Study of the effect of ACYP2 single nucleotide polymorphisms rs843711 and rs843706 in Egyptian patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a multifactorial disease with both genetic and environmental factors contributing to its pathogenesis. ACYP2 is a gene that is related to cell differentiation, apoptosis and prevention of malignant tumors. The ACYP2 gene also affects telomere length. The aim of this study was to evaluate the association between ACYP2 single nucleotide polymorphisms (SNPs) (rs843711), and (rs843706) and incidence of HCC in Egyptian HCC patients. The study included 30 patients with HCC and 30 normal controls. Detection of ACYP2 gene SNPs rs843711, and rs843706 in all study participants was done using real time polymerase chain reaction (RT-PCR). The results showed that all participants including HCC patients and controls carried the heterozygous CA (100%) of the rs843706 SNP (p> 0.05). As for the rs843711, 3.3% of HCC patients had the homozygous TT genotype, 46.7% had the heterozygous CT genotype and 50% had the wild CC genotype, while in the control group, 60% had the heterozygous CT genotype and 40% had the wild CC genotype with no significant difference between both groups (p>0.05). We concluded that there was no association between SNPs ACYP2 rs843706 and rs843711 and occurrence of HCC.

Synthesis and biological evaluation against H. pylori of chitosan menthone Schiff base hybrid with different types of inorganic nanoparticles.

The production of novel natural medicines for the treatment of Helicobacter pylori (H. pylori) has lately attracted a lot of interest. Some bacterial infections have traditionally been alleviated by terpenes. The present work intended to examine the impact of several chitosan menthone Schiff base nanocomposites on the treatment of H. pylori infection as well as on its anti-inflammatory capacity. Chitosan (Cs) was condensed with menthone with different molar ratios of Cs:menthone (1:0.5, 1:1, and 1:2) to produce chitosan Schiff bases namely; Cs-SB1, Cs-SB2, and Cs-SB3, respectively. Cs-SB3 Schiff base nanocomposites were prepared individually by adding 2%Ag, 2%Se, (1%Ag + 1%Se), and 2%Fe2O3 nanoparticles to produce compounds denoted as Cs-SB-Ag, Cs-SB-Se, Cs-SB-Ag/ Se, and Cs-SB-Fe, respectively. The anti-H. pylori activity of Cs-SB-Se was detected at a minimal inhibitory concentration MIC of 1.9 µg/mL making it the most biologically active compound in our study. Cs-SB-Se nanocomposite was tested for its cyclooxygenases (COX-1 and COX-2) inhibitory potential which demonstrated inhibitory efficacy towards COX enzymes with inhibition value against COX-1 (IC50 = 49.86 ± 1.784 µg/mL) and COX-2 (IC50 = 12.64 ± 0.463 µg/mL) which were less than the well-known Celecoxib (22.65 ± 0.081 and 0.789 ± 0.029 µg/mL) and Indomethacin (0.035 ± 0.001 and 0.08 ± 0.003 µg/mL) inhibitors. The selectivity index SI = 3.94 for tested nanocomposites indicated higher selectivity for COX-1. The cytotoxicity of the Cs-SB-Se nanocomposite was evaluated in Vero cells (CCL-81) and it showed that at a concentration of 62.5 µg/mL, cell viability was 85.43 %.

The Experiences of Newly Graduated Nurses during Their First Year of Practice.

The present study aimed to explore the experiences of newly graduated nurses during their first year of practise. A qualitative descriptive design was employed in this study. In-depth, semi-structured interviews were conducted with newly graduated nurses to gather detailed descriptions and experiences during their transition to the workplace in the first year after graduation. Thematic analysis was utilised to identify patterns and themes in the collected data. Ethical considerations were strictly enforced throughout the study. There are two main themes: factors contributing to the integration of new nurses into the workplace and the difficulties faced by new nurses in a work environment. Within the first theme, three subthemes emerged: the positive role of trainers, the gradual handling of patients, and the benefit of pre-employment training and volunteering. The theme of difficulties faced included three subthemes: difficulty dealing with the health system and devices, fear of dealing with new patients, and difficulty applying policies and procedures in the workplace. The study provides insights into the challenges faced by newly graduated nurses and the factors that contribute to their integration into practise settings. Educational departments in hospitals' support and efficient access to policies are crucial for these nurses as they begin their early professional years.

