Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey’s post hoc test and Chi square test. P<0.05 was considered statistically significant.Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects

Perceived responsibility for mechanical ventilation and weaning decisions in intensive care units in the Kingdom of Saudi Arabia

Background: Optimizing patient outcomes and reducing complications require constant monitoring and effective collaboration among critical care professionals. The aim of the present study was to describe the perceptions of physician directors, respiratory therapist managers and nurse managers regarding the key roles, responsibilities and clinical decision-making related to mechanical ventilation and weaning in adult Intensive Care Units (ICUs) in the Kingdom of Saudi Arabia (KSA). Methods: A multi-centre, cross-sectional self-administered survey was sent to physician directors, respiratory therapist managers and nurse managers of 39 adult ICUs at governmental tertiary referral hospitals in 13 administrative regions of the KSA. The participants were advised to discuss the survey with the frontline bedside staff to gather feedback from the physicians, respiratory therapists and nurses themselves on key mechanical ventilation and weaning decisions in their units. We performed T-test and non-parametric Mann-Whitney U tests to test the physicians, respiratory therapists, and nurses’ autonomy and influence scores, collaborative or single decisions among the professionals. Moreover, logistic regressions were performed to examine organizational variables associated with collaborative decision-making. Results: The response rate was 67% (14/21) from physician directors, 84% (22/26) from respiratory therapist managers and 37% (11/30) from nurse managers. Physician directors and respiratory therapist managers agreed to collaborate significantly in most of the key decisions with limited nurses’ involvement (P<0.01). We also found that physician directors were perceived to have greater autonomy and influence in ventilation and waning decision-making with a mean of 8.29 (SD±1.49), and 8.50 (SD±1.40), respectively. Conclusion: The key decision-making was implemented mainly by physicians and respiratory therapists in collaboration. Nurses had limited involvement. Physician directors perceived higher autonomy and influence in ventilatory and weaning decision-making than respiratory therapist managers and nurse managers. A critical care unit’s capacity to deliver effective and safe patient care may be improved by increasing nurses’ participation and acknowledging the role of respiratory therapists in clinical decision-making regarding mechanical ventilation and weaning

Physicochemical characterization and cancer cell antiproliferative effect of silver-doped magnesia nanoparticles

Silver-doped magnesia nanoparticles (Ag/MgO) were synthesized using the precipitation method and characterized by various techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), Brunner-Emmett-Teller (BET) surface area measurements, and dispersive X-ray spectroscopy (EDX). The morphology of Ag/MgO nanoparticles was determined by transmission and scanning electron microscopy, which revealed cuboidal shaped nanoparticles with sizes ranging from 31 to 68 nm and an average size of 43.5 ± 10.6 nm. The anticancer effects of Ag/MgO nanoparticles were evaluated on human colorectal (HT29) and lung adenocarcinoma (A549) cell lines, and their caspase-3, -8, and -9 activities, as well as Bcl-2, Bax, p53, cytochrome C protein expressions were estimated. Ag/MgO nanoparticles showed selective toxicity towards HT29 and A549 cells while remaining relatively innocuous towards the normal human colorectal, CCD-18Co, and lung, MRC-5 cells. The IC50 values of Ag/MgO nanoparticles on the HT29 and A549 cells were found to be 90.2 ± 2.6 and 85.0 ± 3.5 μg/mL, respectively. The Ag/MgO nanoparticles upregulated caspase-3 and -9 activities, downregulated Bcl-2, upregulated Bax and p53 protein expressions in the cancer cells. The morphology of the Ag/MgO nanoparticle treated HT29 and A549 cells was typical of apoptosis, with cell detachment, shrinkage, and membrane blebbing. The results suggest that Ag/MgO nanoparticles induce apoptosis in cancer cells and exhibit potential as a promising anticancer agent.The publication of this article was funded by the Qatar National Library

Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound.The publication of this article was funded by the Qatar National Library

Public Knowledge, Attitudes, and Practice towards COVID-19 Pandemic in Saudi Arabia: A Web-Based Cross-Sectional Survey

