas , Estresse Oxidativo , Plasmodium berghei , Plasmodium falciparum , Óxido de Zinco , Animais , Monoterpenos Acíclicos/farmacologia , Óxido de Zinco/farmacologia , Óxido de Zinco/administração & dosagem , Óxido de Zinco/química , Camundongos , Plasmodium berghei/efeitos dos fármacos , Antimaláricos/farmacologia , Antimaláricos/administração & dosagem , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Monoterpenos/farmacologia , Monoterpenos/administração & dosagem , Monoterpenos/química , Malária/tratamento farmacológico , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Portadores de Fármacos/químicaRESUMO
BACKGROUND: Diabetic retinopathy (DR) stands as a prevalent secondary complication of diabetes, notably Type 1 Diabetes Mellitus (T1D), characterized by immune system involvement potentially impacting the retinal immune response mediated by microglia. Early stages of DR witness blood-retinal barrier permeabilization, facilitating peripheral immune cell interaction with the retinal immune system. Kaempferol (Kae), known for its potent anti-inflammatory activity, presents a promising avenue in DR treatment by targeting the immune mechanisms underlying its onset and progression. Our investigation delves into the molecular intricacies of innate immune cell interaction during DR progression and the attenuation of inflammatory processes pivotal to its pathology. METHODS: Employing in vitro studies, we exposed HAPI microglial and J774.A1 macrophage cells to pro-inflammatory stimuli in the presence or absence of Kae. Ex vivo and in vivo experiments utilized BB rats, a T1D animal model. Retinal explants from BB rats were cultured with Kae, while intraperitoneal Kae injections were administered to BB rats for 15 days. Quantitative PCR, Western blotting, immunofluorescence, and Spectral Domain - Optical Coherence Tomography (SD-OCT) facilitated survival assessment, cellular signaling analysis, and inflammatory marker determination. RESULTS: Results demonstrate Kae significantly mitigates inflammatory processes across in vitro, ex vivo, and in vivo DR models, primarily targeting immune cell responses. Kae administration notably inhibits proinflammatory responses during DR progression while promoting an anti-inflammatory milieu, chiefly through microglia-mediated synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). In vivo, Kae administration effectively preserves retinal integrity amid DR progression. CONCLUSIONS: Our findings elucidate the interplay between retinal and systemic immune cells in DR progression, underscoring a differential treatment response predominantly orchestrated by microglia's anti-inflammatory action. Kae treatment induces a phenotypic and functional shift in immune cells, delaying DR progression, thereby spotlighting microglial cells as a promising therapeutic target in DR management.
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Retinopatia Diabética , Quempferóis , Macrófagos , Microglia , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/imunologia , Retinopatia Diabética/patologia , Microglia/efeitos dos fármacos , Microglia/imunologia , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Ratos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Progressão da Doença , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/imunologia , Retina/efeitos dos fármacos , Retina/patologia , Retina/imunologia , Linhagem Celular , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Modelos Animais de DoençasRESUMO
The effective combination of semen cryopreservation and artificial insemination has a positive effect on the conservation of germplasm resources, production and breeding, etc. However, during the process of semen cryopreservation, the sperm cells are very susceptible to different degrees of physical, chemical, and oxidative stress damage. Oxidative damage is the most important factor that reduces semen quality, which is affected by factors such as dilution equilibrium, change of osmotic pressure, cold shock, and enzyme action during the freezing-thawing process, which results in the aggregation of a large amount of reactive oxygen species (ROS) in sperm cells and affects the quality of semen after thawing. Therefore, the method of adding antioxidants to semen cryoprotective diluent is usually used to improve the effect of semen cryopreservation. The aim of this experiment was to investigate the effects of adding five antioxidants (GLP, Mito Q, NAC, SLS, and SDS) to semen cryoprotection diluent on the cryopreservation effect of semen from Saanen dairy goats. The optimal preservation concentrations were screened by detecting sperm viability, plasma membrane integrity, antioxidant capacity, and acrosomal enzyme activities after thawing, and the experimental results were as follows: the optimal concentrations of GLP, Mito Q, NAC, SLS, and SDS added to semen cryopreservation diluent at different concentrations were 0.8 mg/mL, 150 nmol/L, 0.6 mg/mL, 0.15 mg/ mL, 0.6 mg/mL, and 0.15 mg/mL. The optimal concentrations of the five antioxidants were added to the diluent and analyzed after 1 week of cryopreservation, and it was found that sperm viability, plasma membrane integrity, and mitochondrial activity were significantly enhanced after thawing compared with the control group (P < 0.05), and their antioxidant capacity was significantly enhanced (P < 0.05). Therefore, the addition of the above five antioxidants to goat sperm cryodilution solution had a better enhancement of sperm cryopreservation. This study provides a useful reference for exploring the improvement of goat semen cryoprotection effect.
