Human bone marrow mesenchymal stem cell-driven LncRNA PTCSC3 upregulation within lung adenocarcinoma cells reduces erlotinib resistance by mitigating Wnt/ß-Catenin pathway.

lncRNA PTCSC3, which stands for Papillary Thyroid Carcinoma Susceptibility Candidate 3, has been found to play a role in various cellular processes, including cell proliferation, apoptosis, and migration, acting as either an oncogene or a tumor suppressor depending on the context. This study investigates the influence of lncRNA PTCSC3, derived from human bone marrow mesenchymal stem cell (hBMSC), on the efficacy of erlotinib (Er)-resistant lung adenocarcinoma (LUAD) cells and elucidates underlying mechanism. The hBMSCs and LUAD (PC9 and A549) cells were employed to establish an Er-resistant LUAD cell model. It was observed that exposure to hBMSCs reduced the viability of A549-Er and PC9-Er cells and increased their rate of apoptosis. Further investigations revealed that in the presence of hBMSCs-containing medium, PTCSC3 expression was significantly upregulated, concomitantly with a suppression of the Wnt/ß-Catenin pathway. Conversely, silencing PTCSC3 led to enhanced A549-Er and PC9-Er activities, reduced cell apoptosis, and activated Wnt/ß-Catenin pathway. The effects of PTCSC3 modulation were also examined by transfecting LUAD cells with different PTCSC3 expression vectors and treating them with XAV939, a Wnt/ß-Catenin pathway inhibitor, which similarly decreased cell viability. In the rescue experiment, the effect of hBMSCs on LUAD cells could be counteracted by down-regulation of PTCSC3, and the effect of PTCSC3 down-regulation on cells was mitigated by XAV939. This study revealed that hBMSCs promote the up-regulation of PTCSC3 in LUAD cells, thus inhibiting Wnt/ß-Catenin pathway and reversing Er resistance, offering a potential novel strategy to enhance the efficacy of chemotherapy in LUAD.

CCNA2 and KIF23 are molecular targets for the prognosis of adenoid cystic carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumor type derived from glands. However, relationship between CCNA2 and KIF23, and adenoid cystic carcinoma remains unclear. METHODS: GSE36820 and GSE88804 profiles for ACC were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, the construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed. A gene expression heat map was generated to visually depict the expression difference of core genes between adenoid cystic carcinoma and normal samples. TargetScan was employed to identify miRNAs that regulated central DEGs. Western blotting (WB) was conducted for cell verification. RESULTS: A total of 885 DEGs were identified. GO and KEGG analyses revealed their main enrichment in responses to chemical stimuli, cell proliferation, tissue development, and regulation of cell proliferation. The GO and KEGG results indicated significant enrichment in aldosterone-regulated sodium reabsorption, the cell cycle, and the PPAR signaling pathway. Notably, core genes (CCNA2 and KIF23) were found to be highly expressed in Adenoid Cystic Carcinoma samples and expressed at low levels in normal samples. WB validated the overexpression of CCNA2 and KIF23 in the Adenoid Cystic Carcinoma group, confirming the protein-level changes associated with cell cycle, metastasis, apoptosis, and inflammatory factors in Adenoid Cystic Carcinoma groups with gene overexpression and knockout. CONCLUSIONS: CCNA2 and KIF23 exhibit high expression levels in ACC, suggesting their potential role as molecular targets for this malignancy.

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.

Prognostic Factors and Construction of Nomogram Prediction Model of Lung Cancer Patients Using Clinical and Blood Laboratory Parameters.

