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Abdulkareem M Albekairy,1 Aiman A Obaidat,1 Mansour S Alsharidah,2 Abdulmajeed A Alqasomi,3 Abdulrhman S Alsayari,4 Ahmad A Albarraq,5 Ahmad M Aljabri,6 Alian A Alrasheedy,7 Bader H Alsuwayt,8 Bandar E Aldhubiab,9 Faisal A Almaliki,10 Majed M Alrobaian,11 Mohammad A Aref,12 Najla A Altwaijry,13 Nasser H Alotaibi,14 Saad A Alkahtani,15 Saleh A Bahashwan,16 Yaser A Alahmadi16 1College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2College of Medicine, Qassim University, Buraydah, Saudi Arabia; 3College of Pharmacy, Qassim University, Buraydah, Saudi Arabia; 4College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 5College of Pharmacy, Jazan University, Jazan, Saudi Arabia; 6College of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 7College of Pharmacy, Qassim University, Unaizah, Saudi Arabia; 8College of Pharmacy, Northern Border University, Rafha, Saudi Arabia; 9College of Clinical Pharmacy, King Faisal University, Al Hofuf, Saudi Arabia; 10College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 11College of Pharmacy, Taif University, Taif, Saudi Arabia; 12College of Pharmacy, Albaha University, Albaha, Saudi Arabia; 13College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 14College of Pharmacy, Jouf University, Aljouf, Saudi Arabia; 15College of Pharmacy, Najran University, Najran, Saudi Arabia; 16College of Pharmacy, Taibah University, Madina, Saudi ArabiaCorrespondence: Aiman A ObaidatCollege of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, P.O. Box 3660, Riyadh, 11481, Saudi ArabiaEmail obaidata@ksau-hs.edu.saBackground: With the expansion in pharmacy education in Saudi Arabia, there is a pressing need to maintain quality assurance in pharmacy programs using several tools. The progress test is a formative assessment tool that can serve to provide information to all stakeholders. This study evaluated the results of a unified progress test that was shared among 15 colleges of pharmacy.Methods: The progress test was composed of 100 MCQs where 30% of which cover basic pharmaceutical sciences and 70% cover pharmacy practice. The questions were collected from all the 15 colleges of pharmacy participated in the test. The test was administered online to all undergraduate students in the professional programs of these colleges.Results: The overall attendance rate was 80% from the total number of students enrolled in the participating colleges. Mean scores of students in basic pharmaceutical sciences were relatively higher than in pharmacy practice. The assessment results of the students in the unified program learning outcomes among colleges were higher in the domains of knowledge and skills compared to competence domain. There was a significant increment in the mean scores of the students as they progress through the years of the professional program. No correlation was found between the mean scores in the test and the cumulative grade point average (cGPA) of all students regardless of their level.Conclusion: The results indicated growth and maintenance of the gained knowledge and skills by the students as they progress through the years of the professional program with consistency in the results among the participating colleges. Sharing a unified test was effective as a valuable tool for the colleges of pharmacy for the purposes of benchmarking and improving the curricula. In addition, it could serve to evaluate learning of students and harmonize knowledge and skills gained by students at different institutions.Keywords: progress test, formative test, assessment, learning outcomes, pharmacy education, Saudi Arabia

Colorectal cancer is known for its substantial impact on global morbidity and mortality, with higher prevalence in developed regions. This study delves into the potential treatment advantages of resveratrol (RSV) in addressing colorectal cancer. Apoptosis and gene expression associated with apoptotic factors were explored using Caco-2 cells, a pertinent model for colorectal adenocarcinoma. The effect of RSV on Caco-2 cell viability was investigated using MTT assay and neutral red uptake assay. The level of generated ROS was high in cells exposed to RSV. Likewise, the enzyme superoxide dismutase, responsible for converting ROS into hydrogen peroxide, was concurrently elevated. The effect of RSV on DNA damage was examined through the TUNEL assay. The gene expression analyses for pro-apoptotic elements were studied using qRT-PCR. Furthermore, the impact of RSV on the migration of Caco-2 cells was conducted through a wound-healing assay. Our results reveal RSV’s cytotoxicity on Caco-2 cells, showing dose-dependent inhibition of viability, indicating its promise as a treatment agent. The induction of cell death by apoptosis is substantiated by DNA damage. Notably, the upregulated expression of caspase-3, Bax, and p53 genes suggests RSV’s potential to modulate key apoptosis-related elements. In addition, RSV displayed an inhibitory effect on cellular migration, a significant (p < 0.05 and p < 0.01) in cancer metastasis. These findings underscore RSV’s potential to be a multifaceted therapeutic agent targeting apoptosis and metastatic processes in colorectal cancer.

Objectives: A low handgrip strength (HGS) is a significant risk factor for multiple diseases. However, most relevant studies investigate the complications of a low HGS, while the risk potential of causative factors of low HGS remain poorly characterized., Methods: We investigated the potentials of quality of life, depression, dyslipidaemia, diabetes mellitus, cancer, Alzheimer's disease, stroke, frailty, and difficulties performing daily activities in predicting low HGS (≤ 27 kg for men, ≤ 16 kg for women) in European older adults aged 50 or above from 15 countries (n = 42,183). All data was collected from four successive waves of survey of health, ageing, and retirement in Europe (SHARE) conducted between 2013 and 2020. Logistic models are applied, and estimated effects are presented as odds ratios and probabilities., Results: Collectively, 3016 participants (men; n = 1395; 7.38%, women; n = 1621, 6.97%) developed low HGS during the 6.5 years study period. After adjusting for covariables, we identified an advancing age (1.6-48.1% points higher risk of low HGS), male gender (1.0%-point higher risk of low HGS), lower quality of life (1.6%-point higher), and stroke (1.5%-points) as significant risk factors for low HGS. We also found a dose-dependent association of Euro-D depression scores with the risk of low HGS, as the higher scores were associated with between 0.6- and 2.3%-points higher risk of developing low HGS than participants without depression. Among physical performance indicators, difficulty climbing stairs (2.0%-points higher low HGS risk) or rising from a chair (0.7%-points) were significantly associated with developing low HGS. Lastly, frailty (0.9%-points higher risk of low HGS) and the fear of falling down (1.6%-points higher risk) also increased the risk of developing low HGS., Conclusion: Altogether, we report several risk factors for developing low HGS. Our observations may help evaluating and monitoring high-risk population for developing low HGS in pre-clinical settings., (© 2024. The Author(s).)

Aim: This cross-sectional study investigated the association between metabolic syndrome (MetS) and handgrip strength (HGS) with respect to sex and adiposity in Saudi men ( n  = 287) and women ( n  = 268)., Material and Methods: Anthropometry, body composition, HGS, and blood biochemistry were measured. The average age of the study population was 57.65 ± 9.3 years (men = 55.1 ± 9.3 years, women = 60.4 ± 9.3 years). We report that HGS/body mass index (BMI), HGS/weight, and HGS/fat (%) were significantly higher in controls than in patients with MetS in men but not in women. According to the ROC analysis, relative HGS (RHGS) was higher than HGS alone in the association with MetS, which was significant for men ( p  < 0.01). At lower quartiles of HGS, the probability of MetS was higher in women, and the same was found in men in the lower quartiles of HGS/%Fat. Multinomial regression revealed significant associations between age and adiposity and MetS in men and HGS in women. Additionally, the linear regression of age, HGS, and weight exhibited significant associations between HGS with WC in both sexes., Conclusion: A higher risk of MetS in the lower quartiles of HGS was found in women, and adiposity moderated the relationship between HGS and MetS in men.

