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AIM: This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients. METHODS: Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits. RESULTS: Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes. CONCLUSIONS: Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients. [ABSTRACT FROM AUTHOR]

Liver myofibroblasts (MFB) are crucial mediators of extracellular matrix (ECM) deposition in liver fibrosis. They arise mainly from hepatic stellate cells (HSCs) upon a process termed activation. To a lesser extent, and depending on the cause of liver damage, portal fibroblasts, mesothelial cells and fibrocytes may also contribute to the MFB population. Targeting MFB to reduce liver fibrosis is currently an area of intense research. Unfortunately, a clog in the wheel of antifibrotic therapies is the fact that although MFB are known to mediate scar formation, and participate in liver inflammatory response, many of their molecular portraits are currently unknown. In this review, we discuss recent understanding of MFB in health and diseases, focusing specifically on three evolving research fields: metabolism, autophagy and epigenetics. We have emphasized on therapeutic prospects where applicable and mentioned techniques for use in MFB studies. Subsequently, we highlighted uncharted territories in MFB research to help direct future efforts aimed at bridging gaps in current knowledge.

Binder-free self-assembled 3D architecture electrodes have been fabricated by a novel convienient method. Liquid crystalline graphene oxide (LC GO) was used as precursor to interact with poly(3,4-ethylene-dioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) in dispersion in order to form a conductive polymer entrapped, self-assembled layer-by-layer structure. This advanced network containing PEDOT:PSS enabled us to ascribe the superior electrochemical properties of particular graphene sheets. This layer-by-layer self-assembled 3D architecture of best performing composite (rGO-PEDOT:PSS 25) showed excellent electrochemical performance of 434 F g-1 through chemical treatment. To highlight these advances, we further explored the practicality of the as-prepared electrode by varying the composite material content. An asymmetric supercapacitor device using aqueous electrolyte was also studied of this same composite. The resulting performance from this set up included a specific capacitance of 132 F g-1. Above all, we observed an increase in specific capacitance (19%) with increase in cycle life emphasizing the excellent stability of this device.

Peptic ulcer disease (PUD), often caused by Helicobacter pylori infection, is a prevalent gastrointestinal condition characterized by the erosion of the gastric or duodenal mucosal lining. H. pylori adheres to gastric epithelial cells, secreting toxins and disrupting the stomach's defenses. H. pylori relies on various receptors to establish infection, making these molecules attractive therapeutic targets. This study aimed to develop novel anti-ulcer compounds by combining benzothiazole, pyrazoline, and chalcone pharmacophores. A series of chalcone derivatives 4a-c were synthesized via Claisen-Schmidt condensation and characterized using spectroscopic techniques such as FT-IR, NMR and elemental analysis. The DFT calculations, using B3LYP method with 6-311G basis set, revealed the p -tolyl derivative 4b exhibited the highest thermal stability while the p -bromophenyl derivative 4c showed the lowest stability but highest chemical reactivity. The HOMO-LUMO energy gaps as well as the dipole moments decreased in the order: 4b  >  4a > 4c , reflecting a similar reactivity trend. Molecular docking showed ligands 4a-c bound effectively to the H. pylori urease enzyme, with docking scores from -5.3862 to -5.7367 kcal/mol with superior affinity over lansoprazole. Key interactions involved hydrogen bonds and hydrophobic pi-hydrogen bonds with distances ranging 3.46-4.34 Å with active site residues ASN666, SER714 and ASN810. The combined anti-inflammatory, antimicrobial, and H. pylori anti-adhesion properties make these novel chalcones promising PUD therapeutic candidates., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The purpose of the current investigation was to produce cinammaldehyde-based chalcone derivatives ( 3a - k ) to evaluate their potential effectiveness as antioxidant and inhibitory agents versus human Caco-2 cancer cells. The findings obtained using the DPPH assay showed that compound 3e had the highest effective antioxidant activity with the best IC 50 value compared with the other compounds. Moreover, the cytotoxic findings revealed that compound 3e was the best compound for inhibiting Caco-2 development in contrast to all other produced derivatives, with the lowest IC 50 concentration (32.19 ± 3.92 µM), and it also had no detrimental effects on healthy human lung cells (wi38 cells). Exposure of Caco-2 cells with this IC 50 value of compound 3e resulted in a substantial rise in the number of early and late cells that are apoptotic with a significant comet nucleus when compared with control cells employing the annexin V/PI and comet evaluations, respectively. Furthermore, qRT-PCR and ELISA examinations indicated that compound 3e significantly altered the expression of genes and their relative proteins related to apoptosis in the treated Caco-2 cells, thus significantly inhibiting Caco-2 growth through activating Caspase-3 via an intrinsic apoptotic pathway. As a result, compound 3e could serve as an effective therapy for human colon cancer.

Azo dyes are widely used for dyeing polyester fabrics but require optimization of properties like color strength and fastness. Fourteen novel disperse azo dyes were synthesized from 2,3-naphthalenediol and aniline derivatives to examine their potential for polyester dyeing. The dyes were prepared via diazotization and coupling reactions and characterized using FT-IR, UV-Vis, 1 H NMR, 13 C NMR, and elemental analysis. Furthermore, several techniques were employed to study the azo-hydrazone tautomerism, including UV-Vis spectroscopy, NMR spectroscopy, and computational methods. DFT computations revealed hydrazone tautomers were more stable than azo tautomers. The prepared azo dyes were applied on polyester fabrics at 2% depth using a high temperature pressure technique in water utilizing DYEWELL-002 as a dispersing agent. The color shading of dyed polyester samples ranged from peach amber to apple of my eye, depending on the coupler moieties. The fastness properties, assessed using a grey scale of dyed polyester fabrics, indicated very good to excellent grades for most dyes. Additionally, measurements of color strength (K/S), dye exhaustion (%E), as well as colorimetric colors CILAB of dyed polyester fabrics values, were measured and discussed in terms of the effect of substituents. The findings provide new insights into structure-performance relationships to design optimized disperse dyes for polyester coloration. Overall, the synthesized aryldiazenyl dyes are promising candidates for dyeing polyester fabrics across a spectrum of shades with good fastness properties., (© 2023. The Author(s).)

The goal of the current study was to prepare two new homologous series of N,N'-diarylurea and N,N'-diarylthiourea derivatives to investigate the therapeutic effects of these derivatives on the methodologies of inhibition directed on human MCF-7 cancer cells. The molecular structures of the prepared derivatives were successfully revealed through elemental analyses, 1 H-NMR, 13 C-NMR and FT-IR spectroscopy. The cytotoxic results showed that Diarylthiourea (compound 4 ) was the most effective in suppressing MCF-7 cell growth when compared to all other prepared derivatives, with the most effective IC 50 value (338.33 ± 1.52 µM) after an incubation period of 24 h and no cytotoxic effects on normal human lung cells (wi38 cells). Using the annexin V/PI and comet tests, respectively, treated MCF-7 cells with this IC 50 value of the Diarylthiourea 4 compound displayed a considerable increase in early and late apoptotic cells, as well as an intense comet nucleus in comparison to control cells. An arrest of the cell cycle in the S phase was observed via flow cytometry in MCF-7 cells treated with the Diarylthiourea 4 compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound 4 compared to control cells, suggesting that DNA damage induced by compound 4 may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea 4 compound inhibited the proliferation of MCF-7 cancer cells by arresting the S cell cycle and caspase-3 activation via an intrinsic apoptotic route. These results, however, need to be verified through in vivo studies utilizing an animal model.

