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1.
Dev Biol ; 512: 70-88, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38729405

ABSTRACT

In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast. We have found that we can revert zebrafish support cells back to a migratory progenitor state by pharmacologically altering the signaling environment to mimic that of the migratory primordium, with active Wnt signaling and repressed FGF signaling. The reverted supporting cells migrate anteriorly and posteriorly along the horizontal myoseptum and will re-epithelialize to form an increased number of neuromasts along the midline when the pharmacological agents are removed. These data demonstrate that supporting cells can be readily reprogrammed to a migratory multipotent progenitor state that can form new sensory neuromasts, which has important implications for our understanding of how the lateral line system matures and expands in fish and also suggest avenues for returning mammalian supporting cells back to a proliferative state.


Subject(s)
Cell Movement , Lateral Line System , Zebrafish Proteins , Zebrafish , Animals , Zebrafish/embryology , Lateral Line System/embryology , Lateral Line System/cytology , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Wnt Signaling Pathway , Fibroblast Growth Factors/metabolism , Cell Differentiation , Stem Cells/metabolism , Stem Cells/cytology , Signal Transduction , Cellular Reprogramming
2.
Article in English | MEDLINE | ID: mdl-39189059

ABSTRACT

BACKGROUND: Chronic systemic anticoagulation use is prevalent for various thromboembolic conditions. Anticoagulation (usually through heparin products) is also recommended for the initial management of non-ST-elevation myocardial infarction (NSTEMI). AIMS: To evaluate the in-hospital outcomes of patients with NSTEMI who have been on chronic anticoagulation. METHODS: Using the National Inpatient Sample (NIS) years 2016-2020, NSTEMI patients and patients with chronic anticoagulation were identified using the appropriate International Classification of Diseases, 10th version (ICD-10) appropriate codes. The primary outcome was all-cause in-hospital mortality while the secondary outcomes included major bleeding, ischemic cerebrovascular accident (CVA), early percutaneous coronary intervention (PCI) (i.e., within 24 h of admission), coronary artery bypass graft (CABG) during hospitalization, length of stay (LOS), and total charges. Multivariate logistic or linear regression analyses were performed after adjusting for patient-level and hospital-level factors. RESULTS: Among 2,251,914 adult patients with NSTEMI, 190,540 (8.5%) were on chronic anticoagulation. Chronic anticoagulation use was associated with a lower incidence of in-hospital mortality (adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.65-0.73, p < 0.001). There was no significant difference in major bleeding (aOR: 0.95, 95% CI: 0.88-1.0, p = 0.15) or ischemic CVA (aOR: 0.23, 95% CI: 0.03-1.69, p = 0.15). Chronic anticoagulation use was associated with a lower incidence of early PCI (aOR: 0.78, 95% CI: 0.76-0.80, p < 0.001) and CABG (aOR: 0.43, 95% CI: 0.41-0.45, p < 0.001). Chronic anticoagulation was also associated with decreased LOS and total charges (adjusted mean difference [aMD]: -0.8 days, 95% CI: -0.86 to -0.75, p < 0.001) and (aMD: $-19,340, 95% CI: -20,692 to -17,988, p < 0.001). CONCLUSIONS: Among patients admitted with NSTEMI, chronic anticoagulation use was associated with lower in-hospital mortality, LOS, and total charges, with no difference in the incidence of major bleeding.

3.
Biologicals ; 85: 101726, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37979341

ABSTRACT

Hepatitis B virus (HBV) is responsible for most of the viral hepatitis worldwide. HBV is a partially double stranded DNA virus that is composed of four main open reading frames (ORFs) encoding its important antigens, namely hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), HBV polymerase and hepatitis B X antigen (HBxAg). In this study, we report a successful method for the cloning and expression of HBcAg. The ORF of HBcAg was successfully amplified using polymerase chain reaction (PCR), cloned into the expression vector pRSET-B and transformed to Escherichia coli (E. coli) BL-21 (DE3) pLysS strain for protein expression. Successful expression of HBcAg was accomplished, in which an induced protein with a molecular weight of 24 kDa was obtained and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. The produced HBcAg was successfully used for the diagnosis of HBV infected patient through detection of antibodies against HBcAg (anti-HBcAg) in the serum of the patient utilizing Western blotting. Overall, this study provides a simple, convenient and efficient protocol for the production of HBcAg that can be used as an important candidate to study the diagnosis and prognosis of HBV disease, as well as for understanding the epidemiological prevalence of HBV cases and production of anti-HBcAg.


