Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel

<p>Abstract</p> <p>Background</p> <p>Although a high level of functional voltage-gated sodium channel (VGSC) expression has been found in strongly metastatic human and rat prostate cancer (PCa) cells, the mechanism(s) responsible for the upregulation is unknown. The concentration of epidermal growth factor (EGF), a modulator of ion channels, in the body is highest in prostatic fluid. Thus, EGF could be involved in the VGSC upregulation in PCa. The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated. A quantitative approach, from gene level to cell behaviour, was used. mRNA levels were determined by real-time PCR. Protein expression was studied by Western blots and immunocytochemistry and digital image analysis. Functional assays involved measurements of transverse migration, endocytic membrane activity and Matrigel invasion.</p> <p>Results</p> <p>Exogenous EGF enhanced the cells' <it>in vitro </it>metastatic behaviours (migration, endocytosis and invasion). Endogenous EGF had a similar involvement. EGF increased VGSC Nav1.7 (predominant isoform in PCa) mRNA and protein expressions. Co-application of the highly specific VGSC blocker tetrodotoxin (TTX) suppressed the effect of EGF on all three metastatic cell behaviours studied.</p> <p>Conclusion</p> <p>1) EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2) VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.</p

Acquired Uterine Vascular Anomaly: Experience from a tertiary care center in Pakistan

Objective: To retrospectively review imaging findings and the outcomes of uterine artery embolization (UAE) in symptomatic uterine vascular anomalies. Methods: We identified 15 cases of acquired uterine vascular anomaly from 2010 to 2020 who were evaluated with ultrasound, computed tomography, and magnetic resonance imaging, either alone or in combination. All patients had history of dilatation and curettage or uterine instrumentation. They underwent angiography and embolization of the uterine arteries. Primary outcome post embolization was assessed clinically and/or in combination with ultrasound. Post procedure pregnancies were also recorded. Results: Non-invasive imaging was abnormal in all patients, however this pre intervention imaging was unable to accurately classify the type of vascular anomaly except in the case of pseudoaneurysm. Conventional angiography showed uterine artery hyperemia in 6, arteriovenous malformation in 7 and pseudoaneurysm in 2 patients. The technical success rate was 100% with no repeat embolization needed. Follow up ultrasound in 12 patients revealed resolution of abnormal findings, remaining three were normal on clinical follow up. Seven patients (46.7%) had a normal pregnancy, 15.7 months after the procedure (range 4-28 months). Conclusion: UAE is a safe and effective management option for intractable severe bleeding in patients with uterine vascular anomaly post instrumentation and is seen not to impair future pregnancy. Keywords: Uterine artery embolization; Pseudoaneurysm; Arteriovenous malformation; Ultrasound; Computed tomography; Magnetic resonance imaging

In vivo Evaluation of a Cosmetic Emulsion Containing Soybean Extract for Anti-Aging

Purpose: To develop and assess the anti-aging potential of a cosmetic W/O emulsion containing an extract of soybean, Glycine max (L.) Merr. Fabaceae.Methods: This single-blind placebo-controlled study was performed in 11 healthy male human volunteers. A formulation comprising of 4 % of concentrated extract of soybean was prepared by loading the extract in the internal aqueous phase of the emulsion. A control (base), consisting of theemulsion without the extract, was also prepared. Both formulations were applied to the cheeks of all volunteers for 12 weeks and their effect on different skin parameters, i.e., moisture contents, elasticity and surface evaluation of living skin (SELS) were assessed.Results: The formulation containing 4 % soybean extract showed significant (p ≤ 0.05) effects on skin elasticity and moisture contents but the base showed insignificant effect (p ≤ 0.05). There was significant (p . 0.05) decline in SELS, i.e., SEsc (skin scaliness, from 1.73 } 0.05 to 1.66 } 0.06), SEw (skin wrinkles, from 71.74 ± 1.52 to 68.51 ± 1.64), SEsm (skin smoothness, from 109.01 ± 4.77 to 102.03 ± 4.23), and SEr (skin roughness, from 4.04 ±0.09 to 3.82± 0.08) parameters after applicationof the extract formulation for 12 weeks.Conclusion: Topical application of the cosmetic emulsion containing soybean extract exerts potential skin anti-aging effects.Keywords: Glycine max, Soybean, Anti-aging, Skin elasticity, Cosmetic emulsion, Surface evaluation of living skin (SELS), Skin moisture conten

Overview of the oncogenic signaling pathways in colorectal cancer: Mechanistic insights.