The most dangerous disease in recent decades is lung cancer. The most accurate method of cancer diagnosis, according to research, is through the use of histopathological images that are acquired by a biopsy. Deep learning techniques have achieved success in bioinformatics, particularly medical imaging. In this paper, we present an innovative method for rapidly identifying and classifying histopathology images of lung tissues by combining a newly proposed Convolutional Neural Networks (CNN) model with a few total parameters and the enhanced Light Gradient Boosting Model (LightGBM) classifier. After the images have been pre-processed in this study, the proposed CNN technique is provided for feature extraction. Then, the LightGBM model with multiple threads has been used for lung tissue classification. The simulation result, applied to the LC25000 dataset, demonstrated that the novel technique successfully classifies lung tissue with 99.6% accuracy and sensitivity. Furthermore, the proposed CNN model has achieved the lowest training parameters of only one million parameters, and it has also achieved the shortest processing time of just one second throughout the feature extraction process. When this result is compared with the most recent state-of-the-art approaches, the suggested approach has increased effectiveness in the areas of both disease classification accuracy and processing time.

Background: Aflatoxin (AF), a metabolite of Aspergillus flavus , is injurious to vital body organs. The bacterial defense against such mycotoxins has attracted significant attention. Lactic acid bacteria (LAB) are known to ameliorate AF toxicity., Methods: Thirty adult male rats were divided into six groups (five each) to perform the experiments. The control (Co) group was fed a basal diet and water. Each of the following periods lasted 21 days: the milk (MK) group orally received milk (500 µL); LAB suspension (500 µL) containing 10 7 cfu/mL was orally provided to the LAB group; AF (0.5 mg/kg) was orally given to the AF group; and a combination of AF and LAB was administered to the AF + LAB group. The AF/LAB group was initially given AF for 21 days, followed by LAB for the same period. Finally, the rats were dissected to retrieve blood and tissue samples for hematological, biochemical, and histological studies., Results: The results revealed a significant decrease in RBCs, lymphocytes, total proteins, eosinophil count, albumin, and uric acid, whereas the levels of WBCs, monocytes, neutrophils, creatinine, urea, aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase, and creatinine kinase significantly increased in the AF group in comparison to the control group. The histological examination of the AF group revealed necrosis and apoptosis of the kidney's glomeruli and renal tubules, nuclei vacuolization and apoptosis of hepatocytes, congestion of the liver's dilated portal vein, lymphoid depletion in the white pulp, localized hemorrhages, hemosiderin pigment deposition in the spleen, and vacuolization of seminiferous tubules with a complete loss of testis spermatogenic cells. Meanwhile, protective and therapeutic LAB administration in AF-treated rats improved the hematological, biochemical, and histological changes., Conclusions: The study revealed LAB-based amelioration to AFB1-induced disruptions of the kidney, liver, spleen, and testis by inhibiting tissue damage. The therapeutic effects of LAB were comparatively more pronounced than the protective effects.

Benzidine was coupled with ethyl cyanoacetate, and malononitrile, to give azo-hydrazo products which in turn were cyclized by using hydrazine and phenyl hydrazine to give 4,4'-([1,1'-biphenyl]-4,4'-diylbis(hydrazin-2-yl-1-ylidene))bis pyrazole derivatives 5-7. These compounds were identified by various spectral analysis. The examination of 0.1 M NaOH and 0.1 M HCl in DMF revealed that the λ max of the synthesized dyes are quite sensitive to pH variation and slightly affected by the coupler moieties. Utilizing the dispersion agent DYEWELL-002, polyester fabric (PE-F) was dyed in water. The color strength (K/S), its summation (K/Ssum), dye exhaustion (%E) and reflectance values were measured and discussed. The DFT method estimates the chemical descriptor parameters of the titled dyes, using B3LYP/6-31G(d,p) level to investigate the performance of dyes as well as to postulate a mechanism of dyeing process., (© 2023. The Author(s).)

The effect of the terminal benzyloxy group on the mesomorphic properties of liquid crystalline materials developed from rod-like Schiff base has been described. For this objective, a novel Schiff base liquid crystal family, specifically new series of Schiff base liquid crystals, namely, ( E )-4-(alkyloxy)- N -(4-(benzyloxy)benzylidene)aniline, I n , are prepared and investigated in detail. The length of the terminal alkyloxy chain ( n ) varies amongst the compounds in the series. Where n varies between 6, 8 and 16 carbons. At the other end of the compounds, benzyloxy moiety was attached. The molecular structures of all synthesized compounds were established using different spectroscopic techniques. The molecular self-assembly was explored using differential scanning calorimetry (DSC) and polarized optical microscope (POM). Depending on the length of the terminal alkyloxy chain, only one type of SmA phase with different stability was observed. The previously reported para-substituted systems and the present investigated compounds were compared and discussed. The calculated quantum chemical parameters were computationally correlated using the DFT method via the B3LYP 6-311G(d,p) basis set. The theoretical computations revealed that the length of the alkyl side chain influences the zero-point energy, reactivity and other estimated thermodynamic parameters of benzoyloxy/azomethine derivatives. Furthermore, the FMO energy analysis shows that molecule I 16 have higher HOMO energies than the other compounds, and I 6 has a much lower LUMO level than the rest.

New organic derivatives named, ( E )-3(or4) -(alkyloxy)-N-{(trifluoromethyl)benzylidene}aniline, 1a-f , were synthesized and examined their liquid crystalline behaviors. FT-IR, 1 H NMR, 13 C NMR, 19 F NMR, elemental analyses and GCMS were used to validate the prepared compounds' chemical structures. We used differential scanning calorimetry (DSC) and polarized optical microscopy (POM) to investigate the mesomorphic characteristics of the formed Schiff bases. All tested compounds of series 1a-c have mesomorphic behaviour of nematogenic temperature ranges while the group 1d-f show non-mesomorphic properties. Moreover, it was found that the enantiotropic N phases included all of the homologue 1a-c . Computational studies using DFT (density functional theory) validated the experimental mesomorphic behavior results. All the analyzed compounds had their dipole moments, polarizability, and reactivity characteristics explained. Theoretical simulations showed that as the length of the terminal chain is increased, the polarizability of the stuided compounds increases. Consequently, compounds 1a and 1d have the least polarizability., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background and Aim: Biosecurity implementation is fundamental to combating diseases and antibiotic resistance. Therefore, this study aimed to examine the correlation between the implementation of biosecurity measures in small-scale duck farms and the incidence of infectious diseases that threaten the duck industry., Materials and Methods: Twenty small-scale duck farms of different breeds and production stages were collected as representative samples, focused on two districts in the Qalyoubia governorate, which possesses high-density small-scale farms. A 30-point structured questionnaire was designed to assess the level of biosecurity measures implemented in the sampled farms. These farms were examined for bacterial infection by cultivation, typing, and antibiotic sensitivity tests, in addition to molecular techniques for detecting suspected viral diseases., Results: The results showed that the farms had high or low levels of biosecurity; only 25% possessed high-level biosecurity. Bacteria, including Salmonella , Escherichia coli , Staphylococcus , and Pasteurella , were isolated from all sampled farms. High rates of antimicrobial resistance-reaching up to 100% were observed against some drugs. However, viral causative agents, including HPAI-H5N8, duck viral hepatitis, and goose parvovirus, were isolated from only five farms., Conclusion: The lack of commitment to biosecurity implementation, particularly personal hygiene, was observed in most sampled farms. Increasing the level of biosecurity reduced the incidence of mixed infections., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Adel, et al.)

