Preventive noninvasive vagal nerve stimulation reduces insufficient sleep-induced depression by improving the autonomic nervous system.

BACKGROUND: Depression is closely linked to an imbalance in the autonomic nervous system (ANS). However, the role of this imbalance in mediating the effects of sleep deprivation (SD) and vagus nerve stimulation (VNS) on emotional well-being is not fully understood. METHODS: A population-based analysis was conducted to explore the relationship between sleep duration, depression scores, and heart rate variability (HRV). Additionally, the chronic SD mouse model was established to assess the impact of preventive transcutaneous auricular VNS (taVNS) on pathological and behavioral changes. RESULTS: Our study found a significant link between sleep duration, depression severity, and HRV. Shorter sleep duration was associated with higher depression scores and lower RMSSD (a measure of HRV). In our rat model, insufficient sleep consistently impaired HRV. This effect was mitigated by taVNS, accompanied by corresponding changes in levels of IL-1ß and IL-6, astrocyte and microglia activation, and tail suspension times. CONCLUSIONS: Using VNS as a preventive treatment for depression-risk individuals with insufficient sleep shows promise. It not only broadens the potential applications of VNS but also sheds light on its mechanism-particularly its role in enhancing vagal nerve function and balancing the ANS, as evidenced by HRV measurements.

Protective Effect of Pyrroloquinoline Quinone on TNF-α-induced Mitochondrial Injury in Chondrocytes.

Osteoarthritis (OA) is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity. As a bacterial synthesis of quinine, pyrroloquinoline quinone (PQQ) is a strong redox cofactor with a variety of biological benefits, including antioxidant, anti-inflammation-induced mitochondrial metabolism regulation. This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes. Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α 50 ng/mL, TNF-α 50 ng/mL + PQQ 10 µmol/L for 24 h. Then, morphological study, functional study and mechanism study were taken. The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ, evidenced by elevated number of mitochondria, well-kept mtDNA integrity, preserved ATP level, reestablished mitochondrial membrane potential, and prevented mitochondrial function. The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-α and the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α. PQQ might be a potential chemical for OA intervention.

Patellofemoral MRI Alterations Following Single Bundle ACL Reconstruction with Hamstring Autografts Are Associated with Quadriceps Femoris Atrophy.

High incidence of patellofemoral pain and patellofemoral joint osteoarthritis was found following anterior cruciate ligament (ACL) reconstruction. The unstability of patellofemoral joint might be an important contribution factor. This study was designed to define the relationship between the unstability of patellofemoral joint and quadriceps femoris atrophy. Twenty patients underwent MRI scan before ACL reconstruction and every two weeks after surgery, until 12 weeks. The merchant's patellar congruence angle, lateral inclination angle, and quadriceps femoris muscle cross-sectional area were measured and the relationship between the changes of angles and the ratio of quadriceps femoris atrophy was studied by multiple regression analysis. Significant quadriceps femoris atrophy was observed after ACL reconstruction during the follow-up period of 12 weeks. The merchant's patellar congruence angle and lateral inclination angle significantly changed after surgery. The alterations of the merchant's patellar congruence angle were significantly correlated with the atrophy ratio of vastus medialis (coefficient=-15.76) and vastus lateralis (coefficient=8.35) during the follow-up period of 12 weeks. The alterations of lateral inclination angle were significantly correlated with the atrophy ratio of vastus medialis (coefficient=20.62), vastus lateralis (coefficient=-11.38) and rectus femoris (coefficient=-0.469) during the follow-up period 12 weeks. To sum up, ACL reconstruction can alleviate the dysfunction of patellofemoral joint to a certain extent. But, the unbalanced atrophy of quadriceps femoris once again destroyed the stability of patellofemoral joint following the operation, which might be one cause of patellofemoral joint pain and early onset of osteoarthritis after ACL reconstruction. So, rehabilitation training that focuses on quadriceps femoris especially the vastus medialis shortly following operation is suggested.

