Search Results (181)

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. Results: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1/14:0), PA(10:0/17:0), PA(18:1-O(12,13)/12:0)), PG(a-13:0/a-13:0), ganglioside GA1 (d18:1/18:1), PS(14:1/14:0), TG(20:0/18:4/14:1), and CDP-DG(PGF2alpha/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. Conclusions: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that predominantly affects synovial joints, leading to inflammation, pain, and progressive joint damage. Despite therapeutic advancements, the molecular basis of established RA remains poorly defined. Methods: In this study, we conducted an untargeted plasma proteomic analysis using two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in samples from RA patients and healthy controls in the discovery phase. Results: Significantly (ANOVA, p ≤ 0.05, fold change > 1.5) differentially abundant proteins (DAPs) were identified. Notably, upregulated proteins included mitochondrial dicarboxylate carrier, hemopexin, and 28S ribosomal protein S18c, while CCDC124, osteocalcin, apolipoproteins A-I and A-IV, and haptoglobin were downregulated. Receiver operating characteristic (ROC) analysis identified CCDC124, osteocalcin, and metallothionein-2 with high diagnostic potential (AUC = 0.98). Proteins with the highest selected frequency were quantitatively verified by multiple reaction monitoring (MRM) analysis in the validation cohort. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) revealed the underlying molecular pathways and key interaction networks involved STAT1, TNF, and CD40. These central nodes were associated with immune regulation, cell-to-cell signaling, and hematological system development. Conclusions: Our combined proteomic and bioinformatic approaches underscore the involvement of dysregulated immune pathways in RA pathogenesis and highlight potential diagnostic biomarkers. The utility of these markers needs to be evaluated in further studies and in a larger cohort of patients. Full article

Background: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to nerve atrophy. Ultrasonography has a significant role in the diagnosis of ALS. Aim: We aimed to sonographically assess the size of all peripheral nerves and cervical nerve roots in ALS compared to controls. Methods: We searched MEDLINE (PubMed), Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Scopus using comprehensive MeSH terms for the keywords nerve, ultrasound, and ALS. We extracted data regarding cross-sectional area (CSA) or diameter for the following nerves: vagus, phrenic, tibial, fibular, sural, radial, ulnar, and median nerves, and the roots of C5, C6, C7, and C8 in both ALS patients and controls. Results: Our study included 2683 participants, of which 1631 were ALS patients (mean age = 60.36), 792 were healthy controls (mean age = 57.79), and 260 were patients with other neurological disorders. ALS patients had significantly smaller nerve size compared to controls. Nerve size differences were observed in the vagus nerve [MD = −0.23], phrenic nerve [MD = −0.25], C5 nerve root [SMD = −0.94], C6 nerve root [SMD = −1.56], C7 nerve root [SMD = −1.18], C8 nerve root [MD = −1.9], accessory nerve [MD = −0.32], sciatic nerve [MD = −11], tibial nerve [MD = −0.68], sural nerve [MD = −0.32,], ulnar nerve [MD = −0.80], and median nerve [MD = −1.21]. Conclusions: Our findings showed that ALS patients have a sonographically smaller nerve size than healthy controls. Therefore, this is a potential marker for neuronal diseases. Full article

Egypt must present a more thorough and accurate picture of the state of the air, as this can contribute to better environmental and public health results. Hence, the goal of the current study is to map and track the spatiotemporal air quality over Egypt’s Qena Governorate using remote sensing data. The current investigation is considered a pioneering study and the first attempt to map the air quality index in the studied area. Multisource remote sensing data sets from the Google Earth Engine (GEE) were used to achieve this. The first is Sentinel-5P’s average annual satellite image data, which were gathered for four important pollutants: carbon monoxide (CO), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and ozone (O₃) over a six year period from 2019 to 2024. The second is the MODIS aerosol optical density (AOD) product satellite image data from the GEE platform, which calculate the average annual particulate matter (PM_2.5 and PM₁₀). All mentioned pollutant images were used to calculate the air quality index (AQI) and aggregated air quality index (AAQI). Lastly, we used Landsat’s average yearly land surface temperature (LST) retrieval (OLI/TIRS). The aggregated air quality index (AAQI) was computed, and the U.S. Environmental Protection Agency’s (USEPA) air quality index (AQI) was created for each pollutant. According to the data, the AQI for CO, PM_2.5, and PM₁₀ in the research region ranged from hazardous to unhealthy; at the same time, the AQI for NO₂ varied between harmful and unhealthy for sensitive groups, with values ranging from 135 to 165. The annual average of the AQI for SO₂ throughout the studied period ranged from 29 to 339, with the categories ranging from good to hazardous. The constant AQI for ozone in the study area indicates that the ozone doses in Qena are surprisingly stable. Lastly, with a minimum value of 265 and a maximum of 489, the AAQI ranged from very unhealthy to dangerous in the current study. According to the data, the area being studied has poor air quality, which impacts the environment and public health. The results of this study have significant implications for environmental sustainability and human health and could be used in other areas. Full article

