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Heba Jafar Sabbagh,1 Layla Nizar Khogeer,2 Mona Hassan Ahmed Hassan,3 Hanaa Khalil Allaf2 1Department of Pediatric Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 2Pediatric Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Biostatistics, High Institute of Public Health, Alexandria University, Alexandria, EgyptCorrespondence: Heba Jafar SabbaghDepartment of Pediatric Dentistry, King Abdulaziz University, P.O. Box: 80200, Jeddah 21589, Saudi ArabiaTel +966 505668481Email hsabbagh@kau.edu.saIntroduction: E-cigarette use has been on the rise among children and adolescents. This study aimed to assess the knowledge and attitudes of the health hazards and laws regarding e-cigarette use among parents in Saudi Arabia. In addition, we evaluated the effect of parental smoking on parent’s knowledge.Methods: This study was conducted with parents of children below 18 years of age in Jeddah, Saudi Arabia. Jeddah was divided into four areas (north, south, east, and west) and in each area, the largest shopping mall was selected. Data were gathered using a self-administered questionnaire.Results: Out of 1386 parents, 61.7% were smokers, 13.3% reported that their children used e-cigarettes, and 73.6% did not discuss e-cigarette use with their children. In total, 77.3% of parents thought it was important to be educated about e-cigarette use. However, their ability to discuss e-cigarette use with their children was 13.9% lower than their ability to discuss regular cigarette smoking with their children. Parents who were smokers were more accepting of their children using e-cigarettes (P< 0.0001). Mothers who smoked were more accepting than fathers of their children using e-cigarettes (P< 0.0001).Conclusion: Parents reported a lack of knowledge and attitudes regarding e-cigarette use. Parental smoking, especially among mothers, was statistically significantly related to their e-cigarette use knowledge and attitudes. Parents agreed that it was important to educate parents regarding e-cigarette use.Keywords: electronic-cigarette, smoking, Saudi Arabia, parental smoking

هدفت الدراسة الحالية للمقارنة بين نوعين من السحالي Phoenicolacerta laevis و Ophisops elegans التابعين لفصيلة السحالي الحقيقية Lacertidae وذلك من خلال دراسة مورفولوجيا خلايا الدم المحيطية ( كريات الدم الحمراء - كريات الدم البيضاء - الصفيحات الدموية) عن طريق اجراء مسحات دموية وتلوينها بملون رايت. أظهرت النتائج وجود اختلافات ملحوظة بين المسحات الدموية التابعة لكل نوع حيث كانت قيم قياسات خلايا الدم أكبر في Phoenicolacerta laevis بالاضافة الى عدم وجود العدلات فيها. وظهر الاختلاف أيضاً بين المسحات التابعة لنفس النوع باختلاف مناطق الاعتيان.

Design and hierarchical control of three phase parallel Voltage Source Inverters are developed in this paper. The control scheme is based on synchronous reference frame and consists of primary and secondary control levels. The primary control consists of the droop control and the virtual output impedance loops. This control level is designed to share the active and reactive power correctly between the connected VSIs in order to avoid the undesired circulating current and overload of the connected VSIs. The secondary control is designed to clear the magnitude and the frequency deviations caused by the primary control. The control structure is validated through dynamics simulations.The obtained results demonstrate the effectiveness of the control structure.