Review of clonal hematopoiesis, subtypes and its role in neoplasia and different morbidities.

Clonal hematopoiesis (CH) is the development of a certain cell lineage which is the cornerstone of hematologic malignancy especially myeloid neoplasms, however, can also be found in old age (6th-7th decade). CH is caused by many different somatic mutations most commonly in DNMT3A, TET2, ASXL1, SF3B1 and TP53. It is detected by different sequencing methods, the most commonly used ones are next generation sequencing (NGS) which can be whole exome, whole genome sequencing or a panel for certain genes. CH is divided into multiple categories depending on the clinical picture associated with it into: clonal monocytosis of undetermined significance (CMUS), clonal hematopoiesis of indeterminate significance (CHIP), clonal cytopenia and monocytosis of undetermined significance (CCMUS) and clonal cytopenia of undetermined significance (CCUS). In order to diagose CH, first other hematologic malignancies must be ruled out CH is also associated with many different entities including lung cancer and some studies have shown that COVID-19 infections are affected by CH. Certain traits and infections are associated with CH including smoking, obesity, and cardiovascular disease. A minority of patients with CH progress to a malignant process (between 0.5 %-2 %) which do not require treatment, however, any patient with CH should be kept under surveillance in order to detect any malignancy early and be treated accordingly. SIMPLE SUMMARY: Clonal hematopoiesis (CH) is considered to be the predisposing factor for development of different hematologic neoplasms. With the help of NGS, patients with CH can be monitored more closely. Several studies have shown that these patients might develop hematologic neoplasms in their lifetime. It has been subdivided into multiple groups according to the clinical picture and/or blood counts.

Synthesis and characterization of poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugate hyaluronate for targeted delivery of methotrexate drug to colon cancer cells.

Anti-cancer medications that are delivered specifically to the tumor site possess greater efficacy with less negative effects on the body. So, the current research relies on a novel method for intercalating the anticancer medication methotrexate in poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugated with sodium hyaluronate. The graft copolymers were synthesized through persulfate-initiated grafting of acrylic acid onto a binary mixture of various amounts of chitosan and poly(3-hydroxybutyrate) (2/1, 1/1 and 1/2, w/w) using microwave irradiation. The graft copolymer was conjugated with sodium hyaluronate for targeted delivery of methotrexate drug specifically to colon cancer cell lines (Caco-2). The graft copolymers were characterized by many physical techniques. The maximum drug loading efficiency was observed in case of the graft copolymer/hyaluronate rich in chitosan content 69.7 ± 2.7 % (4.65 mg/g) with a sustained release about 98.6 ± 1.12 %, at pH 7.4. The findings of severe cytotoxicity having a value of the IC50 of 11.7 µg/ml, a substantial proportion of apoptotic cells (67.88 %), and an elevated level of DNA breakage inside the treated Caco-2 cells verified the effective release of methotrexate from the loaded copolymer matrix. Besides, the high stability and biological activity of the released drug was exhibited through occurrence of greater increment of reactive oxygen species and effect on the extent of expression of genes connected to apoptosis and anti-oxidant enzymes within the treated cells. Ultimately, this system can be recommended as potent carrier for methotrexate administration to targeted cancerous cells in the colon.

An effective uranium removal using diversified synthesized cross-linked chitosan bis-aldehyde Schiff base derivatives from aqueous solutions.

