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1.
Clin Genet ; 105(4): 364-375, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38129135

RESUMO

Biallelic loss-of-function mutation of NUP210L, encoding a testis-specific nucleoporin, has been reported in an infertile man whose spermatozoa show uncondensed heads and histone retention. Mice with a homozygous transgene intronic insertion in Nup210l were infertile but spermatozoa had condensed heads. Expression from this insertion allele is undefined, however, and residual NUP210L production could underlie the milder phenotype. To resolve this issue, we have created Nup210lem1Mjmm , a null allele of Nup210l, in the mouse. Nup210lem1Mjmm homozygotes show uniform mild anomalies of sperm head morphology and decreased motility, but nuclear compaction and histone removal appear unaffected. Thus, our mouse model does not support that NUP210L loss alone blocks spermatid nuclear compaction. Re-analyzing the patient's exome data, we identified a rare, potentially pathogenic, heterozygous variant in nucleoporin gene NUP153 (p.Pro485Leu), and showed that, in mouse and human, NUP210L and NUP153 colocalize at the caudal nuclear pole in elongating spermatids and spermatozoa. Unexpectedly, in round spermatids, NUP210L and NUP153 localisation differs between mouse (nucleoplasm) and human (nuclear periphery). Our data suggest two explanations for the increased phenotypic severity associated with NUP210L loss in human compared to mouse: a genetic variant in human NUP153 (p.Pro485Leu), and inter-species divergence in nuclear pore function in round spermatids.


Assuntos
Histonas , Infertilidade Masculina , Masculino , Camundongos , Humanos , Animais , Histonas/genética , Histonas/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Espermatogênese/genética , Sêmen/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Infertilidade Masculina/genética
2.
Arch Biochem Biophys ; 755: 109963, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518815

RESUMO

PURPOSE: Despite the effectiveness of ionizing radiation in treating cancer, it can damage healthy tissues in the vicinity. Due to the high radio-sensitivity of testicular tissues, radiation therapy may affect spermatogenesis, which may result in infertility. Hence, in this study testicular damage model is constructed to investigate the mitigation effect of Maca root powder and its potential radioprotective activity through both oxidative and endoplasmic reticulum (ER) stresses, besides the apoptotic pathway. METHODS: Male albino rats were exposed to 6Gy of whole-body gamma radiation single dose. Maca root powder (1 g/kg b.wt./day, by oral gavage) was administered for a week before irradiation, then d-galactose (300 mg/kg, by oral gavage) and Maca daily for another week. RESULTS: Gamma radiation and d-galactose revealed a significant decrease in serum testosterone, sperm count, and motility and higher percentage of the sperm head abnormality, while Maca root treatment maintained all sperm morphology parameters. Maca root treatment demonstrated a notable defense against radiation-induced oxidative stress and ameliorated malonaldehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), glutathione-S-transferase (GST) levels, reduced glutathione (GSH), oxidized glutathione (GSSG) and the ratio of GSH/GSSG in testis tissues. Exposure to gamma rays and d-galactose displayed a significant elevation in GRP78, CHOP, total caspase-3 as well as active (cleaved) caspase-3 levels, whereas treatment with Maca significantly reduced the ER and apoptotic markers levels. Also, Maca improved the histological changes of the disorganized seminiferous tubules induced by irradiation. CONCLUSION: Our findings show for the first time that Maca has a protective effect on male reproductive damage induced by radiotherapy. Maca root reveals anti-apoptotic effect and protection against testicular damage via GRP78/CHOP/caspase-3 pathway.

