Circulating microRNAs and hepcidin as predictors of iron homeostasis and anemia among school children: a biochemical and cross-sectional survey analysis.

BACKGROUND: MicroRNAs (miRNAs) can control several biological processes. Thus, the existence of these molecules plays a significant role in regulating human iron metabolism or homeostasis. PURPOSE: The study aimed to determine the role of circulating microRNAs and hepcidin in controlling iron homeostasis and evaluating possible anemia among school children. METHODS: The study was based on a biochemical and cross-sectional survey study that included three hundred fifty school children aged 12-18 years old. RT-PCR and immunoassay analysis were accomplished to estimate iron concentration, Hgb, serum ferritin (SF), soluble transferrin receptor (sTfR), total body iron stores (TIBs), total oxidative stress (TOS), total antioxidant capacity (TAC), α-1-acid glycoprotein (AGP), high sensitive C-reactive protein (hs-CRP), and miRNAs; miR-146a, miR-129b, and miR-122 in 350 school adolescents. RESULTS: Iron disorders were cross-sectionally predicted in 28.54% of the study population; they were classified into 14.26% with ID, 5.7% with IDA, and 8.6% with iron overload. The overall proportion of iron depletion was significantly higher in girls (20.0%) than in boys (8.6%). MicroRNAs; miR-146a, miR-125b, and miR-122 were significantly upregulated with lower hepcidin expression in adolescence with ID and IDA compared to iron-overloaded subjects, whereas downregulation of these miRNAs was linked with higher hepcidin. Also, a significant correlation was recorded between miRNAs, hepcidin levels, AGP, hs-CRP, TAC, and other iron-related indicators. CONCLUSION: Molecular microRNAs such as miR-146a, miR-125b, and miR-122 were shown to provide an additional means of controlling or regulating cellular iron uptake or metabolism either via the oxidative stress pathway or regulation of hepcidin expression via activating genes encoding Hfe and Hjv activators, which promote iron regulation. Thus, circulating miRNAs as molecular markers and serum hepcidin could provide an additional means of controlling or regulating cellular iron and be associated as valuable markers in diagnosing and treating cases with different iron deficiencies.

Potential roles of circulating microRNAs in the healing of type 1 diabetic wounds treated with green tea extract: molecular and biochemical study.

Background: Circulating miRNAs have been implicated in various aspects of diabetic wound healing, including inflammation, angiogenesis, and extracellular matrix remodeling. Thus, in alternative herbal medicine strategies, miRNAs will be potential therapeutic molecular targets in nonhealing wounds. These could be valuable elements for understanding the molecular basis of diabetic wound healing and could be used as good elements in bioinformatics. Objectives: To elucidate the molecular mechanisms of microRNAs in association with apoptosis-inducing genes in controlling skin wound healing in diabetic wounds treated with green tea polyphenols (GTPs). Methods: Green tea hydro extract (GTE) at doses of100-200 mg/ml was topically applied to the skin tissues of rats with T1DM induced by a single dose of streptozotocin (STZ; 100 mg/kg, in 0.01 M sodium citrate, pH 4.3-4.5) injected intraperitoneally for seven consecutive days to induce T1DM. The rats were treated with green tea for three weeks. A sterile surgical blade was used to inflict a circular wound approximately 2 cm in diameter on the anterior-dorsal side of previously anesthetized rats by a combination of ketamine hydrochloride (50 mg/kg, i.e., body weight) and xylazine hydrochloride. Afterward, the molecular roles of the circulating miRNAs miR-21, miR-23a, miR-146a, and miR-29b and apoptotic genes were determined by quantitative real-time PCR to evaluate Bax, Caspase-3, and Bcl-2 in wound healing. In addition, HPLC analysis was also performed to estimate the active polyphenols (GTPs) present in the hydro extract of green tea leaves. Results: Wound healing was improved in diabetic skin wounds following treatment with GTE at doses of 100-200 mg/dl for three weeks. The wound parameters contraction, epithelialization, and scar formation significantly improved in a short time (14 days) compared to the longer periods identified in diabetic non-treated rats (20 days) and the standard control (15.5 days). Molecular analyses reported a significant increase in the levels of miR-21, miR-23a, and miR-146a and a decrease in the levels of miR-29b in green tea-treated diabetic rats compared to those in the standard control and STZ-diabetic non-treated rats. In addition, the molecular apoptotic genes Bax and caspase-3 significantly increased, and the BcL-2 gene significantly decreased following treatment with green tea polyphenols. Conclusions: The data showed that active green tea polyphenols (GTPs) present in GTE significantly improved diabetic wound healing by controlling apoptotic genes and the circulating microRNAs miR-21, miR-23a, miR-146a, and miR-29b, which might be involved in cellular apoptosis and angiogenesis processes. Thus, to establish a future model for the treatment of diabetic wounds, further studies are needed to understand the potential association of these biological parameters with the wound-healing process in diabetic wounds.

