69 research outputs found
Trimetazidine Alleviates Bleomycin-Induced Pulmonary Fibrosis by Targeting the Long Noncoding RNA CBR3-AS1-Mediated miRNA-29 and Resistin-Like Molecule alpha 1: Deciphering a Novel Trifecta Role of LncRNA CBR3-AS1/miRNA-29/FIZZ1 Axis in Lung Fibrosis
No full textAbdullah R Alzahrani,1 Doaa I Mohamed,2 Hebatallah H Abo Nahas,3 Dalia Alaa El-Din Aly El-Waseef,4 Abdulmalik S Altamimi,5 Ibrahim H Youssef,6 Ibrahim Abdel Aziz Ibrahim,1 Soha MY Mohamed,7 Yasmine Gamal Sabry,7 Alaa H Falemban,1 Nasser Attia Elhawary,8 Ghazi A Bamagous,1 Mariusz Jaremko,9 Essa M Saied10,11 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 3Zoology Department, Faculty of Science, Port Said University, Port Said, Egypt; 4Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 5Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia; 6Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 7Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 8Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia; 9Smart-Health Initiative and Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia; 10Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt; 11Institute for Chemistry, Humboldt Universität Zu Berlin, Berlin, GermanyCorrespondence: Essa M Saied, Institute for Chemistry, Humboldt Universität zu Berlin, Berlin, 12489, Germany, Email [email protected]: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes.Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis.Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P< 0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p< 0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=− 0.7535, p< 0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis.Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis. Keywords: lung fibrosis, long noncoding RNA CBR3-AS1, miRNA-29, FIZZ1, trimetazidine, histopatholog
Hydroethanolic Extract of <i>Urtica dioica</i> L. (Stinging Nettle) Leaves as Disaccharidase Inhibitor and Glucose Transport in Caco-2 Hinderer
No full textHerbal treatment for diabetes mellitus is widely used. The pharmacological activity is thought to be due to the phenolic compounds found in the plant leaves. The present study aims to investigate the phytochemical composition of Urtica dioica (UD) hydroethanolic extract and to screen its antidiabetic activity by disaccharidase hindering and glucose transport in Caco-2 cells. The results have shown that a total of 13 phenolic compounds in this work, viz. caffeic and coumaric acid esters (1, 2, 4–7, 10), ferulic derivative (3), and flavonoid glycosides (8, 9, 11–13), were identified using HPLC-DAD-ESI/MS2. The most abundant phenolic compounds were 8 (rutin) followed by 6 (caffeoylquinic acid III). Less predominant compounds were 4 (caffeoylquinic acid II) and 11 (kaempferol-O-rutinoside). The UD hydroethanolic extract showed 56%, 45%, and 28% (1.0 mg/mL) inhibition level for maltase, sucrase, and lactase, respectively. On the other hand, glucose transport was 1.48 times less at 1.0 mg/mL UD extract compared with the control containing no UD extract. The results confirmed that U. dioica is a potential antidiabetic herb having both anti-disaccharidase and glucose transport inhibitory properties, which explained the use of UD in traditional medicine
A Comparative Evaluation of ESBL Production and Carbapenem Resistance in UTIs Before and During COVID-19
No full textBackground:
The COVID-19 pandemic has heightened the urgency to address antibiotic resistance, particularly ESBL and carbapenem-resistant UTIs. Our study seeks to assess the pandemic's effect on the prevalence of these resistances, comparing data from before and during COVID-19. By identifying trends in resistance patterns, we aim to enhance antibiotic stewardship and inform healthcare policies. Understanding the pandemic's impact on ESBL and carbapenem resistance is vital for guiding clinical practices and public health initiatives in tackling antibiotic resistance.
