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1.
Antimicrob Agents Chemother ; : e0173423, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38752808

RESUMEN

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.

2.
J Basic Microbiol ; : e202400039, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38690754

RESUMEN

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.

3.
Metab Brain Dis ; 38(2): 483-505, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35344129

RESUMEN

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.


Asunto(s)
Catequina , Mangifera , Ratones , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/química , Mangifera/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Simulación del Acoplamiento Molecular , Catequina/análisis , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Semillas/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico
4.
Metab Brain Dis ; 38(3): 1051-1066, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36437394

RESUMEN

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.


Asunto(s)
Diarilheptanoides , Enfermedad de Parkinson , Ratas , Animales , Diarilheptanoides/uso terapéutico , Haloperidol/farmacología , Haloperidol/uso terapéutico , Acetilcolinesterasa , Modelos Animales de Enfermedad , Enfermedad de Parkinson/tratamiento farmacológico
5.
Molecules ; 28(10)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37241888

RESUMEN

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.


Asunto(s)
Productos Biológicos , Nanopartículas del Metal , Neoplasias , Humanos , Ácido Hialurónico/química , Quercetina/farmacología , Nanopartículas del Metal/química , Células CACO-2 , Plata , Polietilenglicoles/química , Agua , Espectroscopía Infrarroja por Transformada de Fourier
6.
Mar Drugs ; 19(9)2021 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-34564146

RESUMEN

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.


Asunto(s)
Productos Biológicos/metabolismo , Chlorophyta/metabolismo , Phaeophyceae/metabolismo , Rhodophyta/metabolismo , Algas Marinas/metabolismo , Animales , Productos Biológicos/química , Productos Biológicos/farmacología , Humanos , Nanomedicina
7.
Molecules ; 26(22)2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34834112

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Ehrlich , Ácidos Grasos Monoinsaturados/farmacología , Proteínas de Neoplasias/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/química , Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patología , Ciclofosfamida/química , Ciclofosfamida/farmacología , Relación Dosis-Respuesta a Droga , Ácidos Grasos/química , Ácidos Grasos Monoinsaturados/química , Femenino , Ratones
8.
Exp Eye Res ; 175: 103-114, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29928899

RESUMEN

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 1 mM and 2 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 µM) 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.


Asunto(s)
Abietanos/farmacología , Acrilamida/toxicidad , Antioxidantes/farmacología , Embrión no Mamífero/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Pez Cebra/embriología , Animales , Catalasa/metabolismo , Supervivencia Celular/fisiología , Embrión no Mamífero/metabolismo , Glutatión Peroxidasa/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1/metabolismo , Proteínas de Pez Cebra/metabolismo , Glutatión Peroxidasa GPX1
9.
Acta Trop ; 252: 107155, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38373527

RESUMEN

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.


Asunto(s)
Monoterpenos Acíclicos , Antiprotozoarios , Ciclohexanoles , Compuestos de Tritilo , Óxido de Zinc , Animales , Ratones , Óxido de Zinc/farmacología , Antioxidantes/farmacología , Zinc , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Antimoniato de Meglumina , Ratones Endogámicos BALB C
10.
Int Immunopharmacol ; 133: 112021, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38626549

RESUMEN

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.


Asunto(s)
Retinopatía Diabética , Quempferoles , Macrófagos , Microglía , Animales , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/inmunología , Retinopatía Diabética/patología , Microglía/efectos de los fármacos , Microglía/inmunología , Quempferoles/farmacología , Quempferoles/uso terapéutico , Ratas , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Progresión de la Enfermedad , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/inmunología , Retina/efectos de los fármacos , Retina/patología , Retina/inmunología , Línea Celular , Masculino , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Humanos , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/uso terapéutico , Modelos Animales de Enfermedad
11.
Acta Trop ; : 107312, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972561

RESUMEN

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.

12.
Reprod Sci ; 31(7): 1958-1972, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38267808

RESUMEN

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.


