Potential Marker Research Articles

Exosome-transmitted podoplanin promotes tumor-associated macrophage-mediated immune tolerance in glioblastoma.

Glioblastoma is the most frequent and aggressive primary brain tumor, characterized by rapid disease course and poor treatment responsiveness. The abundance of immunosuppressive macrophages in glioblastoma challenges the efficacy of novel immunotherapy. Bulk RNA-seq and single-cell RNA-seq of glioma patients from public databases were comprehensively analyzed to illustrate macrophage infiltration patterns and molecular characteristics of podoplanin (PDPN). Multiplexed fluorescence immunohistochemistry staining of PDPN, GFAP, CD68, and CD163 were performed in glioma tissue microarray. The impact of PDPN on macrophage immunosuppressive polarization was investigated using a co-culture system. Bone marrow-derived macrophages (BMDMs) and OT-II T cells isolated from BALB/c and OT-II mice respectively were co-cultured to determine T-cell adherence. Pathway alterations were probed through RNA sequencing and western blot analyses. Our findings demonstrated that PDPN is notably correlated with the expression of CD68 and CD163 in glioma tissues. Additionally, macrophages phagocytosing PDPN-containing EVs (EVsPDPN ) from GBM cells presented increased CD163 expression and augmented secretion of immunoregulatorycytokine (IL-6, IL-10, TNF-α, and TGF-β1). PDPN within EVs was also associated with enhanced phagocytic activity and reduced MHC II expression in macrophages, compromising CD4+ T-cell activation. This investigation underscores that EVsPDPN derived from glioblastoma cells contributes to M2 macrophage-mediated immunosuppression and is a potential prognostic marker and therapeutic target in glioblastoma.

Delineating immune variation between adult and children COVID-19 cases and associations with disease severity

The SARS-CoV-2 pandemic has emphasized the need to explore how variations in the immune system relate to the severity of the disease. This study aimed to explore inter-individual variation in response to SARS-CoV-2 infection by comparing T cell, B cell, and innate cell immune subsets among primary infected children and adults (i.e., those who had never experienced SARS-CoV-2 infection nor received vaccination previously), with varying disease severity after infection. We also examined immune subset kinetics in convalescent individuals compared to those with persistent infection to identify possible markers of immune dysfunction. Distinct immune subset differences were observed between infected adults and children, as well as among adult cases with mild, moderate, and severe disease. IgM memory B cells were absent in moderate and severe cases whereas frequencies of B cells with a lack of surface immunoglobulin expression were significantly higher in severe cases. Interestingly, these immune subsets remained stable during recovery implying that these subsets could be associated with underlying baseline immune variation. Our results offer insights into the potential immune markers associated with severe COVID-19 and provide a foundation for future research in this area.

Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma

BackgroundNeuroblastoma (NB), a prevalent pediatric solid tumor, presents formidable challenges due to its high malignancy and intricate pathogenesis. The role of disulfidptosis, a novel form of programmed cell death, remains poorly understood in the context of NB.MethodsGaussian mixture model (GMM)-identified disulfidptosis-related molecular subtypes in NB, differential gene analysis, survival analysis, and gene set variation analysis were conducted subsequently. Weighted gene co-expression network analysis (WGCNA) selected modular genes most relevant to the disulfidptosis core pathways. Integration of machine learning approaches revealed the combination of the Least absolute shrinkage and selection operator (LASSO) and Random Survival Forest (RSF) provided optimal dimensionality reduction of the modular genes. The resulting model was validated, and a nomogram assessed disulfidptosis characteristics in NB. Core genes were filtered and subjected to tumor phenotype and disulfidptosis-related experiments.ResultsGMM clustering revealed three distinct subtypes with diverse prognoses, showing significant variations in glucose metabolism, cytoskeletal structure, and tumor-related pathways. WGCNA highlighted the red module of genes highly correlated with disulfide isomerase activity, cytoskeleton formation, and glucose metabolism. The LASSO and RSF combination yielded the most accurate and stable prognostic model, with a significantly worse prognosis for high-scoring patients. Cytological experiments targeting core genes (CYFIP1, EMILIN1) revealed decreased cell proliferation, migration, invasion abilities, and evident cytoskeletal deformation upon core gene knockdown.ConclusionsThis study showcases the utility of disulfidptosis-related gene scores for predicting prognosis and molecular subtypes of NB. The identified core genes, CYFIP1 and EMILIN1, hold promise as potential therapeutic targets and diagnostic markers for NB.

Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial-mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT-related genes and transcription factors are associated with poor prognosis in ccRCC. EMT-related factors suppress E-cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), β-catenin, and E-cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan-Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm-c levels compared to those with low MIFn and MIFm-c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced-stage ccRCC.

CPLX2 is a novel tumor suppressor and improves the prognosis in glioma.

Glioma is a type of malignant cancer that affect the central nervous system. New predictive biomarkers have been investigated in recent years, but the clinical prognosis for glioma remains poor. The function of CPLX2 in glioma and the probable molecular mechanism of tumor suppression were the focus of this investigation. The glioma transcriptome profile was downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases for analysis of CPLX2 expression in glioma. RT-qPCR was performed to detect the expression of CPLX2 in 68 glioma subjects who have been followed up. Kaplan-Meier survival analyses were conducted to assess the effect of CPLX2 on the prognosis of glioma patients. The knockdown and overexpressed cell lines of CPLX2 were constructed to investigate the impact of CPLX2 on glioma. The cell growth, colony formation, and tumor formation in xenograft were performed. The expression of CPLX2 was downregulated in glioma and was negatively correlated with the grade of glioma. The higher expression of CPLX2 predicted a longer survival, as indicated by the analysis of Kaplan-Meier survival curves. Overexpressed CPLX2 impaired tumorigenesis in glioma progression both in vivo and in vitro. Knocking down CPLX2 promoted the proliferation of glioma cells. The analysis of GSEA and co-expression analysis revealed that CPLX2 may affect the malignancy of glioma by regulating the hypoxia and inflammation pathways. Our data indicated that CPLX2 functions as a tumor suppressor and could be used as a potential prognostic marker in glioma.

Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice.

Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention ( P<0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners, as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.

Identification and clinical validation of the role of anoikis-related genes in diabetic foot.

This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.

Asymmetrical positioning of cell organelles reflects the cell chirality of mouse myoblast cells.

Cell chirality is crucial for the chiral morphogenesis of biological tissues, yet its underlying mechanism remains unclear. Cell organelle polarization along multiple axes in a cell body, namely, apical-basal, front-rear, and left-right, is known to direct cell behavior such as orientation, rotation, and migration. Among these axes, the left-right bias holds significant sway in determining the chiral directionality of these behaviors. Normally, mouse myoblast (C2C12) cells exhibit a strong counterclockwise chirality on a ring-shaped micropattern, whereas they display a clockwise dominant chirality under Latrunculin A treatment. To investigate the relationship between multicellular chirality and organelle positioning in single cells, we studied the left-right positioning of cell organelles under distinct cell chirality in single cells via micropatterning technique, fluorescent microscopy, and imaging analysis. We found that on a "T"-shaped micropattern, a C2C12 cell adopts a triangular shape, with its nucleus-centrosome axis pointing toward the top-right direction of the "T." Several other organelles, including the Golgi apparatus, lysosomes, actin filaments, and microtubules, showed a preference to polarize on one side of the axis, indicating the universality of the left-right asymmetrical organelle positioning. Interestingly, upon reversing cell chirality with Latrunculin A, the organelles correspondingly reversed their left-right positioning bias, as suggested by the consistently biased metabolism and contractile properties at the leading edge. This left-right asymmetry in organelle positioning may help predict cell migration direction and serve as a potential marker for identifying cell chirality in biological models.

