bluuebunny/crossref_metadata_2025_split huggingface dataset:
<i>In-silico</i> studies of HMG-Co A reductase inhibitors present in fruits of <i>Withania coagulans</i> Dunal (Solanaceae)
Authors: Lateef Tooba , Naeem Sadaf , Qureshi Shamim A. 
Published: June 2020

Purpose: To evaluate the antihypercholesterolemic effect of chemical constituents of W. coagulans by determining inhibitory effect of the compounds against HMG-CoA reductase, using in-silico methods.
Method: Docking simulations of twenty-one chemical constituents, found in the fruits of W. coagulans were performed against HMGCR(PDB ID: 2Q1L) using Molegro Virtual Docker software. The best docked poses were then selected, based on the docking score and amino acids involved in the interaction within the ligand and active site of protein.
Results: Five compounds viz. Coagulin D (comp no. 11), Ergosta-5,25-diene-3β,24ε-diol (comp no. 13), Withacoagulin (comp no. 15), and Withaferin (comp no. 16), showed the highest MolDock scores. These compounds with highest docking score, also formed hydrogen bond interactions with His (752), Lys (692, 735), Asp (690), Glu (559) within the binding site of HMG-CoA reductase, thus, halting enzyme activity. Whereas, Withanolide D (comp no. 17) with high MolDock score did not show hydrogen bonding interactions.
Conclusion: The high MolDock score and maximum binding with catalytic region of the enzyme indicate that compounds selected from the fruits of W. coagulans are potential blockers of HMG-CoA reductase. Thus, the compounds may be useful for the management of hypercholesterolemia, which untreated, often leads to coronary artery disease.
Keywords: Withania coagulans, Coronary artery disease, HMG-CoA reductase, Molegro virtual docker, Hypercholesterolemia, In silico studies
Phytochemical, antimicrobial and cytotoxicity screening of ethanol extract of <i>Acacia ehrenbergiana</i> Hayne grown in Jazan Region of Saudi Arabia
Authors: Makeen Hafiz A. , Alhazmi Hassan A. , Khalid Asaad , Al Bratty Mohammed , Syame Sohier M. , Abdalla Ashraf N. , Homeida Husham E. , Sultana Shahnaz , Ahsan Waquar 
Published: June 2020

Purpose: To explore the phytoconstituents of Acacia ehrenbergiana Hayne as well as its biological effects.
Methods: Determination of phytoconstituents of ethanol extract of the plant was performed by gas chromatography-mass spectrometry (GC-MS) technique. Antibacterial screening was conducted against the isolates of Gram-positive and Gram-negative microbes while the anti-carcinogenic properties of the ethanol extract on cancerous cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay against breast MCF7, ovary cancer A2780 and colon cancer HT29 cells, respectively, in addition to normal MRC5 fibroblast cells.
Results: GC-MS analysis identified 15 different phytochemicals in the ethanol extract. The extract exerted significant antimicrobial activity with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the range 1.56 - 6.25 and 3.12 – 12.5 mg/L, respectively, against all test bacterial strains. Cytotoxic activity, obtained by MTT assay, was 28.81 ± 0.99, 12.50 ± 2.50, 23.90 ± 0.74 and 50.58 ± 3.24 μg/mL, against the three cancer cell lines and normal fibroblast, respectively. MTT cytotoxicity results was further confirmed by clonogenic survival assay on MCF7 cells.
Conclusion: This study highlights the potential interesting ethnopharmacological applications of Acacia ehrenbergiana Hayne to treat drug-resistant pathogens as standardized extract.
Keywords: Acacia ehrenbergiana, Phytochemistry, Antimicrobial, Cytotoxicity
Synthesis and screening of anticancer potentials of some new terephthaldehyde-derived nitrone compounds
Authors: Salman Husam Hamza , Ali Munther Abduljaleel Mohammed , Ali Eman Tariq 
Published: June 2020