3.
Saudi Pharm J ; 31(9): 101712, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37601142

RESUMO

Aim and Objectives: The study sought to identify parental trends in children's self-medication, health-seeking behavior, knowledge of self-medication, antibiotic use, and antimicrobial resistance in Asir, Saudi Arabia. Methods: A web-based cross-sectional study was carried out by a survey questionnaire. Snow Ball sampling technique was used to select the Eight hundred and sixteen parents with children in the Asir region by WhatsApp and email, and 650 participants who met the inclusion criteria consented to participate in the study. Results: There were 1809 episodes of childhood illnesses reported during the study period. The mean scores are on knowledge at 8.11 ±â€¯2.43, favorable attitude at 17.60 ±â€¯1.17, and practice was 7.72 ±â€¯1.72, and a significant correlation was found between knowledge, attitude, and practice (KAP) at p = 0.01. Out of 624, the majority of parents showed strong knowledge and proficiency in antibiotics. However, the attitude scores of over 50% towards the usage of antibiotics were subpar. Around 54% of parents were self-medicating their children and 43% were unaware that skipping doses contributes to anti-microbial resistance (AMR). The facilitators for self-medication were male gender (aOR: 2.13; 95% CI: 1.26-3.98, p < 0.05), having more children (aOR: 2.78; 95% CI: 1.27-4.12 p < 0.01), professional qualification (aOR:3.07; 95% CI 1.57- 4.68; p < 0.01), residing in urban area (aOR: 3.17; 95% CI: 2.13-5.61, p < 0.05), working in health care (aOR: 5.99; 95% CI: 1.78-18.2, p < 0.01) and high income (aOR: 3.57; 95% CI: 2.08-6.34, p < 0.05). Conclusions: The findings indicated that the majority of parents had unfavorable views and improper practices of antibiotic usage. Strategic education programs to the targeted population, especially to the parents about side effects of antibiotics, dangerous consequences of self-medication, and crucial AMR concerns must be addressed immediately.

4.
J Biochem Mol Toxicol ; 36(7): e23065, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35377964

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in developing countries. Tripartite motif-59 (TRIM59) a member of the TRIM ubiquitin ligase family, is a surface molecule that regulates biological processes such as cell proliferation, apoptosis, and tumorigenesis. Previous studies reported that TRIM59 expression was upregulated in human CRC, however, the expression pattern and role of TRIM59 in benign colorectal lesions remain unclear. Sixty patients diagnosed with CRC and 60 patients with benign lesions (Crohn's disease, ulcerative colitis, adenoma, and familial adenomatous polyposis) were recruited to the present study. TRIM59 gene expression was assessed by real-time quantitative polymerase chain reaction. Expression of TRIM59 protein and p-AKT were determined using, enzyme-linked immunoassay while p53 expression was detected by immunohistochemistry. Antioxidant/oxidant role of glutathione (GSH)/malondialdehyde (MDA) were evaluated by colorimetric methods in all of the studied groups. Our results showed upregulated expressions of TRIM59 gene and protein levels in CRC tissues and benign colonic lesions compared to nontumor tissues. Their levels were higher in inflammatory compared to noninflammatory bowel lesions. There were significant interrelations among TRIM59 gene expression, protein levels, tumor, node, metastasis staging, and the presence of metastasis (p < 0.0001). Receiver-operator characteristic curve analyses showed that at the cutoff point of 2.5 TRIM59 mRNA expression can discriminate between CRC cases and benign bowel group (area under the curve [AUC]: 0.639, sensitivity: 86.7%, specificity: 41.7%), and between CRC and controls (AUC: 0.962, sensitivity: 90%, specificity: 91.7%). TRIM59 could be a potential biomarker in the early detection, diagnosis, and treatment of benign colonic lesions and CRC.


Assuntos
Neoplasias Colorretais , Metaloproteínas , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Metaloproteínas/genética , Metaloproteínas/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo
5.
IUBMB Life ; 73(2): 362-374, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33332722

RESUMO

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.


Assuntos
Colecalciferol/farmacologia , Cisplatino/farmacologia , Modelos Animais de Doenças , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Uretana/toxicidade , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose , Carcinógenos/toxicidade , Colecalciferol/administração & dosagem , Cisplatino/administração & dosagem , Quimioterapia Combinada , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Nanopartículas/química , Ratos , Ratos Wistar , Transdução de Sinais , Vitaminas/administração & dosagem , Vitaminas/farmacologia
6.
Cytokine ; 138: 155398, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33341003

