bluuebunny/crossref_metadata_2025 huggingface dataset:
In-silico studies of HMG-Co A reductase inhibitors present in fruits of Withania coagulans 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 Acacia ehrenbergiana 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 in silico modeling of bioactive secondary metabolites from Ziziphus oxyphylla 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 Escherichia coli 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 Aconitum carmichaelii 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
Gastric cancer cell proliferation is inhibited by α-santonin via targeting of PI3K and AKT activation
Authors: Nie Lin , Zhang Lijiu
Published: June 2020

Purpose: To investigate the effect of α-santonin on proliferation of gastric cancer cells.Methods: Cell proliferation was analysed by 3-4-5-Dimethylthiazol-2-yl-25-diphenyltetrazolium bromide (MTT) assay and migration by wound healing assay. Matrigel coated Transwell chamber was used for determination of cell invasion. Expression of proteins and mRNA was assessed using western blot and RT-PCR assay, respectively.Results: In NUGC4 and MKN45 cell cultures, treatment with α-santonin promoted miR 145 expression significantly when compared to control. Treatment of NUGC4 cells with α-santonin for 48 h significantly increased apoptosis in comparison to control. At 100, 150 and 200 μM concentrations of α-santonin, the level of cell apoptosis increased to 45, 53 and 64 %, respectively (p < 0.05). Treatment with α-santonin caused NUGC4 cell population increase in G1/G0 phase with reduction in S and G2/M phases. A significant reduction in NUGC4 cell invasion was observed following treatment with α-santonin. The α- santonin treatment of NUGC4 cells at 200 μM concentration markedly reduced cell invasion (p < 0.05). Treatment of NUGC4 cells with α-santonin reduced the expression of c Myc, PI3K, and p AKT. The production of MMP-2 and MMP-9 in NUGC4 cells was also decreased by α-santonin treatment.Conclusion: The study demonstrates that α-santonin plays important role in inhibition of gastric cancer cell proliferation by arrest of cell cycle and apoptosis induction. Moreover, the activation of PI3K and AKT was also suppressed by α-santonin. Therefore, α-santonin can potentially be used for the treatment of gastric cancer.

Keywords: Apoptosis, MicroRNA, Tumor suppressor, Metastasis, Infiltration
Metformin exerts renoprotective effect by reducing proteinuria in spontaneously-hypertensive rats
Authors: Liu Yuanyuan , Wang Chengjian , Zhang Enyuan
Published: June 2020

Purpose: To study the mechanism involved in metformin (DMBG)-induced reduction of albuminuria in spontaneously-hypertensive rats (SHRs).

Methods: The SHRs were divided into DMBG SHR group (n = 30) given DMBG (300 mg/kg) and NC SHR group (n = 10) given distilled water (2 ml/day), while Wistar-Kyoto rats (WKY) rats were divided into DMBG WKY group (n = 30) given DMBG (300 mg/kg ) and NC WKY group (n = 10) administered distilled water (2 ml/day). Urinary protein levels were measured and compared. Inflammatory infiltration in renal tissue, and expression of vascular endothelial growth factor (VEGF) were assessed. Abdominal aortic blood was used to measure serum levels of creatinine and blood urea nitrogen (BUN).

Results: Urinary protein was markedly elevated in SHRs, while BUN in SHRs was lowered, relative to WKY rats (p < 0.05). Moreover, inflammatory cell population was lower in DMBG SHRs group than in WKY rats (p < 0.05). Kidney expressions of VEGF in SHR and WKY rats treated with metformin  were significantly reduced, relative to those in untreated rats, but VEGF-A in DMBG SHR rats was markedly elevated, relative to NC SHR group, and was also raised in DMBG WKY, when compared with NC WKY rats (p < 0.05).

Conclusion: Metformin reduces albuminemia in spontaneously hypertensive rats by up-regulating VEGF expression, thereby exerting renoprotective effect. This finding provides ideas for research and development of other therapeutic approaches.

