Deciphering angiotensin converting enzyme 2 (ACE2) inhibition dynamics: Carnosine's modulatory role in breast cancer proliferation - A clinical sciences perspective.

Background: Angiotensin-converting enzyme 2 (ACE2) is a pivotal molecular nexus linking novel coronavirus disease to breast cancer. In-silico investigations have repurposed carnosine for both these conditions based on its potential ACE2 inhibitory properties. Methods: Utilizing an ACE2 inhibitor screening kit, we determined the inhibitory range of carnosine doses. Subsequently, we examined the effect of carnosine on ACE2 expression in supernatants from various breast cancer cell lines (MCF-7, MDA-MB-231, and EMT-6). Additionally, we compared ACE2 activity in cell line pellets with and without carnosine and a putative ACE2 activator using a fluorometric activity assay kit. Finally, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay across overlapping concentrations. Results: Carnosine exhibited dose-dependent ACE2 inhibition within the 100-300 mM range. ACE2 expression significantly diminished after exposure to carnosine for 2 and 24 h in MDA-MB-231 and MCF-7 cell lines, respectively. MTT assay unveiled notable antiproliferative effects in MDA-MB-231 (50 % survival at approximately 265 mM) and EMT-6 cell lines (unquantifiable 50 % survival dose). Conversely, the MCF-7 cell line displayed a modest increase in proliferation (Effective concentration 50-186 mM, ∼40 % increased survival). Conclusion: This pioneering study delineates evident dose-dependent ACE2 inhibition by carnosine. Moreover, it unveils the modulatory impact of this ACE2 inhibitor in breast cancer cell lines. Carnosine demonstrated a significant antiproliferative effect on aggressive cell lines while sparing luminal cell lines from substantial toxic or proliferative effects.

Eco-friendly solvent bar microextraction based on a natural deep eutectic solvent and multivariate optimization for simultaneous determination of spironolactone and canrenone in urine and plasma samples.

Simultaneous measurement of spironolactone and canrenone in urine and plasma provides valuable insight into renal function, and therapeutic efficacy and can be utilized to identify potential health risks and ensure patient safety throughout treatment. By adopting greener methods to analyze these compounds, significant reductions in the environmental impact of such studies can be achieved. For this purpose, a sensitive and eco-friendly solvent bar microextraction method using natural deep eutectic solvent (NDE) followed by high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed to determine spironolactone and canrenone in urine and plasma samples. The extraction solvents were synthesized using NDE-based terpenoids containing menthol and camphor in various ratios. The extraction efficiency percentage (EE%) of both drugs was measured using response surface methodology (RSM) based on central composite design (CCD), and 29 extraction tests were conducted to determine the optimum conditions. Although all parameters were found to be significant, the extraction and elution times were critical for isolating the target analytes. Under optimized conditions, the linear dynamic ranges for spironolactone (SPI)/canrenone (CAN) were 11.7-104/13.1-104 µg L-1 and 21.7-104/24.6-104 µg L-1 in urine and plasma samples, respectively with R2 ≥ 0.993. The ranges of intra-/interprecision (relative standard deviation (RSD) %, n = 5) were 1.31-9.17%/ 2.4-11% with extraction recovery ≥ 88.6% for both drugs. The comparison findings with previously published methods confirmed that the developed NDE-solvent bar microextraction (SBME)-HPLC-DAD method for spironolactone and canrenone analysis displayed confident sensitivity, feasible operation, and simple analysis. Furthermore, the method's applicability and effectiveness were proven by successfully analyzing spironolactone and its metabolite canrenone in patients' urine and plasma samples.

Cosmeceutical formulations of pro-vitamin E phosphate: In-vitro release testing and dermal penetration into excised human skin.

Long-term exposure to solar radiation can lead to skin damage such as photoageing, and photocarcinogenesis. This can be prevented by topically applying α-tocopherol phosphate (α-TP). The major challenge is that a significant amount of α-TP needs to reach viable skin layers for effective photoprotection. This study aims to develop candidate formulations of α-TP (gel-like, solution, lotion, and gel), and investigate formulation characteristics' effect on membrane diffusion and human skin permeation. All the formulations developed in the study had an appealing appearance and no signs of separation. All formulations had low viscosity and high spreadability except the gel. The flux of α-TP through the polyethersulfone membrane was the highest for lotion (6.63 ±â€¯0.86 mg/cm2/h), followed by control gel-like (6.14 ±â€¯1.76 mg/cm2/h), solution (4.65 ±â€¯0.86 mg/cm2/h), and gel (1.02 ±â€¯0.22 mg/cm2/h). The flux of α-TP through the human skin membrane was numerically higher for lotion compared to the gel-like (328.6 vs.175.2 µg/cm2/h). The lotion delivered 3-fold and 5-fold higher α-TP in viable skin layers at 3 h and 24 h, respectively, compared to that of the gel-like. The low skin membrane penetration rate and deposition of α-TP in viable skin layers were observed for the solution and gel. Our study demonstrated that dermal penetration of α-TP was influenced by characteristics of formulation such as formulation type, pH, and viscosity. The α-TP in the lotion scavenged higher DPPH free radicals compared to that of gel-like (almost 73% vs. 46%). The IC50 of α-TP in lotion was significantly lower than that of gel-like (397.2 vs. 626.0 µg/mL). The preservative challenge test specifications were fulfilled by Geogard 221 and suggested that the combination of benzyl alcohol and Dehydroacetic Acid effectively preserved 2% α-TP lotion. This result confirms the suitability of the α-TP cosmeceutical lotion formulation employed in the present work for effective photoprotection.