High-Intensity Interval Training Improves Glycemic Control, Cellular Apoptosis, and Oxidative Stress of Type 2 Diabetic Patients.

Background and Objectives: Physical exercise is an important therapeutic modality for treating and managing diabetes. High-intensity interval training (HIIT) is considered one of the best non-drug strategies for preventing and treating type 2 diabetes mellitus (T2DM) by improving mitochondrial biogenesis and function. This study aimed to determine the effects of 12 weeks of HIIT training on the expression of tumor suppressor protein-p53, mitochondrial cytochrome c oxidase (COX), and oxidative stress in patients with T2DM. Methods: A total of thirty male sedentary patients aged (45-60 years) were diagnosed with established T2DM for more than five years. Twenty healthy volunteers, age- and sex-matched, were included in this study. Both patients and control subjects participated in the HIIT program for 12 weeks. Glycemic control variables including p53 (U/mL), COX (ng/mL), total antioxidant capacity (TAC, nmole/µL), 8-hydroxy-2'-deoxyguanosine (8-OHdG, ng/mL), as well as genomic and mitochondrial DNA content were measured in both the serum and muscle tissues of control and patient groups following exercise training. Results: There were significant improvements in fasting glucose levels. HbA1c (%), HOMA-IR (mUmmol/L2), fasting insulin (µU/mL), and C-peptide (ng/mL) were reported in T2DM and healthy controls. A significant decrease was also observed in p53 protein levels. COX, 8-OhdG, and an increase in the level of TAC were reported in T2DM following 12 weeks of HIIT exercise. Before and after exercise, p53; COX, mt-DNA content, TAC, and 8-OhdG showed an association with diabetic control parameters such as fasting glucose (FG), glycated hemoglobin (HbA1C, %), C-peptide, fasting insulin (FI), and homeostatic model assessment for insulin resistance (HOMA-IR) in patients with T2DM. These findings support the positive impact of HIIT exercise in improving regulation of mitochondrial biogenesis and subsequent control of diabetes through anti-apoptotic and anti-oxidative pathways. Conclusions: A 12-week HIIT program significantly improves diabetes by reducing insulin resistance; regulating mitochondrial biogenesis; and decreasing oxidative stress capacity among patients and healthy controls. Also; p53 protein expression; COX; 8-OhdG; and TAC and mt-DNA content were shown to be associated with T2DM before and after exercise training.

Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines.

In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-ß1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7-54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 µM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers.

Green tea consumption and the management of adrenal stress hormones in adolescents who stutter.

Green tea and its polyphenolic compounds have been shown to exert positive effects in individuals with psychological disorders. The protective role of green tea against stuttering or its related consequences, depression, anxiety and stress, were evaluated in adolescents with moderate stuttering (MS). A total of 60 adolescents aged (12-18) years old were enrolled in this study. Patients were classified according to standardized test material Stuttering Severity Instrument, 4th Edition was used to estimate the severity of stuttering; participants were classified into two groups: a normal healthy group (n=30) and a MS group (n=30). The Depression Anxiety Stress Scale and General Health Questionnaire were used to estimate the degree of depression, anxiety and stress as well as general mental health. The physiological profile of stress hormones, as a measure of the response to green tea response, was also measured amongst participants. Adrenal stress hormones cortisol, dehydroepiandrosterone (DHEA), acetylcholine (ACTH), corticosterone and the cortisol:DHEA ratio were assayed. In addition, the constituent green tea polyphenols and their quantities were determined using liquid chromatography analysis. Decaffeinated green tea was administered six cups/day for 6 weeks, and this significantly improved the depression, anxiety, stress and mental health consequences associated with stuttering in adolescents. In addition, increased consumption of green tea significantly reduced elevated levels of adrenal stress hormones; cortisol, DHEA, ACTH and corticosterone, and increased the cortisol:DHEA ratio in the control and adolescents who stuttered. The data showed that drinking six cups of decaffeinated green tea, which is enriched in catechins (1,580 mg) and other related polyphenols, was sufficient to improve the consequences of mental health associated with stuttering in younger aged individuals.

Rhizopus oryzae AM16; a new hyperactive L-asparaginase producer: Semi solid-state production and anticancer activity of the partially purified protein.

