Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic ...Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and ...stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.
Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal ...obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity.
We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways.
A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation.
Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.
Background
Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the ...prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults.
Materials and methods
Sixty-nine middle-aged (501–64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a highprotein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention.
Results
After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test).
Conclusions
For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.
MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be expressed at higher levels in ovarian ...cancers than in benign tumors. In patients with ovarian cancer, however, higher levels of miR-187 and miR-200a expression were paradoxically associated with better OS and recurrence-free survival. Further, multivariate analysis showed that miR-187 served as an independent prognostic factor for patients with ovarian cancer (n=176). Computational prediction and microarray results indicated that miR-187 directly targeted Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the target site of miR-187 was located at the 3'-UTR of the Dab2 gene. Generally considered as a tumor-suppressor gene, Dab2 may actually promote tumor progression in advanced cancers through epithelial-to-mesenchymal transition (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation, but continued overexpression of miR-187 suppressed Dab2 and inhibited migration. Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes of patients. Collectively, these results demonstrate distinct dual roles of Dab2 in cell proliferation and tumor progression. In the initial steps of tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation. During the later stages, however, continued increased levels of miR-187 inhibits the Dab2-dependent EMT that is associated with tumor invasiveness, which is presumed to be the reason why cancers with high miR-187 levels were associated with better survivals.
Summary
Purpose
Whether patients with inflammatory bowel disease (IBD) exhibit a high risk of developing varicella zoster virus (VZV) infection in Asian populations remains inconclusive. We ...investigated the causal relationship between two diseases by analysing the Taiwan National Health Insurance Research Database.
Patients and methods
Based on a universal insurance claims database, we enrolled 7055 IBD patients and 28,220 age‐ and sex‐matched controls. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the herpes zoster virus (HZV) in the IBD and comparison cohorts, using the Cox proportional hazards regression model.
Results
Patients with IBD exhibited significantly higher risk of the HZV compared with the controls (adjusted HRs, 1.42; 95% CI, 1.27–1.60). Further analysis indicated that male patients (adjusted HRs, 1.61; 95% CI, 1.35–1.92), aged 35–44 (adjusted HRs, 1.47; 95% CI, 1.08–2.01) and aged 65 years and older (adjusted HRs, 1.47; 95% CI, 1.19–1.80), and patients without comorbidities (adjusted HRs, 1.44; 95% CI, 1.26–1.66), exhibited excessive risks of VZV infection. Moreover, our findings show that the overall risk of developing VZV infection increased risk from 1.03 (95% CI, 0.90–1.18) (≤ 2 visits) to 9.76 (95% CI, 7.60–12.5) (> 4 visits), which correlates positively with the frequency of medical visits (trend test p < 0.0001).
Conclusion
Patients with IBD, particularly men aged 35–44/65 years and over, and patients without comorbidities, are associated with a long‐term risk of VZV infection. The excessive risk of VZV infection should be considered for administering vaccines to IBD patients.
The current study aims at investigating and identifying the ionospheric effects of the geomagnetic storm that occurred during 17–19 March 2015. Incidentally, with SYM‐H hitting a minimum of −232 nT, ...this was the strongest storm of the current solar cycle 24. The study investigates how the storm has affected the equatorial, low‐latitude, and midlatitude ionosphere in the American and the European sectors using available ground‐based ionosonde and GPS TEC (total electron content) data. The possible effects of prompt electric field penetration is observed in both sectors during the main phase of the storm. In the American sector, the coexistence of both positive and negative ionospheric storm phases are observed at low latitudes and midlatitudes to high latitudes, respectively. The positive storm phase is mainly due to the prompt penetration electric fields. The negative storm phase in the midlatitude region is a combined effect of disturbance dynamo electric fields, the equatorward shift of the midlatitude density trough, and the equatorward compression of the plasmapause in combination with chemical compositional changes. Strong negative ionospheric storm phase is observed in both ionosonde and TEC observations during the recovery phase which also shows a strong hemispherical asymmetry. Additionally, the variation of equatorial ionization anomaly as seen through the SWARM constellation plasma measurements across different longitudes has been discussed. We, also, take a look at the performance of the IRI Real‐Time Assimilative Mapping during this storm as an ionospheric space weather tool.
Key Points
Simultaneous presence of positive and negative storms in American sector
Equatorward shift and enhancement of the midlatitude density trough in the American longitude sector
Strong hemispheric asymmetry in the negative storm phase during recovery phase
Summary
Background
Few studies have examined the association between psoriasis and glomerulonephritis (GN) as well as chronic kidney disease (CKD).
Objectives
To determine the risk of CKD in patients ...with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis.
Methods
We identified 4344 patients with psoriasis for the study cohort and randomly selected 13 032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD.
Results
After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow‐up period hazard ratio (HR) 1·28; 95% confidence interval (CI) 1·14–1·44. The increased incidence of GN in patients with psoriasis (HR 1·50, 95% CI 1·24–1·81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis (HR 1·62 vs. 1·26). Among drugs, nonsteroidal anti‐inflammatory drugs (NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1·69, 95% CI 1·14–2·49).
Conclusions
Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis.
What's already known about this topic?
There is an increased risk of multiple comorbidities in patients with psoriasis.
What does this study add?
Both mild and severe psoriasis presented an increased risk of chronic kidney disease (CKD) and glomerulonephritis, independent of traditional risk factors for CKD.
The development of CKD in patients with psoriasis was multifaceted. High severity, psoriatic arthritis involvement and concomitant nonsteroidal anti‐inflammatory drug use further increased the risk of CKD in patients with psoriasis.
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
The antiferroelectricity in HfZrO 2 (HZO) annealed at 600 °C with an abrupt turn ON of FET characteristics with SSmin = 23 mV/dec and SSavg = 50 mV/dec over 4 decades of IDS is demonstrated. The near ...non-hysteresis is achieved with an antiferroelectric-like HZO due to a small remanent polarization and a coercive field. A feasible concept of coupling the antiferroelectric and ferroelectric type HZO are used for low-power electronics and the memory applications, respectively.
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