Biomarkers For Early Prediction Research Articles

Longitudinal associations between cerebrospinal fluid glial activation markers, depression, and dopamine transporter availability in patients with Parkinson's disease.

Depression and decreased dopamine transporter (DAT) availability are prevalent in Parkinson's disease (PD), yet early predictive biomarkers are lacking. This study investigates the longitudinal associations between cerebrospinal fluid (CSF) neuroglial activation markers, sTREM2 and YKL-40, and depression, as well as DAT availability, in PD patients. We analyzed data from 172 PD subjects and 80 matched healthy controls from a large longitudinal study. A generalized linear mixed-effects model assessed the longitudinal associations of CSF sTREM2 and YKL-40 with depression and DAT availability. Causal mediation analysis determined if DAT decline mediated the effects of sTREM2 and YKL-40 on depression. Cross-sectional analysis revealed a negative correlation between CSF sTREM2 and baseline depression scores in PD patients. CSF YKL-40 negatively correlated with baseline left caudate nucleus, left anterior putamen, and right anterior putamen specific binding ratios (SBR). Longitudinally, higher baseline CSF sTREM2 predicted faster depression progression (β = 0.828, p < 0.001) and a rapid decline in right putamen SBR (β = 0.072, p = 0.016). Similarly, higher baseline CSF YKL-40 predicted faster depression progression (β = 0.586, p = 0.004) and a decline in left anterior putamen SBR (β = 0.058, p = 0.035). Causal mediation analysis indicated that baseline CSF sTREM2 accelerated depression progression via its effect on right putamen and right anterior putamen SBR (Indirect effect = 0.103, p = 0.020; Indirect effect = 0.129, p = 0.016). CSF sTREM2 and YKL-40 are effective predictors for depression and DAT decline in PD, suggesting that neuroglial activation-induced dopaminergic neuron apoptosis significantly contributes to depression onset in PD.

Multiplexed immunoassay for a serum autoantibody biomarker panel in diagnostic and prognostic prediction of canine mammary tumors

Canine mammary tumor (CMT) is a prevalent and destructive disease often diagnosed at an advanced stage, leading to poor outcomes. Currently, there is a lack of effective biomarkers for early detection and prognostic prediction of CMT. To improve CMT detection, we established a multiplexed immunoassay using a fluorescence bead-based suspension array system to measure serum levels of autoantibodies against four CMT-associated proteins (AGR2, HAPLN1, IGFBP5, and TYMS) in CMT patients. Our data revealed that serum levels of the four autoantibodies (anti-AGR2, anti-HAPLN1, anti-IGFBP5, and anti-TYMS) were significantly elevated in CMT patients (n = 158) compared to healthy individuals (n = 39). Notably, serum levels of anti-AGR2, anti-HAPLN1, and anti-TYMS in the dogs with stage I CMT (n = 56) were higher than those in the healthy group. Using a marker panel consisting of the four autoantibodies for detecting malignant CMT (n = 125) achieved a sensitivity of 50.4% and a specificity of 90%. Furthermore, higher levels of anti-AGR2, anti-HAPLN1, anti-IGFBP5, and anti-TYMS were associated with poorer survival in CMT patients. Collectively, we established a multiplexed immunoassay platform to detect serum autoantibodies and demonstrated that a tailored autoantibody marker panel shows potential clinical applicability for the diagnosis and prognosis of CMT.

TRIM47 promotes hypopharyngeal and laryngeal cancers progression through promoting K63-linked ubiquitination of vimentin.