Purpose: To synthesize and screen some new nitrone compounds derived from terephthaldehyde for their anticancer potential.
Methods: Six new compounds (H, p-Me,p-Br, p-Cl, o-Cl and m-Me) were synthesized via a condensation reaction between terephthaldehyde and a variety of aryl hydroxylamine compounds derived from nitrobenzene and its derivatives. The chemical structures of these compounds were identified using elemental CHN analysis and were elucidated using Fourier Transform infra-red (FT-IR), 1H-nuclear magnetic resonance (1H NMR), mass spectrometry (MS), and elemental analysis. The anticancer effects of the compounds were screened in vitro with respect to their cytotoxicity on MCF7 human cancer cells line. The IC50 values were obtained by MTT assay and their effects on apoptosis of MCF-7 cells were assessed using Acridine orange-ethidium bromide AO/EtBr staining method under a fluorescence microscope.
Results: Only four compounds (2b, 2d, 2e, and 2f) inhibited more than 50 % of the growth of MCF-7 cells. The strongest anti-proliferation effect against MCF-7 cells was exhibited by 2f (m-Me), producing more apoptosis which increased membrane disruption and consistency of lysosome vacuoles; it also exhibited higher cytotoxic effects on human cancer cell lines (IC50 < 7.5) than the other synthesized compounds.
Conclusion: The new nitrone compounds (2b, 2d, 2e, and 2f) synthesized from terephthaldehyde exhibit some anticancer properties, and so are potential anticancer agents.
Keywords: Terephthaldehyde, Nitrone, Cytotoxicity, Anticancer, MCF-7 cells
Isolation, characterization, pharmacological evaluation and <i>in silico</i> modeling of bioactive secondary metabolites from <i>Ziziphus oxyphylla</i> a member of Rhamnaceae family
Authors: Khan Irfan , Zahoor Muhammad , Zeb Alam , Sahibzada Muhammad Umar Khayam , Bari Wasim Ul , Naz Sumaira 
Published: June 2020

Purpose: To investigate the pharmacological properties of the medicinally active metabolites of Ziziphus oxyphylla.
Methods: Compound I-IV were isolated form the root of Ziziphus oxyphylla (compound I = Stigmasterol, II = Betulinic acid, III = 1,2,3 benzene triol and IV = 5-Pentadecanoic acid). Various spectroscopic techniques were used to identify and characterize the isolated compounds. DPPH (2,2-diphenyl-1- picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays were employed to determine the antioxidant potentials of these compounds. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition potential of the isolated compounds were also evaluated.
Results: Amongst the isolated compounds, compound IV was the most potent antioxidant against DPPH and ABTS free radicals, exhibiting half-maximal concentration (IC50) values of 64 and 65 μg/mL, respectively. All the compounds exhibited good inhibition of acetylcholinesterase and butyrylcholinesterase. However, stigmasterol was more potent than the other isolated compounds, showing IC50 of 85.10 ± 1.45 and 84.81 ± 1.17, respectively, against AChE and BChE.
Conclusion: Although, all isolated compounds inhibited the selected free radicals (DPPH and ABTS) and cholinesterases, stigmasterol and 5-penatadecanoic acid were more potent than other two compounds. Thus the former can potentially be used to treat oxidative stress and neurodegenerative diseases.
Keywords: Ziziphus oxyphylla, Stigmasterol, 5-Pentadecanoic acid, Antioxidant, Acetyl Cholinesterase, Butyryl cholinesterase
New insight into single phase formation of capric acid/menthol eutectic mixtures by Fourier-transform infrared spectroscopy and differential scanning calorimetry
Authors: Ali Hiba H. , Ghareeb Mowafaq M. , Al-Remawi Mayyas , Al-Akayleh Faisal T. 
Published: June 2020