Characteristics of Visual Contrast Sensitivity and Ocular Microtremor in Schizophrenia

Background: schizophrenia is a severe mental illness characterized not only by cognitive but also sensory impairments, including the visual system. Research suggests impairments in contrast processing in schizophrenia, but evidence regarding the nature of these impairments is inconsistent. The theory of tremor modulation signal connects contrast sensitivity with the parameters of ocular microtremor – high-frequency and low-amplitude micromovements that are controlled by neurons of the nuclei of the brain stem. The parameters of ocular microtremor in psychopathology, in particular in schizophrenia, have not been described in the scientific literature.The aim of the study was to study the characteristics of contrast sensitivity and microtremor of the eyes of patients with schizophrenia.Patients and methods: to register contrast sensitivity, the method of computer visocontrastometry was used. Gabor elements were presented with spatial frequencies of 0.4, 1.0, 3.0, and 10 cycles/deg. Eye microtremor was recorded using a non-contact high-speed video recording method using an original optical system. The study involved 30 patients diagnosed as paranoid schizophrenia and 30 people without psychopathology and neurological diseases.Results: the contrast sensitivity of patients was reduced in the region of medium and high spatial frequencies compared with conditionally healthy controls, which may be associated with the chronic course of the disease. Ocular microtremor in the patient group was characterized by a lower frequency and a higher amplitude compared to the control group.Conclusions: contrast sensitivity and ocular microtremor are considered as potential markers for determining the functional state in schizophrenia, which requires further research and accumulation of experimental data.

An exploratory investigation of the CSF metabolic profile of HIV in a South African paediatric cohort using GCxGC-TOF/MS

Introduction Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.Aim and objectiveThe aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals.ResultsThe results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann–Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size.ConclusionsThis study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood–brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study’s focus on paediatric HIV research underscores the significance and unique contributions of its findings.

Evaluation of a commercial proAKAP4 kit for the assessment of fresh and frozen-thawed feline spermatozoa.

ProAKAP4 is gaining increasing attention as a potential marker of semen quality in many species, but while there is a commercial kit for assessing proAKAP4 in the domestic cat, there are no publications about its use. The aim of this study was to evaluate the commercial proAKAP4 kit - Cat 4MID® Kit (SPQI - 4BioDx, Lille, France) for the assessment of feline semen. Semen was collected from 54 male cats by urethral catheterization. After a basic semen evaluation (subjective motility, CASA, viability, morphology), proAKAP4 levels in each sample were assessed using the Cat 4MID® Kit according to the manufacturer's protocol or with some modifications related to incubation time, sample storage conditions and number of spermatozoa used. Finally, the Spearman correlation of proAKAP4 concentration and sperm motility parameters was calculated. The most reliable results (acceptable intraassay coefficient of variation) were obtained with an optimized protocol of overnight incubation and isolation of proAKAP4 protein from 1 × 106 spermatozoa stored at -80°C. For fresh semen, there were no significant correlations between proAKAP4 concentration and sperm motility parameters, despite a strong correlation between motility parameters and sperm viability and morphology. A predominant effect of other sperm parameters and highly variable performance of lysis buffer question the usefulness of Cat 4MID® Kit for the assessment of feline semen. For frozen-thawed semen, there was a moderate, negative correlation between proAKAP4 concentration and two CASA parameters, VAP and VSL. As there were no correlations between proAKAP4 concentration in fresh semen and motility parameters in cryopreserved samples, proAKAP4 cannot be used as freezability marker in cats. More studies are needed to establish potential correlation with long-lasting motility.

Sirtuin 1, as a potential prognosis marker in renal clear cell carcinoma, regulates lipid metabolism and immune infiltration.

Renal clear cell carcinoma (ccRCC) is a malignancy with a dismal prognosis, caused by the buildup of fat and glycogen. Sirtuin 1 (Sirt1) is a deacetylase that regulates lipid metabolism. In this study, we collected tumor and paracancer tissues from 386 ccRCC patients and followed their prognosis over an extended time period. The expression of Sirt1 in these tissues was assessed using immunohistochemistry, and LinkedOmics database analysis identified differentially expressed genes associated with Sirt1. The survival curve was generated using the Kaplan-Meier method, and immune infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER) web tool. Our findings revealed that Sirt1 was expressed in tumor tissues, but not in normal tissues, and its high expression was associated with a worse prognosis. Furthermore, we observed a positive correlation between high Sirt1 expression and perirenal fat invasion and necrosis, leading to poorer survival outcomes. We established a nomogram to predict prognosis, and a correlation was observed with immune infiltration. In conclusion, our results suggest that high Sirt1 expression is associated with lipid metabolism disorder and immune infiltration, ultimately contributing to a dismal prognosis in ccRCC.

