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Nephrotoxicity is a common side effect arising from exposure to drugs or toxins. The study investigates the therapeutic effects of Thunbergia alata and Thunbergia erecta flowers on diclofenac-induced renal injury. Secondary metabolite characterization by positive mode high-resolution-ESI (LC-HR-ESI-MS) was followed by assessing their renal protection against diclofenac-induced damage and molecular docking studies. Using positive LC-HR-ESI-MS, 18 compounds from T. erecta and T. alata were identified. Diclofenac administration induced significant deterioration of all parameters in the kidney in addition to renal tissue contents of several inflammatory markers. The flower extracts of T. alata and T. erecta showed a clear improvement in the treated groups compared to the diclofenac-control group. The results were confirmed by histopathological examinations followed by immunohistochemical determination of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2-related factor 2 (Nrf2), and transforming growth factor beta 1 (TGF-ß1) expression. Furthermore, a protein-protein network to understand the complex interplay between the target proteins and their counterparts was done in addition to a molecular docking study of the de-replicated compounds in the active sites of NF-κB, TGF-ß1, and VEGFR.
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The accumulation of chromium in renal tissues promotes the generation of reactive oxygen species (ROS), leading to oxidative stress, genomic and cellular harm, and ultimately necrotic and apoptotic cell death induced by free radicals. Hence, the utilization of antioxidant phytochemicals becomes crucial for cellular defense against oxidative damage. This study endeavors to explore the potential protective effects of an aqueous avocado seed extract (ASE) on rabbit kidneys exposed to chromium-induced damage. Fifteen adult rabbits were distributed into three groups: Group 1 was kept as the control. The second and third groups received a daily dose of K2Cr2O7 (5 mg/kg) intraperitoneally for 2 weeks. While the third group was given an oral dose of ASE (400 mg/kg). In rabbits administered with Cr (VI), kidney homogenates showed a marked increase in Malondialdehyde (MDA) (69.3 ± 4.1 nmol/g) along with a decrease in glutathione (59 ± 5.8 nmol/mg) content and the activity superoxide dismutase (SOD) (0.5 ± 0.05 U/mg protein), glutathione peroxidase (GPx) (16.7 ± 1.1 µmol/mg protein), and catalase (CAT) (73.8 ± 3.9 U/g protein) compared to the levels in control group. Also, the gene expression data for the enzymes SOD, GPx, and CAT dropped dramatically in kidney tissue following Cr (VI) injection. Additionally, Bowman's capsule and glomerulus showed degenerative alterations in the kidney's histopathology and immunohistochemistry. ASE treatment when administered along with Cr (VI) enhanced the activity and gene expression of antioxidant enzymes and improved histopathological conditions. The findings of this study unequivocally show that avocado seed extract, which is rich in phenolic derivatives, is a potent nephroprotective agent that inhibits nephrotoxicity induced by Cr (VI) in rabbits.