Purpose: To evaluate the potential clinical role and reliability of Sonazoid-enhanced ultrasound (SEUS) as a diagnostic tool for liver metastatic lesions. Methods: An extensive literature search was conducted across five electronic databases, PubMed, Scopus, Embase, Cochrane Library, and Web of Science, from their inception up to January 2024 to identify all studies evaluating the use of Sonazoid-enhanced ultrasonography for detecting hepatic metastases. A meta-analysis was performed to assess diagnostic accuracy using the Meta-DiSc 2.0 software. Results: A total of 31 studies were included, 16 of which were eligible for meta-analysis and diagnostic test accuracy evaluation. A total of 13 studies in the meta-analysis evaluated the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for 1347 metastatic and 1565 non-metastatic liver lesions. The pooled sensitivity and specificity for CEUS were 0.88 (95% CI: 0.82–0.92) and 0.92 (95% CI: 0.84–0.96), respectively. The combined positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 11.89 (95% CI: 5.42–26.09), 0.12 (95% CI:0.08–0.19), and 91.99 (95% CI: 32.15–263.17), respectively. Additionally, four studies of the meta-analysis assessed the diagnostic performance of contrast-enhanced intraoperative sonography (CE-IOUS) in detecting 664 metastatic and 246 non-metastatic liver lesions. The pooled sensitivity and specificity for CE-IOUS were 0.93 (95% CI: 0.82–0.97) and 0.84 (95% CI: 0.65–0.93), respectively. The aggregated positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated as 5.95 (95% CI: 2.32–15.25), 0.07 (95% CI: 0.02–0.24), and 77.68 (95% CI: 10.33–583.86), respectively. Conclusions: CE-IOUS and CEUS are reliable approaches for diagnosing liver metastatic lesions. CE-IOUS, in particular, exhibits higher accuracy in identifying liver metastatic lesions, indicating its potential effectiveness in clinical practice. Full article

Ischemia-reperfusion (IR) injury is a major cause of multiple organ failure. The purpose of this study was to look into the role of Tephrosia purpurea (TEP) and its active constituent pseudosemiglabrin (PS) in alleviating severe acute pancreatitis and its associated acute lung injury. We established a rat pancreatic IR model, and the rats were treated with TEP (200 mg/kg and 400 mg/kg) and PS (20 and 40 mg/kg), in addition to the IR control and sham groups. The results showed that the respiratory parameters, including inspiratory time (Ti), expiratory time (Te), duration (Dr), and respiratory rate (RR), were comparable among all groups, while peak inspiratory flow (PIF), forced vital capacity (FVC), and forced expiratory volume at 0.1 s (FEV₀.₁) were significantly impaired. Notably, PS at 40 mg/kg showed normal PIF, FVC, and FEV₀.₁/FVC compared to the IR group, indicating an improved lung function. Additionally, TEP and PS showed protective effects on pancreatic and lung tissues compared to the IR control group, with the following effects: alleviating pathological damage; reducing serum levels of trypsinogen activation peptide (TAP), lipase, and amylase; decreasing oxidative stress markers such as MDA and MPO; restoring antioxidant enzyme activity (GPx); suppressing inflammatory markers TNF-α, IL-6, and NF-κB; downregulating HMGB1 gene in pancreatic tissue; and upregulating the IL-22 gene in lung tissues. In conclusion, the obtained findings demonstrate that oral supplementation of TEP and PS to rats with pancreatic IR alleviates pancreatic and lung injuries by reducing oxidative stress and modulating inflammatory processes, which offers an attractive therapeutic option for severe acute pancreatitis and its associated acute lung injury. Full article

Monoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily through the increased production of reactive oxygen species (ROS). Inhibition of MAO-B impedes cell proliferation, making it a potential therapeutic target. Various monoamine oxidase B inhibitors have shown promise in inhibiting tumor growth and inducing apoptosis across different cancer types. In this review, we investigate MAO-B network biology, which highlighted glycolysis pathways as notable links between MAO-B and cancer. Further molecular modeling analysis illustrated the basis of MAO-B ligand binding, revealing a hydrophobic binding pocket, with key residues such as Tyr398 and Tyr435 playing crucial roles in substrate oxidation. MAO-B inhibitors that were reportsed in the literature (2012–2024) and their potential application in cancer therapy were discussed, highlighting key molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B activated pro-drugs, and natural phenylpropanoid derivatives. The reported literature underscores the therapeutic potential of MAO-B inhibitors as versatile anticancer agents, warranting further investigation to optimize their efficacy and specificity across various malignancies. Full article

This study investigated the impact of varying sowing dates and concentrations of humic acid (HA) on the growth, yield, and essential oil profile of fennel (Foeniculum vulgare) across two consecutive growing seasons (2020/2021 and 2021/2022). The experiment was carried out at Aswan University’s Agricultural Experimental Farm in Egypt, utilizing a split-plot design with three sowing dates (15th October, 1st November, and 15th November) along with four HA concentrations (0, 2.5, 3.75, and 5 kg ha⁻¹). The results revealed that early sowing on 15th October and enrichment with 5 kg ha⁻¹ of HA significantly enhanced plant height, stem diameter, branch number, umbels per plant, and fruit yield. The highest fruit yield (2684 kg ha⁻¹) and essential oil yield (27.3 L ha⁻¹) were obtained from plants sown on 15th October and treated with 5 kg ha⁻¹ HA. Moreover, the essential oil composition was notably affected, with significant increases in the concentration of anethole, estragole, and other critical compounds under the same treatment. Conversely, delayed sowing reduced both the yield and oil content. These findings highlight the importance of optimizing sowing dates and HA application rates to maximize fennel’s yield and essential oil quality, particularly in arid regions. The findings of this study offer practical guidance for optimizing fennel cultivation in arid regions by integrating early sowing dates and humic acid applications, which can significantly enhance yield and essential oil quality. These insights are particularly valuable for the medicinal and aromatic plant industries, supporting sustainable agriculture and improving the commercial viability of fennel production under climate-challenged conditions. Full article

Rapid population growth accelerates changes in land use and land cover (LULC), straining natural resource availability. Monitoring LULC changes is essential for managing resources and assessing climate change impacts. This study focused on extracting LULC data from 1993 to 2024 using the classification and regression tree (CART) method on the Google Earth Engine (GEE) platform in Qena Governorate, Egypt. Moreover, the cellular automata (CA) Markov model was used to anticipate the future changes in LULC for the research area in 2040 and 2050. Three multispectral satellite images—Landsat thematic mapper (TM), enhanced thematic mapper (ETM+), and operational land imager (OLI)—were analyzed and verified using the GEE code editor. The CART classifier, integrated into GEE, identified four major LULC categories: urban areas, water bodies, cultivated soils, and bare areas. From 1993 to 2008, urban areas expanded by 57 km², while bare and cultivated soils decreased by 12.4 km² and 42.7 km², respectively. Between 2008 and 2024, water bodies increased by 24.4 km², urban areas gained 24.2 km², and cultivated and bare soils declined by 22.2 km² and 26.4 km², respectively. The CA-Markov model’s thematic maps highlighted the spatial distribution of forecasted LULC changes for 2040 and 2050. The results indicated that the urban areas, agricultural land, and water bodies will all increase. However, as anticipated, the areas of bare lands shrank during the years under study. These findings provide valuable insights for decision makers, aiding in improved land-use management, strategic planning for land reclamation, and sustainable agricultural production programs. Full article

