Hypertrophic obesity, characterized by an excessive expansion of subcutaneous adipocytes, causes chronic inflammation and insulin resistance. It is the primary feature of obesity in middle-aged and ...elderly individuals. In the adipose microenvironment, a high level of endoplasmic reticulum (ER) stress and changes in the extracellular vesicle (EV) composition of adipocytes may cause the senescence and restrained differentiation of progenitor cells of adipose, including adipose-derived mesenchymal stem cells (ASCs). In this study, a hypertrophic obesity mouse model was established, and the effects of adipocytes on the ER stress and senescence of ASCs were observed in a coculture of control ASCs and hypertrophic obesity mouse adipocytes or their derived EVs. The adipocytes of hypertrophic obesity mice were treated with GW4869 or an iron chelation agent to observe the effects of EVs secreted by adipocytes and their iron contents on the ER stress and senescence of ASCs. Results showed higher ER stress level and senescence phenotypes in the ASCs from the hypertrophic obesity mice than in those from the control mice. The ER stress, senescence phenotypes, and ferritin level of ASCs can be aggravated by the coculture of ASCs with adipocytes or EVs released by them from the hypertrophic obesity mice. GW4869 or iron chelator treatment improved the ER stress and senescence of the ASCs cocultured with EVs released by the adipocytes of the hypertrophic obesity mice. Our findings suggest that EV-mediated transmissible ER stress is responsible for the senescence of ASCs in hypertrophic obesity mice.
Tumor microenvironment (TME) is the cellular environment in which tumor exists, and it contributes to tumor formation and progression. The TME is composed of tumor cells, stromal cells, cytokines, ...and chemotactic factors of which fibroblasts are the main cellular components. In our present study, we found that colorectal cancer (CRC) cells expressing integrin αvβ6 clearly could induce morphological changes in inactive fibroblasts and increased the expression of activated fibroblast markers such as α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Those activated fibroblasts in the TME are called cancer-associated fibroblasts (CAFs). In order to investigate the mechanism by which CRC cells expressing integrin αvβ6 activated CAFs, a series of assays have been carried out in the follow-up. We found that CRC cells could secrete inactive transforming growth factor β (TGF-β); however, integrin αvβ6 activated TGF-β, which subsequently activated fibroblasts. This process was disrupted by knockdown of integrin αvβ6. In contrast, activated fibroblasts could promote CRC cell invasion. In particular, the strengthening effect on expression of integrin αvβ6 in colon cancer cells was obvious. Additionally, we found that CAFs could secrete stromal cell-derived factor-1 (SDF-1) and promote CRC cell metastasis in distant organs via the SDF-1/C-X-C chemokine receptor type 4 (CXCR4) axis. Taken together, we assumed that CRC cells and CAFs activated one another and worked together to promote cancer progression, with integrin αvβ6 playing a role in the bi-directional regulation of these cells. Hence, integrin αvβ6 may serve as a therapeutic target for the future CRC treatment.
Purpose
Several studies have examined the association between glucokinase (GCK)-30G > A polymorphism and gestational diabetes mellitus (GDM). However, the results are still controversial. We ...performed the case–control study to investigate whether GCK-30G > A polymorphism correlates with the susceptibility of GDM in Chinese populations, and then conducted a meta-analysis by combining the previous studies.
Methods
We recruited 948 GDM patients and 975 controls from May 2011 to August 2013. All the subjects were genotyped using the PCR-based invader assay. The differences of allelic frequencies and genotype distributions between GDM patients and controls were investigated in case–control study. A systematic search of all relevant studies was conducted. The observational studies that were related to an association between the glucokinase (GCK)-30G > A polymorphism and GDM were identified. The association between the glucokinase (GCK)-30G > A polymorphism and GDM susceptibility was assessed using genetic models.