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Antioxidantes , Criopreservação , Crioprotetores , Cabras , Preservação do Sêmen , Animais , Masculino , Criopreservação/métodos , Criopreservação/veterinária , Antioxidantes/farmacologia , Preservação do Sêmen/métodos , Preservação do Sêmen/veterinária , Crioprotetores/farmacologia , Espermatozoides/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sêmen/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Análise do Sêmen , Membrana Celular/efeitos dos fármacosRESUMO
BACKGROUND: The growth arrest and DNA damage-inducible 45 (Gadd45) gene has been implicated in various central nervous system (CNS) functions, both normal and pathological, including aging, memory, and neurodegenerative diseases. In this study, we examined whether Gadd45A deletion triggers pathways associated with neurodegenerative diseases including Alzheimer's disease (AD). METHODS: Utilizing transcriptome data from AD-associated hippocampus samples, we identified Gadd45A as a pivotal regulator of autophagy. Comprehensive analyses, including Gene Ontology enrichment and protein-protein interaction network assessments, highlighted Cdkn1A as a significant downstream target of Gadd45A. Experimental validation confirmed Gadd45A's role in modulating Cdkn1A expression and autophagy levels in hippocampal cells. We also examined the effects of autophagy on hippocampal functions and proinflammatory cytokine secretion. Additionally, a murine model was employed to validate the importance of Gadd45A in neuroinflammation and AD pathology. RESULTS: Our study identified 20 autophagy regulatory factors associated with AD, with Gadd45A emerging as a critical regulator. Experimental findings demonstrated that Gadd45A influences hippocampal cell fate by reducing Cdkn1A expression and suppressing autophagic activity. Comparisons between wild-type (WT) and Gadd45A knockout (Gadd45A-/-) mice revealed that Gadd45A-/- mice exhibited significant cognitive impairments, including deficits in working and spatial memory, increased Tau hyperphosphorylation, and elevated levels of kinases involved in Tau phosphorylation in the hippocampus. Additionally, Gadd45A-/- mice showed significant increases in pro-inflammatory cytokines and decreases autophagy markers in the brain. Neurotrophin levels and dendritic spine length were also reduced in Gadd45A-/- mice, likely contributing to the observed cognitive deficits. CONCLUSIONS: These findings support the direct involvement of the Gadd45A gene in AD pathogenesis, and enhancing the expression of Gadd45A may represent a promising therapeutic strategy for the treatment of AD.
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Doença de Alzheimer , Autofagia , Proteínas de Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p21 , Hipocampo , Camundongos Knockout , Animais , Autofagia/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Camundongos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Humanos , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Modelos Animais de Doenças , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Camundongos Endogâmicos C57BL , Mapas de Interação de Proteínas , Proteínas GADD45RESUMO
Aim: To ascertain whether killer cell immunoglobulin-like receptors (KIR) genes polymorphisms and HLA-I ligands are associated with COVID-19 in Saudi Arabia. Methods: Eighty-seven COVID-19 patients who tested positive for SARS-CoV-2 and one hundred and fourteen healthy controls were enrolled in this study for genotyping of the 16 KIR genes, HLA-C1 and -C2 allotypes and HLA-G 14-bp indels polymorphisms using the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency differences and combination KIR-HLA-C ligand were tested for significance. Results: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIR3DP2 were present in all individuals. The frequencies of KIR2DL2 and KIR2D4 were higher in COVID-19 positive patients than in healthy individuals. The frequencies of the combination KIR2DL2-HLA-C2 was also significantly higher in patients affected by COVID-19 compared with healthy controls. Conclusion: It was found that the inhibitory KIR2DL2 gene in isolation or combined with its HLA-C2 ligand could be associated with susceptibility to COVID-19 in the Saudi population.
