Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness.

Background: Although estrogen (ERα/ERß), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured. Methods: ERα/ERß/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs. late-stage III/IV), and anatomical location (right; RSCs vs. left; LSCs). Effects of 17ß-estradiol (E2), progesterone (P4), and testosterone alone or combined with the specific blockers of ERα (MPP dihydrochloride), ERß (PHTPP), PGR (mifepristone), and AR (bicalutamide) on cell cycle and apoptosis were also measured in the SW480 male and HT29 female CRC cell lines. Results: ERα and AR proteins increased, whilst ERß and PGR declined markedly in malignant specimens. Moreover, male neoplastic tissues showed highest AR expression, whilst ERß and PGR weakest alongside ERα strongest expression was seen in cancerous tissues from women aged ≥60 years. Late-stage neoplasms also revealed maximal alterations in the expression of sex steroid receptors. By tumor location, LSCs disclosed significant elevations in ERα with marked declines in PGR compared with RSCs, and ERα strongest alongside PGR weakest expression was detected in advanced LSCs from women aged ≥60 years. Late-stage LSCs from females aged ≥60 years also showed weakest ERß and strongest AR expression. In contrast, male RSC and LSC tissues exhibited equal ERß and AR expression in all clinical stages. ERα and AR proteins also correlated positively, whereas ERß and PGR inversely, with tumor characteristics. Concomitantly, E2 and P4 monotherapies triggered cell cycle arrest and apoptosis in the SW480 and HT29 cells, and while pre-treatment with ERα-blocker enhanced the effects of E2, ERß-blocker and PGR-blocker suppressed the E2 and P4 anti-cancer actions, respectively. In contrast, treatment with the AR-blocker induced apoptosis, whilst co-treatment with testosterone hindered the effects. Conclusions: This study advocates that protein expression of sex steroid receptors in malignant tissues could represent prognostic markers, as well as hormonal therapy could provide an alternative strategy against CRC, and their efficacies could be dependent on gender, clinical stage, and tumor location.

Formulation, optimization, and nephrotoxicity evaluation of an antifungal in situ nasal gel loaded with voriconazole‒clove oil transferosomal nanoparticles.

Fungal infections of the paranasal cavity are among the most widely spread illnesses nowadays. The aim of the current study was to estimate the effectiveness of an in situ gel loaded with voriconazole‒clove oil nano-transferosomes (VRC-CO-NT) in enhancing the activity of voriconazole against Aspergillus flavus, which causes rhinosinusitis. The nephrotoxic side effects of voriconazole may be reduced through the incorporation of the clove oil, which has antioxidant activity that protects tissue. The Box‒Behnken design was applied to formulate the VRC-CO-NT. The particle size, entrapment efficiency, antifungal inhibition zone, and serum creatinine concentration were considered dependent variables, and the soybean lecithin, VRC, and CO concentrations were considered independent ones. The final optimized formulation was loaded into a deacetylated gellan gum base and evaluated for its gelation, rheological properties, drug release profile, permeation capabilities, and in vivo nephrotoxicity. The optimum formulation was determined to be composed of 50 mg/mL lecithin, 18 mg/mL VRC, and 75 mg/mL CO, with a minimum particle size of 102.96 nm, an entrapment efficiency of 71.70%, an inhibition zone of 21.76 mm, and a serum creatinine level of 0.119 mmol/L. The optimized loaded in situ gel released 82.5% VRC after 12 hours and resulted in a 5.4-fold increase in drug permeation. The in vivo results obtained using rabbits resulted in a nonsignificant differentiation among the renal function parameters compared with the negative control group. In conclusion, nasal in situ gel loaded with VRC-CO-NT is considered an efficient novel carrier with enhanced antifungal properties with no signs of nephrotoxicity.

Cytotoxicity, in vivo toxicity, and chemical composition of the hexane extract of Plectranthus amboinicus (Lour.) Spreng.

Cancer is a universal health issue, and many anticancer therapeutic drugs have been isolated from natural products. This study analyzed the cytotoxic and apoptotic activity of Plectranthus amboinicus leaf hexane (PALH) extract in MDA-MB-231 (median inhibitory concentration [IC50] = 39.26 µg/mL) and MCF7 (IC50 = 89.05 µg/mL) breast cancer cell lines. Cells appeared rounded and shrunken, indicating morphological changes due to apoptosis induction. The primary constituent of PALH was phenol, 5-methyl-2-(1-methylethyl) (44%). PALH extract treatment increased the percentage of late apoptotic cells in the MDA-MB231 cell line (58% ± 1.5% at 200 µg/mL) compared to the control group, as evidenced by the activated caspase-3 and caspase-7 identified and captured by fluorescence microscopy. The relative migration rate in MDA-MB-231 cells treated with 10 µg/mL of PALH extract for 48 h was significantly lower compared to the control group. Analysis of acute (2000 mg/kg/BW) and subacute (250 and 500 mg/kg/BW) toxicity of PALH extract in mice showed no mortality or adverse effects in the kidney and liver histology compared to the control group. PALH extract can be considered nontoxic as it does not cause any adverse changes and so can be proposed as a potential breast anticancer agent.

Evaluation of different forms of Egyptian diatomite for the removal of ammonium ions from Lake Qarun: A realistic study to avoid eutrophication.