Background and Aim: Multidrug resistance (MDR) of Escherichia coli has become an increasing concern in poultry farming worldwide. However, E. coli can accumulate resistance genes through gene transfer. The most problematic resistance mechanism in E. coli is the acquisition of genes encoding broad-spectrum β-lactamases, known as extended-spectrum β-lactamases, that confer resistance to broad-spectrum cephalosporins. Plasmid-mediated quinolone resistance genes (conferring resistance to quinolones) and mcr-1 genes (conferring resistance to colistin) also contribute to antimicrobial resistance. This study aimed to investigate the prevalence of antimicrobial susceptibility and to detect β-lactamase and colistin resistance genes of E. coli isolated from broiler farms in Egypt., Materials and Methods: Samples from 938 broiler farms were bacteriologically examined for E. coli isolation. The antimicrobial resistance profile was evaluated using disk diffusion, and several resistance genes were investigated through polymerase chain reaction amplification., Results: Escherichia coli was isolated and identified from 675/938 farms (72%) from the pooled internal organs (liver, heart, lung, spleen, and yolk) of broilers. Escherichia coli isolates from the most recent 3 years (2018-2020) were serotyped into 13 serotypes; the most prevalent serotype was O125 (n = 8). The highest phenotypic antibiotic resistance profiles during this period were against ampicillin, penicillin, tetracycline, and nalidixic acid. Escherichia coli was sensitive to clinically relevant antibiotics. Twenty-eight selected isolates from the most recent 3 years (2018-2020) were found to have MDR, where the prevalence of the antibiotic resistance genes ctx , tem , and shv was 46% and that of mcr-1 was 64%. Integrons were found in 93% of the isolates., Conclusion: The study showed a high prevalence of E. coli infection in broiler farms associated with MDR, which has a high public health significance because of its zoonotic relevance. These results strengthen the application of continuous surveillance programs., Competing Interests: The authors declare that they do not have competing interests., (Copyright: © Abdel-Rahman, et al.)

A variety of structurally different pyrimidines were synthesized. Elemental analysis, FT-IR, 1 H NMR, and 13 C NMR spectroscopy were used to confirm the chemical structures of all prepared compounds. The synthesized pyrimidines were screened against the growth of five human cancer cell lines (prostate carcinoma PC3, liver carcinoma HepG-2, human colon cancer HCT-116, human breast cancer MCF-7, human lung cancer A-549), and normal human lung fibroblasts (MRC-5) using MTT assay. Most of the screened pyrimidines have anti-proliferative activity on the growth of the PC3 cell line. Compounds 3b and 3d were more potent than the reference vinblastine sulfate (~2 to 3 × fold) and they can be considered promising leads for treating prostate cancer disease. Moreover, the screened compounds 3b , 3f , 3g , 3h , and 5 were assessed according to the values of their selectivity index (SI) and were found to be more selective and safer than vinblastine sulfate. Furthermore, using in silico computational tools, the physicochemical properties of all pyrimidine ligands were assessed, and the synthesized compounds fall within the criteria of RO5, thus having the potential to be orally bioavailable.

Background: Polycystic ovary syndrome (PCOS) is commonest endocrine disease occurring in women of reproductive age. This study conducted to clarify altered concentrations of Nesfatin-1, nicotinamide adenine dinucleotide phosphate (NADPH), and dopamine in PCOS women and controls. Also, to assess their role in PCOS pathophysiology and their correlation with measured biochemical parameters., Methods: In this observational study, 60 PCOS patients and 24 controls included. Medical history was recorded and full examinations were done. Serum concentrations of lipid profile, fasting blood glucose (FBG), fasting insulin (FSI), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone, progesterone, estradiol, Nesfatin-1, dopamine, and NADPH were measured by ELISA kits. Values were analyzed using unpaired t-test and Pearson Chi-square test. The p<0.05 was considered statistically significant., Results: In this study, there was significantly elevated waist hip ratio (WHR) and body mass index (BMI) in PCOS patients versus controls (p<0.0001 and p=0.014). There was significant increase in FSH, LH, prolactin, estradiol, testosterone, Nesfatin-1, and dopamine (p=0.021, p=0.015, p<0.0001, p<0.0001, p=0.006, p=0.017, p< 0.0001) and decrease of NADPH (p<0.0001) in PCOS patients. There were significant positive correlations between Nesfatin-1, prolactin, and dopamine levels. Also, there was significant positive correlation between dopamine and BMI, FSI, FSH, LH, estradiol, and prolactin levels; however, significant negative correlations observed between NADPH and BMI, FSI, estradiol, and prolactin levels., Conclusion: Elevated serum Nesfatin-1 concentrations and their association with hyperprolactinemia indicate that they have a role in PCOS pathophysiology. Moreover, elevated dopamine and decreased NADPH concentrations could play role in PCOS pathogenesis., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright© 2022, Avicenna Research Institute.)

A new N , N' -disubstituted piperazine conjugated with 1,3,4-thiadiazole and 1,2,4-triazole was prepared and the chemical structures were identified by IR, NMR and elemental analysis. All the prepared compounds were tested for their antimicrobial activity. The antimicrobial results indicated that the tested compounds showed significant antibacterial activity against gram-negative strains, especially E. coli , relative to gram-positive bacteria. Docking analysis was performed to support the biological results; binding modes with the active site of enoyl reductase amino acids from E. coli showed very good scores, ranging from -6.1090 to -9.6184 kcal/mol. Correlation analysis was performed for the inhibition zone (nm) and the docking score.

This study aimed to assess the impact of high-fat diet (HFD) and vitamin D3 supplementation on cardiac apoptosis, inflammation, oxidative stress, and cardiac uncoupling proteins (UCPs) 2&3 expression. Forty rats were fed either (45%) or (10%) fat diet with or without vitamin D3 (500 U/kg/day) for 6 months, then cardiac tissue expression of Bax, Bcl2, Fas, Fas-L (markers for apoptotic pathways), TNF- α , MDA7, GPX1 (inflammatory and oxidative markers) and UCP 2&3 were assessed. Results revealed the enhancement of intrinsic and extrinsic cardiomyocyte apoptosis cascades and increased inflammatory and oxidative burdens on the heart in HFD rats. Downregulation of UCP2 and upregulation of UCP3 gene expression at 6 months. After vitamin D3 supplementation with HFD, cardiac apoptotic, inflammatory and oxidative markers were mitigated and expression of UCP3 was downregulated and UCP2 was upregulated. This work highlights the novel cardioprotective effect of vitamin D3 in the experimental model of HFD feeding through the downregulation of UCP3.