Background: Fagonia cretica L. (Family: Zygophyllaceae), is a wild shrub mostly found in Mediterranean districts and extensively used in folk medicine for a vast array of purposes such as antidiabetic and anticancer during the early stages. The goal of the current study was to validate the antioxidant, anti-inflammatory, and cytotoxic properties of Egyptian F. cretica using in vitro studies, metabolic profiling, and in silico approaches., Methods: The plant was collected from the Egyptian desert and the alcoholic extract was prepared from its aerial parts, total phenolic and total flavonoid contents were evaluated spectrophotometrically. Antioxidant potential was assessed via 1,1 diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. Anti-inflammatory activity was validated through in vitro COX-2, COX-1, and nitric oxide inhibition. Cytotoxicity was tested against liver (HepG2), breast (MCF-7), and intestinal (CACO2) carcinoma cell lines followed by assessment of its impact on the levels of apoptotic markers namely topoisomerase I and caspase 9 enzymes. Chemical profiling of the extract was performed using LC-HRMS technique. Saponin rich extract was prepared and tested for affecting topo I and caspase 9 enzymes. In silico studies were conducted on anti-inflammatory (COX-2 and COX-1) and cytotoxicity (topoisomerases I, IIα, and IIβ) targets using Autodock vina in PyRx platform., Results: Total phenolic and total flavonoid content of the extract were 2.4 ± 0.12 mg GAE/g and 0.18 ± 0.01 mg RE/g, respectively. In vitro results revealed antioxidant activity calculated as 1.4 ± 0.1 mg AEAC/g. In vitro anti-inflammatory assays unveiled inhibition of COX-2 and COX-1 enzymes with IC 50 values of 13.02 ± 0.61 and 26.51 ± 0.83 µg/ml, respectively and nitric oxide with IC 50 of 147.05 ± 9.61 µg/ml. Cytotoxicity on MCF-7, HepG2, and CACO2 cell line with IC 50 values of 6.9 ± 0.53, 7.6 ± 0.42, and 9.2 ± 0.35 µg/ml, respectively, in addition to in vitro topoisomerase I inhibition (IC 50  = 13.57 ± 0.71 µg/ml) and caspase 9 induction by 5.66 folds. Metabolic profiling using LC-HRMS technique resulted in dereplication of 21 compounds including triterpenoid saponins, flavonoids, diterpenoids, etc. Interestingly, saponin rich fraction and non-saponin fraction exhibited similar effects on topoisomerase I and caspase 9. In silico investigation unveiled high binding affinities of almost all the detected metabolites to the active sites of COX-2, COX-1, topo I, IIα, and IIβ enzymes., Conclusion: Collectively, we can conclude that F. cretica is a new source of many phytochemicals, and a significant natural source as cytotoxic and anti-inflammatory agent., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Metabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC 50 values (2.21 ± 0.06 and 4.81 ± 0.14 μM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC 50 value of 8.75 ± 0.18 μM compared to kojic acid (IC 50  = 9.27 ± 0.19 μM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3-6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity., (© 2024. The Author(s).)

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli . In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds., 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., (© 2024 The Authors. Published by Elsevier B.V.)

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC 50 =3.3, 4.2 and 6.8 μg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

A novel derivative of ciprofloxacin (Cpx) was synthesized and characterized using various analytical techniques, including FT-IR spectroscopy, UV-Vis spectroscopy, TEM and SEM analysis, 1 H NMR, 13 C NMR, and HPLC analysis. The newly prepared Cpx derivative (Cpx-Drv) exhibited significantly enhanced antibacterial properties compared to Cpx itself. In particular, Cpx-Drv demonstrated a 51% increase in antibacterial activity against S. aureus and a 30% improvement against B. subtilis . It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively.

Cefoperazone (Cfz) is a member of the third generation of parenteral cephalosporin antibiotics. It is used on a wide scale in prescribed antibiotic drugs as anti-infection, especially for Gram-negative and also against Gram-positive microorganisms. The current study aimed to find a rapid RP-HPLC method of Cfz analysis with high linearity, repeatability, sensitivity, selectivity, and inexpensive. In our developed method, there is no need to use special chemical reagents, a high percentage of organic solvent, a high flow rate, further guard column. The chromatographic system comprises an ODS column (150 mm × 4.6 mm × 5 μm). The mobile phase was prepared by mixing KH 2 PO 4 solution: acetonitrile (80:20) with a flow rate of 1.0 mL/min at detection wavelength 230 nm, at room temperature using injection volume 20 μL. The method manifested a satisfied linearity regression R 2 (0.9993) with a good repeatability range (0.34-0.92%) with LOD and LOQ; 4.04 μg/mL and 12.24 μg/mL respectively. The method proved its efficiency via system suitability achievement in the robustness and ruggedness conduction according to the validation guidelines. The shorter analysis time makes the method very valuable in quality control to quantify the commercial Cfz in pharmaceutical preparations. This improved HPLC method has been successfully applied for Cfz analysis for Peracef and Peractam vials in our routine finished and stability studies testing laboratories. Additionally, the detection limit of Cfz has been tested in our quality control lab to detect the smallest amount of traces that may be present after the cleaning process of the production machines for cephalosporins preparations. In a precedent for the first time, we were able to use the current analysis method to determine the minimum inhibitory concentration (MIC) and minimum bacteriostatic concentration (MBC). The conventional broth micro-dilution tube method was used to determine MIC at 250 µg/mL and MBC at 125 µg/mL of Cfz against the standard strain of Burkholderia cepacia (B. cepacia) ATCC 25416 as Gram-negative bacteria in vitro., (© 2023. The Author(s).)

