Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

The relationship between serum klotho and cognitive performance in a nationally representative sample of US adults.

Purpose: Aging is the primary risk factor for cognitive decline. Serum klotho, as an anti-aging protein, may be involved in cognitive decline. Thus, we aim to explorer the correlation between serum klotho and cognitive performance among an older adult population in the United States. Methods: We performed a cross-sectional study using data from NHANES 2011-2014. Serum klotho was analyzed by ELISA. Cognitive function was measured by Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test and Digit Symbol Substitution Test (DSST) score. The relationship between serum klotho and cognition was analyzed by a multivariable regression model. Results: A total of 2,171 participants aged 60-79 years were included. Median serum klotho concentration was 851.52 pg./ml (SD = 294.07). We also categorized serum klotho concentrates into quartiles. After fully adjusting pertinent variables, compared to those with lowest klotho levels (206.3-658.4 pg./ml), individuals with highest klotho concentrates (983.3-3,456 pg./ml) had a higher CERAD score [ß (95%CI): 0.97 (0.25, 1.69) p = 0.008] and DSST score [ß (95%CI): 1.86 (0.25, 3.47), p = 0.024]. Conclusion: Our findings indicated that, among the general population of American older adults, serum klotho concentrates may serve as a marker of cognitive health. The benefits of klotho on aging process and neurodegenerative disorders should be paid more attention.

The Association Between Leukocyte Telomere Length and Cognitive Performance Among the American Elderly.

BACKGROUND: Age-related cognitive decline begins in middle age and persists with age. Leukocyte telomere length (LTL) decreases with age and is enhanced by inflammation and oxidative stress. However, whether shorter LTL correlates with cognitive decline remains controversial. AIMS: We aimed to investigate the relationship between LTL and cognitive decline in the American elderly. METHODS: We used data from the 1999 to 2002 U.S. National Health and Nutrition Examination Survey (NHANES). We included participants aged 65-80 with available data on LTL and cognitive assessments. The cognitive function assessment used the digit symbol substitution test (DSST). We applied multivariate modeling to estimate the association between LTL and cognitive performance. Additionally, to ensure robust data analysis, we converted LTL into categorical variables through quartile and then calculated the P for trend. RESULTS: After adjusting for age, cardiovascular disease (CAD) score, gender, race, body mass index (BMI), and educational level, LTL showed a positive correlation with DSST score (odds ratio [OR] 3.47 [0.14, 6.79], P = 0.04). Additionally, to further quantify the LTL-DSST interaction, we found a similar trend when LTL was regarded as a categorical variable (quartile) (P for trend = 0.03). CONCLUSION: LTL was associated with cognitive capabilities among the elderly, implying that LTL might be a biomarker of cognitive aging.

Correlation between low serum calcium concentration and hematoma volume in patients with intracerebral hemorrhage / 中国脑血管病杂志

Objective To investigate the relationship between low serum calcium concentration and hematoma volume in patients with intracerebral hemorrhage.Methods Between January 2012 and October 2014,870 consecutive patients with intracerebral hemorrhage admitted to the Department of Neurosurgery,West China Hospital,Sichuan University were enrolled prospectively.The patients completed laboratory serum calcium concentration and head CT examinations within 24 h after attack,and the baseline data and laboratory findings were collected.According to the normal reference value of laboratory serum calcium concentration,the patients were divided into a hypocalcemia calcium group (<2.1 mmol/L;n=193) and a normal calcium group (2.1-2.7 mmol/L;n=677).Spearman correlation analysis was used to analyze the correlation between the blood serum calcium concentration and the hematoma volume on admission.Results (1) The hypocalcemia group compared with normal calcium group,the proportion of male patients was high (73.6% [n=142] vs.66.0% [n=447]),the median score for Glasgow coma scale was lower (9 vs.11),and the median hematoma volume was larger (33.86 cm3 vs.21.69 cm3).The differences were statistically significant (all P<0.05).(2) Spearman correlation analysis showed that the lower serum calcium level on admission was weakly negatively correlated with the volume of hematoma in patients with intracerebral hemorrhage (r=-0.113,P<0.01).Conclusion The study suggested that the hypocalcemia on admission was mostly males in patients with intracerebral hemorrhage,the condition was serious,the volume of hematoma was larger,and the lower serum calcium concentration was negatively correlated with the hematoma volume.

Antineoplastic agents-induced pulmonary toxicity / 国际肿瘤学杂志

Antineoplastic agents-induced pulmonary toxicity is one of important reasons causing respiratory failure,which clinical manifestations are pulmonary inflammation,allergic reaction,vascular permeability reaction and pulmonary vascular disease.All of these may be caused by drug toxicity,immune response and increased capillary permeability and so on.Because of the nonspecific performance,it is important to exclude the other lung diseases.Once the diagnosis is clear,the antineoplastic gents should be immediately stopped and the patients should be timely administered high-dose eorticosteroid therapy.How to reduce the pulmonary toxicity induced by antineoplastic agents is becoming one of the future focuses about antineoplastic agents research.