The demand for L-asparaginase is predicted to increase several fold in the future due to its potential clinical applications in the treatment of lymphoid system malignancies and leukemia. Thus identifying suitable sources of production should be considered high priority. Fungi are valuable organisms as they are able to convert what would be considered 'useless' materials into materials that have potential value. The present study provides a proof of concept of production of a new hyperactive L-asparaginase producer (Rhizopus oryzae AM16), which was successfully isolated and sequentially optimized using a semi solid-state fermentation method with a simple and cheap medium produced from wheat bran (WB). The fungus was able to produce an appreciable amount of the enzyme (2,875.9 U) after 8 days of incubation under 85.7% moisture, in the presence of magnesium nitrate (5.0 mg N/mg nitrogen per gram of dry WB) at pH 5.8. Testing the anticancer activity confirmed the ability of the resultant enzyme to inhibit the growth of various types of cancer cells (HepG2, MCF-7, HCT and A549). The IC50 values of the dialyzed enzyme were lower than that of the crude product. Thus, this newly identified and purified L-asparaginase may be a promising anticancer drug.

Production of Terretonin N and Butyrolactone I by Thermophilic Aspergillus terreus TM8 Promoted Apoptosis and Cell Death in Human Prostate and Ovarian Cancer Cells.

The anticancer activity of terretonin N (1) and butyrolactone I (2), obtained from the thermophilic fungus Aspergillus terreus TM8, was intensively studied against prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines. According to this study, both compounds showed potent cytotoxicity towards ovarian adenocarcinoma cells (SKOV3) with IC50 1.2 and 0.6 µg/mL, respectively. With respect to metastatic prostate cells (PC-3), the two compounds 1 and 2 showed a significantly promising cytotoxicity effect with IC50 of 7.4 and 4.5 µg/mL, respectively. The tested fungal metabolites showed higher rates of early and late apoptosis with little or no necrotic apoptotic pathway in all treated prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines, respectively. The results reported in this study confirmed the promising biological properties of terretonin N (1) and butyrolactone I (2) as anticancer agents via the induction of cellular apoptosis. However, further studies are needed to elucidate the molecular mechanism by which cellular apoptosis is induced in cancer cells.

Handgrip Strength and Vitamin D as Predictors of Liver Fibrosis and Malnutrition in Chronic Hepatitis C Patients.

BACKGROUND: In patients with chronic hepatitis C (CHC), a negative impact of associated malnutrition on both morbidity and mortality was reported. We aimed to elucidate the efficacy of serum liver fibrosis markers (fibronectin (FN), hydroxyproline (Hyp), and hyaluronic acid (HA)) and their respective indices (HA index, Hyp index, and FN index) and vitamin D status in predicting malnutrition associated with liver fibrosis in CHC patients and to investigate their association with the value of current clinical malnutrition assessment tools subjective global assessment (SGA), handgrip strength (HGS), and muscle mass scores (SGA, BMI, MAMC, and HGS). MATERIALS AND METHODS: A cross-sectional study was conducted on 80 patients aged 40-60 years with proven viremia, HCV antibodies, HCV-RNA positivity, genotype determinations, and established chronic hepatitis C virus for more than 6 years and 80 control subjects. SGA, HGS, and muscle mass score (MAMC) were estimated in both patients and control subjects. Based on SGA scores, CHC patients were classified into three groups: well nourished (n = 12; SGA-A); mild or moderately malnourished (n = 25; SGA-B); and severely malnourished (n = 43; SGA-C). Liver fibrosis markers, inflammatory indicator α-Fetoprotein (AFP), tumor necrosis factor-alpha (TNF-α), 25-hydroxyvitamin D, and PTH were estimated using immunoassay techniques. RESULTS: CHC patients with moderate and severe malnutrition SGA scores showed a significant decline in the levels of vitamin D, increased PTH, and lower values of HGS and muscle mass indices compared to well-nourished patients and control subjects. In addition, malnutrition, vitamin D deficiency, and lower values of HGS, MAC, TSF, and MAMC showed significant correlation with liver severity among CHC patients. Liver fibrosis markers Hyp, HA, FN, APRI, HypI, HAI, and FNI as noninvasive biomarkers showed significant correlation with both severity of liver diseases and associated malnutrition, especially in cirrhotic HCV patients (F4) compared to those with significant fibrosis (F2-F3). CONCLUSION: The results showed that deficiency in vitamin D levels, HGS, SGA, and muscle mass scores (MAC, MAMC, or TSF) could be used as markers of liver pathogenicity in patients with CHC. In addition, the study concluded that noninvasive biomarkers Hyp, HA, FN, APRI, HypI, HAI, and FNI separately or in association with vitamin D status, HGS, SGA, and muscle mass scores (MAC, MAMC, or TSF) were significantly associated with an incidence of malnutrition between ~70.5% and 89.6% of CHC patients with significant fibrosis and cirrhosis.

Phytochemicals of Rhus spp. as Potential Inhibitors of the SARS-CoV-2 Main Protease: Molecular Docking and Drug-Likeness Study.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. AIM: In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). METHODS: 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. RESULTS: The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. CONCLUSION: Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.

Molecular Changes in Circulating microRNAs' Expression and Oxidative Stress in Adults with Mild Cognitive Impairment: A Biochemical and Molecular Study.

