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2.
Noncoding RNA Res ; 8(1): 96-108, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36439973

RESUMO

Background: Cerebrovascular stroke (CVS) is a potentially fatal disease. The most common risk factor for CVS is hypertension. Aim: While most studies in the field have focused on the functional roles of long noncoding RNAs (lncRNAs) NEAT1, GAS5, and HOTAIR in CVS, less attention has been paid to their clinical relevance to stroke incidence and prognosis. Also, a link has not yet been made between these lncRNAs and hypertension, our study aim was to investigate whether the expression of these lncRNAs differed between CVS with and without hypertension, as well as to compare each group to controls. Method: In total, 181 CVS patients were enrolled, including 91 chronic hypertensive patients with stroke, 90 stroke patients without hypertension, and 51 control subjects. blood samples were collected on the day of recruitment from patients with CVS and controls. Real-time qRT-PCR was used to detect the expression of target lncRNAs in serum. Results: When compared to controls, there was a statistically higher level of lncNEAT1 in each case group (median (IQR) = 3.68 (1.35-7.35) and 3.05 (0.95-6.45) for the hypertensive and non-hypertensive groups, respectively, with a significantly higher level in the hypertensive group (P = 0.04). When compared to controls, lncHOTAIR was significantly downregulated in all case groups (medians in hypertensive and non-hypertensive patients were 0.13, and 0.34, respectively), with a significantly lower level in the hypertensive group (P = 0.05). LncGAS5 levels in patients were significantly lower (median (IQR) = 0.16 (0.02-0.55) and 0.25 (0.03-0.99) for the hypertensive and non-hypertensive groups, respectively) compared to controls, with a significantly lower level in the hypertensive group (P = 0.02). There was a significant positive correlation between NEAT1 and GAS5, but a significant negative correlation between each with HOTAIR in both patients' groups. We also detected a significant negative correlation between each NEAT1 or GAS5 and NIHSS score while a significant positive correlation between HOTAIR and NIHSS. ROC curve analysis for GAS5 was able to differentiate patients with CVS hypertensive from patients with CVS non-hypertensive. Conclusion: Patients in each case group had statistically higher levels of NEAT1 and lower levels of HOTAIR and GAS5 compared to control levels, with higher significant NEAT1 but lower significant HOTAIR and GAS5 in the hypertensive group. Therefore, lncRNAs NEAT1, HOTAIR, and GAS5 could be used as diagnostic and prognostic biomarkers of CVS that correlate with NIHSS score and could produce a novel target for CVS therapy.

3.
Microorganisms ; 9(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34835490

RESUMO

Acinetobacter baumannii is a Gram-negative coccobacillus responsible for severe hospital-acquired infections, particularly in intensive care units (ICUs). The current study was designed to characterize the virulence traits of biofilm-forming carbapenem-resistant A. baumannii causing pneumonia in ICU patients using a Galleria mellonella model. Two hundred and thirty patients with hospital-acquired or ventilator-associated pneumonia were included in our study. Among the total isolates, A. baumannii was the most frequently isolated etiological agent in ICU patients with pneumonia (54/165, 32.7%). All A. baumannii isolates were subjected to antimicrobial susceptibility testing by the Kirby-Bauer disk diffusion method, while the minimum inhibitory concentrations of imipenem and colistin were estimated using the broth microdilution technique. The biofilm formation activity of the isolates was tested using the microtiter plate technique. Biofilm quantification showed that 61.1% (33/54) of the isolates were strong biofilm producers, while 27.7% (15/54) and 11.1% (6/54) showed moderate or weak biofilm production. By studying the prevalence of carbapenemases-encoding genes among isolates, blaOXA-23-like was positive in 88.9% of the isolates (48/54). The BlaNDM gene was found in 27.7% of the isolates (15/54 isolates). BlaOXA-23-like and blaNDM genes coexisted in 25.9% (14/54 isolates). Bap and blaPER-1 genes, the biofilm-associated genes, coexisted in 5.6% (3/54) of the isolates. For in vivo assessment of A. baumannii pathogenicity, a Galleria mellonella survival assay was used. G. mellonella survival was statistically different between moderate and poor biofilm producers (p < 0.0001). The killing effect of the strong biofilm-producing group was significantly higher than that of the moderate and poor biofilm producers (p < 0.0001 for each comparison). These findings highlight the role of biofilm formation as a powerful virulence factor for carbapenem-resistant A. baumannii that causes pneumonia in the ICU.