We investigated the risk factors for hip fracture in 48,533 European older adults for 8 years from 2013 onward. We identified female gender, age above 80, low handgrip strength, and depression as significant risk factors for hip fracture. Our findings may help identify high-risk populations for hip fractures in pre-clinical settings., Objectives: Hip fracture is a major cause of functional disability, mortality, and health costs. However, the identification and characterization of its causative factors remain poor., Methods: We investigated demography, handgrip strength (HGS), depression, and multiple age-associated comorbidities for predicting future hip fracture in individuals aged 50 or above from 15 European countries (n = 48,533). All participants were evaluated from 2013 to 2020 using four successive waves of the Survey of Health, Aging, and Retirement in Europe (SHARE)., Results: Altogether, 1130 participants developed hip fractures during the study period. We identified female gender, an advancing age from quinquagenarians onward, and a poor socioeconomic status as critical risk factors for future hip fracture. Having mobility difficulty, a low HGS (< 27 kg in men, < 16 kg in women) and higher scores on Euro-D depression scales were also significant risk factors for hip fracture. Summated scales of hypertension, diabetes mellitus, cancer, Alzheimer's disease, and stroke did not appear as risk factors., Conclusion: Collectively, we report advancing age, female gender, low HGS, and depression as independent risk factors for hip fracture. Our findings are useful in identifying high-risk populations for hip fractures in pre-clinical settings before rigorous evaluation and treatment in clinics., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Plant-derived products or extracts are widely used in folk/traditional medicine to treat several infections, ailments, or disorders. A well-known medicinal herb, Myrtus communis is an evergreen fragrant plant native to the Mediterranean region that has been used for ages in traditional medicine around the world., Materials and Methods: The microplate alamarBlue assay and the well diffusion method were used to evaluate the zone of inhibition and MIC, respectively. The double-disc diffusion method was used to investigate the synergy between antibiotics and the extract. The crystal violet method was used to investigate biofilm development. The SulphoRhodamine-B assay and DNA flow cytometry were used to investigate the proliferation and subsequent distribution of cells among different phases of the cell cycle. The apoptotic and necrotic phases of the cancer cells were examined using flow cytometry in conjunction with Annexin V-FITC/PI labeling. Using the IBM SPSS statistical program, a one-way ANOVA with Tukey's post hoc test was employed for statistical analysis., Results: The ethanolic leaf extract of M. communis showed a strong growth inhibition effect (zone of inhibition: 20.3 ± 1.1-26.3 ± 2.5 mm, MIC: 4.88-312.5 µg/mL, and MBC: 39.07-1250 μg/mL) against several rapidly growing and slow-growing mycobacterial strains in a dose-dependent manner. Damage to the cell wall of bacterial cells was determined to be the cause of the antimycobacterial action. The extract inhibited biofilm formation (MBIC of 9.7 µg/mL) and eradicated already-formed mature and ultra-mature biofilms of M. smegmatis , with MBEC values of 78 µg/mL and 156 µg/mL, respectively. Additionally, the extract exhibited potent anticancer effects against diverse cancer cell lines of the breast (MCF-7), liver (HepG2), cervix (HeLa), and colon (HCT116) (IC 50 for HCT116: 83 ± 2.5, HepG2: 53.3 ± 0.6, MCF-7: 41.5 ± 0.6, and HeLa: 33.3 ± 3.6) by apoptosis after arresting the cells in the G 1 phase of the cell cycle., Conclusions: These results suggest that M. communis leaf extract is a potential source of secondary metabolites that could be further developed as potential anticancer and antimycobacterial agents to treat diverse types of cancers and mycobacterial infections.

Cyclophosphamide (CPM) is a well-established antineoplastic drug with marked clinical outcomes in various types of cancers. Despite being a promising drug, its use is associated with significant renal toxicity and often limits its use, leading to compromised clinical outcomes. Therefore, this study explored the renal protective effect of bergapten (BGP), a natural bioactive compound that showed marked antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Till now, BGP has not been studied for its renal protective effect in an in vivo model. Animals were divided into control, toxic, BGP-3, BGP-10, and BGP Per se . The control group was treated with normal saline for 2 weeks. To the toxic group, CPM 200 mg/kg was given on day 7 as i.p. To BGP-3, 10, and Per se , BGP-3 and 10 mg/kg, ip was given 2 weeks with a single shot of CPM 200 day 7. To the Per se group, only BGP 10 mg/kg, ip was given from day 1 to day 14. After 14 days, animals were sacrificed, and kidneys were removed and studied for the markers of oxidative stress, inflammation, renal injury, renal fibrosis, and renal damage using biochemical, histopathological, and immunohistochemical studies. We found that BGP-10 effectively reversed the damage toward normal, whereas BGP-3 failed to exhibit a significant renal protective effect. We conclude that bergapten could be a potential renal protective drug, and hence, more detailed cellular molecular-based studies are needed to bring this drug from the bench to the bedside., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: Early diagnosis of Parkinson's disease (PD) is critical for optimal treatment. However, the predictive potential of physical and mental health in PD is poorly characterized., Methods: We evaluated the potential of multiple demographic, physical, and mental factors in predicting the future onset of PD in older adults aged 50 years or older from 15 European countries. Individual study participants were followed over four waves of the Survey of Health, Ageing, and Retirement in Europe (SHARE) from 2013-2020., Results: Of 57,980 study participants, 442 developed PD during the study period. We identified male sex and advancing age from the sixth decade of life onward as significant predictors of future PD. Among physical factors, a low handgrip strength (HGS; men <27 kg, women <16 kg), being bothered by frailty, and recent falls were significantly associated with future PD. Among mental factors, a higher depression (Euro-D depression score >6) emerged as an independent predictor of future PD. Finally, the presence of hypertension or Alzheimer's disease (AD) increases the risk of future PD., Conclusions: Altogether, male sex, advancing age, low HGS, frailty, depression, hypertension, and AD were identified as critical risk factors for future PD. Our results may be useful in the early identification and treatment of populations at risk for PD., (Copyright © 2024. Published by Elsevier Inc.)

Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% ( p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.