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This work comprehensively studies both the photocatalytic degradation and the adsorption process of Congo red dye on the surface of a mixed-phase copper oxide-graphene heterostructure nanocomposite. Laser-induced pristine graphene and graphene doped with different CuO concentrations were used to study these effects. Raman spectra showed a shift in the D and G bands of the graphene due to incorporating copper phases into the laser-induced graphene. The XRD confirmed that the laser beam was able to reduce the CuO phase to Cu2O and Cu phases, which were embedded into the graphene. The results elucidate incorporating Cu2O molecules and atoms into the graphene lattice. The production of disordered graphene and the mixed phases of oxides and graphene were validated by the Raman spectra. It is noted from the spectra that the D site changed significantly after the addition of doping, which indicates the incorporation of Cu2O in the graphene. The impact of the graphene content was examined with 0.5, 1.0, and 2.0 mL of CuO. The findings of the photocatalysis and adsorption studies showed an improvement in the heterojunction of copper oxide and graphene, but a significant improvement was noticed with the addition of graphene with CuO. The outcomes demonstrated the compound's potential for photocatalytic use in the degradation of Congo red.
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BACKGROUND: The findings of earlier investigations of antiapoptotic gene genotypes and allele variants on lymphoma risk are ambiguous. This study aimed to examine the relationship between the mutation in the antiapoptotic genes and lymphoma risk among Saudi patients. METHODS: This case-control study included 205 patients, 100 of whom had lymphoma (cases) and 105 who were healthy volunteers (controls). We used tetra amplification refractory mutation polymerase chain reaction (PCR) to identify antiapoptotic genes such as B-cell lymphoma-2 (BCL2-938 C > A), MCL1-rs9803935 T > G, and survivin (BIRC5-rs17882312 G > C and BIRC5-rs9904341 G > C). Allelic-specific PCR was used to identify alleles such as BIRC5-C, MCL1-G, and BIRC5-G. RESULTS: The dominant inheritance model among cases showed that mutations in all four antiapoptotic genes were more likely to be associated with the risk of lymphoma by the odds of 2.0-, 1.98-, 3.90-, and 3.29-fold, respectively, compared to controls. Apart from the BCL-2-A allele, all three specified alleles were more likely to be associated with lymphoma by the odds of 2.04-, 1.65-, and 2.11-fold, respectively. CONCLUSION: Unlike healthy individuals, lymphoma patients are more likely to have antiapoptotic gene genotypes and allele variants, apart from BCL-2-A alterations. In the future, these findings could be used to classify and identify patients at risk of lymphoma.
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Introduction: Obesity is a chronic metabolic disorder that results in excessive energy accumulated in adipose tissue causing dysfunction of adipocytes, inflammation, and oxidative stress. Diosgenin (DG), a steroidal saponin produced by several plants, has been reported to have antioxidant activity. This study aimed to evaluate the effects of diosgenin on oxidative stress and inflammation in mice fed with a high-fat diet (HFD). Methods: Thirty adult male mice were divided into three groups including the control group, mice fed with a normal diet; the HFD group, mice fed with a high-fat diet for 6 weeks; and the HFD+DG group, mice fed with a high-fat diet and diosgenin daily for 6 weeks. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and total antioxidant capacity (TAC) activities were evaluated. Histopathological changes in the adipose tissues have been investigated. Results: Data showed that diosgenin increased TAC activities with a concomitant decrease in MDA levels. As well, DG reduces the TNF and IL-6 levels. The histopathological changes in the adipose tissues due to high-fat consumption were restored upon DG supplementation. Conclusion: Our results suggested that diosgenin is a promising agent for regulating obesity by increasing the levels of antioxidants, modifying oxidative stress and pro-inflammatory cytokines, which might prevent the onset of many diseases.