Subject(s)
Hepatitis B virus , Hepatitis B , Humans , Hepatitis B virus/genetics , Hepatitis B Core Antigens/genetics , Hepatitis B Core Antigens/analysis , Escherichia coli/genetics , Escherichia coli/metabolism , Hepatitis B/diagnosis , Hepatitis B Surface Antigens , DNA, Viral
4.
J Sci Food Agric ; 104(4): 2245-2251, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37941431

ABSTRACT

BACKGROUND: Three different organic sunflower seed cakes, produced from seeds differing in the content of their hulls, were extracted by two different extraction methods - conventional extraction (CE) and ultrasound-assisted extraction (UAE). The total phenolic compound (TPC) content of the extracts was evaluated using Folin-Ciocâlteu reagent (FCR) and high-performance liquid chromatography (HPLC). The antioxidant capacity of extracts was evaluated with the Trolox equivalent antioxidant capacity (TEAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. RESULTS: The results showed that both extracts displayed high TPC content and antioxidant capacity. The UAE method showed significantly higher TPC content and antioxidant capacity values than CE. Individual phenolic compounds such as chlorogenic acid (CGA) isomers (3-, 4- and 5-O-caffeoylquinic acids), di-CGA isomers, and feruloylquinic and coumaroylquinic acids were identified according to their exact masses by HPLC coupled to time-of-flight mass spectrometry. CONCLUSION: The results revealed that the UAE method could be used effectively to facilitate the extraction of phenolic compounds from sunflower seed cake. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Subject(s)
Antioxidants , Helianthus , Antioxidants/chemistry , Ultrasonics , Phenols/chemistry , Plant Extracts/chemistry , Seeds/chemistry
5.
Arch Toxicol ; 97(3): 805-817, 2023 03.
Article in English | MEDLINE | ID: mdl-36695871

ABSTRACT

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.


Subject(s)
Chickens , T-2 Toxin , Humans , Animals , Male , Chickens/metabolism , T-2 Toxin/toxicity , Dietary Supplements , Diet , Antioxidants/metabolism , Oxidation-Reduction , Apoptosis , Inflammation , Homeostasis , Animal Feed/analysis
6.
Int J Mol Sci ; 24(10)2023 May 15.
Article in English | MEDLINE | ID: mdl-37240151

ABSTRACT

Ribosomal S6 kinases (S6Ks) are critical regulators of cell growth, homeostasis, and survival, with dysregulation of these kinases found to be associated with various malignancies. While S6K1 has been extensively studied, S6K2 has been neglected despite its clear involvement in cancer progression. Protein arginine methylation is a widespread post-translational modification regulating many biological processes in mammalian cells. Here, we report that p54-S6K2 is asymmetrically dimethylated at Arg-475 and Arg-477, two residues conserved amongst mammalian S6K2s and several AT-hook-containing proteins. We demonstrate that this methylation event results from the association of S6K2 with the methyltransferases PRMT1, PRMT3, and PRMT6 in vitro and in vivo and leads to nuclear the localisation of S6K2 that is essential to the pro-survival effects of this kinase to starvation-induced cell death. Taken together, our findings highlight a novel post-translational modification regulating the function of p54-S6K2 that may be particularly relevant to cancer progression where general Arg-methylation is often elevated.