A simple fluorescence method is described for measuring rutin dependent on the nitogen-doped carbon dots (NCDs) prepared via simple pyrolysis method from chicken feet biowaste. The as-fabricated NCDs have unique advantages including cost-effectiveness and high quantum yield (42.9 %). The as-prepared NCDs explore an optimal emission band at 430 nm following exciting NCDs at 330 nm. Addition of rutin to blue-emissive NCDs quenched their fluorescence emission by inner-filtration effect (IFE) and static quenching. Under optimized conditions, the fluorescence responses increased as the rutin amount was raised from 100 to 1000 nmol/L with 5.3 nmol/L as a detection limit (S/N = 3). The probe selectivity was improved by adding bovine serum albumin (BSA), which binds other structurally-related compounds (other flavonoids). The as-synthesized NCDs exhibited some advantages towards rutin detection such as: lower LOD value, satisfactorily reproducibility, simplicity, rapidity, selectivity, and stability. The sensing probe was efficiently utilized for determining rutin in different real samples with acceptable results. The sensor offers an efficient biowaste-based approach for the determination of (bio) molecules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A new nanocomposite consisting of lanthanum ferrite nanoparticles (LaFeO 3 NPs) integrated with carbon nanotubes (CNTs) was fabricated via facile sonochemical approach. The engineered nanocomposite was applied to simultaneously determine acetaminophen (ACP) and dopamine (DA) in a binary mixture. The LaFeO 3 NPs@CNT probe possesses several advantages such as superior conductivity, large surface area, and more active sites, improving its electrocatalytic activity towards ACP and DA. Under optimized conditions, the anodic peak currents (Ipa) linearly increased with increasing concentration of ACP and DA in the range 0.069-210 µM and 0.15-210 µM, respectively. The sensitivity of LaFeO 3 NPs@CNTs/glassy carbon electrode (GCE) for detecting ACP and DA is 7.456 and 5.980 μA·μM -1 ·cm -2 , respectively. The detection limits (S/N = 3) for ACP and DA are 0.02 μM and 0.05 μM, respectively. Advantages of LaFeO 3 NPs@CNTs/GCE for the detection of ACP and DA include wide linear ranges, low-detection limits, good selectivity, and long-term stability. The as-fabricated electrode was applied to determine ACP and DA in pharmaceutical formulations and human serum samples with recoveries ranging from 97.7 to 103.3% and an RSD that did not exceed 3.7%, confirming the suitability of the proposed sensor for the determination of ACP and DA in real samples. This study not only presents promising opportunities for enhancing the sensitivity and stability of electrochemical sensors used in the detection of bioanalytes but also significantly contributes to the progress of unique and comprehensive biochemical detection methodologies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objectives: The relationship between handgrip strength (HGS) and quality of life is inconsistent. The purpose of this study was to investigate the potential association between HGS and quality of life in the settings of ageing and Alzheimer's disease (AD)., Methods: We investigated the HGS, CASP-12 (control, autonomy, self-realization, and pleasure) measure of quality of life, and physical capacity in European adults above 50, including controls (n = 38,628) and AD subjects (n = 460) using the survey of health, ageing, and retirement in Europe (SHARE; 2022)., Results: AD subjects exhibited lower HGS and CASP-12 scores than controls (both p < 0.05). Participants with higher CASP-12 quartiles had higher HGS in controls but not in AD subjects. A linear positive relation was found between HGS and CASP-12 in controls (0.0842, p < 0.05) but not in AD subjects (0.0636, p = 0.091). There was no effect of gender on this finding. Lastly, we found significant negative associations of difficulties walking, rising from chair, climbing stairs, and fatigue with CASP-12 scores in controls and AD subjects (all p < 0.05)., Conclusions: Altogether, HGS was not associated with quality of life in individuals with AD. Conversely, difficulties in activities of daily living seem to be negatively associated with quality of life; thus, strategies are recommended to improve physical capacity., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The relevant data about the effects and the associated mechanisms of statins on muscle strength and physical capacity is inconsistent. We investigated the potential contribution of neuromuscular junction (NMJ) degradation to muscle weakness and physical compromise in patients with chronic obstructive pulmonary disease (COPD) on statins., Method: We recruited male COPD patients (age range = 63-75 years, n = 150) as nonusers (n = 71) and users of statin medications (n = 79) along with age-matched controls (n = 76). The COPD patients were evaluated at baseline and one year later. The data about handgrip strength (HGS), body composition, short physical performance battery (SPPB), and plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ disintegration was collected at two time points., Results: We observed lower HGS, SPPB scores, and higher CAF22 levels in all COPD patients than controls, irrespective of the treatment status (all p < 0.05). Statins further reduced HGS and elevated CAF22 in COPD patients (both p < 0.05). The decline in SPPB was relatively modest in statin users (≈3.7%, p = 0.032) than in nonusers (≈8.7%, p = 0.002). The elevated plasma CAF22 exhibited robust negative correlations with a reduction in HGS but not with SPPB in COPD patients taking statins. We also found a reduction in markers of inflammation and no increase in oxidative stress markers following statin use in COPD patients., Conclusion: Altogether, statin-induced NMJ degradation exacerbates muscle decline but does not contribute to physical compromise in COPD patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: To report the incidence, risk factors, and outcome of severe COVID-19 disease in kidney transplant recipients attending a Saudi hospital at a single center in the Kingdom of Saudi Arabia., Methods: A retrospective chart-based cohort study involving all kidney transplant recipients tested for COVID-19 in the Armed Forces Hospital Southern Region, KSA., Results: Of 532 kidney transplant recipients who reported to the center, from March 2020 to June 2022, 180 were tested for COVID-19. Of these recipients, 31 (17%) tested positive. Among the 31 positive recipients, 11 were treated at home, 15 were admitted to the noncritical isolation ward, and 5 were admitted to the intensive care unit (ICU). Older age (P = .0001), higher body mass index (P = .0001), and history of hypertension (P = .0023) were more frequent in the COVID-19-positive recipients. Admission to the ICU was more frequent in older recipients (P = .0322) with a history of ischemic heart disease (P = .06) and higher creatinine baseline (P = .08) presenting with dyspnea (P = .0174), and acute allograft dysfunction (P = .002). In the ICU group, 4 (80%) patients required hemodialysis, and 4 (80%) died., Conclusions: Kidney transplant recipients with COVID-19 could have a higher risk for developing acute kidney injury, dialysis, and mortality than the general population. ICU admission and renal replacement therapy were more evident in older recipients with a history of ischemic heart disease, presenting with shortness of breath (P = .017) and a higher serum creatinine baseline. Acute allograft dysfunction was the independent predictor of mortality among patients admitted to the ICU., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hypertension and skeletal muscle decline are common findings in patients with Alzheimer's disease (AD). Angiotensin-converting enzyme (ACE) inhibitors preserve skeletal muscle and physical capacity; however, the driving mechanisms are poorly understood., Objective: We investigated the effects of ACE inhibitors on the neuromuscular junction (NMJ) with relevance to skeletal muscle and physical capacity in AD patients and age-matched controls., Methods: We evaluated controls (n = 59) and three groups of AD patients, including normotensive (n = 51) and patients with hypertension taking ACE inhibitors (n = 53) or other anti-hypertensive medications (n = 49) at baseline and one year later. We measure plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ degradation, handgrip strength (HGS), and Short Physical Performance Battery (SPPB) as markers of physical capacity., Results: At baseline AD patients demonstrated lower HGS and SPPB scores and higher CAF22 levels than controls, irrespective of the hypertension status (all p < 0.05). The use of ACE inhibitors was associated with higher HGS and relative maintenance of SPPB scores, gait speed, and plasma CAF22 levels. Conversely, other anti-hypertensive medications were associated with an unaltered HGS, reduced SPPB scores and elevated plasma CAF22 levels (both p < 0.05). We also found dynamic associations of CAF22 with HGS, gait speed, and SPPB in AD patients taking ACE inhibitors (all p < 0.05). These changes were associated with reduced oxidative stress in AD patients taking ACE inhibitors (p < 0.05)., Conclusion: Altogether, ACE inhibitors are associated with higher HGS, preserved physical capacity, and the prevention of NMJ degradation in hypertensive AD patients.

Whether morning heart rate variability (HRV) predicts the magnitude of its circadian variation in the absence of disease or is influenced by chronotype is unclear. We aimed to quantify associations between (1) morning HRV and its diurnal change, and (2) morning HRV and a Morningness−Eveningness Questionnaire (MEQ)-derived chronotype. Resting electrocardiograms were obtained in the morning and evening on separate days in a counterbalanced order to determine the mean RR interval, root mean square of successive differences (RMSSD), and standard deviation of normal-to-normal RR intervals (SDNN) in 23 healthy men (24.6 ± 3.4 yrs; body mass index: 25.3 ± 2.8 kg/m2). The MEQ was completed during the first laboratory visit. Morning RMSSD and SDNN were significantly higher (Ps < 0.05) than evening values. Morning RMSSD and SDNN were associated with their absolute (Ps < 0.0001), and relative diurnal changes (Ps < 0.01). No associations were observed between HRV parameters and the MEQ chronotypes (Ps > 0.09). Morning HRV was a stronger determinant of its evening change than chronotype. Greater diurnal variation in HRV was dependent on higher morning values. Strategies to improve basal HRV may therefore support healthier cardio-autonomic circadian profiles in healthy young men.