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INTRODUCTION: Ankle sprains are the second most common sports injury after knee injuries, with about 85% of them affecting the lateral ankle ligaments. These injuries are particularly prevalent in sports like basketball and volleyball. PURPOSE: To investigate the effect of Aquatic therapy as an early rehabilitation protocol for elite athletes with acute lateral ankle sprain grade III on back-to-sport time, dynamic balance, pain, Athletic performance, and muscle power compared to land-based exercise training. METHODS: Thirty elite athletes have ankle sprain grade III with sprain onset from 1 to 7 days, their age ranges from 18-30 years old were recruited. All participants are professional athletes; mainly participating in above-head sports such as volleyball and basketball. The patients were randomly allocated into two treatment groups: Group I (control group): 15 patients received a conventional physical therapy program of structured therapeutic exercise program, manual therapy and land-based exercises, in addition to external support, and Group II (Aquatic therapy group): 15 patients received aquatic training. Visual Analog Scale (VAS) was used to measure the pain intensity, while the dynamic balance was measured by the Star Excursion Balance Test. Athletic performance was measured by HOP Tests (Single, Triple, 6-m, and Cross-over hops) aided by the Agility T-Test (ATT) and Illinois Agility Test (IAT). Muscle power was tested by a Single Leg Press. Finally, back to sports time was recorded for each participant in both groups. RESULTS: There was a significant interaction effect of Aquatic therapy and time for VAS (p < 0.001), single hop (p < 0.001), triple hop (p < 0.001), cross-over hop (p < 0.001), IAT (p = 0.019) and ATT (p < 0.001) of both affected and nonaffected. There was no significant interaction effect of Aquatic therapy and time for 6-MHT of affected (p = 0.923), and nonaffected (p = 0.140). There was a significant main effect of time for all dependent variables (p < 0.001) except for 6-MHT of affected (p = 0.939), nonaffected (p = 0.109), and IAT (p = 0.099). The Star excursion dynamic balance test (SEBT) and Single leg press revealed a significant difference between groups on affected and non-affected sides (p < 0.001*). Lastly and most importantly the back-to-sport time revealed a significant difference in the return-to-sport time in favor of the Aquatic therapy group who returned faster than the control group (p < 0.001*). CONCLUSION: Aquatic therapy is more effective than traditional protocols regarding early rehabilitation of acute ankle sprain grade III in Elite professional athletes for reducing pain intensity, improving dynamic balance and athletic performance and power and accelerating their return to sports time. Because aquatic therapy produces better outcomes, it is advised to be included in the rehabilitation programs of athletic patients with acute ankle sprains grade III.
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Traumatismos do Tornozelo , Humanos , Traumatismos do Tornozelo/reabilitação , Traumatismos do Tornozelo/terapia , Traumatismos do Tornozelo/fisiopatologia , Adulto Jovem , Masculino , Adulto , Adolescente , Feminino , Modalidades de Fisioterapia , Terapia por Exercício/métodos , Entorses e Distensões/reabilitação , Entorses e Distensões/fisiopatologia , Traumatismos em Atletas/reabilitação , Traumatismos em Atletas/terapia , Traumatismos em Atletas/fisiopatologia , Atletas , Hidroterapia/métodos , Equilíbrio Postural , Desempenho Atlético/fisiologia , Resultado do Tratamento , Voleibol/lesõesRESUMO
Monitoring and assessing groundwater quality and quantity lays the basis for sustainable management. Therefore, this research aims to investigate various factors that affect groundwater quality, emphasizing its distance to the primary source of recharge, the Nile River. To this end, two separate study areas have been considered, including the West and West-West of Minia, Egypt, located around 30 and 80 km from the Nile River. The chosen areas rely on the same aquifer as groundwater source (Eocene aquifer). Groundwater quality has been assessed in the two studied regions to investigate the difference in quality parameters due to the river's distance. The power of machine learning to associate different variables and generate beneficial relationships has been utilized to mitigate the cost consumed in chemical analysis and alleviate the calculation complexity. Two adaptive neuro-fuzzy inference system (ANFIS) models were developed to predict the water quality index (WQI) and the irrigation water quality index (IWQI) using EC and the distance to the river. The findings of the assessment of groundwater quality revealed that the groundwater in the west of Minia exhibits suitability for agricultural utilization and partially meets the criteria for potable drinking water. Conversely, the findings strongly recommend the implementation of treatment processes for groundwater sourced from the West-West of Minia before its usage for various purposes. These outcomes underscore the significant influence of surface water recharge on the overall quality of groundwater. Also, the results revealed the uncertainty of using sodium adsorption ratio (SAR), Sodium Percentage (Na%), and Permeability Index (PI) techniques in assessing groundwater for irrigation and recommended using IWQI. The developed ANFIS models depicted perfect accuracy during the training and validation stages, reporting a coefficient of correlation (R) equal to 0.97 and 0.99 in the case of WQI and 0.96 and 0.98 in the case of IWQI. The research findings could incentivize decision-makers to monitor, manage, and sustain groundwater.
