Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study.

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1ß, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/ß-Catenin and RANKL/RANK/OPG signaling pathways.

BACKGROUND: Vascular calcification (VC) is a major predictor of cardiovascular diseases that represent the principal cause of mortality among type-2 diabetic patients. Accumulating data suggest the vital role of some microRNAs on vascular calcification as an epigenetic regulator. Thus, we assessed herein, the role of serum miR-433-3p in vascular calcification in type-2 diabetic patients. METHODS: Twenty healthy subjects (control group) and forty diabetic patients (20 without VC and 20 with VC) were involved in the study. miR-433-3p gene expression was measured. Runx2, Dickkopf-1 (DKK1), ß-catenin, Receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) levels in serum were assessed by ELISA technique. RESULTS: Diabetes patients had significantly lower levels of miR-433-3p expression in comparison to the control group, with the lowest levels being found in diabetic patients with VC. Furthermore, Runx2, ß-catenin, and RANKL levels were significantly increased with concomitant lower DKK1 and OPG levels detected in the two diabetic groups especially those with VC. CONCLUSION: Collectively, the study documented that down-regulation of miR-433-3p may contribute to the development of VC through activating WNT/ß-Catenin and RANKL/RANK/OPG signaling pathways.

Ameliorative effect of sesame oil on experimentally induced polycystic ovary syndrome: A cross-link between XBP-1/PPAR-1, regulatory proteins for lipogenesis/steroids.

Polycystic ovary syndrome (PCOS) is a mixed endocrine/metabolic/reproductive disorder in women of reproductive age. Sesame oil (SO) contains sesame lignans & vitamin E with broad-spectrum antioxidant and anti-inflammatory effects. This study investigates the ameliorative effect of SO on experimentally induced PCOS and elucidates the possible molecular mechanisms with a deeper focus on the different signaling pathways involved. The study was carried out on 28 nonpregnant female Wister albino rats that were divided into four equal groups; Group I (control group) received oral 0.5% wt/vol carboxymethyl cellulose daily. Group II (SO group): orally administered SO (2 mL/kg body wt./day) for 21 days. Group III (PCOS group) received letrozole daily, 1 mg/kg, for 21 days. Group IV (PCOS + SO group): concomitantly administered letrozole and SO for 21 days. The serum hormonal and metabolic panel and the homogenate ATF-1, StAR, MAPK, PKA, and PI3K levels of the ovarian tissue were calorimetrically evaluated. However, endoplasmic reticulum (ER) stress was evaluated by ovarian XBP1 and PPAR-γ messenger RNA expression level using the qRT-PCR technique. Ovarian COX-2 was detected immunohistochemically. The results suggest that SO-treated PCOS rats showed a significantly improved hormonal, metabolic panel, inflammatory, and ER stress status with concomitant decreases in ATF-1, StAR, MAPK, PKA, and PI3K in ovarian rats compared to the correspondent values in PCOS without treatment. CONCLUSIONS: The protective effects of SO against PCOS are triggered by ameliorating regulatory proteins of ER stress, lipogenesis, and steroidogenesis through the PI3K/PKA and MAPK/ERK2 signaling cascades. SIGNIFICANCE STATEMENT: Polycystic ovary syndrome (PCOS) is the most common mixed endocrine-metabolic dysfunction among women within the reproductive period, with an estimated prevalence of 5%-26% worldwide. Doctors traditionally recommend metformin for PCOS patients. However, metformin is known to be associated with significant adverse effects and contraindications. This work aimed at shedding light on the ameliorative effect of sesame oil (SO), natural polyunsaturated fatty acids-rich oil, on the induced PCOS model. SO proved to have a marvelous effect on the metabolic and endocrine derangements in the PCOS rat model. We hoped to provide a valuable alternative treatment for PCOS patients to avoid the side effects of metformin and to help PCOS patients for whom metformin is contraindicated.

The prospective effect of fucoidan on splenic dysfunction caused by oxaliplatin in male rats through endoplasmic stress dynamics.

