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951.
Coirault C Guellich A Barbry T Samuel JL Riou B Lecarpentier Y 《American journal of physiology. Heart and circulatory physiology》2007,292(2):H1009-H1017
Intrinsic muscle abnormalities affecting skeletal muscle are often reported during chronic heart failure (CHF). Because myosin is the molecular motor of force generation, we sought to determine whether its dysfunction contributes to skeletal muscle weakness in CHF and, if so, to identify the underlying causative factors. Severe CHF was induced in rats by aortic stenosis. In diaphragm and soleus muscles, we investigated in vitro mechanical performance, myosin-based actin filament motility, myosin heavy (MHC) and light (MLC) chain isoform compositions, MLC integrity, caspase-3 activation, and oxidative damage. Diaphragm and soleus muscles from CHF exhibited depressed mechanical performance. Myosin sliding velocities were 16 and 20% slower in CHF than in sham in diaphragm (1.9 +/- 0.1 vs. 1.6 +/- 0.1 microm/s) and soleus (0.6 +/- 0.1 vs. 0.5 +/- 0.1 microm/s), respectively (each P < 0.05). The ratio of slow-to-fast myosin isoform did not differ between sham and CHF. Immunoblots with anti-MLC antibodies did not detect the presence of protein fragments, and no activation of caspase-3 was evidenced. Immunolabeling revealed oxidative damage in CHF muscles, and MHC was the main oxidized protein. Lipid peroxidation and expression of oxidized MHC were significantly higher in CHF than in shams. In vitro myosin exposure to increasing ONOO(-) concentrations was associated with an increasing amount of oxidized MHC and a reduced myosin velocity. These data provide experimental evidence that intrinsic myosin dysfunction occurs in CHF and may be related to oxidative damage to myosin. 相似文献
952.
Nada M. Mostafa Muhammad I. Ismail Amr M. El-Araby Dina M. Bahgat Ahmed M. Elissawy Ahmed M. Mostafa Omayma A. Eldahshan Abdel Nasser B. Singab 《Phyton》2022,91(5):1089-1104
Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals. The primary treatment is either supportive or symptomatic. Natural products have an important role in the development of various drugs. Thus, screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses. In the current study, an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents, (e.g., procyanidin B2, theaflavin, quercetin, ellagic acid, caffeoylquinic acid derivatives, berginin, eudesm-1β, 6α, 11-triol and arbutin), on the crystal structure of SARS-CoV-2 main protease (PDB ID: 6w63) using AutoDock-Vina software. Many of the docked compounds revealed good binding affinity, with procyanidin B2 (–8.6 Kcal/mol) and theaflavin (–8.5 Kcal/mol) showing a better or similar binding score as the ligand (–8.5 Kcal/mol). Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin. Procyanidin B2, theaflavin, and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways. Additionally, these phytoconstituents showed good ADME properties and acceptable lipophilicity, as evaluated using WLOGP. Amongst the tested compounds, procyanidin B2 showed the highest lipophilic value. It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns. 相似文献
953.