Keywords: Metformin, Spontaneous hypertension, Renoprotective, Albuminuria, Kidney, Vascular endothelial growth factor (VEGF)
Effect of Evodia rutaecarpa (Juss) Benth extract on Alzheimer disease in mice
Authors: Cai Ang , Xiao Liu , Zhou Yan-Ping , Zhang Zhi-Guo , Yang Quan-Wei
Published: June 2020

Purpose: To investigate the protective effect of Evodia rutaecarpa (Juss.) Benth. extract (ERBE) against Alzheimer's disease in 3xTg-AD mice.

Methods: The cognitive function of 3xTg-AD mice was assessed using Morris water maze test. The levels of amyloid beta deposits and NeuN in the mouse hippocampus were evaluated by immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were determined by western blot analysis.

Results: ERBE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. The escape latency in the animals treated with 400 mg/kg ERBE (20.5 ± 1.3 s) was significantly higher than untreated 3xTg-AD mice (12.4 ± 1.3 s, p < 0.01). In addition, ERBE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expressions of BDNF (1.4 ± 0.2, p < 0.05) and TrkB (1.1 ± 0.2, p < 0.05) in 3xTg AD mice.

Conclusion: The results suggest that ERBE administration may be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.

Keywords: Evodia rutaecarpa, Alzheimer, Memory impairment, NeuN-positive cells
Anti-diabetic effect of the polyphenol-rich extract from Tadehagi triquetrum in diabetic mice
Authors: Lin Xiaowan , Zhou Xinxin , Sun Wanying , Zhang Lu , Zhang Caiyun , Zhang Xiaopo
Published: June 2020

Purpose: To clarify the diabetes-reducing abilities of the polyphenol-rich extract from Tadehagi triquetrum (HC) in diabetic ob/ob mice.Methods: Aerial parts of T. triquetrum were extracted under reflux and partitioned by n-butanol to generate HC. The effects of HC consumption on blood glucose and lipids, insulin resistance, and liver glucose metabolism were evaluated in vivo. The main compounds of HC were tested for their effects on stimulating glucose consumption and uptake by HepG2 hepatocytes and C2C12 myotubes.Results: After HC treatment, body fat, subcutaneous fat, and epidydimal fat masses decreased (p <0.05), while mean daily food intake was  unaffected. HC (200–400 mg/kg) decreased fasting blood glucose, glycosylated serum protein (GSP), and glycosylated hemoglobin (HbAlc); it also lowered hyperinsulinemia, improved oral glucose tolerance, and reduced hyperlipidemia and liver fat content (p < 0.05). HC treatment markedly elevated liver glycogen content and activity of hepatic glucokinase and pyruvate kinase (p < 0.05). Eight polyphenols were isolated from HC, six of which potently stimulated glucose consumption and uptake in vivo.Conclusion: HC has potent antidiabetic activities. Polyphenols are the main compounds accounting for these effects. Chronic oral administration of HC may be an alternative therapy for managing diabetes, but this has to be subjected first to clinical studies.

Keywords: Tadehagi triquetrum, Diabetes, Phenylpropanoid glucosides, Pyruvate kinase, Glucokinase
Ultra-performance liquid chromatography–tandem mass spectrometric determination of ramipril in human plasma
Authors: Abdel-Gawad Sherif A.
Published: June 2020

Purpose: To develop a sensitive and accurate ultra-performance liquid chromatography–tandem mass spectrometric (UPLC-MS) method for quantification of ramipril in human plasma.Methods: Ramipril was extracted from biological fluid using equal volumes of n-hexane and propanol (1:1, v/v), and then chromatographed in a suitable C18 column with methanol: 0.1 % HCOOH (4: 1, v/v) as mobile phase. Atorvastatin was used as an internal standard for the  chromatographic separation and quantification. The method was validated according to the United States Food and Drug Administration guidelines for standard indices.Results: Ramipril was determined in the concentration range 0.05 and 1000 ng/mL the validation procedure exhibited a correlation coefficient of 0.9979 + 0.002 (p = 0.05). The studied drug was quantified with lower ceiling of 0.05 ng/mL, and showed an accuracy of 105.00 %.Conclusion: A sensitive UPLC-MS analytical method has been successfully developed for the quantification of ramipril in human plasma. This method can be applied efficiently for the quantification of ramipril in bioavailability and pharmacokinetic studies.