Introduction:  Pharmacovigilance (PV) is critical in determining the risk-benefit ratio of medicines and encouraging their safe, rational, and effective use, hence enhancing patient safety and care. Pharmacists, as drug experts, share responsibility for ensuring that medicines remain safe., Objective:  The study aimed to assess the knowledge, attitude, and practice of hospital pharmacists towards PV and adverse drug reaction (ADR) reporting and to know factors that discourage them from reporting ADRs in Najran, Saudi Arabia., Methods: A pre-tested self-administered questionnaire was distributed to all the pharmacists working in government hospitals who consented to participate in the study. Data was collected over three months, from 01 June 2018 to 31 Aug 2018. Data were analyzed using Statistical Package for Social Science (SPSS) software for Windows, version 23. Descriptive statistics such as frequency and percentages, mean ± standard deviation (SD) were calculated, and the Pearson's Chi-square test was used to examine the relationship between different variables., Results: A total of 145 questionnaires were distributed, and the response rate obtained was 70.3%. The definition of PV and ADR were correctly identified by 42% and 68.3% of participants, respectively. A noteworthy finding is that 95% of participants were aware of the existence of the ADR reporting system, and 88.9% knew the responsible regulatory agency. Participants showed a positive attitude towards PV and ADR reporting; 90.1% considered ADR reporting a part of professional obligation, and 94.1% believed that there should be collaboration between pharmacists and other healthcare professionals. A majority of participants (86.1%) had identified an ADR during their practice, and 71.3% had reported an ADR. The unavailability of a professional environment to discuss ADR and insufficient pharmacotherapy/clinical knowledge was cited as the main factors discouraging from reporting ADRs., Conclusions: Overall, the pharmacists had an average to good knowledge of and positive attitude towards PV and ADR reporting and a good ADR reporting practice. The concept of PV and ADR reporting should be further strengthened, and there is a vast potential for the same., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: The drug hydroxychloroquine (HCQ) is widely used to treat rheumatoid arthritis (RA) and has been repurposed for the treatment of COVID-19. This study aims to determine whether HCQ concentration levels in individuals with RA alter the incidence of COVID-19 or its complications., Methods: We collected plasma samples from 13 individuals with confirmed rheumatoid arthritis (RA) to measure HCQ concentration levels. The study included individuals at least 18 years old who had been taking HCQ for at least six months at daily doses ranging from 200 to 400 mg., Results: The study enrolled a total of 13 RA patients. All patients were chronic HCQ users. Among the 13 patients, 7 patients were receiving HCQ at a dose of 200 mg per day, and 6 patients were receiving HCQ at a dose of 400 mg per day. COVID-19 confirmed cases accounted for approximately 46% of all patients. Half of the infected patients (n = 3) were taking a daily dose of 200 mg daily, while the other half were taking 400 mg daily. COVID-19 symptoms ranged from mild to moderate, and the intensity of the symptoms was not severe enough to necessitate hospitalization. COVID-19 symptoms in RA patients included headache, fever, fatigue, dry cough, and loss of taste or smell., Conclusions: Our findings indicated that there was no correlation between HCQ concentrations in rheumatoid arthritis patients and the occurrence of COVID-19 or its complications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Ulcerative colitis (UC) is a common chronic, idiopathic inflammatory bowel disease associated with inflammatory perturbation and oxidative stress. Umbelliferone (UMB) is a potent anti-inflammatory and antioxidant coumarin derivative. Depending on the possible mechanisms, we aimed to explore and elucidate the therapeutic potential of UMB on UC-inflammatory response and oxidative injury-induced via intrarectal administration of acetic acid (AA) in rats. Animals were assigned into four groups: control group, UMB (30 mg/kg, oral)-treated group, AA-induced colitis model group (2 ml of AA; 3% v/v), and colitis treated with UMB group. The results showed that UMB improved macroscopic and histological tissue injury caused by the AA. Mechanistically, UMB reduced the elevated colonic TNF-α, IL-6, MPO, and VCAM-1 and downregulated the gene and protein expression of TLR4, NF-κB, and iNOS signaling factors, exhibiting potent anti-inflammatory effects. Moreover, UMB upregulated the gene and protein expression of both SIRT1 and PPARγ signaling pathways, thereby inhibiting both oxidative injury and inflammatory response. Conclusively, UMB protected rats against AA-induced UC by suppressing the TLR4/NF-κB-p65/iNOS signaling pathway and promoting the SIRT1/PPARγ signaling. Our results showed the effectiveness of UMB in alleviating the pathogenesis of UC and introduced it as a possible therapeutic applicant for clinical application., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Hydroxychloroquine (HCQ) has been used during the coronavirus disease 2019 (COVID-19) pandemic because of its reported anti-viral activity. This study examined the association of chronic HCQ use with the incidence and complications of COVID-19., Methods: This retrospective cohort study included adults with rheumatoid arthritis and/or systemic lupus erythematosus who visited rheumatology clinics in three tertiary hospitals in Riyadh, Saudi Arabia between January 2019 and December 2020. Patients were categorized into two groups based on HCQ use. Data were obtained from the electronic health record and by interviews with patients. The primary study objective was the incidence of COVID-19 and its complications from March 2020 to February 2021., Results: Almost 11% of the study cohort was positive for COVID-19, and the incidence of COVID-19 was similar between HCQ users (11.11%) and nonusers (10.86%). Disease complication rates were similar in the study arms, and they mainly included fever, dry cough, fatigue, and breathing difficulty., Conclusions: This study revealed no significant association between chronic HCQ use and the incidence of COVID-19, and disease complications were similar in the study arms.

A gold nanoparticle-modified copper-based metal organic framework (Au NPs@Cu-BDC) was fabricated for the electrochemical determination of cysteine (Cys-SH). The nanocomposites were characterized using different techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), powder X-ray spectroscopy (PXRD), thermogravimetry (TGA), nitrogen adsorption-desorption isotherms, and Fourier transform infrared spectroscopy (FTIR). Formation of a new anodic peak of Cu(II)-Cys complex at + 0.43 V was used to detect Cys-SH. Cyclic and square wave voltammetric studies proved that the Au NPs enhanced the conductivity of Cu-BDC. The proposed electrode exhibited a linear range of 0.0015-10.5 μM and low detection limit of 0.0004 μM with a good sensitivity of 0.78 ± 0.01 μA μM. The as-fabricated electrode was successfully used for the estimation of Cys-SH in real samples (human plasma, urine, and saliva) with recovery % of 99-100% and RSD % of 2.7-3.6%, respectively., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Antinociceptive activity of honey and Nigella sativa (N. sativa) oil are well known. Therefore, aim of this study was to investigate the antinociceptive effect of N. sativa oil and its concurrent administration with honey in rats. The tested animals were randomized into 5 groups: Group (1) Normal saline (0.2ml, p.o.); Group (2) N. sativa oil (1gm/kg, p.o.); Group (3) honey (1gm/kg, p.o.); Group (4) N. sativa oil (1gm/kg, p.o.) + honey (1gm/kg, p.o.): Group (5) pethidine (20mg/kg, S.C.) as positive standard. The antinociceptive activity was tested using radiant heat and tail immersion tests. Antioxidant potential was determined by using in-vitro antioxidant assays. Our findings showed that N. sativa oil and honey have antinociceptive effect, the antinociceptive effect appeared after 30 and 60min of administration and declined after 120 and 180 min. Combined administration of N. sativa oil with Honey increased the antinociceptive effect by 20 to 30% in all models. In addition, the antinociceptive effect of the combination reduced the time for onset of action as well as prolonged its duration of action. In conclusion, combined treatment of N. sativa oil with honey increased its antinociceptive activity, showed faster onset of action and prolonged its duration, the fact that can be utilized in the management of painful conditions in humans.

