Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Celastrol alleviates oxidative stress induced by multi-walled carbon nanotubes through the Keap1/Nrf2/HO-1 signaling pathway.

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Global gene expression changes in human peripheral blood after H7N9 infection.

A novel avian influenza A virus (H7N9) of human infection emerged in eastern China in 2013, causing mild to lethal human respiratory infections. However, the underlying molecular mechanism remains largely unknown. In this work, we attempt to gain insights into the underlying genetic basis of this disease at the transcription level. We collected peripheral blood samples from patients with H7N9 infection and healthy people, and then we performed transcriptome profiling to comprehensively investigate their expression signatures, which would help us to better understand the molecular basis of the etiology upon viral infection. By employing the high throughput RNA-seq analysis of samples with and without H7N9 viral infection, we totally identified 1091 significantly differentially expressed genes. We found that several biological pathways related to the immunity and inflammation response in the differentially expressed genes. A genome-wide screening of gene regulation between H7N9 virus carrier and healthy people provided some insights into understanding and responsiveness to this potential threat.

Prognostic factors associated with rebleeding in cirrhotic inpatients complicated with esophageal variceal bleeding.

BACKGROUND: Esophageal variceal bleeding is a frequent and severe complication in patients with cirrhosis. The aim of this study was to identify prognostic factors of esophageal variceal rebleeding in cirrhotic inpatients. METHODS: Consecutive cirrhotic patients who were admitted to Changhai Hospital because of esophageal variceal bleeding were retrospectively analyzed. To assess the independent factors for recurrent hemorrhage after esophageal variceal bleeding, medical assessment was completed at the time of their initial hospital admission, including documentation of clinical, biochemical, and treatment methods that might contribute to variceal rebleeding. Univariate and multivariate analyses were retrospectively performed. RESULTS: Totally 186 patients (35.8%) were assigned to a rebleeding group and the other 334 patients (64.2%) to a non-rebleeding group. Multivariate stepwise regression analysis showed that four variables were positively correlated with rebleeding: Child-pugh grade B (OR = 2.664, 95%CI 1.680 - 4.223) (compared with Child-pugh grade A), total bilirubin (Tbil) (OR = 1.0006, 95%CI 1.002 - 1.0107), creatinine (OR = 1.008, 95%CI 1.002 - 1.015) and the cumulative volume of blood transfusion (OR = 1.519, 95%CI 1.345 - 1.716). The presence of ascites (OR = 0.270, 95%CI 0.136 - 0.536) and prophylactic antibiotics (OR = 0.504, 95%CI 0.325 - 0.780) were negatively correlated with rebleeding of the cirrhotic inpatients. According to standardized coefficient, the importance of rebleeding predictors ranked from the most to the least was as follows: the cumulative volume of blood transfusion, Child-pugh grade B, Tbil and creatinine. CONCLUSION: Rebleeding in cirrhotic inpatients was associated with more blood transfusions, Child-pugh grade B, higher Tbil and creatinine.

[Relationship of plasma homocysteine and folic acid levels and 5,10-methylenetetrahydrofolate reductase gene mutation with venous thromboembolism].

OBJECTIVE: To investigate the association between concentrations of plasma homocysteine and folic acid, 5,10-methylenetetrahydrofolate reductase (MTHFR) C667T mutation and venous thromboembolism (VTE) and to analyze the effect of MTHFR C667T mutation on concentrations of plasma homocysteine and folic acid. METHODS: In 58 patients with VTE and 58 sex and age matched controls, epidemiological risk factors were surveyed. The concentration of plasma homocysteine was measured by high performance liquid chromatography, and the concentration of plasma folic acid was measured by radioimmunoassay. MTHFR C667T genotype was measured by PCR-RFLP. RESULTS: The concentrations of plasma homocysteine and folic acid showed significant difference between the case group and the control group (OR = 1.5, 95% CI: 1.216 - 2.213 and OR = 0.396, 95% CI: 0.149 - 0.709, respectively). There was no significant difference in the frequency of mutant alleles in site 667 of MTHFR gene between the cases and the controls (P > 0.05). The concentration of plasma folic acid was associated with the concentration of plasma homocysteine (multiple correlation coefficient = -2.061, P < 0.05). The MTHFR C667T polymorphism was associated with the concentration of plasma folic acid but not with the concentration of plasma homocysteine in both the case group and the control group. The multiple correlation coefficient between the MTHFR C667T polymorphism and the concentration of plasma folic acid is 0.5856 (P < 0.01). CONCLUSIONS: The results of our study demonstrate that hyperhomocysteinemia and folic acid deficiency are independent risk factors for VTE. Folic acid deficiency is a cause of hyperhomocystinemia while the MTHFR C667T mutation is one of the possible genetic factors causing folic acid deficiency in this Chinese population.