Potential Marker Research Articles

CEBPA mutation in acute myeloid leukemia: prognostic impact of bZIP domain mutation

Abstract One of the most important prognostic genes for acute myeloid leukemia (AML) is CEPBA, and its mutation (CEBPAmu) is present in nearly 10%–15% of de novo AML cases. CEBPAdm is associated with a favorable prognosis; however, CEBPAsm does not appear to have a better prognosis than CEBPAdm. We reviewed CEBPAmu-bZIP in 8694 cases across studies for prognostic impact in patients with de novo AML. It was observed that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. CEBPA-bZIP mutations were discovered in 562 (6.46%) of 8694 cases, with 366 (65.1%) harboring a second CEBPA mutation (CEBPA-double-mutated [CEBPAdm]) and 196 (34.9%) having a single CEBPA-bZIP only mutation. Multivariate analysis of three studies consisting of 1028, 4708, and 2958 patients showed that CEBPAmu in bZIP was the most potent predictor of overall survival (OS) with overall survivability of 53%, 62%, and 89%, respectively, independently. However, complete remission of disease with bZIP mutation in the same studies was found to be 80%, 62%, and 78.6%, respectively. These findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis.

Predictive biomarkers for low-dose IL-2 therapy efficacy in systemic lupus erythematosus: a clinical analysis

BackgroundLow-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE.MethodsWe pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results.ResultsRash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2.ConclusionsThese findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection

Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p < 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.

Recent Advances in the Molecular Biology of Chronic Lymphocytic Leukemia: How to Define Prognosis and Guide Treatment

Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in Western countries. In recent years, there have been important advances in the knowledge of molecular alterations that underlie the disease’s pathogenesis. Very heterogeneous prognostic subgroups have been identified by the mutational status of immunoglobulin heavy variable genes (IGVH), FISH analysis and molecular evaluation of TP53 mutations. Next-generation sequencing (NGS) technologies have provided a deeper characterization of the genomic and epigenomic landscape of CLL. New therapeutic targets have led to a progressive reduction of traditional chemoimmunotherapy in favor of specific biological agents. Furthermore, in the latest clinical trials, the minimal residual disease (MRD) has emerged as a potent marker of outcome and a guide to treatment duration. This review focuses on recent insights into the understanding of CLL biology. We also consider the translation of these findings into the development of risk-adapted and targeted therapeutic approaches.

Socioeconomic position and sports in the US today: the economic and cultural capital of sports followers

PurposeThis study aims to explore the relationship between social class and sports following in the United States, addressing a gap in research that has largely overlooked spectator sports in sociocultural analyses. The paper seeks to be an expanded update on previous work focusing on how socioeconomic factors such as income and education interact with sports engagement.Design/methodology/approachEmploying 2023 national survey data from the United States, this study analyzes the following of 31 different spectator sports in relation to income and education. The methods include the use of Cramer’s V statistic to assess associations between sports following and socioeconomic variables and multiple logistic regression analysis to understand the relative predictive power of these variables on sports following.FindingsThe study reveals significant socioeconomic associations in sports consumption patterns in American society, with higher income and education levels generally predicting an increased likelihood of following a wide range of sports. Notably, international soccer leagues like the English Premier League and La Liga showed the strongest associations with higher socioeconomic status, suggesting their following might serve as particularly potent markers of sociocultural distinction.Originality/valueThis research provides a contemporary empirical update to the study of social class and spectator sports in the US, expanding the understanding of the evolving landscape of sports consumption and its socioeconomic connections. It underscores the importance of considering sports following as a vital aspect of cultural engagement, reflecting and reproducing broader socioeconomic stratifications. The findings offer new insights into how factors of social class shape sports consumption today, highlighting the role of sports in the cultural life of different social classes in the US.

Epigenomic biomarkers insights in PBMCs for prognostic assessment of ECMO-treated cardiogenic shock patients

ObjectiveAs the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited.MethodsThirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses.ResultsThe ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test).ConclusionsThis study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes.

