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Introduction: Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health. Methods: This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an In silico preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10 mg/kg b.wt.), ACR (20 mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A. Results: ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.
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Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10â¯mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3â¯P and miRNA 325-3â¯P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20â¯mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3â¯P and miRNA 325-3â¯P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3â¯P and miRNA 325-3â¯P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.
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Inflamassomos , MicroRNAs , Extratos Vegetais , Piroptose , Ratos Sprague-Dawley , Transdução de Sinais , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Ratos , Masculino , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acrilamida/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Acrilamidas/toxicidade , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismoRESUMO
Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools. Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models. Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection. Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.
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Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.
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The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of ß-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis.
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Epigenetics plays a vital role in the interaction between living organisms and their environment by regulating biological functions and phenotypic plasticity. Considering that most aquaculture activities take place in open or natural habitats that are vulnerable to environmental changes. Promising findings from recent research conducted on various aquaculture species have provided preliminary evidence suggesting a link between epigenetic mechanisms and economically valuable characteristics. Environmental stressors, including climate changes (thermal stress, hypoxia, and water salinity), anthropogenic impacts such as (pesticides, crude oil pollution, nutritional impacts, and heavy metal) and abiotic factors (infectious diseases), can directly trigger epigenetic modifications in fish. While experiments have confirmed that many epigenetic alterations caused by environmental factors have plastic responses, some can be permanently integrated into the genome through genetic integration and promoting rapid transgenerational adaptation in fish. These environmental factors might cause irregular DNA methylation patterns in genes related to many biological events leading to organs dysfunction by inducing alterations in genes related to oxidative stress or apoptosis. Moreover, these environmental issues alter DNA/histone methylation leading to decreased reproductive competence. This review emphasizes the importance of understanding the effects of environmentally relevant issues on the epigenetic regulation of phenotypic variations in fish. The goal is to expand our knowledge of how epigenetics can either facilitate or hinder species' adaptation to these adverse conditions. Furthermore, this review outlines the areas that warrant further investigation in understanding epigenetic reactions to various environmental issues.
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Epigênese Genética , Peixes , Animais , Peixes/genética , Peixes/fisiologia , Adaptação Fisiológica/genética , Fenótipo , Metilação de DNARESUMO
Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4's genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4's connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4's carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.
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This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN for 60 days. Then, serum renal damage products were assessed. Total antioxidant capacity, reactive oxygen species, interleukin 1ß (IL-1ß), malondialdehyde, NF-κB P65, cleaved-Caspase-1, and Caspase-8 were estimated in kidney homogenates. The cleaved Caspase-3 and TNF-α immunoexpression and pyroptosis-related genes were determined in renal tissues. The results showed that CU-CS-NPS significantly repressed the FPN-induced increment in kidney damage products (urea, uric acid, and creatinine). Moreover, the FPN-associated hypo-proteinemia, renal oxidative stress and apoptotic reactions, and impaired renal histology were considerably repaired by CU and CU-CS-NPs. Additionally, compared to FPN-exposed rats, CU, and CU-CS-NPs-treated rats had considerably lower immunoexpression of cleaved Caspase-3 and TNF-α in renal tissue. The pyroptosis-related genes NLRP3, GSDMD, IL-18, Caspase-3, Caspase-1, IL-1ß, Caspase-8, TNF-α, and NF-κB dramatically upregulated by FPN exposure in the renal tissues. Yet, in CU and CU-CS-NPs-treated rats, the gene above expression deviations were corrected. Notably, CU-CS-NPs were superior to CU in preventing oxidative damage and inflammation and regulating pyroptosis in the renal tissues of the FPN-exposed group. The results of the present study conclusively showed the superior favorable effect of CU-CS-NPs in counteracting renal impairment linked to environmental pollutants.