Purpose: To examine the structural changes of a eutectic mixture comprising capric acid and menthol which are commonly used in pharmaceutical applications.
Methods: A phase diagram was constructed by quantitative mixing of capric acid and menthol under controlled conditions until a single liquid phase was formed. Eutectic mixtures of capric acid: menthol at the ratios of 3:2, 1:4, 1:1, 2:3, and 1:4 were prepared. Hydrogen bond formation and conformational changes were analyzed using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Microscopic imaging was carried out to capture phase change events upon increasing temperature.
Results: Menthol confirmed the intact structure of a hexagonal ring. The high degree of broadening of the menthol O-H groups indicates hydrogen bond formation. FTIR band changes related to capric acid suggest a break-up of the methylene arrangement structure due to changes in the C-H band frequencies. The red shift encountered in C=O stretching band emphasizes hydrogen bond formation taking place between the oxygen atom of the hydroxyl group comprising the carboxylic moiety of capric acid and the hydrogen atom of menthol hydroxyl group. DSC results indicate the presence of two polymorphs of the capric acid/ menthol complex. Both exhibited crystallization and conformational change exotherms in addition to two melting endotherms as result of transformation of crystalline components to become partially crystalline due to hydrogen bond formation.
Conclusion: The interaction between capric acid and menthol results in a typical preparation of deep eutectic systems that can act as natural-based solvents in numerous pharmaceutical applications.
Keywords: Eutectic system, Capric acid, Menthol, Differential scanning calorimetry, DSC, Fourier transform infrared spectroscopy, FTIR
A prospective antibiotic point prevalence survey in two primary referral hospitals during and after pilgrims stay in Madinah, Saudi Arabia
Authors: Yaser M.  , Aljabri Ahmad K. , Alsaadi Faisal N. , Rizk Lamiaa M. , Alahmadi Renad Y. , Aljuhani Sami R. , Aljohani Sultan H. , Al Thagfan Sultan S. , Alamuddin Walaa A. , Alonazie Wedad S. , Alowayyidh Yasir A. 
Published: June 2020

Purpose: To assess current patterns of antibiotic use by carrying out two point-prevalence surveys (PPS) in Madinah after the return of hajj pilgrims from Makkah and when Madinah is free from pilgrims.
Methods: In September 2016 and November 2016, a prospective PPS was conducted on two separate dates (during the hajj pilgrims stay in Madinah and after they leave). Data on antibiotics use were generated during these two periods. This involved an audit from all the departments of two referral hospitals (King Fahad Hospital (KFH) - 425 beds, and Al Ansar Hospital - 100 beds) of inpatients records. Data were collected using standard forms adapted from the European Centre for Disease Control (ECDC).
Results: A total of 675 inpatients were included in PPS; among them, 332 (49.18 %) patients were receiving antibiotic therapy. In September 2016, 168 patients were treated with antibiotics, with a prevalence rate of 50.60 %, whereas, in November 2016, the prevalence rate was 49.40 %. Overall, 198 patients were identified in surgical wards, of which 132 patients (66.6 %) were receiving antibiotic therapy; 121 patients in ICU of which 70 patients (57.8 %) received antibiotics; 13 patients in other wards of which 6 (46.1 %) received antibiotic treatment; and 343 patients in medical wards of which 126 patients (36.7 %) were treated with antibiotics. There was no significant difference in prevalence of antibiotic prescribing between the two surveys (Pearson Chi-square test, p = 0.56) and with regards to patient age between the two surveys (Mann-Whitney U-test, p = 0.32).
Conclusion: The results demonstrate that antibiotic use with adherence to hospital guidelines and PPS helps in identifying targets for quality improvement. Moreover, to escalate the prudent use of antibiotics in hospitals, PPS provides a useful tool. Furthermore, this survey provides a background to evaluate antibiotic use by a standardized methodology.
Keywords: Point prevalence survey, Antibiotic use, Prescribing practices, Antibiotic resistance, Quality improvement, Antibiotic stewardship, Hajj, Pilgrims
Extraintestinal pathogenic <i>Escherichia coli</i> in Saudi Arabia: A review of antimicrobial resistance and molecular epidemiology
Authors: Alqasim Abdulaziz 
Published: June 2020