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Água Subterrânea , Qualidade da Água , Água Subterrânea/química , Egito , Rios/química , Monitoramento Ambiental , Lógica Fuzzy , Poluentes Químicos da Água/análiseRESUMO
Recent national reports have indicated an increasing trend of dental decay among school-aged children. National school-based data are required to guide decision-making to ensure effective public health efforts to manage dental decay. This study aimed to assess the prevalence of dental decay among school-age children in Saudi Arabia and explore the possible link between dental decay and weight status. This was a cross-sectional analysis of a national sample including 1,134,317 Saudi children in the 1st, 4th, 7th, and 10th grades who participated in a national school screening program. Data for weight, height, body mass index (BMI), dental decay prevalence, and decayed, missing, and filled teeth (DMFT) index were analysed. An independent t-test, one-way analysis of variance, and chi-square test were used to compare the means, while Pearson's r correlation and multiple linear regression were used to examine the relationships between the study variables. The prevalence of dental decay was 24.20%, and dental decay was the highest among female students (26.5%), students in primary school (25.9%), students living in the eastern region (35.2%), in the administrative capital (27.6%), and in rural areas (23.4%). Dental decay was the highest among students who were underweight. Female sex and living in rural areas significantly predicted higher DMFT while being overweight/obese significantly predicted lower DMFT. Dental decay is highly prevalent among underweight students, female students, and students living in rural areas and the eastern regions of Saudi Arabia. To reduce the prevalence of dental decay and related health disparities, dental health screening programs should be designed to detect dental decay early among children at high risk due to abnormal BMIs and sociodemographic factors. In addition, dental health screening and management programs should utilize standardized dental decay assessment methods and ethnically representative growth charts.
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Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.
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Neoplasias da Mama , Paclitaxel , Humanos , Feminino , Paclitaxel/efeitos adversos , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP3A/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genótipo , Sistema Enzimático do Citocromo P-450/genéticaRESUMO
World Health Day underscores the scientific community's commitment to achieving health equity for all. It is paramount to eliminate bias in research that has traditionally focused on men, neglecting the specific needs of diverse populations. Innovative clinical trial designs are being developed with more inclusive enrollment. Ensuring equitable access to essential antibiotics, coupled with robust infection prevention and control measures, is vital to safeguarding public health. The pursuit of health equity extends beyond the realm of medicine. Investments in local food production and robust social safety nets are critical for mitigating the effects of climate change on access to healthy diets. Additionally, in times of polycrisis, prioritizing the unique needs of children and empowering community-led healthcare initiatives in conflict zones are essential steps. By taking these actions, we can move closer to realizing everyone's fundamental right to health.
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Saúde Global , Equidade em Saúde , Humanos , Serviços de Saúde Comunitária , Grupos Populacionais , Saúde PúblicaRESUMO
Tribulus terrestris L. (Tt) has been recently gaining attention for its pharmacological value, including its neuroprotective activities. In this study, we explore the neuroprotective effects of a Tribulus terrestris extract in a zebrafish (Danio rerio) model of scopolamine (SCOP)-induced memory impairment and brain oxidative stress. SCOP, an anticholinergic drug, was employed to replicate fundamental aspects of Alzheimer's disease (AD) in animal models. The fish were treated with ethanolic leaf extract (ELE) from Tt (1, 3, and 6 mg/L) for 15 days. SCOP (100 µM) was administered 30 min before behavioral tests were conducted. Molecular interactions of the major compounds identified via UPLC-PDA/MS in Tt fractions with the active site of acetylcholinesterase (AChE) were explored via molecular docking analyses. Terrestrosin C, protodioscin, rutin, and saponin C exhibited the most stable binding. The spatial memory performance was assessed using the Y-maze test, and memory recognition was examined using a novel object recognition (NOR) test. Tt extract treatment reversed the altered locomotion patterns that were caused by SCOP administration. Biochemical analyses also verified Tt's role in inhibiting AChE, improving antioxidant enzyme activities, and reducing oxidative stress markers. The present findings pave the way for future application of Tt as a natural alternative to treat cognitive disorders.
