Search Results (80)

Background: Chronic rhinosinusitis with or without nasal polyps (CRSwNPs/CRSsNPs) is an inflammatory disease that is becoming increasingly associated with laryngopharyngeal reflux disease (LPRD). Although symptom-based questionnaires, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score (RSS), are widely used, there is a lack of objective endoscopic tools for assessing the nasopharyngeal and nasal manifestations of reflux. The Nasopharyngeal Reflux Endoscopic Score (NRES) is a novel endoscopic scoring system that was developed to address this issue. Objective: The objective of this study was to evaluate the diagnostic accuracy of the NRES in identifying LPRD in patients with CRS, compared with a clinical reference standard. Methods: A prospective diagnostic accuracy cohort study was conducted at two tertiary care centers in Astana, Kazakhstan, from September 2023 to February 2025. A total of 216 adults were enrolled and divided into three groups: CRS with suspected LPRD (n = 116), CRS without LPRD (n = 69), and healthy controls (n = 31). CRS was diagnosed according to the EPOS 2020 criteria. LPRD was defined using a composite reference standard comprising clinical assessment, RSS > 13, RSI, and selective 24 h pH monitoring and gastrointestinal endoscopy. All participants underwent nasopharyngeal and laryngeal endoscopy, with NRES, L-K, RFS, RSI, and RSS assessments at baseline and at 6 and 12 months. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance, and Wilcoxon tests were used to analyze the changes in scores. Correlation and regression analyses were used to explore associations between scales and predictive factors. Results: At baseline, NRES scores were significantly higher in the CRS with LPRD group (mean: 11.59) than in the CRS without LPRD group (mean: 3.10) and the healthy control group (mean: 2.16) (p < 0.001). ROC analysis demonstrated excellent diagnostic accuracy, with an area under the curve (AUC) of 0.998 (95% confidence interval (CI): 0.994–1.000), a sensitivity of 98% (95% CI: 94–100%) and a specificity of 96% (95% CI: 91–99%) at an optimal cut-off point of 8.5. NRES scores showed strong correlations with RSI, RSS, and RFS scores (r > 0.76, p < 0.001). A longitudinal assessment revealed significant reductions in all scores after treatment with proton pump inhibitors and lifestyle modifications, with sustained improvement at 12 months. Regression analysis found no significant effect of age, gender, or GERD severity (LA classification) on NRES scores. Conclusions: The NRES is a highly sensitive and specific endoscopic tool for identifying nasopharyngeal changes associated with LPRD in CRS patients. It demonstrates strong correlations with established symptom-based and laryngoscopic reflux assessments and responds to anti-reflux therapy over time. The NRES may, therefore, be a valuable objective adjunct in the comprehensive evaluation and longitudinal monitoring of LPRD-associated CRS. Full article

Background/Objectives: The evidence regarding the efficacy of probiotics in chronic rhinosinusitis (CRS) is very limited, prompting the EPOS2020 steering group to advise against their use in CRS treatment. Therefore, further research to evaluate the impact of probiotics on microbial communities is particularly important. This study aimed to assess the influence of probiotic nasal rinses on nasal microbiota profiles in patients with primary CRS, granulomatosis with polyangiitis (GPA), and nasal septal perforation (NSP) using 16S rRNA sequencing. Methods: Thirty-six patients with nasal mucosal diseases, including sixteen with primary CRS, eleven with GPA, and nine with NSP, were randomly assigned to either a study group receiving nasal rinses with probiotics containing Lactobacillus plantarum and Bifidobacterium animalis, or a control group using nasal rinses with saline. Metagenomic analysis targeting the V3–V4 hypervariable region of the 16S rRNA gene was performed to characterize bacterial and archaeal populations. Results: At the genus level, the most abundant co-colonizers included Staphylococcus, Streptococcus, and Haemophilus. After one month of probiotic rinsing, a decrease in abundance of the genera Finegoldia (p = 0.010), Haemophilus (p = 0.020), Streptococcus (p = 0.027), Staphylococcus (p = 0.033), Micrococcus (p = 0.035), Corynebacterium (p = 0.049), Gemella (p = 0.055), Rubrobacter (p = 0.055), and Pseudonocardia (p = 0.058) was observed. Conversely, the abundance of probiotic species Lactobacillus plantarum and Bifidobacterium animalis increased. Moreover, increases in the genera Dolosigranulum and Stenotrophomonas were observed, although they did not reach statistical significance. Conclusions: Probiotic nasal rinses may contribute to restoring microbial homeostasis by reducing genera associated with inflammatory dysbiosis in nasal inflammatory diseases, warranting further research on their clinical benefits. Full article