Due to changing lifestyles and socioeconomic status, obesity prevalence has been rising in Saudi Arabia, and community pharmacists often counsel patients about its management. The study aimed to evaluate practices of community pharmacists involved in dispensing products for weight control in four cities located in the eastern province of Saudi Arabia. A cross-sectional study was conducted involving community pharmacists in Dammam, Dhahran, Khobar, and Al-Ahsa, using a Likert format questionnaire. Only those who consented to participate were handed the questionnaire. A total of 100 complete responses were analyzed. The median value for packs sold per month for tea containing products Al-Diafa Slimming Tea, Jamue Tea, and Green Tea was ≥6 while the same for orlistat and apple cider vinegar were ≤4. Moreover, >50% of pharmacists mentioned that orlistat and apple cider vinegar were effective while ≥35% mentioned that metformin and Jamue tea were effective. Furthermore, ≥25% mentioned that green tea and Al-Diafa slimming tea were effective. Excluding orlistat, >50% of pharmacists did not know about adverse effects for other products. The rate of dispensing of several weight loss products was significant for participants' background characteristics, such as time duration of consultation, gender, and age of patients, and pharmacist work experience ( p < 0.05). The tea products and orlistat were the most frequently sold products, and community pharmacists appeared most knowledgeable about the effectiveness and adverse effect of orlistat. The pharmacists seemed to be aware about the effectiveness of other weight loss products; however, their knowledge about their potential adverse effects was unsatisfactory.

Background: Gram-negative organisms harbouring carbapenem resistance genes (CRGs) are spreading globally, including in Gulf Cooperation Council (GCC) countries. However, relatively few data are available about carriage of CRGs in hospitalized patients in this region., Aim: To determine prevalence of CRG carriage and risk factors for colonization among patients in GCC hospitals., Methods: Rectal swabs were obtained from ∼50 intensive care unit (ICU) patients from each of 11 hospitals in five GCC countries between March and November 2019. The swabs were tested for the presence of bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA-48 CRG using a commercial polymerase chain reaction test. Data on risk factors for colonization were collected and analysed., Findings: Of 529 specimens screened, 138 (26.1%) were positive for one or more CRGs. The positivity rates among the hospitals ranged from 8.0% to 67.3%; ∼20% of the positive specimens harboured ≥2 CRGs. The most common CRG detected was bla OXA-48 , which was present in 82 specimens (15.5%). Additional CRGs included bla NDM , bla VIM , bla KPC , and bla IMP either alone or in combination. Overall, 31.1% of patients on antibiotics on admission to the ICU were positive for CRGs compared to 16.5% not on antibiotic therapy (P < 0.001). CRG detection was also more common among patients aged >65 years (P = 0.027) and increased with hospital length of stay (P = 0.025)., Conclusion: The rate of CRGs detected in hospitalized patients in GCC countries varied considerably. Prior antibiotic exposure, increasing age, and prolonged length of stay were associated with CRG detection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Herein, a rational combination of dispersive solid-phase sorbent and 2-(2, 4-Dihydroxyphenyl)-3, 5, 7-trihydroxychromen-4-one (morin) was proposed for sensitive and selective determination of Al 3+ ion. Nickel ferrite nanospheres (NiFe 2 O 4 NS) functionalized with morin was used to preconcentrate and estimate Al 3+ via the formation of fluorescent complex at pH 7.0. The functionalization was assisted by anionic surfactant sodium dodecyl sulphate (SDS) and ultrasonication. The results revealed that the fluorescence intensity of Al-morin/SDS@ NiFe 2 O 4 NS is higher than Al-morin. Functionalization of NiFe 2 O 4 NS with morin was confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometer (PXRD), and fluorescence spectroscopy. Under the optimum conditions, the fluorescence intensity increased with increasing of Al 3+ concentrations in the range of 0.28-500.0 ng mL -1 with LOD (S/N = 3) of 0.09 ng mL -1 . The method was applied for the determination of Al 3+ in natural waters and human serum samples with recoveries % of 97-104% and RSDs % of 2-4%., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, zinc sulfide nanoparticles were loaded on reduced graphene oxide (ZnS NPs/rGO) using simple sonochemical method. The nanocomposite was characterized using different morphological and electrochemical techniques such as TEM, SEM, PXRD, EDX, Raman spectroscopy, FTIR, N 2 -adsorption-desorption, CV, and EIS. The ZnS NPs/rGO modified glassy carbon electrode (GCE) was used to simultaneously estimate hydroxychloroquine (HCQ) and daclatasvir (DAC) in a binary mixture for the first time. The modified nanocomposite exhibited good catalytic activity towards HCQ and DAC detection. In addition, it showed higher sensitivity, good selectivity and stability; and high reproducibility towards HCQ and DAC analysis. The activity of the modified electrode was noticeably improved due to synergism between ZnS NPs and rGO. Under optimum conditions of DPV measurements, the anodic peak currents (Ipa) were obviously increased with the increase of HCQ and DAC amounts with linear ranges of 5.0-65.0 and 7.0-65.0 nM with LODs of 0.456 and 0.498 nM for HCQ and DAC, respectively. The ZnS NPs/ rGO modified GCE was used to quantify HCQ and DAC in biological fluids with recoveries of 98.7-102.7% and 96.9-104.5% and RSDs of 1.89-3.57% and 1.91-3.70%, respectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

The relationship between the Renin-Angiotensin-Aldosterone System (RAAS) and modulation of the Autonomic Nervous System (ANS) is reported as complex and bidirectional. Thus, the present study aimed to compare autonomous heart control, through symbolic analysis parameters, in the older adults carrying different ACE I/D gene polymorphisms (rs4646994). Two hundred four older adults comprised the study population and were grouped according to the ACE I/D gene polymorphism: II + ID genotype and DD genotype. Successive RR intervals were recorded along 5 min and analyzed with Symbolic Analysis (SA) method. 0 V%, 1 V% and 2 V% patterns were quantified and compared between groups. A linear mixed model analysis was used to determine between-group differences in symbolic analysis parameters (0 V%, 1 V% and 2 V%), taken groups as fixed factor and sex, use of ACE inhibitors and Angiotensin II receptor type I blockers as random factors. The Bayesian analysis was carried out to check the magnitude of the evidence. The results of this study indicate that older adults carrying the DD genotype have statistically greater sympathetic modulation (0 V%) and poor sympathovagal balance (1 V%), but the Bayesian analysis indicate only an anecdotal effect. Sympathetic predominance is recognized a worrying condition, since may predisposes to cardiovascular risk., (Copyright © 2021. Published by Elsevier Inc.)

Herein, a novel and rapid fluorometric nanoprobe was constructed for quantitation of dopamine (DA) in presence of biologically interfering compounds. The nanoprobe based on synthesis of yellow emissive nitrogen doped graphene quantum dots (N@GQDs) by advanced thermal driven oxidation. After that, the synthesized N@GQDs was capped with β-cyclodextrin (β-CD), followed by interaction with pyridoxal (PYL) vitamin B 6 cofactor. This interaction resulted in diminishing the yellow fluorescence of β-CD/N@GQDs, and appearance of blue emission peak at 420 nm. Upon addition of DA, the blue emission of β-CD/N@GQDs was increased after excitation at λ = 330 nm. Under optimum conditions, the nanoprobe exhibited a linear range of 0.36-400 nM with limit of detection (LOD) of 0.117 nM. In addition, the fluorescent nanoprobe shows high selectivity and can be used for detection of DA in complicated biological matrices and human serum. This strategy might provide a potential tool for clinical diagnosis and biomedical research for DA related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To determine the influence of caffeine on pharmacokinetics and pharmacodynamics of pioglitazone (PIO) in diabetic rats., Methods: This was a preclinical study conducted in the College of Pharmacy, Najran University, Saudi Arabia, using 5 groups of Wistar rats: normal rats, untreated diabetic rats, diabetic rats + caffeine (20 mg/kg), diabetic rats + PIO (10 mg/kg), and diabetic rats + PIO (10 mg/kg) + caffeine (20 mg/kg). The drugs were administered for 14 days, and fasting plasma glucose concentrations were determined on the first day, and thereafter at weekly intervals. On day 14, rat sacrifice was followed with assay of levels of biomarkers. To estimate the pharmacokinetic parameters, the diabetic animals were assigned to 2 groups: one group received PIO (10 mg/kg), while the other received PIO + caffeine (20 mg/kg). Blood samples were drawn from the retro-orbital plexus at different time intervals, and pharmacokinetic parameters were measured using high performance liquid chromatography., Results: Caffeine caused statistically marked increases in area under the curve, C max , T max , and half-life of PIO, and decreased clearance. Combination of PIO and caffeine produced a synergistic effect on percentage reduction in blood glucose, with 67.1% reductions observed on day 7 and 68.9% reductions observed on day 14. Liver and cardiac biomarkers were significantly decreased, suggesting cardioprotective and hepatoprotective effects., Conclusion: Co-administration of PIO with caffeine enhances its antidiabetic effect, probably due to enhanced bioavailability of PIO, leading to clinical benefits in diabetic patients., (Copyright: © Saudi Medical Journal.)