The polymorphisms of candidate pharmacokinetic and pharmacodynamic genes and their pharmacogenetic impacts on the effectiveness of risperidone maintenance therapy among Saudi children with autism.

Antipsychotics, including risperidone (RIS), are frequently indicated for various autism spectrum disorder (ASD) manifestations; however, "actionable" PGx testing in psychiatry regarding antipsychotic dosing and selection has limited applications in routine clinical practice because of the lack of standard guidelines, mostly due to the inconsistency and scarcity of genetic variant data. The current study is aimed at examining the association of RIS effectiveness, according to ABC-CV and CGI indexes, with relevant pharmacokinetics (PK) and pharmacodynamics (PD) genes. Eighty-nine ASD children who received a consistent RIS-based regimen for at least 8weeks were included. The Axiom PharmacoFocus Array technique was employed to generate accurate star allele-predicted phenotypes of 3 PK genes (CYP3A4, CYP3A5, and CYP2D6). Genotype calls for 5 candidate PD receptor genes (DRD1, DRD2, DRD3, HTR2C, and HTR2A) were obtained and reported as wild type, heterozygous, or homozygous for 11 variants. Based on the ABC total score, 42 (47.2%) children were classified as responders, while 47 (52.8%) were classified as nonresponders. Multivariate logistic regression analyses, adjusted for nongenetic factors, suggested nonsignificant impacts of the star allele-predicted phenotypes of all 3 PK genes on improvement in ASD symptoms or CGI scores. However, significant positive or negative associations of certain PD variants involved in dopaminergic and serotonergic pathways were observed with specific ASD core and noncore symptom subdomains. Our significant polymorphism findings, mainly those in DRD2 (rs1800497, rs1799978, and rs2734841), HTR2C (rs3813929), and HTR2A (rs6311), were largely consistent with earlier findings (predictors of RIS effectiveness in adult schizophrenia patients), confirming their validity for identifying ASD children with a greater likelihood of core symptom improvement compared to noncarriers/wild types. Other novel findings of this study, such as significant improvements in DRD3 rs167771 carriers, particularly in ABC total and lethargy/social withdrawal scores, and DRD1 rs1875964 homozygotes and DRD2 rs1079598 wild types in stereotypic behavior, warrant further verification in biochemical and clinical studies to confirm their feasibility for inclusion in a PGx panel. In conclusion, we provide evidence of potential genetic markers involved in clinical response variability to RIS therapy in ASD children. However, replication in prospective samples with greater ethnic diversity and sample sizes is necessary.

Single-cell RNA sequencing reveals the altered innate immunity in immune checkpoint inhibitor-related myocarditis.

Myocarditis has emerged as a rare but lethal immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterise the transcriptomic profiles based on single-cell RNA sequencing from ICI-related myocarditis. Peripheral blood mononuclear cell (PBMC) samples were collected from four groups for single-cell RNA sequencing: (1) patients with newly diagnosed lung squamous cell carcinoma before treatment (Control Group); (2) patients with lung squamous cell carcinoma with PD-1 inhibitor therapy who did not develop myocarditis (PD-1 Group); (3) patients during fulminant ICI-related myocarditis onset (Myocarditis Group); and (4) Patients with fulminant ICI-related myocarditis during disease remission (Recovery Group). Subcluster determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were performed after scRNA-seq. Bulk-RNA sequencing was performed for further validation. Our results revealed the diversity of cellular populations in ICI-related myocarditis, marked by their distinct transcriptional profiles and biological functions. Monocytes, NKs as well as B cells contribute to the regulation of innate immunity and inflammation in ICI-related myocarditis. With integrated analysis of scRNA-seq and bulk sequencing, we identified S100A protein family as a potential serum marker for ICI-related myocarditis. Our study has created a cell atlas of PBMC during ICI-related myocarditis, which would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI-related myocarditis in continuous exploration.