Asunto(s)
Antioxidantes , Criopreservación , Crioprotectores , Cabras , Preservación de Semen , Animales , Masculino , Criopreservación/métodos , Criopreservación/veterinaria , Antioxidantes/farmacología , Preservación de Semen/métodos , Preservación de Semen/veterinaria , Crioprotectores/farmacología , Espermatozoides/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Semen/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Análisis de Semen , Membrana Celular/efectos de los fármacos
13.
Biochim Biophys Acta Mol Basis Dis ; : 167353, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39004381

RESUMEN

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.

14.
J King Saud Univ Sci ; 35(1): 102416, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36338940

RESUMEN

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.

15.
Materials (Basel) ; 16(10)2023 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-37241347

RESUMEN

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.

16.
Cancers (Basel) ; 15(4)2023 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-36831357

RESUMEN

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.

17.
Diabetes Metab Syndr Obes ; 15: 1589-1596, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35637860

RESUMEN

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.

18.
Carbohydr Polym ; 286: 119207, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35337492

RESUMEN

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.

19.
Biomed Res Int ; 2022: 7233997, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35528154

RESUMEN

Objective: The present study was aimed at evaluating the antitumor effects of royal jelly (RJ) obtained from Apis mellifera compared with cyclophosphamide against the Ehrlich solid tumors (EST) in mice. Methods: 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), nitric oxide (NO), antioxidant enzymes (glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in EST mice treated with RJ (200 and 400 mg/kg orally once a day for 2 weeks). Results: The results showed that treatment of EST-suffering mice with RJ at the doses of 200 and 400 mg/kg causes significant reduction in tumor volume and inhibition rate, body weight, 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 EST mice receiving the normal saline; whereas RJ at the doses of 200 and 400 mg/kg/day significantly increased (p < 0.05) the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusion: The findings revealed that oral administration of royal jelly especially at the doses of 200 and 400 mg/kg exhibited promising antitumor effects against EST in mice through induction of apoptosis as well as its antioxidant and anti-inflammatory effects, which suggest it as a novel anticancer agent against tumor; however, additional surveys especially in clinical setting are necessary to approve these findings.


Asunto(s)
Antioxidantes , Neoplasias , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Abejas , Peso Corporal , Ácidos Grasos , Ratones , Neoplasias/tratamiento farmacológico , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , alfa-Fetoproteínas/metabolismo
20.
Saudi J Biol Sci ; 29(4): 2656-2673, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35531235

RESUMEN

Many studies worldwide have been done on the effect of medicinal uses of lovage plant but, very little works have been done on its production. In this study the effect of different planting density and soaking seeds in different concentration of melatonin solution as well as their combination treatments on yield, secondary products content and antimicrobial activity of lovage plant were studied. It was observed that using planting space of 15 cm gave the maximum mean values of total phenolic and antioxidant content and essential oil percentage. Using 30 cm planting space gave the maximum mean values of plant height, yield of herb fresh and dry weight per hectare, yield of roots dry weight and essential oil per hectare. While the plant space of 45 cm recorded the maximum mean values of fresh and dry weight of herb and roots fresh weight per plant and chlorophyll content. For melatonin levels, using 100 µM melatonin solution had the minimum mean values of number of days to emergence. While, soaking seeds in 75 µM melatonin solution recorded the best results of all studied parameters. Regarding the combination treatments, measurements comprising of herb fresh and dry weight as well as essential oil yield per hectare showed that the combination treatment of 30 cm between plants in row plus soaking seeds in 75 µM melatonin solution was able to achieve the maximum values of these parameters. While the combination treatment of 15 cm between plants in row plus soaking solution of 75 µM melatonin is recommended for getting the maximum yield of root fresh and dry weight per hectare and the maximum total phenolic and antioxidant contents per herb in both cuts of both studied season. The first major compound of lovage essential oil of herb is α-terpinyle acetate followed by ß-Phellandrene. The percentages of these compounds were affected by the applied treatments. The volatile oil of lovage plant exhibits high antibacterial and antifungal properties in the concentrations range of 75-100 µg mL-1.

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