Thiopental sodium (Tho) is an intravenous anesthetic. The current study aimed to find a rapid RP-HPLC method of Tho analysis with high linearity, repeatability, sensitivity, selectivity, and inexpensive. In our developed method, there is no need to use special chemical reagents, a high percentage of organic solvent, a high flow rate, or a further guard column. The chromatographic system consists of an ODS column (150 mm × 4.6 mm × 5 μm). The mobile phase was prepared by mixing KH 2 PO 4 solution: methanol (40:60) with a flow rate of 1.2 mL/min at a detection wavelength of 230 nm, at room temperature using an injection volume of 10 μL. The method manifested a satisfied linearity regression R 2 (0.9997) with a good repeatability precision range (0.16-0.47%) with LOD and LOQ; 14.4 μg/mL and 43.6 μg/mL respectively. Additionally, the method proved its efficiency via system suitability achievement in robustness and ruggedness, according to the validation guidelines. The shorter analysis time makes the method very valuable in quality control to quantify the commercial Tho in pharmaceutical preparations. This improved HPLC method has been successfully applied for Tho analysis for Thiopental UP Pharma 500 mg vials and Thiopental Eipico 1.0 g vials in our routine finished and stability studies testing laboratories. Additionally, the detection limit of Tho has been tested in our quality control lab to detect the smallest amount of traces that may be present after the cleaning process of the production machines for cephalosporins preparations. The method has shown positive results for Tho in low-level raw materials and pharmaceutical formulations., (© 2023. The Author(s).)

Several precipitating factors of hepatic encephalopathy have been recognized and studied. Hepatic encephalopathy which is a frequent and grave complication of liver failure, is associated with multiple biochemical changes like high serum ammonia, mercaptan and phenol levels, low albumin levels and derangements in electrolytes. It is characterized by a range of neuronal and psychological aberrations mainly due to the inability of liver to metabolize different neurotoxic chemicals produced in the body. Hypokalemia is one of the most important findings in hepatic encephalopathy and postulated as a precipitating factor of the condition. The authors aimed to know the frequency of hypokalemia and its relation to the severity of hepatic encephalopathy., Methods: After taking approval from the hospital ethical review committee, a total of 5000 patients with hepatic encephalopathy were recruited by consecutive sampling. They were interviewed, examined and investigated for serum potassium levels and other precipitating factors of hepatic encephalopathy., Results: Total of 5000 patients including 3070 (61.4%) males and 1930 (38.6%) females, aging 13 years and above were studied. The frequency of hypokalemia was 78% (3900 patients). Relating the serum potassium level with the severity of hepatic encephalopathy, 1200 (60%) out of 2000 patients with serum potassium below 2.5 mEq/l were in grade 4 (40%) and 800 out of 2000 were in grade 3 encephalopathy. On the other hand, only 700 patients (6.4%) out 1100 with serum potassium above 3.4 mEq/l were in grade 4 encephalopathy., Conclusion: Hypokalemia is a frequent finding in patients with hepatic encephalopathy and found to be directly related to its severity., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Environmental tobacco smoke (ETS) is associated with several congenital anomalies, including non-syndromic orofacial clefts (NSOFCs). This systematic review aimed to update the literature on the association between ETS and NSOFCs., Methods: Four databases were searched up to March 2022, and studies that evaluated the association between ETS and NSOFCs were selected. Two authors selected the studies, extracted the data, and evaluated the risk of bias. Comparing the association of maternal exposure to ETS and active parental smoking with NSOFCs allowed for the creation of pooled effect estimates for the included studies., Results: Twenty-six studies were deemed eligible for this review, of which 14 were reported in a previous systematic review. Twenty five were case-control studies, and one was a cohort study. In total, these studies included 2142 NSOFC cases compared to 118129 controls. All meta-analyses showed an association between ETS and the risk of having a child with NSOFC, based on the cleft phenotype, risk of bias, and year of publication, with a pooled increased odds ratio of 1.80 (95% CI: 1.51-2.15). These studies had a marked heterogeneity, which decreased upon subgrouping based on the recent year of publication and the risk of bias., Conclusions: ETS exposure was associated with more than a 1.5-fold increase in the risk of having a child with NSOFC, showing a higher odds ratio than paternal and maternal active smoking., Trial Registration: The study is registered on the International Prospective Register of Systematic Reviews database # CRD42021272909., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2023 Sabbagh H.J. et al.)

