LC/MS/MS and GC/MS/MS metabolic profiling of Leontodon hispidulus, in vitro and in silico anticancer activity evaluation targeting hexokinase 2 enzyme.

Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main secondary metabolites of the optimized ethanolic extract of the plant using Quadrupole Time-of-Flight Liquid chromatography-mass spectrometry and Gas chromatography-mass spectrometry. It also aims to assess the anticancer activity of its different fractions against the prostate carcinoma cell line. Moreover, an in-silico docking study was performed using the Hexokinase-two enzyme. LC-qToF-MS analysis revealed the tentative identification of 36 phenolic compounds including the glycosides of (luteolin, quercetin, kaempferol, apigenin, isorhamnetin, and daidzein), coumarines (esculin, esculetin, and daphnetin), and phenolic acids (chlorogenic, caffeic, quinic, P-coumaric, and rosmarinic). GC-MS/MS analysis revealed the presence of 18 compounds where palmitic acid, myristic acid, alpha-amyrin, and beta-amyrin were the major ones. The cytotoxic activity results revealed that methylene chloride and ethyl acetate fractions showed the highest cytotoxic activity against the PC3 cell line, with IC50 values of 19, and 19.6 µg/ml, respectively. Interestingly, the docking study demonstrated that apigenin-7-O-glucoside, luteolin-7-O-glucoside, kaempferol-3-O-glucuronide, quercetin-4'-O-glucoside, esculin, rosmarinic acid, chlorogenic acid, and α-amyrin exhibited high affinity to the selected target, HEK-2 enzyme.

Dimensions, Ratios, Volumes, and Weights of the Fatty Parts of the Vulva (Mons Pubis and Labia Majora).

BACKGROUND: The anatomy of the fatty parts of the vulva, specifically the mons pubis and labia majora, has not been extensively studied. OBJECTIVES: This study aimed to provide a comprehensive 3-dimensional picture of the mons pubis and labia majora by defining and measuring their dimensions. Furthermore, the study sought to calculate the different ratios, volumes, and weights of these structures. METHODS: The study included 214 women, who were divided into 2 groups based on their BMI. The researchers defined 27 dimensions to describe the width, height, and length of the mons pubis and labia majora, and specified the measuring methodology. RESULTS: The height of the mons pubis was approximately three-quarters of its length and half its width. The labia majora were wider and taller anteriorly than posteriorly, and their ratios decreased as they went posteriorly, from 4 to 2. The ratio of monal height to maximum labial height and to labial length was 3 and 1, respectively, whereas the ratio of monal width to the sum of maximum labial widths was nearly 1.5. The calculated volumes and weights of the mons pubis and labium majus were 200 mL, 30 mL, 180 g, and 27 g in Group 1, and 300 mL, 40 mL, 270 g, and 36 g in Group 2, respectively. CONCLUSIONS: The dimensions, ratios, weights, and volumes defined and measured in this study can serve as the basis for any aesthetic measures involving the mons pubis and labia majora. Moreover, BMI and the different ratios should be considered in such measures.

Application of Box-Behnken design for optimization of phenolics extraction from Leontodon hispidulus in relation to its antioxidant, anti-inflammatory and cytotoxic activities.

To the best of our knowledge, there have been no phytochemical studies concerning the wild plant Leontodon hispidulus Boiss. (Asteraceae). Optimization of the green extraction process of the plant aerial parts, identification of main phenolic compounds, evaluation of antioxidant, anti-inflammatory and anticancer activities of the optimized extract have been carried out. HPLC-analysis was performed using 95% ethanolic extract. 3-Level Box-Behnken Design was applied for optimization of extraction yield and total phenolic content using 3-factors (ethanol/water ratio, material/solvent ratio and extraction time). Antioxidant, anticancer and anti-inflammatory activities were evaluated by ABTS-assay, prostate and cervical carcinoma human cell lines and carrageenan-induced rat paw edema model, respectively. HPLC-analysis showed the presence of quercetin, rutin, kaempferol, chlorogenic and ρ-coumaric acids. Increasing both ethanol/water ratio and material/solvent ratio decreased the yield, while, it increased by prolongation of the extraction time. High material/solvent ratio increased the phenolic content. The optimized extract showed high total phenolic content (104.18 µg/mg) using 201 ml of 74.5% ethanol/water at 72 h and good biological activities. Antioxidant activity was found to be 41.89 mg Trolox-equivalent/gm, with 80% free radicals inhibition. For anti-inflammatory activity, 100 mg/kg of the extract inhibited the edema in rats by 83.5% after 4 h of carrageenan injection as compared to 81.7% inhibition by indomethacin. Prostate carcinoma cell line was more sensitive to the anticancer activity of the extract than cervical carcinoma cell line (IC50 = 16.5 and 23 µg/ml, respectively). The developed extraction procedure proved to be efficient in enriching the extract with phenolic compounds with promising anticancer, anti-inflammatory and antioxidant activities.