Clear-cell renal cell carcinoma (ccRCC) is associated with the mutated von Hippel–Lindau (VHL) gene leading to the activation of hypoxia-inducible factor 1A (HIF1A) and subsequent overexpression of erythropoietin (EPO). We analyzed tumor and healthy tissues from 43 ccRCC patients after radical nephrectomy and cultured 786-O (biallelic VHL inactivation) and Caki-1 (wild-type VHL) cells in normal (21% O₂) and low oxygen (3% O₂) with 10% and 2% fetal bovine serum (FBS). DNA sequencing, including Sanger sequencing, MLPA and LOH, revealed 27 somatic mutations of VHL in ccRCC. HIF1A protein showed decreased or no expression in tumors compared to healthy tissue, independent of VHL alteration. The 786-O cells showed increased HIF1A protein expression after 48 h under low oxygen and 10% FBS. EPO and erythropoietin receptor (EPOR) were significantly decreased in ccRCC without HIF1A expression. EPO mRNA increased in the 786-O cells at 3% O₂ after 48 h, while the Caki-1 cells had low or no EPO expression. Hypoxia increased EPOR mRNA in the Caki-1 cells at 10% FBS, but decreased in the 786-O cells at 2% FBS after 48 h. JAK2/STAT5A activity was increased only in HIF1A-positive tumors. These results suggest that EPO/EPOR activation in ccRCC is mainly driven by low oxygen, not VHL regulation of hypoxia-related responses. Full article

The use of recombinant human erythropoietin (rHuEPO) has been found to improve different cardiopulmonary-related variables that ultimately enhance endurance performance. The main goal of this systematic review was to analyze the hematological, physiological, and performance effects (both maximal and submaximal) of rHuEPO in well-trained endurance athletes. A literature search was conducted in three different databases (PubMed, Web of Science, and Scopus) on 20 January 2025; including studies published from 1 January 2010 to the search date. After analyzing 985 resultant articles and 5 records identified outside of the databases through citation tracking, 10 studies that met the inclusion criteria were included in the systematic review. We found that, regardless of the total dose of rHuEPO used, this substance improves the main hematological (total hemoglobin mass, hemoglobin concentration, and hematocrit) and physiological (maximal oxygen uptake and peak oxygen uptake) parameters, while the maximal performance-related parameters (mainly, maximal power output, and peak power output) also tend to increase. However, further research is needed to determine if rHuEPO can also improve submaximal parameters, which are also major determinants of performance in endurance sports. Full article

Erythropoietin (EPO) is a key regulator of erythrocyte production, promoting erythroid progenitor cell survival, division, and differentiation in the fetal liver and adult bone marrow. Mice lacking EPO or its receptor (EPOR) die in utero due to severe anemia. Beyond hematopoiesis, EPO influences non-hematopoietic tissues, including glucose and fat metabolism in adipose tissue, skeletal muscle, and the liver. EPO is used to treat anemia associated with chronic kidney disease clinically and plays a role in maintaining metabolic homeostasis and regulating fat mass. EPO enhances lipolysis while inhibiting lipogenic gene expression in white adipose tissue, brown adipose tissue, skeletal muscle, and the liver, acting through the EPO-EPOR-RUNX1 axis. The non-erythroid EPOR agonist ARA290 also improves diet-induced obesity and glucose tolerance providing evidence for EPO regulation of fat metabolism independent of EPO stimulated erythropoiesis. Therefore, in addition to the primary role of EPO to stimulate erythropoiesis, EPO contributes significantly to EPOR-dependent whole-body metabolic response. Full article