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Ion-imprinting methodology was utilized in the fabrication of mercury ion-imprinted sorbent derived from modified chitosan derivatives. The Schiff base ligand was first derived from 4-amino-3-hydroxybenzoic acid and 2-pyridinecarboxaldehyde (HPB) and then incorporated with chitosan via amide bonds. The obtained modified chitosan polymeric ligand (PBCS) was combined with Hg(II) ions to produce the corresponding polymeric complex and the imprinting was then achieved upon the glutaraldehyde cross-linking and eliminating the incorporated Hg(II) ions to finally have the Hg(II) ion-imprinted sorbent material (Hg-PBCS). The materials have been investigated using various techniques such as NMR and FTIR and the obtained sorbent was examined to evaluate its selective affinity to capture the target Hg(II) ions. The developed Hg-PBCS sorbent exhibited a higher tendency toward the targeted Hg(II) ions compared to the control non-imprinted sorbent particle (NI-PBCS) with a maximum capacity of 315 mg/g. Also, the sorbent displayed relatively rapid adsorption kinetics that best correlated with the pseudo-second-order model.
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One of the main issues limiting plant productivity is a lack of soil nutrient resources, especially in calcareous soil, which covers more than one third of the world's land surface area. On the other hand, despite rising demand for all parts of the Moringa oleifera tree, several studies have focused on its leaf production as an herbaceous plant, rather than as a tree, and no extensive research has been carried out on leaf and inflorescence production in the mature tree. As a result, the influence of vermicompost and NPK (minerals and nanoparticles), as well as their combination, under calcareous soil conditions, was investigated in this study. The experiment was set up as a split plot in Randomized Complete Block Design (RCBD) with three replicates. In both seasons considered in this study, it was discovered that increasing the quantity of vermicompost and employing NPK fertilization, as well as their combination treatments, greatly enhanced all parameters and yield of distinct Moringa oleifera tree parts. Furthermore, the combination treatment T21 yielded the highest mean values of growth, leaves, and chemical composition parameters, as well as the highest yield from the Moringa oleifera tree. In both seasons, the highest number of inflorescences per tree, as well as the yield of fresh and dry inflorescences, was measured using combination treatment T18. In both seasons, however, increasing the level of vermicompost, NPK, and their combination treatments significantly reduced the total phenolic and flavonoid content and antioxidant activity of dry Moringa oleifera leaves.
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Background: Using a variety of chemical compounds and biomolecules, researchers have been working on new antidiabetic drugs for many years. Anti-diabetic research is increasingly using nanomaterials because of their unique qualities, such as their tiny size, biocompatibility, and ability to penetrate cell membranes for drug delivery. Using extract of T. couneifolia coated with silver nanoparticles as a model for diabetes mellitus research was one of the goals of this work. Methods: Uv-Vis spectroscopy was used to measure the TAgNPs surface plasmon resonance. FTIR spectroscopy confirmed the attached functional groups, XRD analysis confirmed the size and crystallinity, scanning electron microscopy revealed that the majority of the particles were spherical, and EDX performed the elemental analysis. For 21 days, alloxan-induced diabetic Wistar rats (N = 25, n = 5/group) were administered 10 mg/kg body weight of photosynthesized AgNPs as a standard animal model, while those in the untreated normal control group C, received distilled water as a control, diabetics who were treated with 0.5 mg/kg of body weight of glibenclamide, 10 mg/kg of methanolic T. couneifolia extract, and diabetics who were given 10 mg/kg of body weight of synthetic AgNPs derived from T. couneifolia in the DAgNPs group. At the conclusion of the treatment, lipid, liver and kidney profiles were re-examined to determine whether or not the treatment had been effective (day 21). Oral glucose doses of 2 g/kg of body weight were administered to each group, and blood glucose levels were measured at various intervals (day 21). Fasting glucose levels were measured using a glucometer. Each animal's urine was tested for leukocytes, nitrites, and bilirubin using lab-made prepared assay kits. One-way ANOVA and Dunnett's test were used for statistical analysis. Results: The surface plasmon resonance effect was examined with UV-vis, it showed a sharp peak at 412 nm. X-ray diffraction measurements indicated that the produced nanoparticles were between 15 to 31.44 nm in size. Alloxan-induced diabetic rats were fed AgNPs derived from phytosynthesized AgNPs, compared to diabetic control rats, diabetic rats treated with AgNPs showed a considerable improvement in their dyslipidemia status. Over the course of the days, it also lowered blood glucose levels. A reduction in blood glucose levels, a rise in body weight, and significant improvements in the lipid, liver, and renal profiles were also seen. Conclusions: The present findings revealed that plant mediated silver nanoparticles significantly improved the alloxan induced diabetic changes in various treated rats and might be used for the treatment of diabetes.