The association of polymorphisms in lncRNA-H19 with hepatocellular cancer risk and prognosis.

Hepatocellular cancer (HCC) is one of the major causes of cancer-related mortality. Genetic polymorphisms may affect the susceptibility and clinical outcomes of cancers. We aim to manifest the association of single nucleotide polymorphisms (SNPs) of lncRNA-H19 gene with the risk and prognosis of HCC. A total of 944 samples composed of 472 HCC patients and 472 matched controls were included in the risk analysis and amongst them 350 HCC samples were investigated in the prognosis analysis. KASP method was conducted for the SNP genotyping. The TT + CT genotype of rs2839698 was found to be associated with a 1.32-fold increased HCC risk (P=0.037, 95% confidence interval (CI) = 1.02-1.70). In the stratified analysis, rs2839698 (odds ratio (OR) = 1.57, P=0.007, 95% CI = 1.13-2.18) and rs3024270 (OR = 1.71, P=0.019, 95% CI = 1.09-2.68) were found to show more obvious increased HCC risk in the age ≤60 subgroup. And we found that rs2839698 showed an increased HCC risk in the ever smoking subgroup. But in the male subgroup of rs2735971, it showed a decreased HCC risk. Furthermore, haplotype analysis showed that rs2735971-rs2839698-rs3024270 G-T-C significantly increased the risk of HCC (OR = 1.23, 95% CI = 1.01-1.51, P=0.043). Multilogistic analysis revealed no significant results of the interaction effects of the SNPs and environment factors. And in our study, rs2839698 showed a significant poor prognosis in the ever smoking subgroup (hazard rate (HR) = 5.19, 95% CI = 1.12-24.07, P=0.035). lncRNA-H19 rs2839698 SNP has the potential to be predictors for HCC risk and prognosis.

Serum CA125 level predicts prognosis in patients with multiple brain metastases from non-small cell lung cancer before and after treatment of whole-brain radiotherapy.

This study was to evaluate the effect of serum CA125 level on the prognosis of patients with multiple brain metastases from non-small cell lung cancer before and after treatment of whole-brain radiotherapy. Sixty-six patients with multiple brain metastases from non-small cell lung cancer before and after treatment of radiotherapy were reviewed retrospectively. Radiotherapy was given to the whole brain using opposed 6MV lateral beams with a dose of 30 Gy in 15 fractions in 3 weeks. Elevated CA125 was defined as >35 U/mL. The survival rate was calculated using the Kaplan-Meier method, and the univariate and multivariate analyses were used to identify significant factors associated with prognosis, using a Cox proportional hazards model. During the median (range) follow-up of 1.25 (0.25-2.50) years, 62 patients died from non-small cell lung cancer; the 1-year cancer-specific survival (CSS) rate was 43.08 %. Thirty patients had a high CA125 level before chemoradiotherapy (>35U/mL), and their CSS rate was significantly worse than that in the remaining patients (P = 0.024). Multivariate analysis showed that CA125 level, number of metastases and total tumor volume were independent prognostic indicators for CSS, with a hazard ratio of 1.99, 1.67 and 2.02, respectively. The elevation of CA125 before treatment predicts a poor prognosis in patients with multiple brain metastases from non-small cell lung cancer before and after treatment of whole-brain radiotherapy.

Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human hepatoblastoma.

