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At present, the standard treatment approach for locally advanced cervical cancer is concurrent chemoradiotherapy (CCRT). An elevated pretreatment squamous cell carcinoma antigen (SCC Ag) level is associated with extensive tumors and poor survival for patients with cervical cancer treated with definitive CCRT. SCC Ag levels can be used to help physicians make decisions regarding surgery, avoiding the complications of double treatment modalities. Elevated SCC Ag is associated with radiotherapy resistance, and the rate of SCC Ag reduction during CCRT can predict tumor response after treatment. Moreover, the failure of SCC Ag levels to normalize posttreatment can predict tumor relapse, with a specificity higher than 70%, and adjuvant therapies should be considered for these patients. SCC Ag also plays an important role in the early detection of tumor relapse in patients with cervical cancer during follow-up after CCRT, with high sensitivity and good cost-effectiveness.

In the present study, the CA III and IV autoantibodies, CA activity, antioxidant enzymes and cytokines in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), diabetes, hypertensive renal disease, and heart failure were investigated. The anti-CA III antibody titers in patients with RA, SLE, and type 1 diabetes (T1D) were significantly higher than that in control groups (P < 0.05). The anti-CA IV antibody titers in patients with RA, SLE, type 1 diabetic nephropathy (T1DN), and heart failure were significantly higher than that in control groups (P < 0.05) while anti-CA IV antibody could suppress the total CA activity. The SOD and GPx levels in patients with RA, SLE, and T1DN were significantly lower than that in control groups (P < 0.05). IL-6, IL-17, IFN-γ, and TNF-α levels were significantly higher in SLE group compared with the control group (P < 0.05). Weak but significant correlations were found between anti-CA III antibodies and ESR in RA (r = 0.403, P = 0.013) and SLE patients (r = 0.397, P = 0.007). These results suggested that the generation of CA III and IV autoantibodies, antioxidant enzymes, and cytokines might influence each other and CA autoantibodies might affect the normal physiology function of CA.

Abnormalities of autophagy can result in neurodegenerative disorders such as Alzheimer’s disease (AD). Nevertheless, the regulatory mechanisms of autophagy in AD are not well understood. Here, we describe our findings that microRNA (miR)-299-5p functions as an autophagy inhibitor by suppressing Atg5 and antagonizing caspase-dependent apoptosis. We observed decreased levels of miR-299-5p both in primary neurons under conditions of starvation and in hippocampi of APPswe/PS1dE9 mice. Additionally, low levels of miR-299-5p were observed in cerebrospinal fluid of AD patients. MiR-299-5p treatment resulted in attenuation of Atg5 and autophagy in primary neurons from APPswe/PS1dE9 mice, N2a cells and SH-SY5Y cells, whereas antagomiR-299-5p enhanced autophagy. Atg5 was verified as a direct target of miR-299-5p by dual luciferase reporter assays. Furthermore, transfection of miR-299-5p into primary hippocampal neurons caused the attenuation of caspase-mediated apoptosis, which was reversed upon starvation-induced autophagy. Inhibition of autophagy by shRNA knockdown of LC3β reduced apoptotic neuron death induced by antagomiR-299-5p. Injection of agomiR-299-5p into the cerebral ventricles of AD mice inhibited both autophagy and apoptosis and also improved the cognitive performance of mice. Overall, our results suggest that miR-299-5p modulates neuron survival programs by regulating autophagy. Thus, miR-299-5p serves as a potential neuroprotective factor in AD.