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Introduction: Citrus sinensis L. is a candidate plant with promising antimicrobial potential. In the current study, the phytochemical investigation of C. sinensis leaf extract led to the isolation of three coumarins, namely bergapten, xanthotoxin, and citropten. Methods: The chemical structures of the isolated coumarins were elucidated using NMR and ESI-MS techniques. The total aqueous ethanol leaf extract and the isolated coumarins were evaluated for their antimicrobial effects against Helicobacter pylori using the MTT-micro-well dilution method and its anti-biofilm activity using MBEC assay, as compared to clarithromycin. Results: The results showed that citropten scored the lowest MIC value at 3.9 µg/mL and completely inhibited the planktonic growth of H. pylori. In addition, it completely suppressed H. pylori biofilm at 31.25 µg/mL. These findings have been supported by molecular docking studies on the active sites of the H. pylori inosine 5'-monophosphate dehydrogenase (HpIMPDH) model and the urease enzyme, showing a strong binding affinity of citropten to HpIMPDH with seven hydrogen bonds and a binding energy of -6.9 kcal/mol. Xanthotoxin and bergapten showed good docking scores, both at -6.5 kcal/mol for HpIMPDH, with each having four hydrogen bondings. Furthermore, xanthotoxin showed many hydrophobic interactions, while bergapten formed one Pi-anion interaction. Concerning docking in the urease enzyme, the compounds showed mild to moderate binding affinities as compared to the ligand. Thus, based on docking results and good binding scores observed with the HpIMPDH active site, an in-vitro HpIMPDH inhibition assay was done for the compounds. Citropten showed the most promising inhibitory activity with an IC50 value of 2.4 µM. Conclusion: The present study demonstrates that C. sinensis L. leaves are a good source for supplying coumarins that can act as naturally effective anti-H. pylori agents.
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BACKGROUND: Elevated serum levels of MMP-13 are linked to tumor growth and metastasis, while miR-138 dysregulation is observed in breast cancer cases. The aim of this study is to investigate the expression of miR-138 and MMP-13 levels as potential biomarkers for the prognosis of breast cancer. PATIENTS AND METHOD: In this retrospective case-control study, 119 female subjects were recruited and divided into three groups. MMP-13 level was measured using Enzyme Linked Immunosorbent Assay (ELISA), while real-time PCR technique was employed to quantify miR-138 expression. RESULTS: Both non-metastatic and metastatic groups showed significantly higher levels of serum MMP-13 compared to other groups. MMP-13 levels are significantly increased among patients with advanced tumor size, lymph node metastasis, and triple-negative breast cancer cases. An inverse significant association between MMP-13 levels and response to treatment was observed. Expression of miR-138 underwent a significant down-regulation in breast cancer patients, and a statistically significant association was established between miR-138 expression and triple-negative breast cancer cases. A positive association was detected between the increase in miR-138 expression and the good response to treatment. The expression of miR-138 was inversely correlated with the MMP-13 levels. CONCLUSION: MMP-13 levels were significantly higher in breast cancer, especially in advanced cases, suggesting its role in promoting tumor invasion and metastasis. MiR-138 was down-regulated in breast cancer, especially in triple-negative breast cancer patients, rendering it a promising biomarker for triple-negative breast cancer. Modulation of miR-138 expression and MMP-13 levels may represent therapeutic targets for breast cancer.
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Neoplasias da Mama , MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Prognóstico , Estudos de Casos e Controles , Estudos Retrospectivos , Egito , Metaloproteinase 13 da Matriz/metabolismo , Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.