Hypopharyngeal and laryngeal cancers which belong to head and neck squamous cell carcinoma (HNSCC) are the two most malignant types of head and neck cancer, characterized by a low 5-year survival rate, high recurrence and metastasis rate. It is vital to explore strategies to suppress metastasis and improve prognosis for patients with these cancers. In this research, we analyzed the clinical data and found that E3 ubiquitin ligase TRIM47 was upregulated in cancer tissues of hypopharyngeal cancer and was closely associated with poor survival outcomes. In terms of mechanism, we performed tandem affinity chromatography and denatured Ni-NTA Agarose pulldown. As a result, TRIM47 was found to interact with vimentin and control vimentin stabilization through ubiquitination, specifically in the form of K63 chains. Importantly, through experiments of cancer cell viability and migration, we found that TRIM47 could enhance the proliferation and metastasis abilities of cancer cells in a vimentin-dependent manner, thus promoting the advancement of hypopharyngeal and laryngeal cancers. TRIM47 was verified to regulate cancer cells metastasis invivo using metastasis models. All these results imply that TRIM47 emerges as a potential biomarker for early diagnosis and metastasis prediction of hypopharyngeal and laryngeal cancers and represents a promising therapeutic target.

Value of Serum Retinol-Binding Protein, Lipoprotein A and Inflammatory Nutritional Indexes and their Interactions in Predicting Acute Kidney Injury after Coronary Angiography

Background: Contrast-induced acute kidney injury (CI-AKI) is a serious condition that can arise after undergoing coronary angiography (CAG). This complication is primarily caused by the toxic impact of contrast agents on the kidneys, along with oxidative stress and inflammatory responses. Identifying reliable biomarkers for early prediction remains essential due to the limited accuracy of existing clinical risk scores. Methods: This retrospective case-control study included 365 patients undergoing CAG between December 2021 and December 2023. Patients were categorized into non-AKI (n = 320) and AKI (n = 45) groups based on post-procedural renal function. Biomarkers including serum retinol-binding protein (RBP), lipoprotein A (Lp(a)), interleukin-6 (IL-6), and nutritional markers were measured. Baseline demographics, lipid profiles, and procedure details were recorded. Results: Baseline characteristics revealed no significant differences between groups in terms of age, BMI, gender, and prevalence of hypertension or diabetes mellitus. Notably, RBP (41.83 ± 10.22 mg/L vs. 32.45 ± 8.76 mg/L, p &lt; 0.001), Lp(a) (42.35 ± 13.87 mg/dL vs. 35.76 ± 11.54 mg/dL, p &lt; 0.001), and IL-6 (6.23 ± 2.14 pg/mL vs. 4.87 ± 1.59 pg/mL, p &lt; 0.001) levels were significantly higher in the AKI group. Total protein levels were significantly lower in the AKI group (6.88 ± 0.62 g/dL vs. 7.12 ± 0.54 g/dL, p = 0.006). Multivariate logistic regression identified RBP (OR 1.118, 95% CI 1.072–1.166, p &lt; 0.001), Lp(a) (OR 1.047, 95% CI 1.014–1.080, p = 0.005), and IL-6 (OR 1.710, 95% CI 1.355–2.157, p &lt; 0.001) as independent predictors of AKI, while higher total protein levels were protective (OR 0.497, 95% CI 0.257–0.960, p = 0.037). Conclusion: Serum RBP, Lp(a), IL-6, and total protein levels are valuable biomarkers for predicting CI-AKI after CAG. Elevated RBP, Lp(a), and IL-6 indicate higher risk, while higher total protein suggests protective effects.

Multiplex digital PCR for the simultaneous quantification of a miRNA panel

BackgroundmicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression. They have attracted significant interest as biomarkers for early diagnosis, prediction and monitoring of treatment response in many diseases. As individual miRNAs often lack the required sensitivity and specificity, miRNA signatures are developed for clinical applications. Digital PCR (dPCR) is a sensitive fluorescent-based quantification method, that can be used to detect the expression of miRNAs in patient samples. Our study presents the first proof-of-concept of a multiplexed dPCR assay for the simultaneous analysis and quantification of multiple miRNAs. ResultsAfter reverse transcription (RT) using a pool of miRNA-specific stem-loop primers, dPCR was performed with a universal reverse primer and miRNA-specific forward primers along with fluorescently-labelled hydrolysis probes. Multiple experimental parameters were evaluated and strategies for modulating the observed signals were devised. The optimised assay was applied to the analysis of miRNAs from cell lines and biological samples. Although absolute quantification was lost, due to the reverse transcription step, quantification was linear for the dilution series and results were highly reproducible for independent dPCR and RT reactions. Our results confirmed the high sensitivity of dPCR for patient samples. ConclusionsWe demonstrate the feasibility and reliability of multiplexed detection and quantification of miRNAs by dPCR that can be applied in a clinical setting to evaluate miRNA signatures.