Subject(s)
Biological Phenomena , Ribosomal Protein S6 Kinases, 90-kDa , Animals , Phosphorylation , Ribosomal Protein S6 Kinases, 90-kDa/genetics , Ribosomal Protein S6 Kinases, 90-kDa/metabolism , Ribosomal Protein S6 Kinases/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Mammals/metabolism
7.
Catheter Cardiovasc Interv ; 100(2): 245-253, 2022 08.
Article in English | MEDLINE | ID: mdl-35758231

ABSTRACT

OBJECTIVE: To examine the rate of readmission for permanent pacemaker (PPM) implantation with early versus late discharge after transcatheter aortic valve replacement (TAVR). BACKGROUND: There is a current trend toward early discharge after TAVR. However, paucity of data exists on the impact of such practice on readmissions for PPM implantation. METHODS: The Nationwide Readmission Database 2016-2018 was queried for all hospitalizations where patients underwent TAVR. Hospitalizations were stratified into early (Days 0 and 1) versus late (≥Day 2) discharge groups. Observations in which PPM was required in the index admission were excluded. Multivariable regression analyses involving patient- and hospital-related variables were utilized. The primary outcome was 90-day readmission for PPM implantation. RESULTS: The final analysis included 68,482 TAVR hospitalizations, 20,261 (29.6%) with early versus 48,221 (70.4%) with late discharge. Early discharge after TAVR increased over the study period (16.2% in 2016 vs. 37.9% in 2018, Ptrend < 0.01). Nevertheless, 90-day readmission for PPM implantation remained stable (1.8% in 2016 vs. 2.0% in 2018, Ptrend = 0.32). The 90-day readmission rate for PPM implantation (2.0% vs. 1.8%; adjusted odds ratio: 1.15; 95% confidence interval: 0.95-1.39; p = 0.15) and median time-to-readmission (5 days [interquartile range, IQR 3-9] vs. 5 days [IQR 3-14], p = 0.92) were similar with early versus late discharge. Similar rates were observed regardless of whether readmission was elective versus not. Early discharge was associated with lower hospitalization cost ($39,990 ± $13,681 vs. $46,750 ± $18,218, p < 0.01) compared with late discharge. CONCLUSION: In patients who did not require PPM during the index TAVR hospitalization, the rate of readmission for PPM implantation was similar with early versus late discharge.


Subject(s)
Aortic Valve Stenosis , Pacemaker, Artificial , Transcatheter Aortic Valve Replacement , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Humans , Patient Discharge , Patient Readmission , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
8.
BMC Ophthalmol ; 22(1): 492, 2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36522705

ABSTRACT

BACKGROUND: The goal of this work is to assess progression of diabetic macular edema (DME) following intravitreal ranibizumab injection compared to subtenon triamcinolone acetonide injection at cataract operation. METHODS: Retrospective analysis of 73 eyes of 65 participant with DME, with central macular thickness (CMT) ≥ 300 µm. The included eyes were separated into three groups; phacoemulsification with intravitreal Ranibizumab injection group, phacoemulsification with subtenon Triamcinolone acetonide injection group and phacoemulsification only group. Main measures involved best corrected visual acuity (BCVA) one week, one month and three months post-operative. The CMT was compared preoperative and postoperative (one and three months). RESULTS: After 1 month of operation, there was a statistical substantial distinction in the median of CMT between ranibizumab & control group (p < 0.001), between subtenon TA & control group (p < 0.001) and in ranibizumab and subtenon TA group (p = 0.023). After 3 months, the variance between ranibizumab & control group was considerable (p < 0.0001) and the variance between subtenon TA & control group was considerable (p = 0.030). CONCLUSIONS: Combined phacoemulsification with intravitreal injections of ranibizumab or subtenon triamcinolone acetonide may prevent further progression in CMT in individuals with DME following cataract operation.


Subject(s)
Cataract , Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Macular Edema/drug therapy , Macular Edema/etiology , Macular Edema/prevention & control , Ranibizumab/therapeutic use , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , Intravitreal Injections , Retrospective Studies , Visual Acuity , Triamcinolone Acetonide/therapeutic use , Glucocorticoids/therapeutic use , Cataract/complications , Treatment Outcome
9.
Molecules ; 28(1)2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36615296