RESUMO

Obesity has emerged as a leading cause of death in the last few decades, mainly due to associated cardiovascular diseases. Obesity, inflammation, and insulin resistance are strongly interlinked. Lisofylline (LSF), an anti-inflammatory agent, demonstrated protection against type 1 diabetes, as well as reduced obesity-induced insulin resistance and adipose tissue inflammation. However, its role in mitigating cardiac inflammation associated with obesity is not well studied. Mice were divided into 4 groups; the first group was fed regular chow diet, the second was fed regular chow diet and treated with LSF, the third was fed high fat diet (HFD), and the fourth was fed HFD and treated with LSF. Cardiac inflammation was interrogated via expression levels of TNF α, interleukins 6 and 10, phosphorylated STAT4 and lipoxygenases 12 and 12/15. Apoptosis and expression of the survival gene, AMPK, were also evaluated. We observed that LSF alleviated obesity-induced cardiac injury indirectly by improving both pancreatic ß-cell function and insulin sensitivity, as well as, directly via upregulation of cardiac AMPK expression and downregulation of cardiac inflammation and apoptosis. LSF may represent an effective therapy targeting obesity-induced metabolic and cardiovascular complications.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Coração/fisiologia , Inflamação/metabolismo , Insulina/metabolismo , Miocárdio/enzimologia , Miocárdio/metabolismo , Obesidade/metabolismo , Pentoxifilina/análogos & derivados , Tecido Adiposo/metabolismo , Animais , Apoptose , Glicemia/metabolismo , Peso Corporal , Modelos Animais de Doenças , Resistência à Insulina/fisiologia , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pentoxifilina/farmacologia , Transdução de Sinais , Regulação para Cima
7.
Mol Biol Rep ; 48(5): 4601-4610, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34132944

RESUMO

Colorectal cancer is one of the most prevalent and deadly cancers worldwide. MicroRNAs are short single stranded non-coding RNAs that play important roles in carcinogenesis, tumor growth and tumor survival. Circulating microRNAs are increasingly becoming efficient and important biomarkers for several types of cancers. Herein, we aim to evaluate the diagnostic potentials of plasma microRNA-211 and microRNA-25 in colorectal cancer patients. Forty-four patients diagnosed with colorectal cancer and 40 healthy controls were recruited for the present study. Expressions of circulating microRNAs -211 and 25 were assessed by quantitative real-time polymerase chain reaction (RT-qPCR). Expression of transforming growth factor-beta, a key factor in tumorigenesis and a key inducer of epithelial to mesenchymal transition was assessed by enzyme-linked immunosorbent assay (ELISA) in patients' tissue and plasma. Our results demonstrated upregulated expressions of plasma microRNAs-211 and 25 correlated with the high transforming growth factor-beta (TGF-ß1) expression in patients. In addition, plasma levels were positively correlated with lymph node metastasis. Moreover, receiver operating characteristic analysis demonstrated the reliability of microRNAs-211 and 25 for discriminating colorectal cancer patients from healthy individuals. MicroRNA-211 and microRNA-25 might have a tumorigenic role in colorectal cancer and their plasma levels could be potential biomarkers in its diagnosis.


Assuntos
Neoplasias Colorretais/diagnóstico , MicroRNAs/genética , Fator de Crescimento Transformador beta1/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/sangue
8.
J Mol Cell Cardiol ; 143: 15-25, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32311415

RESUMO

Metabolic (Met) syndrome is characterized by hypertension, insulin resistance and dyslipidaemia with high risk of cardiovascular disease. Endoplasmic reticulum (ER) stress is a key contributor in the pathogenesis of Met syndrome. The current study investigates the effect of Tauroursodeoxycholate (TUDCA), an ER stress inhibitor, on Met syndrome-induced cardiovascular complications and the possible underlying signalling mechanisms. Met syndrome was induced in rats, which were then treated with TUDCA. Body weight, blood pressure, glucose tolerance and insulin tolerance tests were performed. ER stress, survival and oxidative stress markers were measured in heart and aorta tissue. The results showed that TUDCA improved metabolic parameters in rats with Met syndrome. Treatment mitigated the Met syndrome-induced cardiovascular complications through upregulating survival markers and downregulating ER and oxidative stress markers. These results highlight the protective effect of ER stress inhibition as a potential target in the management of cardiovascular complications associated with Met syndrome.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Animais , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Endotélio/metabolismo , Imuno-Histoquímica , Síndrome Metabólica/etiologia , Fenótipo , Ratos , Ácido Tauroquenodesoxicólico/farmacologia
9.
Ecotoxicol Environ Saf ; 171: 539-548, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30641315