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Quitosana , Curcumina , Piretrinas , Piroptose , Animais , Masculino , Ratos , Caspase 1 , Caspase 3 , Caspase 8 , Curcumina/farmacologia , Rim , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piretrinas/toxicidade , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
Bats have the ability to fly without eye application in the darkness. In this study, we aimed to characterize the functional and structural acclimations of the lenses of two common bats with a various lifestyle in the Egyptian environment: the insectivorous bat (IB) (Pipistrellus kuhlii) and Egyptian fruit bat (FB) (Rousettus aegyptiacus). From each species, seven lenses were extracted from adult eyes. The scanning electron microscopic (SEM) and light microscopic examination of the lens were carried out. FB lenses were made up primarily of fiber cells and sheets, which were encapsulated by a thin collagenous capsule and covered by single epithelial layer anteriorly. On the other hand, the IB lens had two poles and was visibly oval shaped. Both lenses had epithelial cells of the same cuboidal form that were subjected to continuous division and differentiation into new fiber cells at the center. SEM revealed that the normal FB lens had regularly organized shells of fiber cells of intact lens fibers which were connected by membrane interdigitations with different shapes mainly ball-and-socket junctions through the superficial cortical fiber cells. The IB lens was composed of parallel, evenly spaced fibers with various types of interdigitations between fibers that can be seen and increased close to the middle region revealing tiny bumps along the scrubby portions and sockets and balls in the center of the wide portions. Near the center of both lenses, there were large interlocking paddles with little and lengthy protrusions along their short sides. In conclusion, our study discovered several ultrastructural and structural variations among the investigated species. The detection of specialized membrane interdigitations with different shapes protruding from the lens fiber sheets is considered the most characteristic of the FB lens. RESEARCH HIGHLIGHTS: FB lens has more organized sheets of fibers parallel to each other than IB lens. Different shapes of interdigitations protruded from the FB lens have been detected. Interlocking paddles, balls, and sockets with tongue-like fiber flabs are characteristic to FB lens.
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Quirópteros , Cristalino , Microscopia Eletrônica de Varredura , Animais , Quirópteros/anatomia & histologia , Cristalino/ultraestrutura , Microscopia/métodos , Egito , Células Epiteliais/ultraestruturaRESUMO
Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.
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Curcumina , Piretrinas , Humanos , Ratos , Animais , Curcumina/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo , Piretrinas/toxicidade , Apoptose , Corantes , PulmãoRESUMO
Angiogenesis is one of the defining characteristics of cancer. Vascular endothelial growth factor (VEGF) is crucial for the development of angiogenesis. A growing interest in cancer therapy is being caused by the widespread use of antiangiogenic drugs in treating several types of human cancer. However, this therapeutic approach can worsen resistance, invasion, and overall survival. As we proceed, refining combination strategies and addressing the constraint of targeted treatments are paramount. Therefore, major challenges in using novel combinations of antiangiogenic agents with cytotoxic treatments are currently focused on illustrating the potential of synergistic therapeutic strategies, alongside advancements in nanomedicine and gene therapy, present opportunities for more precise interference with angiogenesis pathways and tumor environments. Nanoparticles have the potential to regulate several crucial activities and improve several drug limitations such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance based on their unique features. The goal of this updated review is to illustrate the enormous potential of novel synergistic therapeutic strategies and the targeted nanoparticles as an alternate strategy for t treating a variety of tumors employing antiangiogenic therapy.
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Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neovascularização Patológica/metabolismo , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêuticoRESUMO
BACKGROUND: Attempts to use dietary lysozyme (LYZ) as an alternative to antibiotics in broilers have been successful, but further research is needed for effective use. Here, we compared the differences between LYZ and avilamycin (AVI) feed additives for growth performance, gut health and immunity of broilers. One-day old, one hundred and twenty broiler chicks (Ross 308) were randomly allocated into three groups consisting forty birds in each group. Standard diet without supplementation was applied as the control group (I), while the chicks of the other groups were supplemented with 100 mg of AVI per kg diet (AVI, group II), and 90 mg LYZ per kg diet (LYZ, group III) for five consecutive weeks. RESULTS: Body weight, feed conversion ratio, body weight gain, and European production efficiency factor were markedly (p < 0.05) increased in both AVI and LYZ groups in relation to CON group, but the feed intake and protein efficiency ratio were not affected. Both AVI and LYZ significantly (p < 0.001) upregulated the mRNA expression of ileal interleukin-18 (IL-18), interferon-gamma (IFN-γ), and interleukin-10 (IL-10), interleukin-2 (IL-2), and glutathione peroxidase (GSH-PX) genes compared to CON group. However, IL-2, IL-10, IL-18, and GSH-PX genes were markedly (p < 0.01) upregulated in LYZ compared to the AVI group. LYZ treated group had a significant increase (p < 0.05) in the serological haemagglutination inhibition titers of H5N1 vaccination and a significant decrease (p < 0.0001) in coliform counts compared to control and AVI groups, but all growth parameters were nearly similar between AVI and LYZ groups. The VH and VH/CD were markedly higher in LYZ than AVI and control groups. CONCLUSION: Exogenous dietary lysozyme supplementation by a dose of 90 mg/kg broilers' diet induced better effects on intestinal integrity, fecal bacterial counts, immune response, and growth performance which were comparable to avilamycin. Therefore, dietary lysozyme could safely replace avilamycin in the broiler chickens' diet. However, further experimental studies regarding the use of lysozyme in commercial broilers, both in vitro and in vivo, targeting more communities of intestinal microbiome and explaining more details about its beneficial effects need to be conducted.