Objective: This work aimed to explore the prognostic risk factors of lung cancer (LC) patients and establish a line chart prediction model. Methods: A total of 322 LC patients were taken as the study subjects. They were randomly divided into a training set (n = 202) and a validation set (n = 120). Basic information and laboratory indicators were collected, and the progression-free survival (PFS) and overall survival (OS) were followed up. Single-factor and cyclooxygenase (COX) multivariate analyses were performed on the training set to construct a Nomogram prediction model, which was validated with 120 patients in the validation set, and Harrell's consistency was analyzed. Results: Single-factor analysis revealed significant differences in PFS (P<0.05) between genders, body mass index (BMI), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCCA), treatment methods, treatment response evaluation, smoking status, presence of pericardial effusion, and programmed death ligand 1 (PD-L1) at 0 and 1-50%. Significant differences in OS (P<0.05) were observed for age, tumor location, treatment methods, White blood cells (WBC), uric acid (UA), CA125, pro-gastrin-releasing peptide (ProGRP), SCCA, cytokeratin fragment 21 (CYFRA21), and smoking status. COX analysis identified male gender, progressive disease (PD) as treatment response, and SCCA > 1.6 as risk factors for LC PFS. The consistency indices of the line chart models for predicting PFS and OS were 0.782 and 0.772, respectively. Conclusion: Male gender, treatment response of PD, and SCCA > 1.6 are independent risk factors affecting the survival of LC patients. The PFS line chart model demonstrates good concordance.

Evaluation of white matter microstructural alterations in premature infants with necrotizing enterocolitis.

Background: Preterm infants with necrotizing enterocolitis (NEC) are at high risk of adverse neurodevelopmental outcomes. The aim of this study was to explore the value of diffusion tensor imaging (DTI) combined with serum C-reactive protein (CRP) and procalcitonin (PCT) in evaluating alterations of white matter (WM) microstructure in preterm infants with NEC. Methods: A retrospective cross-sectional study was conducted in which all participants were consecutively enrolled at The Third Affiliated Hospital of Zhengzhou University from June 2017 and October 2021. Data from 30 preterm infants with NEC [mean gestational age at birth 31.41±1.15 weeks; mean age at magnetic resonance imaging (MRI) 37.53±3.08 weeks] and 40 healthy preterm infants with no NEC were recorded (mean gestational age at birth 32.27±2.09 weeks; mean age at MRI 37.15±3.23 weeks). WM was used to obtain the fractional anisotropy (FA) and mean diffusivity (MD) values of the regions of interest (ROIs). Additionally, serum levels of CRP and PCT were determined. Spearman correlation analysis was performed between the WM-derived parameters, CRP level, and the PCT serum index. Results: Preterm infants with NEC had reduced FA values and elevated MD values in WM regions [posterior limbs of the internal capsule (PLIC), lentiform nucleus (LN), frontal white matter (FWM)] compared to the control group (P<0.05). Additionally, the FA of the PLIC was negatively correlated with serum CRP (r=-0.846; P<0.05) and PCT (r=-0.843; P<0.05). Meanwhile, the MD of PLIC was positively correlated with serum CRP (r=0.743; P<0.05) and PCT (r=0.743; P<0.05, respectively). The area under the curve (AUC) of FA and MD combined with CRP and PCT in the diagnosis of WM microstructure alterations with NEC was 0.968, representing a considerable improvement in predicted efficacy over single indicators, including FA [AUC: 0.938; 95% confidence interval (CI): 0.840-0.950], MD (AUC: 0.807; 95% CI: 0.722-0.838), CRP (AUC: 0.867; 95% CI: 0.822-0.889), and PCT (AUC: 0.706; 95% CI: 0.701-0.758). Conclusions: WM can noninvasively and quantitatively assess the WM microstructure alterations in preterm infants with NEC. WM combined with serum CRP and PCT demonstrated superior performance in detecting and evaluating WM microstructure alterations in preterm infants with NEC.

Gas/Liquid Chromatography-Mass Spectrometry Analysis of Key Functional Substances Regulating Poll Gland Secretion in Male Camels during Seasonal Estrus.