RESUMO

Extensive use of fertilizers and pesticides led to dangerous ecological effects and therefore the biological approaches have been widely recommended to prevent further deterioration for the environment. The current study was conducted to explore the potentiality of using single or combined inoculations by mycorrhizae, Bacillus subtilis and Pseudomonas fluorescence for controlling the infection of common bean plants with Sclerotium rolfsii on one hand and as bio-fertilizers for improving plants nutritional status on the other hand. The soil of study was mildly infected with S. rolfsii and contained high total-P content. Thus, minimal P inputs were added to the inoculated soil in the form of rock phosphate. Activities of plant defense enzymes i.e. chitinase, peroxidase and polyphenol oxidase were determined under the greenhouse conditions and the results obtained herein indicated that activities of such enzymes increased significantly owing to bio-agent inoculations. In this concern, combined treatments resulted in further significant increases over the single ones. A field study was then conducted for two successive years and the results reveal that single inoculations increased straw and green pod yields as well as the uptake of P and Fe by plants as compared with the non-inoculated treatment. Combined inoculants recorded further significant increases in these parameters even when compared with the fungicide treated plants. Generally, straw and pod yields obtained from the second growing season were significantly higher than those attained in the first growing one. Our study confirms the success of the used bio-treatments in minimizing soil pollution through fertilizer and/or pesticide inputs.


Assuntos
Basidiomycota/patogenicidade , Micorrizas/fisiologia , Phaseolus/crescimento & desenvolvimento , Microbiologia do Solo , Bacillus subtilis/fisiologia , Agentes de Controle Biológico , Fertilizantes , Phaseolus/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Pseudomonas fluorescens/fisiologia , Solo/química , Poluentes do Solo/análise
10.
Ecotoxicol Environ Saf ; 186: 109783, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31629192

RESUMO

Chemical fungicides are effective tools in controlling plant pathogens; however, these chemicals can, on the other hand, distress the ecosystem. Accordingly, the current research investigates the potentiality of substituting traditional chemical fungicides by inducing plant resistance against infection with soil-born pathogens i.e. Sclerotium rolfsii in the presence of mycorrhizae (AMF) as plant inoculants and one of the following amendments: humic acid, sulphex (a mixture of canola oil and diluted sulphuric acid) and paclobutrazol (ABZ). To attain the abovementioned objective, a field (mildly infected with S. rolfsii) was cultivated with Helianthus tuberosus (a perennial plant belongs to the Asteraceae family) for two successive seasons (2014 and 2015) and the above-mentioned treatments were tested for their feasibilities in controlling S. rolfsii infection against the chemical fungicide "Vitavax-200" either solely or in combinations in a complete randomized block design. Inoculating plants with AMF or amending soils with either humic acid, Sulphex or ABZ solely increased significantly the activities of plant defense enzymes by approximately 1.5-2.1 folds higher than the control treatment. These treatments also improved NPK availability in soil and; hence, increased their contents within plant tubers. Consequently, these treatments decreased the disease incidence and severity caused by S. rolfsii while improved shoot biomass and tuber yield. In spite of that, these results stood below the prospective of the fungicide treatment. The integrated treatments i.e. "humic acid + AMF", "Sulphex + AMF" and "ABZ + AMF" caused further significant improvements in both NPK availabilities in soil and plant areal bio-masses. This probably induced further plant resistance against the investigated soil-borne pathogen while recorded insignificant variations in disease incidence and severity when compared with the fungicide treatment. Moreover, the integrated treatments increased the tuber yields beyond those attained for the fungicide treatment. Accordingly, such integrated strategies can completely substitute the chemical fungicides; thus, minimize their negative impacts on the ecosystem.