Longitudinal evaluation of hemodynamic blood and echocardiographic biomarkers for the prediction of BPD and BPD-related pulmonary hypertension in very-low-birth-weight preterm infants

Very-low-birth-weight infants (VLBW, < 1500 g) are at risk of developing bronchopulmonary dysplasia (BPD) and are at risk for BPD-related pulmonary hypertension (PH). The longitudinal measurement of innovative blood and echocardiographic biomarkers might allow for a risk stratification of these infants. A prospective single-center cohort study was conducted between 01/2021 and 06/2023. Inclusion criteria were the combination of a birth weight < 1500 g and a gestational age (GA) ≤ 30/0 weeks. Assessment timepoints: T1 (day 7), T2 (day 28), and T3 (at 36 weeks post-menstrual age, PMA). Overall, 71 preterm infants were included for final analysis. The Zlog-transformed NTproBNPZlog (at T1 AUC 0.772; p = 0.019; at T2 AUC 0.874, p = 0.002), and endothelin-1 (ET1, at T1 AUC 0.789, p = 0.013) were identified as an early predictive biomarker for BPD/death in the univariate analysis. Additionally, echocardiographic markers of ventricular function and PH at T1 were predictive for BPD/death in the univariate analysis, with the highest predictivity found for the tricuspid annular plane systolic excursion-TAPSE (AUC 0.748, p = 0.016) and the pulmonary artery acceleration time to right ventricular ejection time (PAAT/RVET; AUC 0.744, p = 0.043). Regarding predictability of mortality alone NTroBNPZlog (at T1 AUC 0.973, p = 0.000), and CA125 (at T1 AUC 0.747, p = 0.008) were identified as potential predictors, as well as TAPSE (AUC 0.926, p = 0.000), and PAAT/RVET (AUC 0.985, p = 0.000) Several biomarkers including ET-1 (at T1 AUC 0.893, p = 0.000), TAPSE (AUC 0.974, p = 0.000), and PAAT/RVET (AUC 1.0, p = 0.000) at T1 were identified as univariate predictors for BPD-PH. In the multivariate analysis, no biomarker was identified as an independent predictor of the primary endpoint. Conclusion: Mainly at an early stage of postnatal neonatal care in VLBW preterm infants, several biomarkers were found to be associated with the combined endpoint BPD/death and BPD-PH. New candidates of blood biomarkers (NTproBNPZlog, ET-1, and CA125) and echocardiographic markers (TAPSE, PAAT/RVET) might serve as innovative predictors for BPD, BPD-PH, and adverse outcomes in VBLW infants. What is Known:• VLBW infants are at risk for the development of BPD and BPD-related PH, which both are main contributors for short and long-term morbidity and mortality. Several studies in the past focused on the evaluation of circulating blood biomarkers and biomarkers from echocardiographic assessment of these infants. But to date, there is still a lack on longitudinal prospective studies especially in VLBW infants.What is New:• For the first time, this set of selected blood biomarkers (with the first description of Zlog-transformed NTproBNP and CA125 in preterm infants) and several echocardiographic markers were analyzed in a prospective longitudinal study from birth until 36 weeks post menstrual age in VLBW infants. Our data help clinicians to identify preterm infants at risk for BPD, BPD-PH and death and to offer new candidates of biomarkers. This might help to facilitate decision making and guidance of therapy in these highly vulnerable patients.

LOXL1 promotes gastric cancer progression by β-catenin-cyclinD mediated proliferation

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1. In conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway.

Anti‑phenolic glycolipid‑I seropositivity among household contacts of leprosy patients in Egypt.