Keywords: Liquid chromatography–tandem mass, Ramipril, Stability, Biological fluids, Plasma
MiR-624-5p enhances cell resistance against cisplatin via PDGFRA/Stat3/PI3K axis in ovarian cancer
Authors: I-Ju Lin , YongJie Tian
Published: June 2020

Purpose: The purpose of this study was to evaluate the role of miR-624-5p in ovarian cancer.Methods: MiR-624-5p expression in ovarian cancer {OC) cell lines and normal cells (NCs) was evaluated and compared the differential miR-624-5p in OC A2780 cells and cisplatin-resistant OC cell line (A2780/DDP). CCK-8 was used to evaluate changes in cell viability of the A2780 and A2780/DDP cell lines as well as silenced miR-624-5p. Western Blot examined the Stat3 and phosphorylated Pi3k. The binding between PDGFRA and miR-624-5p was predicted on Targetscan and verified through Luciferase Reporter Assay. The role of PDGFRA in A2780/DDP by overexpressing PDGFRA was evaluated by RT-qPCR and CCK-8 assays. RT-qPCR assay also measured miR-624-5p expression responsive to different dosages of cisplatin and CCK8 examined viability levels correspondingly. In addition, the interplay of PDGFRA and miR-624-5p by combined downregulation of both miR-624-5pand PDGFRA were evaluated.Results: OC cells had higher miR-624-5p expression than NCs but lower compared to cisplatinresistant A2780/DDP cells. A2780/DDP cells had higher viability than OC cell line A2780. Stat3 and phosphorylated PI3K were activated in A2780/DDP cells. Silencing miR-624-5p led to lower viability inA2780/DDP cells. miR-624-5p expression dropped as the cisplatin concentration increased, resulting in decreasing viability respectively. Luciferase Reporter assay validated the binding of miR-624-5p and PDGFRA in A2780/DDP cells. Overexpressed PDGFRA induced lower cell viability in A2780/DDP cells. Downregulation of PDGFRA partially restored the lowered viability and inhibited Stat3 as well as phosphorylated Pi3k induced by miR-624-5p inhibitor.Conclusion: MiR-624-5p could add to the cellular resistance to cisplatin in OC in-vitro model, which indicated that it might help unveil the mystery of drug-resistance in clinical stage of ovarian cancer.

Keywords: MiR-624-5p, resistance, cisplatin, PDGFRA/Stat3/PI3K, ovarian cancer
Cytochrome P450 expression-associated multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD) in HepG2 cells
Authors: Sukkasem Nadta , Chatuphonprasert Waranya , Jarukamjorn Kanokwan
Published: June 2020

Purpose: To establish a free fatty acid (FFA)-induced non-alcoholic fatty liver disease (NAFLD) model in HepG2 cells.Methods: HepG2 cells were incubated with 0.1, 1, or 5 mM oleic acid (OA) or palmitic acid (PA) for 24 h. Histological features were examined by oil-red-O staining. Expression levels of metabolic genes (peroxisome proliferator activated receptors α/γ, sterol regulatory element binding proteins 1a/1c, acetyl-CoA carboxylase, acyl-CoA oxidase, and fatty acid synthase), antioxidative genes (catalase and superoxide dismutases 1/2), and  cytochrome P450 genes (CYP1A2, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11) were determined by reverse transcription-real time polymerase chain reaction (RT-qPCR).Results: Intracellular lipid storage was observed in cells treated with 1 mM OA or PA while cell shrinkage was present at 5 mM concentrations of both. Expression of all metabolic genes were elevated by 1 mM PA and 5 mM OA and PA. Expression of all antioxidative genes were diminished by 5 mM OA whereas 5 mM PA only reduced superoxide dismutase-2 expression. Expression of CYP1A2, CYP2D6, and CYP3A4 genes were down-regulated by both FFAs, CYP2C19 was induced by PA, while CYP2E1 and CYP4A11 were up-regulated in a concentration-dependent manner.Conclusion: PA was the more potent steatogenic agent in an OA- or PA- induced NAFLD model in HepG2 cells. Increase in intracellular hepatic lipid and expression of metabolic genes, suppression of antioxidative genes, suppression of CYP1A2, CYP2D6, and CYP3A4, and induction of CYP2E1 andCYP4A11 correlated with the multiple-hit pathogenesis model of NAFLD. These findings suggest that PA-induced NAFLD model in HepG2 cells is a suitable in vitro model for studying novel therapeutic approaches to NAFLD treatment.