Increased poll gland secretion is a major characteristic and indicator of estrus in male Bactrian camels; however, research on these poll glands and their secretion is extremely rare. In this study, we determine the chemical composition of poll gland secretions and identify the key functional substances that regulate seasonal estrus in male camels. A GC/LC-MS dual platform was used to analyze ventral hair (control) and neck mane samples containing poll gland secretions from male Bactrian camels during estrus. Multidimensional and single-dimensional analyses were used to screen differentially expressed metabolites (DEMs) between groups. Functional prediction of enriched metabolites was performed using a Human Metabolome Database comparison and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which were then compared with a behavioral analysis of male Bactrian camels in estrus. A total of 1172 DEMs and 34 differential metabolic pathways were identified. One metabolite group was found to relate to steroid synthesis and metabolism, and another metabolite group was associated with neural metabolism. Therefore, we speculate that steroids and neurochemicals jointly regulate estrous behavior in male Bactrian camels, thus providing theoretical insights into the development and function of poll glands in Bactrian camels.

Improved Differential Diagnosis Based on BI-RADS Descriptors and Apparent Diffusion Coefficient for Breast Lesions: A Multiparametric MRI Analysis as Compared to Kaiser Score.

RATIONALE AND OBJECTIVES: To develop the nomogram utilizing the American College of Radiology BI-RADS descriptors, clinical features, and apparent diffusion coefficient (ADC) to differentiate benign from malignant breast lesions. MATERIALS AND METHODS: A total of 341 lesions (161 malignant and 180 benign) were included. Clinical data and imaging features were reviewed. Univariable and multivariable logistic regression analyses were performed to determine the independent variables. ADC as a continuous or classified into binary form with a cutoff value of 1.30 × 10-3 mm2/s, incorporated other independent predictors to construct two nomograms, respectively. Receiver operating curve and calibration plot was employed to test the models' discriminative ability. The diagnostic performance between the developed model and the Kaiser score (KS) was also compared. RESULTS: In both models, high patient age, the presence of root sign, time-intensity curves (TICs) types (plateau and washout), heterogenous internal enhancement, the presence of peritumoral edema, and ADC were independently associated with malignancy. The AUCs of two multivariable models (AUC, 0.957; 95% CI: 0.929-0.976 and AUC, 0.958; 95% CI: 0.931-0.976) were significantly higher than that of the KS (AUC, 0.919, 95% CI: 0.885-0.946; both P < 0.001). At the same sensitivity of 95.7%, our models showed an increase in specificity by 5.56% (P = 0.076) and 6.11% (P = 0.035), respectively, as compared to the KS. CONCLUSION: The models incorporating MRI features (root sign, TIC, margins, internal enhancement, and presence of edema), quantitative ADC value, and patient age showed improved diagnostic performance and might have avoided more unnecessary biopsies in comparison with the KS, although further external validation is required.

CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells.

Hydrogen sulfide (H2S), as an endogenous gaseous signaling molecule, plays an important role in the inflammatory process. Our previous study found that Cystathionine-γ-lyase (CTH) and H2S are correlated with the occurrence and development of Clinical Mastitis (CM) in Holstein cows. However, the functions and regulatory mechanisms of CTH/H2S are still unknown. In this study, the inflammatory mammary cell model based on the MAC-T cell line was established by Lipopolysaccharide (LPS)-induced manner to further explore the function and regulatory mechanism of CTH/H2S in cows with CM. In the inflammatory MAC-T cell, the CTH expression and H2S production were both repressed in an LPS-dose dependent manner, which demonstrated that CTH/H2S is related to the progression of inflammation. The inhibition of CTH/H2S using a selective CTH inhibitor, ß-cyano-l-Alanine (BCA), promoted LPS-induced inflammation response and the expression of inflammatory cytokines. However, this was reversed by the H2S donor NaHS, demonstrating that H2S can protect cells from inflammatory damage. Intriguingly, interleukin-8 (IL-8) showed an inverse expression pattern correlated with the H2S-mediated cell protection effect during the inflammation process, and the inhibition test using a selective IL-8 receptor antagonist, SB225002, showed that IL-8 signaling plays a critical role in mediating endogenous H2S synthesis, and CTH/H2S exerts its anti-inflammation via IL-8-mediated signaling. This study provided support for the prevention and treatment of CM and the development of a novel anti-inflammatory strategy.

