Dexamethasone (Dex) is a synthetic glucocorticoid (GC) drug commonly used clinically for the treatment of several inflammatory and immune-mediated diseases. Despite its broad range of indications, the long-term use of Dex is known to be associated with specific abnormalities in several tissues and organs. In this study, the metabolomic effects on five different organs induced by the chronic administration of Dex in the Sprague–Dawley rat model were investigated using the chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS) platform, which targets the amine/phenol submetabolomes. Compared to controls, a prolonged intake of Dex resulted in significant perturbations in the levels of 492, 442, 300, 186, and 105 metabolites in the brain, skeletal muscle, liver, kidney, and heart tissues, respectively. The positively identified metabolites were mapped to diverse molecular pathways in different organs. In the brain, perturbations in protein biosynthesis, amino acid metabolism, and monoamine neurotransmitter synthesis were identified, while in the heart, pyrimidine metabolism and branched amino acid biosynthesis were the most significantly impaired pathways. In the kidney, several amino acid pathways were dysregulated, which reflected impairments in several biological functions, including gluconeogenesis and ureagenesis. Beta-alanine metabolism and uridine homeostasis were profoundly affected in liver tissues, whereas alterations of glutathione, arginine, glutamine, and nitrogen metabolism pointed to the modulation of muscle metabolism and disturbances in energy production and muscle mass in skeletal muscle. The differential expression of multiple dipeptides was most significant in the liver (down-regulated), brain (up-regulation), and kidney tissues, but not in the heart or skeletal muscle tissues. The identification of clinically relevant pathways provides holistic insights into the tissue molecular responses induced by Dex and understanding of the underlying mechanisms associated with their side effects. Our data suggest a potential role for glutathione supplementation and dipeptide modulators as novel therapeutic interventions to mitigate the side effects induced by Dex therapy.

Thyroid cancer (TC) is the most common endocrine cancer, which contributes to more than 43,600 deaths and 586,000 cases worldwide every year. Among the TC types, PTC and FTC comprise 90% of all TCs. Genetic modifications in genes are responsible for encoding proteins of mitogen-associated protein kinase cascade, which is closely related with numerous cellular mechanisms, including controlling programmed cell death, differentiation, proliferation, gene expression, as well as in genes encoding the PI3K (phosphatidylinositol 3-kinase)/protein kinase B (AKT) cascade, which has contribution in controlling cell motility, adhesion, survival, and glucose metabolism, have been associated with the TC pathogenesis. Various genetic modifications including BRAF mutations, RAS mutations, RET mutations, paired-box gene 8/peroxisome proliferator-activated receptor-gamma fusion oncogene, RET/PTC rearrangements, telomerase reverse transcriptase mutations, neurotrophic tyrosine receptor kinase fusion genes, TP53 mutations, and eukaryotic translation initiation factor 1A X-linked mutations can effectively serve as potential biomarkers in both diagnosis and prognosis of TC. On the other hand, epigenetic modifications can lead to aberrant functions or suppression of a range of signalling cascades, which can ultimately result in cancer. Various studies have observed the link between epigenetic modification and multiple cancers including TC. It has been reported that several epigenetic alterations including histone modifications, aberrant DNA methylation, and epigenetic modulations of non-coding RNAs can play significant roles as potential biomarkers in the diagnosis and prognosis of TC. Therefore, a good understanding regarding the genetic and epigenetic modifications is not only essential for the diagnosis and prognosis of TC, but also for the development of novel therapeutics. In this review, most of the major TC-related genetic and epigenetic modifications and their potential as biomarkers for TC diagnosis and prognosis have been extensively discussed.

