MEX3A induces the development of thyroid cancer via targeting CREB1.

Thyroid cancer is a prevalent form of endocrine cancer, and its global incidence has been steadily increasing. MEX3A is a protein that is known to be highly expressed in various human malignant tumors, including thyroid cancer, and it has been linked to patient prognosis. However, the molecular mechanisms underlying MEX3A's tumorigenic capabilities in thyroid cancer are not fully understood. In this study, we aimed to investigate the role of MEX3A in thyroid cancer. We confirmed that MEX3A was overexpressed in both thyroid cancer tissues and cell lines. Additionally, we found a positive correlation between high levels of MEX3A and the AJCC stage. To further understand the functional significance of MEX3A in thyroid cancer, we depleted MEX3A expression in B-CPAP and TPC-1 cells. Interestingly, we observed a significant reduction in thyroid cancer cell proliferation and migration, as well as ameliorated cell apoptosis and arrested tumor growth upon MEX3A depletion. These findings strongly suggested that MEX3A played a critical role in the development of thyroid cancer. Furthermore, our study uncovered an important interaction between MEX3A and CREB1 (cAMP response element-binding protein 1). The interaction between MEX3A and CREB1 appeared to contribute to the tumor-promoting effects of MEX3A in thyroid cancer by directly targeting CREB1. Silencing CREB1 was observed to alleviate the malignant phenotypes promoted by MEX3A in thyroid cancer cells. Together, this study highlighted the importance of the MEX3A-CREB1 interaction in thyroid cancer development and suggested the therapeutic potential of targeting MEX3A for the treatment of this disease.

Abnormal causal connectivity of left superior temporal gyrus in drug-naïve first- episode adolescent-onset schizophrenia: A resting-state fMRI study.

This study aimed to investigate the alterations of causal connectivity between the brain regions in Adolescent-onset schizophrenia (AOS) patients. Thirty-two first-episode drug-naïve AOS patients and 27 healthy controls (HC) were recruited for resting-state functional MRI scanning. The brain region with the between-group difference in regional homogeneity (ReHo) values was chosen as a seed to perform the Granger causality analysis (GCA) and further detect the alterations of causal connectivity in AOS. AOS patients exhibited increased ReHo values in left superior temporal gyrus (STG) compared with HCs. Significantly decreased values of outgoing Granger causality from left STG to right superior frontal gyrus and right angular gyrus were observed in GC mapping for AOS. Significantly stronger causal outflow from left STG to right insula and stronger causal inflow from right middle occipital gyrus (MOG) to left STG were also observed in AOS patients. Based on assessments of the two strengthened causal connectivity of the left STG with insula and MOG, a discriminant model could identify all patients from controls with 94.9% accuracy. This study indicated that alterations of directional connections in left STG may play an important role in the pathogenesis of AOS and serve as potential biomarkers for the disease.

Distinguishing hypochondriasis and schizophrenia using regional homogeneity: a resting-state fMRI study and support vector machine analysis.

OBJECTIVE: A few former studies suggested that there are partial overlaps in abnormal brain structure and cognitive function between hypochondriasis (HS) and schizophrenia (SZ). But their differences in brain activity and cognitive function were unclear. METHODS: Twenty-one HS patients, 23 SZ patients, and 24 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) with the regional homogeneity analysis (ReHo), subsequently exploring the relationship between ReHo value and cognitive functions. The support vector machines (SVM) were used on effectiveness evaluation of ReHo for differentiating HS from SZ. RESULTS: Compared with HC, HS showed significantly increased ReHo values in right middle temporal gyrus (MTG), left inferior parietal lobe (IPL), and right fusiform gyrus (FG), while SZ showed increased ReHo in left insula, decreased ReHo values in right paracentral lobule. Additionally, HS showed significantly higher ReHo values in FG, MTG, and left paracentral lobule, but lower in insula than SZ. The higher ReHo values in insula were associated with worse performance in MATRICS consensus cognitive battery (MCCB) in HS group. SVM analysis showed a combination of the ReHo values in insula and FG was able to satisfactorily distinguish the HS and SZ patients. CONCLUSION: Our results suggested that the altered default mode network (DMN), of which abnormal spontaneous neural activity occurs in multiple brain regions, might play a key role in the pathogenesis of HS, and the resting-state alterations of insula are closely related to cognitive dysfunction in HS. Furthermore, the combination of the ReHo in FG and insula was a relatively ideal indicator to distinguish HS from SZ.

Altered Effective Connectivity in the Default Network of the Brains of First-Episode, Drug-Naïve Schizophrenia Patients With Auditory Verbal Hallucinations.

Although the default mode network (DMN) is known to be abnormal in schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs), it is still unclear whether AVHs that occur in SZ are associated with certain information flow in the DMN. This study collected resting-state functional magnetic resonance imaging data from 28 first-episode, drug-naïve SZ patients with AVHs, 20 SZ patients without AVHs, and 38 healthy controls. We used Granger causality analysis (GCA) to examine effective connectivity (EC) of two hub regions [posterior cingulate cortex (PCC) and anteromedial prefrontal cortex (aMPFC)] within the DMN. We used two-sample t-tests to compare the difference in EC between the two patient groups, and used Spearman correlation analysis to characterize the relationship between imaging findings and clinical assessments. The GCA revealed that, compared with the non-AVHs group, EC decreased from aMPFC to left inferior temporal gyrus (ITG) and from PCC to left cerebellum posterior lobe, ITG, and right middle frontal gyrus in SZ patients with AVHs. We also found significant correlations between clinical assessments and mean strengths of connectivity from aMPFC to left ITG and from PCC to left ITG. Moreover, receiver operating characteristic analysis revealed that the above-mentioned effective connectivities had a diagnostic value for distinguishing SZ patients with AVHs from non-AVHs patients. These findings suggest that AVHs in SZ patients may be associated with the aberrant information flows of the DMN, and the left ITG may probably serve as a potential biomarker for the neural mechanisms underlying AVHs in SZ patients.

DNA methylation of trefoil factor 1 (TFF1) is associated with the tumorigenesis of gastric carcinoma.

Trefoil factor 1 (TFF1) is a tumor suppressor gene that encodes a peptide belonging to the trefoil factor family of protease­resistant peptides. Although TFF1 expression is frequently lost in gastric carcinomas (GCs), the tumorigenic pathways that are affected have yet to be determined. The aim of the current study was to identify the mechanism(s) by which the TFF1 gene is regulated in gastric carcinogenesis. In this study, TFF1 was shown to be silenced or downregulated in gastric tumor tissue compared with matched non­cancerous tissue. In addition, human gastric cells weakly expressed TFF1. The hypermethylation status in the promoter CpG islands appeared to be correlated with TFF1 expression levels in gastric cell lines or specimen tissue. Further molecular analysis indicated that the CpG islands play a role in the promoter activity of the TFF1 gene. The expression of TFF1 and DNA methylation of its promoter affected cell proliferation and apoptosis. The expression of TFF1 in gastric cell lines was restored with a demethylating agent, 5­azacytidine. Low expression of TFF1 in gastric cell lines and cancer tissue is associated with TP 53. In conclusion, the current study demonstrates that DNA methylation is a key mechanism of silencing TFF1 expression in human gastric cells and TFF1 gene hypermethylation of the CpG islands is a potential biomarker for GC.