Leprosy is a chronic, debilitating disease lacking a definitive diagnostic biomarker. Serum anti-phenolic glycolipid-I (PGL-I) IgM antibody level is considered an important diagnostic and prognostic marker for leprosy patients. However, there is limited evidence on the role of anti-PGL-I IgM antibody level as early predictive biomarker of subclinical infection among Egyptian household contacts of leprosy patients. This study investigates the relationship between specific leprosy risk factors, diagnostic parameters of eighty-three leprosy cases, and serum anti-PGL-I IgM antibody levels in their corresponding household contacts. Our results demonstrate that anti-PGL-I IgM antibody level was significantly higher among contacts when more than four residents shared the same room with a leprosy case (p = 0.032). Additionally, anti-PGL-I IgM antibody level markedly increased in contacts of leprosy cases with disabilities (p = 0.001) or damaged nerves (p = 0.001). Our ROC curve analysis of anti-PGL-I antibody level as a predictor of exposure or infection among contacts revealed a cut-off value of 0.1, with a sensitivity of 75.0% and a specificity of 54.5%, indicating that most exposed household contacts are correctly identified. The overall accuracy of the ROC curve analysis was 72.3%, highlighting the practical utility of anti-PGL-I antibody level as a predictor for exposure or infection among household leprosy contacts. In conclusion, seropositivity of anti-PGL-I antibodies (> 0.1) among household leprosy contacts may be associated with a higher leprosy exposure risk. Continuous monitoring of anti-PGL-I antibody level in household leprosy contacts may potentially contribute to early detection and management of leprosy.

Novel miRNA markers and their mechanism of esophageal squamous cell carcinoma (ESCC) based on TCGA

MicroRNAs(miRNAs) are promising biomarkers for early esophageal squamous cell carcinoma (ESCC) detection and prognostic prediction. This study aimed to explore the potential biomarkers and molecular pathogenesis in the early diagnosis of ESCC. Firstly, 48 differentially expressed miRNAs (DEMs) and 1319 differentially expressed genes (DEGs) were identified between 94 ESCC tissues and 13 normal esophageal tissues in TCGA. From miRNA–mRNA regulatory network, there are 6558 target genes of the 48 DEMs, where 400 target genes are also among 1319 DEGs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicate that the 400 DEGs significantly enriched in cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and oocyte meiosis. And there are 66 DEGs among these six biological pathways, which we called GO-DEGs. From miRNA–mRNA regulatory network, 32 DEMs regulated the 66 GO-DEGs, where 22 DEMs were verified by different types of experiments in ESCC tissues, cells, or serum from the literature. For the other novel 10 DEMs, single-factor Cox regression analysis show that only hsa-miR-34b-3p showed no significant correlation with the overall survival of ESCC patients. Finally, we obtained the novel 9 ESCC-related DEMs, where three are down-regulated, and six are up-regulated. We analyzed the expression trends of target genes for five miRNAs and identified three significantly different miRNAs (hsa-miR-205-3p, hsa-miR-452-3p, and hsa-miR-6499-3p) confirmed by qPCR. Moreover, the stage-specific miRNAs were also suggested. These three qPCR validated miRNAs are also specific to the early stages of ESCC: hsa-miR-452-3p is specific to Stage I, II and III; hsa-miR-205-3p is specific in Stage II and III; and hsa-miR-6499-3p is Stage II specific. They might be the potential biomarkers for ESCC stage diagnosis. This study identified three novel miRNA markers potentially related to the diagnosis of ESCC and participated in the occurrence and development of ESCC through cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and signaling pathway for oocyte meiosis.