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BACKGROUND: Adenoid cystic carcinoma (AdCC) is considered one of the most common destructive types of malignant salivary gland tumor that have high affinity to perineural invasion (PNI). This study was conducted to access different histological features of AdCC, and assessment of the immunohistochemical expression of CDC-7. METHODS: Thirty formalin-fixed paraffin incorporated tissue blocks of AdCC were classified according to the WHO histopathological types. The immune-expression of CDC-7 positive area was evaluated according to percentage area as following: Negative = 0 %, Weak = 1-10 %, Moderate = 11-49 %, and Strong = 50-100. The correlations between expression of the marker and different clinico-pathological variables were investigated using Chi-square (χ2) test. The P-value ≤ 0.05 was considered statistically significant. RESULTS: The expression of CDC-7 revealed statistical significant difference between the different tumor types (p ≤ 0.05). CONCLUSION: The biological behavior of AdCC can be predicated from the expression of CDC-7.
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Biomarcadores Tumorais , Carcinoma Adenoide Cístico , Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinases , Neoplasias das Glândulas Salivares , Humanos , Masculino , Feminino , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/química , Carcinoma Adenoide Cístico/patologia , Estudos Transversais , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/genética , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: One of the 11 recognized mucopolysaccharidosis (MPS) diseases is Sanfilippo. It is autosomal recessive in its mode of transmission. There are four subtypes of Sanfilippo (A, B, C, and D). The most worldwide prevalent subtypes of mucopolysaccharidosis type III (MPS III) are A and B followed by C and D subtypes. To estimate the frequency of MPS IIIA among MPS III patients, we diagnose and compare their clinical features with those of MPS IIIB and also compare the prevalence of MPS IIIB versus MPS IIIA among diagnosed cases at the Biochemical Genetic Department at NRC. For every case that was referred, the quantitative determination of urine Glycosaminoglycans (GAGs) was assessed. Two-dimensional electrophoresis (2DE) of GAGs extracted from urine was performed on all cases with high urinary GAG levels. Both N-sulphoglucosamine sulphohydrolase (MPS IIIA) and N-alpha-acetylglucosaminidase (MPS IIIB) enzyme activity were determined fluorometrically. RESULTS: From November 2019 to May 2022, 535 cases were referred to the National Research Centre's Biochemical Genetics Department. 233 (43%) MPS cases were diagnosed with high urinary GAG levels for their ages. 73 (31.3%) MPS III cases were diagnosed by 2DE out of the 233 MPS cases. Plasma N-alpha-acetylglucosaminidase enzyme assay was insufficient in 36 (49.3%) patients (Sanfilippo type B), while N-sulphoglucosamine sulphohydrolase enzyme activity was deficient in 15 (20.6%) patients. The other 22 (30.1%) patients are either Sanfilippo type C or D. CONCLUSION: N-sulphoglucosamine sulphohydrolase enzyme activity was measured for the first time in Egypt. Thirty-one percent of all diagnosed MPS cases during the last 3 years were MPS type III, making Sanfilippo the most common MPS type among the referred cases to our Biochemical Genetics Department. MPS IIIA accounts for 20.6% of MPSIII cases in this study. Still, MPS type IIIB is the commonest type among diagnosed patients.
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Background: Recent reports indicated an increasing prevalence of obesity among children and adolescents in Saudi Arabia, making it an impending national epidemic. However, obesity prevalence data in children and adolescents in Saudi Arabia are largely inconsistent. Objectives: This study analyzed and compared the prevalence of obesity among a national sample of children and adolescents across sexes, school grades, regions, and city types in Saudi Arabia using the Growth Charts for Saudi Children and Adolescents. Methods: Weight, height, and body mass index (BMI) data from 1 134 317 children in first, fourth, seventh, and tenth school grades who participated in the national school screening program were analyzed cross-sectionally. BMI values were classified using the Growth Charts for Saudi Children and Adolescents. Results: Nearly 10.4% of students were overweight, 10.7 % were obese, and 4.50% were severely obese. Male students had a higher prevalence of overweight and obesity than their female counterparts. The prevalence of overweight and obesity was the highest among students in intermediate school, the Central region, and administrative capitals. Conclusion: Managing childhood obesity is challenging due to its multifaceted nature Therefore, utilizing clinical and community-based participatory approaches is essential to develop nationwide obesity prevention and management program that is effective and sustainable. This program must utilize dynamic BMI surveillance systems using ethnically representative growth references, conduct national pediatric obesity research with careful consideration for demographic and regional differences, lead targeted pediatric obesity awareness campaigns, provide obesity management interventions in a pediatric multi-disciplinary clinic, and evaluate the program outcomes periodically.