Background: Metabolic syndrome patients are commonly prone to major health problems as cardiovascular diseases, diabetes mellitus, chronic kidney disease, cancer and neuropsychological complications including dementia., Objectives: This research investigates mechanisms linking metabolic syndrome to cognitive impairment and possible impact of vitamin D supplementation., Methods: Forty male Wistar rats were divided into 4 groups. Control, metabolic syndrome (20% fructose solution in drinking water for 12 weeks, vitamin D supplemented (500 IU/kg/day)) and metabolic syndrome supplemented with vitamin D. Animals were assessed for spatial memory, hippocampal expression of SNAP 25, VAMP and mGlut2 receptor and hippocampus histological examination. Animals with metabolic syndrome showed prolonged acquisition and retention latencies in morris water maze, decreased hippocampal expression of SNAP 25 and VAMP and increased mGlut2 expression. Histologically CA1, CA3 regions and dentate nucleus revealed increase in degenerated neurons and glia cells with decreased pyramidal cell layer thickness. Vitamin D supplementation mitigated alterations induced by metabolic syndrome., Conclusions: Metabolic syndrome decreased hippocampal synaptic proteins and altered glutamatergic transmission and increased hippocampal neuronal degeneration. Vitamin D supplementation offered neuroprotective effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: This prospective randomized case control study aimed to investigate effect of oral agar administration in reducing total serum bilirubin (TSB) levels in full-term neonates with jaundice in comparison with control., Materials and Methods: One hundred sixty full-term neonates were enrolled with TSB 10-19 mg/dl at first week of age from Assiut University Children's Hospital. Neonates were divided according to TSB into outpatient group ( n  = 100) (TSB 10-15 mg/dl) and admitted group ( n  = 60) (TSB > 15-19 mg/dl). Outpatients group were subdivided into agar group received oral agar and control group received placebo. Admitted group were subdivided into agar group received oral agar plus phototherapy combination and control group received phototherapy alone. Neonates in the agar supplementation received oral agar 600 mg/kg/day dissolved in 10 ml distilled water twice daily till TSB decreased to 7 mg/dl. Daily weight, stool frequency and side effects of treatment were observed for each group. TSB was determined pretreatment then serially every 48 h until TSB level reaching ≤7 mg/dl., Results: Agar fed was effective in lowering TSB in neonates with TSB 10-15 mg/dl. TSB percentage changes were not significantly lower in agar-fed newborn with TSB >15-19 mg/dl compared with control groups after 24 h and 7 days. Age fed shortened the time required to decrease TSB and increased stooling frequency., Conclusions: Oral agar supplemented feeding at 600 mg/kg/day is safe for full-term neonates and useful in decreasing TSB and phototherapy duration. The efficacy of phototherapy in decreasing TSB level in neonatal hyperbilirubinemia can be augmented with oral agar usage.

Multidrug resistance poses a global threat to the poultry industry and public health, so the direction towards eliminating the use of antibiotics and finding alternatives is a vital step to solve this problem. Thyme microemulsion (10% oil/water) had nanodrop size 28.65 ± 0.89 nm, with a polydispersity index (PDI) of 0.28 with greater homogeneity. It showed IC 50  > 100 ug/ml on cytotoxicity assay and 14 active components by GC-Mass. The study was carried out using 210 Cobb chicks divided into fourteen groups. The infected groups were challenged using two Salmonella Enteritidis multidrug resistance (MDR) and Salmonella Enteritidis sensitive strains to the sulpha-trimethoprim antibiotic. The challenged inoculum was 1 × 10 9  CFU of Salmonella Enteritidis by oral route. The MIC treatments doses were 1 ml/liter water for thyme oil and thyme microemulsion and 33.34 mg/kg b.wt sulfadiazine for 5 days. The results showed that both thymol oil (0.1%) and microemulsion (0.01%) are able to decrease the count of Salmonella Enteritidis in cecal content and fecal dropping and the mortality rates after five days of treatment. In addition, thyme oil and microemulsion had no pathological alteration on chickens' tissues that were collected two weeks after giving the treatment. By the robust HPLC method, the SDZ and TMP residues in tissues of infected groups treated with Cotrimazine® + thyme oil microemulsion had a slight significant economic impact ( P < 0.05) compared to Cotrimazine® alone. In conclusion, thymol oil and microemulsion could be an alternative economic choice for multidrug resistance Salmonella Enteritidis treatment in poultry farms., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Engy Ahmed Hamed et al.)

Structurally diverse piperazine-based compounds hybrid with thiadiazole, isatin or with sulfur/nitrogen, functionalities were synthesized. The structures of the new compounds were established based on their spectral data and elemental analysis. The physicochemical, bioactivity scores and pharmacokinetic behavior of all the prepared ligands were evaluated using in silico computational tools. The new piperazine ligands have been screened for their inhibition activity against SARS-CoV-2 protease enzyme using molecular docking analysis. The docking studies showed that all the ligands have been docked with negative dock energy onto the target protease protein. Moreover, Molecular interaction studies revealed that SARS-CoV-2 protease enzyme had strong hydrogen bonding interactions with piperazine ligands. The present in silico study thus, provided some guidance to facilitate drug design targeting the SARS-CoV-2 main protease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

The current situation of antibiotic resistance of most bacterial pathogens was a threat to the poultry and public health with increasing economic losses. Regarding this problem, monitoring of the circulating microorganisms occurred with the antibiotic resistance profile. A total of 657 different samples from internal organs (liver, heart, lung, and yolk) and paper-lining chick boxes were collected from native chicken farms which were submitted to the Reference Laboratory for Veterinary Quality Control on Poultry Production in the period from 2014 to 2018 for the detection of Salmonella , Escherichia coli ( E . coli) , and Staphylococcus . The bacterial isolates were tested for their antimicrobial susceptibility by disk diffusion technique. Salmonella was isolated from 128 out of 657 (19.5%), E . coli was isolated from 496 out of 657 (75.5%), and Staphylococcus species was isolated from 497 out of 657 (75.6%). All Salmonella positive samples were examined for antibiotic resistance against 10 different antibiotics, and the highest percentage all over the five years was against penicillin, ampicillin, and tetracycline. All E. coli positive samples were examined for antibiotic resistance against 14 different antibiotics, and the highest percentage all over the five years was with ampicillin, tetracycline, norfloxacin, streptomycin, and danofloxacin. All Staphylococcus positive sample species were examined for antibiotic resistance against 14 different antibiotics, and the highest percentage of resistance all over the five years was shown with tetracycline, streptomycin, ampicillin, and nalidixic acid., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Engy Ahmed Hamed et al.)

In the present study, 200 Brown commercial egg-type layers (60 wk old) were used to study the effects of different levels of ecofriendly synthesis of calcium (Ca) nanoparticles (0.0, 0.50, 1.0, and 1.5 g/kg diet) with biocompatible Sargassum latifolium algae extract (SL-CaNps) on exterior egg quality traits, electronic microscopic view of eggshells, Ca and phosphorus (P) retention, serum Ca and P concentrations, and the histology of the uterus. Hens fed with dietary SL-CaNps powder had higher egg weight and shell weight % values than those of the control group. All SL-CaNps treatment groups had the greatest values of shell weight per unit surface area and shell thickness. Dietary supplementation of SL-CaNps at graded levels up to 1.5 g/kg diet had higher serum Ca and inorganic P levels than that of the control. Laying hens fed with SL-CaNps-added diets had beneficial effects on shell ultrastructure in terms of well-developed palisade and mammillary layers. The numbers of apical cells along the branched tubular gland were greater in SL-CaNps-treated groups than those of control. Conclusively, supplementing SL-CaNps powder up to 1.5 g/kg to the diet of laying hens improved eggshell thickness, shell weight% and shell weight per unit surface and has no adverse effect on their eggshell quality or electronic microscopic view of their eggshell., (Copyright © 2020. Published by Elsevier Inc.)