BACKGROUND: The release of miRNAs in tissue fluids significantly recommends its use as non-invasive diagnostic biomarkers for the progression and pathogenesis of mild cognitive impairment (MCI) in aged patients. OBJECTIVE: The potential role of circulated miRNAs in the pathogenesis of MCI and its association with cellular oxidative stress, apoptosis, and circulated BDNF, Sirtuin 1 (SIRT1), and dipeptidyl peptidase-4 (DPP4) were evaluated in older adults with MCI. METHODS: A total of 150 subjects aged 65.4±3.7 years were recruited in this study. The participants were classified into two groups: healthy normal (n=80) and MCI (n=70). Real-time PCR analysis was performed to estimate the relative expression of miRNAs; miR-124a, miR-483-5p, miR-142-3p, and miR-125b, and apoptotic-related genes Bax, Bcl-2, and caspase-3 in the sera of MCI and control subjects. In addition, oxidative stress parameters; MDA, NO, SOD, and CAT; as well as plasma DPP4 activity, BDNF, SIRT1 levels were colorimetrically estimated. RESULTS: The levels of miR-124a and miR-483-5p significantly increased and miR-142-3p and miR-125b significantly reduced in the serum of MCI patients compared to controls. The expressed miRNAs significantly correlated with severe cognitive decline, measured by MMSE, MoCA, ADL, and memory scores. The expression of Bax, and caspase-3 apoptotic inducing genes significantly increased and Bcl-2 antiapoptotic gene significantly reduced in MCI subjects compared to controls. In addition, the plasma levels of MDA, NO, and DPP4 activity significantly increased, and the levels of SOD, CAT, BDNF, and SIRT1 significantly reduced in MCI subjects compared to controls. The expressed miRNAs correlated positively with NO, MDA, DPP4 activity, BDNF, and SIRT-1, and negatively with the levels of CAT, SOD, Bcl-2, Bax, and caspase-3 genes. CONCLUSION: Circulating miR-124a, miR-483-5p, miR-142-3p, and miR-125b significantly associated with severe cognitive decline, cellular oxidative stress, and apoptosis in patients with MCI. Thus, it could be potential non-invasive biomarkers for the diagnosis of MCI with high diagnostic performance.

Moderate aerobic training modulates cytokines and cortisol profiles in older adults with cognitive abilities.

Excessive expression of cortisol and pro-inflammatory cytokines exerts a negative affect on cognitive functioning and hippocampal structure in older adults. Although the interrelation between cortisol and cytokines was fully elucidated previously, few studies considered how their association with exercise can affect brain structures or play an anti-inflammatory role in preserving cognitive function among older adults. To evaluate both the neuro-protective and anti-inflammatory activities of moderate aerobic exercise in improving cognitive performance among healthy older adults, the serum levels of CRP, TNF-α, IL-6, and cortisol and their correlation with cognitive performance were estimated in all participants. A total of 60 healthy older adults aged 50-85 years were included in this study. The Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) test, colorimetric testing, and ELISA immunoassays were used to measure cognitive abilities; blood sugar; and glycated hemoglobin (HbA1c), cortisol, IL-6, TNF-α, and CRP, respectively, in older adults before and after 12-week exercise interventions. Exactly 50% of the participants showed moderate cognitive impairment (MCI) (LOTCA scores: 84.8 ± 8.2), and the remaining 50% of the participants (n = 30) were diagnosed as normal healthy subjects (LOTCA scores: 98.7 ± 8.1). There was a significant association between cognitive decline in LOTCA scores of motor praxis, vasomotor organization, thinking operations, and attention and concentration and higher levels of cortisol, CRP, TNF-α, and IL-6, as well as adiposity markers BMI and WHR, in the MCI group compared to control subjects. However, significant improvements in the same LOTCA score domains in MCI subjects were recorded along with decrements in the levels of cortisol and cytokine CRP, TNF-α, and IL-6, as well as improved adiposity markers, following a 12-week moderate exercise program. Cognitive performance correlated positively with cortisol levels and negatively with physical activity, adiposity markers, and cytokine levels. Also, in participants with normal and abnormal cortisol profiles, there was a positive interrelation between cytokine levels and cortisol. Moderate aerobic exercise for 12 weeks showed beneficial effects on cognitive performance in older adults. Our results suggest that 12 weeks of aerobic exercise improves cognitive disorders in older adults via modulating stress and pro-inflammatory cytokines. This may have been due to significant changes in the levels of cortisol, IL-6, TNF-α, and CRP, and physical activity may thus be used as non-drug strategy for treating cognitive disorders.