Three new cross-linked chitosan derivatives were yielded through intensification of chitosan with diverse types of bis-aldehydes. The prepared cross-linked chitosan was characterized by FTIR, 1H NMR, XRD, and TGA techniques. TGA indicated an improvement in thermal stability of the cross-linked chitosan compared with pure chitosan. Batch adsorption experiments showed that the three novel cross-linked chitosan bis-aldehyde derivatives possessed good adsorption capacity against U(VI) in the order of BFPA > BFB > BODB (adsorption capacity of the three adsorbents for U(VI) reaches 142, 124, and 114 mg/g respectively) and the adsorption isotherm and kinetic were well described by the Langmuir and the pseudo-second-order kinetic model, respectively. In addition, the prepared cross-linked chitosan bis-aldehyde derivatives were examined as U(VI) catcher from waste solutions.

Betanin ameliorates fipronil-induced nephrotoxicity via activation of Nrf2-HO-1/NQO-1 pathway in albino rat model.

Fipronil (FPN) is phenylpyrazole insecticide extensively used to control a wide variety of pests. Betanin (BET) is a natural colorant with promising antioxidant and anti-inflammatory effects. This study aimed to investigate the potential protective effect of BET on FPN induced nephrotoxicity in adult male albino rats. Forty rats were assigned into 4 equal groups; Group I (Control); Group II (BET) received 20 mg/kg b.wt/day; Group III (FPN) received 4.8 mg/kg b.wt/day; and Group IV (BET/FPN). All treatments were given orally for 90 days. At the end of experiment, blood samples were collected for analysis of serum urea and creatinine. Kidneys were harvested for determination of kidney injury molecule-1(KIM-1) level; gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO-1); oxidative stress biomarkers including malondialdehyde (MDA), protein carbonyl content (PCC), catalase activity (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH). Histopathological examination and immunohistochemical investigation of Nrf2, nuclear factor kappa B (NF-κB), and caspase-3 were also undertaken. The results revealed kidney dysfunction, downregulation of Nrf2, HO-1, and NQO-1 genes, redox imbalance, structural damage, decreased Nrf2 and increased NF-κB immune-expression, in addition to strong caspase-3 immunoreactivity in FPN-treated group. In the combined group, BET co-administration resulted in functional and structural amelioration, up-regulation of Nrf2, HO-1, and NQO-1 genes, mitigation of redox imbalance, and strong anti-inflammatory and antiapoptotic effects. In conclusion, BET via activation of Nrf2-HO-1/NQO-1 pathway, exhibits beneficial antioxidant, anti-inflammatory, and antiapoptotic effects against FPN-induced nephrotoxicity.

Chitosan Schiff bases-based polyelectrolyte complexes with graphene quantum dots and their prospective biomedical applications.

Chitosan (Cs) bis-aldehyde Schiff base derivatives were synthesized by condensation of Cs with three bis-aldehydes namely; butane-1,4-diyl bis(4-formylbenzoate), N,N'-(butane-1,4-diyl)bis(2-(4-formylphenoxy)acetamide) and 4,4'-(butane-1,4-diylbis(oxy))dibenzaldehyde. The prepared Cs derivatives were blended with carboxymethyl chitosan(CMC) and graphene quantum dots (GQDs) to produce semi-IPNs polyelectrolyte complexes (PECs). and characterized with respect to their molecular structure and physio-chemical properties. The antibacterial activity against H. pylori (and in vitro Inosine 5'-monophosphate dehydrogenase IMPDH inhibitory assay) was evaluated. Additionally, a preliminary in vitro assessment for wound healing was performed against PECs in which wound closure percentages, and rates were investigated indicating an accelerated wound healing compared with untreated cells. The PEC based on Schiff base PEC containing amide linkage showed the highest wound healing ability. A minimal inhibitory concentration (MIC) was obtained for the PEC sample containing Cs Schiff base derived from 4,4'-(butane-1, 4-diylbis(oxy))dibenzaldehyde at a dose of 0.98 µg/ml inhibiting H. pylori growth by 100%. Additionally, the selected above-mentioned compound was selected to test its inhibitory activity against the HpIMPDH enzyme in addition to its selectivity towards the hIMPDH2 enzyme and was found to have promising activity against the HpIMPDH enzyme with IC50 value of 0.65 µM, and to be safer and less active against the hIMPDH2 enzyme with IC50 > 10 µM, reflecting its selectivity.

