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1.
Antioxidants (Basel) ; 10(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34829524

RESUMO

The precise analysis of the contents of the red carrot is still ambiguous and its role in the maintenance of male fertility needs to be further reconnoitered. Hence, this study targets the physiological impacts of either red carrot methanolic extract (RCME) or vitamin E (Vit. E), co-administrated with cadmium chloride (CdCl2) on rat testes, specifically those concerned with apoptosis and oxidative challenge. Four groups of adult male rats (n = 12) are used; control, CdCl2, CdCl2 + Vit. E and CdCl2 + RCME. LC-MS analysis of RCME reveals the presence of 20 different phytochemical compounds. Our data clarify the deleterious effects of CdCl2 on testicular weights, semen quality, serum hormonal profile, oxidative markers and Bax/Bcl-2 ratio. Histopathological changes in testicular, prostatic and semen vesicle glandular tissues are also observed. Interestingly, our data clearly demonstrate that co-administration of either RCME or Vit. E with CdCl2 significantly succeeded in the modulation (p < 0.05) of all of these negative effects. The most striking is that they were potent enough to modulate the Bax/Bcl-2 ratio as well as having the ability to correct the impaired semen picture, oxidant status and hormonal profile. Thus, RCME and Vit. E could be used as effective prophylactic treatments to protect the male reproductive physiology against CdCl2 insult.

2.
PLoS One ; 16(11): e0257895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780475

RESUMO

BACKGROUND: Globally, iron-deficiency anemia (IDA) remains a major health obstacle. This health condition has been identified in 47% of pre-school students (aged 0 to 5 years), 42% of pregnant females, and 30% of non-pregnant females (aged 15 to 50 years) worldwide according to the WHO. Environmental and genetic factors play a crucial role in the development of IDA; genetic testing has revealed the association of a number of polymorphisms with iron status and serum ferritin. AIM: The current study aims to reveal the association of TMPRSS6 rs141312 and BMP2 rs235756 with the iron status of females in Saudi Arabia. METHODS: A cohort of 108 female university students aged 18-25 years was randomly selected to participate: 50 healthy and 58 classified as iron deficient. A 3-5 mL sample of blood was collected from each one and analyzed based on hematological and biochemical iron status followed by genotyping by PCR. RESULTS: The genotype distribution of TMPRSS6 rs141312 was 8% (TT), 88% (TC) and 4% (CC) in the healthy group compared with 3.45% (TT), 89.66% (TC) and 6.89% (CC) in the iron-deficient group (P = 0.492), an insignificant difference in the allelic distribution. The genotype distribution of BMP2 rs235756 was 8% (TT), 90% (TC) and 2% (CC) in the healthy group compared with 3.45% (TT), 82.76% (TC) and 13.79% (CC) in iron-deficient group (P = 0.050) and was significantly associated with decreased ferritin status (P = 0.050). In addition, TMPRSS6 rs141312 is significantly (P<0.001) associated with dominant genotypes (TC+CC) and increased risk of IDA while BMP2 rs235756 is significantly (P<0.026) associated with recessive homozygote CC genotypes and increased risk of IDA. CONCLUSION: Our finding potentially helps in the early prediction of iron deficiency in females through the genetic testing.

3.
Front Vet Sci ; 8: 705619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765663

RESUMO

Goats can be infected by multiple groups of external and internal parasites. Haemonchus spp. are among abomasal parasites that can result in higher mortality and several considerable economic losses in goats. Early detection of parasites and better understanding of the major risk factors associated with infection are among the main strategies for controlling the infection. Considering this, information on hemonchosis in goats from Egypt, and the contribution of goats in the maintenance of the epidemiological foci of the disease is limited. This study investigated the prevalence of Haemonchus species among 240 abomasum samples collected during postmortem examination of goat carcasses from Assiut Governorate, Egypt. Moreover, the association of the major risk factors to describe the epidemiological pattern of the disease was explored. This study demonstrated that 16.66% of abomasa samples harbored Haemonchus species. Additionally, age, sex, and sampling season were the most significant risk factors associated with infection. Following the variable factors under study, goats aged 1 year or older were at higher risk, with an infection rate of 22.14% (31 of 140), than those younger than 1 year (9%) [p = 0.008; odds ratio (OR) = 2.87; 95% confidence interval (CI), 1.30-6.35]. The infection rate was 25% (19 of 76) in males and 12.8% (21 of 164) in females [p = 0.024; odds ratio (OR) = 2.26; 95% confidence interval (CI), 1.13-4.53]. Moreover, the exposure to infection was higher in summer (22.22%) than in winter (8.33%) (p = 0.007; odds ratio (OR) = 0.318; 95% confidence interval (CI), 0.139-0.725). More importantly, three species of the parasite-Haemonchus contortus, Haemonchus placei, and Haemonchus longistipes-were identified for the first time, and the confirmation of the identification and morphological characterization of the worms was performed using light microscopy and SEM. Collectively, this study reveals interesting epidemiological, morphological, and morphometric findings associated with the occurrence of hemonchosis among goats in Egypt. This study suggests further research for exploring the major circulating species of the parasite in Egypt, which is mandatory for controlling the disease.