Physical activity impact on motor development and oxidative stress biomarkers in school children with intellectual disability

SUMMARY OBJECTIVE Lower physical fitness and poor motor performance were shown to be linked with higher levels of oxidative stress in children and adolescents with intellectual disabilities. Therefore, a moderate aerobic exercise for 12-weeks was performed to evaluate the effects of physical activity scores on motor functions, oxidative stress, and intelligence quotients (IQ) in school children with intellectual disability. METHODS A total of 65 school children aged (12-18 Yrs) were randomly included in this study. Intellectual disability (ID),motor skills,physical fitness(VO2max), total energy expenditure (TEE), MDA, 8-OHdG, TAC, NO, and total oxidative stress(OS)were assessed using pre-validated WISC-IQ score test, BOT-2 test, PA questionnaire, and immunoassay techniques respectively. RESULTS WISC-IQ and BOT-2 set scores of intellectual and motor skills performance showed a significant correlation with physical activity status and the regulation of oxidative stress-free radicals in school children with mild and moderate ID following 12 weeks of moderate exercise. The intellectual and motor skills performance of the participants correlated positively with the increase in TAC activity and physical fitness scores and negatively with MDA, 8-OHdG, NO, and Total-OS, respectively. Stepwise multiple regression analysis of the demographic, physical status and oxidative stress parameters explained around78.0 to 93.4 % of intellectual disability variation among schoolchildren. CONCLUSION Moderate aerobic training for12 weeks has a positive impact on improving intellectual ability of schoolchildren with ID via modulating redox status, improves physical fitness, and motor skills proficiency.

RESUMO OBJETIVO A baixa aptidão física e o baixo desempenho motor mostraram-se associados a níveis mais altos de estresse oxidativo em crianças e adolescentes com deficiência intelectual. Portanto, foi realizado um exercício aeróbico moderado por 12 semanas para avaliar os efeitos dos escores de atividade física nas funções motoras, estresse oxidativo e quocientes de inteligência (QI) em escolares com deficiência intelectual. MÉTODOS Um total de 65 crianças em idade escolar (12 a 18 anos) foi incluído aleatoriamente neste estudo. A incapacidade intelectual (DI), habilidades motoras, aptidão física (VO2máx), gasto energético total (ETE), MDA, 8-OHdG, TAC, NO e estresse oxidativo total (SG) foram avaliados pelo teste de pontuação Wisc-IQ pré-validado, teste BOT-2, questionário de PA e técnicas de imunoensaio, respectivamente. RESULTADOS Os escores do conjunto Wisc-IQ e BOT-2 do desempenho das habilidades intelectuais e motoras mostraram uma correlação significativa com o status da atividade física e a regulação dos radicais livres do estresse oxidativo em escolares com DI leve e moderada após 12 semanas de exercício moderado. O desempenho das habilidades intelectuais e motoras dos participantes correlacionou-se positivamente com o aumento dos escores de atividade TAC e aptidão física e negativamente com MDA, 8-OHdG, NO e Total-OS, respectivamente. Houve uma melhora significativa nas habilidades motoras, como áreas específicas de precisão motora fina, velocidade de corrida, agilidade, coordenação de membros superiores, força, coordenação bilateral e equilíbrio entre crianças em idade escolar após o programa de exercícios. A análise de regressão múltipla passo a passo dos parâmetros demográficos, do estado físico e do estresse oxidativo explicou em torno de 78,0 a 93,4% da variação da incapacidade intelectual entre os escolares. CONCLUSÃO O treinamento aeróbico moderado por 12 semanas tem um impacto positivo na melhoria da capacidade intelectual de escolares com DI por meio da modulação do status redox, melhora da aptidão física e proficiência em habilidades motoras.

Plasmatic adipocyte biomarkers and foot pain associated with flatfoot in schoolchildren with obesity.

OBJECTIVE: The aim of this study was to determine the potential association of foot pain and plasmatic adipocytes as physiological biomarkers of childhood obesity with the incidence of flatfoot in a cohort of Egyptian school children aged 6 -12 years. METHODS: A total of 550 Egyptian schoolchildren (220 boys and 330 girls) aged 6-12 years were randomly invited to participate in this descriptive survey analysis. For all children, we assessed the diagnosis and severity of flatfoot as well as plasma adipocytes, as well as adiponectin, leptin, resistin, IL-6, and TNF-α, using the Dennis method and immunoassay techniques respectively. Foot pain was assessed by using a standard VAS of 100 mm and Faces Pain Scale, respectively. RESULTS: Flat foot was predicted in 30.4% of school-age children, most of them showed a higher frequency of overweight (33.3%) and obesity (62.5%). Boys showed higher ranges of flat foot than girls. Foot pain significantly correlated with flat foot and obesity among the studied populations. In overweight-obese children, plasmatic adipocyte variables, as well as adiponectin, leptin, resistin, IL-6, TNF-α showed significant correlations with foot stance, especially in boys. Also, the studied adipocyte variables along with BMI, age, gender explained about~65% of the variance of flatfoot with pain among our school-age students. CONCLUSION: Foot pain showed an association with flat foot and childhood obesity in 30.4% of school-age students (6-12 years). Foot pain was shown to correlate positively with the incidence of flat foot and changes in adiposity markers, as well as adiponectin, leptin, resistin, Il-6, TNF-α.

