Suchergebnisse

Meiling Lu,1,* Jinghua Li,1,* Zaili Luo,2,3,* Shuai Zhang,3 Shaobo Xue,1 Kesheng Wang,1 Yan Shi,4 Cunzhen Zhang,3 Haiyang Chen,3 Zhong Li1,5 1Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China; 2International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, People's Republic of China; 3Institution of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China; 4Department of Gastroenterology, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China; 5Zhangjiang Center for Translational Medicine, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Tumor metastasis is the most common cause of death and poor prognosis for cancer patients. Therapeutics that prevent tumor metastasis are the key to prolonging the lifespan of cancer patients. Cancer stem cells are believed to be critical in the metastatic process. Recently, drug screening for cancer stem cells reports that antipsychotic drugs displayed potential anticancer activity. Thioridazine, one of the antipsychotic drugs for dopamine receptors (DRs), is shown to induce the differentiation of cancer stem cells in leukemic disease and breast cancer, but it is not known if this drug would affect liver cancer. In this study, expression of DR5 was higher in tumors than in nontumor adjacent tissues, while DR1 was lower in human hepatocellular carcinoma (HCC) than those in the adjacent tissues. Other DRs were very low or undetectable. Treatment of HCC cells with thioridazine displays a dose-dependent response in HCC cell lines SNU449, LM3, and Huh7. Thioridazine treatment reduced cell viability and sphere formation of HCC cell lines through induction of G0/G1 cell cycle arrest and suppression of stemness genes CD133, OCT4, and EpCam. It also inhibited cell migration via suppression of epithelial–mesenchymal transition (EMT)-related genes such as twist2 and E-cadherin. Thioridazine-pretreated LM3 cells decreased the capacity of tumorigenesis in nude mice. Taken together, our data suggest that thioridazine may have the potential role in treatment of HCC. Keywords: antipsychotic, thioridazine, HCC, dopamine receptors, metastasis

Background COVID-19 lockdowns may lead to physical inactivity, a major risk factor for non-communicable diseases. This study aims to determine: 1) the trajectory in daily step counts before, during and after the lockdown in China, and 2) the characteristics associated with the trajectories. Methods From December 2019 to July 2020, smartphone-based step counts were continuously collected in 815 Chinese adults residing in Shanghai over 202 days across three phases: before, during, and after the lockdown. Participant characteristics were reported, and height, weight and body composition measured before the lockdown. A 'sharp' regression discontinuity design with cluster robust standard errors was used to test the effect of the lockdown and reopening on daily steps and a linear mixed model was used to examine the characteristics associated with trajectories during the observed period. Results Based on 164,630 person-days of data, we found a sharp decline in daily step counts upon the lockdown (24/01/2020) by an average of 3796 (SE = 88) steps, followed by a significant trend of increase by 34 steps/day (SE = 2.5; p < .001) until the end of the lockdown (22/03/2020). This increasing trend continued into the reopening phase at a slower rate of 5 steps per day (SE = 2.3; p = 0.029). Those who were older, married, university educated, insufficiently active, had an 'at risk' body composition, and those in the control group, were slower at recovering step counts during the lockdown, and those who were older, married, without university education and with an 'at risk' body composition recovered step counts at a slower pace after the reopening. Conclusions Despite later increases in step counts, COVID-19 lockdown led to a sustained period of reduced physical activity, which may have adverse health implications. Governments and health professionals around the world should continue to encourage and facilitate physical activity during the pandemic.

BACKGROUND: COVID-19 lockdowns may lead to physical inactivity, a major risk factor for non-communicable diseases. This study aims to determine: 1) the trajectory in daily step counts before, during and after the lockdown in China, and 2) the characteristics associated with the trajectories. METHODS: From December 2019 to July 2020, smartphone-based step counts were continuously collected in 815 Chinese adults residing in Shanghai over 202 days across three phases: before, during, and after the lockdown. Participant characteristics were reported, and height, weight and body composition measured before the lockdown. A 'sharp' regression discontinuity design with cluster robust standard errors was used to test the effect of the lockdown and reopening on daily steps and a linear mixed model was used to examine the characteristics associated with trajectories during the observed period. RESULTS: Based on 164,630 person-days of data, we found a sharp decline in daily step counts upon the lockdown (24/01/2020) by an average of 3796 (SE = 88) steps, followed by a significant trend of increase by 34 steps/day (SE = 2.5; p < .001) until the end of the lockdown (22/03/2020). This increasing trend continued into the reopening phase at a slower rate of 5 steps per day (SE = 2.3; p = 0.029). Those who were older, married, university educated, insufficiently active, had an 'at risk' body composition, and those in the control group, were slower at recovering step counts during the lockdown, and those who were older, married, without university education and with an 'at risk' body composition recovered step counts at a slower pace after the reopening. CONCLUSIONS: Despite later increases in step counts, COVID-19 lockdown led to a sustained period of reduced physical activity, which may have adverse health implications. Governments and health professionals around the world should continue to encourage and facilitate physical activity during the pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary ...