A nanohybrid prepared from green source (nanocellulose, NC) and nitrogen, sulfur co-doped graphene quantum dots (N, S@GQDs) was prepared for the electrochemical detection of olanzapine (OLZ), atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. Polar groups on the surface of NC and N, S@GQDs provide more anchoring sites for adsorption of OLZ onto the electrode surface. In addition, it provides high conductivity, good mechanical strength, large surface area, and excellent electrical conductivity. The nanocomposite was characterized morphologically and electrochemically by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDX), transmission electron microscope (TEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave adsorptive stripping voltammetry (SWAdSV). Under the optimized conditions, the modified electrode has a good response in the range of 1.5-90.0 × 10 -8  M with LOD of 0.5 × 10 -8  M. The proposed electrode offers high sensitivity, selectivity, and reliability towards OLZ detection. The SWAdSV was used to determine OLZ in pharmaceutical tablets, human plasma and urine with good recoveries % and reasonable RSD% values., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to (a) evaluate the agreement between ultra-short-term and criterion resting heart rate variability (HRV) measures in military trainees, and (b) compare associations between HRV recording lengths and body composition. HRV recordings were performed for 10 min in 27 military male students. Mean RR interval, the root-mean square of successive differences (RMSSD), RMSSD:RR interval ratio, standard deviation of normal-to-normal RR intervals (SDNN), and SDNN:RR interval ratio were determined from the last 5 min of the 10-min recording and considered the criterion. Parameters were also recorded in successive 1-min epochs from the 5-min stabilization period. No differences were observed between criterion values and any of the 1-min epochs ( p > 0.05). Effect sizes ranged from -0.36-0.35. Intra-class correlations ranged from 0.83-0.99. Limits of agreement ranged from 38.3-78.4 ms for RR interval, 18.8-30.0 ms for RMSSD, 1.9-3.1 for RMSSD:RR, 24.1-31.4 ms for SDNN, and 2.5-3.0 for SDNN:RR. Body fat% was associated ( p < 0.05) with all HRV parameters at varying time segments. A 1-min HRV recording preceded by a 1-min stabilization period seems to be a suitable alternative to criterion measures. Ultra-short procedures may facilitate routine HRV tracking in tactical populations for status-monitoring purposes.

In this study, an electrochemical aptamer based sensor (aptasensor) was proposed for specific recognition of histamine (HIS). The electrochemical aptasensor based on fabrication of glassy carbon electrode (GCE) with molecular imprinted polymer (MIP) and DNA aptamers on gold nanoparticles (AuNPs) and carboxylated carbon nanotubes (cCNTs) (MIP-apta/AuNPs/cCNTs/GCE). The aptasensor exhibits high selectivity towards HIS detection as it has two recognition elements which are MIP cavities and aptamer interaction. Upon exposure of MIP-apt/AuNPs/cCNTs/GCE to HIS, the current of redox probe was decreased that depends on the template (HIS) concentration. The effects of aptamer concentration, incubation time, pH and AuNPs electro-deposition time were optimized. Differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques were used to analyze HIS in complicated matrices. Favorable performance of MIP-apt/AuNPs/cCNTs/GCE was achieved with linearity ranges of 0.46-35 nmol L -1 and 0.35-35 nmol L -1 with limits of detection (LODs, S/N = 3) of 0.15 nmol L -1 and 0.11 nmol L -1 using DPV and EIS, respectively. The fabricated aptasensor displayed high selectivity, desirable reproducibility and stability. The MIP-apt/AuNPs/cCNTs/GCE was used to detect HIS in human plasma and canned tuna samples with good recoveries % and RSDs %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The fact that methotrexate (MTX) is hepatotoxic is an important reason to limit its clinical use. Rebamipide (REB) has antioxidant and anti-inflammatory properties and is useful for the treatment of gastro-duodenal ulcers. This study investigated the impact and protective mechanisms of REB against MTX-induced hepatotoxicity in rats., Materials and Methods: Animals were divided into four groups of six rats each: a control group, REB group (REB 100 mg/kg/day, orally), MTX control group (20 mg/kg, single i.p.), and MTX + REB group., Results: The administration of MTX induced marked hepatic injury in the form of hepatocyte inflammatory swelling, degeneration, apoptosis, and focal necrosis. In parallel, our biochemical investigations revealed a marked hepatic dysfunction associated with the disturbance of the oxidant/antioxidant balance in the group treated with only MTX. Moreover, MTX led to the down-regulation of the hepatic Nrf2 and Bcl-2 expressions along with a marked elevation in the hepatic NF-κβ-p65, GSK-3β, JAK1, STAT3, PUMA, and Bax expressions. On the other hand, co-treatment with REB significantly ameliorated the aforementioned histopathological, biochemical, and molecular defects caused by MTX treatment., Conclusion: the outcomes of the present study showed REB's ability to protect from hepatic injury induced by MTX, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These effects could be attributed to REB's ability to modulate, at least in part, the Nrf2/GSK-3β,NF-κβ-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2signaling pathways.

A novel bioaptasensing-based electrochemical method for determination of amifostine (AMF) is proposed. The electrochemical aptasensor is based on modification of a glassy carbon electrode with a nanocomposite consisting of silver nanoparticles @ MnFe Prussian blue analogue nanospheres (AgNPs@MnFePBA NS), followed by immobilization of aptamer via Ag-N bonds (aptamer/AgNPs@MnFePBA NS/GCE). Experimental parameters including pH, incubation time, and aptamer concentrations were optimized. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetric (DPV) techniques were utilized to quantify AMF. The anodic peak current (∆Ipa) and charge transfer resistance (∆Rct) differences increase in the presence of AMF. Under the optimal conditions, using the redox probe, the electrochemical aptasensor exhibited linear ranges of 0.34-45 nmol L -1 and 0.69-45 nmol L -1 with LODs of 0.11 nmol L -1 and 0.23 nmol L -1 for EIS and DPV, respectively. The aptasensor was used to determine AMF in human plasma and in the presence of interfering species with recoveries and RSDs in the range 97.8-103.2% and 2.2-4.2%, respectively. Graphical abstract.