(1) Background: COVID-19 has become a worldwide public health problem. No previous study has investigated factors associated with COVID-19 knowledge, attitude, and practice (KAP) after completely lifting the curfew in all Saudi Arabia regions and cities. Therefore, adequate knowledge, a positive attitude, and correct control of COVID-19 are essential to eradicate the disease. Hence, this study aims to assess factors associated with KAP of COVID-19; (2) Methods: This cross-sectional web-based survey was performed with the participation of 4305 individuals aged over 15 years living in Saudi Arabia from 11 to 19 August 2020. They were included using the snowball sampling method; (3) Results: Of the 4305 participants, 94.9% were Saudis, 60% females, and 45.4% were in the age group of 20–34 years, 61.7% married, and 49.3% from the Eastern Province of Saudi Arabia. Most of the participants demonstrated good KAP levels (89.6%, 87.2%, and 87.2%) towards the COVID-19 pandemic, respectively. In addition, most of the participants (85.8%) used the internet and social media as a source for COVID-19 information (4) Conclusions: The finding showed that most of the participants demonstrated good knowledge of COVID-19, positive attitudes, and demonstrated good practices for preventing the spread of disease infection

Time Trends and Regional Variation in Prevalence of Asthma and Associated Factors in Saudi Arabia: A Systematic Review and Meta-Analysis

Background. Asthma is the most common reason for emergency visits to hospital and loss of productive hours. In Saudi Arabia, asthma affects more than 2 million people and majority of them have uncontrolled asthma with their quality of life adversely being impacted. It is well known that the prevalence of asthma has been increasing in many places around the world in the last few decades. The present review attempted to identify studies on asthma and associated factors in Saudi Arabian population and assess their time trends and regional variation. Methods. The titles and abstracts of retrieved articles were compared to delete duplication and irrelevant data. A data collection form was designed to extract several key components from selected articles like bibliographic information on the article, study population, and sample size. Extracted information was grouped appropriately for data analysis. Database search retrieved 71 articles. Applying inclusion and exclusion criteria, 40 articles were excluded and 31 qualified full articles were included for the review. Results. Among 31 retained studies, Riyadh had the highest publication output followed by Jeddah. Ten studies were based on ISAAC and 5 on non-ISAAC questionnaires while 5 studies were genetic studies conducted to unravel the genetic basis of asthma. Most of the studies were conducted on pediatric subjects of less than 16 years of age. Sample sizes ranged from less than 150 to more than 10000 with study settings being predominantly urban (22 studies). The pooled weighted prevalence rates of asthma, lifetime wheeze, and rhinitis were 14.3% (95% CI: 13.4–15.2), 16.5 (95% CI 15.5–17.4), and 21.4 (95% CI 20.5–22.3), respectively. An increase in asthma prevalence from 1990 to 2000 along with a stabilized or not so significant decline in the prevalence from 2010 to 2016 was observed. Conclusion. The prevalence of asthma varied in different regions without any disparity in prevalence in the rural and urban areas of Saudi Arabia. The understanding of genetic variability and recognition of risk factors in asthma patients can greatly help in individualizing the therapy for the management and control of asthma

Tamarix articulata Induced Prevention of Hepatotoxicity Effects of In Vivo Carbon Tetrachloride by Modulating Pro-Inflammatory Serum and Antioxidant Enzymes to Reverse the Liver Fibrosis

This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels

Inferring Therapeutic Targets in <i>Candida albicans</i> and Possible Inhibition through Natural Products: A Binding and Physiological Based Pharmacokinetics Snapshot