BACKGROUND: Hepatoblastoma (HB) is the most common primary, malignant pediatric liver tumor in children. The treatment results for affected children have markedly improved in recent decades. However, the prognosis for high-risk patients who have extrahepatic extensions, invasion of the large hepatic veins, distant metastases and very high alpha-fetoprotein (AFP) serum levels remains poor. There is an urgent need for the development of novel therapeutic approaches. METHODS: An attenuated strain of measles virus, derived from the Edmonston vaccine lineage, was genetically engineered to produce carcinoembryonic antigen (CEA). We investigated the antitumor potential of this novel viral agent against human HB both in vitro and in vivo. RESULTS: Infection of the Hep2G and HUH6 HB cell lines, at multiplicities of infection (MOIs) ranging from 0.01 to 1, resulted in a significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72-96 h after infection. Both of the HB lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. The efficacy of this approach in vivo was examined in murine Hep2G xenograft models. Flow cytometry assays indicated an apoptotic mechanism of cell death. Intratumoral administration of MV-CEA resulted in statistically significant delay of tumor growth and prolongation of survival. CONCLUSIONS: The engineered measles virus Edmonston strain MV-CEA has potent therapeutic efficacy against HB cell lines and xenografts. Trackable measles virus derivatives merit further exploration in HB treatment.

Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human neuroblastoma through a CD46 and nectin 4-independent pathway.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. In this study, we investigated the potential antitumor capability of the engineered Edmonston strain of the carcinoembryonic antigen-expressing measles virus (MV-CEA) against human NB. The infection of a variety of NB cell lines, including SK-N-SH, SMS-KCNR, and primary NB cells, resulted in significant cytopathic effects. None of the NB cell lines showed an overexpression of the measles virus receptor CD46 and nectin 4, but the cell lines did support robust viral replication. The efficacy of this approach was examined in murine SK-N-SH xenograft models. Flow cytometry and TUNEL assays indicated an apoptotic mechanism of cell death. In summary, MV-CEA has potent therapeutic efficacy against NB mediated by a CD46- and nectin 4-independent pathway.

Identification of microRNA target genes in vivo.

MicroRNAs (miRNAs) are short non-coding RNAs transcribed from intergenic or intronic sequences as long precursors that are sequentially processed by the endonucleases Drosha and Dicer into short double-stranded sequences. It is clear that miRNAs play essential roles in gene expression, development, and cell fate specification in animals. However, one of the barriers of miRNA research is how to find the target genes. In this study, we have developed a rapid and effective method to isolate miRNA target genes in vivo. MicroRNA was synthesized in vitro and labeled by biotin. After transfected into cells, the miRNA/mRNA complexes were isolated by streptavidin-coated magnetic beads. hsa-miR155 was taken as model to validate this method, which is a very important modulator in tumor development. It is useful for validation of targets predicted in silico, and, potentially, for discovery of previously uncharacterized targets.

Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome.

BACKGROUND: The combination of partial absence of the sacrum, anorectal anomalies, and presacral mass constitutes Currarino syndrome (CS), which is associated with mutations in HLXB9. METHODS: We analyzed 5 CS families and 6 sporadic cases for HLXB9 mutations by direct sequencing. Potentially pathologic expansions of HLXB9 GCC repeats were analyzed in patients, 4 general populations [Chinese, Japanese, Yoruba, and Centre du Etude Polymorphisme Human (CEPH)] from the HapMap project, and 145 healthy Chinese. RESULTS: We identified 6 novel mutations affecting highly conserved residues (Ser185X, Trp215X, Ala26fs, Ala75fs, Met1Ile, and Arg273Cys). GCC allele and genotype distributions showed marked statistically significant differences. (GCC)11 was the most common allele overall; its frequency ranged from 90% in CEPH to 68% in Yoruba and 50% in Chinese and Japanese populations. (GCC)9 was almost as common as (GCC)11 in Chinese and Japanese populations, whereas its frequency was <10% in Yoruba and CEPH populations. The Yoruba population had the highest frequency of the largest alleles [(GCC)12 and (GCC)13], which were almost absent in the other groups. CONCLUSIONS: Lack of HLXB9 mutations in some patients and the presence of variable phenotypes suggest DNA alterations in HLXB9 noncoding regions and/or in other genes encoding HLXB9 regulatory molecules or protein partners. If HLXB9, like other homeobox genes, has a threshold beyond which triplet expansions are pathologic, those populations enriched with larger alleles would be at a higher risk. The data illustrate the importance of ethnicity adjustment if these polymorphic markers are to be used in association studies.