4.
5.
PLoS One ; 16(4): e0249346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861750

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.


Assuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Síndrome do Desconforto Respiratório/virologia , Adulto , Idoso , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/virologia , Creatinina/sangue , Creatinina/metabolismo , Egito/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Contagem de Linfócitos , Linfopenia/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/epidemiologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
6.
Heliyon ; 7(2): e06205, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33644474

RESUMO

BACKGROUND: The plant kingdom is considered one of the most common sources for structural and biological diversity. In particular, the wild category acquires our attention to investigate the phytochemical and the biological evaluations. METHODS: Dobera glabra was exposed to phytochemical examination using HPLC-ESI-MS analysis. Furthermore, the anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema model, whereas both the central and peripheral analgesic activities were tested via hot plate test in rats and acetic acid-induced writhing in mice, respectively. RESULTS: Twenty phenolic compounds of D. glabra aqueous leaves extract were emphasized by liquid chromatography coupled with mass spectrometry. Moreover, D. glabra exhibited both anti-inflammatory and peripheral analgesic activities. Furthermore, D. glabra significantly decreased the immune expression of MMP-9, TNF-α and TGF-ß1 in the hind paw of rats. CONCLUSION: D. glabra possess peripheral anti-nociceptive and anti-inflammatory effects in rats mediated through its anti-oxidant and anti-inflammatory activities. The activity of D. glabra leaves extract might be attributed to the presence of hydroxy and keto structures.

7.
Front Mol Biosci ; 8: 758742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35237654

RESUMO

Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke. Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays. Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke. Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.

8.
Pharm Biol ; 55(1): 139-145, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27659804

RESUMO

CONTEXT: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations. OBJECTIVE: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials. MATERIALS AND METHODS: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200 mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl4 (0.5 mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats. RESULTS: Isorhamnetin-3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside, isorhamnetin-3-O-α-rhamnopyranoside-7-O-ß-glucopyranoside, kaempferol-3,7-di-O-α-rhamnopyranoside, isorhamnetin-3-O-ß-glucopyranoside, kaempferol-3-O-ß-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200 mg/kg bw) + CCl4 exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl4, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8 U/mg protein/min compared to CCl4 (1.8 U/mg protein/min). DISCUSSION AND CONCLUSION: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity.


Assuntos
Antioxidantes/farmacologia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Salvadoraceae/química , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Antioxidantes/isolamento & purificação , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Transportador 1 de Aminoácido Excitatório/genética , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/metabolismo , Flavonoides/isolamento & purificação , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Masculino , Metanol/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Solventes/química , Regulação para Cima
9.
Acta Pol Pharm ; 73(6): 1587-1592, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29634113

RESUMO

The present study describes the in vitro cytotoxic effects of soft coral (Sarcophyton tiocheliophorum). Soft corals of genus Sarcophyton were reported to contain compounds that are active against brine shrimp and promote paclitaxel cytotoxicity in the human colon cancer Caco-2 cell line. The n-hexane extract of the soft coral Sarcophyton tiocheliophorum induced significant dose-dependent toxicity (LC50 96.7 ppm) compared with ethyl acetate (LC50. 120 ppm). We reported the most active cytotoxic level to be correspondence to LC50 values of 20.2, 59.2 ppm and 18.9 and 26 ppm. Accordingly, bio-assay guided fractionation was conducted to identi- fy the bioactive compounds. Arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid were characterized based on GC-MS analyses. Our results demonstrate the value of marine products as a natural source of medicinally interesting cytotoxic compounds.


Assuntos
Antozoários/metabolismo , Artemia/efeitos dos fármacos , Produtos Biológicos/isolamento & purificação , Acetatos/química , Animais , Ácido Araquidônico/isolamento & purificação , Produtos Biológicos/administração & dosagem , Produtos Biológicos/toxicidade , Células CACO-2 , Ácidos Docosa-Hexaenoicos/isolamento & purificação , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Hexanos/química , Humanos , Oceano Índico , Dose Letal Mediana
10.
Mar Drugs ; 12(4): 1977-86, 2014 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-24699113

RESUMO

Chemical investigations of the Egyptian soft coral Sarcophyton ehrenbergi have led to the isolation of compounds 1-3 as well as the previously reported marine cembranoid diterpene sarcophine (4). Structures were elucidated by comprehensive NMR and HRMS experimentation. Isolated compounds were in vitro assayed for cytotoxic activity against human hepatocarcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines.


