A5020091276- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Adenosine and Purinergic Signaling
- Phosphodiesterase function and regulation
- Advanced Glycation End Products research
- Eicosanoids and Hypertension Pharmacology
- Pulmonary Hypertension Research and Treatments
- Phytochemicals and Medicinal Plants
- Metabolism, Diabetes, and Cancer
- Sulfur Compounds in Biology
- Neurological Disease Mechanisms and Treatments
- Genetics, Bioinformatics, and Biomedical Research
- Heme Oxygenase-1 and Carbon Monoxide
- Metabolomics and Mass Spectrometry Studies
- Peptidase Inhibition and Analysis
- Obstructive Sleep Apnea Research
- Redox biology and oxidative stress
- Antiplatelet Therapy and Cardiovascular Diseases
- Hemoglobin structure and function
- Inflammatory Bowel Disease
- Muscle metabolism and nutrition
- Phytochemicals and Antioxidant Activities
Zagazig University
2018-2025
Maastricht University
2018-2025
Cedars-Sinai Medical Center
2024
Personalis (United States)
2018
Second Affiliated Hospital of Zhejiang University
2016
Significance Current one drug–one target–one disease approaches in drug discovery have become increasingly inefficient. Network pharmacology defines mechanisms as networks best targeted by multiple, synergistic drugs. Using the high unmet medical need indication stroke, we here develop an integrative silico approach based on a primary target, NADPH oxidase type 4, to identify mechanistically related cotarget, NO synthase, for network pharmacology. Indeed, validate both vivo and vitro,...
Dysfunctional reactive oxygen species (ROS) signaling is considered an important disease mechanism. Therapeutically, non-selective scavenging of ROS by antioxidants, however, has failed in multiple clinical trials to provide patient benefit. Instead, pharmacological modulation disease-relevant, enzymatic sources appears be alternative, more promising and meanwhile successfully validated approach. With respect targets, the family NADPH oxidases (NOX) stands out as main dedicated sources....
Hypertension is the most important cause of death and disability in elderly. In 9 out 10 cases, molecular cause, however, unknown. One mechanistic hypothesis involves impaired endothelium-dependent vasodilation through reactive oxygen species (ROS) formation. Indeed, ROS forming NADPH oxidase ( Nox ) genes associate with hypertension, yet target validation has been negative. We re-investigate this association by network analysis identify NOX5, not present rodents, as a sole neighbor to human...
Introduction:Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa) are the most common Gram-negative bacteria associated with pneumonia coinfecting same patient. Despite their high virulence, there is no effective vaccine against them. Methods: In current study, screening of several proteins from both pathogens highlighted FepA OmpK35 for K. in addition to HasR OprF P. as promising candidates epitope mapping. Those four were linked form a multitope vaccine, that...
Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' and quality of life, substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) 50 (aspirin, statins, vorapaxar). This randomized, placebo-controlled, double-blinded crossover interventional trial aims measure the effect L-citrulline tetrahydrobiopterin (H4Bip) walking distance in patients PAD,...
Background Most human disease definitions, except for rare and communicable diseases, are based on symptoms in specific organs, not causal molecular mechanisms. This limits treatments to imprecise symptomatic approaches with high numbers needed treat. Systems medicine, instead, has a holistic approach defines diseases an organ‐agnostic manner the basis of associated risk genes, their encoded proteins, protein–protein interactions. Dysregulation such modules is best corrected by multitarget,...
Atherosclerosis and its complications are major causes of cardiovascular morbidity death. Apart from risk factors such as hypercholesterolemia inflammation, the causal molecular mechanisms unknown. One proposed mechanism involves elevated levels reactive oxygen species (ROS). Indeed, early expression ROS forming NADPH oxidase type 5 (Nox5) in vascular endothelial cells correlates with atherosclerosis aortic aneurysm. Here we test pro-atherogenic Nox5 hypothesis using mouse models. Because is...
Acute kidney injury (AKI) induced by renal ischemia-reperfusion (RIRI) is associated with a high incidence of mortality. Existing therapies are mainly supportive, no available nephroprotective agent. The purpose this study to examine the potential protective effect Agathis robusta Bark Extract (ARBE) in RIRI.The chemical composition ARBE was examined LC-ESI-MS/MS. Network pharmacology utilized identify RIRI molecular targets that could be aimed at identified major components ARBE....
Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted, for example, in pulmonary hypertension. Its dysregulation disease incompletely understood. Here we show artery endothelial cells that feedback inhibition by NO of the receptor, cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous from synthase and exogenous donor compounds decreased sGC protein activity. This effect was not mediated as NO-independent...
Toll-like receptors (TLRs) are involved in the progression of ischemic brain injury and hence vascular dementia; however, underlying mechanisms largely unknown. Here, we have investigated interrelationship between stress-responsive heme oxygenase (HO)-1 isoenzyme TLR4 during chronic hypoperfusion. The right unilateral common carotid artery occlusion was performed by ligation C57BL/6J mice. cortex or hippocampus removed for western blotting confocal immunofluorescence analysis. link HO-1...
Abstract Background The nicotinamide adenine dinucleotide phosphate oxidase isoform 4 (Nox4) mediates reactive oxygen species (ROS) production and renal fibrosis in diabetic kidney disease (DKD) at the level of podocyte. However, mitochondrial localization Nox4 its role as a bioenergetic sensor has recently been reported. Whether drives pathology DKD within proximal tubular compartment, which is densely packed with mitochondria, not yet known. Methods We generated tubular–specific knockout...
Abstract Unphysiological reactive oxygen species (ROS) formation is considered an important pathomechanism for several disease phenotypes with high unmet medical need. Therapeutically, antioxidants have failed multiple times. Instead, focusing on only disease-relevant, enzymatic sources of ROS appears to be a more promising and highly validated approach. Here the family five NADPH oxidases (NOX) stands out as drug targets. Validation has been restricted, however, mainly genetically modified...
<p class="first" dir="auto" id="d1176686e339">Haem, a fundamental prosthetic group, mediates oxygen transport and metabolism in proteins while exerting signalling functions haemolytic disorders through its pro-oxidant, pro-inflammatory, cytotoxic effects when unbound. In addition to established functions, haem plays crucial role regulating haem-responsive such as apo-soluble guanylate cyclase (apo-sGC) the REV-ERB nuclear receptors, both of which are targets for clinical drug development....
Ulcerative colitis (UC) is an inflammatory bowel disease that often resistant to current treatment options, leading a need for alternative therapies. Herbal products have shown promise in managing various conditions, including UC. However, the potential of Casuarina glauca branchlets ethanolic extract (CGBRE) treating UC has not been explored. This study aimed analyze chemical composition CGBRE and evaluate its efficacy through silico vivo experiments. LC-ESI-MS/MS was used identify 86...
ABSTRACT Background Heart failure with preserved ejection fraction (HFpEF) is a significant public health concern limited treatment options. Dysregulated nitric oxide-mediated signaling has been implicated in HFpEF pathophysiology, however, little known about the role of endogenous hydrogen sulfide (H2S). Objectives This study evaluated H2S bioavailability patients and two animal models cardiometabolic assessed impact on severity through alterations production pharmacological...
Introduction: Cardiometabolic heart failure with preserved ejection fraction (HFpEF) results in severe exercise intolerance. Dysregulated skeletal muscle metabolism and mitochondrial function are key drivers of intolerance cardiometabolic HFpEF. Mitochondrial hydrogen sulfide (H 2 S) generated by 3-mercaptopyruvate sulfur transferase (3-MST) exerts potent bioenergetic properties. We have recently shown that H S bioavailability is significantly attenuated The role H2S tolerance HFpEF...