Utility of ctDNA as an early predictive biomarker of response to radiation in gynecologic malignancies

Utility of ctDNA as an early predictive biomarker of response to radiation in gynecologic malignancies

3D echocardiography and biomarkers for early diagnosis and prediction of chemotherapy induced right ventricular dysfunction in non-Hodgkin lymphoma patients

Abstract Background RCHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisone) use in non-Hodgkin's lymphoma (NHL) is limited by the risk of cardiotoxicity. Although the prognostic value of right ventricular (RV) function in mortality and morbidity has been well established, its involvement in chemotherapy-induced cardiotoxicity remains unclear. Aim To define new parameters able to detect early RV cardiotoxicity. Methods 51 patients (22 men, 61±14 years) with NHL scheduled for RCHOP, with three dimensional (3D) left ventricular (LV) ejection fraction (EF) &amp;gt;50%, were assessed at baseline, after 3rd and 6th cycle for right ventricular (RV) parameters: 3D EF, two dimensional (2D) global longitudinal strain (GLS) and free wall LS (FWLS), peak systolic annular velocity (S’), tricuspid annulus systolic excursion (TAPSE) and fractional area change (FAC). Biomarkers (troponin I, NT-pro-BNP) were measured. Cardiotoxicity was defined as LVEF reduction below 50% or preserved LVEF with LV LS decrease more than 15% from baseline. Results 15 (29%) of patients developed LV cardiotoxicity (group 1) while 36 did not fulfill this criteria (group 2). There was a significant reduction of RVEF, GLS, and FWLS, but not of RV S’, FAC, and TAPSE, starting with the 3rd cycle, with greater changes in group 1 vs. group 2 (see Table). RVEF reduction correlated with changes of FWLS, GLS, RV S’, and troponin (r=0.612, r=0.513, r=0.362, r=-0.358, respectively; all p&amp;lt;0.05). Reduction of FWLS after the 3rd cycle was the best independent predictor for RVEF decrease after the 6th cycle (R²=0.433, p&amp;lt;0.0001). FWLS decrease with more than 26% predicted cardiotoxicity after the 6th cycle (sensitivity of 81%; specificity of 78%). Conclusion 3D EF, 2D systolic deformation, and troponin I are able to detect early chemotherapy-induced right ventricular cardiotoxicity, and to predict further decline of RVEF in NHL patients. Thus, routine follow-up of RV function, along with the LV function, should be assessed during and after chemotherapy.RV parameters and troponin during RCHOP

Maternal serum Numb in the first trimester of pregnancy as a biomarker for early prediction of pre-eclampsia: A prospective cohort study.

Early identification of women at risk of developing pre-eclampsia is beneficial as it allows for timely intervention strategies. This study aimed to evaluate the potential of serum Numb in the first trimester as a biomarker for early prediction of pre-eclampsia. This prospective observational cohort study was carried out at a tertiary teaching hospital between January 2021 and December 2022. A total of 1024 women were recruited during their 8-13 weeks of pregnancy and were followed up until delivery. Serum Numb levels were measured during 8-13 weeks of gestation for all participants. At the same time, the participants' anthropometric, clinical, and laboratory data were collected. A logistic regression model was used to investigate the potential association between serum Numb levels and the risk of pre-eclampsia. Receiver operating characteristic curves (ROCs) and area under the curves (AUCs) were utilized to evaluate the predictive efficacy of serum Numb levels for pre-eclampsia in the first trimester. Serum Numb levels were found to be significantly higher in pregnant women who developed pre-eclampsia compared to those who did not develop pre-eclampsia. Increased serum Numb levels were identified as an independent risk factor for pre-eclampsia, with an odds ratio (OR) of 3.27 (95% CI: 2.05-4.53) for the risk of pre-eclampsia. Numb levels showed a significant positive correlation with the risk of pre-eclampsia. Furthermore, Numb levels demonstrated a strong predictive efficacy for pre-eclampsia in the first trimester of pregnancy, with an AUC value of 0.86, a cutoff value of 48.73 ng/mL, a sensitivity of 79.24%, and a specificity of 75.73%. Serum Numb in the first trimester of pregnancy can serve as a biomarker for the early prediction of pre-eclampsia. This provides a valuable approach in clinical practice to identify pregnant women in the first trimester of pregnancy, who are at a higher risk of developing pre-eclampsia.