Purpose: The proximal tibia is a common location for osteosarcoma. Modular endoprosthesis is a popular reconstructive option, yet it has been associated with many complications. Our study aimed to evaluate the functional outcome and complications of proximal tibial osteosarcoma patients treated by limb salvage using modular endoprosthesis., Methods: A retrospective study of a prospective database was performed during the period between January 2000 and July 2017. Fifty-five patients with proximal tibial osteosarcoma underwent resection and modular endoprosthetic reconstruction. The functional outcome was evaluated using the Musculoskeletal tumor society scoring system and knee range of motion. Postoperative complications were classified according to Henderson classification; Type 1 (soft tissue failure), Type 2 (aseptic loosening), Type 3 (structural failure), Type 4 (infection) and Type 5 (local tumor progression)., Results: The mean follow-up period was 71.69 ± 49.76 months. The mean musculoskeletal tumor society score was 26.5 ± 2.22; the mean range of motion was 72.63 ± 25.07, and the mean extension lag was 15.09 ± 15.38. Type 1, type 2, type 3, type 4, and type 5 complications occurred in 7.3%, 14.5%, 21.8%, 23.6%, and 5.5%, respectively. Chest metastasis developed in 10 patients (18.2%). The estimated 5-year and 10-year survival rates for the treated patients were 83.6% and 79.9%., Conclusions: Proximal tibial osteosarcoma reconstruction with a modular endoprosthesis is a reliable treatment option for retaining limb function. Most complications are manageable., (© 2022. The Author(s).)

This review summarizes the recent advances in the elicitation approaches used to activate the actinomycete genome's cryptic secondary metabolite gene clusters and shows the diversity of natural products obtained by various elicitation methods up to June 2022, such as co-cultivation of actinomycetes with actinomycetes, other non-actinomycete bacteria, fungi, cell-derived components, and/or algae. Chemical elicitation and molecular elicitation as transcription factor decoys, engineering regulatory genes, the promoter replacement strategy, global regulatory genes, and reporter-guided mutant selection were also reported. For researchers interested in this field, this review serves as a valuable resource for the latest studies and references., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Natural products continue to provide inspiring chemical moieties that represent a key stone in the drug discovery process. As per our previous research, the halophyte Agathophora alopecuroides was noted as a potential antidiabetic plant. However, the chemical profiling and highlighting the metabolite(s) responsible for the observed antidiabetic activity still need to be investigated. Accordingly, the present study presents the chemical profiling of this species using the LC-HRMS/MS technique followed by a study of the ligand-protein interaction using the molecular docking method. LC-HRMS/MS results detected twenty-seven compounds in A. alopecuroides extract (AAE) belonging to variable chemical classes. Among the detected compounds, alkaloids, flavonoids, lignans, and iridoids were the most prevailing. In order to highlight the bioactive compounds in AAE, the molecular docking technique was adopted. Results suggested that the two alkaloids (Eburnamonine and Isochondrodendrine) as well as the four flavonoids (Narirutin, Pelargonidin 3-O-rutinoside, Sophora isoflavanone A, and Dracorubin) were responsible for the observed antidiabetic activity. It is worth mentioning that this is the first report for the metabolomic profiling of A. alopecuroides as well as the antidiabetic potential of Isochondrodendrine, Sophora isoflavanone A, and Dracorubin that could be a promising target for an antidiabetic drug.