Results
The case–control study showed that GCK-30G > A polymorphism was associated with the susceptibility of GDM in a Chinese population. Furthermore, other six previously reported studies were included to perform meta-analysis. The meta-analysis showed that GCK-30G > A polymorphism was associated with GDM in Caucasian and Asian.
Conclusions
This study suggested that GCK-30G > A polymorphism may be associated with the susceptibility of GDM in a Chinese population. The further meta-analysis provides additional evidence supporting the above result that the risk allele of the GCK-30G > A polymorphism may increase GDM risk.
The health impacts of dietary fat-to-energy ratio (FER) compared to carbohydrate-to-energy ratio (CER) are widely discussed topics in public health. This study aimed to assess the health impacts of ...FER and CER by establishing trajectory-patterns of FER and CER over the course of adult life.
This study used the weighted longitudinal data of the China Health and Nutrition Survey, including eight surveys from 1991 to 2011. The trajectories of FER and CER were determined via latent class trajectory modeling. The trajectories were then cross-grouped into different trajectory-patterns. Multivariate Cox regression models were used to assess the relationship between these trajectory-patterns and cardio-metabolic diseases and all-cause mortality. Ten thousand nine hundred and twenty-six adults with a total of 50,693 observations across eight surveys were included.
Compared to the trajectory-pattern of persistently low-FER (increased from 10 to 20%) and moderate-CER (stable and ranging from 55 to 65%) over the adult life-course, the two trajectory-patterns that showed changing to high-FER and low-CER were significantly associated with obesity HR 1.83 95% CI, 1.10-3.04; HR 1.46 95% CI, 1.02-2.17, diabetes HR 1.80 95% CI, 1.03-3.16; HR 1.49 95% CI, 1.01-2.25, and all-cause mortality HR 2.29 95% CI, 1.35-3.87; HR 1.62 95% CI, 1.18-2.22. In contrast, the trajectory-pattern of a persistently low-FER and high-CER diet was not associated with obesity HR 1.19 95% CI, 0.82-1.17, diabetes HR 1.41 95% CI, 0.98-2.02, cardiovascular-disease HR 1.48 95% CI, 0.91-2.39, and all-cause mortality HR 1.23 95% CI, 0.94-1.61.
This study indicates that changing to a high-FER and low-CER diet over the course of adult life was significantly associated with obesity, diabetes, and all-cause mortality in the Chinese adult population. In addition, low-FER and high-CER were not associated with cardio-metabolic disease and all-cause mortality. These observations may provide insights into nutritional policy and dietary guidelines.
The hadal zone and Antarctic Ocean are two of the least-explored habitats. Knowledge about human impacts on these two extreme environments is limited. Here, we analyzed the metal accumulations of two ...amphipod species, Eurythenes gryllus, from the Mariana Trench (6040 m, 11.36° N, 142.41° E) in the West Pacific Ocean, and Pseudorchomene plebs, from the Ross Sea (600 m, 77.12° S, 167,67° E) in the Antarctic. Bioaccumulation of thirteen elements (Na, Mg, K, Ca, Cu, Fe, Al, Cr, Mn, Zn, As, Se, and Cd) in three tissues (exoskeleton, leg muscle, and gut) of the two amphipods was investigated using inductively coupled plasma mass spectrometry (ICP-MS). Comparing the trace element concentrations between the different amphipoda species, we found higher element concentrations in the Antarctic amphipod, and an oligotrophication of the Mariana Trench. The concentrations of Cu, Zn, As, and Se in the three tissues all had a significant difference in abundance, and the Cd in the gut of P. plebs was comparably higher than that in E. gryllus, consistent with special environment adaptation. Compared with non-abyssal and shallow water decapoda and amphipoda species, hadal amphipods possessed comparably higher concentrations of Cd and Cr elements and displayed a very high environmental specificity for amphipods’ metal-element bioaccumulation strategy. This study reveals the amphipods of remote and uncontaminated areas as potential indicator species for metal-element bioaccumulation to measure anthropogenic impacts.