Methods:
This retrospective study, conducted at King Fahad Medical City in Riyadh, Saudi Arabia, analyzed positive urine cultures from January 2018 to December 2022 to assess the prevalence of antibiotic resistance among UTIs. Using WHO-recommended semiquantitative culturing methods on CLED and blood agar, bacterial isolates were identified via the BD Phoenix system and antimicrobial susceptibility was assessed following CLSI guidelines. ESBL detection employed the Double-Disc Synergy Test. Data analysis involved SPSS for statistical evaluation, utilizing chi-square and t-tests for categorical and continuous variables, respectively, and logistic regression to explore associations between variables and antibiotic resistance, with significance set at p [SJEMed 2024; 5(1.100): S19-S19
Axial Oscillation Tool Significantly Mitigates the Vibration Level and Enhances Drilling Performance in Conjunction With Standard RSS Systems
No full textImproved constraints on models of glacial isostatic adjustment: a review of the contribution of ground-based geodetic observations
No full textThe provision of accurate models of Glacial Isostatic Adjustment (GIA) is presently a priority need in climate studies, largely due to the potential of the Gravity Recovery and Climate Experiment (GRACE) data to be used to determine accurate and continent-wide assessments of ice mass change and hydrology. However, modelled GIA is uncertain due to insufficient constraints on our knowledge of past glacial changes and to large simplifications in the underlying Earth models. Consequently, we show differences between models that exceed several mm/year in terms of surface displacement for the two major ice sheets: Greenland and Antarctica. Geodetic measurements of surface displacement offer the potential for new constraints to be made on GIA models, especially when they are used to improve structural features of the Earth's interior as to allow for a more realistic reconstruction of the glaciation history. We present the distribution of presently available campaign and continuous geodetic measurements in Greenland and Antarctica and summarise surface velocities published to date, showing substantial disagreement between techniques and GIA models alike. We review the current state-of-the-art in ground-based geodesy (GPS, VLBI, DORIS, SLR) in determining accurate and precise surface velocities. In particular, we focus on known areas of need in GPS observation level models and the terrestrial reference frame in order to advance geodetic observation precision/accuracy toward 0.1 mm/year and therefore further constrain models of GIA and subsequent present-day ice mass change estimate
Decline in ESBL Production and Carbapenem Resistance in Urinary Tract Infections among Key Bacterial Species during the COVID-19 Pandemic
No full textThe COVID-19 pandemic has led to significant changes in healthcare practices, including increased antibiotic usage. This study aimed to investigate the impact of the pandemic on the prevalence of extended-spectrum β-lactamase (ESBL) production and carbapenem resistance among key bacterial species causing urinary tract infections (UTIs). Conducted at King Fahad Medical City in Riyadh from January 2018 to December 2022, the study analyzed urine samples from 9697 UTI patients. Patients were categorized into ‘pre-COVID-19’ and ‘during COVID-19’ groups. Bacterial isolates were identified, and antimicrobial susceptibility testing was performed following guidelines. ESBL production was detected using the Double-Disc Synergy Test. Escherichia coli and Klebsiella pneumoniae were the main pathogens. During the pandemic, ESBL production decreased in E. coli by 1.9% and in K. pneumoniae by 6.0%. Carbapenem resistance also declined, with E. coli displaying a 1.2% reduction and K. pneumoniae and Pseudomonas aeruginosa displaying 10.7% and 7.9% reductions, respectively. Notably, logistic regression analysis revealed that the odds of ESBL presence were 10% lower during the COVID-19 pandemic (OR 0.91; 95% CI 0.83–0.99; p = 0.040), and there was a significant reduction in the odds of carbapenem resistance (OR 0.43; 95% CI 0.37–0.51; p < 0.001). This study reveals a significant decrease in ESBL production and carbapenem resistance among UTI pathogens during the COVID-19 pandemic, hinting at the impact of modified antibiotic and healthcare approaches. It emphasizes the need for persistent antimicrobial resistance surveillance and policy adaptation to address resistance challenges, offering key directions for future public health actions
Semi-kinematic geodetic reference frame based on the ITRF2014 for Malaysia
