CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Fibroblast growth factor-21 and Visfatin as potential predictors for metabolic risk factors in obese children.

Fibroblast growth factor-21 (FGF-21) and Visfatin are associated with obesity. However; reviewing the literature; no studies were found to assess their role as potential markers for the metabolic disorders related to obesity in children. Assess the relations between serum FGF-21 and Visfatin with obesity and its metabolic disorders, and their use as potential predictors for metabolic risk factors in a sample of Egyptian obese children. This cross-sectional study included 111 Egyptian children (45 males and 66 females); aged 6-10 years to avoid the effect of puberty (prepubertal). The exclusion criteria (by full History taking and clinical examination) were the presence of any sign of puberty according to Tanner stage, the presence of identified causes of obesity (genetic syndromes, chromosomal or endocrinal disorders), chronic diseases (cardiovascular, gastrointestinal, and respiratory), or drug use like steroids; that would interfere with the type of obesity and affect the normal growth of the children. Also, any child with a BMI between 85 and 95th percentiles (overweight) was excluded from the study. All participating obese children were suffering from exogenous simple obesity. They were classified according to their body mass index (BMI) percentiles into 72 obese (BMI ≥ 95th), and 39 control non-obese ones (BMI > 15th to < 85th), based on the Egyptian Growth Charts for children and adolescents. Ethical approvals were granted from both the Ethics Committee of the "National Research Centre" and the "Faculty of Postgraduate Childhood Studies" (Approval No. 17/125). Also, informed written consent was taken from either of the parents and assent from the participating children. They were subjected to blood pressure assessment, anthropometric measurements (weight [Wt], height [Ht], BMI, waist [WC], and hip [HC] circumferences), and laboratory evaluation (Visfatin, FGF-21, LDL, HDL, TG, cholesterol, fasting glucose, insulin, and calculation of HOMA-IR). Mann-Whitney test and Spearman's correlation test were applied. Obese children had significantly higher values than control ones regarding all the studied clinical (SBP, DBP), anthropometric parameters (Wt, Ht, BMI, WC, and HC), FBG, Insulin, HOMA-IR, Visfatin, and FGF-21, and had significantly lower values regarding HDL and Cholesterol. Among obese children, both FGF-21 and Visfatin had significant negative correlations with BMI and HC. At the same time, serum FGF-21 had a highly significant positive correlation with HDL. Visfatin and FGF-21 had highly significant positive correlations with each other. In the control group, both serum Visfatin or FGF-21 had insignificant correlations with each other and with all the studied clinical and anthropometric parameters. FGF-21 and Visfatin are related to the obesity markers, but they cannot be used as potential predictors for metabolic disturbance in obese prepubertal children; both had insignificant correlations with the metabolic risk factors.

Detection of AZFc gene deletion in a cohort of Egyptian patients with idiopathic male infertility.

BACKGROUND: The deletions of azoospermic factor regions (AZF) are considered risk factor of spermatogenic failure. AZF duplications or complex copy number variants (CNVs) were rarely studied because STS-PCR could not always detect these changes. The application of multiplex ligation-dependent probe amplification (MLPA) as a valuable test for detection of the deletion and or duplication was introduced to investigate the AZF sub-region CNVs. The MLPA technique is still not applied on a large scale, and the publications in this area of research are limited. The aim of this work was to evaluate the efficacy of MLPA assay to detect AZF-linked CNVs in idiopathic spermatogenic failure patients and to evaluate its importance as a prognostic marker in the reproduction outcome. RESULTS: Forty infertile men (37 with azoospermia and 3 with severe oligozoospermia) and 20 normal fertile men were subjected to thorough clinical, pathological, and laboratory assessment, chromosomal study, MLPA, STS-PCR assays, histopathology study, and testicular sperm retrieval (TESE). Out of the 40 patients, 7 patients have shown CNV in the AZFc region, 6 patients have partial deletion, and one patient has partial duplication. Only one of the normal control has AZFc duplication. STS-PCR was able to detect the deletion in only 4 out of the 7 positive patients and none of the control. CONCLUSION: We concluded that MLPA should be applied on a larger scale for the detection of Y chromosome microdeletion as a rapid, efficient, and cheap test.

Porous Silica as Drug Carrier for Controlled Delivery of Sulfasalazine: The Effect of Alginate-N, O-Carboxymethyl Chitosan Gel Coating and Amine Functionalization.

