Search

In the past few years, immune checkpoint blockade (ICB) therapy has emerged as a breakthrough treatment for cancers and has demonstrated inspiring effects in tumor patients with Epstein-Barr virus (EBV) infection. To allow more patients to benefit from immunotherapy, exploring novel biomarkers based on EBV-related tumors and immunotherapy cohorts was pursued in the present study. The essential biomarkers that may enhance antitumor immunity across EBV-related tumors were identified using the large-scale transcriptomic profiles of EBV-associated tumors and tumor immunotherapy cohorts. The clinical significance of vital genes was evaluated in multiple tumor immunotherapy cohorts. Moreover, the potential function of essential genes in immunotherapy was explored via bioinformatic analyses and verified by qRT-PCR, Western blot analysis, CCK8 assay and flow cytometry. Apolipoprotein L6 (APOL6) was considered the essential biomarker for enhancing antitumor immunity across EBV-positive tumors. The upregulation of APOL6 was correlated with increased response rates and prolonged survival in multiple tumor immunotherapy cohorts. Bioinformatic analyses suggested that APOL6 may enhance tumor immunotherapy by inducing immunogenic cell death. Pancreatic cancer cells transfected with APOL6 overexpression plasmid underwent apoptosis, necroptosis, and pyroptosis with immunogenic features. The biomarker upregulated in EBV-related tumors could further elucidate the drivers of immunotherapy response. The upregulation of APOL6 could improve immunotherapy by triggering immunogenic cell death, thus offering a new target to optimize cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The corticocortical vestibular network (CVN) plays an important role in maintaining balance and stability. In order to clarify the specific relationship between the CVN and the balance ability of patients with mild cognitive impairment (MCI), we recruited 30 MCI patients in the community. According to age and sex, they were 1:1 matched to 30 older adults with normal cognitive function. We evaluated balance ability and performed MRI scanning in the two groups of participants. We analyzed functional connectivity within the CVN based on the region of interest. Then, we performed a Pearson correlation analysis between the functional connection and the Berg Balance Scale scores. The research results show that compared with the control group, there were three pairs of functional connections (hMST_R–Premotor_R, PFcm_R–SMA_L, and hMST_L–VIP_R) that were significantly decreased in the CVNs of the MCI group (p < 0.05). Further correlation analysis showed that there was a significant positive correlation between hMST_R–Premotor_R functional connectivity and BBS score (r = 0.364, p = 0.004). The decline in balance ability and increase in fall risk in patients with MCI may be closely related to the change in the internal connection mode of the corticocortical vestibular network. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the advance in therapeutic strategy, the prognosis of pancreatic ductal adenocarcinoma (PDAC) is still unsatisfactory, with a 5-year survival rate of less than 9%. As a member of the S100 protein family, S100A10 has been identified as an oncogene in multiple cancers. In PDAC, S100A10 has been reported to be not only up-regulated in tumor tissues but also associated with survival outcomes. However, the specific function of S100A10 in PDAC is still unknown. Here, we suggest that S100A10 promotes PDAC cells proliferation, migration, and adhesion by activating JNK/LAMB3-LAMC2 axis in vitro and accelerates pancreatic tumor growth in vivo, indicating that S100A10 may be a potential therapeutic target for PDAC patients. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, characterized by diagnosis at an advanced stage and a poor prognosis. As a member of the S100 protein family, S100A10 regulates multiple biological functions related to cancer progression and metastasis. However, the role of S100A10 in PDAC is still not completely elucidated. In this study, we reported that S100A10 was significantly up-regulated in PDAC tissue and associated with a poor prognosis by integrated bioinformatic analysis and human PDAC tissue samples. In vitro, down-regulation of S100A10 reduced the proliferation, migration, and adhesion of PDAC cell lines, whereas up-regulation of S100A10 showed the opposite effect. Furthermore, LAMB3 was proved to be activated by S100A10 using RNA-sequencing and western blotting. The effect of LAMB3 on the proliferation, migration, and adhesion of PDAC cells was similar to that of S100A10. Up-regulation or down-regulation of LAMB3 could reverse the corresponding effect of S100A10. Moreover, we validated S100A10 activates LAMB3 through the JNK pathway, and LAMB3 was further proved to interact with LAMC2. Mice-bearing orthotopic pancreatic tumors showed that S100A10 knocked-down PANC-1 cells had a smaller tumor size than the control group. In conclusion, S100A10 promotes PDAC cells proliferation, migration, and adhesion through JNK/LAMB3-LAMC2 axis. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is one of the important comorbidities of type 2 diabetes mellitus (T2DM). It is critical to find appropriate methods for early diagnosis and objective assessment of mild cognitive impairment patients with type 2 diabetes (T2DM-MCI). Our study aimed to investigate potential early alterations in phase lag index (PLI) and determine whether it can distinguish between T2DM-MCI and normal controls with T2DM (T2DM-NC). EEG was recorded in 30 T2DM-MCI patients and 30 T2DM-NC patients. The phase lag index was computed and used in a logistic regression model to discriminate between groups. The correlation between the phase lag index and Montreal Cognitive Assessment (MoCA) score was assessed. The α-band phase lag index was significantly decreased in the T2DM-MCI group compared with the T2DM-NC group and showed a moderate degree of classification accuracy. The MoCA score was positively correlated with the α-band phase lag index (r = 0.4812, moderate association, p = 0.015). This work shows that the functional connectivity analysis of EEG may offer an effective way to track the cortical dysfunction linked to the cognitive deterioration of T2DM patients, and the α-band phase lag index may have a role in guiding the diagnosis of T2DM-MCI. [ABSTRACT FROM AUTHOR]