Background and Objectives: Primary monosymptomatic nocturnal enuresis (PMNE) is a common distressing condition to children and parents. This study aimed to determine frequencies, severities and characteristics of behavioral problems with PMNE., Methods: This cross-sectional study included 80 children with PMNE (age: 12.58 ± 1.24 yrs.; boys = 58, girls = 22) and 60 healthy children. Behavioral symptoms were assessed by Strength and Difficulties Questionnaire (SDQ)., Results: This study included 80 children (boys/girls ratio = 2.64:1) with PMNE. They had mean age of 12.58 ± 1.24 yrs. The majority (70%) had good response to medical treatment. Compared to controls, children with enuresis had higher frequencies of emotional, conduct and hyperactivity-inattention symptoms and peer relationship and prosocial problems and higher total (P = 0.001) and different subscales' scores of SDQ. There was an overlap of behavioral problems in 52.2% of children with nocturnal enuresis. Compared to children without behavioral symptoms, children with behavioral symptoms were significantly older at age at presentation (P = 0.046) regardless of gender, residence and type or response to medications. Multiple regression analysis showed that emotional [β = 0.053 (95%CI = 0.037-0.084), P = 0.024] and hyperactivity-inattention symptoms [β = 0.063 (95%CI = 0.028-0.097), P = 0.001] were significantly associated with enuresis independent to other problems., Conclusion: PMNE is associated with higher risk of behavioral problems particularly emotional and hyperactivity-inattention symptoms indicating externalizing and internalizing problems, therefore, the importance of early non-pharmacological or/and drug interventions. The comorbid behavioral disorders should be treated separately according to evidence-based recommendations to prevent persistence of enuresis and the development of psychiatric disorders in the future., Competing Interests: Declaration of Competing Interest All authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Brachidontes pharaonis (Bivalvia:Mytilidae) is one of the most successful Lessepsian migrants. Its extensive populations' expansion and phenotypic plasticity might reshape the Mediterranean biodiversity. Individuals of B. pharaonis were collected from various sites in the Mediterranean Sea and the Red Sea in Egypt. Species-specific primers for Cytochrome Oxidase Subunit 1 gene were designed. They were applied for analysis of mussel's population genetics and assessment of its aquatic environmental DNA (eDNA) abundance. Morphological, allometric and morphometric characteristics were also described. The newly designed primers could efficiently detect the species presence, abundance, and genetic diversity. The Northern Red Sea and north-westward populations exhibited higher nucleotide diversities than southwards. Phylogeny and principal coordinates' analysis (PCoA) detected three geographical categories for B. pharaonis: one of the Indian Ocean, other of the Middle Red Sea and southwards, and the other extends from the Northern Red Sea to the westernmost part of the Mediterranean. Intraspecific differences in the shell shape, colour, and biometrics were noted. The shells were significantly smaller and lighter in rocky habitats than in sandy ones. The morphometric indices and allometry were significantly different between rocky and sandy environments. In general, B. pharaonis genetic and morphological features appeared to contribute much to the species success in versatile habitats., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: Antimicrobial resistance is a global health threat. This study investigated the prevalence of Escherichia coli in imported 1-day-old chicks, ducklings, and turkey poults., Materials and Methods: The liver, heart, lungs, and yolk sacs of 148 imported batches of 1-day-old flocks (chicks, 45; ducklings, 63; and turkey poults, 40) were bacteriologically examined for the presence of E. coli ., Results: We isolated 38 E. coli strains from 13.5%, 6.7%, and 5.4% of imported batches of 1-day-old chicks, ducklings, and turkey poults, respectively. They were serotyped as O91, O125, O145, O78, O44, O36, O169, O124, O15, O26, and untyped in the imported chicks; O91, O119, O145, O15, O169, and untyped in the imported ducklings; and O78, O28, O29, O168, O125, O158, and O115 in the imported turkey poults. The E. coli isolates were investigated for antibiotic resistance against 16 antibiotics using the disk diffusion method and were found resistant to cefotaxime (60.5%), nalidixic acid (44.7%), tetracycline (44.7%), and trimethoprim-sulfamethoxazole (42.1%). The distribution of extended-spectrum β-lactamase (ESBL) and ampC β-lactamase genes was bla TEM (52.6%), bla SHV (28.9%), bla CTX-M (39.5%), bla OXA-1 (13.1%), and ampC (28.9%)., Conclusion: Imported 1-day-old poultry flocks may be a potential source for the dissemination of antibiotic-resistant E. coli and the ESBL genes in poultry production., (Copyright: © AbdelRahman, et al.)

A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity for the prepared compounds was investigated against four bacterial species and two fungal strains. The symmetrically disubstituted quinoxalines 2 , 3 , 4 , and 5 displayed the most significant antibacterial activity, while compounds 6a , 6b , and the pentacyclic compound 10 showed considerable antifungal activity. Furthermore, compounds 3f, 6b showed broad antimicrobial spectrum against most of the tested strains.

Objective: This study aimed to evaluate fibrosis and elastin destruction in childhood interstitial lung disease (chILD) patients., Methods: Sixty patients and twenty healthy children were recruited. On admission, evaluation of chILD severity was made using Fan chILD score. Participants provided urine and blood samples. Plasma levels of transforming growth factor (TGF)-β 1 , connective tissue growth factor (CCN2), soluble factor related apoptosis (sFas) and long non-coding RNAs and urinary levels of desmosine/urinary creatinine (UDes/UCr) were measured., Results: In patients, clinical findings were crackles (100.00%), tachypnea (65.00%), cardiomegaly (45.00%), digital clubbing (43.30%), cough (33.00%), cyanosis (26.70%), hepatomegaly (28.30%) and wheezes (23.30%). Categorizing of the patients with Fan chILD clinical score revealed that most patients 33.30% scored (3, symptomatic with abnormal saturation/cyanosis during exercise) then 28.30% scored (5, symptomatic with clinical and echocardiographic features of pulmonary hypertension), 18.30% scored (2, symptomatic with normal room air saturations), 15.00% scored (1, asymptomatic) and 5.00% scored (4, symptomatic with abnormal room air saturation/cyanosis at rest). TGF-β 1 , CCN2, sFas, lncrRNA-2700086A05Rik relative gene expression and UDes/UCr levels were higher in patients than controls (P=0.002, P=0.001, P=0.001, P=0.001, P=0.001, respectively). In patients, significant positive correlations were found between TGF-β 1 and CCN2, sFas, UDes/UCr; between CCN2 and both sFas and UDes/UCr; between UDes/UCr and sFas. Morbidity and mortality rates were 46.70% and 10.00%, respectively., Conclusion: Markers of fibrosis (TGF-β 1 , sFas, CCN2) and elastin destruction (UDes/UCr) were increased in chILD especially in patients with long disease duration. So blockage of their pathways signals may offer novel therapeutic targets., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Chemokines have been recently recognized to play a role in chronic pain syndromes' pathophysiology. This study investigated the role of monocyte chemoattractant protein-1 (MCP-1), stromal cell derived factor-1 (SDF-1), and retinoic acid (RA) as targets for the therapeutic approach of neuropathic pain., Methods: A chronic constriction injury (CCI) model of neuropathic pain by unilateral ligation of left sciatic nerve was performed in adult female Wistar rats. The effects of doxycycline (Dox, 50 mg/kg/day i.p. for 7 days), single dose of bicyclam (5 mg/kg i.p.), RA (15 mg/kg/day i.p. for 7 days), and their combination(s) on behavioral tests of nociception (Von Frey filaments; paw pressure test) on days 0, 1, 3, 5, and 7 of operation were studied. Serum concentrations of MCP-1 and SDF-1 were measured by ELISA. Histological examination of the sciatic nerve was investigated., Results: CCI of sciatic nerve significantly induced mechanical allodynia and hyperalgesia and an increase of MCP-1 and SDF-1 serum levels. Dox-treated groups (Dox, Dox+bicyclam, Dox+RA, Dox+bicyclam+RA) and bicyclam-treated groups (bicyclam, Dox+bicyclam, bicyclam+RA, Dox+bicyclam+RA) attenuated CCI-induced behavioral and biochemical changes. RA inhibited CCI-induced mechanical hyperalgesia but produced a time-dependent reversal of allodynia. Histological findings showed degenerative changes of sciatic nerve after CCI that were partially recovered in Dox-treated groups., Conclusions: These findings demonstrate an association between serum MCP-1 and SDF-1 concentrations and behavioral manifestations of neuropathic pain. RA administration decreased neuropathic pain (antihyperalgesic effect) but did not cause any improvement in sciatic nerve tissues, either alone or in combination with chemokine antagonists. Thus, chemokines may serve as potential targets for drug development in neuropathic pain treatment.