ABSTRACT

This study aims to investigate the effect of magnesium (Mg) doping on the characteristics and antibacterial properties of copper oxide (CuO) nanoparticles (NPs). The Mg-doped CuO NPs were fabricated by the co-precipitation method. NPs were characterized by X-ray Powder Diffraction (XRD), Transmission Electron Microscope (TEM), Energy Dispersive X-ray (EDX) analysis, Fourier Transform Infrared Spectroscopy (FTIR), and Photoluminescence (PL). Broth microdilution, agar-well diffusion, and time-kill assays were employed to assess the antibacterial activity of the NPs. XRD revealed the monoclinic structure of CuO NPs and the successful incorporation of Mg dopant to the Cu1-xMgxO NPs. TEM revealed the spherical shape of the CuO NPs. Mg doping affected the morphology of NPs and decreased their agglomeration. EDX patterns confirmed the high purity of the undoped and Mg-doped CuO NPs. FTIR analysis revealed the shifts in the Cu-O bond induced by the Mg dopant. The position, width, and intensity of the PL bands were affected as a result of Mg doping, which is an indication of vacancies. Both undoped and doped CuO NPs exhibited significant antibacterial capacities. NPs inhibited the growth of Gram-positive and Gram-negative bacteria. These results highlight the potential use of Mg-doped CuO NPs as an antibacterial agent.


Subject(s)
Metal Nanoparticles , Nanoparticles , Anti-Bacterial Agents/chemistry , Magnesium , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Gram-Negative Bacteria/metabolism , Gram-Positive Bacteria/metabolism , Nanoparticles/chemistry , Copper/chemistry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared
10.
Psychiatr Danub ; 34(3): 544-546, 2022.
Article in English | MEDLINE | ID: mdl-36257005

ABSTRACT

There is paucity of Electroconvulsive therapy (ECT) utilization surveys from the Arabian Gulf region and none available from Qatar. There is no literature available on impact of Coronavirus Disease 2019 (COVID-19) pandemic on ECT provision. ECT is a lifesaving treatment in psychiatric practice requiring anesthetic support and there were concerns that redeployment of anesthetists due to COVID-19 pandemic might have comparatively bigger impact on the provision of ECT. These concerns stem from the fact that psychiatric patients often get discriminated against in health care systems; largely due to stigma and the belief among healthcare providers that psychiatric illness is somehow not as serious as other types of medical or surgical illness. In this brief report we present pre-COVID ECT utilization from Qatar. We also report findings on ECT utilization during COVID-19 and compare changes with other elective and non-elective surgeries. ECT provision was down by 40% during March to August 2020 in our setting. The decline in ECT provision was comparable to other elective and non-elective surgeries.


Subject(s)
COVID-19 , Electroconvulsive Therapy , Mental Disorders , Humans , Pandemics , Qatar/epidemiology , Mental Disorders/therapy
11.
World J Urol ; 39(5): 1413-1419, 2021 May.
Article in English | MEDLINE | ID: mdl-32572556

ABSTRACT

PURPOSE: We sought to discuss the updates in the 8th edition (8E) of The American Joint Committee on Cancer (AJCC) staging for penile cancer and to provide relevant evidence associated with the major changes that occurred. METHODS: A comprehensive search of PubMed® and Web of Science® was performed for relevant English language articles from 2004 through 2019. Literature resulting from this search were reviewed and articles pertinent to penile cancer staging changes were included. RESULTS: Modifications were observed in the tumor and nodal staging. In the 8E AJCC, Ta disease indicates noninvasive localized squamous cell carcinoma, which allows for inclusion of other historical variants. T1 is subcategorized into T1a and T1b according to existence of lymphovascular invasion, perineural invasion and high-grade tumor. This subcategorization demonstrates different risks for lymph node (LN) metastases and will affect decision strategy when opting for inguinal lymphadenectomy. Urethral invasion is no longer a differentiator between T2 and T3 disease, as T2 includes invasion of the corpus spongiosum and T3 involves invasion of the corpus cavernosum. For nodal staging, pN1 has been increased from a single LN metastases to two unilateral inguinal LN metastases, while pN2 has been modified to three or more inguinal LN metastases. This change was evidenced by demonstrating no significant difference in disease specific mortality between the previous edition's pN1 and pN2. CONCLUSIONS: The 8E penile cancer staging provides several modifications that have relevant clinical implications in the management of penile cancer. Nevertheless, it requires refinements that allow for better staging of penile tumors.