Evaluation of the differentiation of benign and malignant breast lesions using synthetic relaxometry and the Kaiser score.

Objective: To investigate whether there is added value of quantitative parameters from synthetic magnetic resonance imaging (SyMRI) as a complement to the Kaiser score (KS) to differentiate benign and malignant breast lesions. Materials and methods: In this single-institution study, 122 patients who underwent breast MRI from March 2020 to May 2021 were retrospectively analyzed. SyMRI and dynamic contrast-enhanced MRI were performed using a 3.0-T system. Two experienced radiologists independently assigned the KS and measured the quantitative values of T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) from SyMRI. Pathology was regarded as the gold standard. The diagnostic values were compared using the appropriate statistical tests. Results: There were 122 lesions (86 malignant and 36 benign) in 122 women. The T1 value was identified as the only independent factor for the differentiation of malignant and benign lesions. The diagnostic accuracy of incorporating the T1 into the KS protocol (T1+KS) was 95.1% and 92.1% for all lesions (ALL) and The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions, respectively, which was significantly higher than that of either T1 (ALL: 82.8%, P = 0.0001; BI-RADS 4: 78.9%, P = 0.002) or KS (ALL: 90.2%, P = 0.031; BI-RADS 4: 84.2%, P = 0.031) alone. The sensitivity and specificity of T1+KS were also higher than those of the T1 or KS alone. The combined diagnosis could have avoided another 15.6% biopsies compared with using KS alone. Conclusions: Incorporating T1 into the KS protocol improved both the sensitivity and specificity to differentiate benign and malignant breast lesions, thus avoiding unnecessary invasive procedures.

Sulfur Amino Acid Metabolism and the Role of Endogenous Cystathionine-γ-lyase/H2S in Holstein Cows with Clinical Mastitis.

H2S plays an important role in various inflammatory diseases. However, the role of H2S and synthetic enzymes in Holstein cows with CM is unknown. The aim of this study was to identify DEPs associated with sulfide metabolism and further investigate their roles in dairy cows with CM. From 3739 DEPs generated by data-independent acquisition proteomics, we identified a total of 17 DEPs included in 44 GO terms and five KEGG pathways related to sulfide metabolism, including CTH and cystathionine-ß-synthase (CBS). Immunohistochemical and immunofluorescence staining results showed that CTH and CBS proteins were present mainly in the cytoplasm of mammary epithelial cells. Endogenous H2S production in the serum of the CM group was significantly lower than that of the healthy Holstein cows. CTH and CBS mRNA and protein levels in the mammary glands of the CM group were significantly downregulated compared to those of the healthy group. These results indicate that CTH and H2S were correlated with the occurrence and development of CM in Holstein cows, which provides important insights into the function and regulatory mechanism of CTH/H2S in Holstein cows.

Classifying early stages of cervical cancer with MRI-based radiomics.

This study aims to establish a MRI-based classifier to distinguish early stages of cervical cancer with improved diagnostic performance to assist clinical diagnosis and treatment. 57 patients with pathological diagnosis of cervical cancer from January 2018 to May 2019 were enrolled in this study. MRI examinations, including T1-weighted image(T1WI), T2-weighted image(T2W), diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE), were performed before surgery. MR images from patients of stage Ib or IIa cervical cancer with tumor segmented were used as input. Feature extraction process extracted first-order statistics and texture and applied filters. The dimensionality of the radiomic features was reduced using the least absolute shrinkage and selection operator (LASSO). Models were trained by three machine-learning (k-nearest neighbor (KNN), support vector machine (SVM), and logistic regression (LR)) and diagnostic performance in differentiating stage Ib and stage IIa cases was evaluated. A total of 27 features were extracted to establish models, including 2 features from T1WI, 5 features from T2WI, 5 features from DWI (b = 50), 4 features from DWI (b = 800), 5 features from DCE, and 6 features from ADC. For each machine learning (ML) classifier, six sequences of training set and testing set are modeled and analyzed. Among all the models, the training set and testing set of T2WI model built by SVM classifier were the best (Area under the curve (AUC) 0.915) / (AUC 0.907). Radiomic analysis of ML-based texture features and first-order statistics features can be used to stage the early cervical cancer pre-operatively.