Thirty-three isolates of Campylobacter coli and three isolates of Campylobacter jejuni were recovered from 150 1-day-old ducklings. All isolates were sensitive to chloramphenicol and amikacin, but resistant to sulfamethoxazole-trimethoprim (SXT) by the disc diffusion method. Most isolates were susceptible to tetracycline and erythromycin, but resistant to ofloxacin and ciprofloxacin. Of the 33 C. coli isolates, nine were positive for the tetracycline resistance gene tet(O), although only two of these were resistant to tetracycline in the disc diffusion test. None of the isolates possessed mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene infrequently linked to FQ-resistance. The finding indicated that ducklings may be a source of antibiotic resistant Campylobacter spp. with potential poultry and public health hazard., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Diabetic foot ulcer (DFU) is the major global and devastating complication of diabetes mellitus that affects at least 20% of diabetic patients during their lifetime. This article presents an overview of the research evidence on maggot debridement therapy that serves as a guide to health professionals who may be users of this form of treatment now and in the future. It is a time to apply this sample and safe worldwide approved method for diabetic foot ulcer to save money and avoid surgical intervention.

New Findings: What is the central question of this study? Does chronic administration of nicotine by different routes affect gastric hormonal secretions and morphology in rats? What is the main finding and its importance? Chronic nicotine administration increased levels of gastrin, ghrelin and histamine but decreased prostaglandin E2 . Nicotine administered orally and by inhalation had a marked negative impact on the histological structure of the gastric mucosa compared with intraperitoneal administration. The negative impact of nicotine administration on gastric structure was associated with an increased concentration of gastrin and decreased prostaglandin E2 , which might be the cause of gastric/peptic ulcers in heavy smokers. The increase in ghrelin concentration and its effect following chronic nicotine administration needs further investigation. The aim was to assess the effects of different routes of chronic nicotine administration on gastric morphology and hormonal secretion; mainly gastrin, ghrelin, histamine and prostaglandin E2 (PGE2 ). Forty adult male albino rats were randomly assigned into four groups (10 rats per group), treated for 21 days as follows: control group (given standard rat pellets and water only); oral nicotine-treated group [50 μg (ml drinking water)(-1) ]; intraperitoneal nicotine-treated group [0.5 mg (kg body weight)(-1) ]; and inhaled nicotine-treated group [0.5 mg (kg body weight)(-1) ]. Concentrations of gastrin, ghrelin, PGE2 and histamine in serum and gastric tissue homogenates were assessed using ELISA kits. Stomach fundus was processed for histopathology and immunohistochemistry using light and electron microscopy. Different routes of chronic nicotine administration resulted in a significant increase in serum and gastric homogenate gastrin and ghrelin concentrations and a significant decrease in serum and homogenate PGE2 concentrations compared with the control group. Moreover, nicotine administration via oral and inhalation routes caused gastric erosion, transformation of peptic cells into the mucous variety, a significant increase in parietal cell numbers and an increase in expression of gastrin. In conclusion, the negative impact of nicotine administration on gastric structure that is associated with an increased concentration of gastrin and decreased concentration PGE2 might be the leading cause of gastric/peptic ulcers in heavy smokers. The increased ghrelin concentration and its effect following nicotine chronic administration needs further investigation. Based on these findings, we suggest that the alteration in gastric structure following chronic administration of nicotine can be prevented by reducing gastrin secretion and/or targeting its receptors., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested., Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos., Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between 2-20 μM in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034)., Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

Series of Schiff bases of valproic acid hydrazide, N-valproylglycine hydrazide and N-valproyl-4-aminobenzoyl hydrazide derivatives were synthesized and characterized by IR, NMR ((1)H- and (13)C-NMR) and elemental analysis. The prepared compounds were evaluated in transgenic zebrafish embryos (Tg: flil-1: enhanced green fluorescent protein (EGFP)) for antiangiogenic activity and in HepG2 liver carcinoma cell line for anti cancer activity. The Schiff bases of N-valproylglycine hydrazide derivatives were most potent in term of suppressing angiogenic blood vessels formation and anticancer activity at very low concentration, followed by the Schiff bases of valproic acid hydrazide derivatives which exhibited moderate activity, while the Schiff bases of N-valproyl-4-aminobenzoyl hydrazide derivatives, ethyl 4-(2-propylpentanamido)benzoate (VABE) and N-(4-(hydrazinecarbonyl)phenyl)-2-propylpentanamide (VABH) in contrast exhibited pro-angiogenic activity and weaker anticancer activity which mean that these derivatives targeted a common signaling pathway in term of affecting the blood vessels formation.

Background: Glioblastoma multiform (GBM) is a highly aggressive tumor with median survival of approximately 14 months. Management consists of maximal surgical resection followed by post-operative chemoradiation with concurrent then adjuvant temozolamide. The standard radiotherapy dose is 60 Gy in 2-Gy fractions recommended by the radiation therapy oncology group (RTOG). With the vast majority of tumor recurrences occurring within the previous irradiation field and the poor outcome associated with standard therapy, regimens designed to deliver higher radiation doses to improve local control and enhance survival are needed. In this study, we report a single institutional experience in treatment of 68 consecutive patients with GBM, treated with resection, and given post-operative radiotherapy followed by concurrent and/or adjuvant chemotherapy., Results: Of the 80 patients who entered this study, 68 completed the treatment course; 45 (66.2%) males and 23 (33.8%) females with a mean age at diagnosis of 49.0 ± 12.9 (21-75) years. At a median follow up of 19 months, 39 (57.3%) patients had evidence of tumor progression and 36 (52.9%) had died. The median over all survival for all patients was 16 months and progression free survival for all patients was 6.02 months. All potential prognostic factors were analyzed to evaluate their effects on overall survival. Age ≤ 50 year, concurrent and adjuvant chemotherapy and extent of surgery had significant p values. We found lower progression rate among patients who received higher doses of radiotherapy (>60 Gy). Higher radiation doses improved progression free survival (p=0.03). Despite increasing overall survival, this elevation was not significant., Conclusions: This study emphasize that higher radiation doses of (>60 Gy) can improve local control and potentially survival, so we strongly advise prospective multi centric studies to evaluate the role of higher doses of radiotherapy on GBM patient outcome.