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Galinhas , Virus da Influenza A Subtipo H5N1 , Oligossacarídeos , Animais , Interleucina-2 , Interleucina-10 , Interleucina-18 , Muramidase , Dieta/veterinária , Suplementos Nutricionais , Peso Corporal , Ração Animal/análiseRESUMO
Heat stress (HS) is still the essential environmental agent influencing the poultry industry. Research on HS in poultry has progressively acquired growing interest because of increased attention to climate alteration. Poultry can survive at certain zone of environmental temperatures, so it could be considered homoeothermic. In poultry, the normal body temperature is essential to enhance the internal environment for growth, which is achieved by normal environmental temperature. Recently, many studies have revealed that HS could cause mitochondrial dysfunction in broilers by inducing redox dysfunction, increasing uncoupling protein, boosting lipid and protein oxidation, and oxidative stress. Moreover, HS diminished the energy suppliers supported by mitochondria activity. A novel strategy for combating the negative influences of HS via boosting the mitochondria function through enrichment of the diets with mitochondria enhancers was also described in this review. Finally, the current review highlights the mitochondria dysfunction induced by HS in broilers and attempts to boost mitochondria functionality by enriching mitochondria enhancers to broiler diets.
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Galinhas , Aves Domésticas , Animais , Estresse Oxidativo , Resposta ao Choque Térmico , Mitocôndrias/metabolismoRESUMO
Aflatoxin B1 (AFB1) is a widely distributed mycotoxin, causing hepatotoxicity and oxidative stress. One of the most famous unicellular cyanobacteria is Spirulina platensis (SP) which is well known for its antioxidant characteristics against many toxicants. Therefore, this study aimed to investigate the antioxidant potential and hepatoprotective ability of SP against oxidative stress and cytotoxicity in male Wistar albino rats intraperitoneally injected with AFB1. Rats were separated into five groups as follows: negative control administered with saline; SP (1000 mg/kg BW) for two weeks; AFB1 (2.5 mg/kg BW) twice on days 12 and 14; AFB1 (twice) + 500 mg SP/kg BW (for two weeks) and AFB1 (twice) + 1000 mg SP/kg BW (for two weeks). Liver and blood samples were assembled for histological and biochemical analyses. AFB1 intoxicated rats showed a marked elevation in serum biochemical parameters (ALP, ALT, and AST), hepatic lipid peroxidation (MDA and NO), and proliferating cell nuclear antigen (PCNA) indicating DNA damage. Moreover, AFB1 caused suppression of antioxidant biomarkers (SOD, GHS, GSH-Px, and CAT). However, the elevated serum levels of biochemical parameters and PCNA expression were reduced by SP. Moreover, SP lowered oxidative stress and lipid peroxidation markers in a dose-dependent manner. To sum up, SP supplementation is capable of decreasing AFB1 toxicity through its powerful antioxidant activity.
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Aflatoxina B1 , Antioxidantes , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Aflatoxina B1/toxicidade , Aflatoxina B1/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Wistar , Catalase/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Dano ao DNARESUMO
The glutamine synthetase (GS) facilitates cancer cell growth by catalyzing de novo glutamine synthesis. This enzyme removes ammonia waste from the liver following the urea cycle. Since cancer development is associated with dysregulated urea cycles, there has been no investigation of GS's role in ammonia clearance. Here, we demonstrate that, although GS expression is increased in the setting of ß-catenin oncogenic activation, it is insufficient to clear the ammonia waste burden due to the dysregulated urea cycle and may thus be unable to prevent cancer formation. In vivo study, a total of 165 male Swiss albino mice allocated in 11 groups were used, and liver cancer was induced by p-DAB. The activity of GS was evaluated along with the relative expression of mTOR, ß-catenin, MMP-14, and GS genes in liver samples and HepG2 cells using qRT-PCR. Moreover, the cytotoxicity of the NH3 scavenger phenyl acetate (PA) and/or GS-inhibitor L-methionine sulfoximine (MSO) and the migratory potential of cells was assessed by MTT and wound healing assays, respectively. The Swiss target prediction algorithm was used to screen the mentioned compounds for probable targets. The treatment of the HepG2 cell line with PA plus MSO demonstrated strong cytotoxicity. The post-scratch remaining wound area (%) in the untreated HepG2 cells was 2.0%. In contrast, the remaining wound area (%) in the cells treated