Abstract
Purpose
Papillary lesions (PL) account for 1–2 % of all breast neoplasms and fiberoptic ductoscopy is a practical and direct method compared with open biopsy in diagnosis and treatment of ...intraductal papillary lesions. This study aimed to assess efficacy of ductoscopy in the diagnosis and management of single intraductal papillary lesion.
Methods
A total of 232 patients at China-Japan Union Hospital of Jilin University who were diagnosed with single intraductal papillary lesion by fiberoptic ductoscopy were enrolled from March 2011 to November 2013. All patients underwent ductoscopic papillomectomy before open surgery. The final pathologic diagnoses were made by using specimen from both ductoscopic papillomectomy and surgeries. Any intraductal papillomatous lesion or surface abnormalities were considered as positive findings during ductoscopy.
Results
Histopathologic investigations of surgically excised or ductoscopically removed lesions revealed that 217 out of 232 cases were positive. In 187 cases pathological changes were only found in ductoscopic papillomectomy specimen, while the number of cases which was only found in open biopsy was 24. In 6 cases ductoscopic papillomectomy and surgeries specimen both showed positive.
Conclusions
The accuracy of ductoscopy biopsy in diagnosis was 88.9% (193/217) and specificity was 100%. In 187 out of 217 cases (86.2%) ductoscopic papillomectomy alone could completely remove the lesion. Ductoscopy is an effective tool for diagnosis and treatment of single intraductal papillary lesion.
Citation Format: Zheli Xu, Wanying Xing, Qiang Li, Deli Xing, Yiqi Gu. Assessment of diagnostic and therapeutic value of ductoscopy biopsy in single intraductal papillary lesion compared with open surgery abstract. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-10.
With the economic impact and increasing popularity of the electronic gaming industry, EGS (Electronic Gaming Sports) had become an important topic of debate in sports academia regarding its ...conceptual delineation and attribute characteristics. This paper jumped out of the hotspot academic perspective of the concept, characteristics, and impacts of EGS. In response to the gaps in the spatial development of the EGS industry and the lack of empirical research findings, an interpretive empirical research method was adopted, focusing on Wuhan as the study area to gain insight into the situation where the spatial development of the EGS industry was unclear. The spatial evolution of the EGS industry in the main town area of Wuhan was interpreted through a quantitative approach and based on the spatial data of EGS companies from 2006 to 2022 using Average Nearest Neighbor (ANN), Kernel Density Estimation (KDE), and Ordinary Kriging (OK) of geospatial analysis. The results indicated closure to the gradual release of the EGS industry, with specific findings as follows. (1) The EGS industry in the main town area of Wuhan from 2006 to 2022 developed rapidly, and the overall spatial distribution showed a process from discrete to cluster, accompanied by an apparent deepening of aggregation in recent years. The local aggregation of the EGS industry transformed from dual to multiple cores, and the multiple cores formed stronger groups of aggregation as the cluster spread and merged. (2) The spatial interpolation of the registered capital of companies predicted the hot spot of high-capital distribution of EGS companies in the Optics Valley vice town area of Hongshan to the southeast, indicating that more competitive EGS companies and larger EGS industry groups might emerge in Optics Valley in the future. (3) The spatial evolution of the EGS industry in the main town area of Wuhan could be divided into an early start phase from 2006-2010, a rapid development phase from 2010-2014, an aggregate explosion phase from 2014-2018, and a cluster integration phase from 2018-2022. (4) The spatial evolution of the EGS industry was influenced not only by the main factors of industrial economic agglomeration, industrial chain derivation, and industrial policy environment but also by the other factors of land and talent market, adjacent infrastructure support, city industrial promotion, and globalization dissemination. The future development of the EGS industry could be guided by the government's industrial policies, supported by high-quality talent teams, and driven by local promotion and international communication to provide an essential impetus for the optimal EGS industry.
