Explore the vast range of titles available.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle loss, leading to difficulties in movement. Mutations in the DMD gene that code for the protein dystrophin are responsible for the development of DMD disorder, where the synthesis of this protein is completely halted. Therefore, circulating dystrophin protein could be a promising biomarker of DMD disease. Current methods for diagnosing DMD have sensitivity, specificity, and reproducibility limitations. Herein, a quantitative liquid chromatography–tandem spectrometry (LC–MS/MS) technique in multiple reaction monitoring (MRM) mode was designed and validated for accurate dystrophin protein measurement in a dried blood spot (DBS). The method was successfully validated on the basis of international guidelines regarding calibration curves, precision, and accuracy. In addition, patients and healthy controls were used to test the amount of dystrophin protein circulating in DBS samples as a potential biomarker for DMD disorders. DMD patients were found to have considerably lower levels than controls. To the best of our knowledge, this is the first study to report dystrophin levels in DBS through LC–MS/MS as a diagnostic marker for DMD to the proposed MRM method, providing a highly specific and sensitive approach to dystrophin quantification in a DBS that can be applied in DMD screening.

Chronic kidney disease (CKD) is a serious public health problem characterized by progressive kidney function loss leading to end-stage renal disease (ESRD) that demands dialysis or kidney transplantation. Early detection can prevent or delay progression to ESRD. The study aimed to gain new insights into the perturbed biochemical reactions and to identify novel distinct biomarkers between ESRD and CKD. Serum samples of 32 patients with ESRD (n = 13) and CKD (n = 19) were analyzed using chemical isotope labeling liquid chromatography-mass spectrometry metabolomics approach. A total of 193 metabolites were significantly altered in ESRD compared to CKD and were mainly involved in aminoacyl-tRNA biosynthesis, branched-chain amino acid (BCAA) biosynthesis, taurine metabolism, and tryptophan metabolism. Three kynurenine derivatives, namely, 2-aminobenzoic acid, xanthurenic acid, and hydroxypicolinic acid were upregulated in ESRD compared to CKD due to the significant decrease in glomerular filtration rate with the progression of CKD to ESRD. N -Hydroxy-isoleucine, 2-aminobenzoic acid, and picolinic acid yielded AUC > 0.99 when analyzed using Receiver Operating Characteristic (ROC) analysis. Our findings suggest that inhibiting the kynurenine pathway might be a promising target to delay CKD progression and that metabolites with high discriminative ability might serve as potential prognostic biomarkers to monitor the progression of CKD to ESRD or used in combination with current markers to indicate the status of kidney damage better.

Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST treatments effectively counteracted the toxic effects of PA and normalized most biochemical parameters in rats. DHA and AST can be useful food additives to prevent and reverse PA food-induced toxicity.

The surface protein overexpressed on cancer cells can be used as biomarkers for early detection of specific diseases. Anti-VCAM-1 and anti-IL4Rα DNA aptamers specific to VCAM-1 and IL4Rα receptors that are overexpressed in 4T1 tumor-bearing mice could be used as potential biomarker for both diagnostic and therapeutic applications in cancer biology. Cell Viability and luciferase assay of 4T1-Luc2 cancer cells in the presence of anti-VCAM-1 ssDNA or anti-IL4Rα RNA aptamers was assessed by monitoring the changes in the absorbance and the fluorescence of Alamar blue dye. The aptamer-conjugated SPIO magnetic beads, used for the selective targeting to tumor sites, were monitored using noninvasive MRI and Bioluminescence imaging (BLI). Cell viability and luciferase assays showed that both anti-VCAM-1 and anti-IL4Rα aptamers favor the depletion of cancer cells and limit tumor progression. Microscopic analyses confirmed that the target specific aptamers significantly trigger tumor cell apoptosis and limit cancer cell growth in vitro. The intravenous injection of SPIO nanoparticle-conjugated aptamers were further confirmed using noninvasive MRI and Bioluminescence imaging. Anti-VCAM1 and anti-IL4Rα aptamers, specific to VCAM-1 and IL4Rα receptors overexpressed in 4T1-Luc2 tumor-bearing mice, were used as diagnostic and therapeutic tools.