Oxidative stress is involved in the pathophysiology of multiple health complications, and it has become a major focus in targeted research fields. As known, black seeds are rich sources of bio-active compounds and widely used to promote human health due to their excellent medicinal and pharmaceutical properties. The present study investigated the antioxidant potency of various black seeds from plants and their derived mycoendophytes, and determined the total phenolic and flavonoid contents in different extracts, followed by characterization of major constituents by HPLC analysis. Finally, in silico docking determined their binding affinities to target myeloperoxidase enzymes. Ten dominant mycoendophytes were isolated from different black seed plants. Three isolates were then selected based on high antiradical potency and further identified by ITS ribosomal gene sequencing. Those isolated were Aspergillus niger TU 62, Chaetomium madrasense AUMC14830, and Rhizopus oryzae AUMC14823. Nigella sativa seeds and their corresponding endophyte A. niger had the highest content of phenolics in their n- butanol extracts (28.50 and 24.43 mg/g), flavonoids (15.02 and 11.45 mg/g), and antioxidant activities (90.48 and 81.48%), respectively, followed by Dodonaea viscosa and Portulaca oleracea along with their mycoendophytic R. oryzae and C. madrasense . Significant positive correlations were found between total phenolics, flavonoids, and the antioxidant activities of different tested extracts. The n -butanol extracts of both black seeds and their derived mycoendophytes showed reasonable IC 50 values (0.81-1.44 mg/ml) compared to the control with significant correlations among their phytochemical contents. Overall, seventeen standard phenolics and flavonoids were used, and the compounds were detected in different degrees of existence and concentration in the examined extracts through HPLC analysis. Moreover, the investigation of the molecular simulation results of detected compounds against the myeloperoxidase enzyme revealed that, as a targeted antioxidant, rutin possessed a high affinity (-15.3184 kcal/mol) as an inhibitor. Taken together, the black seeds and their derived mycoendophytes are promising bio-prospects for the broad industrial sector of antioxidants with several valuable potential pharmaceutical and nutritional applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hassane, Hussien, Abouelela, Taha, Awad, Mohamed, Hassan, Hassan, Abo-Dahab and El-Shanawany.)

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides , Anabasis lachnantha , Atriplex leucoclada , Cornulaca aucheri , Halothamnus bottae , Halothamnus iraqensis , Salicornia persia , Salsola arabica , and Salsola villosa , growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC 50 117.9 µg/mL noting better activity than Acarbose (IC 50 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC 50 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase ( p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.

Five sesquiterpene lactones were isolated and identified from Ambrosia maritima L. Hymenin showed highest cytotoxic activity against HCT-116, A-549, and MCF-7 cell lines (IC 50 = 3.83 ± 0.2, 5.48 ± 0.3, 10.1 ± 0.6 µg/mL, respectively). Damsin has significant COX-2 inhibitory activity (IC 50 =33.97 ± 1.62 µg/mL) while hymenin showed highest selectivity to COX-1 (IC 50 = 18.21 µg/mL) and significant inhibition of NO (IC 50 =18.19 ± 0.75 µg/mL). The docking study revealed nice fitting into COX-1/2 and a higher binding affinity for maritimolide towards human Src kinase compared to the native ligand, Bosutinib. Results suggested that both COXs/Src kinase inhibition could contribute even partially to the overall mechanism of cytotoxic activity of the five compounds. The structure-activity relationship revealed that α-methylene-γ-lactone moiety enhances the cytotoxic activity, OH group at C-1 increase activity of hymenin. However, the reduction of the double bond at C-2 as in damsin resulted in a significant decrease in activity against HCT-116 and MCF-7 cells.