In vivo antidiabetic potential of standardized Gymnocarpos decandrus Forssk. Extract.

BACKGROUND: Gymnocarpos decandrus (Caryophyllaceae) is a well-known wild plant used as a food for grazing animals. Recently it showed potent antidiabetic potential beside its established anti-inflammatory, analgesic and diuretic activities. G. decandrus antidiabetic potential was reported through in-vitro models and resulted in promising α-amylase, α-glucosidase and antiviral Coxsackie B4 inhibitory activities; however no in-vivo studies were conducted. PURPOSE: This study aims to examine Gymnocarpos decandrus ethanol extract (GDEE) safety and to evaluate its in vivo antidiabetic potential. METHOD: Adult albino rats were injected intraperitoneally with alloxan to induce diabetes mellitus and the glucose level was measured after two and four weeks against metformin as a standard drug. Additionally, GDEE characterization and standardization were carried out. RESULTS: GDEE LD50 was up to 5.8 mg/kg and exhibited significant antidiabetic activity 77.17% comparable to the standard drug metformin. Its total phenolics, and flavonoids amounted 127.2 ± 0.23 and 85.5 ± 0.21 mg/g respectively. Vitexin was used as a marker compound for GDEE (140.70 mg/100 gm). CONCLUSION: This study represents the sole in vivo scientific validation of G. decandrus recently documented in vitro antidiabetic potential.

FSH versus AMH: age-related relevance to ICSI results.

BACKGROUND: Women's fecundity is known to decrease with the increase in chronologic age. Several biomarkers of the ovarian reserve, including follicle stimulating hormone (FSH), anti Müllerian hormone (AMH), have been proposed as possible predictors for the response to controlled ovarian stimulation (COS). Although there are assumptions indicating that the relationship between age and ovarian reserve is highly variable and the potential different validity of ovarian reserve markers in women in different age groups remains to be demonstrated. The purpose of our study was evaluating FSH and AMH as potential predictors of response to controlled ovarian stimulation and prediction of intracytoplasmic sperm injection (ICSI) outcome according to age. This prospective study has been carried out on 218 women having ICSI cycles. Cases were divided into two groups, group 1 (n 148), their age < 35 years, and group 2 (n 70), their age ≥ 35 years. All women received antagonist protocol during their ICSI cycles. Basal FSH and AMH were measured and correlated to the number of follicles on the day of trigger, the number of oocytes retrieved, chemical, and clinical pregnancies. RESULTS: The fertilization rate in group 1 was 68.15%, while in group 2 was 77.82% (p = 0.003) while the implantation rate (number of gestational sacs observed at 6 weeks of pregnancy divided by the number of transferred embryos) was 18.95 and 11.98% in group 1 and group 2, respectively (p = 0.041). The clinical pregnancy rate among both groups was 38.51% in group 1, while 24.29% in group 2 (p = 0.038). Women who got pregnant among those aged < 35 years had significantly lower basal FSH (p < 0.001), while women who got pregnant among those aged ≥ 35 years had significantly higher AMH levels (p value < 0.001) and higher E2 levels on the day of trigger (p = 0.007). CONCLUSION: We found that below the age of 35 years, the chances of pregnancy are more correlated to FSH levels, while above the age of 35 years, AMH was a more relevant test.