4.
Vet Sci ; 8(10)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34679045

RESUMO

Leishmaniasis remains one of the major neglected tropical diseases. The epidemiological profile of the disease comprises a wide range of hosts, including dogs and cats. Despite several studies about feline Leishmaniosis, the role of cats in disease epidemiology and its clinical impact is still debated. The present study raises awareness about the impact of leishmaniasis in cats from an endemic region in of Northwestern Italy (Liguria). A total number of 250 serum and 282 blood samples were collected from cats, then assessed for Leishmania infantum (L. infantum) serologically using western blot (WB) and molecularly using polymerase chain reaction (PCR). We also tested the association of Leishmania infection with some infectious agents like haemotropic Mycoplasma, Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) together with the hematobiochemical status of the examined animals. Interestingly, all tested animals were asymptomatic and out of 250 examined serum samples, 33 (13.20%) samples (confidence interval (CI) 95% 9.56-17.96%) were positive at WB for L. infantum, whereas of the 282 blood samples, 80 (28.36%) returned a positive PCR (CI 95% 23.43-33.89%). Furthermore, there was a statistical association between PCR positivity for L. infantum and some hematological parameters besides FIV infection as well as a direct significant correlation between Mycoplasma infection and WB positivity. Taken together, the present findings report high prevalence of L. infantum among cats, which reinforces the significance of such positive asymptomatic animals and confirms the very low humoral response in this species. In addition, the laboratory values provide evidence that infection by the parasite is linked to alteration of some hematological parameters and is correlated to some infectious agents. These data are of interest and suggest future research for accurate diagnosis of such zoonosis.

5.
Viruses ; 13(10)2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696358

RESUMO

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting "PVQLSY" motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 Mpro, NSP7, NSP10, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders.

6.
Inflammopharmacology ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550498

RESUMO

Aim of this study was to evaluate and compare the efficacy of anti-arthritic drugs (naproxen, prednisolone, and hydroxychloroquine) alone and in combination. The in vitro anti-arthritic activity was evaluated by stabilization of human erythrocytes (HRBCs) membrane assays. In vivo activity was carried out using Complete Freund's Adjuvant (CFA) induced arthritic model in Wistar rat. Individual and combination drugs were administered for 21 days in rats 8 days post inoculation with CFA (0.15 ml injected in right hind paw). Body weight and paw edema were measured at different intervals. Combination treatments exhibited more HRBC stabilization than individual treatments. All individual and combination treatments reduced the level of C-reactive protein (CRP), liver function enzymes, malondialdehyde, white blood cells and platelets, with the most pronounced activity exhibited by the combination of three drugs. The level of oxidative stress biomarkers (reduced glutathione, catalase, and superoxide dismutase), red blood cells, and hemoglobin were notably increased in all treatment groups in contrasts to diseased control rats. Histopathological evaluation of the paw showed that all the treatments had reduced (p < 0.05-0.001) the arthritic indices in contrasts to diseased control rats. The serum concentrations of TNF-α and PGE2 were provoked in diseased control rats but had been notably (p < 0.0001) restored by treatments with individual and combination drugs. It was also found that combination treatments, more precisely triple drug was remarkably effective in treating arthritis. It can be concluded that naproxen, prednisolone, and hydroxychloroquine effectively ameliorated the CFA-induced arthritis and were more effective in combination as compared to individual drug therapy probably due to reduction in oxidative stress and inflammatory markers. Moreover, two lower doses (half NPH/2 and one-third NPH/3) of triple combination therapy naproxen, prednisolone, and hydroxychloroquine (NPH) showed no significant difference in anti-arthritic effect as compared to the highest dose level of NPH.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34562213