Different laboratory methods are used to measure serum ferritin levels as a marker of iron status in the general population. This study aimed to compare serum ferritin levels using enzyme-linked immunosorbent assay (ELISA) versus immunochemiluminescence (Cobas e411) and immunoturbidimetric (Cobas Integra 400) methods in terms of sensitivity, specificity and accuracy, and whether they can be used interchangeably. A comparative cross-sectional study enrolled one hundred and six adult Yemeni patients (33 males and 73 females) aged 18–55 years, recruited from the dermatology and cosmetic center of Hadhramout Modern Hospital, Mukalla, Yemen. Serum ferritin levels were measured using ELISA, Cobas e411, and Cobas Integra 400 methods. For method comparison, a paired-sample t-test was used. For the consistency between the three methods, they were analyzed with regression and Pearson correlation coefficient. For determining accuracy, a receiver operating curve (ROC) was used. Bias error between the methods was determined through a Bland–Altman plot analysis. Our results did not show any significant statistical difference between ELISA and Cobas e411 (52.55 ± 7.4 µg/L vs. 52.58 ± 7.5 µg/L, p = 0.967), while there were significantly higher values from Cobas Integra 400 results than Cobas e411 (56.31 ± 7.8 µg/L vs. 52.58 ± 7.5 µg/L, p < 0.001) and ELISA (52.55 ± 7.4 µg/L vs. 56.31 ± 7.8 µg/L, p < 0.001). According to the correlation coefficient and linear regression analysis, a strong association between ELISA with Cobas e411 (r = 0.993, p < 0.001) and Cobas Integra 400 results (r = 0.994, p < 0.001) were revealed. For determining accuracy, Cobas e411 and Cobas Integra 400 results showed higher sensitivity (92.0%; 90.0%) and specificity (97.7%; 99.9%) respectively. Additionally, the Bland–Altman plot analysis showed a high agreement between the ELISA and Cobas e411 methods (bias: −0.035). In contrast, there was a low agreement between the ELISA and Cobas Integra 400 methods (bias: −3.75). Similarly, the agreement between Cobas e411 and Cobas Integra 400 methods was low (bias: −3.72). Serum ferritin levels were measured by Cobas e411, and Cobas Integra 400 methods were strongly correlated with the ELISA results, with higher sensitivity, specificity, and accuracy. However, further investigations with larger samples are required for improved accuracy and more precise results, and to determine whether they can be used interchangeably.

Background and Objectives: In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin and serum glucose leptin levels in obese Saudi patients. Materials and Methods: A total of 206 Saudi adults (80 obese normotensive nondiabetics, 76 obese hypertensive with Type 2 Diabetes and 50 normotensive nondiabetic controls) were genotyped for -2548G>A LEP polymorphism using the polymerase chain reaction-restriction fragment-length polymorphism technique. Results: Participants with minor AA genotype had significantly higher blood glucose levels (6.8 ± 0.55 mmol/L vs. 5.8 ± 0.30 mmol/L; p < 0.04) and HOMA-IR (4.1 ± 0.84 vs. 2.6 ± 0.67; p = 0.03) against those carrying major GG genotype. Participants with heterozygous GA genotype had significantly higher serum leptin levels against those carrying major GG genotype (40.0 ± 2.6 ng/mL vs. 29.6 ± 2.6 ng/mL; p = 0.04). Further investigation showed that individuals with AA, GA, GA + AA genotypes are at greater risk of developing hyperglycemia compared to those with GG genotype [OR 3.7(1.6–8.4), p = 0.001; 3.2 (1.2–8.6), p = 0.03; 3.5 (1.6–7.7), p = 0.001, respectively]. Additionally, the -2548AA allele was shown to be a risk factor for hyperglycemia [OR 1.9 (1.2–3.0), p = 0.006]. Our data revealed no relationship between this variant of the LEP gene with systolic and diastolic BP, signifying that this genetic variant is not a significant marker of obesity and hypertension in the Saudi population. Conclusions: AA and GA genotypes and LEP gene -2548AA alleles may signify potent risk factors predisposing healthy individuals to develop T2DM regardless of blood-pressure profile.

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.

Background: Pneumonia is a ubiquitous health condition with severe outcomes. The advancement of ultrasonography techniques allows its application in evaluating pulmonary diseases, providing safer and accessible bedside therapeutic decisions compared to chest X-ray and chest computed tomography (CT) scan. Because of its aforementioned benefits, we aimed to confirm the diagnostic accuracy of lung ultrasound (LUS) for pneumonia in adults. Methods: A systematic literature search was performed of Medline, Cochrane and Crossref, independently by two authors. The selection of studies proceeded based on specific inclusion and exclusion criteria without restrictions to particular study designs, language or publication dates and was followed by data extraction. The gold standard reference in the included studies was chest X-ray/CT scan or both. Results: Twenty-nine (29) studies containing 6702 participants were included in our meta-analysis. Pooled sensitivity, specificity and PPV were 92% (95% CI: 91–93%), 94% (95% CI: 94 to 95%) and 93% (95% CI: 89 to 96%), respectively. Pooled positive and negative likelihood ratios were 16 (95% CI: 14 to 19) and 0.08 (95% CI: 0.07 to 0.09). The area under the ROC curve of LUS was 0. 9712. Conclusions: LUS has high diagnostic accuracy in adult pneumonia. Its contribution could form an optimistic clue in future updates considering this condition.