Naima Asghar Abida Aziz Muhammad Farooq Azhar Mohamed El-Sharnouby Uzma Irfan Iqra Rafiq Husnain Farooq Muhammad Ishaq Asif Rehmani Mohamed I. Sakran A. Altalhi Fahad M. Alzuaibr Ayman El Sabagh 《Phyton》2022,91(8):1817-1829
Moringa oleifera is a miracle plant rich in nutrients, antioxidants, and antibiotic properties. Present study was
designed to evaluate various biochemical attributes of leaves and flowers of M. oleifera. Plant parts (leaves, flowers) of M. oleifera, collected from different roadsides of Multan district, Punjab, Pakistan, were used as experimental material. Result indicates that alkaloids, saponin, carbohydrates, fats, and protein had a high value in the
aqueous extract of both leaves and flowers of M. oleifera. Whereas phenol content was high in methanolic leaves
extract and the phenol contents were high in aqueous extract of flowers. The extract yield of M. oleifera leaves and
flowers both showed a higher percentage in aqueous extract (57.5%), followed by methanol extract and lowest in
ethyl acetate extract. Flavonoids contents were higher in ethyl acetate extract of leaves (33.67%) and aqueous
extract of flowers (53.71%). While crude fiber was high in methanolic extract of leaves (12.40%) and in flowers
crude fiber was high in ethyl acetate extract (15.86%). The moisture contents were higher in leaves (8.87%) than
flowers (7.3%) and similarly, ash percentage in flowers (52.60%) than leaves (41.84%). Ethyl acetate extracts of
M. oleifera leaves show antibacterial activity against Pseudomonas aeruginosa while methanolic extract of M. oleifera flowers shows antibacterial activity against Xanthomonas sp. Maximum growth inhibits show in all extracts of
leaves against Aspergillus flavus, F. oxysporum, and P. glabrum except for the concentrated aqueous extract of
leaves. While in flowers maximum growth inhibits all extracts against P. glabrum, A. niger, and A. flavus except
the diluted ethyl acetate extract. Phytochemicals present in different parts of moringa have significant edible and
commercial potential. Moringa extracts exhibited significant antimicrobial activity, therefore have applications in
pharmaceuticals. 相似文献
954.
Negi Rahul Haritha Vemanamanda Aziz Nuzhat Siddiqui Athar H. 《Molecular and cellular biochemistry》2022,477(6):1765-1774
Molecular and Cellular Biochemistry - Preeclampsia (PE) is a multisystem disorder of pregnancy characterized by sudden onset of hypertension and proteinuria. The appearance and diagnosis of the... 相似文献
955.
Manar G. Salem Yasmine M. Abdel Aziz Marwa Elewa Hosam A. Elshihawy Mohamed M. Said 《Bioorganic & medicinal chemistry》2019,27(15):3383-3389
Novel non-sulfonylureas derivatives bearing an acetamide linker between a spirohydantoin scaffold and a phenyl ring were prepared and their hypoglycemic activity was estimated in vivo. Their abilities to discriminate in vitro between aldehyde reductase (ALR1) and aldose reductase (ALR2) were determined. The molecular docking and the in silico prediction studies were performed to rationalize the obtained biological results and to predict the physicochemical properties and drug-likeness scores of the new compounds. N-(2,4-Dichlorophenyl)-2-(2′,4′-dioxospiro[fluorene-9,5′-imidazolidine]-3′-yl)acetamide (3e) displayed an 84% reduction in blood glucose level superior to that of repaglinide 66% and showed an IC50 value of 0.37 μM against ALR2 that is superior to that of sorbinil 3.14 µM. Compound (3e) was selective 96 fold towards ALR2 which is closely related to serious diabetic complications. Based on the identification of this hit candidate, a new generation of safe and effective antidiabetic agents could be designed. 相似文献
956.
Aziz Inan Celik Mehmet Kanadasi Mesut Demir Ali Deniz Rabia Eker Akilli Onur Sinan Deveci Caglar Emre Cagliyan Caglar Ozmen Firat Ikikardes Muhammet Bugra Karaaslan 《Indian pacing and electrophysiology journal》2019,19(1):9-14
Background
Cryoballoon-based pulmonary vein isolation (PVI) is a treatment option for atrial fibrillation (AF). Left atrial volume (LAV) and left atrial volume index (LAVi) are important parameters for long term success of PVI. Galectin-3 (Gal-3) and neutrophil to lymphocyte ratio (N/L ratio) are biomarkers to demonstrate the cardiac fibrosis and remodelling.Methods
50 patients with symptomatic PAF despite ≥1 antiarrhythmic drug(s), who underwent PVI were enrolled. LAV, LAVi, Gal-3 and N/L ratio were calculated before ablation and after ablation at 6 and 12 months. According to AF recurrence patients were divided into two groups, recurrent AF (n?=?14) and non-recurrent AF (n?=?36).Results
In both groups (recurrent and non-recurrent), initial and 12 months follow-up LAV values were 41.39?±?18.13?ml and 53.24?±?22.11?ml vs 48.85?±?12.89?ml and 42.08?±?13.85 (p?=?0.037). LAVi were 20.9?±?8.91 ml/m2 and 26.85?±?11.28 ml/m2 vs 25.36?±?6.21 and 21.87?±?6.66 (p?=?0.05) for recurrent and non-recurrent AF groups, respectively. In both groups PVI had no significant effect on serum Gal-3 levels and N/L ratio during 12 months follow-up. The comparison between two groups at the end of 12th month showed Gal-3 values of 6.66?±?4.09?ng/ml and 6.02?±?2.95?ng/ml (p?=?0.516), N/L ratio values of 2.28?±?1.07 103/μl and 1.98?±?0.66?103/μl (p?=?0.674).Conclusion
LAV and LAVi are useful to predict the remodelling of the left atrium and AF recurrence after cryoballoon-based PVI. However, biomarkers such as Gal-3 and N/L ratio are not associated with AF recurrence. 相似文献957.