with PA, MSO, and PA + MSO for 48 h was 61.1, 55.8, and 78.5%, respectively. The combination of the two drugs had the greatest effect, resulting in the greatest decrease in the GS activity, ß-catenin, and mTOR expression. MSO and PA are both capable of suppressing mTOR, a key player in the development of HCC, and MMP-14, a key player in the development of HCC. PA inhibited the MMP-14 enzyme more effectively than MSO, implying that PA might be a better way to target HCC as it inhibited MMP-14 more effectively than MSO. A large number of abnormal hepatocytes (5%) were found to be present in the HCC mice compared to mice in the control group as determined by the histopathological lesions scores. In contrast, PA, MSO, and PA + MSO showed a significant reduction in the hepatic lesions score either when protecting the liver or when treating the liver. The molecular docking study indicated that PA and MSO form a three-dimensional structure with NF-κB and COX-II, blocking their ability to promote cancer and cause gene mutations. PA and MSO could be used to manipulate GS activities to modulate ammonia levels, thus providing a potential treatment for ammonia homeostasis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Camundongos , Animais , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , beta Catenina/metabolismo , Glutamato-Amônia Ligase/genética , Glutamato-Amônia Ligase/metabolismo , Amônia/metabolismo , Amônia/uso terapêutico , Nitrogênio/uso terapêutico , Metaloproteinase 14 da Matriz , Simulação de Acoplamento Molecular , Serina-Treonina Quinases TOR , Homeostase , Ureia/uso terapêuticoRESUMO
Chronic immobilization stress plays a key role in several neuropsychiatric disorders. This investigation assessed the possible ameliorative effect of chia seed oil (CSO) against the neurodisturbance-induced in rats by chronic immobilization. Rats were randomly allocated into control, CSO (1 ml/kg b.wt./orally), restrained (6 h/day), CSO pre-restraint, and CSO post-restraint for 60 days. Results revealed a significant reduction in serum corticosterone level, gene expression of corticotrophin-releasing factor, pro-inflammatory cytokines, and oxidative biomarkers in restrained rats treated with CSO. The histopathological findings revealed restoring necrosis and neuronal loss in CSO-treated-restraint rats. The immunohistochemical evaluation revealed a significant reduction in the immuno-expression of caspase-3, nuclear factor kappa B, interleukin-6, and cyclooxygenase-2 (COX-2), and an elevation of calbindin-28k and synaptophysin expression compared to non-treated restraint rats. The molecular docking showed the CSO high affinity for several target proteins, including caspase-3, COX-2, corticotropin-releasing hormone binding protein, corticotropin-releasing factor receptors 1 and 2, interleukin-1 receptor types 1 and 2, interleukin-6 receptor subunits alpha and beta. In conclusion, CSO emerges as a promising candidate against stress-induced brain disruptions by suppressing inflammatory/oxidative/apoptotic signaling pathways due to its numerous antioxidant and anti-inflammatory components, mainly α-linolenic acid. Future studies are necessary to evaluate the CSO therapeutic impacts in human neurodisturbances.
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Anti-Inflamatórios , Antioxidantes , Humanos , Ratos , Animais , Antioxidantes/análise , Caspase 3 , Ciclo-Oxigenase 2/análise , Simulação de Acoplamento Molecular , Anti-Inflamatórios/análise , Transdução de Sinais , Sementes/químicaRESUMO
The reproductive activity of the male dromedary camel (Camelus dromedarius) as a seasonal breeder is affected by various seasonal changes that reflect on the reproductive performance. In the current study, we explored a differential cellular localization of lectins in eight dromedary camel testes utilizing lectin histochemistry (LHC). The glycoconjugates' localizations were detected within the testicular tissue utilizing 13 biotin-labeled lectins (PNA, ConA, LCA, RCA120, GS IB4, WGA, BPL, DBA, ECA, PHA-E4, UEA-1, PTL-II, and SBA) distributed into six sets. The cellular structures revealed diverse lectins distribution that may reflect various glycoproteins' structures and their compositional modifications during spermatogenesis. Some of the investigated lectins were restricted to acrosomes of spermatids that will help study different stages during the spermatogenic cycle of dromedary camel, particularly PNA, and ECA. The statistical analysis showed a marked positive correlation between the response intensity of various lectins and the breeding season (P < 0.05). We can conclude that lectins have a fundamental role during camel spermatogenesis and are associated with the reproductive activity of dromedary camel.