Development of a novel crAss-like phage detection method with a broad spectrum for microbial source tracking

CrAssphage has been recognized as the most abundant and human-specific bacteriophage in the human gut. Consequently, crAssphage has been used as a microbial source tracking (MST) marker to monitor human fecal contamination. Many crAss-like phages (CLPs) have been recently discovered, expanding the classification into the new order Crassvirales. This study aims to assess CLP prevalence in South Korea and develop a detection system for MST applications. Thirteen CLPs were identified in six human fecal samples and categorized into seven genera via metagenomic analysis. The major head protein (MHP) displayed increased sequence similarity within each genus. Eight PCR primer candidates, designed from MHP sequences, were evaluated in animal and human feces. CLPs were absent in animal feces except for those from raccoons, which hosted genera VI, VIIa, and VIIb. CLPs were detected in 91.52% (54/59) of humans, with genus VI (38 out of 59) showing the highest prevalence, nearly double that of p-crAssphage in genus I (22 out of 59). This study highlights genus VI as a potent MST marker, broadening the detection range for CLPs. Human-specific and selectively targeted MST markers can significantly impact hygiene regulations, lowering public health costs through their application in screening liver, sewage, wastewater, and various environmental samples.

Ultrasensitive Electrochemiluminescence Biosensor Based on DNA-Bio-Bar-Code and Hybridization Chain Reaction Dual Signal Amplification for Exosomes Detection.

Exosomes have received considerable attention as potent reference markers for the diagnosis of various neoplasms due to their close and direct relationship with the proliferation, adhesion, and migration of tumor. The ultrasensitive detection of cancer-derived low-abundance exosomes is imperative, but still a great challenge. Herein, we report an electrochemiluminescence (ECL) biosensor based on the DNA-bio-bar-code and hybridization chain reaction (HCR)-mediated dual signal amplification for the ultrasensitive detection of cancer-derived exosomes. In this system, two types of aptamers were modified on the magnetic nanoprobe (MNPs) and gold nanoparticles (AuNPs) with numerous bio-bar-code DNA, respectively, which formed "sandwich" structures in the presence of specific target exosomes. The "sandwich" structures were separated under magnetic field, and the numerous bio-bar-code DNA were released by dissolving AuNPs. The released bio-bar-code DNA triggered the HCR procedure to produce a good deal of long DNA duplex structure for embedding in hemin, which generated strong ECL signal in the presence of coreactors for ultrasensitive detection of exosomes. Under the optimal conditions, it exhibited a good linearly of exosomes ranging from 10 to 104 exosomes particle μL-1 with limit of detection down to 5.01 exosome particle μL-1. Furthermore, the high ratio of ECL signal and minor change of ECL intensity indicated the good specificity, stability, and repeatability of this ECL biosensor. Given the good performance for exosome analysis, this ultrasensitive ECL biosensor has a promising application in the clinical diagnosis of early cancers.

The solvation shell probed by resonant intermolecular Coulombic decay

Molecules involved in solvation shells have properties differing from those of the bulk solvent, which can in turn affect reactivity. Among key properties of these molecules are their nature and electronic structure. Widely used tools to characterize this type of property are X-ray-based spectroscopies, which, however, usually lack the capability to selectively probe the solvation-shell molecules. A class of X-ray triggered “non-local” processes has the recognized potential to provide this selectivity. Intermolecular Coulombic decay (ICD) and related processes involve neighbouring molecules in the decay of the X-ray-excited target, and are thus naturally sensitive to its immediate environment. Applying electron spectroscopy to aqueous solutions, we explore the resonant flavours of ICD and demonstrate how it can inform on the first solvation shell of excited solvated cations. One particular ICD process turns out to be a potent marker of the formation of ion pairs. Another gives a direct access to the electron binding energies of the water molecules in the first solvation shell, a quantity previously elusive to direct measurements. The resonant nature of the processes makes them readily measurable, providing powerful new spectroscopic tools.