Nesreen Ishak Mahmoud Basim Anwar Shehata Messiha Ali Ahmed Abo‐Saif Mohamed Sadek Abdel‐Bakky 《Journal of biochemical and molecular toxicology》2019,33(5)
Activated factor X has a central role in the coagulation activation and also contributes to chronic inflammation and tissue fibrosis. In this study, rivaroxaban, a direct factor X inhibitor, attenuates liver fibrosis induced by carbon tetrachloride (CCl4). Male rats were randomly allocated into three groups: a control group, CCl 4 fibrotic group, and CCl 4+rivaroxaban (5 mg/kg) group. Liver fibrosis was induced by subcutaneous injection of CCl 4 twice a week for 6 weeks. Rivaroxaban significantly restored the biochemical parameter including inflammatory and fibrosis markers with histopathological evidence using routine and Masson trichrome staining. It reduced also the expression of tissue factor, fibrin, transforming growth factor and α‐smooth muscle actin in the liver tissues. This concludes that rivaroxaban attenuates liver injury caused by CCl 4, at least in part by inhibiting coagulation and proinflammatory activation. In conclusion, rivaroxaban may be used for the management of liver fibrosis. 相似文献
958.
Eric R. Morgan Nor-Azlina A. Aziz Alexandra Blanchard Johannes Charlier Claude Charvet Edwin Claerebout Peter Geldhof Andrew W. Greer Hubertus Hertzberg Jane Hodgkinson Johan Höglund Hervé Hoste Ray M. Kaplan María Martínez-Valladares Siân Mitchell Harm W. Ploeger Laura Rinaldi Georg von Samson-Himmelstjerna Jozef Vercruysse 《Trends in parasitology》2019,35(1):52-71
959.
Alexey Larionov Eileen Dahlke Madlen Kunke Luis Zanon Rodriguez Ina M. Schiessl Jean‐Luc Magnin Ursula Kern Abdel A. Alli Geraldine Mollet Oliver Schilling Hayo Castrop Franziska Theilig 《Journal of cellular and molecular medicine》2019,23(10):6543-6553
The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a proteinuria‐dependent fashion have been made responsible; however, referring to the timeline of symptoms occurring and underlying mechanisms, contradictory results have been published. Characterizing the mouse model of podocyte inactivation of NPHS2 (Nphs2?pod) with respect to volume handling and proteinuria revealed that sodium retention, hypertension and gross proteinuria appeared sequentially in a chronological order. Detailed analysis of Nphs2?pod during early sodium retention, revealed increased expression of full‐length ENaC subunits and αENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na+/K+‐ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process αENaC. Renal expression levels of precursor and active cathepsin B were increased and could be localized to glomeruli and intercalated cells. Inhibition of cathepsin B prevented hypertension. With the appearance of gross proteinuria, plasmin occurs in the urine and additional cleavage of γENaC is encountered. In conclusion, characterizing the volume handling of Nphs2?pod revealed early sodium retention occurring independent to aberrantly filtered plasma proteases. As an underlying mechanism cathepsin B induced αENaC processing leading to augmented channel activity and hypertension was identified. 相似文献