Three types of diatomite-based adsorbents-diatomaceous earth (DE), purified diatomite (PD), and diatomite@MgO/CaO (D@MgO) were used for adsorption decontamination of ammonium from Lake Qarun water (28.7 mg/L). The adsorption properties of the three diatomite-based adsorbents were evaluated by both batch and fixed-bed column adsorption studies. The kinetic results demonstrated removal percentages of 97.2%, 69.5%, and 100% using DE, PD, and D@MgO, respectively, at a 1 g/L adsorbent dosage. The adsorption results using DE and D@MgO showed the best fitness with pseudo-first-order kinetic and Langmuir isotherm models, while the obtained results using PD demonstrate better fitness with the Freunlidich model. The recognised fitting results with the pseudo-first-order model and estimated adsorption energies demonstrated physical uptake of ammonium by DE (5.93 kJ/mol), PD (4.05 kJ/mol), and D@MgO (7.81 kJ/mol). The theoretical maximum ammonium uptake capacity of DE, PD, and D@MgO were 63.16 mg/g, 59.5 mg/g, and 78.3 mg/g, respectively. Using synthetic adsorbents in a fixed-bed column system for treating ammonium ions in Lake Qarun water resulted in removal percentages of 57.4%, 53.3%, and 62.6% using a DE bed, PD bed, and D@MgO bed, respectively, after treating approximately 7.2 L of Lake Qarun water using a bed thickness of 3 cm, a flow rate of 5 mL/min, pH 8, and the determined ammonium concentration in Lake Qarun water (28.7 mg/L). The curves demonstrated breakthrough times of 900 min, 900 min, and 960 min for the DE bed, PD bed, and D@MgO bed, respectively, with 1440 min as the saturation time. The columns' performances also were studied based on the Thomas model, the Adams-Bohart model, and the Yoon-Nelson model.

The efficiency of blackberry loaded AgNPs, AuNPs and Ag@AuNPs mediated pectin in the treatment of cisplatin-induced cardiotoxicity in experimental rats.

Cisplatin (cis-Diaminedichloroplatinum) is one of the most effective chemotherapeutic because of its anti-neoplastic properties against various types of tumor. However, it has a wide variety of side effects such as hepato, gastrointestinal, neuro, nephro, and cardiotoxicity (acute and/or chronic) that highly restricted its usage. Thus, research work was planned to detect the role of gold (AuNPs), silver nanoparticles (AgNPs) and their corepshell (Ag@AuNPs) as a carrier for blackberry extract and to enhance its benifit in treatment of cisplatin-induced cardiotoxicity. In our work, solid-state process was used in order to prepare these nanoparticles using pectin as an ecologically friendly-polymer acting as reductant for ions and at the same time as stabilizing agent for the produced nanoparticles. This nominated method for large-scale preparation of nanoparticles is simple, efficient, and convenient. The presence of individual metallic Ag, Au and both has been proven by UV-vis spectroscopy. Transmission electron microscopy (TEM) and particle size analyzer confirmed the preparation of spherical small size with a main diameter <40 nm. The data obtained from zeta potential evaluation displayed the well stabilization for the produced nanoparticles. Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and particle size analyzer have verified that the spherical small size is <40 nm in diameter. Data from zeta potential assessment revealed the good stability of the produced nanoparticles. To this end, fifty sex rats were used in this study and divided into control, cisplatin (cispt), and five treated groups. After the experimental period, lipid profile was estimated and atherogenic coefficient (AC), atherogenic index (AI), and cardiac risk ratio (CRR) were calculated. Oxidant and antioxidant parameters were also estimated. Cardiovascular disease markers were estimated by ELISA. The mean levels of cholesterol, triglycerides, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and cardiovascular markers were significantly increased in cispt group compared to control; whereas these parameters were attenuated in all treated groups in particular that received blackberry (bb) loaded Ag@AuNPs. Based on these results, it can be concluded that bb has antioxidant and antilipidemic effect that help in protecting against cardiovascular disease specially when loaded with Ag@AuNPs.

Clinical epidemiology and phenotypic characteristics of Crohn's disease in the central region of Saudi Arabia.

BACKGROUND/AIMS: Despite the remarkable increase in the incidence of Crohn's disease among Saudis in recent years, data about Crohn's disease in Saudi Arabia are scarce. The aim of this study was to determine the clinical epidemiology and phenotypic characteristics of Crohn's disease in the central region of Saudi Arabia. PATIENTS AND METHODS: A data registry, Inflammatory Bowel Disease Information System (IBDIS), was used to register Crohn's disease patients who presented to the gastroenterology clinics in four tertiary care centers in Riyadh, Saudi Arabia between September 2009 and February 2013. Patients' characteristics, disease location, behavior, age at diagnosis according to the Montreal classification, course of the disease, and extraintestinal manifestation were recorded. RESULTS: Among 497 patients with Crohn's disease, 59% were males with a mean age at diagnosis of 25 years [95% Confidence Interval (CI): 24-26, range 5-75 years]. The mean duration from the time of complaint to the day of the diagnosis was 11 months, and the mean duration of the disease from diagnosis to the day of entry to the registry was 40 months. Seventy-seven percent of our patients were aged 17-40 years at diagnosis, 16.8% were ≤16 years of age, and 6.6% were >40 years of age. According to the Montreal classification of disease location, 48.8% of patients had ileocolonic involvement, 43.5% had limited disease to the terminal ileum or cecum, 7.7% had isolated colonic involvement, and 16% had an upper gastrointestinal involvement. Forty-two percent of our patients had a non-stricturing, non-penetrating behavior, while 32.8% had stricturing disease and 25.4% had penetrating disease. CONCLUSION: Crohn's disease is frequently encountered in Saudi Arabia. The majority of patients are young people with a predilection for males, while its behavior resembled that of western societies in terms of age of onset, location, and behavior.