Effect of some non-genetic factors on the productivity and profitability of Holstein Friesian dairy cows.

BACKGROUND AND AIM: Milk yield (MY) is one of the main factors that affect the economic profitability of dairy farms. Thus, increasing the MY per animal and decreasing the feed cost can lead to economic gains, so the objective of this study was to evaluate the effect of dry period length (DPL), days open (DO), and days in milk (DIM) on the productivity and profitability of dairy cow farms. MATERIALS AND METHODS: Data used in this study were taken from 3095 lactation records of Friesian dairy cows of private and governmental sectors. The data were classified into 4 DPL categories: DPL1 <45 days; DPL2 45-60 days; DPL3 61-75 days, and DPL4 >75 days, 3 DO categories: DO1 ≤90 days; DO2 91-110 days and DO3 >111 days, and 8 DIM categories: DIM1 180-210 days; DIM2 211-240 days; DIM3 241-270 days; DIM4 271-300 days; DIM5 301-330 days; DIM6 331-360 days; DIM7 361-447 days; and DIM8 >447 days. RESULTS: The average net profit (NP) was significantly different (p<0.05) among different categories of DPL, DO, and DIM in both production sectors, where high estimates of NP were calculated for DPL3 (30667.3 EGP), and it was the lowest for DPL1 (19690.6 EGP). DO2 had the highest NP (30754.1 EGP), while DO3 had the lowest NP (24875.5 EGP). DIM3 had the highest NP (29569.3 EGP), while DIM8 had the lowest NP (19528.4 EGP). CONCLUSION: Finally, we can conclude that DPL 61-75 days, DO 91-110 days, and DIM 241-270 days had the highest level of total MY, total return, and NP. Private dairy cow farms achieve a higher level of NP than governmental ones under subtropical Egyptian conditions.

Synthesis, characterization and antimicrobial activity of a novel chitosan Schiff bases based on heterocyclic moieties.

Three heteroaryl pyrazole derivatives; namely 1-phenyl-3-(thiophene-2-yl)-1H-pyrazole-4-carbaldehyde, 1-phenyl-3-(furan-2-yl)-1H-pyrazole-4-carbaldehyde and 1-phenyl-3-(pyridine-3-yl)-1H-pyrazole-4-carbaldehyde were synthesized and reacted with chitosan to form Schiff bases of chitosan. All newly synthesized compounds have been characterized by solubility tests, elemental analysis, spectral (FTIR, 1H NMR) analyses, thermogravimetric analysis and X-ray diffraction (XRD). The Schiff bases were screened for their biological activity against gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans) and fungi (Asperagillus fumigatus and Candida albican). The results indicated that the antimicrobial activity was dependent on the type of the Schiff base moiety. Cytotoxicity of the prepared chitosan derivatives was evaluated by MTT assay and the results indicated the absence of cytotoxic activity.

Correlation of Specimen/Breast Volume Ratio to Cosmetic Outcome After Breast Conserving Surgery.

Breast conserving surgery (BCS) is currently the standard of care for early breast cancer. One of the key determinants for the line of treatment in breast cancer is the size of the tumor in relation to the breast size. The aim of this study is to determine the effect of the ratio of the excised specimen to breast volume on the cosmetic outcome after conventional BCS. This is a retrospective study conducted on female patients with early stage breast cancer who underwent BCT at National Cancer Institute, Cairo University. The study included 41 patients with stage I and II breast cancer. Breast volume was calculated using mammography, and ratio of the specimen to breast volume was determined. This ratio was correlated with the cosmetic outcome using the BCCT.core software. Thirty-six out of the 41 breast cancer patients completed the study. Favorable outcome (excellent + good) was detected in 52.7% of patients, while 47.3% had unfavorable outcome (fair + poor). Breast volume, tumor site, patients' age, and weight did not seem to alter the cosmetic result. The only statistically significant factors affecting the cosmetic outcome were the specimen volume and the ratio of the specimen to the normal breast volume (p = 0.006 and 0.019 respectively). In order to obtain a satisfactory cosmetic outcome after conventional BCS, the ratio of the excised specimen to breast volume has to be seriously considered.