Colorectal cancer is a multifaceted disease which is therapeutically challenging. Based on insights gleaned from almost a quarter century of research, it is obvious that deregulation of spatio-temporally controlled signaling pathways play instrumental role in development and progression of colorectal cancer. High-throughput technologies have helped to develop a sharper and broader understanding of the wide ranging signal transduction cascades which also contribute to development of drug resistance, loss of apoptosis and, ultimately, of metastasis. In this review, we have set the spotlight on role of JAK/STAT, TGF/SMAD, Notch, WNT/β-Catenin, SHH/GLI and p53 pathways in the development and progression of colorectal cancer. We have also highlighted recent reports on TRAIL-mediated pathways and molecularly distinct voltage-gated sodium channels in colorectal cancer

Statistical analysis of factors influencing patient length of stay in emergency departments

Purpose – Patient length of stay (LOS) is an important indicator of emergency department (ED) performance. Investigating factors that influence LOS could thus improve healthcare delivery and patient safety. Previous studies have focused on patient-level factors to explain LOS variation, with little research into service-related factors. This study examined the association between LOS and multi-level factors including patient-, service- and organization-level factors. Design/methodology/approach – This study uses a retrospective observational design to identify a cohort of patients from arrival to discharge from ED. A year-long data regarding patients flow trhoguh ED were analyzed using analytics techniques and multi-regression models. The response variable was patient LOS, and the independent variables were patient characteristics, service-related factors and organizational variables. Findings – The findings of this study showed that older patients, middle triage and hospitalization were all associated with longer LOS. Service-related factors such as complexity of care provided, initial ward designation and ward transfer had a significant impact as well. Finally, prolonged LOS was associated with a higher ratio of patients per medical doctor and per nurse. In contrast, a higher number of residents in the ED were associated with longer patient LOS. Originality/value – Previous studies on patient LOS have focused on patient-level factors, with little research on service-related factors. This study has addressed that gap by examining the association between LOS and multi-level factors including patient-, service- and organization-level factors. Patient-level factors included demographics, acuity, arrival shift, arrival mode and discharge type. Service-level factors consisted of first ward, ward transfer and complexity of care provided. Organizational factors consisted of three ratios: patients per MD, patients per nurse and patients per resident. The results add to the current understanding of factors that increase patient LOS in EDs and contribute to the body of knowledge on ED performance, operation management and quality of care. The study also provides practical and managerial insights that could be used to improve patient flow in EDs and reduce LOS

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Computational study on organochlorine insecticides extraction using ionic liquids