Assuntos
Basidiomycota/fisiologia , Resistência à Doença/fisiologia , Recuperação e Remediação Ambiental/métodos , Helianthus/microbiologia , Micorrizas/fisiologia , Microbiologia do Solo , Biomassa , Fungicidas Industriais/análise , Helianthus/metabolismo , Helianthus/fisiologia , Nutrientes/análise , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Distribuição Aleatória , Solo/química
11.
Am J Pathol ; 187(11): 2590-2601, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28837799

RESUMO

Recently, IL-12 emerged as a critical player in type 2 diabetes complications. We previously reported that ischemia-induced angiogenesis is compromised in type 2 diabetic mice. In this study, we determined that IL-12 disruption rescued angiogenesis and arteriogenesis in type 2 diabetic mice. To induce type 2 diabetes, wild-type (WT), p40IL-12-/- (p40-/-), and p35IL-12-/- (p35-/-) mice were fed a high-fat diet (HFD) for 12 weeks. Body weight, glucose test tolerance, and insulin test tolerance were assessed. After 12 weeks of an HFD, the femoral artery was ligated and blood flow recovery was measured every week for 4 weeks. WT, p40-/-, and p35-/- mice fed an HFD become obese after 12 weeks and exhibit glucose intolerance and insulin resistance. Blood flow recovery was fully restored in 2 to 3 weeks after femoral artery ligation in all groups of mice fed a normal diet. However, after 12 weeks of an HFD, blood flow recovery was compromised in WT mice, whereas it was fully recovered in p40-/- and p35-/- mice. The mechanism of blood flow recovery involves an increase in capillary/arteriole density, endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2 signaling, and a reduction in oxidative stress and inflammation. The disruption of IL-12 promotes angiogenesis and increases blood flow recovery in obese type 2 diabetic mice by an endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2/oxidative stress-inflammation-dependent mechanism.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Endotélio Vascular/metabolismo , Interleucina-12/metabolismo , Neovascularização Patológica/metabolismo , Animais , Dieta Hiperlipídica , Endotélio Vascular/patologia , Resistência à Insulina/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Estresse Oxidativo
12.
Ecotoxicol Environ Saf ; 162: 348-353, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30005408

RESUMO

The current study aims to investigate the implications of amending a soil contaminated with Cd with peanut residues biochar (BP) solely or in combination with cow manure (CMPB) at different rates on phytotoxicity of Cd for wheat plants and its distribution in a mine contaminated soil. Soil pH and EC increased progressively in soils amended with either PB or CMPB. Exchangeable Cd was decreased while its non-exchangeable fractions were increased. Dry weights of wheat straw, roots and grains increased when soils amended with either PB or CMPB, especially at the higher application rate. Such increases were correlated significantly with the extractable soil-Cd. Concentrations of Cd in roots were higher than those in straw; whereas, the concentrations in grains seemed to be the lowest. Generally, values of bio-concentration and translocation factors did not exceed "1" and decreased with application of either PB or CMPB. In conclusion, enriching biochar with cow manure is a recommended strategy to reduce Cd uptake and translocation to straw and seeds. Moreover, Concentrations of Cd did not exceed the permissible levels in grains when soils amended with the highest rate of CMPB.


Assuntos
Cádmio/química , Carvão Vegetal , Esterco , Poluentes do Solo/química , Solo/química , Triticum/química , Animais , Cádmio/análise , Bovinos , Fracionamento Químico , Recuperação e Remediação Ambiental/métodos , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Poluentes do Solo/análise , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
13.
Biochim Biophys Acta Mol Basis Dis ; 1863(9): 2120-2125, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28572006