In recent years, trafficking and abuse of hallucinogenic mushrooms have become a serious social problem. It is therefore imperative to identify hallucinogenic mushrooms of the genus Psilocybe for national drug control legislation. An internal transcribed spacer (ITS) is a DNA barcoding tool utilized for species identification. Many methods have been used to discriminate the ITS region, but they are often limited by having a low resolution. In this study, we sought to analyze the ITS and its fragments, ITS1 and ITS2, by using high-resolution melting (HRM) analysis, which is a rapid and sensitive method for evaluating sequence variation within PCR amplicons. The ITS HRM assay was tested for specificity, reproducibility, sensitivity, and the capacity to analyze mixture samples. It was shown that the melting temperatures of the ITS, ITS1, and ITS2 of Psilocybe cubensis were 83.72 ± 0.01, 80.98 ± 0.06, and 83.46 ± 0.08 °C, and for other species, we also obtained species-specific results. Finally, we performed ITS sequencing to validate the presumptive taxonomic identity of our samples, and the sequencing output significantly supported our HRM data. Taken together, these results indicate that the HRM method can quickly distinguish the DNA barcoding of Psilocybe cubensis and other fungi, which can be utilized for drug trafficking cases and forensic science.

Background: COVID-19 lockdowns may lead to physical inactivity, a major risk factor for non-communicable diseases. This study aims to determine: 1) the trajectory in daily step counts before, during and after the lockdown in China, and 2) the characteristics associated with the trajectories. Methods: From December 2019 to July 2020, smartphone-based step counts were continuously collected in 815 Chinese adults residing in Shanghai over 202 days across three phases: before, during, and after the lockdown. Participant characteristics were reported, and height, weight and body composition measured before the lockdown. A 'sharp' regression discontinuity design with cluster robust standard errors was used to test the effect of the lockdown and reopening on daily steps and a linear mixed model was used to examine the characteristics associated with trajectories during the observed period. Results: Based on 164,630 person-days of data, we found a sharp decline in daily step counts upon the lockdown (24/01/2020) by an average of 3796 (SE = 88) steps, followed by a significant trend of increase by 34 steps/day (SE = 2.5; p <.001) until the end of the lockdown (22/03/2020). This increasing trend continued into the reopening phase at a slower rate of 5 steps per day (SE = 2.3; p = 0.029). Those who were older, married, university educated, insufficiently active, had an 'at risk' body composition, and those in the control group, were slower at recovering step counts during the lockdown, and those who were older, married, without university education and with an 'at risk' body composition recovered step counts at a slower pace after the reopening. Conclusions: Despite later increases in step counts, COVID-19 lockdown led to a sustained period of reduced physical activity, which may have adverse health implications. Governments and health professionals around the world should continue to encourage and facilitate physical activity during the pandemic.

Tunica Interna endothelial cell kinase (Tie2)-expressing macrophages (TEMs) are a subgroup of tumor-associated macrophages that are associated with a poor prognosis in numerous types of cancer. The present study aimed to assess the prognostic impact of Tie2 expression in gastric cancer tissues. Between January 2009 and December 2009, 76 newly diagnosed patients with gastric cancer at the Southwest Hospital, Third Military Medical University (Chongqing, China) were enrolled. TEMs were detected using immunohistochemistry. Tie2, cluster of differentiation (CD)68 and carbonic anhydrase IX (CAIX) were analyzed using immunohistochemistry and immunofluorescent microscopy. Tie2 protein expression was analyzed using western blot analysis in hypoxic and normoxic gastric cancer tissues. The number of TEMs positively staining for Tie2 increased with the tumor-node-metastasis (TNM) stage: 0, 53.9, 75.6 and 100% in stages I, II, III and IV, respectively (P<0.001). Tumor size and lymph node involvement were significantly associated with the presence of Tie2 in the tumor stroma (P<0.001). There was no significant difference between Tie2 and CAIX, irrespective of how the patients were grouped (tumor size, lymph node involvement, TNM stage or histological grade). Tie2 protein expression was increased in the hypoxic regions of gastric tumors.Tie2 and CD68 expression colocalized in hypoxic and normoxic gastric cancer tissues. The 1-, 2- and 3-year recurrence rates of the TEM-positive group were 31.4, 56.9 and 66.7%, respectively, as compared with 8, 28 and 48%, respectively, for the TEM-negative group (P<0.05). In the TEM-negative group, 2 patients succumbed to the disease, as compared with 21 patients in the TEM-positive group (P<0.05). Therefore, high quantities of TEMs, represented by Tie2 expression, in gastric tumors may be associated with poor survival.