Neutrophil CD10 and CD16 as markers of generalized infection development in newborns

BACKGROUND: Neonatal sepsis remains a critical concern. Thus, predictors of infection development and generalization should be determined. AIM: This study aimed to determine novel neutrophil surface biomarkers for early prediction of the infections in newborns. MATERIALS AND METHODS: This observational, single-center, prospective, selective, uncontrolled, unblinded experimental study included 261 newborns, with a mean postconceptual age of 38.7 (38.4–39.0) weeks and a mean gestation age of 38.0 (37.7–38.2) weeks. Blood samples were collected into vacutainers on hospitalization day 1. Patients were enrolled between April 2022 and December 2023. The primary endpoints were length of stay in the ICU and total length of hospitalization in patients with normal and decreased values of CD16 and CD10 neutrophils and HLA-DR monocytes. The expression of CD16 on CD62Lhigh neutrophils, total neutrophil CD10, and monocyte HLA-DR were evaluated by flow cytometry. RESULTS: We assessed infants in the “control” (n = 96), “localized infection” (n = 95), and “generalized infection” (n = 70) subgroups. In all patients, a decrease in CD16 was associated with an increase in the median ICU stay from 4 to 8 days (p = 9.33 × 10–8) and total stay from 14 to 22 days (p = 1.58 × 10–7). A decrease in CD10 was associated with an increase in median ICU stay from 4 to 8 days (p = 3.01 × 10–6) and in the total stay from 14 to 19 days (p = 2.78 × 10–5). A decrease in monocytic HLA-DR was associated with a longer ICU and total hospital stay: 4 vs 8 days (p = 7.16 × 10–5) and 14 vs 21 days (p = 4.03 × 10–5), respectively. The median ICU stay in patients with a decrease in CD16 but normal CD10 was 4 days, whereas a decrease in both indicators was associated with prolonged hospital stay to 11 days (p = 2.13 × 10–5). The median hospital stay in patients with decreased CD16 but normal CD10 was 16 days, whereas the drop of both markers was related with increase of hospitalization stay to 23 days (p = 3.36 × 10–6). In the “localized infection” subgroup, low CD16 was associated with an increased median ICU stay from 4 to 6 days (p = 0.010) and the median hospital stay from 13 to 19 days (p = 4.14 × 10–4). In the “generalized infection” subgroup, decreased CD10 was related with prolongation of the median ICU stay from 7 to 11 days (p = 0.011) and the median total duration of hospitalization from 19 to 27 days (p = 0.037). CONCLUSIONS: A decrease in CD10 and CD16 on the neutrophils at the start of clinical is an unfavorable prognostic factor of infectious and septic complications in newborns.

Mismatch responses of basic auditory temporal processing: early predictive biomarkers of Chinese Reading

ABSTRACT The study aimed to explore whether neurophysiological measures of auditory processing in preschoolers can predict Chinese reading after going to school. Mismatch responses (MMRs) to auditory frequency, duration, and temporal pattern deviants were examined in 24 Chinese preschoolers (6.59 ± 0.25 years old). Reading abilities were tracked in Grades 2 (8.09 ± 0.29 years old) and 4 (9.65 ± 0.28 years old). We found that temporal pattern MMRs in preschoolers continuously contributed to Chinese reading fluency in Grades 2 and 4. However, MMRs to frequency or duration deviants did not predict their reading abilities in Grades 2 or 4. These findings suggest that MMRs of basic auditory temporal processing in preliterate children can serve as predictive biomarkers for future Chinese reading acquisition, thus holding promise for identifying Chinese children at risk of dyslexia before formal school education and further guiding early intervention to support their reading development.

Serum neutrophil gelatinase-associated lipocalin and cystatin C is associated with blood pressure in ex-preterm children and adolescents.