RESUMO

Febrile seizures (FS) are convulsions associated with high body temperature. It has a high incidence in children from the age of 6months to 5years and may have adverse consequences in adulthood. The experimental model of FS could be induced in animals via hyperthermia. The present study was designed to investigate persistent electroencephalographic (EEG), neurochemical and behavioral alterations in adult animals that had experienced complex FS at their immature age. EEG signals were obtained from the cortex of both FS and control normothermic groups of animals. A spectrophotometric assay was carried out to determine oxidative stress parameters (malondialdehyde, nitric oxide, reduced glutathione) and acetylcholinesterase activity in the cortex and hippocampus of FS and control animals. Behavioral assessment of seizure threshold and severity were investigated via a sub-convulsive dose of nicotine in adult animals. Alterations in the oxidant/antioxidant system and AChE activity were obtained in the cortex and hippocampus of FS animals in comparison to control animals. EEG spectral analysis displayed significant changes in all EEG frequency bands. A decrease in seizure latency and an increase in seizure severity were also observed. The present study provides evidence for long-lasting abnormalities in the cortex and hippocampus of adult animals subjected to complex FS at their developmental age, which may be correlated to the underlying mechanism of epileptogenesis and its related co-morbidities.


Assuntos
Comportamento Animal , Eletrocardiografia , Hipocampo/fisiopatologia , Convulsões Febris/fisiopatologia , Acetilcolinesterase/metabolismo , Animais , Modelos Animais de Doenças , Proteínas Ligadas por GPI/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Nicotina/efeitos adversos , Nicotina/farmacologia , Ratos , Ratos Wistar , Convulsões Febris/induzido quimicamente , Convulsões Febris/metabolismo , Convulsões Febris/patologia , Fatores de Tempo
14.
Biochim Biophys Acta ; 1853(10 Pt A): 2404-10, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26036345

RESUMO

We previously determined that augmented EGFR tyrosine kinase (EGFRtk) impairs vascular function in type 2 diabetic mouse (TD2). Here we determined that EGFRtk causes vascular dysfunction through NADPH oxidase activity in TD2. Mesenteric resistance arteries (MRA) from C57/BL6 and db-/db- mice were mounted in a wired myograph and pre-incubated for 1h with either EGFRtk inhibitor (AG1478) or exogenous EGF. The inhibition of EGFRtk did not affect the contractile response to phenylephrine-(PE) and thromboxane-(U46619) or endothelium-dependent relaxation (EDR) to acetylcholine in MRA from control group. However, in TD2 mice, AG1478 reduced the contractile response to U46619, improved vasodilatation and reduced p22phox-NADPH expression, but had no effect on the contractile response to PE. The incubation of MRA with exogenous EGF potentiated the contractile response to PE in MRA from control and diabetic mice. However, EGF impaired the EDR and potentiated the vasoconstriction to U46619 only in the control group. Interestingly, NADPH oxidase inhibition in the presence of EGF restored the normal contraction to PE and improved the EDR but had no effect on the potentiated contraction to U46619. Vascular function improvement was associated with the rescue of eNOS and Akt and reduction in phosphorylated Rho-kinase, NOX4 mRNA levels, and NADPH oxidase activity. MRA from p47phox-/- mice incubated with EGF potentiated the contraction to U46619 but had no effect to PE or ACh responses. The present study provides evidence that augmented EGFRtk impairs vascular function by NADPH oxidase-dependent mechanism. Therefore, EGFRtk and oxidative stress should be potential targets to treat vascular dysfunction in TD2.


Assuntos
Grupo dos Citocromos b/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Angiopatias Diabéticas/enzimologia , Receptores ErbB/metabolismo , NADPH Oxidases/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Grupo dos Citocromos b/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/patologia , Receptores ErbB/genética , Camundongos , Camundongos Knockout , NADPH Oxidase 4 , NADPH Oxidases/genética , Fenilefrina/farmacologia , Quinazolinas/farmacologia , Tirfostinas/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/genética , Vasodilatação/efeitos dos fármacos , Vasodilatação/genética
15.
Am J Geriatr Psychiatry ; 23(2): 160-70, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25081819