A Modern Interpretation of Cold-Heat Pattern in Traditional Medicine with a Focus on Thermo-Regulation

Cold-heat patterns (C-HPs) in Traditional East Asian Medicine are essential for individually diagnosing and treating patients. However, the concept of C-HPs and their biological mechanisms (thermoregulation) remains unclear. C-HPs studies published between January 2000 and May 2023 were retrieved from 5 databases (PubMed, Google Scholar, OASIS, Korean studies Information Service System, and Research Information Sharing Service). Among the 8,373 articles screened, 132 were included in the review and categorized. Nineteen articles were clinical studies related to traditional concept of C-HP identification, 14 studies investigated diseases affecting thermosensation or thermoregulation, and 99 studies identified candidate genes as potential markers for C-HP identification. Further analysis, including gene ontology, and gene set enrichment analysis of the candidate genes, revealed 3 primary biological processes closely associated with thermoregulation-related genes, including localization, responses to stimuli, and homeostatic processes. Notably there was a significant association between the candidate genes and inflammatory mediator regulation of transient receptor potential channels (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). A significant association between C-HPs and inflammation-related pathways across thermosensation-related and thermoregulation-related clinical and preclinical studies was observed, suggesting that the traditional concept of C-HPs should be studied further from an immunological perspective.

Capillary electrophoresis using triple layer modified capillary facilitating salivary ion analyses: Application to search for potential stress markers induced by cold pressure test

In this study, we introduce a novel approach for the analysis of salivary ions using capillary electrophoresis (CE) with a triple-layer coated capillary. The capillary is sequentially coated with cationic silylating reagents, poly(vinylsulfonate), and polybrene to form a custom designed surface that effectively inhibits adsorption of protein matrix on the capillary inner wall and allows for reproducible ion analysis. For the CE with capacitively coupled contactless conductivity detection, we used suitable background electrolytes (BGEs) for salivary ion analysis. Anions were separated using a mixture of 2-(N-morpholino)ethanesulfonic acid and l-arginine, and cations were separated using that with 18-crown-6. This setup enabled rapid separation, within 4 min, together with sensitive detection. We quantified nine common anions and five cations typically found in saliva samples using this CE method, both before and after a cold pressure test (CPT, a standard stress test). The CE system demonstrated consistent ion separation across 30 consecutive measurements without requiring capillary replacement. Notably, the salivary ion balance remained predominantly anion-rich, regardless of the CPT. Cold water exposure induced greater variation in the total anion concentration than in the total cation concentration. Further analysis using multiple regression analysis revealed strong relationships between nitrate and nitrite, formate and phosphate, and potassium and nitrate, before and after the CPT. Notably, potassium and nitrate ions exhibited variations in response to stress. These results provided a method for assessing salivary ion composition and insights into the potential of salivary ions as biomarkers for stress.

Effect of CHRDL1 on angiogenesis and metastasis of colorectal cancer cells via TGF-β/VEGF pathway.

Colorectal cancer (CRC) is a common digestive tract tumor with the third incidence and death in the world. There is still an urgent need for effective therapeutic targets and prognostic markers for CRC. Herein, we report a novel potential target and marker, Chordin like-1 (CHRDL1). The function of CHRDL1 has been reported in gastric cancer, breast cancer, and oral squamous cell carcinoma. However, the biological effect of CHRDL1 in CRC remains unrevealed. Transwell and tube formation experiments were used to determine the biological function of CHRDL1. Western blot and rescue experiments were used to determine the specific mechanisms of CHRDL1. Results showed CHRDL1 is significantly downregulated in CRC cell lines and tissues. In vitro, experiments confirmed that CHRDL1 can inhibit cell growth, migration, invasion, angiogenesis and reverse epithelial-mesenchymal transformation. In vivo, experiments proved that it can inhibit tumor growth and metastasis. Mechanistically, we newly find that CHRDL1 exerts biological functions through the transforming growth factor-beta (TGF-β)/vascular endothelial growth factor signaling axis in vitro and in vivo. Therefore, we concluded that CHRDL1 reduces the growth, migration, and angiogenesis of CRC cells by downregulating TGF-β signaling. Our new findings on CHRDL1 may provide a basis for clinical antiangiogenesis therapy and the prognosis of CRC.

Metabolomic analysis of plasma biomarkers in children with autism spectrum disorders.