Male reproductive toxicity is a well-known adverse effect of cisplatin (CIS), an important antineoplastic agent used to control several types of cancers. Tadalafil (TDF), is a long-acting phosphodiesterase-5 (PDE5) inhibitor commonly used as treatment for erectile dysfunction. The aim of this work was to study the possible protective effect of TDF against CIS-induced testicular toxicity in rats and the possible involvement of Nrf2/HO-1 pathway, which demonstrates antioxidant and inflammatory activities utilizing zinc protoporphyrin-IX (ZnPP) as HO-1 inhibitor. Results revealed that TDF attenuated the CIS-induced disturbances in sperm count and activities, normalized the serum testosterone level, improved the CIS-induced changes in epididymal and testicular weights and restored the normal structure of testicular tissues. In addition, TDF upregulated the gene expression levels of Nrf2 and HO-1 and the activity of HO-1 whereas, it reduced the CIS-induced changes in testicular oxidative stress markers and the levels of inflammatory mediators (TNF-α and iNOS). Furthermore, TDF antagonized the CIS-induced increase in testicular gene expression of apoptotic markers caspase-3 and Bax, and the decrease in Bcl-2. However, ZnPP co-administration significantly attenuated all TDF-mediated improvements in CIS-induced testicular toxicity, biochemical changes, and apoptosis. In conclusion, TDF exerts a protective effect against CIS-induced reproductive toxicity in males, through different mechanisms, besides its inhibitory action to PDE5, possibly mediated by the upregulation of Nrf2/HO-1, along with its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, the use of TDF represents a promising therapeutic approach to protect the male reproductive system from the harmful toxic effects of CIS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Herein, a novel "ON-OFF" colorimetric and fluorometric chemosensor; 1N-allyl-2-(2, 5-dimethoxyphenyl)-4, 5-diphenyl-1H-imidazole (ADPPI), was constructed for sequential determination of Cu 2+ and S 2 - ions in aqueous media. The interaction between chemosensor ADPPI and different metal cations was investigated using UV-VIS and fluorimetric spectroscopy. ADPPI showed a favorable and good interaction with Cu 2+ ions producing blue colored solution peaked at 610 nm with blue fluorescence at λ em.  = 447 nm. The produced complex between Cu 2+ ions and ADPPI can be used as a cascade probe for detection of S 2 - ions. The detection limits (LODs) were 1.01 nM and 1.25 μM for Cu 2+ and S 2 - ions, respectively (the lowest between the family of colorimetric and fluorometric chemosensors). To further increase the applicability of the proposed method, Cu 2+ and S 2 - ions concentrations were measured in environmental water samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An innovative electrochemical nanoprobe, for analysis of salinomycin (SAL), was proposed. The nanoprobe based on decoration of glassy carbon electrode (GCE) with 3D rose like La 3+ @ ZrO 2 supported on reduced graphene oxide (RGO) nanosheets. The 3D rose like La 3+ @ ZrO 2 was synthesized via sintering process. The successful decoration of 3D rose like La 3+ @ ZrO 2 on the surface of RGO was characterized using different spectroscopic and analytical techniques. The obtained voltammetric results confirmed the good electrochemical performance of 3D rose like La 3+ @ ZrO 2 in terms of lower peak potential (E pc ) and higher cathodic current (I pc ). Moreover, the modified nanoprobe showed wide linearity range (0.34-115 × 10 -8  M), lower detection limit (0.11 × 10 -8  M) and higher selectivity. Besides, the nanocomposite showed good applicability for analysis of SAL in biological fluids and during pharmacokinetic evaluation in rabbit plasma. The obtained results opens a new venue for the determination of futuristic drug, SAL, during pharmacokinetic and pharmacodynamics studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An innovative electrochemical sensor was proposed for simultaneous determination of mycophenolate mofetil (Mph) and tacrolimus (TAC) for the first time. A novel sensor based on electro-polymerization of multi-walled carbon nanotubes (MWCNTs) and a novel Cu-1N-allyl-2-(2,5-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole metal organic framework (Cu-ADPPI MOF) on disposable pencil graphite electrode (dPGE). Many techniques were used to characterize the electrochemical activity and surface structure of the fabricated sensor. The proposed sensor exhibited good catalytic performance towards Mph and TAC oxidation due to the synergistic effect. Under optimal conditions, the proposed sensor has achieved a linear range of 0.85-155 × 10 -8 M and 1.1-170.0 × 10 -8 M with LODs of 0.28 × 10 -8 M and 0.36 × 10 -8 M for Mph and TAC, respectively. The designated sensor showed good reproducibility, repeatability, stability, and selectivity for the determination of Mph and TAC. Moreover, the simultaneous determination of Mph and TAC in different human biological fluids was carried out with acceptable results. As a result, the proposed sensor opens a new venue for the use of electro-polymerized MOFs in combination with other conductive materials such as MWCNTs for electrochemical sensing of different analytes with the desired sensitivity and selectivity. Graphical abstract Construction of disposable graphite electrode, based on electro-deposition of multilayer films of multi-walled carbon nanotubes and a new generation of Cu-MOFs, for simultaneous analysis of tacrolimus and mycophenolate mofetil for the first time.

A molecularly imprinted polymer (MIP) was developed for the electrochemical determination of the antiviral drug sofosbuvir (SOF). The MIP was obtained by polymerization of p-aminothiophenol (p-ATP) on N,S co-doped graphene quantum dots (N,S@GQDs) in the presence of gold nanoparticles to form gold-sulfur covalent network. The presence of quantum dots improves the electron transfer rate, enhances surface activity and amplifies the signal. The nanocomposites were characterized by FTIR, TEM, EDX, and SEM. The electrochemical performance of the electrode was investigated by differential pulse voltammetry and cyclic voltammetry. The sensor uses hexacyanoferrate as the redox probe and is best operated at a potential of around 0.36 V vs. Ag/AgCl. It has a linear response over the concentration range of 1-400 nM SOF, with a detection limit of 0.36 nM. Other features include high selectivity, good reproducibility and temporal stability. The sensor was applied to the determination of SOF in spiked human plasma. Graphical abstract Novel sofosbuvir imprinted p-ATP polymer was synthesized by the aid of gold nanoparticles on N,S co-doped graphene quantum dots as a good conductive support. The imprinted polymer was used for detection of sofosbuvir in real samples by using the ferri/ferrocyanide redox probe.

This study showed that procollagen type 1 amino-terminal pro-peptide and N-MID osteocalcin significantly increased after exercise independent of the form of muscle contraction. Thus, these preliminary results will be useful for future studies that will consider bone turnover characteristics of responders and non-responders to acute and chronic aerobic exercise., Introduction: The aim of the current study was to compare the effects of acute flat running (FR) and downhill running (DHR) on bone turnover markers in men., Methods: Fourteen healthy young active men performed three exercise tests in a counterbalanced order, including rest condition, FR, and DHR, at 60% maximal aerobic capacity on a treadmill with 0 and - 12% inclines. Blood samples were taken in the pre-exercise, immediately post-exercise, and 24-h post-exercise periods, and bone markers included total procollagen type 1 amino-terminal pro-peptide (total PINP) and N-MID osteocalcin., Results: Total P1NP significantly increased after exercise independent of the form of muscle contraction (p > 0.05). N-MID osteocalcin increased after DHR by 17% compared to after pre-exercise, but the difference did not reach significance (p = 0.07; partial eta square, 0.21). Biomarker responses to exercise were dependent on the exercise form and independent of hormone type in half of the participants who were classified as responders. Physiological parameters and changes in muscle voluntary contraction did not explain the differences between responders and non-responders., Conclusion: The effect of acute DHR on bone turnover is determined by biomarker type and participant characteristics. Future studies should discriminate between the characteristics of responders and those of non-responders.