Insecticides pose hazardous environmental effects and can enter the food chain and contaminate water resources. Ionic liquids (ILs) have recently drawn much interest as environmentally friendly solvents and have been an efficient choice for extracting pesticides because of their outstanding thermophysical characteristics and tunable nature. In this study, ILs were screened using COSMO-RS (Conductor-like Screening Model for Real Solvents) to extract organochlorine insecticides from water at 289 K. A total of 165 ILs, a combination of 33 cations with five anions, were screened by COSMO-RS to predict the selectivity and capacity of the organochlorine insecticides at infinite dilution. The Organochlorine insecticide compounds, such as benzene hexachloride (BHC), Heptachlor, Aldrin, Gamma-Chlordane (γ-Chlordane), Endrin, and Methoxychlor are selected for this study. Charge density profiles show that Endrin and Methoxychlor compounds are strong H-bond acceptors and weak H-bond donors, while the rest of the compounds are H-bond donors with no H-bond acceptor potential. Moreover, it has been shown that ILs composed of halides and heteroatomic anions in conjunction with cations have enhanced selectivity and capacity for insecticides. Moreover, the hydrophobic phosphonium-based ILs have enhanced selectivity and capacity for insecticides. In BHC extraction, the selectivity of 1,3-dimethyl-imidazolium chloride was found to be the highest at 1074.06, whereas 2-hydroxyethyl trimethyl ammonium chloride exhibited the highest capacity being 84.0.1,3-dimethyl-imidazolium chloride exhibits the highest performance index, which is 57064.77. In addition, the ILs that have been chosen are well-recognized as environmentally friendly and very effective solvents to extract insecticides from water. As a result, this study evaluated that ILs could be promising solvents that may be further developed for the extraction of insecticides from contaminated water.This work was made possible by the support of an International Research Collaboration Co-Fund (IRCC ) grant from Qatar University , grant reference number IRCC-2022-607. Open Access funding provided by Qatar National Library . The statements made herein are solely the responsibility of the authors.Scopu

Adsorption of 4-Nitrophenol onto Iron Oxide Bentonite Nanocomposite: Process Optimization, Kinetics, Isotherms and Mechanism

Despite its importance in chemical industry, 4-Nitrophenol (4-NP) is a persistent organic pollutant that has serious effects on the ecosystem. In the present study, Box–Behnken design in response surface methodology was used to optimize the adsorption process parameters for the maximum 4-NP removal at 30 ℃ using Fe3O4/Bt NC. The regression model results suggested that the optimum adsorbent dosage, initial concentration, pH and contact time were 0.3182 g, 85 mg/L, 11 and 137.2 min, respectively. The regression model showed an optimum removal of 100%, while 99.5% removal was obtained from batch experiments at the optimum conditions suggested by the regression model, which confirm the model validity. The adsorption data best fitted to Freundlich isotherm model and Pseudo second-order kinetic model suggesting the existence of physical and chemical interaction between the fabricated composite and 4-NP. FTIR analysis suggested that the adsorption mechanism included an electrostatic attraction and the formation of new chemical bonds. Obtained results suggest that Fe3O4/Bt NC can be an effective adsorbent for complete 4-NP removal at the indicated optimum conditions.This research was made possible by an NPRP Grant # 10-0127-170270 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. The author Dina Ewis acknowledged the financial support of QNRF through the Graduate Sponsorship Research Award (GSRA) number GSRA#6-2-0516-19029.Scopu

Preparation of TiO2/WO3/C/N Composite Nanofibers by Electrospinning Using Precursors Soluble in Water and Their Photocatalytic Activity in Visible Light

Extending the absorption range of TiO2 nanofibers to visible light is a great improvement of the photocatalytic property of TiO2. In this study, TiO2/WO3/C/N nanofibers were prepared by electrospinning using precursors soluble in water then annealing in argon. Titanium(IV) bis(ammonium lactato)dihydroxide (TiBALDH) and ammonium metatungstate (AMT) were used as the precursor for TiO2 and WO3 respectively. Different volume ratios of the precursors were added to a solution of PVP before electrospinning. The fibers were studied by XPS, SEM-EDX, TEM, FTIR, XRD, Raman spectroscopy and UV–VIS diffuse reflectance spectroscopy (DRS). The photocatalytic degradation of methylene blue by the fibers in visible light was investigated. The fibers had anatase TiO2 and monoclinic WO3. Based on UV–VIS DRS and Kubelka-Munk function the fibers could absorb visible light. Moreover, 100% TiBALDH had an indirect band gap of 2.9 eV, and the band gap decreased with increase in AMT, i.e., for 0% TiBALDH, band gap was 2.4 eV. The fibers degraded methylene blue dye in visible light, and 90% TiBALDH had the highest photocatalytic activity, i.e., it degraded 40% of the dye after 240 min