RESUMO

Monosodium glutamate (MSG), a commonly used flavor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 g/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for 7 days. Results showed that MSG augmented the hepatic and renal functions markers as well as glucose, triglycerides, total cholesterol, and low-density lipoprotein levels. Moreover, marked increases in malondialdehyde levels accompanied by declines in glutathione levels and notable decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were observed in MSG-treated group. The MSG-mediated oxidative stress was further confirmed by downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal inflammation as witnessed by increased inflammatory cytokines (interleukin-1b and tumor necrosis factor-α) and elevated nuclear factor-κB (NF-κB) levels. Further, significant increases in Bcl-2-associated X protein (Bax) levels together with decreases in B-cell lymphoma 2 (Bcl-2) levels were observed in MSG administration. Histopathological screening supported the biochemical and molecular findings. In contrast, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of inflammatory mediators, and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatorenal injuries through modulation of oxidative, inflammatory and apoptotic alterations.

8.
Hematology ; 26(1): 628-636, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34494505

RESUMO

Over the past 20 years, granulocyte colony-stimulating factor (G-CSF) has driven the attention of researchers as a therapeutic agent for curing patients suffering from neutropenia. Despite the successful use of G-CSF, it currently requires daily injections, which are inconvenient, expensive, and distressing for children. Therefore, an alternative strategy for using G-CSF for treatment is needed. Understanding the G-CSF structure, expression, mechanism of action, and how it induces neutrophils mobilization is crucial to producing promising cancer therapy. The ability of G-CSF to mobilize hematopoietic stem cells from the bone marrow into the blood circulation was consequently exploited and altered the practice of hematopoietic stem cell transplantation. This is the motivation for the current review, which sheds light on the history of G-CSF and then focuses on the mechanism of action upon binding to its receptor (G-CSFR) and how that had led to the stimulation of neutrophils mobilization. The findings of this review show new insight into the mechanism of G-CSF that induces neutrophils mobilization. Thus, Understanding the G-CSF will provide a more effective treatment for all neutropenia patients.


Assuntos
Fator Estimulador de Colônias de Granulócitos/metabolismo , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Neutropenia/metabolismo , Neutrófilos/metabolismo , Fator Estimulador de Colônias de Granulócitos/história , Células-Tronco Hematopoéticas/patologia , História do Século XX , História do Século XXI , Humanos , Neutropenia/patologia , Neutropenia/terapia , Neutrófilos/patologia
9.
J Food Biochem ; 45(10): e13915, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34472624

RESUMO

Here, we investigated the protective efficacy of protocatechuic acid (PCA) against lipopolysaccharide (LPS)-induced septic lung injury. Eighty-two male Balb/c mice were divided into six groups: control, PCA30 (30 mg/kg), LPS (10 mg/kg), PCA10-LPS, PCA20-LPS, and PCA30-LPS treated with 10, 20 and 30 mg/kg PCA, respectively, for seven days before intraperitoneal LPS injection. PCA pre-treatment, especially at higher dose, significantly reduced LPS-induced lung tissue injury as indicated by increased heat shock protein 70 and antioxidant molecules (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) accompanied by lower oxidative stress indices (malondialdehyde and nitric oxide). PCA administration decreased inflammatory mediators including myeloperoxidase, nuclear factor kappa B (NF-κB p65), and pro-inflammatory cytokines, and prevented the development of apoptotic events in the lung tissue. At the molecular level, PCA downregulated mRNA expression of nitric oxide synthase 2, C/EBP homologous protein, and high mobility group box1 in the lungs of all PCA-LPS treated mice. Thus, PCA-pre-treatment effectively counteracted sepsis-induced acute lung injury in vivo by promoting and antioxidant status, while inhibiting inflammation and apoptosis. PRACTICAL IMPLICATIONS: Sepsis-mediated organ dysfunction and high mortality is aggravated by acute lung injury (ALI). Therefore, new therapeutic approaches are needed to encounter sepsis-mediated ALI. Protocatechuic acid (PCA) is a naturally occurring phenolic acid with various biological and pharmacological activities. PCA is abundant in edible plants including Allium cepa L., Oryza sativa L., Hibiscus sabdariffa, Prunus domestica L., and Eucommia ulmoides. In this investigation we studied the potential protective role of pure PCA (10, 20 and 30 mg/kg) on LPS-mediated septic lung injury in mice through examining oxidative challenge, inflammatory response, apoptotic events and histopathological changes in addition to evaluating the levels and mRNA expression of heat shock protein 70, C/EBP homologous protein and high mobility group box1 in the lung tissue. The recorded results showed that PCA pre-administration was able to significantly abrogate the damages in the lung tissue associated septic response. This protective effect comes from its strong antioxidant, anti-inflammatory, and anti-apoptotic activities, suggesting that PCA may be applied to alleviate ALI associated with the development of sepsis.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Apoptose , Hidroxibenzoatos , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo
10.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502071