Assuntos
Antozoários/metabolismo , Antineoplásicos/farmacologia , Terpenos/farmacologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Adenocarcinoma/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Neoplasias da Mama/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Egito , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Células MCF-7 , Espectroscopia de Ressonância Magnética , Terpenos/química , Terpenos/isolamento & purificação
11.
Nat Prod Commun ; 7(5): 609-10, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22799088

RESUMO

Bioactivity-guided fractionation of an ethanolic extract of Vitis repens led to the isolation of resveratrol (1), 11-O-acetyl bergenin (2), and stigmast-4-en-3-one (3). The compounds were examined for their in vitro antitrypanosomal activities against trypomastigotes of Trypanosoma evansi. Resveratrol showed antitrypanosomal activity with an IC50 value of 0.13 microM, whereas 11-O-acetyl bergenin and stigmast-4-en-3-one exhibited IC50 values of 0.17 and 0.15 microM, respectively.


Assuntos
Extratos Vegetais/análise , Plantas Medicinais/química , Tripanossomicidas/isolamento & purificação , Vitis/química , Mianmar , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos
12.
J Nat Med ; 66(1): 233-40, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21822605

RESUMO

The crude extract of Brucea javanica showed strong in vitro inhibitory activity against Trypanosoma evansi. Among the isolated quassinoids, bruceines A, C, and bruceantinol were found to be the most potent compounds against T. evansi. To gain a deeper understanding of the relationship between the free hydroxyl groups and the activity, several O-acetylated derivatives of bruceines A and C were synthesized and their in vitro antitrypanosomal activities against trypomastigotes of T. evansi were examined and compared with those of the original compounds. The following structure-activity relationships were observed: (1) the free hydroxyl groups at positions C-3, C-11, and C-12 are essential for antitrypanosomal activity; (2) the C-11 and C-12 hydroxyl groups are more important for the activity than the enolic hydroxyl group at C-3, and; (3) the free hydroxyl group at C-4' of bruceine C does not have any significant effect on the activity.


Assuntos
Quassinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Acetilação , Brucea/química , Frutas , Estrutura Molecular , Quassinas/química , Quassinas/isolamento & purificação , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação
13.
Nat Prod Commun ; 6(12): 1801-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22312709

RESUMO

We have previously reported a tetraketide origin for theobroxide and its related compound. In the present study, bioconversion of natural and deuterium-labeled precursors of this proposed biosynthetic pathway by Lasiodipoldia theobromae was investigated. Theobroxide was quantified after bioconversion from each proposed precursor. The transformation of the isotopically labeled precursor to products was tracked by 2H NMR measurement.


Assuntos
Ascomicetos/metabolismo , Cicloexanos/metabolismo , Compostos de Epóxi/metabolismo , Biotransformação , Deutério , Espectroscopia de Ressonância Magnética
14.
Vet Parasitol ; 158(4): 288-94, 2008 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-18986767

RESUMO

The medicinal plant Brucea javanica (L.) Merr. (Simaroubaceae) is widely distributed throughout Asia where its bitter fruits have been used in traditional medicine for various ailments. Fifteen C-20 quassinoids were isolated from the fruits of B. javanica and examined for their in vitro antitrypanosomal activities against trypomastigotes of Trypanosoma evansi. Bruceine A, bruceantinol, bruceine C, brusatol, and bruceine B showed strong antitrypanosomal activities with IC(50) values in the range of 2.9-17.8nM, which compared well with the standard trypanocidal drugs diminazene aceturate (IC(50)=8.8nM) and suramin (IC(50)=43.2nM). However, dehydrobruceine A, dehydrobruceine B, and dehydrobrusatol were about 2100, 900, and 1200 times less active, respectively, than bruceine A, bruceine B, and brusatol. The relationship of the structure and antitrypanosomal activity of these quassinoid compounds suggested that the presence of a diosphenol moiety in ring A and the nature of the C-15 side chain are important for their activities against T. evansi. This is the first report on the antitrypanosomal activity of isolated quassinoids.


Assuntos
Antiprotozoários/farmacologia , Brucea/química , Frutas/química , Quassinas/farmacologia , Trypanosoma/efeitos dos fármacos , Animais , Antiprotozoários/química , Estrutura Molecular , Extratos Vegetais/química , Quassinas/química
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