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Objective Diabetes is a chronic disease resulting from insufficient insulin secretion or impaired insulin function. Diabetic nephropathy (DN) is one of the most common complications of diabetes and a leading cause of end‐stage renal disease. Early diagnosis of DN is crucial for timely intervention and effective disease management. Methods Gene expression profiles GSE142025 and GSE220226 were retrieved from the GEO database and combined into a metadata cohort, while GSE189007 was obtained as an independent validation dataset. Differentially expressed genes (DEGs) were identified in 46 glomerular samples from DN patients and 31 control samples. Gene Ontology (GO) and Disease Ontology (DO) enrichment analyses, gene set enrichment analysis (GSEA), least absolute shrinkage and selection operator (LASSO) regression, support vector machine‐recursive feature elimination (SVM‐RFE) analysis, and area under the curve (AUC) calculations were performed. Results A total of 109 DEGs were identified. Among them, DUSP1, EGR1, FPR1, G6PC, GDF15, LOX, LPL, PRKAR2B, PTGDS, and TPPP3 were selected as potential diagnostic biomarkers for DN. These biomarkers exhibited a positive correlation with immune cell infiltration. Experimental validation identified LOX as the most promising novel diagnostic biomarker for DN. This study provides new insights into the early diagnosis, pathogenesis, and molecular mechanisms of DN. Diabetic nephropathy (DN) is a major complication of diabetes, leading to end‐stage renal disease. This study identified 109 differentially expressed genes (DEGs) and validated LOX as a novel diagnostic biomarker through integrated bioinformatics and experimental analysis. The findings highlight key molecular mechanisms and immune cell interactions, offering new insights for early DN diagnosis and treatment.

Background In individuals with Duchenne muscular dystrophy (DMD), exon skipping treatment to restore a wild-type phenotype or correct the frame shift of the mRNA transcript of the dystrophin ( DMD ) gene are mutation-specific. To explore the molecular characterization of DMD rearrangements and predict the reading frame, we simultaneously screened all 79 DMD gene exons of 45 unrelated male DMD patients using a multiplex ligation-dependent probe amplification (MLPA) assay for deletion/duplication patterns. Multiplex PCR was used to confirm single deletions detected by the MLPA. Results There was an obvious diagnostic delay, with an extremely statistically significant difference between the age at initial symptoms and the age of clinical evaluation of DMD cases ( t value, 10.3; 95% confidence interval 5.95–8.80, P  < 0.0001); the mean difference between the two groups was 7.4 years. Overall, we identified 147 intragenic rearrangements: 46.3% deletions and 53.7% duplications. Most of the deletions (92.5%) were between exons 44 and 56, with exon 50 being the most frequently involved (19.1%). Eight new rearrangements, including a mixed deletion/duplication and double duplications, were linked to seven cases with DMD. Of all the cases, 17.8% had duplications with no hot spots. In addition, confirmation of the reading frame hypothesis helped account for new DMD rearrangements in this study. We found that 81% of our Saudi patients would potentially benefit from exon skipping, of which 42.9% had a mutation amenable to skipping of exon 51. Conclusions Our study could generate considerable data on mutational rearrangements that may promote future experimental therapies in Saudi Arabia.

Background. Mammography is a method widely used for the diagnosis of breast disorders in women and may help detect breast cancer in its early stages. Male breast cancer often remains undiagnosed or is poorly controlled until serious complications arise; therefore, the use of screening methods is needed to help with early diagnosis. Methods. From a total of 1,667 registered mammography cases screened, 17 male breast disease cases were included in this study. Mammography and ultrasound data were analyzed by Statistical Package of Social Sciences v.22 (SPSS). Diagnosis was made following biopsy in suspicious cases, and histopathological and immunological findings of all such patients were obtained for final diagnosis. Results. The mean age of the patients was 35 years (range, 14-70 years); 17.6% of the cases were aged 37 yrs, and 2 cases were aged 51 and 52 yrs. Of the 17 cases, 11 had breast lesions, and skin thickening was observed in only 1 case. The different patterns of lesions detected were asymmetry of the parenchyma, mastitis, and hamartoma (n=1 each), malignant lesions (n=2), and gynecomastia (n=6). According to the BI-RADS categorization, 8 cases were benign, one case was probably benign, and 2 cases were likely malignant. In the 2 cases with malignant lesions, pathological diagnosis was made after hematoxylin and eosin and immunocytochemistry examination as invasive ductal carcinoma (IDC) of no special type (NST), grade II and grade III. Conclusions. Most breast lesions in this study population were benign, while IDC was the most common malignancy encountered. Mammography is currently the most accurate and cost-effective method for detecting breast lesions. The findings of our study may help increase awareness of male breast cancer and encourage Saudi men at risk to perform self-breast exam and undergo routine breast screening.