The necessity of colon-specific drug delivery systems has been well recognized. Porous silica (PSi) coated with a pH-sensitive, biocompatible, and biodegradable polymer can be useful in colon delivery. In this study, porous silica was synthesized and sulfasalazine was loaded into it to investigate the release rate in a simulated intestinal media. The media was kept at 37 °C and pH 6.8 and 7.4, and subjected to continuous ultrasonic waves to simulate body fluid flow. Aqueous alginate and N, O-Carboxymethyl chitosan (NOCC) solutions, with a distinct composition (3% W/V) in different ratios, were prepared and coated on pressed porous silica disks. Porous silica (PSi) was also functionalized by aminopropyltrimethoxysilane grafting and was studied as a potential carrier for the controlled drug release of sulfasalazine. The release was studied in simulated gastric and intestinal media and results show that no burst release occurred in both coated and functionalized samples and the swelling degree of coats at basic and neutral media decreased by the presence of alginate in the network. It is concluded that the coat with a 50:50 ratio can release the colon drugs in 24 h at a suitable rate. It is also envisioned that functionalization was a factor boosting drug uptake, however, the release rate was lower in the functionalized samples. This study opens the gates to new ideas for the potential safe and localized delivery of sulfasalazine.

Oxidative stress and hepcidin expression in pediatric sickle cell anemia with iron overload.

BACKGROUND: Blood transfusion (BT) is essential in treating sickle cell disease (SCD); however, it leads to iron overload (IO) and oxidative stress. We studied the relationship between oxidative stress, iron status parameters, hepcidin mRNA gene expression, and IO in SCD patients. METHODS: We classified all SCD patients (n = 90) into two groups: Group I, 45 children (s.ferritin ≥ 938 ng/mL) and Group II, 45 children (s.ferritin < 938 ng/mL). A total of 55 children, age and sex matched, participated as a control group. Malondialdehyde (MDA), nitrite, s.iron, s.total iron-binding capacity (sTIBC), transferrin saturation %, s.ferritin, s.hepcidin, and hepcidin mRNA gene expression were assessed. RESULTS: Among SCD BT-dependent patients (>3 times/year), 63% were from Group I and 37% from Group II, p < .01. The two patient groups had significantly lower s.hepcidin and hepcidin gene expression than controls ( p < .001). TIBC, s.iron, s.ferritin, transferrin saturation %, ferritin/hepcidin ratio, and MDA levels were higher among SCD patients than controls ( p < .001). Group I had higher mean level of ferritin/hepcidin ratio and MDA than Group II ( p < .01). The higher level of MDA and increased frequency of BT were the significant predicting risk factors for IO ( p < .05). A receiver-operating characteristic curve indicates that MDA is the outstanding significant biomarker for high level of s.ferritin with subsequent IO progression. CONCLUSION: MDA may serve as a biomarker of oxidative stress and IO in SCD patients. This result paid attention for urgent initiation of antioxidant and chelation therapy on detecting increased MDA level.

Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies.

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world's population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.

Feed intake, nutrient digestibility and ruminal fermentation activities in sheep-fed peanut hulls treated with Trichoderma viride or urea.

This study aimed to assess impacts of fungal treatment on the nutritional value of peanut hulls (PH) or urea at the rate of 5 kg/100 g of PH. Fermented sugar beet pulp inoculated with Trichoderma viride was supplemented to PH at rates of 5.0, 10.0 and 15.0 g/100 g air dry of PH and mixed well before aerobic incubation for 21 days. Organic matter (OM) content of PH declined with increased levels of fermented sugar beet pulp inoculums, while crude protein (CP), ether extract (EE), and ash increased. Fiber contents were decreased with both treatments of fermented sugar beet pulp and urea. Total N of PH increased with urea treatment, which reduced the true protein N to total protein N ratio. In sacco degradabilities of dry matter (DM), OM, and CP with urea treatment increased compared with fungal treatment. The DM intake of peanut hulls treated with fungus (PHF) was higher (P < 0.05) than with peanut hulls treated with urea (PHU). Digestibility of OM, CP, neutral detergent fiber, and non-fiber carbohydrate by native breed Ossimi sheep with PH were higher (P < 0.05) than with PH or urea treated PH. The intakes, losses, and balance of N increased (P < 0.01) with PHF versus PH feeding. Feeding PHF increased (P < 0.01) ruminal concentrations of NH3-N, acetic acid, butyric acid, and the acetic to propionic acid ratio. Bacterial and protozoal counts increased (P < 0.05) with feeding PHF or PHU versus PH. Overall, this fungal treatment of peanut hulls created a higher nutritive value feed for ruminants.