Despite being responsible for invasive infections, fungal pathogens have been underrepresented in computer aided therapeutic target mining and drug design. Excess of Candida albicans causes candidiasis, causative of thrush and vaginal infection due to off-balance. In this study, we attempted to mine drug targets (n = 46) using a subtractive proteomic approach in this pathogenic yeast and screen natural products with inhibition potential against fructose-bisphosphate aldolase (FBA) of the C. albicans. The top compound selected on the basis of best docking score from traditional Indian medicine/Ayurvedic library was (4-Hydroxybenzyl)thiocarbamic acid, from the ZINC FBA inhibitor library was ZINC13507461 (IUPAC name: [(2R)-2-hydroxy-3-phosphonooxypropyl] (9E,12E)-octadeca-9,12-dienoate), and from traditional Tibetan medicine/Sowa rigpa was Chelerythrine (IUPAC name: 1,2-Dimethoxy-12-methyl-9H-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium), compared to the control (2E)-1-(4-nitrophenyl)-2-[(4-nitrophenyl)methylidene]hydrazine. No Ames toxicity was predicted for prioritized compounds while control depicted this toxicity. (4-Hydroxybenzyl)thiocarbamic acid showed hepatotoxicity, while Chelerythrine depicted hERG inhibition, which can lead to QT syndrome, so we recommend ZINC13507461 for further testing in lab. Pharmacological based pharmacokinetic modeling revealed that it has low bioavailability and hence, absorption in healthy state. In cirrhosis and renal impairment, absorption and plasma accumulation increased so we recommend further investigation into this occurrence and recommend high dosage in further tests to increase bioavailability

Pan-Genomics of <i>Escherichia albertii</i> for Antibiotic Resistance Profiling in Different Genome Fractions and Natural Product Mediated Intervention: In Silico Approach

Escherichia albertii is an emerging, enteric pathogen of significance. It was first isolated in 2003 from a pediatric diarrheal sample from Bangladesh. In this study, a comprehensive in silico strategy was followed to first list out antibiotic-resistant genes from core, accessory and unique genome fractions of 95 available genomes of E. albertii. Then, 56 drug targets were identified from the core essential genome. Finally, ZipA, an essential cell division protein that stabilizes the FtsZ protofilaments by cross-linking them and serves as a cytoplasmic membrane anchor for the Z ring, was selected for further downstream processing. It was computationally modeled using a threading approach, followed by virtual screening of two phytochemical libraries, Ayurvedic (n = 2103 compounds) and Traditional Chinese Medicine (n = 36,043 compounds). ADMET profiling, followed by PBPK modeling in the central body compartment, in a population of 250 non-diseased, 250 cirrhotic and 250 renally impaired people was attempted. ZINC85624912 from Chinese medicinal library showed the highest bioavailability and plasma retention. This is the first attempt to simulate the fate of natural products in the body through PBPK. Dynamics simulation of 20 ns for the top three compounds from both libraries was also performed to validate the stability of the compounds. The obtained information from the current study could aid wet-lab scientists to work on the scaffold of screened drug-like compounds from natural resources and could be useful in our quest for therapy against antibiotic-resistant E. albertii

Formulation, In Vitro and In Silico Evaluations of Anise (<i>Pimpinella anisum</i> L.) Essential Oil Emulgel with Improved Antimicrobial Effects

Over the past decade, researchers have made several efforts to develop gel-based formulations that provide an alternative to traditional hydrogels and emulgel. Due to its excellent antibacterial properties, anise, the main constituent of Pimpinella anisum L., widely used in pharmaceuticals, was selected as the active ingredient in this study. Since many bacteria have developed considerable antibiotic resistance, this research aimed to develop an herbal emulgel for treating skin infections caused by bacteria. Given these obstacles, we developed and evaluated a new, cost-effective topical emulgel solution containing anise essential oil against Escherichia coli (E. coli). Anise-based emulgels, potential drug delivery platforms, have been evaluated for various parameters, including physical properties, viscosity, pH, rheology, encapsulation efficiency, and in vitro release research. The AEOs emulgel demonstrated remarkable colloidal stability, with a zeta potential of 29 mV, a size of 149.05 nm, and considerable polydispersity. The efficacy of anise-loaded emulgels as antibacterial formulations was evaluated in vitro. E. coli was used as a model microbial organism for the antibacterial study. Human keratinocytes (HaCaT) were used to examine the biocompatibility of the emulgel. Molecular docking revealed that the essential oil components of Pimpinella anisum L. possess a high affinity for the bacterial adhesin protein FimH of E. coli. These findings indicate that the developed AEOs have the potential to be analyzed using E. coli as a model organism