Fucoidans (FUCs) are highly sulfated polysaccharides demonstrating multiple actions in different systems. Oxaliplatin (OXA) is a platinum-containing chemotherapeutic agent with several side effects that restrict its usage. The current study aimed to determine the potential effect of FUC in male rats with splenic dysfunction induced by OXA. Eighty adult male rats aged (8-9 weeks) weighing (190-230 g) were divided into four groups: (Group I: the control group): Rats were administrated normal saline; (Group II: controls treated by FUC): Rats were treated with FUC; (Group III: Splenic dysfunction group): Rats were treated with 8 mg/kg OXA. (IV: Splenic dysfunction treated by FUC): Rats were treated by OXA as Group III, then fucoidan was given. At the end of the experiment, blood was collected to determine red blood cells and white blood cells. Splenic tissues were divided into one part for biochemical assays, oxidative stress markers as MDA and catalase, inflammatory markers (TNF-alpha, IL6), and apoptotic markers (caspase 3) and gene expression of Nrf2, Mapk1 gene expression, and endoplasmic stress parameters and the other part was used for immunohistochemical and histopathological analysis. Compared to the OXA-induced splenic dysfunction group, FUC significantly decreased high levels of MDA, TNF- alpha, IL6, caspase-3, Mapk1, endoplasmic stress induced by OXA, and increased the level of catalase and Nrf2. Fucoidan has corrected the histopathological and immunohistochemical changes compared to the OXA-induced splenic dysfunction group. In conclusion, our findings suggest that fucoidan has a significant role in the treatment of splenic dysfunction induced by OXA.

Clinical Significance of MAP-7 and FOXC1 in Egyptian Acute Myeloid Leukemia Patients.

PURPOSE: The present study aimed to report the clinical correlations and prognostic significance of microtubule-associated protein-1 (MAP-7) and forkhead box transcription factor-C1 (FOXC1) expression in Egyptian patients with newly diagnosed acute myeloid leukemia (AML). METHODS: The study included 80 adults with newly diagnosed AML. Laboratory investigations included complete blood count, morphological examination of bone marrow aspirate, immunophenotyping, conventional karyotyping and molecular study for fms-like tyrosine kinase 3 (FLT3), nucleophosmin-1 (NPM1) and CCAAT/enhancer binding protein α (CEBPA) mutations. MAP-7 and FOXC1 expressions in bone marrow were determined using RT-PCR. Patients were followed for a median (range) period of 6.4 (1.0-35) months. The study outcomes included treatment response, progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with low FOXC1 expression had significantly lower mortality rate (60.0 % versus 84.6 %, p=0.021), significantly longer PFS duration and significantly longer OS. No significant differences were noted between MAP7 expression groups regarding treatment response, mortality rate, PFS duration and OS duration. Interestingly, a significant direct correlation was noted between FOXC1 and MAP7 expressions (r=0.25, p=0.027). CONCLUSIONS: FOXC1 and MAP7 expressions are significantly correlated. High expression of FOXC1 in Egyptian population may be related to shorter OS and PFS.

Possible protective effects of CO Q10 against vincristine-induced peripheral neuropathy: Targeting oxidative stress, inflammation, and sarmoptosis.

Vincristine is a chemotherapy drug that belongs to the vinca alkaloids group. It is used for treatment of hematologic malignancies and several solid tumors. Vincristine-induced peripheral neuropathy is a major dose-limiting side effect. Coenzyme Q10 (Co Q10), an essential component of the mitochondrial electron transport chain, participates in energy production. It is a powerful fat-soluble antioxidant and also exerts anti-inflammatory effects. Therefore, this study was aimed to focus on the mechanistic insights of vincristine-induced peripheral neuropathy in addition to shedding the light on the modulatory effect of Co Q10. Twenty-eight rats were randomly divided into four groups. Peripheral neuropathy was induced by intraperitoneal injection of vincristine (0.1 mg/kg body weight). Co Q10 was injected intraperitoneally (10 mg/kg body weight) for 24 days. Sciatic nerve MDA, TAC, GSH, 8-OHdG, TNF-α, IL-1ß, and NF-κB levels were assessed. Gene expression of SARM1 and Nrf2 was also assessed. Serum neurofilament light chain was immunoassayed, in addition to the behavioral assessment. Co Q10 significantly improved oxidative stress and inflammatory biomarkers. It also decreased serum NFL levels. It enhanced Nrf2 and decreased SARM1 gene expression. Histopathological findings proved the biochemical and molecular findings. Our results support Co Q10 as a potential protective agent against vincristine-induced peripheral neuropathy.

Computed tomography virtual cystoscopy for follow-up of patients with superficial bladder tumours in comparison to conventional cystoscopy: An exploratory study.