Subject(s)
Penile Neoplasms/pathology , Humans , Male , Neoplasm Staging
12.
Int J Clin Pract ; 75(11): e14735, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34387909

ABSTRACT

AIM: The coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, China, and quickly escalated into a significant pandemic threat. COVID-19 is associated with variable morbidity and mortality rates, which differ greatly from one country to another. This study aimed to investigate the clinical findings of SARS-CoV-2 infection in different ethnic groups, as well as to identify the radiological manifestations and various biomarkers for the assessment of COVID-19 patients. MATERIALS AND METHODS: The clinical data of 210 COVID-19 patients with respiratory disorders, who attended the chest clinic at Mouwasat Hospital, Jubail, in the Eastern area of the Kingdom of Saudi Arabia from April to May 2020, were thoroughly reviewed. The patients were divided into seven groups based on their ethnicities (Saudi, Egyptian, Nepali, Filipino, Pakistani, Bangladeshi and Indian). The differences in the clinical findings, laboratory data and radiological manifestations between these groups were statistically analysed. RESULTS: The study included 210 COVID-19 patients from seven ethnic groups (Saudi, Egyptian, Nepali, Filipino, Pakistani, Bangladeshi and Indian). Comorbidities were reported among 60.9% of patients, which were significantly higher among Filipinos at 73.3%. Dyspnoea was prevalent in the Saudi and Pakistani groups, while hypoxaemia was prevalent in the Indian group (40%). In terms of laboratory assessment, Bangladesh patients had the highest median of serum ferritin and lactate dehydrogenase (LDH) levels with a significant P value (<.001), while Saudi patients had the highest median of C-reactive protein (CRP) levels with a significant P value (<.001). According to computed tomography (CT) findings, structural destruction was the most common finding in bilateral parenchymal affection among 88.6% of patients. Filipinos and Bangladeshis had the highest morbidity rates. CONCLUSION: There were great variations in clinical, radiological and even laboratory findings among different ethnic groups of COVID-19 patients.


Subject(s)
COVID-19 , Ethnicity , Humans , Male , Pandemics , Retrospective Studies , SARS-CoV-2
13.
Curr Treat Options Oncol ; 22(1): 4, 2020 11 23.
Article in English | MEDLINE | ID: mdl-33230601

ABSTRACT

OPINION STATEMENT: Management of penile cancer represents a challenge to urologic oncologists due to the disease's rarity and sparse data in the literature. Squamous cell carcinoma represents the most common histologic subtype of penile cancer. Penile cancer has a disastrous effect on patients' psychological and physical health. Penile cancer accounts for approximately 1% of cancer deaths in the USA annually. However, in recent years, the management of penile cancer has achieved marked progress in both diagnostic and therapeutic approaches with the intent to avoid radical surgeries. The traditional total penile amputation has been replaced by penile preserving procedures in many patients. Nowadays, total penile amputation (total penectomy) is preserved only for patients with proximal lesions. The introduction of minimally invasive surgical techniques in the management of penile cancer-infiltrated lymph nodes has been reported. Given the dismal prognosis with conventional cytotoxic therapies, new systemic therapies have been investigated in patients with locally advanced or metastatic penile cancer. Multiple studies have shown promising outcomes. All these efforts have resulted in a remarkable improvement in patient quality of life. The objectives of our review are to update clinicians on the advances in the management of penile cancer and to summarize the recent guidelines and recommendations.


Subject(s)
Penile Neoplasms/diagnosis , Penile Neoplasms/therapy , Clinical Decision-Making , Disease Management , Disease Susceptibility , Humans , Incidence , Male , Neoplasm Grading , Neoplasm Staging , Penile Neoplasms/epidemiology , Penile Neoplasms/etiology , Practice Guidelines as Topic , Risk Assessment , Risk Factors , Treatment Outcome
14.
Int J Neurosci ; 130(5): 515-521, 2020 May.
Article in English | MEDLINE | ID: mdl-31790618