Biological activities of ginger against cadmium-induced renal toxicity.

Our aim was to evaluate the protective and antioxidant effects of ginger extract against cadmium-induced renal toxicity in animal models and to support the use of ginger as anti-renal failure natural remedy. Seventy rats were examined in a 4-week experiment to evaluate the effect of Ginger (Zingiber officinale) at doses of 100 and 200 mg/kg body weight on molecular DNA content, antioxidant status, and renal function in rats intoxicated with cadmium at dose of (5 mg/kg) using biochemical and histological analysis. Renal dysfunction, kidney tissue damage, and oxidative effect were evident in cadmium intoxicated rats as estimated by significant increase in (creatinine, urea), decrease in (creatinine clearance and reabsorption rate of urine albumin), increase in MDA, decrease in total antioxidant status (TAC), reduction in DNA content, and histopathological changes of kidneys' tissues compared to control rats. Treatment with ginger resulted in significant restoring of renal function biomarkers, TAC, molecular DNA, and histological improvements which occurs via free radical scavenging and regenerative mechanisms. The activity of ginger was supported by estimation of bioactive phenolic and falvinods constituents. Twenty-eight polyphenolic compounds were estimated in ginger extract; [6]-gingerol, [6]-shogaol, citral and pyrogallol were the highest amounts in ginger, and supposed to be responsible for its major antioxidant and free radical scavenging activity as shown by In vitro DPPH/ß-carotene-linolic acid assay tests. Consequently, ginger extracts could have a potent protective effects against nephrotoxicity induced by various toxicants.

Plasmatic adipocyte biomarkers and foot pain associated with flatfoot in schoolchildren with obesity

SUMMARY OBJECTIVE The aim of this study was to determine the potential association of foot pain and plasmatic adipocytes as physiological biomarkers of childhood obesity with the incidence of flatfoot in a cohort of Egyptian school children aged 6 -12 years. METHODS A total of 550 Egyptian schoolchildren (220 boys and 330 girls) aged 6-12 years were randomly invited to participate in this descriptive survey analysis. For all children, we assessed the diagnosis and severity of flatfoot as well as plasma adipocytes, as well as adiponectin, leptin, resistin, IL-6, and TNF-α, using the Dennis method and immunoassay techniques respectively. Foot pain was assessed by using a standard VAS of 100 mm and Faces Pain Scale, respectively. RESULTS Flat foot was predicted in 30.4% of school-age children, most of them showed a higher frequency of overweight (33.3%) and obesity (62.5%). Boys showed higher ranges of flat foot than girls. Foot pain significantly correlated with flat foot and obesity among the studied populations. In overweight-obese children, plasmatic adipocyte variables, as well as adiponectin, leptin, resistin, IL-6, TNF-α.; showed significant correlations with foot stance, especially in boys. Also, the studied adipocyte variables along with BMI, age, gender explained about~65% of the variance of flatfoot with pain among our school-age students. CONCLUSION Foot pain showed an association with flat foot and childhood obesity in 30.4% of school-age students (6-12 years). Foot pain was shown to correlate positively with the incidence of flat foot and changes in adiposity markers, as well as adiponectin, leptin, resistin, Il-6, TNF-α

RESUMO OBJETIVO O objetivo deste estudo foi determinar a potencial associação de dor no pé e adipócitos plasmáticos como biomarcadores fisiológicos da obesidade infantil com incidência de pé plano em uma coorte de escolares egípcios de 6 a 12 anos. MÉTODOS Um total de 550 escolares egípcios (220 meninos e 330 meninas) com idades entre 6 e 12 anos foram convidados aleatoriamente para participar desta análise descritiva. Para todas as crianças, diagnóstico e gravidade do flatfoot, bem como adipócitos plasmáticos; adiponectina, leptina, resistina, IL-6 e TNF-α; foram avaliados pelo método de Dennis e técnicas de imunoensaio, respectivamente. A dor no pé foi avaliada usando uma EVA padrão de 100 mm e a Faces Pain Scale, respectivamente. RESULTADOS O pé plano foi predito em 30,4% das crianças em idade escolar; a maioria apresentou maior frequência de sobrepeso (33,3%) e obesidade (62,5%). Os meninos apresentaram maiores faixas de pé plano do que as meninas. A dor no pé correlacionou-se significativamente com pé plano e obesidade entre as populações estudadas. Em crianças obesas com sobrepeso, variáveis adipocitárias plasmáticas; adiponectina, leptina, resistina, IL-6 e TNF-α; apresentaram correlação significativa com a postura do pé, em meninos e meninas. Além disso, as variáveis estudadas dos adipócitos, juntamente com o IMC, idade e sexo, explicaram cerca de 65% da variância do pé plano com a dor entre os nossos alunos em idade escolar. CONCLUSÃO A dor no pé mostrou associação com pé plano e obesidade infantil em 30,4% dos estudantes em idade escolar (6-12 anos). A dor no pé se correlacionou positivamente com a incidência de pé plano e a mudança nos marcadores de adiposidade; adiponectina, leptina, resistina, IL-6, TNF-α.

MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome.

BACKGROUND: Numerous experimental models have shown that microRNAs (miRNAs)play an important role in regulating pain processing in clinical pain disorders. In this study, we evaluated a set of miRNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS). We then correlated the expression of these miRNAs with the levels of inflammatory markers and pain-related comorbidities in adolescents with CFS and healthy controls (HCs). METHODS: A total of 150 adolescents, 12 to 18 years of age, participated in this study between April 2016 and April 2017. The participants were classified into 2 groups: adolescents with CFS (n = 100) and HCs (n = 50). Reverse-transcription polymerase chain reaction was used to evaluate the expression of miR-558, miR-146a, miR-150, miR-124, and miR-143. Immunoassay analysis was used to assess the levels of immune inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). RESULTS: Adolescents with CFS showed significantly higher pain thresholds than comparable nonfatigued HCs. Ability to enjoy life and relations with others were the parameters least influenced by pain in CFS patients. Differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143 was significantly downregulated and notably interfered with pain intensity and frequency in patients with CFS. Also, the expression of these miRNAs was significantly correlated with that of IL-6, TNF-α, and COX-2, which have been shown to mediate pain intensity in patients with CFS. Girls with CFS showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CFS. Girls with CFS also showed increased expression of the inflammatory pain-related markers IL-6, TNF-α, and COX-2 compared with the levels of boys with CFS. CONCLUSIONS: The intensity and consequences of pain were influenced by differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143, which was directly associated with higher expression of the immune inflammatory-related genes TNFα, IL-6, and COX-2 in adolescents with CFS. Further studies of larger patient cohorts will help clarify the role of miRNAs in the pathogenesis of CFS.

GENO PROTECTIVE AND ANTI-APOPTOTIC EFFECT OF GREEN TEA AGAINST PERINATAL LIPOPOLYSACCHARIDE-EXPOSURE INDUCED LIVER TOXICITY IN RAT NEWBORNS.

BACKGROUND: This study aims to examine the protective effect of green tea on the disturbances in oxidative stress and apoptosis related factors, mostly produced due to perinatal lipopolysaccharide (LPS) exposure, that subsequently induces liver cell damage. MATERIALS AND METHODS: Anti-free radical, Antioxidant, scavenging, geno-protective, and antiapoptotic activity of aqueous green tea extract (AGTE) were assessed against LPS-induced hepatic dysfunction in newborn-rats. AGTE at doses of 100 & 200 mg/kg was orally administered daily to rat dams, during gestation and lactation. RESULTS: AGTE was observed to exhibit protective effects by significantly attenuating LPS-induced alterations in serum AST, ALT, bilirubin, and albumin levels. Significant increase in the total antioxidant capacity (TAC), DNA contents, and reduction in nitric oxide (NO) levels were observed in AGTE treated rats comparing LPS-toxicated ones. Additionally, AGTE treatment significantly down-regulated apoptotic markers and this effect was directly correlated to the degree of hepatic fibrosis. The possible mechanisms of the potential therapeutic-liver protective effect of AGTE could be due to free radical scavenging potential and antiapoptotic properties caused by the presence of antioxidant polyphenolic components in AGTE. CONCLUSION: We thereby propose, based on our findings, that the anti-free radical and anti-apoptotic inducing properties of AGTE active constituents attribute to its functional efficacy as anti-fibrotic agent.

Exercise intervention as a protective modulator against metabolic disorders in cigarette smokers.