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC 50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC 50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC 50 = 559.4 µg/mL) better than that of the standard Acarbose (IC 50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC 50 = 0.77 µg/mL) compared to Acarbose (IC 50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

Pro-inflammatory cytokines and reactive oxygen species (ROS) are produced in acute spinal cord injury, leading to myelin breakdown, inflammation, mitochondrial dysfunction, and apoptosis of neurons and glial cells. The aim of the present study was to investigate possible protective effects of L-carnitine (carn) or atorvastatin (ator) on spinal cord ischemia-reperfusion injury (IRI). Rats were randomized into nine equal groups (n = 8): control and control taking carn (100 mg/kg BW), ator (2.5 mg/kg BW) or both, as well as sham-operation, IRI and IRI taking same doses of carn, ator or both. Neurological assessments were done 48 hours after IRI, and serum nitrite/nitrate was measured. Finally, lumbar segments of spinal cord were excised, and part was homogenized and prepared for measuring tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), advanced oxidation protein products (AOPP), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. The other part was sectioned for evaluation of histopathological changes and for immunostaining by glial fibrillary acidic protein (GFAP), Bax and Bcl-2. The IRI increased ROS (nitrite/nitrate, MDA, AOPP) and pro-inflammatory cytokines (TNF-α, IL-1β), and decreased antioxidants (GSH, GPx, SOD, catalase) with impaired sensory and motor functions. Astrogliosis was detected by GFAP, and increased apoptosis was demonstrated by increasing Bax and decreasing Bcl-2. Treatment with carn or ator alone decreased TNF-α, IL-1β, nitrite/nitrate, MDA and AOPP, and increased GSH, GPx, SOD, and catalase with improvement of neurological functions and histological studies. Combination of carn and ator improved most of measured IRI-affected parameters better than isolated carn or ator administration.

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease M pro in vitro. The extract of Penicillium citrinum , TDPEF34, showed potential inhibition and was further analysed to identify potential M pro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 M pro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2 , and 4 were found to have promising in vitro inhibitory activity towards M pro , with an IC 50 values range of 0.36-0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent M pro inhibitors., Competing Interests: The authors declare no conflict of interest.

The era dominated by the liberal world order, dating back to the end of World War II in 1945 and gaining unchallenged dominance with the fall of the Berlin Wall in 1989, is now coming to an end. Yet the universal principles that the era personified in its rhetoric, and in the best of its actions, lives on. The global community has a moral obligation to continue on its journey to build a more equitable, secure and prosperous world for all of its citizens and must devise investment strategies that enable progress to both endure and accelerate. "The Declaration on Science and the Use of Scientific Knowledge," issued at the conclusion of the inaugural World Conference on Science in 1999, contained a broad range of insights and recommendations that remain as significant today as they did 20 years ago. We would be wise to heed the challenges that the declaration conveyed by recognizing that the journey for equity in science, technology and innovation (STI) is by no means over and, in fact, remains as relevant now as it did then-both as an economic and social necessity and as a moral obligation. This paper seeks to explore how patterns of investment in STI have changed over the past 2 decades-and how they have not., (© 2020. Akadémiai Kiadó Zrt.)

Coculture is a productive technique to trigger microbes' biosynthetic capacity by mimicking the natural habitats' features principally by competition for food and space and interspecies cross-talks. Mixed cultivation of two Red Sea-derived actinobacteria, Actinokineospora spheciospongiae strain EG49 and Rhodococcus sp. UR59, resulted in the induction of several non-traced metabolites in their axenic cultures, which were detected using LC-HRMS metabolomics analysis. Antimalarial guided isolation of the cocultured fermentation led to the isolation of the angucyclines actinosporins E ( 1 ), H ( 2 ), G ( 3 ), tetragulol ( 5 ) and the anthraquinone capillasterquinone B ( 6 ), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the Actinokineospora spheciospongiae strain EG49 was treated with signalling molecule N -acetyl-d-glucosamine (GluNAc); this finding confirmed the effectiveness of coculture in the discovery of microbial metabolites yet to be discovered in the axenic fermentation with the potential that could be comparable to adding chemical signalling molecules in the fermentation flask. The isolated angucycline and anthraquinone compounds exhibited in vitro antimalarial activity and good biding affinity against lysyl-tRNA synthetase (PfKRS1), highlighting their potential developability as new antimalarial structural motif.