ABSTRACT

Introduction: Multiple sclerosis (MS) is an immune-mediated disorder. Long noncoding RNAs (lncRNAs, LncR, Linc RNA) have role in many autoimmune and inflammatory disorders, including MS. LincR-Gng2-5 AS locus in T helper 1 cell (TH1) and LincR-Epas1-3AS in T helper 2 cell (TH2) cell were located in a genomic region rich in genes code for proteins with immune regulatory function. Our aim was to evaluate the LincR-Gng2-5' and LincR-Epas1-3'AS fold change in blood of MS patients versus healthy controls and correlate it with disease severity, assessed based on Expanded Disability Status Scale (EDSS).Material and Methods: Sixty MS patients 42 relapsing remitting (RR, RRMS), 18 Secondary progressive (SP, SPMS) and sixty controls (age-matched and sex-matched) were studied. Blood of patients and control group undergone the investigation of LincR-Gng2-5' and LincR-Epas1-3'AS fold change by real-time PCR. Fold change >2 and p < .05 represent significant result.Results: LincR-Gng2-5' was significantly upregulated in MS patients with mean fold change (2.559) and (p = .03). Meanwhile, LincR-Epas1-3'AS levels were significantly downregulated with mean fold change (0.5964) and (p < .004). Patients with SP showed a significantly higher level of LincR-Gng2-5-fold change (3.71 ± 0.7) than that of RR (1.33 ± 0.3). LincR-Epas1-3'AS was markedly reduced among SP (0.43 ± 0.2) than that of RR (0.66 ± 0.1) but with no significant difference. As regards disease severity (EDSS); there was a significant positive correlation with LincR-Gng2-5 and negative correlation with LincR-Epas1-3'AS. LincR- Gng2-5and LincR-Epas1-3'AS, both are dysregulated in MS patient suggesting a role in disease pathogenesis.Conclusion: LincR-Gng2-5 AS and LincR-Epas1-3'AS fold change are correlated to MS severity (EDSS).


Subject(s)
Multiple Sclerosis, Chronic Progressive/blood , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/physiopathology , RNA, Long Noncoding/blood , RNA, Long Noncoding/chemistry , Adult , Case-Control Studies , Cross-Sectional Studies , Egypt , Female , Humans , Male , Severity of Illness Index
15.
Curr Ther Res Clin Exp ; 92: 100589, 2020.
Article in English | MEDLINE | ID: mdl-32714471

ABSTRACT

BACKGROUND: Gallotannin (GT) is a polyphenol that possesses interesting anticancer properties. However, the mechanisms underlying its antitumor effects have not been well defined. OBJECTIVE: This study was designed to clarify the mechanisms underlying GT antitumor effects in colon cancer cell lines. METHODS: Three isogenic HCT116 cell lines (p53+/+, p53-/-, and p21-/-) were treated with GT for different time points then Western blot, flow cytometry, and senescence analysis were performed to examine the effect of GT on Mitogen-activated protein kinase (MAPK) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) effectors, STAT3 downstream apoptotic targets, Sub-G1 phase, and programmed cell death induction. Transfection using Invitrogen Lipofectamine 2000 Transfection Reagent (Thermo Fisher Scientific, Waltham, Massachusetts) were used to identify the role of p53 and p21 in the p53-/- and p21-/- cell lines. RESULTS: Both low and high GT concentrations caused MAPKs activation marked by upregulation of extracellular signal-regulated kinase (p-ERK). The preincubation with the antioxidant Tiron (Sigma-Aldrich, St Louis, Missouri) showed that GT's antitumor effects were not mediated by reactive oxygen species. We then examined the effect of GT on the JAK/STAT pathway, which is known to be activated in colorectal cancer. GT totally inhibited the JAK/STAT pathway effectors JAK2, STAT1, and STAT3 and their downstream apoptotic regulators B-cell lymphoma-extra large (Bcl-xL) and c-Myc in all 3 cell lines. HCT116 cancer cells exhibited differential sensitivity to GT with p21-/- cells being the most sensitive and p53+/+ cells that express p21 protein being the least sensitive. In p53+/+ cells, GT induced senescence, whereas in p53-/- and p21-/- cells, GT induced apoptosis in a caspase independent manner marked by Poly(ADP-Ribose) Polymerase (PARP) cleavage, Bcl-2 downregulation, and upregulation of the Bcl-2 associated X (Bax) to B-cell lymphoma 2 (Bcl-2) ratio. In addition, the sub-G1 phase exceeded 50% in p21-/- cells. CONCLUSIONS: Considered together, our results indicate that GT is potent inhibitor of the JAK/STAT pathway in colon cancer irrespective of the p53 and p21 status, which provides insights into its mechanism of anticancer activities and future potential for clinical translation. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