No full textMalaysia is located at the stable part of the tec-tonic Sundaland platelet in SE Asia. The platelet is surrounded in almost every direction by tectonically active convergent boundaries, at which the Philippine Sea, the Australian and the Indian Plates are subducting respectively from the East, South and West.The current Malaysia geodetic reference frame called MGRF2000 is a static reference frame and hence did not incorporate the effects of plate motion and the ensuing deformation from (megath-rust) earthquakes. To prevent degradation of Continuously Operating Reference Station (CORS) coordinates, a new time-dependent national reference frame was developed. Taking advantage of the availability of the GNSS data of the CORS network in Malaysia, notably the Malaysia Active GPS System (MASS) and Malaysia Real-Time Kinematic GNSS Network (MyRTKnet), a more accurate and robust Malaysian geodetic reference frame was determined, fully aligned and compatible with ITRF2014. The cumulative solution obtained from stacking Malaysian CORS position time series formed the basis of the new MGRF2020 realization. It consists of 100+ station positions at epoch 2020.0, station velocities and Post-Seismic Deformation (PSD) parametric models for stations subjected to major earthquakes. The (1999-2018) position time series exhibit Weighted Mean Root Square (WRMS) values of 3.0, 3.2 and 7.6 mm in respectively the East, North and Vertical components. A new semi-kinematic geodetic datum (GDM2020) for Malaysia, useable for GIS, mapping and cadastre applications is proposed to replace the existing static datum (GDM2000). A transformation suite to convert the spatial databases from GDM2000 to GDM2020 was also developed. Astrodynamics & Space Mission
Turmeric oil-fortified nutraceutical-SNEDDS: An approach to boost therapeutic effectiveness of dapagliflozin during treatment of diabetic patients
No full textEffectiveness of granisetron in controlling pediatric gastroenteritis-related vomiting after discharge from the ED
No full textObjective: The objective of the study is to determine the efficacy of oral granisetron (a long-acting 5-HT3 receptor antagonist) in stopping vomiting subsequent to discharge from emergency department (ED), in 6-month-old to 8-year-old patients with gastroenteritis-related vomiting and dehydration, who had failed an initial trial of oral rehydration (ORT). Methods: Eligible patients were offered ORT on a slowly advancing schedule. Patients who tolerated the initial ORT were discharged home. Patients who vomited were randomized to receive either 40 μg-kg of granisetron or placebo, and ORT was resumed. Patients who tolerated the postrandomization ORT were discharged home with another dose of the study drug. Parents were contacted by telephone every 24 hours until complete resolution of symptoms. The primary outcome was the proportion of patients with vomiting at 24 hours. Results: Of the 900 eligible patients, 537 (60percent) tolerated the initial ORT and were discharged home. Of the patients who vomited during the initial ORT, 165 were included in the final study sample (placebo, n = 82; granisetron, n = 83). There was no statistically significant difference in the proportion of patients with vomiting at 24 hours (granisetron, n = 38; placebo, n = 45; odds ratio, 0.64; 95percent confidence interval, 0.34-1.19; P = .16). A similar trend in the proportion of patients with vomiting was noted for the entire follow-up period (granisetron, n = 43; placebo, n = 47; odds ratio, 0.73; P = .33; 95percent confidence interval, 0.39-1.36). Conclusion: Granisetron was not effective in controlling gastroenteritis-related vomiting subsequent to discharge from ED. It did not change the expected course of the illness. © 2014 Elsevier Inc. All rights reserved.Carter B, 2012, BMJ OPEN, V2; Fonseca BK, 2004, ARCH PEDIAT ADOL MED, V158, P483, DOI 10.1001-archpedi.158.5.483; Freedman SB, 2006, NEW ENGL J MED, V354, P1698, DOI 10.1056-NEJMoa055119; Guarino A, 2008, J PEDIATR GASTR NUTR, V46, pS81, DOI 10.1097-MPG.0b013e31816f7b16; Kovac Anthony L, 2007, Paediatr Drugs, V9, P47, DOI 10.2165-00148581-200709010-00005; Matson DO, PREVENTION TREATMENT; Montori VM, 2005, JAMA-J AM MED ASSOC, V294, P2203, DOI 10.1001-jama.294.17.2203; Phillips RS, 2010, COCHRANE DB SYST REV, DOI 10.1002-14651858.CD007786.pub2; Pocock SJ, 2006, CLIN TRIALS, V3, P513, DOI 10.1177-1740774506073467; Ramsook C, ANN EMERG MED, V39, P397; Reid SR, 1996, ANN EMERG MED, V28, P318, DOI 10.1016-S0196-0644(96)70032-X; Roslund G, 2008, ANN EMERG MED, V52, P22, DOI 10.1016-j.annemergmed.2007.09.010; Taketomo C, 2013, LEXICOMP PEDIAT NEON, P891; World Health Organization Oral Rehydration Salts, 2006, WHO OR REH SALTS; Yilmaz HL, 2010, ANN EMERG MED, V510
Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents in the Mediterranean Region of Europe
No full textLittle is known about the prevalence of functional gastrointestinal disorders (FGIDs) in children from the Mediterranean area of Europe. We aimed to assess the prevalence of FGIDs in children and adolescents in this region
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