Using progesterone to follicular index ratio is better correlated with intracytoplasmic sperm injection outcome than using serum progesterone level alone.

to investigate the possibility of using the ratio of serum progesterone level to the number of follicles, according to ovarian response in the day of human chorionic gonadotrophin trigger, as a predictor of cycle outcome. A prospective intervensional study was conducted at Kamal Al-Samarai Hospital for Infertility Treatment and IVF during the period from December 2020 to September 2021. Ninety infertile women underwent intracytoplasmic sperm injection (ICSI) cycles using antagonist protocol. Moreover, once the patient reached triggering criteria, meticulous recording of follicular index together with serum estrogen level and serum progesterone level are measured. Fresh embryo transfer of cleavage stage embryo is done once serum progesterone level was less than 1.5 ng/mL. A follow-up to confirm pregnancy rate and cycle outcome was done. The study showed a positive pregnancy rate of 28.9%. The relationship between progesterone follicular index (Prog/FI) ratio and (ICSI) outcome was highly significant with a p value of 0.001. Additionally, an inverse relationship, as the ratio was lower the pregnancy rate was improved, was documented. The receiver operating characteristic (ROC) curve for progesterone follicular index ratio was 0.711 with a cut off value of 0.0354 ng/mL in addition to a sensitivity of 65.6 and a specificity of 65.4. The serum progesterone level is an independent factor for the prediction of intracytoplasmic sperm injection (ICSI) outcome, whereas the progesterone follicular index ratio can be used as a potential marker for predicting ICSI outcome in fresh embryo transfer.

ICTP concentration in cervical-vaginal fluid as a potential marker of membrane collagen degradation before labor.

Numerous physical and chemical processes lead to rupture of membranes. Within the fetal membranes there are numerous types of metalloproteinases, which cause collagen type I degradation. The C-terminal telopeptide of colagen type I (ICTP) is the breakdown product of type I collagen. The aim of the study was to determine whether ICTP is secreted into the vaginal-cervical fluid (VCF) in the case of physiological rupture of the membranes of the fetus before delivery. The study was conducted in March 2021 at the Department of Obstetrics and Perinatology of the Jagiellonian University in Cracow, Poland. Twenty-three cases were included in the study. During routine gynecological examination with the use of specula, VCF was collected twice in a volume of 50 µL. The obtained material was then subjected to enzyme immunoassay using the Human C-telopeptide of type I collagen (ICTP) ELISA Kit (Catalog Number. CSB-E10363h). The concentration of ICTP in the sample was calibrated. The concentration range that the device can detect was 25 ng /mL-800 ng/mL. The presence of ICTP in the VCF was confirmed. The minimum concentration was 43.72 ng/mL, the maximum was 762.59, in five cases the concentration was outside the maximum scale of the device. ICTP was confirmed in the VCF of pregnant women before physiological delivery. Further studies are required to accurately evaluate ICTP as a marker of the processes of collagen degradation in fetal membranes in the mechanism of physiological labor and premature rupture of the membranes.

The effect of two anti-inflammatory dietary components, omega-3 and resveratrol, on endometriosis.

Endometriosis is an inflammatory condition defined by the presence of endometrial glands and stroma outside the uterine cavity. Given the substantial body of evidence supporting the role of inflammation in the pathophysiology of various chronic illnesses, the concept of an anti-inflammatory diet has garnered significant attention in recent research. Some nutrients, such as omega-3 fatty acids and resveratrol (RES), have demonstrated distinct anti-inflammatory properties. Therefore, the objective of this systematic review was to search the Embase, Medline, and PubMed databases for literature from August 2008 to August 2023 regarding the effects of two anti-inflammatory dietary components, omega-3 and RES, on endometriosis. A total of 215 records were identified, out of which 58 were screened, 23 met the eligibility criteria, and 19 were included in this review. The results of this systematic review indicate that EPA is suggested to have anti-inflammatory properties and may serve as a potential marker for illness severity. RES offers a range of advantages, including inflammation reduction, angiogenesis suppression, proliferation inhibition, and apoptosis induction. To validate these findings and assess their clinical relevance, future research and clinical trials are warranted.