Monosodium glutamate (MSG), a commonly used flavor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 g/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for 7 days. Results showed that MSG augmented the hepatic and renal functions markers as well as glucose, triglycerides, total cholesterol, and low-density lipoprotein levels. Moreover, marked increases in malondialdehyde levels accompanied by declines in glutathione levels and notable decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were observed in MSG-treated group. The MSG-mediated oxidative stress was further confirmed by downregulation of nuclear factor erythroid 2–related factor 2 (Nrf2) gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal inflammation as witnessed by increased inflammatory cytokines (interleukin-1b and tumor necrosis factor-α) and elevated nuclear factor-κB (NF-κB) levels. Further, significant increases in Bcl-2-associated X protein (Bax) levels together with decreases in B-cell lymphoma 2 (Bcl-2) levels were observed in MSG administration. Histopathological screening supported the biochemical and molecular findings. In contrast, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of inflammatory mediators, and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatorenal injuries through modulation of oxidative, inflammatory and apoptotic alterations.

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. However, its application is accompanied by renal impairments. Apigenin is a flavonoid found in many edible plants with potent therapeutic values. This study was designed to elucidate the therapeutic effects of apigenin on GM-induced nephrotoxicity. Animals were injected orally with three different doses of apigenin (5 mg kg −1  day −1 , 10 mg kg −1  day −1 , and 20 mg kg −1  day −1 ). Apigenin administration abolished the alterations in the kidney index and serum levels of kidney-specific functions markers, namely blood urea nitrogen and creatinine, and KIM-1, NGAL, and cystatin C following GM exposure. Additionally, apigenin increased levels of enzymatic (glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase) and non-enzymatic antioxidant proteins (reduced glutathione) and decreased levels of lipid peroxide, nitric oxide, and downregulated nitric oxide synthase-2 in the kidney tissue following GM administration. At the molecular scope, apigenin administration was found to upregulate the mRNA expression of Nfe2l2 and Hmox1 in the kidney tissue. Moreover, apigenin administration suppressed renal inflammation and apoptosis by decreasing levels of interleukin-1β, tumor necrosis factor-alpha, nuclear factor kappa-B, Bax, and caspase-3, while increasing B-cell lymphoma-2 compared with those in GM-administered group. The recorded data suggests that apigenin treatment could be used to alleviate renal impairments associated with GM administration.

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease associated with extensive mucosal damage. Prodigiosins (PGs) are natural bacterial pigments with well-known antioxidant and immunosuppressive properties. In the current study, we examined the possible protective effect of PGs loaded with selenium nanoparticles (PGs-SeNPs) against acetic acid (AcOH)-induced UC in rats. Thirty-five rats were separated into five equal groups with seven animals/group: control, UC, PGs (300 mg/kg), sodium selenite (Na 2 SeO 3 , 2 mg/kg), PGs-SeNPs (0.5 mg/kg), and 5-aminosalicylates (5-ASA, 200 mg/kg). Interestingly, PGs-SeNPs administration lessened colon inflammation and mucosal damage as indicated by inhibiting inflammatory markers upon AcOH injection. Furthermore, PGs-SeNPs improved the colonic antioxidant capacity and prevented oxidative insults as evidenced by the upregulation of Nrf2- and its downstream antioxidants along with the decreased pro-oxidants [reactive oxygen species (ROS), carbonyl protein, malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and nitric oxide (NO] in the colon tissue. Furthermore, PGs-SeNPs protected intestinal cell loss through blockade apoptotic cascade by decreasing pro-apoptotic proteins [Bcl-2-associated X protein (Bax) and caspase-3] and increasing anti-apoptotic protein, B cell lymphoma 2 (Bcl2). Collectively, PGs-SeNPs could be used as an alternative anti-colitic option due to their strong anti-inflammatory, antioxidant, and anti-apoptotic activities.

Colorectal carcinoma (CRC) represents a considerable public health burden in Saudi Arabia. Several candidate genes and genetic variants have been associated with morbidity and mortality among patients with CRC. We explored whether allelic variants of the (rs4646903 and rs1048943), and (rs1042522) genes predisposed nonsmoking Saudi individuals to increased risk for CRC. DNA from buccal cells of 158 participants (80 with CRC and 78 healthy controls) were analyzed for five SNPs using conventional PCR and TaqMan genotyping assays. The SNPStats software was utilized to choose the best interactive inheritance mode for selected SNPs (https://www.snpstats.net). The mean age of diagnosis was 62.4±13.5 years (range, 40-83 years), with those aged 71-80 years and those aged 40-50 years accounting for the most diagnoses (35.7% and 28.6% of diagnosis, respectively). The and rs1042522 SNPs were associated with CRC (OR= 3.7; < 0.0001, and OR= 1.6; = 0.033, respectively). A plausible contribution to CRC was observed for the and rs1042522 SNPs ( = 14.7; = 0.00013, and = 11.2; = 0.0008, respectively), while the null variant did not affect risk. Heterozygosity in the (rs4646903 and rs1048943 SNPs) was associated with a significant risk for CRC. The / and rs4646903/rs1048943 SNP pairs were in linkage disequilibrium, and the associations were statistically significant ( = 0.01 and = 4.6x10 , respectively). The and rs1042522 variants can increase the development of CRC in Saudi nonsmokers. Even the presence of one copy of a variant allele in the gene can predispose CRC risk. Additional studies should also examine other SNP combinations with lifestyle factors that may help prevent, rather than facilitate, colorectal tumorigenesis.