Keywords: NAFLD, Multiple-hit pathogenesis, Free fatty acid, Oleic acid, Palmitic acid
Protective effects of 4, 5-O-dicaffeoylquinic acid against mouse sepsis via down-regulation of TNF-α, IL-6 and IL-8
Authors: Wang XiaoBo , Wu JianHua , Ni BuKao
Published: June 2020

Purpose: To investigate the protective effects of 4, 5-O-dicaffeoylquinic acid (DCQA) isolated from Xanthium sibiricum Patr. against mouse sepsis caused by cecal ligation/puncture (CLP) in vivo, as well as the molecular mechanisms of action involved.Methods: DCQA (7.5, 15, and 30 mg/kg/day) were administered to the mice with sepsis and the survival rate was obtained. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were examined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the lipopolysaccharide (LPS) neutralizing ability of DCQA (2, 4, and 8 μg/mL) was measured using limulus amebocyte lysate (LAL) test in vitro. Furthermore, the effect of DCQA (10, 20, and 40 μg/mL) on mRNA expression of TNF-α, IL-6, and IL-8 in LPS (100 ng/mL)-treated RAW 264.7 cells was assessed using quantitative real time-polymerase chain reaction (RT-qPCR) assay.Results: DCQA significantly improved the survival rate of mice with sepsis caused by CLP (35, 50, and 65 %, respectively vs. 15 % for control, p < 0.05). LPS levels fell on co-incubation with DCQA in vitro. Moreover, ELISA and RT-qPCR results revealed that DCQA treatment lowered tendency in the mRNA expression of TNF-α, IL-6, and IL-8 (p < 0.01).Conclusion: DCQA exhibits protective effects against sepsis in mice mediated by downregulating TNF-α, IL-6, and IL-8. Further studies, in animals and humans are requied to determine the safety and efficacy of DCQA in both animal and clinical management of sepsis.

Keywords: Xanthium sibiricum, 4,5-O-Dicaffeoylquinic acid, Sepsis, Cecal ligation and puncture, Lipopolysaccharide, TNF-α, IL-6, IL-8
Anhuienoside C ameliorates atherosclerosis in rats via regulation of the NFκB/eNOS/NO signaling pathway
Authors: Xu Xianghua , Ma Qiang , Qin Hao , Zhang Junbo , Zhang Bo , Pang Honggang
Published: June 2020

Purpose: To investigate the protective effect of anhuienoside C (AC) against high cholesterol dietinduced atherosclerosis in a rat model.

Methods: Atherosclerosis was induced in rats by administration of high fat diet for 8 weeks, and AC (20 and 40 mg/kg) was administered orally. The effect of AC was determined by assessing serum lipid profiles and mediators of inflammation, as well as oxidative stress parameters in aortic tissue using enzyme-linked immunosorbent assay (ELISA). Western blot assay and reverse transcription polymerase chain reaction (RT-PCR) were used for the evaluation of protein expressions.