RESUMO

We evaluated the role of allicin in periodontitis using an in silico and in vitro design. An in silico docking analysis was performed to assess the plausible interactions between allicin and PD-L1. The cytokine profile of gingival crevicular fluid (GCF) samples obtained from periodontitis patients was estimated by cytometric bead array. CD3+ lymphocytes isolated from the peripheral blood were sorted and characterized using immunomagnetic techniques. Cultured and expanded lymphocytes were treated with the GCF samples to induce T-cell exhaustion. Optimum concentrations of allicin were added to exhausted lymphocytes to compare the expression of TIM-3 and LAG-3 gene expression at baseline and post-treatment. Allicin was found to bind to the PD-L1 molecule as revealed by the in-silico experiment, which is possibly an inhibitory interaction although not proven. GCF from periodontitis patients had significantly higher concentrations of TNF-α, CCL2, IL-6, IFN-γ, and CXCL8 than controls. GCF treatment of CD3+ lymphocytes from the periodontitis patients significantly increased expression of T-cell exhaustion markers TIM-3 and LAG-3. Allicin administration with GCF treatment resulted in significant lowering of the expression of exhaustion markers. Allicin may exert an immunostimulatory role and reverse immune-destructive mechanisms such as T-cell exhaustion.


Assuntos
Antígeno B7-H1/metabolismo , Dissulfetos/farmacologia , Periodontite/metabolismo , Ácidos Sulfínicos/farmacologia , Linfócitos T/efeitos dos fármacos , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno B7-H1/química , Sítios de Ligação , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL6/genética , Quimiocina CXCL6/metabolismo , Dissulfetos/química , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ligação Proteica , Ácidos Sulfínicos/química , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
J Vet Intern Med ; 35(5): 2196-2204, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34464464

RESUMO

BACKGROUND: Diagnosis of gastric ulcers by methods other than gastroscopy in dogs has been problematic for many years and biomarkers such as serum gastrin (SG) concentrations have been introduced as a noninvasive way to evaluate gastric diseases. OBJECTIVES: To determine the time course changes in hematology, SG concentrations, and gastroscopic images of meloxicam-induced gastric ulceration in dogs and identify a relationship between SG and gastroscopic image analysis in a clinical setting. ANIMALS: Fifteen crossbreed dogs. METHODS: Two groups: control (n = 5) and meloxicam-treated (n = 10). The meloxicam-treated group received meloxicam 0.2 mg/kg PO for 15 days. Clinical signs, hematology, SG, and image analysis (PI, pixel intensity; ID, integrated density; RA, relative area; and UI, ulcer index) of the gastroscopic examination were evaluated across time (T5, time 5 day; T10, time 10 day; and T15, time 15 day). RESULTS: Significant changes were observed among 3 time points and between the 2 groups in terms of SG, hematology, and gastroscopic image analysis. In the meloxicam-treated group, decreases in hemoglobin concentration, red blood cell count and packed cell volume at T10 and T15 (P = .0001) were observed, whereas SG, ID, and UI increased over time (P < .0001). The PI decreased significantly (P = .0001) in the meloxicam-treated group compared to controls. Significant correlations were found between SG and PI, and ID and ulcer area (r = -0.89, 0.81, 0.64), respectively. CONCLUSION AND CLINICAL IMPORTANCE: Gastroscopy is the gold standard for early descriptive diagnosis of gastric ulcerations in dogs, and SG is a good indicator for meloxicam-induced gastric ulcers in dogs and can predict the gastroscopic score of the lesion.