In this study, new pyrazolopyrimidine derivatives were designed and evaluated for anticancer activity. PIM-1 inhibitiory activity were measured for the most potent compounds. Molecular docking study and molecular dynamics were also done. Thus, the novel derivatives of pyrazolo[1,5-a]pyrimidine have been synthesized and characterized using different spectroscopic techniques. HMBC and NOESY experiments were used to confirm regiospecific structure of pyrimidine ring. The newly synthesized derivatives were evaluated for their antitumor activities against HCT-116 and MCF-7 cell lines. These derivatives showed clear in vitro antitumor activities. Compound 5h showed the highest bioactivity (IC 50  = 1.51 µM) against HCT-116 cell line. While, compound 6c was the most potent derivative, its IC 50 was 7.68 µM against MCF-7 cell line. Compounds 5c, 5g, 5h, 6a and 6c showed PIM-1 inhibitory activity with IC 50 of 1.26, 0.95, 0.60, 1.82, 0.67, respectively µM that could be correlated with their cytotoxic effect. Molecular docking study was done to predict the mode of binding of the target compounds inside PIM-1 active site. The molecular dynamic simulation was conducted in order to evaluate stability of binding of the tested compounds., 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 Inc. All rights reserved.)

Background: In the Kingdom of Saudi Arabia, the nursing profession faces significant challenges including; failure to recruit high school students into nursing education, poor nursing identity, and lack of awareness about the nursing profession. The level of community awareness and public image of the nursing profession are critical to recruit and retain students into nursing education, and to improve nurses' sense of identity., Aim: To explore the level of community awareness and public image of the nursing profession in Saudi Arabia., Methods: We conducted a cross-sectional study with a convenient sample of 502 adults including106 males and 396 females, their mean age was 22.93 ± 6.76 years. Data collected included; socio-cultural data, gender preference in getting nursing care, awareness, and perceived socio-cultural barriers to pursue a nursing career. Data were analyzed using SPSS version 21.0., Results: Only 32.5% preferred to get nursing care by Saudis. The nursing profession was not viewed as a respected job as 71.5% of participants would be ashamed of having a nurse in their families. The study revealed a low median knowledge score (50.0, IQR: 50.0-66.7)). The study highlighted a number of socio-cultural barriers to pursue a nursing career including; the gender-mixed working environment (35.9%), delayed marriage of female nurses (20.3%), and the negative effect of nursing profession on social life (64.5%)., Conclusions: Half of the sample had a knowledge score below 50.0 out of 100. This level of poor awareness, in addition to socio-cultural perceived barriers are the main factors contributing to the negative public image of the nursing profession in Saudi Arabia. Understanding these factors could contribute to implementing focused intervention to improve the negative stereotype of the nursing profession among Saudis., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

The prevalence of multidrug-resistant microbial pathogens due to the continued misuse and overuse of antibiotics in agriculture and medicine is raising the prospect of a return to the preantibiotic days of medicine at the time of diminishing numbers of drug leads. The good news is that an increased understanding of the nature and extent of microbial diversity in natural habitats coupled with the application of new technologies in microbiology and chemistry is opening up new strategies in the search for new specialized products with therapeutic properties. This review explores the premise that harsh environmental conditions in extreme biomes, notably in deserts, permafrost soils and deep-sea sediments select for micro-organisms, especially actinobacteria, cyanobacteria and fungi, with the potential to synthesize new druggable molecules. There is evidence over the past decade that micro-organisms adapted to life in extreme habitats are a rich source of new specialized metabolites. Extreme habitats by their very nature tend to be fragile hence there is a need to conserve those known to be hot-spots of novel gifted micro-organisms needed to drive drug discovery campaigns and innovative biotechnology. This review also provides an overview of microbial-derived molecules and their biological activities focusing on the period from 2010 until 2018, over this time 186 novel structures were isolated from 129 representatives of microbial taxa recovered from extreme habitats., (© 2019 The Society for Applied Microbiology.)