As preterm birth is a risk factor for hypertension (HTN), biomarkers for early prediction of HTN in childhood is an emerging need. The aims of the study were to evaluate serum biomarkers in ex-preterm children and examine for associations with office peripheral and central SBP (cSBP), ambulatory BP parameters and pulse wave velocity (PWV). This case-control study included children and adolescents born prematurely (ex-preterms) and at full term (controls). All participants underwent office and ambulatory BP monitoring, assessment of cSBP, PWV and serum biomarkers at the same visit. Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-2, metalloproteinase-9 (MMP-2, MMP-9) and Cystatin C (CysC) were measured using ELISA. The study population included 52 ex-preterm individuals and 26 controls. Mean age was 10.7 ± 3.6 years. NGAL, MMP-2, MMP-9, and CysC levels were similar between the ex-preterm and the control group. In the ex-preterm group, NGAL is associated with office SBP z score ( β = 1.007, 95% CI 1.001-0.014, P = 0.049), CysC with office DBP z score ( β = 1.003, 95% CI 1.001-0.005, P = 0.018) and cSBP z score ( β = 1.003, 95% CI 1.001-0.005, P = 0.006) independently of age, sex and BMI z score. Among ex-preterm children and adolescents 17% had ambulatory HTN and 31% had white-coat HTN. NGAL levels were higher in ex-preterm children with WCH compared with children with normal BP [57.9 (IQR 50.8) versus 34.6 (IQR 46.2)], P = 0.018]. WCH is common in ex-preterm children and adolescents and is associated with higher NGAL levels and CysC presents positive association with cSBP. The findings in this study provides preliminary evidence that NGAL and CysC may have a role in predicting the risk of developing hypertension later in life. Further studies are warranted.

Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

Maternal Plasma miRNAs as Early Biomarkers of Moderate-to-Late-Preterm Birth.

Globally, preterm birth (PTB) is a primary cause of mortality and morbidity in infants, with PTB rates increasing worldwide over the last two decades. Biomarkers for accurate early prediction of PTB before the clinical event do not currently exist. Given their roles in the development and progression of many disease states, there has been increasing interest in the utility of microRNAs (miRNAs) as early biomarkers for pregnancy-related disorders, including PTB. The present study was designed to examine potential differences in miRNA abundances in maternal plasma from mothers with infants born following a moderate to late (28-36 weeks' gestation, n = 54) spontaneous PTB (SPTB) compared to mothers with matched term infants (n = 54). Maternal plasma collected at 15 weeks' gestation were utilised from the Auckland and Adelaide cohorts from the Screening for Pregnancy Endpoints (SCOPE) study. miRNAs in plasma were quantified using the NanoString nCounter expression panel (800 miRNAs). The top four most abundant miRNAs were significantly decreased in the plasma of mothers in the SPTB group with results consistent across both cohorts and pathway analysis was undertaken to examine the biological processes linked to the dysregulated miRNAs. The top candidate miRNAs (miRs-451a, -223-3p, let-7a-5p, and -126-3p) were linked to gene pathways associated with inflammation, apoptosis, and mitochondrial biogenesis. Moreover, miRNAs were consistently less abundant in the plasma of mothers of preterm infants across both sites, suggesting potential global dysregulation in miRNA biogenesis. This was supported by a significant downregulation in expression of key genes that are involved in miRNA biogenesis (DROSHA, DICER, and AGO2) across both sites in the SPTB group. In summary, the present study has identified miRNAs in maternal plasma that may provide predictive utility as early biomarkers for the risk of later SPTB. Importantly, these observations were conserved across two independent cohorts. Further, our data provide evidence for a persistent decrease in miRNA abundance in mothers who later experienced an SPTB, which is likely to have widespread consequences for gene regulation and epigenetic processes.

Early screening of post-stroke fall risk: A simultaneous multimodal fNIRs-EMG study.