Assuntos
Doenças do Cão , Hematologia , Úlcera Gástrica , Tiazinas , Animais , Doenças do Cão/induzido quimicamente , Doenças do Cão/diagnóstico , Cães , Gastrinas , Gastroscopia/veterinária , Meloxicam , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/veterinária , Tiazinas/efeitos adversos , Tiazóis/efeitos adversos
12.
Int J Nanomedicine ; 16: 4335-4349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234429

RESUMO

Purpose: Selenium nanoparticles (SeNPs) have recently gained much attention in nanomedicine applications owing to their unique biological properties. Biosynthesis of SeNPs using nutraceuticals as lycopene (LYC) maximizes their stability and bioactivities. In this context, this study aimed to elucidate the renoprotective activity of SeNPs coated with LYC (LYC-SeNPs) in the acute kidney injury (AKI) model. Methods: Rats were divided into six groups: control, AKI (glycerol-treated), AKI+sodium selenite (Na2SeO3; 0.5 mg/kg), AKI+LYC (10 mg/kg), AKI+LYC-SeNPs (0.5 mg/kg) and treated for 14 days. Results: Glycerol treatment evoked significant increases in rhabdomyolysis-related markers (creatine kinase and LDH). Furthermore, relative kidney weight, Kim-1, neutrophil gelatinase-associated lipocalin (NGAL), serum urea, and creatinine in the AKI group were elevated. Glycerol-injected rats displayed declines in reduced glutathione level, and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, paralleled with downregulations in Nfe2l2 and Hmox-1 expressions and high renal MDA and NO contents. Glycerol-induced renal inflammation was evident by rises in TNF-α, IL-1ß, IL-6, and upregulated Nos2 expression. Also, apoptotic (elevated caspase-3, Bax, and cytochrome-c with lowered Bcl-2) and necroptotic (elevated Pipk3 expression) changes were reported in damaged renal tissue. Co-treatment with Na2SeO3, LYC, or LYC-SeNPs restored the biochemical, molecular, and histological alterations in AKI. In comparison with Na2SeO3 or LYC treatment, LYC-SeNPs had the best nephroprotective profile. Conclusion: Our findings authentically revealed that LYC-SeNPs co-administration could be a prospective candidate against AKI-mediated renal damage via antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic activities.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Glicerol/efeitos adversos , Licopeno/química , Nanopartículas/química , Selênio/química , Selênio/farmacologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Antioxidantes/metabolismo , Creatinina/sangue , Química Verde , Lipocalina-2/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Selênio/uso terapêutico
13.
Front Pharmacol ; 12: 669679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093197

RESUMO

Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1ß, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34073421

RESUMO

This study investigated the PAH levels in Wistar rats exposed to ambient air of the Port Harcourt metropolis. Twenty Wistar rats imported from a nonpolluted city (Enugu) were exposed to both indoor and outdoor air. Following the IACUC regulation, baseline data were obtained from 4 randomly selected rats, while the remaining 16 rats (8 each for indoor and outdoor) were left till day 90. Blood samples were obtained by cardiac puncture, and the PAH levels were determined using Gas Chromatography Flame-Ionization Detector (GC-FID). GraphPad Prism (version 8.0.2) Sidak's (for multiple data set) and unpaired t-tests (for two data sets) were used to evaluate the differences in group means. Seven of the PAHs found in indoor and outdoor rats were absent in baseline rats. The mean concentrations of PAH in indoor and outdoor animals were higher than those of baseline animals, except for Benzo(a)pyrene, which was found in baseline animals but absent in other animal groups. Additionally, Dibenz(a,h)anthracene, Indeno(1,2,3-c,d)pyrene, Pyrene, 2-methyl, and other carcinogenic PAHs were all significantly higher (p < 0.05) in outdoor groups. The vulnerable groups in Port Harcourt are at the greatest risk of such pollution. Therefore, urgent environmental and public health measures are necessary to mitigate the looming danger.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Animais , Monitoramento Ambiental , Nigéria , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Ratos , Ratos Wistar
15.
J Ovarian Res ; 14(1): 52, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794989

RESUMO

BACKGROUND: The clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART. MATERIAL & METHODS: Two hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured. RESULTS: P/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn't whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5). CONCLUSIONS: In patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Metáfase/genética , Oócitos/metabolismo , Reserva Ovariana/genética , Progesterona/sangue , Adulto , Gonadotropina Coriônica/farmacologia , Feminino , Fertilização In Vitro , Humanos , Gravidez
16.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915968