Results: Serum levels of total cholesterol (TC), triglycerides (TGs), high density lipoprotein (HDL), low density lipoprotein (LDLP), and IL-1β, IL-18, TNF-α and NF-κB were significantly reduced in AC-treated group, relative to atherosclerotic rats (p < 0.01). Moreover, parameters of oxidative stress were attenuated in the aortic tissues of AC-treated group, when compared with atherosclerotic rats. There was significant increase in eNOS expression, and marked decrease in the expressions of MAPK and NF-kB protein in the aortic tissue homogenate of AC treated group, relative to atherosclerotic group (p <0.01). Treatment with AC attenuated the mRNA expressions of ICAM-1, VCAM-1 and MCP-1 in aortic tissue of the atherosclerotic rats.

Conclusion: These results reveal that AC prevents atherosclerosis in rats by modulating the NFκB/eNOS/NO signaling pathway, and thus, can thus potentially be developed as anti-atherosclerotic agent.

Keywords: Anhuienoside C, Atherosclerosis, Inflammation, Oxidative stress, Cholesterol
Deficiencies in paediatric research applications delaying ethics committee approval
Authors: Bergstraesser Eva , Nadal David , Özgü Hilal , Kleist Peter
Published: June 2020

BACKGROUND
A clinical research application must be submitted for approval by a competent ethics committee (EC) before a study can be executed. There is very limited information on how such submissions could be optimised, especially regarding research in children and adolescents, which requires particular caution and age-adapted patient information.

METHODS
We assessed all research applications from the University Children’s Hospital Zurich submitted to the EC of the Canton of Zurich in 2014–2015, i.e., in the first two years after Switzerland’s new Human Research Act came into effect. Moreover, we validated our findings by assessing a randomly selected sample of applications from the same hospital in 2018–2019.

RESULTS
We assessed a total of 86 applications from 2014–2015, originating from 29 departments and sub-specialties. The EC judged that it was not responsible for three applications and declined an assessment for another three because the studies had already been conducted. Thus, we included 80 applications in the present analysis (18 clinical trials, 52 research projects, 10 further use projects). Applicants withdrew four applications before the EC’s final decision and the EC rejected two after assessment. The EC had objections in 46 (62%) of the remaining 74 applications. Formal, including formal legal, objections (n = 503) and legal objections (n = 287) accounted for the vast majority of objections. There were also 71 ethical and 82 scientific objections. The most frequent formal and formal legal objections were incomplete or missing age-adapted patient information (49%) and incorrect templates for informed consent and signature forms (46%). A review of the 20 randomly selected applications from 2018–2019 confirmed that four out of the five most frequent deficiencies relating to informed consent were identical to those observed in the 2014–2015 applications.

CONCLUSIONS
Careful preparation of submission documents by the investigators and close adherence to formal and legal requirements have the potential to considerably optimise and expedite the EC review process, and thus the commencement of the clinical research.
Frailty, underweight and impaired mobility are associated with institutionalisation after post-acute care
Authors: Tröster Thomas , Thalmann Marion , Fischer Karina , Bieri-Brüning Gabriela , Beeler Patrick E. , Bischoff-Ferrari Heike A. , Gagesch Michael
Published: June 2020

AIMS OF THE STUDY
Post-acute care (PAC) is intended for older adult patients who are unable to return home directly after acute hospitalisation but who do not otherwise qualify for specific rehabilitation. However, data on potential predictors of PAC outcomes remain limited. Our aim was to identify patient characteristics upon admission to PAC that are associated with subsequent institutionalisation.

METHODS
Prospective cohort study enrolling 140 former acute care inpatients aged 60 and older who were referred to PAC units at nursing homes in Zurich, Switzerland.

MEASURES
Geriatric assessment at admission included Barthel Index (BI), Short Physical Performance Battery (SPPB), frailty status (Fried phenotype), nutrition and cognitive status. Logistic regression was used to determine statistically significant associations.