Microbial co-culture or mixed fermentation proved to be an efficient strategy to expand chemical diversity by the induction of cryptic biosynthetic pathways, and in many cases led to the production of new antimicrobial agents. In the current study, we report a rare example of the induction of silent/cryptic bacterial biosynthetic pathway by the co-culture of Durum wheat plant roots-associated bacterium Pantoea aggolomerans and date palm leaves-derived fungus Penicillium citrinum . The initial co-culture indicated a clear fungal growth inhibition which was confirmed by the promising antifungal activity of the co-culture total extract against Pc. LC-HRMS chemical profiling demonstrated a huge suppression in the production of secondary metabolites (SMs) of axenic cultures of both species with the emergence of new metabolites which were dereplicated as a series of siderophores. Large-scale co-culture fermentation led to the isolation of two new pulicatin derivatives together with six known metabolites which were characterised using HRESIMS and NMR analyses. During the in vitro antimicrobial evaluation of the isolated compounds, pulicatin H ( 2 ) exhibited the strongest antifungal activity against Pc, followed by aeruginaldehyde ( 1 ) and pulicatin F ( 4 ), hence explaining the initial growth suppression of Pc in the co-culture environment., Competing Interests: The authors declare no conflict of interest.

Objective: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP., Methods: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect., Results: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: odds ratio [OR] 2.16 [95% CI 1.38-3.4]; mothers: OR 2.39 [95% CI 1.53-3.71]; and infants: OR 2.77 [95% CI 1.77-4.34]) and CP (fathers: OR 2.24 [95% CI 1.15-4.36] and infants: OR 2.43 [95% CI 1.25-4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05-2.86]; mothers: OR 2.43 [95% CI 1.49-3.97]; and infants: OR 2.34 [95% CI 1.44-3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls (p = 0.001)., Conclusion: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity.

To understand the source-to-sink of pollutants in the Kelantan River estuary and the adjacent shelf area in Malaysia, a total of 42 surface sediment samples were collected in the Kelantan River-estuary-shelf system to analyze for grain size, total organic carbon (TOC) content, Al and heavy metals (Cr, Ni, Cu, Zn, Cd and Pb). The surficial sediments were mainly composed of clayey silt and the TOC content in sediments decreased from the river to the shelf. The surficial sediments experienced Pb pollution; Cr only showed a certain level of pollution in the coastal area of the estuary but not in other areas, and Ni, Cu, Zn, and Cd showed no pollution. The heavy metals mainly originated from natural weathering and erosion of rocks and soils in the catchment and enriched near the river mouth. Total organic carbon can promote the enrichment of heavy metals in sediments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Modern mangroves are among the most carbon-rich biomes on Earth, but their long-term (≥10 6 years) impact on the global carbon cycle is unknown. The extent, productivity and preservation of mangroves are controlled by the interplay of tectonics, global sea level and sedimentation, including tide, wave and fluvial processes. The impact of these processes on mangrove-bearing successions in the Oligo-Miocene of the South China Sea (SCS) is evaluated herein. Palaeogeographic reconstructions, palaeotidal modelling and facies analysis suggest that elevated tidal range and bed shear stress optimized mangrove development along tide-influenced tropical coastlines. Preservation of mangrove organic carbon (OC) was promoted by high tectonic subsidence and fluvial sediment supply. Lithospheric storage of OC in peripheral SCS basins potentially exceeded 4,000 Gt (equivalent to 2,000 p.p.m. of atmospheric CO 2 ). These results highlight the crucial impact of tectonic and oceanographic processes on mangrove OC sequestration within the global carbon cycle on geological timescales.