Development of Dioctyl Phthalate@Fe3O4 Nanocomposite Reinforced Hollow Fiber Solid/ Liquid Phase Microextraction Followed by HPLC-DAD for the Determination of Atorvastatin and Gemfibrozil in Human Urine.

BACKGROUND: The desirable levels of lipids, especially in patients with coronary artery disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drugdrug interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil) is recommended only when other options for reducing lipids have been exhausted. OBJECTIVES: Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological fluids and tablets; however, the simultaneous determination of the two drugs in complex biological matrices is limited. Consequently, the development of a sensitive method for simultaneous determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes associated with the adverse drug-drug interaction. METHODS: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite (DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation. Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLCDAD analysis. The main factors influencing the adsorption and desorption process of the selected drugs have been optimized. RESULTS: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples using the optimized conditions. In spiked urine samples, the method showed a good linearity R2˃ 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were 0.11/ 0.36 and 0.73/ 2.42 µg L-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and 99.0%, respectively. The developed method demonstrated comparable results against referenced methods and a satisfactory result for determining the selected drugs in the patient's urine samples. CONCLUSION: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient, sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin and gemfibrozil in the biological fluid matrix.

Community Pharmacy Practice During COVID-19 Pandemic: A Perspective From the Middle East.

The coronavirus disease 2019 (COVID-19) pandemic poses serious challenges to pharmaceutical care services, and innovative responses by community pharmacists and regulatory bodies are needed. The experience in Jordan, located in the Middle East, is shared in this article in light of available international guidelines to provide insight into the efforts made by the pharmacists to safely maintain pharmaceutical services during the current pandemic. In addition, unique roles played by community pharmacists in other countries are discussed to shed light on the important role of community pharmacists in this outbreak.

Women's perceptions of the benefits and risks of skin-lightening creams in two South African communities.

BACKGROUND: Skin-lightening products are commonly used by black communities in South Africa and worldwide. This practice has deep historical and cultural roots and is associated with adverse cutaneous effects. METHODS: A cross-sectional survey of 579 African and Indian women aged 18-70 years was conducted in two large public hospitals in Durban, South Africa. RESULTS: There were 292 Africans and 287 Indians included in the survey sample. Of these 32.3% had used skin-lightening products (60% of Africans and 40% of Indians). Most of those who had used skin lighteners (85 of Africans and 76% of Indians) claimed awareness of the adverse effects of the products, although this did not appear to inform knowledge of the product, how it was used, nor the decision to use the product. Most users (90%) expressed satisfaction with results achieved but 32% reported adverse events. CONCLUSION: Skin-lightening products are used by a third of African and Indian women in South Africa Cultural and historical perceptions equating a fairer skin with social advantage are pervasive and strongly reinforced by the media. There is a poor understanding of the risks associated with the use of these products. Public education campaigns are required to teach consumers about these risks and the importance of concomitant use of sunscreens with these products.

Short-term and long-term effects of electrical stimulation on skin properties.

BACKGROUND: Electrical stimulation (ES) has been used in treating different medical conditions; however, not much is known about the effect of this application on skin properties. The purpose of this study was to investigate the short-term and long-term effects of ES on biophysical properties of the skin. METHODS: A pretest-posttest control design was used in the study. Thirteen men (N = 13, age (M ± SD), 19 ± 5.6 years) were free of skin abnormality on the volar aspect of both forearms. Four areas were allocated and marked with a layout template of two circles 2 cm in diameter and 2 cm apart. Areas 1 and 2 were allocated on the experimental forearm and area 3 and 4 on the control forearm. ES was applied for 15 minutes with two rubber electrodes 8 cm apart surrounding areas 1 and 2 on the experimental forearm three times a week for 2 weeks. Skin properties including transepidermal water loss (TEWL), melanin content, erythema, elasticity and pH were measured pre-ES, during ES and post-ES, and after 2 weeks of applying ES to find out the short-term and long-term effects on skin. RESULTS: The TEWL was increased during ES at 7, 15 and 15-minutes post-ES compared with the baseline (p < 0.01) and to the control forearm (p = 0.04) measurements, and no increase have been noticed of TEWL on the control forearm (p = 0.11). Also, we found no difference in the other skin properties (p > 0.05) on both forearms, and there were no long-term effects (p > 0.05) in any tested variable. CONCLUSION: Electrical stimulation caused temporary increase in TEWL with no effects on other skin properties.

Does massage postapplication improve moisturizer's efficacy? A 2-week regression study.