Background: Mutations in the EPOR gene can disrupt its normal signaling pathways, leading to hematological disorders such as polycythemia vera and other myeloproliferative diseases. Methodology: In this study, a range of bioinformatics tools, including SIFT, PolyPhen-2, SNAP2, SNPs & Go, PhD-SNP, I-Mutant2.0, MuPro, MutPred, ConSurf, HOPE, and Interpro were used to assess the deleterious effects of missense nonsynonymous single nucleotide polymorphisms (nsSNPs) on protein structure and function. Furthermore, molecular dynamics simulations (MDS) were conducted to assess the structural deviations of the identified mutant variants in comparison to the wild type. Results: The results identified two nsSNPs, R223P and G302S, as deleterious, significantly affecting protein structure and function. Both substitutions occur in functionally conserved regions and are predicted to be pathogenic, associated with altered molecular mechanisms. The MDSs indicated that while the wild-type EPOR maintained optimal stability, the G302S and R223P variants exhibited substantial deviations, adversely affecting overall protein stability and compactness. Conclusions: The computational analysis of missense nsSNPs in the EPOR gene identified two missense SNPs, R223P and G302S, as deleterious, occurring at highly conserved regions, and having substantial effects on erythropoietin receptor (EPO-R) protein structure and function, suggesting their potential pathogenic consequences. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial disease with unknown etiology and no effective cure, posing a great health burden to society. Erythropoietin (EPO) has been demonstrated to have protective roles in various tissues such as brain, spinal cord, heart, kidney and lung tissues. In this study, we investigate the specific anti-inflammatory, antioxidant and antiapoptotic effects of erythropoietin on lung tissue in a bleomycin-induced rat model of idiopathic pulmonary fibrosis. Methods: Recombinant human EPO or saline was injected, and the animals were monitored for 14 days after bleomycin instillation. Their hematocrit and serum EPO levels were determined. Histological and immunohistochemical analyses were performed. Results: The extent of tissue injury, determined through morphometric analysis, was significantly decreased in size in animals treated with erythropoietin. An immunohistochemical analysis of the expression of cyclooxygenase-2 (COX-2), inducible synthase of nitric oxide (i-NOS), metalloproteinase-9 (MMP-9), erythropoietin receptor (EPO-R), and cytochrome-C (cyt-C) found these enzymes to be decreased in a statistically significant manner in animals treated with erythropoietin when compared to a non-treated group. Conclusions: The reduced expression of COX-2, i-NOS, MMP-9, EPO-R, and i-NOS in the lung tissues of animals treated with EPO indicates the anti-inflammatory, antioxidant and antiapoptotic action of erythropoietin, suggesting its potential therapeutic role in pulmonary fibrosis. Full article

Erythropoietin (EPO), a hormone secreted mainly by the kidney, exerts its biological function by binding to its cell-surface receptor (EpoR). The presence of EPO and EpoR in the male and female reproductive system has been verified. Therefore, some of the key properties of EPO, such as its antioxidant and antiapoptotic effects, could improve the fertilizing capacity of spermatozoa. In the present study, the effect of two different concentrations of EPO (10 mIU/μL and 100 mIU/μL) on bovine sperm-quality parameters was evaluated during a post-thawing 4-h incubation at 37 °C. EPO had a positive effect on sperm motility, viability, and total antioxidant capacity. Moreover, EPO inhibited apoptosis, as it reduced both BCL2-associated X apoptosis regulator (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and cleaved cysteine-aspartic proteases (caspases) substrate levels in a dose-dependent manner. In addition, EPO induced sperm capacitation and acrosome reaction in spermatozoa incubated in capacitation conditioned medeia. These results establish a foundation for the physiological role of EPO in reproductive processes and hopefully will provide an incentive for further research in order to fully decipher the role of EPO in sperm physiology and reproduction. Full article

Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The objective of this project is to evaluate the downstream targets of miR-365 to determine any potential pathways or effects. Downstream targets for miR-365 (miRdatabase target scores > 90) were used for qPCR screening of oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27). Each oral cancer cell line expressed miR-365 downstream targets molybdenum cofactor synthesis-2 (MOCS2), erythropoietin receptor (EPOR), IQ motif containing-K (IQCK), carboxypeptidase A3 (CPA3), solute carrier family 24 member-3 (SLC24A3), and coiled-coil domain containing 47 (CCDC47)—although the expression levels varied somewhat. However, differential results were observed with ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ). These data suggest that many of the miR-365 targets are expressed in the oral cancers screened, with the differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12, which may be correlated with chemoresistance among two specific oral cancer cell lines (SCC25, SCC9). These results suggest this differential expression may signal potential targets for patient treatment with tumors exhibiting miR-365 and chemotherapeutic resistance. Full article

Soil moisture strongly interferes with the spectra of soil organic matter (SOM) in the near-infrared region, which reduces the correlation between organic matter and spectra and decreases accuracy in the prediction of SOM. In this study, we explored the feasibility of two types of spectral indices, two- and three-band mixed (SI) and three-band spectral indices (SI3), and two water removal algorithms, direct standardization (DS) and external parameter orthogonalization (EPO), to estimate SOM in wet soils using a total of 192 soil samples at six water content gradients. The estimation accuracies of spectral indices combined with water removal algorithms were better than those of full spectral data combined with water removal algorithms: the prediction accuracies of SI-EPO (R² = 0.735, RMSEp = 3.4102 g/kg) were higher than those of EPO (R² = 0.63, RMSEp = 4.1021 g/kg), and those of SI-DS (R² = 0.70, RMSEp = 3.7085 g/kg) were higher than those of DS (R² = 0.61, RMSEp = 4.2806 g/kg); SI3-EPO (R² = 0.752, RMSEp = 3.1344 g/kg) was better than SI-EPO; both EPO and DS effectively mitigated the influence of soil moisture, with EPO demonstrating superior performance in small-sample prediction scenarios. This study introduces a novel approach to counteract the impact of soil moisture on SOM estimation. Full article