RESUMO

Neurodegenerative diseases, for example Alzheimer's, are perceived as driven by hereditary, cellular, and multifaceted biochemical actions. Numerous plant products, for example flavonoids, are documented in studies for having the ability to pass the blood-brain barrier and moderate the development of such illnesses. Computer-aided drug design (CADD) has achieved importance in the drug discovery world; innovative developments in the aspects of structure identification and characterization, bio-computational science, and molecular biology have added to the preparation of new medications towards these ailments. In this study we evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies, in comparison with standard drugs. The results indicated that the pharmacophore models produced from structures of AChE, BChE and MAO could identify the active compounds, with a recuperation rate of the actives found near 100% in the complete ranked decoy database. Moreso, the robustness of the virtual screening method was accessed by well-established methods including enrichment factor (EF), receiver operating characteristic curve (ROC), Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC), and area under accumulation curve (AUAC). Most notably, the compounds' pIC50 values were predicted by a machine learning-based model generated by the AutoQSAR algorithm. The generated model was validated to affirm its predictive model. The best models achieved for AChE, BChE and MAO were models kpls_radial_17 (R2 = 0.86 and Q2 = 0.73), pls_38 (R2 = 0.77 and Q2 = 0.72), kpls_desc_44 (R2 = 0.81 and Q2 = 0.81) and these externally validated models were utilized to predict the bioactivities of the lead compounds. The binding affinity results of the ligands against the three selected targets revealed that luteolin displayed the highest affinity score of -9.60 kcal/mol, closely followed by apigenin and ellagic acid with docking scores of -9.60 and -9.53 kcal/mol, respectively. The least binding affinity was attained by gallic acid (-6.30 kcal/mol). The docking scores of our standards were -10.40 and -7.93 kcal/mol for donepezil and galanthamine, respectively. The toxicity prediction revealed that none of the flavonoids presented toxicity and they all had good absorption parameters for the analyzed targets. Hence, these compounds can be considered as likely leads for drug improvement against the same.


Assuntos
Descoberta de Drogas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Relação Quantitativa Estrutura-Atividade , Acetilcolinesterase/química , Doença de Alzheimer/tratamento farmacológico , Sítios de Ligação , Butirilcolinesterase/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Humanos , Ligantes , Conformação Molecular , Estrutura Molecular , Ligação Proteica
17.
Pak J Biol Sci ; 24(1): 146-150, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33683041

RESUMO

BACKGROUND AND OBJECTIVE: Hepcidin, a key element in iron hemostasis, is a small antimicrobial peptide encoded by the HAMP gene on 19q13. Several studies have revealed that the expression of hepcidin is influenced by single nucleotide polymorphisms located in the promoter region of HAMP. Therefore, this research aimed to study the frequency distribution of HAMP promoter genetic variants and their associations with serum iron, serum transferrin and serum ferritin levels in Saudi Arabian women (aged 15-25). MATERIALS AND METHODS: The study was conducted on 108 female subjects, among whom 50 had normal levels of iron and 58 were iron deficient. All participants were enrolled at the University of Tabuk. The HAMP promoter rs10421768 A>G gene polymorphism (c.-582 A>G) was detected by using an allele-specific or amplification-refractory mutation PCR system. The AS-PCR primers were designed by using Primer3 software. RESULTS: The frequencies of HAMP promoter rs10421768 genotypes AA, AG and GG were 3.45, 96.55 and 0% in the iron-deficient women and 12, 88 and 0% in the healthy women, respectively. The distributions of the HAMP promoter c.-582 A>G genotypes observed between the iron-deficient and normal women were not significantly different (p = 0.239). A significant difference in the HAMP genotype (c.-582 A>G) between the iron-deficient women and healthy women was associated with reduced serum iron (p = 0.049). CONCLUSION: The results indicated that the HAMP genotype (c.-582 A>G) was associated with reduced serum iron in women in northern Saudi Arabia. However, no significant difference was found between healthy women and iron-deficient women.