The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for ovarian ...cancer. However, ovarian cancer cells are resistant to PP242, a dual inhibitor of mTORC1 and mTORC2. Interestingly, blockage of GLS1 with a selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. The anti-cancer activity of CB-839 and PP242 was abrogated by the addition of the TCA cycle product α-ketoglutarate, indicating the critical function of GLS1 in ovarian cancer cell survival. Finally, glutaminolysis inhibition activated apoptosis and synergistically sensitized ovarian cancer cells to priming with the mTOR inhibitor PP242. GLS1 inhibition significantly reduced phosphorylated STAT3 expression in ovarian cancer cells. These findings show that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy to overcome resistance to PI3K/Akt/mTOR inhibition.
Halogenation of terminal of acceptors has been shown to give dramatic improvements in power conversion efficiencies (PCEs) of organic solar cells (OSCs). Similar significant results could be expected ...from the halogenation of the central units of state‐of‐the‐art Y‐series acceptors. Herein, a pair of acceptors, termed CH6 and CH4, featuring a conjugation‐extended phenazine central unit with and without fluorination, have been synthesized. The fluorinated CH6 has enhanced molecular interactions and crystallinity, superior fibrillar network morphology and improved charge generation and transport in blend films, thus affording a higher PCE of 18.33 % for CH6‐based binary OSCs compared to 16.49 % for the non‐fluorinated CH4. The new central site offers further opportunities for structural optimization of Y‐series molecules to afford better‐performed OSCs and reveals the effectiveness of fluorination on central units.
A series of CH molecules with a new modification site on the central unit of Y‐series electron acceptors has been designed and synthesized to afford better‐performing organic solar cells (OSCs). Further fluorination on the largely unexplored central unit enabled significantly improved photovoltaic performance with over 18% efficiency for CH6‐based binary OSCs.
Hyperglycemia has been reported to activate the nuclear factor-κB (NF-κB) pathway. We have previously demonstrated that exogenous hydrogen sulfide (H2S) protects cardiomyocytes against high glucose ...(HG)-induced injury by inhibiting the activity of p38 mitogen-activated protein kinase (MAPK), which can activate the NF-κB pathway and induce interleukin (IL)-1β production. In the present study, we aimed to investigate the hypothesis that exogenous H2S protects cardiomyocytes against HG-induced injury and inflammation through the inhibition of the NF-κB/IL-1β pathway. H9c2 cardiac cells were treated with 35 mM glucose (HG) for 24 h to establish a model of HG-induced damage. Our results demonstrated that treatment of the cells with 400 μM sodium hydrogen sulfide (NaHS, a donor of H2S) or 100 μM pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) for 30 min prior to exposure to HG markedly attenuated the HG-induced increase in the expression levels of the phosphorylated (p)-NF-κB p65 subunit. Notably, pre-treatment of the H9c2 cardiac cells with NaHS or PDTC significantly suppressed the HG-induced injury, including cytotoxicity, apoptosis, oxidative stress and mitochondrial insults, as evidenced by an increase in cell viability, as well as a decrease in the number of apoptotic cells, the expression of cleaved caspase-3, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial membrane potential (MMP). In addition, pre-treatment of the cells with NaHS or PDTC ameliorated the HG-induced inflammatory response, leading to a decrease in the levels of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α). Importantly, co-treatment of the H9c2 cells with 20 ng/ml IL-1 receptor antagonist (IL-1Ra) and HG markedly reduced the HG-induced increase in p-NF-κB p65 expression, cytotoxicity, the number of apoptotic cells, as well as the production of TNF-α. In conclusion, the present study presents novel mechanistic evidence that exogenous H2S protects H9c2 cardiac cells against HG-induced inflammation and injury, including cytotoxicity, apoptosis, overproduction of ROS and the dissipation of MMP, by inhibiting the NF-κB/IL-1β pathway. We also provide new data indicating that the positive interaction between the NF-κB pathway and IL-1β is critical in HG-induced injury and inflammation in H9c2 cardiac cells.
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