[Purpose] assess the impact of exercise intensity on desire to smoke, serum cotinine, stress hormones, total antioxidant capacity, and oxidative free radicals as potential markers of cardiopulmonary metabolic disorders were measured.in cigarette smokers. [Subjects and Methods] The participants (150 randomly selected healthy men, aged 18-55 years) were classified into 4 smoking groups: control (non-smokers; N= 30); mild (N = 33); moderate (N = 42), and heavy (N = 45). The participants were assigned to either moderate (8 weeks) or short-term (20-45 min) exercise training. The desire to smoke, Mood and Physical Symptoms Scale, and Subjective Exercise Experiences Scale scores, cotinine, stress hormones (cortisol and testosterone), free radicals (malondialdehyde, nitric oxide), and total antioxidant capacity were evaluated. [Results] Significant increases in serum cotinine, cortisol, testosterone, nitric oxide, and malondialdehyde levels and a reduction in total antioxidant capacity activity were observed in all smoker groups; heavy smokers showed a higher change in metabolites. In all smoker groups, both short and moderate- intensity exercises significantly reduce cotinine, cortisol, testosterone, and malondialdehyde and increased nitric oxide levels and total antioxidant capacity activity; further, the desire to smoke, Mood and Physical Symptoms Scale, and Subjective Exercise Experiences Scale scores were reduced. This supports the ability of exercise to increase nitric oxide bioavailability, enhance of blood vessels function and ultimately decrease the incidence of cardiopulmonary disorders. [Conclusion] Exercise interventions with varying intensities may be used as nicotine replacement therapy or protective aids against smoking-related cardiopulmonary disorders.

Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4.

BACKGROUND: Vitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association. OBJECTIVE: In this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4. SUBJECTS AND METHODS: A total of 120 adult individuals aged 30-68 years were recruited in this study. Of these, 20 healthy subjects (15 men and five women) with a mean age of 48.3±6.1 years were selected as controls, and 100 patients with a mean age of 47.8±4.9 years with chronic HCV (CHC) who had undergone liver biopsy (80 men and 20 women) were included in this study. Based on liver radiographic (computed tomography, magnetic resonance imaging) and histological Metavir system analyses, the CHC patients were classified into three groups: asymptomatic CHC carriers (n=30), fibrosis (n=25), and cirrhosis (n=45). HCV RNA, HCV genotypes, inflammatory cytokines AFP and TNFα, 25-hydroxyvitamin D (25[OH]D) levels, apoptotic markers single-stranded DNA (ssDNA) and soluble Fas (sFas), and oxidative stress markers nitric oxide (NO) and total antioxidant capacity (TAC) were estimated by using molecular, immunoassay, and colorimetric techniques. RESULTS: Approximately 30% of the study population (n=30) were diagnosed as asymptomatic CHC carriers, and 70% of the study population (n=70) had severe fibrosis; these were classified into fibrosis and cirrhosis. There was a significant reduction in 25(OH)D levels and TAC activity, along with an increase in levels of NO, AFP, TNFα, ssDNA, and sFas in fibrosis and cirrhosis subjects compared with those of asymptomatic CHC carriers and health controls. The deficiency in 25(OH)D levels correlated positively with sFas, ssDNA, AFP, TNFα, NO, and TAC, and negatively with age, sex, liver function, body mass index, homeostatic model assessment - insulin resistance, HCV RNA, and viral load. Significant intercorrelation was reported between serum 25(OH)D concentrations and apoptotic and oxidative markers, which suggested progression of liver pathogenesis and fibrogenesis via oxidative and apoptotic mechanisms. CONCLUSION: The data showed that vitamin D status was significantly correlated with pathogenesis and fibrogenesis of the liver in geriatric patients infected with HCV genotype 4. The deficiency in 25(OH)D levels was shown to have a pivotal role in the pathogenesis of liver via apoptotic, oxidative stress, and inflammatory mechanistic pathways. The data point to adequate vitamin D levels being recommended for a good response to treatment strategies, especially in older CHC patients.

Physical activity and lifestyle effects on bone mineral density among young adults: sociodemographic and biochemical analysis.

[Purpose] The purpose of this study was to assess the possible role of physical activities, calcium consumption and lifestyle factors in both bone mineral density and bone metabolism indices in 350 young adult volunteers. [Subjects and Methods] All volunteers were recruited for the assessment of lifestyle behaviors and physical activity traits using validated questioners, and bone mineral density (BMD), serum osteocalcin (s-OC), bone-specific alkaline phosphatase (BAP), and calcium were estimated using dual-energy X-ray absorptiometry analysis, and immunoassay techniques. [Results] Male participants showed a significant increase in BMD along with an increase in bone metabolism markers compared with females in all groups. However, younger subjects showed a significant increase in BMD, OC, BAP, and calcium compared with older subjects. Osteoporosis was more common in older subjects linked with abnormal body mass index and waist circumference. Bone metabolism markers correlated positively with BMD, physically activity and negatively with osteoporosis in all stages. Also, moderate to higher calcium and milk intake correlated positively with higher BMD. However, low calcium and milk intake along with higher caffeine, and carbonated beverage consumption, and heavy cigarette smoking showed a negative effect on the status of bone mineral density. Stepwise regression analysis showed that life style factors including physical activity and demographic parameters explained around 58-69.8% of the bone mineral density variation in young adults especially females. [Conclusion] body mass index, physical activity, low calcium consumption, and abnormal lifestyle have role in bone mineral density and prognosis of osteoporosis in young adults.