Anti-Müllerian hormone levels in patients with turner syndrome: Relation to karyotype, spontaneous puberty, and replacement therapy.

Most girls with Turner syndrome (TS) suffer from incomplete sexual development, premature ovarian failure, and infertility due to abnormal ovarian folliculogenesis. Serum anti-Müllerian hormone (AMH) levels reflect the ovarian reserve in females, even in childhood. Thus, we aimed to assess serum AMH levels in girls with TS and its relation to karyotype, spontaneous puberty, and growth hormone (GH) therapy. Fifty TS were compared to 50 age- and sex-matched controls. All subjects were subjected to history, anthropometric assessment, Tanner pubertal staging and measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and AMH. Karyotype results were obtained from patients' records. Serum AMH was measurable in 12 TS patients (24%). The lowest frequency of measurable AMH was in patients with a karyotype of 45,X. The measurable AMH was associated with spontaneous breast development (p = .003) and spontaneous menarche (p = .001). AMH correlated negatively with FSH (r = -.846, p = .000) and LH (r = -.83, p = .034). GH therapy increased the odds of having measurable AMH in TS girls (p = .002). In conclusion, AMH was associated with karyotype, spontaneous pubertal development, LH, and FSH in TS girls and may serve as a useful marker of ovarian function and ongoing follicular development in prepuberty.

Vitamin D status in prepubertal children with isolated idiopathic growth hormone deficiency: effect of growth hormone therapy.

Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels <30 ng/mL and 20 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. 25(OH)D was lower in cases than controls. Forty per cent of children with GHD were 25(OH)D insufficient and 44% deficient, while 16% were sufficient at baseline. There was a positive correlation between 25(OH)D and peak GH levels. Peak GH was a significant predictor of 25(OH)D levels. After 1 year of GH therapy, 25(OH)D increased (18.42±5.41 vs 34.5±10.1 ng/mL; P<0.001). Overall, 22% of cases remained insufficient and 24% deficient, with an increase in prevalence of children with normal levels (54%; P<0.001). 25(OH) correlated negatively with PTH (r=-0.71, P=0.01). In conclusion, hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy. 25(OH)D should be assessed in children with GHD at diagnosis and during follow-up.

Dietary fructose intake in obese children and adolescents: relation to procollagen type III N-terminal peptide (P3NP) and non-alcoholic fatty liver disease.

BACKGROUND: Excessive use of fructose has been incriminated as a risk factor for hepatic steatosis. Procollagen type III N-terminal peptide (P3NP) is a marker for steatohepatitis. Thus, we aimed to assess fructose intake in obese children and its relation to nonalcoholic fatty liver disease (NAFLD) and P3NP. METHODS: Fifty-five obese children were compared to 30 controls. All were subjected to dietary fructose and anthropometric assessment, fasting blood sugar (FBS), fasting insulin (FI) and homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, uric acid, alanine aminotransferase (ALT), P3NP and abdominal ultrasound. RESULTS: Patients had higher fructose intake which was associated with increased NAFLD grade. There was an increase in P3NP with increased NAFLD grade. P3NP correlated positively with fructose intake (processed sources and total) and caloric intake. CONCLUSIONS: High fructose intake is associated with NAFLD and P3NP may serve as a marker of NAFLD in obese children with a proposed cutoff value of 8.5 ng/mL.

Serum Chemerin in Obese Children and Adolescents Before and After L-Carnitine Therapy: Relation to Nonalcoholic Fatty Liver Disease and Other Features of Metabolic Syndrome.