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Numerous studies have shown that stress in plant cells and organelles with transport electron chains is related to RNA editing. The ATP synthase complex present in mitochondria plays a crucial role in cellular respiration and consists of several subunits. Among them is the b subunit, which is encoded by the mitochondrial atp4 gene. Computing-based analysis of the effects of RNA editing of the Withania somnifera atp4 gene in mitochondria leading to alterations in the b subunit of ATP synthase. Using the CLC Genomic Workbench 3, RNA editing analysis between the control and salt stress conditions was not significantly different. Depending on RNA editing, the tertiary structure model revealed a change in the states of the b subunit, reflecting differences in the central stalk and F1-catalytic domain. The study found that polar edits in the N-terminus of the b subunit allow for efficient H + ion selectivity and introduce a new coiled-coil alpha-helical structure that may help stabilize the complex. The most noteworthy finding of this study was the strong impact of these editing events on the tertiary structure of the b subunit, which has the potential to affect the ATPase activity and indicate that the editing in this subunit aimed to restore the original active protein and not as a response to salt stress.
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Among the promising therapeutic targets for treating cancer are the continuously active STAT proteins, which are important in the progression of many malignancies. Here, we detail the STAT3/5 inhibitory action and thiopyrimidine/chalcone hybrid design, production, and anti-hepatocellular carcinoma activity. The prepared hybrids were assessed for their cytotoxic effect on HepG2 and Huh7 liver cancer cells. The most active compounds 5e and 5h (IC50 range from 0.55 to 2.58 µM) were further evaluated against normal THLE cells to examine their safety profiles. The hybrids 5e and 5h were additionally tested for their potential to inhibit STAT3 and STAT5a. They showed dual inhibitory action, with a decrease in the level of STAT3 by 65 and 87 times, respectively, and a decrease in the level of STAT5 by 60 and 79.5 times, respectively, compared to the control. Additionally, western blot analysis of compound 5h revealed inhibition of STAT3 and STAT5 phosphorylation at Tyr705 and Tyr694, respectively, with only a slight decrease in the total expression of STAT3 and STAT5 proteins. And lastly, molecular docking research provided additional insight on the 5h binding mechanism in the STAT3 and STAT5 SH2 domains.
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The increasing demand for natural products and biotechnological activities from bees facilitate their widespread use in food preservation and beneficial effects on humans. This study aimed to prepare and characterize the nano-capsules of Qaluiobia (PQG) governorates propolis extracted with water, ethanol and supercritical fluid-carbon dioxide at 50 °C with co-solvent. Propolis bioavailability was analyzed and introduced to prepare crackers to extend their shelf life. Nano-encapsulation was examined using transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and antioxidant activity. Ethanol and supercritical fluid-carbon dioxide (SCF-CO2) at 50 °C with ethanol as co-solvent recorded higher yield, antioxidant activities, total phenolics and total flavonoids. SCF-CO2 extracts had a higher flavonoid concentration. It was revealed that propolis nano-capsules had high-temperature stability and cytotoxic effects against the three tested human cancer cell lines (i.e. PC3, MCF7 and HePG2). The higher overall acceptability of crackers fortified with PQG was achieved with SCF-CO2 at 50 °C and ethanol extract nano-capsules, i.e. 86.57% and 86.29% respectively. The higher ability to retain antioxidant activity reduces the increase of peroxide value (PV), preventing rancidity and increasing the shelf life of crackers during the storage period. Practical application: This study can provide a suitable method for extracting bioactive compounds from propolis, and improve the biological properties and activities by nano-encapsulation, also reveals the extent of its use as a natural antioxidant and anticancer and its application in bakery products as a functional food.