The CD44s Isoform is a Potential Biomarker for Predicting Craniopharyngioma Recurrence in Children

Adamantinomatous craniopharyngioma (ACP) is an intracranial tumor considered partly malignant due to its ability to infiltrate surrounding structures and tendency to relapse despite radical resection. CD44 is a known stem cell marker in ACP and is upregulated in cell clusters of invasive ACP protrusions; however, the functions of its alternative splicing isoform variants, CD44s and CD44v1-10, have not yet been studied in terms of ACP recurrence, despite their confirmed roles in cancer development and progression. In this study, we first confirmed the difference in total CD44 expression between samples from patients who experienced relapse and those from patients who did not. Moreover, our findings showed that, in recurrent samples, the predominant isoform expressed was CD44s, which might indicate its significance in predicting ACP recurrence. The association between increased CD44 expression and recurrence may lead to the development of prognostic markers of ACP aggressiveness and relapse potential; however, further studies are needed to clarify the exact mechanism of CD44 expression.

NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway.

Nucleolar protein 16 (NOP16) is present in the protein complex of the nucleolus. The NOP16 promoter contains a c-Myc binding site, and the transcriptional regulation by c-Myc directly regulates NOP16 expression levels. Dysregulation of NOP 16 is currently reported in only a small number of cancers. In this study, the expression profile of NOP 16 in hepatocellular carcinoma (LIHC) and its clinical significance were analyzed. NOP16 expression in hepatocellular carcinoma (LIHC) and its relationship with the clinical characters of LIHC were examined using the Cancer Genome Atlas (TCGA), the Gene Expression comprehensive database (GEO), Kaplan-Meier survival analysis, univariate Cox analysis, multivariate Cox analysis, ROC curve analysis of KEGG enrichment, GSEA enrichment, in vitro experiments (e.g., siRNA interference of NOP16 expression in hepatoma cells, Keap1-Nrf2 pathway, cell cycle, cell apoptosis and Transwell assays), and LIHC single-cell sequencing (scRNA). Pan-cancer analysis revealed that NOP16 was highly expressed in 20 cancer types, including LIHC, and high NOP16 expression was an independent adverse prognostic factor in LIHC patients. The expression levels of NOP16 mRNA and protein were significantly increased in tumour tissues of LIHC patients compared to normal tissues. The functions of co-expressed genes were primarily enriched in the cell cycle and reactive oxygen species metabolism. The experimental results showed that knockdown of NOP16 activated the Keap/Nrf2 signalling pathway and inhibited the invasion, migration, and EMT progression of LIHC cells. LIHC scRNA-seq data showed that NOP16 was primarily expressed in T lymphocytes. NOP16 promoted cancer development in LIHC and caused an imbalance in Keap/Nrf2 signalling, which subsequently caused the aberrant expression of genes typical for EMT, cell cycle progression and apoptosis. NOP16 is a potential prognostic marker and therapeutic target for hepatocellular carcinoma progression.

Image Sensing of Gaseous Acetone Using Secondary Alcohol Dehydrogenase-Immobilized Mesh for Exhaled Air.

Human-borne acetone is a potent marker of lipid metabolism. Here, an enzyme immobilization method for secondary alcohol dehydrogenase (S-ADH), which is suitable for highly sensitive and selective biosensing of acetone, was developed, and then its applicability was demonstrated for spatiotemporal imaging of concentration distribution. After various investigations, S-ADH-immobilized meshes could be prepared with less than 5% variation by cross-linking S-ADH with glutaraldehyde on a cotton mesh at 40 °C for 15 min. Furthermore, high activity was obtained by adjusting the concentration of the coenzyme nicotinamide adenine dinucleotide (NADH) solution added to the S-ADH-immobilized mesh to 500 μM and the solvent to a potassium phosphate buffer solution at pH 6.5. The gas imaging system using the S-ADH-immobilized mesh was able to image the decrease in NADH fluorescence (ex 340 nm, fl 490 nm) caused by the catalytic reaction of S-ADH and the acetone distribution in the concentration range of 0.1-10 ppm-v, including the breath concentration of healthy people at rest. The exhaled breath of two healthy subjects at 6 h of fasting was quantified as 377 and 673 ppb-v, which were consistent with the values quantified by gas chromatography-mass spectrometry.

N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats.

Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS. The results of different studies over the past decades have established the protective effect of NAE on many pathological conditions. This study aimed to investigate the cardioprotective effects of C18:0 NAE- N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE- N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues. The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis. The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes. The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.