Background: Male breast cancer accounts for less than 1% of all cancer in men and only around 1% of all diagnosed breast cancer. Despite a significant raise in the last 25 years, it still remains a rare disease., Materials and Methods: We conducted a retrospective study from 2004-2011 with 21 male breast cancer patients. We aimed to analyze the epidemiologic data (age, personal and family history), tumor characteristics (size, histological type, location, TNM stage, receptors), surgery, adjuvant chemotherapy and radiation therapy, hormonal therapy and survival (relapse, follow up, death) who reffered to our center with breast cancer., Results: The median age was 49.2±14.2 years (range 30-83 years). A family history of breast cancer was noted in four cases. The main clinical complaint was a retroareolar mass in 85.7%of patients (n=18). Histologically, 85.7% (n=18)were invasive ductal carcinoma and 4.7% (n=1) had ductal carcinoma in situ and 9.4% (n=2) had mixed histology including invasive medullary and ductal carcinoma. Hormonal therapy was delivered to 16 cases (76.1%) due to ER or PR positivity. During median follow up of 30 months (3-84 month), distant metastases were evident in 4 cases (19%). During the follow-up period, only one patient died due to metastatic disease. The mean time to recurrence detection was 30 months., Conclusions: The percentage of cases of male breast cancer is very low compared to breast cancer in females, explaining why very few investigations have been conducted in Iran. Limited coverage in the literature make gender-specific findings difficult so future research of this entity involving multi-institutional cooperation and longer follow up is essential to provide new insights about the biological and clinical factors of this rare cancer.

Background: Tissue injury due to hypoxia and/or free radicals is common in a variety of disease processes. This cross-sectional study aimed to investigate effect of chronic kidney diseases (CKD) and hemodialysis (HD) on hypoxia and oxidative stress biomarkers., Methods: Forty pediatric patients with CKD on HD and 20 healthy children were recruited. Plasma hypoxia induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) were measured by specific ELISA kits while, total antioxidant capacity (TAC), total peroxide (TPX), pyruvate and lactate by enzymatic/chemical colorimetric methods. Oxidative stress index (OSI) and lactate/pyruvate (L/P) ratio were calculated., Results: TAC was significantly lower while TPX, OSI and VEGF were higher in patients at before- and after-dialysis session than controls. Lactate and HIF-1α levels were significantly higher at before-dialysis session than controls. Before dialysis, TAC and L/P ratio were lower than after-dialysis. In before-dialysis session, VEGF correlated positively with pyruvate, HIF-1α and OSI correlated positively with TPX, but, negatively with TAC. In after-dialysis session, HIF-1α correlated negatively with TPX and OSI; while, OSI correlated positively with TPX., Conclusions: CKD patients succumb considerable tissue hypoxia with oxidative stress. Hemodialysis ameliorated hypoxia but lowered antioxidants as evidenced by decreased levels of HIF-1α and TAC at before- compared to after-dialysis levels.

Purpose: Breast cancer (BC) is a complex, multi-stage disease involving deregulation of different signaling cascades. The present study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with different stages of BC as an approach to disease biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-α as apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide (NO) as oxidative stress and angiogenic indices were measured in patients with BC., Methods: Thirty-seven newly diagnosed patients with BC, 30 patients with benign breast masses, and 30 healthy controls were recruited. Plasma levels of sFas, bcl-2, IL-8, and TNF-α were measured by immunosorbent assay kits and LPO and NO by chemical methods., Results: Plasma sFas and LPO were significantly higher in BC patients versus benign breast masses and healthy controls (P < 0.0001). Bcl-2, IL-8, TNF-α, and NO were significantly higher in benign breast masses (P < 0.0001, P < 0.037, P < 0.0001, P < 0.001) and BC (P < 0.0001) versus controls and in BC versus benign breast masses (P < 0.0001). sFas, bcl-2, IL-8, TNF-α, LPO, and NO were increased with advanced tumor stages. There were positive correlations between sFas, bcl-2, IL-8 TNF-α, LPO, and NO., Conclusions: BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth and survival. However, this coincides with activation of physiologic regulatory mechanisms, as increased IL-8, TNF-α, LPO, and NO, which try to stop tumor cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor progression as IL-8, TNF-α, and NO are also angiogenic stimulators.

Type 2 diabetes mellitus (T2DM) is largely defined by hyperglycemia that promotes vascular complications. Abnormal angiogenesis has been claimed to have a role in this disease. This study aimed to investigate serum levels of both conventional and other markers of angiogenesis not well studied before in diabetes, and to correlate findings with age of the patients, glycemic control, presence of microvascular complications, and oxidative stress. Thirty-eight patients with T2DM and 13 age- and sex-matched healthy persons representing controls were recruited. Serum levels of basic fibroblast growth factor (b-FGF) was measured by immunosorbent assay kit; advanced glycosylation end products, platelet-derived endothelial cell growth factor (PD-ECGF), cathepsin-D (CD), gangliosides, hyaluronic acid (HA), nitric oxide (NO), lipid peroxides (LPER), superoxide dismutase, and total thiols by chemical methods; and copper (Cu) by atomic absorption flame photometry. Advanced glycosylation end products and angiogenic factors (b-FGF, PD-ECGF, CD, gangliosides, HA, and Cu) were significantly higher in patients than controls. Oxidative stress markers, NO, and LPER were significantly higher while total thiols were significantly lower in patients than controls. These changes were more pronounced with age, poor glycemic control, and presence of microvascular complications. Angiogenesis dysfunction coinciding with elevated levels of many angiogenic growth factors may point to their malfunctioning due to oxidative stress and/or protein glycation at the factor and the receptor levels. This necessitates further investigations.

Background: Skeletal involvement in patients with type 1 diabetes mellitus (T1DM) has complex pathogenesis and despite numerous researches on this problem, many questions remain unanswered., Objective: This study aimed to assess bone status by measurement parathormone (PTH), 25-hydroxy vitamin D [25(OH)D] serum levels in children and adolescents with T1DM and its relation to insulin-like growth factor-1 (IGF-1), disease duration, puberty stage, and metabolic control., Patients and Methods: This study included 36 children and adolescents with T1DM and 15 apparently healthy controls. Serum levels of 25(OH)D, PTH, IGF-1 measured using enzyme-linked immunosorbent assay (ELISA), while glycosylated hemoglobin (HbA1c), calcium (Ca), inorganic phosphorus (PO(4) ) using autoanalyzer. Bone quality assessed using dual energy X-ray absorptiometry (DEXA)., Results: Diabetic patients showed significant increase in PO(4) and PTH levels, while significant decrease in Ca, IGF-1, and 25(OH)D serum levels. As much as 52.8% of patients showed reduced 25(OH)D, and 30.65% showed elevated PTH serum levels. In diabetic patients, abnormal bone status (osteopenia-osteoporosis) found mostly in total body (94.40%) then lumber-spine (88.90%), ribs (88.90%), pelvis (86.10%), thoracic-spine (80.60%), arms (80.60%) and legs (77.80%), while head bones showed no abnormalities. Long diabetic duration had negative; meanwhile PTH, onset age, and puberty age had positive impact on bone status., Conclusions: Children and adolescent with T1DM have abnormal bone status mostly in axial skeleton which may be contributed to impairment of formation of 25(OH)D and IGF-1. Physical activity, calcium and vitamin D supplement seem important in T1DM. Elevated serum PTH level in diabetic patients is not uncommon and its positive correlation with bone status needs further investigations., (© 2011 John Wiley & Sons A/S.)