RESUMO

OBJECTIVE: This study compares different nonpharmacological interventions for persons with behavioral symptoms and dementia on frequency of use and perceived efficacy in terms of change in behavior and interest. METHODS: Participants were 89 nursing home residents from six Maryland nursing homes with a mean age of 85.9 years (SD: 8.6 years). Research assistants presented interventions tailored to the participants' needs and preferences in a pre-intervention trial phase and in an intervention phase. The impact of each intervention on behavioral symptoms and on the person's interest was rated immediately after the intervention by a research assistant. RESULTS: The most utilized interventions in both trial and treatment phases were the social intervention of one-on-one interaction, simulated social interventions such as a lifelike doll and respite video, the theme intervention of magazine, and the sensory stimulation intervention of music. In contrast, the least utilized interventions in both phases were sewing, fabric book, and flower arrangement. Interventions with the highest impact on behavioral symptoms included one-on-one social interaction, hand massage, music, video, care, and folding towels. Other high impact interventions included walking, going outside, flower arranging, food or drink, sewing, group activity, book presentation, ball toss, coloring or painting, walking, and family video. CONCLUSIONS: The results provide initial directions for choosing specific interventions for persons with dementia and also demonstrate a methodology for increasing knowledge through ongoing monitoring of practice.


Assuntos
Sintomas Comportamentais/terapia , Demência/terapia , Psicoterapia/métodos , Idoso , Demência/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Fatores Sexuais , Resultado do Tratamento
16.
Lasers Med Sci ; 30(1): 109-15, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25030404

RESUMO

Photodynamic therapy (PDT) is regarded as a treatment option for basal cell carcinoma (BCC). The aim of this study is to investigate the efficacy of methylene blue (MB)-based PDT in patients suffering from nodular or ulcerative BCCs. This study is a prospective clinical trial with a 6-months follow-up. The study setting is at the Dermatology Clinic at NILES, Cairo University, Egypt. Seventeen patients complaining of nodular BCC (nBCC) and three patients complaining of ulcerative BCC (uBCC) were taken as samples. Methylene blue, the photosensitizer, was prepared in two different formulas: liposomal-loaded MB (LMB) was prepared and formulated in hydrogel (MB 0.2%) to be used topically alone for treating BCCs <2 cm in diameter or to be combined with intralesional injection (ILI) of free MB 2% aqueous solution for treating BCCs ≥2 cm in diameter. A session was performed every 2 weeks until complete response (CR) of the lesion or for a maximum of six sessions. Clinical assessments of clinical improvement, dermatological photography, monthly follow-up visits for 6 months, and skin biopsy after 3 months of follow-up to confirm the response, recurrence, or both in cases in which the clinical evaluation was ambiguous. Seventeen patients of the 20 completed the study, 11 patients achieved CR with very good cosmetic outcome, photosensitizer tolerance, and minimal reported side effects. MB is a cheap promising alternative photosensitizer for PDT of nBCC.


Assuntos
Carcinoma Basocelular/tratamento farmacológico , Azul de Metileno/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Ácido Aminolevulínico/uso terapêutico , Carcinoma Basocelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia , Estudos Prospectivos , Indução de Remissão , Neoplasias Cutâneas/patologia , Resultado do Tratamento
17.
Int J Biol Macromol ; 257(Pt 1): 128597, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38056740

RESUMO

Breast cancer is the second most prevalent cancer affecting both males and females, comprising nearly 30 % of all cancer cases. While chemotherapeutic agents, such as cisplatin (Cis), have proven successful in cancer treatment, concerns persist regarding their efficacy and the potentially dangerous side effects. Consequently, there is a crucial and ongoing need to develop approaches that minimize side effects associated with chemotherapy. In the present work, various types of nanoparticles (NPs) were synthesized and loaded with Cis. Cis was conjugated with nanocarriers such as zinc oxide (ZnO), ZnO modified with mandelic acid and graphene oxide (GO), chitosan (CS), and CS modified with ZnO and GO to enhance the selectivity of Cis towards cancer cells. Zeta potentials and particles size were assessed using electrophoretic light scattering and dynamic light scattering. NPs were characterized using transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. The impact of standalone Cis as well as its nanoconjugated form on the behavior of MCF-7 cell line was investigated using WST-1 cell proliferation and apoptosis/necrosis assays. Experimental findings revealed that among the various NPs tested, ZnO, and CS NPs exhibited the highest loading percentage of Cis, surpassing the loading percentages achieved with other NPs. Cytotoxicity assay showed the enhanced effect of Cis when conjugated with ZnO and CS NPs. Flow cytometry-based assays and confocal microscopy confirmed that ZnO/Cis and CS/Cis induced apoptosis. The cisplatin-nanocomplex exhibited a descending order of early apoptosis and late apoptosis in the following order: ZnO, Cis, CS, ZnO-M, CS-GO, ZnO-GO, CS-ZnO, and CS-ZnO, Cis, CS, CS-GO, ZnO-M, ZnO, ZnO-GO, respectively. None of the nanoparticle complexes displayed a significant percentage of necrotic cells, with the highest percentage reaching 4.65 % in the case of CS-GO/Cis.