Stroke is the third-leading cause of death and disability, and poststroke falls (PSF) are common at all stages after stroke and could even lead to injuries or death. Brain information from functional near-infrared spectroscopy (fNIRs) may precede conventional imaging and clinical symptoms but has not been systematically considered in PSF risk prediction. This study investigated the difference in brain activation between stroke patients and healthy subjects, and this study was aimed to explore fNIRs biomarkers for early screening of PSF risk by comparing the brain activation in patients at and not at PSF risk. In this study, we explored the differences in brain activation and connectivity between stroke and healthy subjects by synchronizing the detection of fNIRs and EMG tests during simple (usual sit-to-stand) and difficult tasks (sit-to-stand based on EMG feedback). Thereby further screened for neuroimaging biomarkers for early prediction of PSF risk by comparing brain activation variability in poststroke patients at and not at fall risk during simple and difficult tasks. The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic effect. A total of 40 patients (22 not at and 18 at PSF risk) and 38 healthy subjects were enrolled. As the difficulty of standing task increased, stroke patients compared with healthy subjects further increased the activation of the unaffected side of supplementary motor area (H-SMA) and dorsolateral prefrontal cortex-Brodmann area 46 (H-DLFC-BA46) but were unable to increase functional connectivity (Group*Task: p < 0.05). More importantly, the novel finding showed that hyperactivation of the H-SMA during a simple standing task was a valid fNIRs predictor of PSF risk [AUROC 0.74, p = 0.010, sensitivity 77.8%, specificity 63.6%]. This study provided novel evidence that fNIR-derived biomarkers could early predict PSF risk that can facilitate the widespread use of real-time assessment tools in early screening and rehabilitation. Meanwhile, this study demonstrated that the higher brain activation and inability to increase the brain functional connectivity in stroke patients during difficult task indicated the inefficient use of brain resources.

Novel Biomarkers in Early Prediction of Diabetic Nephropathy: A Systematic Review

Diabetes mellitus (DM) is a metabolic illness that is highly prevalent and intricate. Because of the high incidence of diabetic complications and disease mortality, the condition is one of the biggest medical and social issues in the world. Due to its rising prevalence, diabetes mellitus (DM), which raises blood glucose levels, is one of the world's health challenges and is anticipated to impact 495 million people. Diabetic kidney disease, or DKD, is a widespread ailment all over the world. It is the main cause of end-stage kidney disease (ESKD) and one of the most common consequences of diabetes mellitus (DM). Three essential elements play a role in its pathogenesis: the inflammatory, metabolic, and hemodynamic axis. Clinically, DKD is characterized by persistent albuminuria and a gradual reduction in glomerular filtration rate (GFR). These changes, however, are not unique to DKD, emphasizing the necessity to find new biomarkers originating from the disease's pathophysiology to support diagnosis, monitoring, treatment response, and prognosis. Cystatin C, also known as CysC, is a member of the cysteine protein inhibitor family and is a low-molecular-weight protein with 122 amino acids. The CST3 housekeeping gene, which is found on chromosome 20 (20pl1. 2, encodes it. Protein turnover, pro-protein processing, bone remodeling, antigen presentation, and apoptosis are among the physiological processes in which cysteine cathepsins are involved.

Inflammatory factors and risk of lung adenocarcinoma: a Mendelian randomization study mediated by blood metabolites.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation and metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships and specific mechanisms remain unclear. This study employed a two-sample Mendelian randomization (MR) approach to systematically evaluate the causal associations between 91 circulating inflammatory factors, 1,400 serum metabolites, and LUAD. We utilized LUAD genome-wide association studies (GWAS) data from the FinnGen biobank and GWAS data of metabolites and inflammatory factors from the GWAS catalog to conduct two-sample MR analyses. For the identified key metabolites, we further used mediator MR to investigate their mediating effects in the influence of IL-17A on LUAD and explored potential mechanisms through protein-protein interaction and functional enrichment analyses. The MR analyses revealed that IL-17A (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 metabolites were significantly associated with LUAD. Among them, ferulic acid 4-sulfate may play a crucial mediating role in the suppression of LUAD by IL-17A (OR 0.87, 95%CI 0.78-0.97). IL-17A may exert its anti-LUAD effects through extensive interactions with genes related to ferulic acid 4-sulfate metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress and inflammatory responses, as well as downstream tumor-related pathways of ferulic acid 4-sulfate (such as MAPK, NF-κB, etc.). This study discovered causal associations between IL-17A, multiple serum metabolites, and LUAD occurrence, revealing the key role of inflammatory and metabolic dysregulation in LUAD pathogenesis. Our findings provide new evidence-based medical support for specific inflammatory factors and metabolites as early predictive and risk assessment biomarkers for LUAD, offering important clues for subsequent mechanistic studies and precision medicine applications.