Recent studies have shown that lead (Pb) could disrupt tissue prooxidant/antioxidant balance which lead to physiological dysfunction. Natural antioxidants are particularly useful in such situation. Current study was designed to investigate efficacy of green tea extract (GTE), on oxidative status in brain tissue and blood caused by chronic oral Pb administration in rats. Four groups of adult male rats (each 15 rats) were utilized: control group; GTE-group (oral 1.5% w/v GTE for 6 weeks); Pb-group (oral 0.4% lead acetate for 6 weeks), and Pb+GTE-group (1.5% GTE and 0.4% lead acetate for 6 weeks). Levels of prooxidant/antioxidant parameters [lipid peroxides (LPO), nitric oxides (NO), total antioxidant capacity (TAC), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD)] in plasma, erythrocytes, and brain tissue homogenate were measured using colorimetric methods. Pb concentrations in whole blood and brain tissue homogenate were measured by atomic absorption. In Pb-group, levels of LPO were higher while NO and GSH were lower in plasma, erythrocytes, and brain tissue than controls. TAC in plasma, SOD in erythrocytes, and GST in brain tissue homogenate were lower in Pb-group versus control. GTE co-administrated with Pb-reduced Pb contents, increased antioxidant status than Pb-group. In erythrocytes, Pb correlated positively with LPO and negatively with NO, GSH, SOD, and Hb. In brain tissue homogenate, Pb correlated positively with LPO and negatively with GSH. This study suggests that lead induce toxicity by interfering balance between prooxidant/antioxidant. Treatment of rats with GTE combined with Pb enhances antioxidant/ detoxification system which reduced oxidative stress. These observations suggest that GTE is a potential complementary agent in treatment of chronic lead intoxication.

Background: In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies mainly in adult demonstrating renal involvement in beta-thalassemia. This prospective study was aimed to investigate renal involvement in pediatric patients with transfusion dependent beta-thalassemia major (TD-betaTM), using both conventional and early markers of glomerular and tubular dysfunctions, and to correlate findings to oxidative stress and iron chelation therapy., Methods: Sixty-nine TD-betaTM patients (aged 1-16 years) and 15 healthy controls (aged 3-14 years) were enrolled in this study. Based on receiving chelation therapy (deferoxamine, DFO), patients were divided into two groups: group [I] with chelation (n=34) and group [II] without chelation (n=35). Levels of creatinine (Cr), calcium (Ca), inorganic phosphorus (PO4), uric acid (UA) and albumin were measured by spectrophotometer. Serum (S) levels of cystatin-C (SCysC) and total antioxidant capacity (STAC) and urinary (U) levels of beta2-microglobulin (Ubeta2MG) were measured by immunosorbent assay (ELISA). Urinary N-acetyl-beta-D-glucosaminidase (UNAG) activity and malondialdehyde (UMDA) were measured by chemical methods. Estimated glomerular filtration rate (eGFR) was determined from serum creatinine., Results: In patient with and without chelation, glomerular [elevated SCysC, SCr, Ualbumin/Cr and diminished eGFR]; and tubular dysfunctions [elevated SUA, SPO4, UNAG/Cr, Ubeta2MG/Cr] and oxidative stress marker disturbances [diminished STAC and elevated UMDA/Cr] were reported than controls. In patients with chelation, SCysC was significantly higher while, STAC was significantly lower than those without chelation. In all patients, SCysC showed significant positive correlation with SCr and negative correlation with eGFR; STAC showed significant positive correlation with eGFR and negative correlation with SCysC, SCr, UNAG/Cr; UMDA/Cr showed significant positive correlation with Ualbumin/Cr, Ubeta2MG/Cr, UNAG/Cr., Conclusions: Our data confirm high frequency of glomerular and tubular dysfunctions in TD-betaTM pediatric patients which could be attributed to oxidative stress and DFO therapy.

Bone disease in beta-thalassemia major (betaTM) remains poorly understood. Receptor activator of nuclear factor-kappabeta ligand (RANKL) regulates osteoclast formation and function. RANKL activity is balanced by interaction with its receptor (RANK) and binding to osteoprotegerin (OPG). L-Carnitine (LC) enhances osteoblastic activity by furnishing fuel. This study hypothesized that abnormal bone metabolism in betaTM involves imbalanced RANKL/OPG and LC/free fatty acids (FFAs) metabolism. Sixty-nine transfusion-dependent betaTM patients and 15 healthy controls were enrolled. One group of patients (n=34) received desferrioxamine (DFO) and the other (n=35) did not. Serum OPG, soluble RANKL (sRANKL), FFAs, LC [total LC (TC), free LC (FC), and esterified LC (EC)], calcium, and inorganic phosphate were measured by specific immuno and colorimetric assays; bone mineral density was examined by dual x-ray absorptiometry. Patients showed lower levels of OPG, TC, FC, EC and higher levels of sRANKL, sRANKL/OPG ratio, and FFAs than controls. Patients on DFO showed lower levels of OPG, TC, FC and higher levels of sRANKL, sRANKL/OPG ratio, and FFAs than those without chelation. In patients, sRANKL correlated negatively with TC and OPG and FC correlated positively with OPG and negatively with sRANKL, sRANKL/OPG ratio, and FFAs. In conclusion, altered bone metabolism owing to imbalanced osteoclastic bone resorption versus constructive osteoblastic activities in betaTM pediatric patients could be due to abnormal sRANKL-OPG and LC-FFAs systems that were worsened by DFO.

Recent studies indicated that migraine is associated with specific vascular risk profile. However, the functional and structural vascular abnormalities in migraine are rarely addressed. We evaluated the vascular risk factors, endothelial function, and carotid artery (CA)-intima-media thickness (IMT), segregators of preclinical atherosclerosis, in migraineurs. This preliminary study included 63 adults with headache (migraine with aura [n=14], migraine without aura [n=24], transformed migraine [n=6], and tension headache [n=19]) and 35 matched healthy subjects. The following vascular risks were assessed: body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures (DBP), serum levels of C-reactive protein, fasting glucose, fasting insulin, total cholesterol, and triglycerides. Plasma endothelin (ET)-1, a vasoactive peptide produced by vascular smooth muscle cells and marker for endothelial injury and atherosclerosis, was measured. Endothelial-dependent vasoreactivity was assessed using brachial artery flow-mediated dilatation (FMD) in response to hyperemia. CA-IMT, structural marker of early atherosclerosis, was measured. Compared with control subjects, SBP, DBP, glucose, insulin, ET-1, and CA-IMT were elevated with migraine. FMD% was inversely correlated with SBP (P < .001), DBP (P < .01), glucose (P < .001), and insulin levels (P < .01). CA-IMT was correlated with BMI (P < .05), SBP (P < .01), total cholesterol (P < .01), triglycerides (P < .001), glucose (P < .001), insulin (P < .01), and FMD% (P < .05). In multivariate analysis, ET-1 was correlated with duration of illness, SBP, DBP, glucose, insulin, IMT, and FMD%. We conclude that endothelial injury, impaired endothelial vasoreactivity, and increased CA-IMT occur with migraine and are associated with vascular risk factors that strongly suggest that migraine could be a risk for atherosclerosis., (Copyright 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO) and reactive oxygen species in the complex pathophysiology of bacterial meningitis., Methods: In the present study, serum and CSF levels of NO, lipid peroxide (LPO) (mediators for oxidative stress and lipid peroxidation); total thiol, superoxide dismutase (SOD) (antioxidant mediators) and S-100B protein (mediator of astrocytes activation and injury), were investigated in children with bacterial meningitis (n = 40). Albumin ratio (CSF/serum) is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio) is indicative of intrathecal synthesis., Results: Compared to normal children (n = 20), patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p < 0.05); CSF-LPO with CSF-protein (r = 0.423, p < 0.01); total thiol with LPO indices (r = 0.725, p < 0.0001); S-100B and Pediatric Glasow Coma Scores (0.608, p < 0.0001); CSF-LPO with CSF-S-100B (r = 0.482, p < 0.002); serum-total thiol with serum S-100B (r = 0.423, p < 0.01)., Conclusion: This study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.