Near-infrared Spectroscopy for Remote Sensing of Porosity, Density, and Cubicity of Crystalline and Amorphous H2O Ices in Astrophysical Environments

We present laboratory spectra of pure amorphous and crystalline H2O ices in the near-infrared (NIR, 1–2.5 μm/10,000–4000 cm−1) at 80–180 K. The aim of this study is to provide spectroscopic reference data that allow remotely accessing ice properties for icy objects such as icy moons, cometary ice, or Saturn rings. Specifically, we identify new spectral markers for assessing three important properties of ices in space: (i) porosity/fluffiness, (ii) bulk density of amorphous ice, and (iii) cubicity in crystalline ice. The analysis is based on the first OH-stretching overtone (2ν OH) and the combinational band at 5000 cm−1/2 μm, which are potent spectral markers for these properties. By comparison of vapor-deposited, microporous amorphous solid water, pore-free low-, high-, and very-high-density amorphous ice, we are able to separate the effect of (bulk) density from the effect of porosity on NIR-spectra of amorphous ices. This allows for clarifying a longstanding inconsistency about the density of amorphous ice vapor-deposited at low temperatures, first brought up by Jenniskens & Blake. Direct comparison of NIR spectra with powder X-ray diffractograms allows us to correlate spectral features with the number of cubic stacking layers in stacking-disordered ice Isd, ranging from fully cubic ice Ic to fully hexagonal ice Ih. We show that exposure times for instruments on the James Webb Space Telescope are in the hour range to distinguish these properties, demonstrating the usefulness of the neglected NIR spectral range for identifying ices in space.

Potential role of serum copeptin among smoker T2DM patients with emphasis to ACE I/D gene polymorphism predicting DN

Diabetic nephropathy represents one of the main long-term complications in T2DM patients. Cigarette smoking represents one of modifiable renal risk factors to kidney damage due to lead (Pb) exposure in these patients. Our goal is to investigate serum copeptin and Kidney injury molecule-1 (KIM-1) and urinary lead (UPb) in type 2 diabetes mellitus (T2DM) patients even smokers and non-smokers groups and compared to corresponding health controls and assess its associations with Angiotensin-Converting enzyme Insertion/Deletion polymorphism [ACE (I/D)] polymorphism in diabetic nephropathy progression in those patients. In present study, 106 T2DM patients and 102 healthy control individuals were enrolled. Serum glucose, copeptin, KIM-1, total cholesterol (TChol), triglycerides (TG), estimated glomerular filtration rate (eGFR) and UPb levels and ACE (I/D) polymorphisms were assessed in both groups. Results mentioned to significant variations in all parameters compared to in T2DM group compared to control group. Serum copeptin and UPb demonstrated significant difference in diabetic smokers (DS) and diabetic non-smokers (DNS) groups while KIM-1 exhibited significant change between DNS and healthy control non-smokers (CNS) groups. Positive relation was recorded between serum glucose and KIM-1 while negative one was found between serum copeptin and TChol. D allele was associated with significant variation in most parameters in T2DM, especially insertion/deletion (ID) polymorphism. ROC curve analysis (AUC) for serum copeptin was 0.8, p < 0.044 and for Kim-1 was 0.54, p = 0.13 while for uPb was 0.71, p < 0.033. Serum copeptin and UPb might be a prognostic biomarker for renal function decline in smoker T2DM patients while KIM-1 was potent marker in non-smoker T2DM with association with D allele of ACE I/D gene polymorphism.

Serum IgA/C3 ratio: a useful marker of disease activity in patients with IgA nephropathy.