Alalfy modified cervical inversion technique as a tamponade in controlling PPH in placenta previa, a multicentric double blind randomized controlled trial.

INTRODUCTION: Postpartum hemorrhage that occurs frequently with placenta previa is one of the causes of maternal mortality in 14% in developing countries. OBJECTIVE: To assess efficacy of cervical inversion as a tamponade in controlling bed of placenta in cases of placenta previa. PATIENTS AND METHOD: A prospective randomized controlled study was conducted among a total of 240 pregnant women with placenta previa (120 subjected to Alalfy modified cervical inversion technique plus hemostatic sutures and 120 was not subjected cervical inversion and only was subjected to hemostatic sutures in Obstetrics and Gynecology Department at Suez Canal University hospital, Helwan University and Algezeerah hospital for a planned cesarean section). RESULTS: The mean intraoperative blood loss, the intraoperative time, and the postoperative hemoglobin show a statistically significant difference between cases with placenta previa who were exposed to cervical inversion in comparison to cases that had no cervical inversion with a p-value <.001. CONCLUSION: Modified cervical inversion (Alalfy technique) as a tamponade when added to hemostatic sutures to the placental bed is an easy, rapid, and efficient procedure that can decrease the amount of blood loss, time needed to stop bleeding per bed, total operative time, also it can decrease the need for blood transfusion.

Validation of Antidiabetic Potential of Gymnocarpos decandrus Forssk.

Gymnocarpos decandrus Forssk. is a well-known grazing wild plant. This study targets scientific validation of its claimed antidiabetic activity and exploring its bioactive metabolites. Chromatographic purification of G. decandrus ethanol extract (GDEE) allowed isolation of vitexin (C1), protocatechuic acid (C2) and quercetin (C3). HPLC-PDA-MS/MS enabled identification of nineteen metabolites; 13 flavonoids, 5 saponins, and 1 phenolic acid in G. decandrus and four in the genus Gymnocarpos for the first time. The antidiabetic potential was evaluated via testing the Coxsackie B4 virus and α-glucosidase inhibitory potentials. C3 exhibited its potent antiviral activity through blocking of the virus attachment (96.28%, SI 4.41) and virus inactivation before adsorption (91.47%, SI 4.78). GDEE and C1-C3 showed dose dependent α-glucosidase inhibitory activity with IC50 of 733.9, 293.3, 118.1 and 69.1 µg/mL, respectively. Our study represents the sole complete map for G. decandrus secondary metabolites and presents it as promising drug for diabetes management.

Maternal, fetal, and neonatal outcomes among different types of hypertensive disorders associating pregnancy needing intensive care management.

Objective: To assess the relationship between maternal, fetal, and neonatal outcomes and different forms of hypertensive disorders associating pregnancy in women needed intensive care units (ICUs) admission.Methods: A prospective case control study was conducted on 1238 women admitted to hypertensive ICU at three university hospitals. They were classified into four groups. Group I included 472 women with severe preeclampsia (PE), Group II included 243 women with eclampsia (E), Group III included 396 women diagnosed with E associated with HELLP syndrome, and Group IV included 127 women diagnosed as HELLP syndrome. All women received magnesium sulfate to prevent and/or control convulsions and nifedipine to control their blood pressure. Primary outcome parameter was maternal mortality. Other outcomes included maternal morbidities, fetal, and neonatal outcomes.Results: There was a significant difference among the study groups regarding the need for blood transfusion (58.1%, 70%, 84.3%, and 42.5% respectively, p < .001), number of transferred units (2.4 ± 1, 2.9 ± 0.9, 3.4 ± 1.1, and 3.5 ± 0.8 respectively, p < .001), placental abruption (23.3%, 16.5%, 30.3%, and 19.7% respectively, p < .001), pulmonary edema (14.8%, 22.6%, 19.9%, and 34.6% respectively, p < .001), multiple complications (12.5%, 12.3%, 19.9%, and 26% respectively, p < .001), and maternal mortality (1.9%, 4.1%, 6.1%, and 5.5% respectively, p < .001). Regarding fetal and neonatal outcomes, there was a significant difference among the four groups regarding Apgar score at 1 and 5 min, neonatal birth weight, neonatal intensive care unit (NICU) admission, NICU admission days, intrauterine growth restriction, perinatal death, respiratory distress syndrome, intraventricular hemorrhage, sepsis, and the need for mechanical ventilation (p < .001). Higher rate of vaginal delivery was reported in women with HELLP (40.9%) and severe PE (39.8%) and higher rates of performing cesarean section (CS) in women with eclampsia (77.8%). Maternal mortality is significantly related to delivery with CS, younger maternal age with lower parity, and the presence of placental abruption or pulmonary edema. For Groups III and IV, which included HELLP cases, there are significant differences between both groups as regards HELLP classes according to Mississippi classification, also significant differences were seen between both groups as regards, maternal mortality, abruptio placenta, pulmonary edema, multiple organ damage, NICU admission, perinatal deaths, and need for mechanical ventilation.Conclusion: Both maternal mortality and morbidity (placental abruption and need for blood transfusion) are significantly higher in women with HELLP syndrome worsens to become class 1 regardless of whether eclampsia is present or not.Synopsis: Maternal mortality and unfavorable outcome are significantly higher in women with HELLP syndrome whether it was associated with eclampsia or not.