BACKGROUND AND AIMS: Chemerin plays an important role in metabolic syndrome (MetS) including nonalcoholic fatty liver disease (NAFLD). L-carnitine (LC) may reduce plasma glucose, lipid profile, and improve liver function. The aim of the study was to assess serum chemerin in obese children with suspected NAFLD, the effect of LC on NAFLD grade, chemerin and metabolic profile. METHODS: Fifty obese children were compared to 50 controls. All were subjected to anthropometric assessment, liver function, fasting lipid profile, glucose/insulin (G/I) ratio, homeostasis model assessment (HOMA) index, serum chemerin and abdominal ultrasonography before and after LC. RESULTS: Serum chemerin was higher in cases than controls. Eighty percent of cases had NAFLD with increase in chemerin as severity of NAFLD increased. There was a decrease in frequency of NAFLD and its severity after LC therapy. CONCLUSIONS: Noninvasive monitoring of serum chemerin in obese patients with suspected NAFLD could be used to diagnose NAFLD. LC supplementation is effective in treatment of NAFLD and reducing chemerin.

Iron homeostasis and serum hepcidin-25 levels in obese children and adolescents: relation to body mass index.

BACKGROUND/AIMS: The etiology of the hypoferremia of obesity is unclear. Hepcidin is the body's main regulator of systemic iron (Fe) and has been reported to be elevated in obese patients. Thus, we aimed to assess Fe status and serum hepcidin-25 levels and their relationship with body mass index (BMI) in obese Egyptian children and adolescents. METHODS: Fifty obese children were compared to 50 age-, sex- and pubertal stage- matched controls. All subjects were subjected to history and anthropometric assessment and measurement of serum Fe, total iron binding capacity (TIBC), ferritin, transferrin saturation (TS), soluble transferrin receptor (sTfR) and hepcidin. RESULTS: Fe, TS and TIBC were lower, while ferritin, sTfR and hepcidin-25 were higher in obese patients than controls. BMI standard deviation score (SDS) correlated negatively with Fe (r = -0.82, p < 0.01), TS (r = -0.79, p = 0.02) and TIBC (r = -0.69, p = 0.02), and positively with ferritin (r = +0.73, p < 0.001), sTfR (r = +0.80, p < 0.01) and hepcidin (r = +0.95, p < 0.001). Higher BMI SDS and hepcidin were risk factors for iron deficiency (ID). CONCLUSIONS: Hypoferremia and elevated hepcidin-25 are prevalent in obese children and correlated with BMI SDS. The connection between hepcidin and inflammation could explain the association of ID with obesity.

R620W polymorphism of protein tyrosine phosphatase PTPN22 in Egyptian children and adolescents with systemic lupus erythematosus: relation to thyroid autoimmunity.

BACKGROUND: Some studies showed associations of the minor T allele of the C1858T single nucleotide polymorphism (SNP) corresponding to the R620W amino acid substitution of protein tyrosine phosphatase (PTPN22) with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). OBJECTIVES: To study the frequency of PTPN22 R620W polymorphism among Egyptian patients with SLE and to test the association of the T allele with autoimmune thyroid disease in such patients. METHODS: Clinical evaluation, measurement of thyroid hormones and antibodies, and genotyping of PTPN22 R620W polymorphism were done for 60 SLE patients and 60 age- and sex-matched healthy subjects. RESULTS: Nineteen SLE cases (31.67%) had thyroid dysfunction with subclinical hypothyroidism being the most frequent form of thyroid dysfunction (20%) followed by primary hypothyroidism (6.67%), subclinical hyperthyroidism (3.33%) and primary hyperthyroidism (1.67%). Autoimmune thyroid disease was detected in 36.67% of cases. Systemic lupus erythematosus disease activity index (SLEDAI) score did not differ between patients with thyroid dysfunction and euthyroid patients (p=0.061) nor with the frequency of positive thyroid peroxidise antibodies (TPOAb, p=0.092) and antithyroglobulin antibodies (ATGAb, p=0.1). T allele frequency did not differ between cases and controls (p=1.19) and was associated with autoimmune thyroid disease in Egyptian SLE patients (p=0.002). CONCLUSIONS: R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility among Egyptian SLE patients but appears to be a risk factor for concurrent autoimmune thyroid disease and SLE.