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy.

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.

Isolated trochleoplasty for recurrent patellar dislocation has lower outcome and higher residual instability compared with combined MPFL and trochleoplasty: a systematic review.

PURPOSE: To identify the efficacy of isolated trochleoplasty (TP) as an independent treatment for severe trochlear dysplasia compared with TP combined with medial patellofemoral ligament (MPFL) reconstruction. METHODS: Search of current literature using terms (trochleoplasty and medial patellofemoral ligament reconstruction) in the electronic search engines PubMed and Embase, and Medline databases was performed on February 25, 2018, and it yielded 515 abstracts for review. At the end of the search, six articles met specific inclusion criteria and were included in this review. Means were calculated for population size, age and follow-up time. The Kujala score was analyzed as the primary clinical outcome parameter in the meta-analysis. Pooled estimates were calculated for postoperative complications. RESULTS: Six studies with a total of 192 knees (168 patients) were included in this analysis. The isolated TP group comprised of 3 articles with a total of 111 knees, and the TP combined with MPFL group comprised of 3 articles with a total of 81 knees. At the final follow-up, the preoperative Kujala score increased significantly by 21.39 (95% CI 18.94, 23.84; P < 0.00001) points in the isolated TP group and by 24.91 (95% CI 15.47, 34.36; P < 0.00001) points in the TP combined with MPFL group. The rates of subjective patellar instability including subluxation and anterior knee pain were 1.03% and8.45% respectively. Meanwhile, the rate of objective patellar redislocation was 2.06% in isolated TP group and 0% in TP combined with MFPL group. A total of 8.24% returned to the operating room for additional procedures in the isolated TP group and 7.04% in the TP combined with MPFL group. CONCLUSION: Trochleoplasty is a useful and reliable surgical technique to improve patellofemoral instability in patients with a dysplastic trochlea. However, it as isolated treatment for patients has lower outcome and higher residual instability compared with combined MPFL and trochleoplasty.

LXRα is expressed at higher levels in healthy people compared to atherosclerosis patients and its over-expression polarizes macrophages towards an anti-inflammatory MΦ2 phenotype.

OBJECTIVES: (1) To investigate the expression patterns of MΦ1 and MΦ2 phenotype markers of peripheral blood monocyte (PBMC)-derived macrophages in atherosclerosis patients and healthy controls, as well as the expression correlation among these genes. (2) To elucidate whether a high level of liver X receptor α (LXRα) expression is associated with anti-inflammatory MΦ2-type polarization. DESIGN: Peripheral blood monocytes (PBMCs) were obtained from 28 patients with carotid artery plaques and 10 normal persons, who did not have carotid artery plaques. M1 and M2 phenotype markers were analyzed after cellular differentiation into macrophages. Human macrophages derived from healthy donors were transfected with plasmid DNA encoding LXRα and control null-plasmids. Gene expression levels were quantified after further differentiation. RESULTS: Three genes (LXRα, CD68, and CD36) were expressed at a significantly lower rate in the atherosclerotic group than normal patients. There were correlations between the expression of LXRα, CD68, and peroxisome proliferator-activated receptor (PPARγ), and between CD163, CD36 and scavenger receptor class A (SRA1). Macrophages over-expressing LXRα exhibited enhanced expression level of MΦ2-type genes and decreased expression level of MΦ1-type genes. CONCLUSIONS: PBMCs from healthy persons were predisposed to the MΦ2 differentiation phenotype, which exhibits elevated cholesterol uptake and anti-inflammatory properties. LXRα over-expression polarizes macrophages towards the anti-inflammatory MΦ2 phenotype.