With the target of recovering rare earth elements (REEs) from acidic leachates, a new functionalized hydrogel was designed, based on the phosphorylation of algal/polyethyleneimine beads. The functionalization strongly increased the sorption efficiency of the raw material for Pr(III) and Tm(III). Diverse techniques were used for characterizing this new material and correlating the sorption performances and mechanisms to the physicochemical structure of the sorbent. First, the work characterized the sorption properties from synthetic solutions with the usual procedures (study of pH effect, uptake kinetics, sorption isotherms, metal desorption and sorbent recycling, and selectivity from multi-element solutions). Optimum pH was found close to 5; sorption isotherms were fitted by the Langmuir equation (maximum sorption capacities close to 2.14 mmol Pr g−1 and 1.57 mmol Tm g−1). Fast uptake kinetics were modeled by the pseudo-second order rate equation. The sorbent was highly selective for REEs against alkali-earth and base metals. The sorbent was remarkably stable for sorption and desorption operation (using 0.2 M HCl/0.5 M CaCl2 solutions). The sorbent was successfully applied to the leachates of Egyptian ore (pug leaching) after a series of pre-treatments (precipitation steps), sorption, and elution. The selective precipitation of REEs using oxalic acid allows for the recovery of a pure REE precipitate.

Nephrotic syndrome (NS) is a kidney illness characterized by excessive proteinuria, hypoalbuminemia, edema, and hyperlipidemia, which may lead to kidney failure and necessitate renal transplantation. End-stage renal disease, cardiovascular issues, and mortality are much more common in those with NS. Therefore, the present study aimed to identify potential new biomarkers associated with the pathogenesis and diagnosis of NS. The liquid chromatography–mass spectrometry (LC–MS) metabolomics approach was applied to profile the metabolome of human serum of patients with NS. A total of 176 metabolites were significantly altered in NS compared to the control. Arginine, proline, and tryptophan metabolism; arginine, phenylalanine, tyrosine, and tryptophan biosynthesis were the most common metabolic pathways dysregulated in NS. Furthermore, alanyl-lysine and isoleucyl-threonine had the highest discrimination between NS and healthy groups. The candidate biomarkers may lead to understanding the possible metabolic alterations associated with NS and serve as potential diagnostic biomarkers.

Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second–fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth–seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.

The aqueous extract of Portulaca oleracea was used as a biocatalyst for the reduction of Na2SeO3 to form Se-NPs that appeared red in color and showed maximum surface plasmon resonance at a wavelength of 266 nm, indicating the successful Phyto-fabrication of Se-NPs. A FT-IR chart clarified the role of plant metabolites such as proteins, carbohydrates, and amino acids in capping and stabilizing Se-NPs. TEM, SAED, and XRD analyses indicated the formation of spherical, well-arranged, and crystalline Se-NPs with sizes in the range of 2–22 nm. SEM-EDX mapping showed the maximum peaks of Se at 1.4, 11.3, and 12.4 KeV, with weight and atomic percentages of 36.49 and 30.39%, respectively. A zeta potential of −43.8 mV also indicated the high stability of the synthesized Se-NPs. The Phyto-synthesized Se-NPs showed varied biological activities in a dose-dependent manner, including promising activity against pathogenic bacteria and Candida species with varied MIC values in the range of 12.5−50 µg·mL−1. Moreover, the Se-NPs showed antiviral activity toward HAV and Cox-B4, with percentages of 70.26 and 62.58%, respectively. Interestingly, Se-NPs showed a target orientation to cancer cell lines (HepG2) with low IC50 concentration at 70.79 ± 2.2 µg·mL−1 compared to normal cell lines (WI−38) with IC50 at165.5 ± 5.4 µg·mL−1. Moreover, the as-formed Se-NPs showed high activity against various instar larvae I, II, III, and IV of Culex pipiens, with the highest mortality percentages of 89 ± 3.1, 73 ± 1.2, 68 ± 1.4, and 59 ± 1.0%, respectively, at 50 mg L−1. Thus, P. oleracea-based Se-NPs would be strong potential antimicrobial, anti-viral, anti-cancer, and anti-insect agents in the pharmaceutical and biomedical industries.

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.