Objective: The present single-center observational study determined the prevalence and coexistence of sarcopenia, pre-sarcopenia, and metabolic syndrome (MetS) among apparently healthy Arab men and whether having both conditions present a unique cardiometabolic profile that is distinct than having the conditions separately., Methods: A total of 471 out of 530 Arab men aged 20-77 years old were included after screening for the presence of pre-sarcopenia (ALM/ht 2  < 7.26 kg/m 2 ), sarcopenia (presence of both low muscle mass and low function), and MetS. MetS screening was done using the definition by the NCEP-ATP III. Based on the screening results, the participants were classified as control (normal) group (N = 328), MetS only (N = 73), pre-sarcopenia only (N = 64), and MetS + pre-sarcopenia (N = 6)., Results: Pre-sarcopenia without MetS was observed in 64 participants (13.6%), while MetS without pre-sarcopenia was observed in 73 participants (15.5%). MetS + pre-sarcopenia was observed only in 6 participants (1.3%). None of the participants had sarcopenia. Age- and BMI-adjusted comparisons showed that those with MetS + pre-sarcopenia had the highest diastolic blood pressure and triglyceride levels as compared to all groups (p values < 0.001). MetS + pre-sarcopenia group also had the highest levels of glucose and the lowest lean arms-legs/BMI ratio than control and pre-sarcopenia groups (p values < 0.001 and 0.005, respectively)., Conclusion: The prevalence of pre-sarcopenia + MetS is low among young adult Arab men, but shows a unique cardiometabolic profile that is worse than those having only one of the conditions. Further investigations should be done among Arab women and the elderly.

Purpose: Chronic hepatitis C has infected approximately 170 million people worldwide. The novel direct-acting antivirals have proven their clinical efficacy to treat hepatitis C infection but still very expensive and beyond the financial range of most infected patients in low income and even resource replete nations. This study was conducted to establish an in vitro stable human hepatoma 7 (Huh-7) cell culture system with consistent expression of the non-structural 5B (NS5B) protein of hepatitis C virus (HCV) 1a genotype and to explore inhibitory effects of sequence-specific short interference RNA (siRNA) targeting NS5B in stable cell clones, and against viral replication in serum-inoculated Huh-7 cells., Materials and Methods: In vitro stable Huh-7 cells with persistent expression of NS5B protein was produced under gentamycin (G418) selection. siRNAs inhibitory effects were determined by analysing NS5B expression at mRNA and protein level through reverse transcription-polymerase chain reaction (PCR), quantitative real-time PCR, and Western blot, respectively. Statistical significance of data (NS5B gene suppression) was performed using SPSS software (version 16.0, SPSS Inc.)., Results: siRNAs directed against NS5B gene significantly decreased NS5B expression at mRNA and protein levels in stable Huh-7 cells, and a vivid decrease in viral replication was also exhibited in serum-infected Huh-7 cells., Conclusions: Stable Huh-7 cells persistently expressing NS5B protein should be helpful for molecular pathogenesis of HCV infection and development of anti-HCV drug screening assays. The siRNA was effective against NS5B and could be considered as an adjuvant therapy along with other promising anti-HCV regimens., Competing Interests: None

Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in different matrices. The designed sensor was based on 3D spinel ferromagnetic NiFe 2 O 4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe 2 O 4 /MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites, RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe 2 O 4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4-350 ng mL -1 ) with LOD of 0.133 ng mL -1 . Additionally, the proposed sensor demonstrated good selectivity, stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni ® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ultrasound (US) waves have been recently developed for the treatment of different chronic wounds with promising therapeutic outcomes. However, the clinical efficacy of these techniques is still not fully understood and standard guidelines on dose ranges and possible side effects should be determined. This paper aims to comprehensively review the recent advances in US techniques for chronic wound treatment, their therapeutic efficacies, and clinical considerations and challenges. The databases of PubMed (1985-2017), EMBASE (1985-2017), Web of Sciences (1985-2017), Cochrane central library (1990-2017), and Google Scholar (1980-2017) were searched using the set terms. The obtained results were screened for the title and abstract by two authors and the relevant papers were reviewed for further details. Preclinical and clinical studies have shown strong evidence on the therapeutic efficiency of US in chronic wounds. The main limitation on developing clinical standard protocols of US for treatment of wounds is the lack of definite dose-response for each wound. However, spatial average temporal average is the main parameter for defining US dosage in wound treatment. The range of 0.5 to 3 W/cm 2 is a range of dose exerting significant therapeutic outcomes and minimum adverse effects. Low-frequency US waves can accelerate the healing speed of open wounds as well as deep-tissue injuries. In addition, US waves show promising therapeutic efficacy for chronic wounds. To develop clinical US protocol for each wound type, further in vitro and in vivo preclinical and clinical trials are needed to reach an exact dose-response for each wound type., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The purpose of this study was to investigate the association between selected major modifiable risk factors including life style habits, household income and smoking on health., Methods: This cross-sectional study was conducted during 2015-2016 among 104 healthy men aged 38 ± 8 years. The data were collected using a self-administered questionnaire that enquired about clinical information about blood pressure and body mass index. Venous blood samples were taken to assess the fasting blood glucose (FBG), lipid profile, high density lipoprotein and triglyceride., Results: Current smoking status and consumed energy drinks were significantly positive risk factors for increased systolic blood pressure and FBG, respectively. Participants with monthly income of more than 10,000 Saudi Riyals showed significantly lower diastolic pressure than those with lower income. However, there was a significant decrease in body weight among those who consumed vegetables., Conclusion: This study highlights the effect of major modifiable risk factors on health. There is a great need for improving and enhancing a healthy lifestyle behaviour.

Objective: To explore inhibitory effects of genome-specific, chemically synthesized siRNAs (small interference RNA) against NS3 gene of hepatitis C virus (HCV) 1a genotype in stable Huh-7 (human hepatoma) cells as well as against viral replication in serum-inoculated Huh-7 cells., Methods: Stable Huh-7 cells persistently expressing NS3 gene were produced under antibiotic gentamycin (G418) selection. The cell clones resistant to 1000 μg antibiotic concentration (G418) were picked as stable cell clones. The NS3 gene expression in stable cell clone was confirmed by RT-PCR and Western blotting. siRNA cell cytotoxicity was determined by MTT cell proliferation assay. Stable cell lines were transfected with sequence specific siRNAs and their inhibitory effects were determined by RT-PCR, real-time PCR and Western blotting. The viral replication inhibition by siRNAs in serum inoculated Huh-7 cells was determined by real-time PCR., Results: RT-PCR and Western blot analysis confirmed NS3 gene and protein expression in stable cell lines on day 10, 20 and 30 post transfection. MTT cell proliferation assay revealed that at most concentrated dose tested (50 nmol/L), siRNA had no cytotoxic effects on Huh-7 cells and cell proliferation remained unaffected. As demonstrated by the siRNA time-dependent inhibitory analysis, siRNA NS3-is44 showed maximum inhibition of NS3 gene in stable Huh-7 cell clones at 24 (80%, P = 0.013) and 48 h (75%, P = 0.002) post transfection. The impact of siRNAs on virus replication in serum inoculated Huh-7 cells also demonstrated significant decrease in viral copy number, where siRNA NS3-is44 exhibited 70% (P < 0.05) viral RNA reduction as compared to NS3-is33, which showed a 64% (P < 0.05) decrease in viral copy number. siRNA synergism (NS3-is33 + NS3-is44) decreased viral load by 84% (P < 0.05) as compared to individual inhibition by each siRNA (i.e., 64%-70% (P < 0.05)) in serum-inoculated cells. Synthetic siRNAs mixture (NS5B-is88 + NS3-is33) targeting different region of HCV genome (NS5B and NS3) also decreased HCV viral load by 85% (P < 0.05) as compared to siRNA inhibitory effects alone (70% and 64% respectively, P < 0.05)., Conclusions: siRNAs directed against NS3 gene significantly decreased mRNA and protein expression in stable cell clones. Viral replication was also vividly decreased in serum infected Huh-7 cells. Stable Huh-7 cells expressing NS3 gene is helpful to develop anti-hepatitis C drug screening assays. siRNA therapeutic potential along with other anti-HCV agents can be considered against hepatitis C., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)