Multicenter randomized controlled trial assessing the impact of a cervical traction maneuver (Amr's maneuver) on the incidence of postpartum hemorrhage.

OBJECTIVE: To assess the impact of a cervical traction maneuver (Amr's maneuver) used in conjunction with active management of the third stage of labor (AMTSL) on the incidence of postpartum hemorrhage (PPH). METHOD: The present multicenter randomized controlled trial was conducted in Cairo between March 1, 2016, and June 30, 2017. Women aged at least 18 years who had singleton pregnancies and were candidates for vaginal delivery were enrolled. After block randomization, AMTSL was performed for all participants. Following placental delivery, Amr's maneuver using cervical traction for 90 seconds was carried out in the study group. The primary outcome, incidence of PPH (>500 mL blood loss) within 6 hours of delivery, was compared between the study and control groups in an intention-to-treat analysis. RESULTS: There were 852 patients randomized to the study (n=426) and control (n=426) groups. The incidence of PPH was significantly lower in the study group compared with the control group (6 [1.4%] vs 19 [4.5%]; P=0.015). Absolute risk reduction of 3.1% (95% CI 0.8-5.6), relative risk reduction of 0.32 (95% CI 0.13-0.78), and number needed to treat of 33 (95% CI 129-18) were observed in the study group. CONCLUSION: Amr's maneuver was effective in decreasing the incidence of PPH. ClinicalTrials.gov Identifier: NCT02660567.

Effect of body mass index on the outcome of IVF cycles among patients with poor ovarian response.

OBJECTIVE: To assess the effects of body mass index (BMI) on the outcome of IVF cycles among poor responders. METHODS: A prospective cohort study in Egypt enrolled 185 poor responders who underwent intracytoplasmic sperm injection via an antagonist protocol between 2012 and 2017. Participants were classified into three groups by BMI (calculated as weight in kilograms divided by the square of height in meters): 18.5-24.9 (normal, n=48); 25-29.9 (overweight, n=54); 30 or higher (obese, n=83). Outcomes were clinical pregnancy rate, implantation rate, chemical pregnancy rate, gonadotropin dose, number of oocytes and embryos, and cancellation rate. RESULTS: There was no significant difference among the three groups in gonadotropin dose; duration of stimulation; endometrial thickness on trigger day; number of oocytes retrieved, injected, or fertilized; number of embryos, transferred embryos, or frozen embryos; or day of embryo transfer. Frequency of implantation (11/81 [14%] vs 6/96 [6%] or 5/155 [3%]), chemical pregnancy (20 [42%] vs 14 [30%] or 12 [14%]) and clinical pregnancy (15 [31%] vs 12 [22%] and 9 [11%]) was significantly higher for normal than for overweight or obese women, respectively. CONCLUSION: Implantation, chemical pregnancy, and clinical pregnancy rates were inversely related to increasing BMI. CLINICALTRIALS.GOV: NCT03457233.