Assuntos
Anemia Ferropriva/genética , Hepcidinas/genética , Polimorfismo de Nucleotídeo Único , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Ferritinas/sangue , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Ferro/sangue , Fenótipo , Regiões Promotoras Genéticas , Arábia Saudita , Transferrina/metabolismo
18.
Front Nutr ; 8: 592340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33644107

RESUMO

In this study, we initiated an effort to generate information about beef safety in Uganda. Our entry point was to assess by atomic absorption spectrophotometry the levels of essential elements copper (Cu), cobalt (Co), iron (Fe) and zinc (Zn), and non-essential elements lead (Pb), chromium (Cr), nickel (Ni), and cadmium (Cd) in 40 beef samples collected from within and around Soroti (Uganda). The information was used to evaluate the safety of consuming such beef against the World Health Organization (WHO) limits. The latter was accomplished by (i) estimating the daily intake (EDI) of each metal in the study area, (ii) modeling the non-cancer health risk using the target hazard quotient (THQ) and (iii) modeling the cancer risk using the incremental lifetime cancer risk (ILCR). The study finds that the mean concentrations (±95% CI) and EDI were in the order of Fe > Zn > Cr > Ni > Pb > Co > Cu > Cd. Cancer risk was found to be due to Ni > Cr > Cd > Pb and significantly higher in children than adults. The latter particularly demonstrates the importance of Ni poisoning in the study area. Overall, while essential elements in our beef samples were below WHO limits (hence no health risks), non-essential elements had high health and cancer risks due to higher levels of Cr and Ni.

19.
J Med Virol ; 93(5): 2815-2819, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33128396

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a Betacoronavirus that results in a severe fatal respiratory disease; however, it is also associated with mild inapparent infections. The western part of the Kingdom of Saudi Arabia (KSA) contains the holy places where millions of Muslims gathered from all over the world, all year round, with a high probability of mass disease transmission. The aim of this study was to estimate the prevalence of MERS-CoV among military personnel and their families during the period 2014-2019, in the western part of the KSA. A total of 35,203 sputum samples collected from patients with respiratory distress were screened for the presence of MERS-CoV using real-time reverse-transcription polymerase chain reaction in the examined patients. MERS-CoV infections were detected at a very low percentage in the examined patients. Only 42 of the examined subjects (0.12%) were found positive for MERS-CoV. Most infected cases (32/42) cases were detected in 2014, and the rest of the cases were reported in 2015-2019. The cases with fatal consequences (n = 20) were only detected in 2014. It was concluded that there is a very low prevalence of MERS-CoV infections among the military personnel and their families.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Militares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/métodos , Síndrome do Desconforto Respiratório/epidemiologia , Arábia Saudita/epidemiologia
20.
Environ Sci Pollut Res Int ; 28(5): 6195-6206, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32989703

RESUMO

Arsenic (As) exposure is associated with adverse health outcomes to the living organisms. In the present study, the hepato-protective ability of thymoquinone (TQ), the active principle of Nigella sativa seed, or ebselen (Eb), an organoselenium compound, against As intoxication in female rats was investigated. For this purpose, animals were allocated randomly into control, As (20 mg/kg), TQ (10 mg/kg), Eb (5 mg/kg), As+TQ, and As+Eb groups that were orally administered for 28 consecutive days. Arsenic exposure resulted in hepatic oxidative damage which was evidenced by marked decreases in antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)) concomitant with high malondialdehyde (MDA) level. Furthermore, As toxicity induced significant elevations in liver accumulation of As, serum hepatic indices (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB)), and apoptotic marker (B cell lymphoma 2(Bcl2), Bcl-2-associated X protein (Bax), and caspase 3) levels. Additionally, notable increments in hepatic fibrotic markers (epidermal growth factor (EFG) and transforming growth factor beta 1 (TGF-ß1)) associated with high nitric oxide, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) levels were noticed following As intoxication. Biochemical findings were well-supported by hepatic histopathological screening. The co-treatment of As-exposed rats with TQ or Eb considerably improved liver function and antioxidant status together with lessened hepatic As content, inflammation, apoptosis, and fibrosis. The overall outcomes demonstrated that TQ or Eb ameliorates As-induced liver injury through their favorable antioxidant, anti-inflammatory, anti-apoptotic, and fibrolytic properties.


Assuntos
Arsênio , Doença Hepática Induzida por Substâncias e Drogas , Animais , Antioxidantes/metabolismo , Arsênio/metabolismo , Arsênio/toxicidade , Azóis , Benzoquinonas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Feminino , Fígado/metabolismo , Compostos Organosselênicos , Estresse Oxidativo , Ratos
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