Extra-intestinal pathogenic Escherichia coli (ExPEC) is commonly associated with causing urinary tract and bloodstream infections. Over the past two decades, the antimicrobial resistance of ExPEC has increasingly been reported [1]. Given that Saudi Arabia annually hosts mass religious events, such as Hajj, this review investigated several aspects of antimicrobial resistance of ExPEC in this country including the current prevalence of resistance and molecular epidemiology of ExPEC isolates. Generally, the overall prevalence of antibiotic resistance of ExPEC in Saudi Arabia is on increase. The current emergence of colistin resistance in ExPEC represents a major challenge to public health. Local molecular epidemiological studies have shown the dominance of E. coli sequence type 131 (E. coli ST131) over other major ExPEC STs. This is an important observation given that this clone has been associated with high multidrug resistance and extended-spectrum β-lactamases carriage. To reduce the burden of this resistance in the future, it would be crucial to avoid uncontrolled use of antibiotics in either clinical settings or animal food industry.
Keywords: Extra-intestinal pathogenic Escherichia coli, Antimicrobial resistance, ST131, Saudi Arabia, Colistin resistance, Extended-spectrum β-lactamases
Aqueous extract of <i>Aconitum carmichaelii</i> Debeaux attenuates sepsis-induced acute lung injury via regulation of TLR4/NF-ΚB pathway
Authors: You Qinghai , Wang Jinmei , Jiang Lijuan , Chang Yuanmin , Li Wenmei 
Published: June 2020

Purpose: To investigate the therapeutic effect of aqueous extract of Aconitum carmichaelii Debeaux (AEACD) on sepsis-induced acute lung injury (ALI), as well as explore the underlying mechanism of action.
Methods: C57BL/6 mice were treated with AEACD by gavage (4.0 g/kg/day) for 5 days before cecal ligation and puncture (CLP) challenge. After 24 h, the pathological morphology of lung tissue and the biochemical parameters in bronchoalveolar lavage fluid (BALF) were determined by H&E staining and enzyme-linked immunosorbent assay (ELISA). Furthermore, the total protein content and lactate dehydrogenase (LDH) level of BALF, as well as the oxidative biomarkers (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD)) were evaluated in the lung homogenates by ELISA assay. The levels of pro-inflammatory cytokines, TNFα, IL-1β, and IL-6, in lung tissue were measured by qRT-PCR or ELISA. Finally, key proteins in Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in lung tissue were evaluated by western blot.
Results: CLP challenge induced abnormal changes in the histological structures of lung tissue, lung wet-to-dry weight (W/D) ratio, protein content and LDH levels of BALF, which were remarkably reversed by AEACD. In addition, AEACD decreased MDA levels, and increased GSH levels and SOD activity in the lung tissue of CLP–treated mice (p < 0.05). Furthermore, AEACD attenuated the CLP challengeinduced upregulation of TNFα, IL-1β, and IL-6. Finally, AEACD inactivated TLR4/NF-κB pathway by upregulating IκBα and downregulating TLR4 and phosphorylated-p65 levels.
Conclusion: AEACD administration protects mice against sepsis-induced ALI through the regulation of oxidative stress and inflammatory responses in lung tissues. The underlying mechanism occurs by inhibiting TLR4/NF-κB signaling pathway.
Keywords: Aconitum carmichaelii Debeaux, Acute lung injury, Sepsis, TLR4, NF-κB
Aqueous leaf extract of Sutherlandia frutescens attenuates ROS-induced apoptosis and loss of mitochondrial membrane potential in MPP+-treated SH-SY5Y cells
Authors: Enogieru Adaze B. , Omoruyi Sylvester I. , Ekpo Okobi E. 
Published: June 2020