BACKGROUND: Combining massage with moisturizer application is a popular technique in beauty spa sessions. The subjective positive psychological effects of massage with moisturizer application in hand and face beauty treatment are documented by many people attending spa sessions. The aim of this study was to objectively evaluate the effect of local effleurage massage as an external intervention on moisturizer efficacy. METHODS: In a regression-type study of 2-week, twice-daily application followed by 1 week of regression, 13 female subjects applied "off the shelf" moisturizer twice daily on both forearms followed by 1 min superficial massage for one forearm randomized among subjects. The influence of massage after moisturizer application on skin barrier properties was evaluated by noninvasive measurements of transepidermal water loss (TEWL), skin capacitance, and skin elasticity at baseline, day 7, and day 14 during the treatment phase, and day 21 following a 1-week regression period, in which no moisturizer and no massage were performed on forearms. RESULTS: The tested "off the shelf" moisturizer in both "massage" and "no-massage" application protocols caused a comparable progressive improvement in skin hydration level and barrier permeability over the 2-week treatment period, which was maintained during the 1-week regression (no moisturizer) period. In addition, skin elasticity was similarly improved by both application protocols. CONCLUSION: In this long-term study, the daily performance of massage after moisturizer application was not an effective external intervention for enhancing moisturizer efficacy.

Construction, in vitro and in vivo evaluation of an in-house conductance meter for measurement of skin hydration.

Different probes are used in dermato-cosmetic research to measure the electrical properties of the skin. The principle governing the choice of the geometry and material of the measuring probe is not well defined in the literature and some device's measuring principles are not accessible for the scientific community. The purpose of this work was to develop a simple inexpensive conductance meter for the objective in vivo evaluation of skin hydration. The conductance meter probe was designed using the basic equation governing wave propagation along Transverse Electromagnetic transmission lines. It consisted of two concentric copper circular electrodes printed on FR4 dielectric material. The performance of the probe was validated by evaluating its measurement depth, its ability to monitor in vitro water sorption-desorption and in vivo skin hydration effect in comparison to that of the Corneometer CM 825. The measurement depth of the probe, 15 µm, was comparable to that of CM 825. The in vitro readings of the probe correlated strongly with the amount of water adsorbed on filter paper. Skin hydration after application of a moisturizer was monitored effectively by the new probe with good correlation to the results of CM 825. In conclusion, a simple probe for evaluating skin hydration was made from off-the-shelf materials and its performance was validated in comparison to a commercially available probe.

Skin-lightening practice among women living in Jordan: prevalence, determinants, and user's awareness.

BACKGROUND: The use and misuse of skin-lightening products among women living in Arab communities have not been documented previously. This study investigates the determinants, the prevalence and users awareness associated with the use and misuse of skin-lightening products among women living in Jordan. METHOD: Female customers arriving at selected pharmacy stores were randomly asked to complete a questionnaire. RESULTS: A total of 318 women completed the questionnaire, of which 60.7% reported the use of skin-lightening products. Users included women from different age and economic groups. Main reasons for use were preference of lighter skin tone, the treatment of hyperpigmentary disorders or both. More than a third of the users were not aware of the potential side effects of these products. A significantly larger proportion of skin-lightening product users believed that lighter skin tone plays a role in self-esteem, perception of beauty and youth, marriage and employment opportunities when compared with nonusers. CONCLUSION: Skin lightening is a common practice among women living in Jordan. It is reinforced by the association of lighter skin tone with a number of perceived benefits including perception of beauty, job and marriage opportunity. User's awareness regarding the safety of skin-lightening products and instructions for proper use are important considerations when developing interventions to control the misuse of these products.

Comparative efficacy and safety of deoxyarbutin, a new tyrosinase-inhibiting agent.

Several tyrosinase inhibitors have been developed and utilized to ameliorate various cutaneous hyperpigmentary disorders and complexion discolorations. Deoxyarbutin (dA) (i.e., 4-[(tetrahydro-2H-pyran-2-yl)oxy]phenol), designed using quantitative structure-activity relationships (QSAR), demonstrates effective inhibition of mushroom tyrosinase and skin-lightening capability (1). However, its comparative safety, effectiveness, and reversibility to other known tyrosinase inhibitors in human melanocytes had not been determined. The effect of dA was assessed in cultured human skin cells, on xenographs, and with a clinical trial. Using cultured human melanocytes, the maximum concentration of dA that allowed 95% viability was fourfold greater than for hydroquinone (HQ), indicating that dA is less cytotoxic/cytostatic than HQ. The viability of cultured human keratinocytes and fibroblasts was also less compromised by increasing concentrations of dA as opposed to HQ. At the maximum concentration allowing normal cellular viability, dA effectively inhibited tyrosinase activity and melanin content in human melanocytes, whereas HQ was marginally inhibitory. Upon removal of dA, tyrosinase activity and melanin content was normalized within five days. Topical application of dA on human xenografts resulted in a gradual and visually apparent skin lightening effect during an eight-week period. In a clinical trial, dA facilitated fading of pre-tanned skin to a statistically significant greater extent than either HQ or no treatment. These results demonstrate that dA is a potentially safe, effective, and reversible tyrosinase inhibitor.