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Camelus , Testículo , Masculino , Animais , Camelus/fisiologia , Lectinas , Estações do Ano , GlicoconjugadosRESUMO
The protein calbindin-D28k modulates calcium reabsorption in the kidney. Here, we aimed to study the influence of proliferation and apoptosis in different compartments of the kidney on the developmental function of calbindin. Using immunohistochemistry, we investigated the postnatal development of rats' kidneys by using calbindin, proliferative cell nuclear antigen (PCNA), and apoptotic single-stranded DNA (ssDNA). In the neonatal stage (1-day and 1-week-old rats), calbindin showed a positive reaction in the distal convoluted tubule (DCT), a short nephron segment between the macula densa, collecting ducts, and tubules. Moreover, the localization of calbindin was restricted to immature nephrons and mesenchymal tissues. Furthermore, PCNA immunoreactivity was moderate in early-developed podocytes with no reactivity in other renal tubules. The ssDNA immunoreactivity was moderate in the undifferentiated nephron. Then, in the mature stage (3 and 6 weeks old), there was an intense calbindin reaction in DCT but a moderate reaction to PCNA and ssDNA in podocytes. A more intense calbindin reactivity was found in the adult stage (2- and 3-month-old rats) in DCT and collecting tubules. Therefore, in this study, calbindin localization showed an inverse relationship with PCNA and ssDNA of the nephron compartments, which might reflect the efficiency of bone-building and muscle contraction during animal development.
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Non-alcoholic fatty liver (NAFL) is a prevalent hepatic disorder of global significance that can give rise to severe complications. This research endeavor delves into the potential of nano-liposomal formulated Lycopene (Lip-Lyco) in averting the development of obesity and insulin resistance, both of which are major underlying factors contributing to NAFL. The investigation further scrutinizes the impact of Lip-Lyco on intricate cellular pathways within the liver tissue of rats induced with NAFL, specifically focusing on the progression of steatosis and fibrosis. To establish an obesity-NAFL model, twenty rats were subjected to a high-fat diet (HFD) for a duration of twelve weeks, after which they received an oral treatment of Lip-Lyco (10mg/kg) for an additional eight weeks. Another group of sixteen non-obese rats were subjected to treatment with or without Lip-Lyco, serving as a control for comparison. Results: The rats on a hypercaloric diet had high body mass index (BMI) and insulin resistance, reflected in disturbed serum adipokines and lipid profiles. Oxidative stress, inflammation, and apoptosis were evident in hepatic tissue, and the autophagic process in hepatocytes was inhibited. Additionally, the hedgehog pathway was activated in the liver tissue of NAFL group. Lip-Lyco was found to counteract all these aspects of NAFL pathogenesis. Lip-Lyco exhibited antioxidant, anti-inflammatory, hypoglycemic, antiapoptotic, autophagy-inducing, and Hedgehog signaling inhibitory effects. This study concludes that Lip-Lyco, a natural compound, has promising therapeutic potential in combating NAFLdisease. However, more experimental and clinical studies are required to confirm the effectiveness of lycopene in treating NAFLdisease.
Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Licopeno/farmacologia , Licopeno/uso terapêutico , Proteínas Hedgehog/metabolismo , Fígado/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/genética , Dieta Hiperlipídica/efeitos adversos , Genômica , AutofagiaRESUMO
Oxidative stress results from the imbalance between reactive oxygen species (ROS) production and antioxidant defence and is primarily involved in aging. The current study investigated the antioxidant activity of rutin in aging in rats induced by D-galactose (D-gal) for 42 days. Rutin was orally used at doses of 50 and 100 mg kg-1 daily. Results showed that D-gal induced oxidative alterations in the brain and liver recognized via upregulation of aging and oxidative markers. In contrast, rutin ameliorated the oxidative stress induced by D-gal by enhancing antioxidant markers such as superoxide dismutase-1, glutathione peroxidase-1, and glutathione S-transferase-α. Also, rutin significantly decreased the accumulation of ß-galactosidase and reduced the expression of p53, p21, Bcl-2-associated X protein (Bax), caspase-3 (CASP3), and mammalian target of rapamycin (mTOR) in brain and hepatic tissues. Rutin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Moreover, rutin markedly reduced the increased immunohistochemical expression of ß-galactosidase, 8-hydroxy-2'-deoxyguanosine, calcium-binding adapter molecule 1, glial fibrillary acidic protein, Bax, and interleukin-6 and significantly increased Bcl2, synaptophysin, and Ki67. Furthermore, a molecular docking study revealed that rutin exhibited high affinity to rat and human caspases, PI3K/AKT/mTOR, and the IL-6 receptor. Finally, we can conclude that rutin supplementation can be a promising natural protective compound that could delay aging and maintain health.