Purpose: To investigate the neuroprotective activity of the aqueous extract of Sutherlandia frutescens (SF) against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in SH-SY5Y neuroblastoma cells.
Methods: SH-SY5Y neuroblastoma cells were divided into different treatment groups: untreated cells, cells treated with MPP+ alone (2 mM), cells pretreated with SF (20 μg) prior to MPP+ (2 mM) treatment and cells treated with SF (20 μg) alone. Twenty-four hours after treatment with MPP+, cell viability was assessed by MTT assay, and changes in cell morphology, intracellular reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) as well as caspases 3/7 and 9 activities were determined.
Results: Treatment of SH-SY5Y cells with MPP+ alone significantly altered cellular morphology, increased ROS production (p = 0.005), induced a significant loss of MMP (p = 0.0011) and caused significant apoptotic cell death, via the activation of caspases 3/7 and 9 (p ≤ 0.0359). These effects were however significantly (p ≤ 0.0359) attenuated in cells pre-treated with the aqueous leaf extract of SF, indicating the possible neuroprotective activity of the SF extract.
Conclusion: The results of this study suggest that the aqueous leaf extract of SF may be neuroprotective against MPP+-induced toxicity via apoptotic cell death and inhibition of ROS production. Further mechanistic studies are required to validate the results of the present study using additional PD models, different extract preparations and active compounds derived from SF.
Keywords: Parkinson’s disease, MPP+, Sutherlandia frutescens, Reactive oxygen species, Apoptosis, Neurodegeneration
Comparative pharmacokinetic study of five flavonoids in normal rats and rats with gastric ulcer following oral administration of Mongolian medicine, Shudage - 4 by UPLC – ESI – MS/MS
Authors: Jia Xin , Du Yinfei , Xu Jia , Dong Yu 
Published: June 2020

Purpose: To develop a simple, rapid and sensitive ultra-performance liquid chromatography - electrospray ionization-mass spectrometry (UPLC–ESI–MS/MS) method was developed and fully validated for the simultaneous determination of galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin in rat plasma after oral administration of Mongolian Medicine, Shudage-4 extracts.
Methods: The galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin were separated on a C18 column using 0.1 % formic acid at a flow rate of 0.4 mL / min and detected by a mass spectrometer in negative-ion mode with selected reaction monitoring (SRM) mode. Plasma samples were processed with a simple deproteinization technique using ethyl acetate and acetonitrile. Following the protein precipitation, the plasma samples were evaporated under gentle stream of nitrogen and analyzed by above method. Naringin was used as an internal standard (IS). Method validation was performed according to the Chinese Food and Drug Administration guidelines.
Results: A good linearity (r2 ≥ 0.9990) was showed by the UPLC – ESI – MS / MS method, the low limits of quantification for galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin were 229.8, 78.8, 32.0, 123.7 and 137.8 ng / mL, respectively. The results of inter-day and intra-day precisions met the experimental requirement (< 7.8 %). The matrix effect and recovery efficiency of the five analytes were more than 72.9 and 88.7 % respectively. The stability of the analytes were satisfactory. The UPLC – ESI – MS / MS method has been used for the five analytes’ pharmacokinetics study successfully after gastrointestinal route of the Mongolian Medicine Shudage-4. The pharmacokinetic parameters showed significant differences (P < 0.05) between the normal and gastric ulcer groups. The metabolism and transport of the five analytes in gastric ulcer rates were faster than in normal rats after administration of Shudage - 4 extract. Double-peak phenomenon appeared in galangin, galangin – 3 - methylether and quercetin.
Conclusion: The results suggest that the metabolism and transport of Mongolian Medicine Shudage-4 in gastric ulcer rats is faster than in normal rats and may be enriched and acted on at the lesion site.
Keywords: UPLC – ESI – MS / MS; Mongolian medicine; Shudage - 4; pharmacokinetics; gastric ulcer
Comparison of the efficacy of half ticagrelor loading doses and clopidogrel in elderly acute coronary syndrome patients in China
Authors: Xue Jian , Li Mingming , Wang Lijie , Ma Minjun , Zhang Jin 
Published: June 2020