This study examined the phytochemical profile and biomedical activities of Nitraria retusa, a halophytic and drought-resistant shrub. HPLC analysis showed gallic acid (1905.1 μg/g), catechin (1984.1 μg/g), and ellagic acid (2671.1 μg/g) as the primary constituents, while FT-IR analysis revealed a complex organic profile with significant functional groups. The extract demonstrated strong antioxidant activity in DPPH assays, outperforming ascorbic acid (IC₅₀ = 18.7 ± 1.0 μg/mL) with an IC₅₀ of 16.4 ± 4.4 μg/mL. It demonstrated specific antiproliferative effects on cancer cell lines as it showed selective cytotoxicity against cancer cell lines; normal WI38 cells were largely unaffected, showing 50.0% viability at 125 μg/mL. The most sensitive cell line was Caco2, which showed 50.0% viability at 125 μg/mL. Anti-diabetic properties were exhibited by means of inhibition of α-amylase (IC₅₀ = 68.2 ± 4.2 μg/mL) and α-glucosidase (IC₅₀ = 22.8 ± 3.3 μg/mL). Additionally, antimicrobial activity was observed to be broad-spectrum, and it was most effective against E. coli (32.6 mm inhibition zone at 400 μg/mL) and Penicillium glabrum (35.3 mm at 400 μg/mL). These findings highlight the potential of N. retusa in developing plant-based therapeutic approaches. Full article

Proximal sensing has become increasingly popular due to developments in soil observation technologies and the demands of timely information gathering through contemporary methods. By utilizing the morphological, physical, and chemical characteristics of representative pedogenetic profiles established in various soils of the Sohag governorate, Egypt, the current research addresses the characterization of surface reflectance spectra and links them with the corresponding soil classification. Three primary areas were identified: recently cultivated, old cultivated, and bare soils. For morphological analysis, a total of 25 soil profiles were chosen and made visible. In the dark room, an ASD Fieldspec portable spectroradiometer (350–2500 nm) was used to measure the spectrum. Based on how similar their surface spectra were, related soils were categorized. Ward’s method served as the basis for the grouping. Despite the fact that the VIS–NIR spectra of the surface soils from various land uses have a similar reflectance shape, it is still possible to compare the soil reflectance curves and the effects of the surface soils. As a result, three groups of soil curves representing various land uses were observed. Cluster analysis was performed on the reflectance data in four ranges (350–750, 751–1150, 1151–1850, and 1851–2500 nm). The groups derived from the soil surface ranges of 350–750 nm and 751–1150 nm were not the same as those derived from the ranges of 1151–1850 nm and 1851–2500 nm. The last two categories are strikingly comparable to various land uses with marginally similar features. Based on the ranges of 1151–1850 nm and 1851–2500 nm in surface spectral data, the dendrogram effectively separated and combined the profiles into two separate clusters. These clusters matched different land uses exactly. The results can be used to promote the widespread usage of in situ hyperspectral data sets for the investigation of various soil characteristics. Full article

Salinity and water security are significant challenges in arid climates, necessitating effective practices to enhance crop productivity in these stressful environments. To address this, a study was conducted during the summer seasons of 2022 and 2023 using a randomized, completely block setup with three replications. The research assessed the effects of different mulch materials, unmulched (bare soil), white plastic, rice straw, and sawdust, combined with biostimulant foliar applications (control, bulk chitosan at 250 mg/L, and two concentrations of chitosan nanoparticles at 125 mg/L and 62.5 mg/L) on physiochemical and biological properties of salt-affected soil, as well as on the growth and yield of cowpeas. The findings of this study indicate that different mulch materials exert distinct effects based on their type. For instance, white plastic mulch with chitosan nanoparticles at a concentration of 62.5 mg/L markedly decreased soil salinity (by 10.80% and 14.64%) and ESP (by 6.93% and 6.80%). In contrast, white plastic mulch paired with a control foliar application significantly increased the soil moisture content (by 23.93% and 27.63%) compared to un-mulched soil. The combination of organic mulches and biostimulant foliar treatments significantly enhanced soil health by increasing the pH, organic carbon, nutrient content, and beneficial bacteria while reducing the bulk density and suppressing harmful fungi. Biostimulant foliar treatments have a modest affected soil property. Additionally, this study highlights that integrating specific mulching materials with biostimulant foliar treatments can significantly improve cowpea’s vegetative growth, yield, and nutrient content. This suggests that combining mulches and biostimulants may provide a sustainable solution for enhancing cowpea production in saline environments. Full article