OBJECTIVE: To evaluate and analyse the efficacy of computed tomography (CT) virtual cystoscopy in comparison to conventional cystoscopy for the follow-up of patients with non-muscle-invasive bladder cancer. PATIENTS AND METHODS: The study was done over 3 years, from April 2010 to June 2013, and included 30 patients who all had non-muscle-invasive transitional cell carcinoma (Ta, T1). The patients all underwent complete transurethral resection of the tumour and presented for first follow-up check cystoscopy. The examination was performed using a 16-slice multi-detector (MD) CT scanner. The results were compared for sensitivity and specificity in relation to the site, size, and shape of the tumour. RESULTS: In all, 20 lesions were detected by CT virtual cystoscopy in 18 patients, whilst the remaining 12 were lesion free. Conventional cystoscopy, detected 23 lesions in 19 patients. The sensitivity of the virtual images was 87%; its specificity in identifying lesions was 100%, with a positive predictive value of 100% and negative predictive value of 78.5%. CONCLUSION: CT virtual cystoscopy is a promising technique for detecting bladder tumours and some other bladder lesions. However, the detection rate for recurrent NMIBC does not appear to be adequate to replace conventional cystoscopy.

Value of Computed Tomography for Predicting the Outcome After Percutaneous Nephrolithotomy.

INTRODUCTION: Computerized tomography of the urinary tract (CT-UT) has been established as the diagnostic procedure of choice for urinary stones. This study aimed to evaluate its role in predicting the outcome of percutaneous nephrolithotomy (PCNL) in terms of stone free rate and residual fragments. METHOD: This prospective cohort study was conducted on 34 patients in the Urology Department of Theodor Bilharz Research Institute from January 2013 to March 2014. The patients who had large and/or multiple renal stones, including staghorn stones, in 19 renal units scheduled for PCNL were included in this study. All had a pre-operative CT-UT to determine the stones' characteristics and renal anatomy. CT-UT, together with a kidney-Ureter-Bladder (KUB) film, was taken on the first post-operative day. The data were analyzed by SPSS version 17 using independent-samples t-test and the chi-squared test. RESULTS: CT-UT showed a statistical significant sensitivity in detecting residual fragments over standard KUB, yet this significance was lost when corrected to significant residual. Stone size and density were independent factors for the presence of residual stones. CONCLUSION: CT-UT post PCNL was sensitive to detect residual fragments, yet it showed no superiority over standard KUB in detecting significant residual.

Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery.

BACKGROUND AND AIM: Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of surgical site infection (SSI) after a clean contaminated cancer surgery. Our aim is to compare the use of two prophylactic antibiotic (PA) regimens as regards efficacy, timing, and cost. PATIENTS AND METHODS: Two hundred patients with gastric, bladder, or colorectal cancer were randomized to receive preoperative PA, group A received penicillin G sodium and gentamicin and group B received clindamycin and amikacin intravenously. The demographic data of patients were collected, and they were observed for wound infections. RESULTS: Infected wounds occurred in 19 patients with a rate of 9.5%. Highest incidence of SSI was among bladder cancer patients (14.2%); p=0.044. The rate of SSI was 11% in group A, and 8% in group B, p=0.469. The cost of PA administered in group A was significantly less than that of group B (21.96±3.22LE versus 117.05±12.74LE, respectively; p<0.001). SSI tended to be higher among those who had longer time for antibiotic and incision (≥30min) than those who had shorter time interval (<30min), (13% vs. 6.5%, respectively). CONCLUSION: Both penicillin+gentamicin and clindamycin+amikacin are safe and effective for the prevention of SSI in clean contaminated operative procedures. In a resource limited hospital, a regimen including penicillin+gentamicin is a cost-effective alternative for the more expensive and broader coverage of clindamycin+amikacin. Timing of PA is effective in preventing SSIs when administered 30min before the start of surgery.

A new validated HPTLC method for quantitative determination of 1, 5-dicaffeoylquinic acid in Inula crithmoides roots.

1, 5-Dicaffeoylquinic acid (1, 5-DCQA), a potent HIV-1 integrase inhibitor, is currently undergoing an evaluation as a promising novel HIV therapeutic agent. This work aims at developing an accurate, rapid, repeatable and robust HPTLC method for the determination of 1, 5-DCQA in its natural sources. 1, 5-DCQA is the major component of the n-butanol fraction, the most biologically active hepatoprotective fraction, of Inula crithmoides roots extract. Thus, it will be of interest to evaluate the plant roots as a potential source of 1, 5-DCQA using a fully validated HPTLC method. The percentage of 1, 5-DCQA in the studied plant (0.035% w/w) was found to be approximately similar to those previously determined in other antioxidant herbal drugs, in which 1, 5- DCQA is the main phenolic constituent. The results obtained showed that the described HPTLC method is suitable for routine use in quality control of herbal raw material, extracts and pharmaceutical preparations containing 1, 5-DCQA. No HPTLC method has been reported in literature for the determination of 1, 5-DCQA in medicinal plants.