High serum IgA and low serum C3 levels resulting from lectin and alternative pathway activation might be related to IgA nephropathy (IgAN) progression and exacerbation. This study examined whether the serum IgA/C3 ratio can serve as an IgAN progression marker. (1) This nationwide multicenter retrospective study in Japan included 718 patients with biopsy-confirmed IgAN. The patients whose serum creatinine levels at the time of renal biopsy had doubled were defined as having disease progression. (2) Furthermore, to investigate the pathological significance of a reduction in serum IgA/C3 ratio, we reviewed 63 patients whose serum IgA and C3 data at the end of the observation period were obtained. (1) A Kaplan-Meier analysis of the patients with IgAN revealed that the group with a high serum IgA/C3 (≥ 3.3) had a significantly worse renal outcome. In a multivariate analysis of eGFR ≥ 60mL/min per 1.73m2 at the time of biopsy, poor renal outcome was significantly predicted by a serum IgA/C3 ratio of ≥ 3.3. (2) A 15% reduction in the change of serum IgA/C3 ratio was associated with a significantly higher percentage of complete remission of proteinuria. Among the four groups divided by treatment, both the serum IgA/C3 ratio and proteinuria were reduced only in the tonsillectomy and steroid pulse group. The serum IgA/C3 level might reflect the disease activity and be a potent surrogate marker of therapeutic efficacy in patients with IgAN.

Identification of Diagnosis and Typological Characteristics Associated with Ferroptosis for Ulcerative Colitis via Bioinformatics and Machine Learning

Objective: To investigate and validate ferroptosis genes (FRGs) in ulcerative colitis (UC) for diagnostic, subtype, and biological agent reactivity, with the goal of providing a foundation for the identification of novel therapeutic targets and the rational use of infliximab in clinical practice. Methods: UC datasets and FRGs were selected from the Gene Expression Omnibus (GEO) and FerrDb databases. WGCNA was used to identify characteristic genes of UC. LASSO and SVM models were used to discover key FRGs in UC. A nomogram was constructed for diagnosing UC using logistic regression (LR), We performed internal and external validation for the model. Furthermore, we constructed a hub-gene-signature prediction model for the effectiveness of infliximab in treating UC and deployed it on the website. Finally, the hub gene-drug interaction networks were constructed. Results: Nineteen ferroptosis-related genes associated with UC were identified through bioinformatics analysis. FTH1 and GPX4 were two of the down-regulated genes.The seventeen upregulated genes consisted of DUOX1, DUOX2, SOCS1, LPIN1, QSOX1, TRIM21, IDO1, SLC7A11, MUC1, HSPA5, SCD, ACSL3, NOS2, PARP9, PARP14, LCN2, and TRIB2. Five hub genes, including LCN2, QSOX1, MUC1, IDO1, and TRIB2, were acquried via machine learning. The mean auc of internal validation was 0.964 and 0.965 respectively, after using cross-validation and bootstrap in the training set based on the 5 hub-gene diagnostic models. In the external validation set, the AUC reached 0.976 and 0.858. RF model performs best in predicting infliximab effectiveness. In addition, we identified two ferroptosis subtypes. Cluster A mostly overlaps with the high-risk score group, with a hyperinflammatory phenotype. method: UC datasets and FRGs were selected from the Gene Expression Omnibus (GEO) and FerrDb databases. WGCNA was used to identify characteristic genes of UC. LASSO and SVM models were used to discover key FRGs in UC. A nomogram was constructed for diagnosing UC using logistic regression (LR), We performed internal and external validation for the model. Furthermore, we constructed a 5 hub-gene-signature prediction model for the effectiveness of infliximab in treating UC and deployed it on the web site. Finally, 5 hub gene-drug interaction networks were constructed. Conclusions: This research indicated that five hub genes related to ferroptosis might be potential markers in diagnosing and predicting infliximab sensitivity for UC. result: A total of 362 genes were found to be closely associated with UC . These genes were enriched in immune response, response to stress, oxidoreductase activity, glycerolipid metabolism, ferroptosis, etc. Five ferroptosis-related hub genes were identified through machine learning, including LCN2, QSOX1, MUC1, IDO1, and TRIB2. The mean auc of internal validation was 0.964 and 0.965 respectively, after using cross-validation and booststrap in the training set. In the external validation set, the AUC of the diagnostic model reached 0.858. RF model performs best in predicting infliximab effectiveness. In addition, we identified two ferroptosis subtypes. ClusterA mostly overlaps with the highrisk score group, with a hyperinflammatory phenotype. conclusion: This research indicated that five hub genes related to ferroptosis might be potential markers in diagnosing and predicting infliximab sensitivity for UC.