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletics has become a concern. However, there is still room for improvement in gene-doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9, including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future. Full article

The present work presents a study of jet production in the central region ($\left|\eta \right|$ < 2.5) and the forward region (3 < $\left|\eta \right|$ < 5) in proton–proton collisions at different energies: $\sqrt{s}$ = 13.6 TeV, $\sqrt{s}$ = 20 TeV, and $\sqrt{s}$ = 27 TeV. These energies are the present and expected future energies of the Large Hadron Collider. In addition, the measurement of dijets—where the dijet selected is the one leading the jet in the central region and the second jet is the one with the sub-leading role in the forward region—was investigated with the same collision energies. Jets are reconstructed with the anti-kT (R = 0.5) algorithm in the transverse momentum range pT = 15–1000 GeV/c. Different Monte Carlo event generators were used: PYTHIA, HERWIG, and EPOS-LHC. The momentum, multiplicity, energy, pseudorapidity, and azimuthal angle of the jets were measured. In addition, the dijet multiplicity and the difference in the azimuthal angle were measured. The generation of events was carried out using the Rivet analysis framework. It is observed that, when the energy of the collision increases, the production of the jets in the central and forward regions and the dijets multiplicity increase; overall an agreement is observed between the three event generators. The disagreement between the different generators points to potential areas for development or additional study. Full article

Postoperative recurrence (POR) is the rule in patients with Crohn’s disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare the rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single-center randomized open-label clinical study in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 postoperatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score ≥ i2. We enrolled 35 patients (25 males, mean age 35 ± 1.4 years, median disease duration 5 ± 6.1 years) following ileocecectomy. Of these, seven (20%) were current smokers and nine (26%) biologics-experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs. 69%, p = 0.004) and 58 (47% vs. 75%), (p = 0.03, HR = 0.39, 95% CI = 0.16–0.93). POR was associated with an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628). Full article

Chronic hepatitis C virus (HCV) infection is commonly associated with depression and cognitive dysfunction, the cause of which could be related to the HCV neuroinvasion and/or state of chronic inflammation. Viral sequences and proteins were previously detected in the brain and since blood leukocytes can cross the blood–brain barrier, they could provide viral access to the CNS. Eighty chronic hepatitis C patients were tested for viral replication in PBMCs (detection of the HCV RNA-negative strand) and serum cytokines. Depression was assessed by the Beck Depression Inventory (BDI), neuroticism by the Eysenck Personality Inventory (N/EPO-R), and anxiety by the State-Trait Anxiety Inventory (STAI) while neurocognitive testing included the Wisconsin Card Sorting Test (WCST), Ruff Figural Fluency Test (RFFT), California Verbal Learning Test (CVLT), and Grooved Pegboard Test (GPT). The HCV RNA-negative strand was detected in PBMCs from 24 (30%) patients and these patients had significantly higher BDI scores (median 12.5 [IQR] 6.3–20.5 vs. median 8.00 [IQR] 3–12; p = 0.013). Both depression and anxiety correlated positively with IL-8 while cognitive flexibility, executive function, problem-solving skills, memory, and motor functioning correlated negatively with some proinflammatory cytokines. Our findings suggest that due to chronic HCV infection, the brain function is negatively affected by both viral replication in PBMCs and by the immune activation state. Full article

B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection. Using Nextflow, we developed a simplified workflow containing the algorithms FusionCatcher, Arriba, and STAR-Fusion. We analysed samples from 35 patients harbouring IGH fusions (IGH::CRLF2 n = 17, IGH::DUX4 n = 15, IGH::EPOR n = 3) and assessed the detection rates for each caller, before optimizing the parameters to enhance sensitivity for IGH fusions. Initial results showed that FusionCatcher and Arriba outperformed STAR-Fusion (85–89% vs. 29% of IGH fusions reported). We found that extensive filtering in STAR-Fusion hindered IGH reporting. By adjusting specific filtering steps (e.g., read support, fusion fragments per million total reads), we achieved a 94% reporting rate for IGH fusions with STAR-Fusion. This analysis highlights the importance of filtering optimization for IGH gene fusion events, offering alternative workflows for difficult-to-detect high-risk B-ALL subtypes. Full article