Autism spectrum disorder (ASD) presents a significant risk to human well-being and has emerged as a worldwide public health concern. Twenty-eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9-O-18:0), DL-2-hydroxystearic acid, and 7(S),17(S)-dihydroxy-8(E),10(Z),13(Z),15(E),19(Z)-docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three-biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.

Detection of Frank's sign in the dental setting: A population-based cohort study.

In 1973, Saunders T. Frank described the diagonal earlobe crease (DELC) as a potential marker of cardiovascular disease. However, this anatomical finding is not routinely examined. The aim of this study was to assess the presence of this crease in the general population attending a dental setting and describe its anatomical variations to be able to categorize it as a physical sign. A study group of 1050 white adults were selected, as participants in the framework of the "A Estrada Study of Glycation and Inflammation" (AEGIS), a cross-sectional, population-based descriptive study of a representative sample of the general adult population of the municipality of A Estrada (Pontevedra, Spain). Each participant's age, sex, and preferred head position when sleeping were recorded. Both earlobes were visually inspected and the anatomical variables of the crease were recorded (unilateral or bilateral, length, depth, and presence of secondary creases). The relationship between the study variables was analyzed using the chi-squared test, Student's t-test, the analysis of variance (ANOVA), and the nonparametric tests of Mann-Whitney and Kruskal-Wallis. The DELC was observed in 65.2% of the participants. In 71.5% of the cases, the sign was complete (occupying the space from the tragus to the posterior edge of the earlobe); in 56.9% of the cases, the sign was bilateral; in 45.1% of the cases it was deep; and in the 43.6% of the cases, accessory creases were identified. Neither sex nor the habitual head position when sleeping were related to the prevalence or characteristics of the DELC. The prevalence, extent and depth of Frank's sign increased significantly with age (p<.001). The prevalence of the DELC increases significantly with age, and its morphological characteristics are accentuated. This finding, therefore, gains special relevance as a marker of potential cardiovascular disease when observed in young adults.

Exploring the Relationship between E-Cadherin and β-Catenin Cell Adhesion Proteins and Periacinar Retraction Clefting in Prostatic Adenocarcinoma.

Periacinar retraction clefts represent a histopathological criterion supporting the diagnosis of prostatic adenocarcinoma. The origin of these clefts in prostatic adenocarcinoma remains unclear. Exploring the established functions of E-cadherin and β-catenin as intercellular adhesion proteins, and aiming to elucidate the origin of periacinar retraction clefting, we conducted a correlation study between the immunohistochemical expression of E-cadherin and β-catenin and the presence of periacinar retraction clefts in prostatic adenocarcinoma. We examined 53 cases of morphologically diagnosed prostatic adenocarcinoma, assessing both the neoplastic and adjacent nonneoplastic prostatic tissues for the existence and degree of periacinar retraction clefts. Additionally, we analyzed the immunohistochemical expression of E-cadherin and β-catenin proteins in prostatic tissue and explored their correlation with periacinar retraction clefts, and Gleason score, Grade Group, preoperative serum prostate specific-antigen (sPSA) levels, surgical margin status, and Tumor, Node, Metastasis (TNM) stage in prostatic adenocarcinoma. Our study confirms that periacinar retraction clefting is significantly more extensive in prostatic adenocarcinoma than in nonneoplastic prostatic tissue (p < 0.001). We report a decreased expression of E-cadherin and β-catenin immunostaining in prostatic adenocarcinoma and a negative correlation with Gleason score and Grade Group. Periacinar retraction clefting positively correlated with E-cadherin and β-catenin ((rho = 0.350; p = 0.010) and (rho = 0.340; p = 0.012)) immunostaining in prostatic adenocarcinoma. Periacinar retraction clefts stand out as a dependable criterion in the diagnosis of prostatic adenocarcinoma. E-cadherin and β-catenin proteins are potential markers indicative of tumor progression and invasiveness in prostatic adenocarcinoma. Our discovery of a positive correlation between immunostaining of E-cadherin and β-catenin proteins and periacinar retraction clefts in prostatic adenocarcinoma aligns with the notion that periacinar retraction clefting is more characteristic of Gleason Grade3 pattern in prostatic adenocarcinomas, whereas the immunohistochemical expression of E-cadherin and β-catenin shows a decrease with increasing histopathological tumor grade.