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Ascomicetos , Própole , Humanos , Antioxidantes/farmacologia , Dióxido de Carbono , Egito , Própole/farmacologia , Cápsulas , Etanol , Flavonoides , Alimento Funcional , Extratos Vegetais/farmacologiaRESUMO
AIMS: This study aimed to assess the quality of life of schoolchildren with type 1 diabetes mellitus (T1DM) and determine their guardians' satisfaction of diabetes health care in Saudi Arabian schools. METHODS: A cross-section multicenter study was conducted from February to July 2022 among Schoolchildren with T1DM in Saudi Arabia. The study included T1DM school children aged 6-18 years. The patients' health-related quality of life (HRQoL) data were collected and determined using a modified version of the PedsQL 3.0 Diabetes Module. RESULTS: The grand total median PedQL-DM score among the included participants (N = 283) was 64.7, while items related to diabetes symptoms and diabetes management were 61.1 and 68.7, respectively. Schoolchildren who have lower HbA1c levels and take care of regular monitoring of their blood glucose showed significantly better quality of life concerning diabetes symptoms. A significant number of guardians claimed they were not satisfied with the current status of diabetes management at schools. CONCLUSIONS: The overall HRQoL among schoolchildren with T1DM was average and acceptable to some extent. The PedsQL-DM median score was higher among those who received health care during school time. The guardians' satisfaction of diabetes health care was low, emphasizing the role of health clinics in schools.
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Diabetes Mellitus Tipo 1 , Qualidade de Vida , Criança , Humanos , Diabetes Mellitus Tipo 1/terapia , Arábia Saudita , Inquéritos e Questionários , Satisfação PessoalRESUMO
Locomotor disorders caused by multidrug-resistant (MDR) bacterial pathogens denote one of the most detrimental issues that collectively threaten the poultry industry leading to pronounced economic losses across the world. Hence, searching for effective alternatives, especially those extracted from plant origins became of great priority targeting a partial or complete replacement of chemical antimicrobials to tackle their developing resistance. Therefore, we aimed to determine the prevalence and antimicrobial resistance of Staphylococcus aureus (S. aureus), Salmonella species, Mycoplasma synoviae (M. synoviae), and Escherichia coli (E. coli) recovered from 500 broilers and ducks (250 each) with locomotor disorders in various farms in Dakahlia and Sharkia Governorates, Egypt. Additionally, we assessed, for the first time, the in vitro antimicrobial effectiveness of marjoram, garlic, ginger and cinnamon essential oils (EOs) against MDR and multivirulent bacterial isolates as well as the in vivo efficiency of the most effective antibiotics and EOs either separately or in combination in the treatment of experimentally induced poultry leg disorders. The overall prevalence rates of S. aureus, E. coli, Salmonella species, and M. synoviae were 54, 48, 36, and 2%, respectively. Salmonella species and S. aureus prevailed among ducks and broilers (36 and 76%, respectively). Notably, MDR was observed in 100, 91.7, 81.1, and 78.5% of M. synoviae, E. coli, Salmonella, and S. aureus isolates, respectively. Our in vitro results displayed that marjoram was the most forceful EO against MDR and multivirulent chicken vancomycin-resistant S. aureus (VRSA) and duck S. Typhimurium isolates. The current in vivo results declared that marjoram in combination with florfenicol or amoxicillin/clavulanic acid succeeded in relieving the induced duck and chicken leg disorders caused by S. Typhimurium and VRSA, respectively. This was evidenced by improvement in the clinical and histopathological pictures with a reduction of bacterial loads in the experimental birds. Our encountered successful in vitro and in vivo synergistic effectiveness of marjoram combined with florfenicol or amoxicillin/clavulanic acid recommends their therapeutic application for leg disorders and offers opportunities for reducing the antibiotics usage in the poultry industry.