BackgroundThe activity of eukaryotic DNA polymerase delta (Pol δ) plays an essential role in genome stability through its effects on DNA replication and repair. The p125 catalytic subunit of Pol δ is encoded by POLD1 gene in human cells. To clarify biological functions of POLD1, we investigated the effects of POLD1 overexpression or downregulation on cell proliferation, cell cycle progression, DNA synthesis and oxidative DNA damage induced by H2O2.MethodsHEK293 cells were transfected with POLD1 expression plasmid or shRNA, cell proliferation, cell cycle progression, and DNA synthesis in HEK293 cells were analyzed.ResultsHEK293 cells were transfected with POLD1 expression plasmid or shRNA. POLD1 downregulation by shRNA suppressed cell proliferation, cell cycle progression, and DNA synthesis in HEK293 cells. However, POLD1 overexpression had no significant effects on these processes. Finally, comet assay showed that POLD1 downregulation led to increased DNA damage.ConclusionsOur results suggest that human POLD1 plays important role in the regulation of cell cycle progression and DNA damage repair.

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Objective We aimed to establish a method to determine whether amyloid‐β (Aβ) protein and miR‐384 in peripheral blood neural cell adhesion molecule (NCAM)/ATP‐binding cassette transporter A1 (ABCA1) dual‐labeled exosomes may serve as diagnostic markers for the diagnosis of Alzheimer's disease (AD). Methods This was a multicenter study using a two‐stage design. The subjects included 45 subjective cognitive decline (SCD) patients, 50 amnesic mild cognitive impairment (aMCI) patients, 40 AD patients, and 30 controls in the discovery stage. The results were validated in the verification stage in 47 SCD patients, 45 aMCI patients, 45 AD patients, and 30 controls. NCAM single‐labeled and NCAM/ABCA1 double‐labeled exosomes in the peripheral blood were captured and detected by immunoassay. Results The Aβ42, Aβ42/40, Tau, P‐T181‐tau, and miR‐384 levels in NCAM single‐labeled and NCAM/ABCA1 double‐labeled exosomes of the aMCI and AD groups were significantly higher than those of the SCD, control, and vascular dementia (VaD) groups (all p < 0.05). The Aβ42 and miR‐384 levels in NCAM/ABCA1 dual‐labeled exosomes of the aMCI and AD groups were higher than those of the control and VaD groups (all p < 0.05). The exosomal Aβ42, Aβ42/40, Tau, P‐T181‐tau, and miR‐384 levels in peripheral blood were correlated with those in cerebrospinal fluid (all p < 0.05). Conclusion This study, for the first time, established a method that sorts specific surface marker exosomes using a two‐step immune capture technology. The plasma NCAM/ABCA1 dual‐labeled exosomal Aβ42/40 and miR‐384 had potential advantages in the diagnosis of SCD.

β-amyloid (Aβ) deposition, neurofibrillary tangles induced by phosphorylation of tau protein, and neuronal apoptosis are pathological hallmarks of Alzheimer’s disease (AD). The dementia rate in alcoholic abusers were found to be higher than in control people. The present study explored the potential roles of alcohol dehydrogenase 1B (ADH1B) in AD pathology by determining the ADH1B levels in AD patient sera, in the hippocampus of APP/PS-1 AD model mice, and in an AD model cell line treated with Aβ1-42. The results show that ADH1B levels decreased significantly both in the serum of AD patients and in the hippocampus of APP/PS-1 AD model mice. In addition, the apoptotic rate was reduced and viability was significantly increased in AD model cells transfected with ADH1B overexpression vector. The levels of the p75 neurotrophin receptor (p75NTR), an Aβ1-42 receptor, were down-regulated in the ADH1B overexpressing AD model cell and up-regulated in cells transfected with the shRNA vector of ADH1B. Protein levels of cleaved caspase-3 and Bax decreased significantly, whereas Bcl-2 levels increased in cells overexpressing ADH1B. The opposite trend was observed for cleaved caspase-3, Bax, and Bcl-2 levels in cells transfected with the shRNA vector of ADH1B. The levels of reactive oxygen species (ROS) were found to be reduced in ADH1B overexpressing cells and increased when cells were transfected with the shRNA vector of ADH1B. These results indicate that ADH1B might be important in the prevention of AD, especially for abusers of alcohol, and a potential new target of AD treatment.