16.
Nat Chem Biol ; 13(7): 750-756, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28504676

ABSTRACT

The discovery of inhibitors of methyl- and acetyl-binding domains has provided evidence for the 'druggability' of epigenetic effector molecules. The small-molecule probe UNC1215 prevents methyl-dependent protein-protein interactions by engaging the aromatic cage of MBT domains and, with lower affinity, Tudor domains. Using a library of tagged UNC1215 analogs, we screened a protein-domain microarray of human methyllysine effector molecules to rapidly detect compounds with new binding profiles with either increased or decreased specificity. Using this approach, we identified a compound (EML405) that acquired a novel interaction with the Tudor-domain-containing protein Spindlin1 (SPIN1). Structural studies facilitated the rational synthesis of SPIN1 inhibitors with increased selectivity (EML631-633), which engage SPIN1 in cells, block its ability to 'read' H3K4me3 marks and inhibit its transcriptional-coactivator activity. Protein microarrays can thus be used as a platform to 'target-hop' and identify small molecules that bind and compete with domain-motif interactions.


Subject(s)
Benzamides/pharmacology , Cell Cycle Proteins/antagonists & inhibitors , Microtubule-Associated Proteins/antagonists & inhibitors , Phosphoproteins/antagonists & inhibitors , Piperidines/pharmacology , Protein Array Analysis , Small Molecule Libraries/pharmacology , Benzamides/chemical synthesis , Benzamides/chemistry , Cell Cycle Proteins/chemistry , Dose-Response Relationship, Drug , Humans , Microtubule-Associated Proteins/chemistry , Models, Molecular , Molecular Structure , Phosphoproteins/chemistry , Piperidines/chemical synthesis , Piperidines/chemistry , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Structure-Activity Relationship
17.
Phys Chem Chem Phys ; 21(46): 25720-25727, 2019 Nov 27.
Article in English | MEDLINE | ID: mdl-31720609

ABSTRACT

Chromium disilicide (CrSi2) particles were synthesized by using an arc melting furnace followed by mechanical milling. XRD and DLS analyses show that aggregates of around 3 µm containing about 10 nm sized crystallites were obtained. These aggregates were functionalized in solution by coupling agents with different anchoring groups (silane, phosphonic acid, alkene and thiol) in order to disperse them into an organic polymer. Dodecene was used to modify the CrSi2 surface during mechano-synthesis in a grinding bowl with quite little solvent quantity and the optimization step allowed the aggregate size to be reduced to 500 nm. A thermoelectric composite was then made of alkene CrSi2 grafted samples and poly(p-phénylène-2,6-benzobisoxazole). This study opens the route for new surface grafting of intermetallic silicides for applications linked to electronics and/or energy.

18.
J Nutr ; 148(8): 1209-1216, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30137478

ABSTRACT

Background: Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects. Objective: This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities. Methods: Thirty-five 21-d-old female Sprague-Dawley rats (n = 7/diet) were fed a control diet (Ctrl) or Ctrl plus 20 mg ZEN/kg or Ctrl plus 20 mg ZEN/kg with 100, 200, or 500 mg silymarin/kg for 6 wk. Serum, livers, ovaries, and uterus were collected at week 6 for biochemistry, hormone, and redox status and selected gene and protein assays. Results: The consumption of ZEN decreased (P < 0.05) the final body weight by 17.9%, induced liver injury, increased (P < 0.05) aspartate aminotransferase and alkaline phosphatase activities, and decreased (P < 0.05) total protein and albumin concentrations in serum by 16.7-40.6%. ZEN also caused reproductive toxicity, including decreased (P < 0.05) 17ß-estradiol and increased (P < 0.05) follicle-stimulating hormone concentrations in serum by 12.7-46.3% and induced histopathologic alterations in the liver, ovaries, and uterus. Interestingly, these alterations induced by ZEN were alleviated (P < 0.05) by silymarin supplementation at 100, 200, and 500 mg/kg. Moreover, silymarin supplementation at the 3 doses mitigated (P < 0.05) ZEN-induced impairment in hepatic glutathione peroxidase activity, total antioxidant capacity, and malondialdehyde concentration by 17.6-100%. Meanwhile, silymarin supplementation at all doses upregulated (P < 0.05) phospho-ribosomal protein S6 kinase 1 (p-RPS6KB1) and 3ß-hydroxysteroid dehydrogenase (HSD3B) by 43.0-121% but downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 3α-hydroxysteroid dehydrogenase (HSD3A) in the liver relative to the ZEN group by 11.2-40.6%. In addition, silymarin supplementation at all doses elevated (P < 0.05) HSD3B by 1.8- to 2.5-fold and decreased (P < 0.05) estrogen receptor 1 (ESR1), ATP binding cassette (ABC) c1, and Abcc5 in ovaries and the uterus by 10.7-63.2%. Conclusion: Dietary silymarin supplementation at 100, 200, and 500 mg/kg protected rats from ZEN-induced hepatotoxicity and reproductive toxicity, potentially through improvement in the antioxidant capacity and regulation in the genes related to protein synthesis, ZEN metabolism, hormone synthesis, and ABC transporters in the tissues.