Assuntos
Antineoplásicos , Neoplasias da Mama , Cisplatino , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Quitosana/farmacologia , Cisplatino/farmacologia , Nanopartículas/química , Óxido de Zinco/farmacologia , Masculino , Antineoplásicos/farmacologia
18.
Cureus ; 16(5): e59534, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826953

RESUMO

A total of 22 patients with cleft palate aged 8 to 12 years were selected and categorized into two groups: the first group was treated with alternate rapid maxillary expansion and constriction (Alt-RAMEC) using an expander with differential opening (EDO) and facemask, while the second group was treated using slow maxillary expansion (SME) using an EDO. Finally, the pharyngeal airway volume in the two groups was compared using cone beam computed tomography (CBCT). CBCT scans were performed before expansion and six months following the expansion. Alveolar crest level, maxillary breadth, nasal cavity width, arch width, inclination of the molar teeth, buccal and palatal alveolar bone thickness, and maxillary alveolar width were all assessed. Paired t-tests (p=0.05) were applied to compare interphase data. The two groups showed a non-significant difference in terms of nasopharyngeal volume (cm3), oropharyngeal volume (cm3), and overall pre- and post-treatment results (p>0.005). Results of comparison of pre- and post-treatment periods in the Alt-RAMEC group revealed a significantly higher cleft volume (cm3) (p=0.001). Results of comparison of pre- and post-treatment periods in the SME group revealed a substantial rise in cleft volume (cm3) (p=0.003). Results from a comparison of the cleft volume (cm3) between the two study groups pre- and post-intervention revealed a non-significant difference (p=0.200 and 0.054, respectively).

19.
J Multidiscip Healthc ; 17: 867-876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434481

RESUMO

Background: Cutaneous Leishmaniasis (CL) is a vector-borne skin infection that remains prevalent in regions with poor socioeconomic conditions. Stigmatization occurs when individuals with physical or psychological disorders interact with societal stereotypes. The aim of this study was to explore the perceived social stigma surrounding CL among people residing in Hubuna, Saudi Arabia. Methods: This cross-sectional community-based survey recruited 618 individuals aged 18 years and above using the snowball sampling technique to reach hidden cases within the target population. Data was collected using a self-administered questionnaire and the Explanatory Model Interview Catalogue for Perceived Social Stigma (EMIC-SS-12) was used to assess the level of perceived social stigma. It includes questions on demographic variables, behaviors, and experiences. The analysis was performed using SPSS. Results: The study included 618 participants, the majority of whom were women and girls (54.2%), with a mean age of 28 ± 12.7 years. The median score for perceived social stigma was 26.0. Only 2.1% (n = 13) of participants had the highest EMIC-SS-12 score of 36, while 7.6% (n = 47) scored zero. The mean score for overall perceived social stigma was 1.89 ± 0.91, while the mean score for experienced stigma was 1.99 ± 1.02. Univariate analysis showed that sex, employment, location of lesions, and number of lesions were insignificantly associated with stigmatization (P-value < 0.05), because these associations were uncertain because the CI includes or very close to 1. Conclusion: The study reveals insights into stigmatization associated with CL in the Habuna area of Saudi Arabia. It found that the median of perceived social stigma was 26. Factors such as sex, employment status, and location of the lesion are uncertainly associated with stigma. It is crucial to explore negative behaviors and perceptions and develop suitable health education programs.

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