The   and  immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in   and  . We determined any associations between these SNPs and susceptibility to UBC in the Saudi community. Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the   rs17587 G>A and   rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model. The   rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21,   < 0.0001). In contrast, the   rs2071543 SNP showed no association with UBC risk (OR = 1.13,   = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1;   = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4;   = 0.0026) models. Genotypic distribution of the   rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (  > 0.05). These results suggest a potential role for   as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.

The antigen processing 1 ( ) and proteasome 20S subunit beta 9 ( ) genes are associated with strong susceptibility to many autoimmune diseases. Here, we explored whether genetic variants, individually or combined, affected susceptibility to the complex, autoimmune-based skin disorder vitiligo. Samples of genomic DNA from buccal cells of 172 patients with vitiligo and 129 healthy controls were analyzed using genotyping assays for the rs1135216 (A>G) and rs17587 (A>G) single nucleotide polymorphisms (SNPs). SNPStats software (https://www.snpstats.net) was utilized to choose the best interactive inheritance mode for selected SNPs. The genotype frequencies for the rs1135216 and rs17587 SNPs were in Hardy-Weinberg equilibrium for cases ( = 0.11 and = 0.10, respectively) but not for controls ( < 0.05). The rs1135216 (D637G) and rs17587 (R60H) SNPs increased the risk of vitiligo four-fold and two-fold, respectively (odds ratio [OR]= 4.6; 95% confidence interval [CI], 3.2-6.5; < 0.0001 and OR= 2.2; 95% CI, 1.5-3.1; < 0.0001). The recessive model (G/G-D/G versus D/D) and the codominant model (R/R versus R/H) were the best models of inheritance for the rs113526 and rs17587 SNPs, respectively (OR= 16.4; 95% CI, 2.0-138; = 0.0006 and OR= 1.7; 95% CI, 0.3-1.8; = 0.013). Vulgaris, focal vulgaris, and acryl/acrofacial were the most common vitiligo subtypes in our sample (51%, 21%, and 19%, respectively). Heterozygous rs113526 (637D/G) and rs17587 (60R/H) were the most common genotypes in most vitiligo subtypes. The heterozygous 637D/G genotype and the 637G variant allele were significantly more common in patients with active disease than in patients with stable disease ( = 0.000052 and = 0.0063, respectively). Our findings suggest a crucial role for rs1135216 and rs17587 in the risk and progression of vitiligo in the Saudi community. Genomic analyses are needed to identify more candidate genes and more genetic variants associated with vitiligo.

Diamond-like carbon (DLC) coatings have emerged as one of the most promising surface coatings for applications involving boundary lubrication regime. Some of the characteristics that distinguish DLC coatings from other hard coatings include high hardness, low friction coefficient, wear resistance, and chemical inertness. Because of their low surface energies, these coatings cannot react effectively with different lubricant constituents. Doping of DLC coatings with metals and nonmetals, such as titanium, tungsten, silicon, chromium, fluorine, and nitrogen, can improve their interaction with lubricants to form tribologically beneficial films. Many experimental studies have been conducted on different types of DLC coatings using various lubricant formulations in the last few decades. The results obtained from these experimental studies are very scattered and contradictory, so the data should be consolidated in a more organized and apprehensible manner. By doing so, tribological behavior of various DLC–lubricant combinations can be understood in a better way, and a more logical continuation of research on DLC coatings can be carried out. In this review paper, most widely investigated metal- and nonmetal-doped DLC coatings, such as Ti-DLC, W-DLC, Si-DLC, Cr-DLC, WC-DLC, and multilayered a-C:H/W-DLC coatings, are considered for evaluation. Tribological performance of the aforementioned DLC coatings, in combination with various base oils and lubricant additives, is analyzed by comparing their average friction and wear coefficient values, which have been calculated from published experimental data. Only self-mated doped DLC contacts are considered in this study to eradicate the interference of ferrous and nonferrous counterbodies.