RESULTS
Mean age was 84.1 (standard deviation [SD] 8.6) years; 62.9% of participants were women. Mean body mass index (BMI) was 25.0 (SD 5.8) kg/m2, with 12.1% being underweight (BMI <20 kg/m2). Mean BI at admission was 62.1 (SD 19.1), mean SPPB score was 5.2 (SD 2.8), and 55% were frail (≥3 Fried criteria present). After a mean length of stay in PAC of 30.9 (SD 16.5) days, 48.6% were institutionalised. Patients who were frail at admission had a 2.97-fold higher (odds ratio [OR] 2.9,7 95% confidence interval [CI] 1.04–8.42), and patients who were underweight had a 4.94-fold higher (OR 4.94, 95% CI 1.11–22.01) chance of institutionalisation. Conversely, each points increment on the SBBP score lowered the likelihood of institutionalisation by 23% (OR 0.77, 95% CI 0.65–0.92).

CONCLUSIONS
Frailty, low SPPB score and being underweight at admission to PAC were significantly associated with a higher chance of subsequent institutionalisation. Strategies to improve these factors could improve PAC outcomes.
Use of Information Sources and Knowledge of Child Sexual Abuse in Ogun State, Nigeria
Authors: Omole Funke , Olatunji Rotimi , Oyero Olusola , Okorie Nelson , Adesina Evaristus
Published: June 2020

Child Sexual Abuse (CSA) constitutes a severe threat to the social well-being of not only children but extends to their families, societies. In response to the global challenge of reducing the growing effect of CSA, this study investigated the use of information sources on child sexual abuse in Ogun State. The study further tested two hypothesis to find out if communication channels for child sexual abuse education has no significant influence on the knowledge of the residents of Ogun State as well as Communication channels for child sexual abuse has no significant influence on the perception of residents of Ogun State. The study revealed that residents of Ogun state Nigeria depended on the internet as an information source for child sexual abuse. In addition, it was revealed that communication channels for child sexual abuse has significant influence on the knowledge and perception of the residents of Ogun State. Consequent upon these findings, the study recommends an urgent development of advocacy messages against CSA in form of edutainment, drama, songs that will fit the new media platform
De la ontología al arte. Los caminos medievales de la belleza
Authors: García-Lomas Gago OSB Fr. Luis Javier
Published: June 2020

El presente artículo pretende rastrear los caminos por los que la noción de belleza ha transitado durante el pensamiento medieval, identificando dos grandes líneas de pensamiento: la belleza ontológica y la belleza formal. Ambos vienen a coincidir en la reflexión de Tomás de Aquino, cuya mirada abrirá el camino hacia una reflexión más autónoma del arte.
NOTAS SOBRE NARRATIVAS AUTOBIOGRÁFICAS DE AUTORES SURDOS
Authors: Tonani do Patrocínio Paulo Roberto
Published: June 2020

O presente artigo analisa narrativas de natureza autobiográfica publicadas em língua portuguesa assinadas por autores surdos brasileiros com o objetivo de investigar os modos de autorrepresentação da diferença surda, colocando em foco a heterogeneidade de tal experiência. O referencial teórico adotado para dar materialidade ao objetivo traçado dialoga com pesquisas sobre narrativas autobiográficas e outras formas de escrita de si, além das contribuições de pesquisadores vinculados ao campo dos Estudos Culturais e em especial dos Estudos Surdos.
A Situational Analysis Of Issues And Challenges Faced By Social Work Students During Their Field Placements In Karachi, Pakistan
Authors: Riaz Sakina
Published: June 2020

Field work is viewed as the important pillar of Social Work profession. The aim of this study is to examine the issues and challenges faced by the Social Work Students during their Field Placement in different agency settings. This study articulates the teaching philosophy, conceptual framework, and fieldwork practices followed by Student of Social Work Department at Karachi University. Qualitative research design was employed in this study and purposive sampling strategy was used for data collection. The results of the study drawn that the main constraints stem from a lack of social work agency supervisors, lack of training for agency supervisors, the lack of a fieldwork curriculum and nonexistent or insufficient funding of fieldwork related activities.