Subject(s)
Antioxidants/therapeutic use , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Reproduction/drug effects , Silybum marianum/chemistry , Silymarin/therapeutic use , Zearalenone/toxicity , AMP-Activated Protein Kinases/metabolism , ATP-Binding Cassette Transporters/metabolism , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Blood Proteins/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Dietary Supplements , Estrogen Receptor alpha/blood , Female , Glutathione Peroxidase/metabolism , Hormones/blood , Hydroxysteroid Dehydrogenases/metabolism , Liver/enzymology , Liver/pathology , Malondialdehyde/blood , Multidrug Resistance-Associated Proteins/metabolism , Ovary/drug effects , Ovary/pathology , Phytotherapy , Rats, Sprague-Dawley , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Silymarin/pharmacology , Uterus/drug effects , Uterus/pathology
19.
Rev Environ Contam Toxicol ; 240: 169-195, 2017.
Article in English | MEDLINE | ID: mdl-27300015

ABSTRACT

The northwestern part of Suez Gulf region is a strategic area in Egypt. It includes important sources of national income. To achieve the development goals, the government has established huge projects in this area (e.g. establishment and expanding of a large commercial port at Ain Sokhna, many industrial zones as well as tourism projects). The utilization of the Suez Gulf resources and their continuing development mainly depend on the creation of actual pollution control programs. The environmental quality control and pollution reduction activities are important ingredients of any economic development program. These different activities in this area depend mainly on the groundwater that is pumped intensively from different water bearing formations or aquifers. The main objective of the present work is compiling the previous studies from the 1980s up to 2015. These studies are concerned with estimating the concentrations of different pollutants in various ecosystems in the northwestern Suez Gulf region. Also, to provide an explanation for the movement of different pollutants such as organic and heavy metals from contaminated land to ground and surface (Gulf) waters. This issue has not been extensively surveyed before, and this review, gives specific directions for future monitoring and remediation strategies in this region.


Subject(s)
Water Pollutants, Chemical/analysis , Ecosystem , Groundwater/analysis
20.
J Pak Med Assoc ; 67(2): 300-304, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28138189

ABSTRACT

Progress test's distinguishing characteristics make it pertinent worldwide. We explored medical students' perceptions and opinions about Progress Test (PT) with a view to identifying areas concomitant with it's execution. This cross-sectional study took place at College of Medicine, Saudi Arabia, during the academic year 2015-16. A questionnaire (14 items) was administered. Reason for majority n=96 (89.7%) of the total participants to take the PT was their keenness to compare their academic standing with their peers from other participating medical colleges. The majority of students were highly satisfied with PT implementation; i.e. its orientation (58.9%) and allocated time (90.7%). Students (76.6%) considered PT to offer academic support as future physicians. Students (75.7%) also agreed to participate in the future PT. Students being highly satisfied with the organization of PT. They found it to be a tool helping them to focus on improving the knowledge domain.


Subject(s)
Education, Medical, Undergraduate/standards , Educational Measurement/standards , Students, Medical/psychology , Students, Medical/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Male , Personal Satisfaction , Saudi Arabia/epidemiology , Schools, Medical
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