Purpose: To evaluate the effects of half-load doses (HLD) of ticagrelor and clopidogrel on elderly acute coronary syndrome patients (ACS) over a period of 90 days.
Methods: Seventy-four patients diagnosed as ACS were included in this trial. The patients were randomly distributed into group 1 (treated with HLD ticagrelor, 90 mg LD) and group 2 (treated with clopidogrel, 300 mg LD). The interaction of treatment effect was evaluated using Multivariate Cox proportional hazards regression models.
Results: Within three months, a total of 12 patients (16.21 %) died of myocardial infarction or stroke. The endpoint of HLD ticagrelor-treated elderly ACS patients was 20 %, and the incidence of clopidogreltreated endpoints was 14.81 %.
Conclusion: In the first 45 patients treated with HLD ticagrelor, their cumulative incidence of cardiac events was relatively high. However, there were no considerable changes in the therapeutic benefits of these two drugs in elderly ACS patients.
Keywords: Elder patients, Acute coronary syndrome, Ticagrelor, Clopidogrel
Exosomes: Salivary Biomarkers?
Authors: Qamar Zeeshan , Niazi Fayez Hussain , Tanveer Syed Bilal , Zeeshan Tayyaba 
Published: June 2020

Saliva is a bio-fluid considered similar to blood in that it contains various DNAs, RNAs and proteins. Therefore, it is a fluid with diagnostic potential. In recent time, exosomes are emerging as nano-vesicles which enhance intra-cellular communication. Exosomal content, which is dependent on the cell of origin, reflects physiological status of cells. Exosomes have potentials for use as biomarkers for variant diseases, based on their stability and availability in various body fluids. Current studies have proposed the role of exosomes as immuno-modulators in the etiology of auto-immune diseases and cancers. The present study focused on the role of exosomes as biomarkers and their therapeutic potentials in particular diseases related to the oral cavity.
Keywords: Exosomes, Auto-immune, Biomarkers, Saliva, Diagnosis
Lysine demethylase 1A exacerbates LPS-induced inflammation of vascular smooth muscle cells through modulation of NF-κB activation
Authors: Liang Ling , Sun Mingliang , Qi Zhongquan , Li Weihua 
Published: June 2020

Purpose: To study the effect of lysine demethylase 1A (LSD1) on inflammatory responses of vascular smooth muscle cells (VSMCs), and investigate the mechanism.
Methods: VSMCs were treated with lipopolysaccharide (LPS). Overexpression and knockdown of LSD1 in VSMCs were performed by transfecting with LSD1 overexpression plasmid and small interfering RNAs (siRNAs), respectively. Western blot and quantitative real-time polymerase chain reaction (qRTPCR) were used to measure protein and mRNA levels. Enzyme-linked immunosorbent (ELISA) assay was used to determine the levels of inflammatory cytokines.
Results: Phosphorylation of LSD1 (p-LSD1) was significantly increased in LPS-induced VSMCs. Monocyte chemoattractant protein-1 and IL-6 levels were also increased by LPS, but attenuated by LSD1 knockdown in VSMCs. Activation of NF-κB was increased by LPS, but was also decreased by LSD1 knockdown. Level of methylated p65 (p65-me) in VSMCs was increased by treatment with SET7/9 (p65 methyltransferase), but this effect was attenuated by overexpression of LSD1. Besides, the increased levels of MCP-1 and IL-6 induced by overexpression of LSD1 were reversed by NF-κB signaling inhibitor, PDTC.
Conclusion: LSD1 exacerbates LPS-induced inflammation of VSMCs through NF-κB activation via p65 demethylation, which indicates that LSD1 might be a potential target for the treatment of cardiovascular diseases.
Keywords: Vascular smooth muscle cells, Lysine demethylase 1A, Phosphorylation, NF-κB, p65, Demethylation