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.
We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping ...Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.
Summary Objective To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and ...the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. Methods OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. Results OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. Conclusions Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.
The NAD(+)-dependent deacetylase, sirtuin 1 (SIRT1), has been recently been suspected to have a role in tumorigenesis. We investigated the expression of SIRT1 in pancreatic cancer and the effect of ...SIRT1-targeted RNA interference (RNAi) on cell proliferation and tumor formation in a pancreatic cancer cell line, PANC1. The expression of SIRT1 was investigated in 49 specimens of pancreatic cancer and adjacent normal pancreatic tissues. SIRT1 was overexpressed in pancreatic cancer tissues at both the mRNA and protein levels, with increased SIRT1 positivity associated with tumors from patients over 60 years old, tumors larger than 4 cm, higher TNM (extent of tumor (T), the extent of spread to lymph nodes (N), and presence of distant metastasis (M)) stage or the presence of lymph node or hepatic metastases. The PANC-1 was stably transfected with a SIRT1 small hairpin RNA (shRNA) expression plasmid and compared with untransfected and PANC-1-negative RNAi cells. Proliferation of PANC-1-SIRT1-RNAi cells was significantly reduced, accompanied by increased rates of apoptosis, G1 arrest and senescence. Furthermore, FOXO3a expression was markedly upregulated in PANC-1-SIRT1-RNAi cells, but no significant difference in p53 expression was observed. The invasive ability of PANC-1-SIRT1-RNAi cells was markedly reduced in vitro, which was linked to increased E-cadherin and reduced-MMP expression. Additionally, PANC-1-SIRT1-RNAi cells had a significantly reduced capacity to form tumors in vivo compared with untransfected and PANC-1-negative RNAi cells. These results suggest that SIRT1 may promote cell proliferation and tumor formation in pancreatic cancer, and downregulation of SIRT1 using shRNA could provide a novel therapeutic treatment.
Multiple growth pathways lead to enhanced proliferation in malignant cells. However, how the core machinery of DNA replication is regulated by growth signaling remains largely unclear. The sliding ...clamp proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA machinery responsible for replicating the genome and maintaining genomic integrity. We previously reported that epidermal growth factor receptor (EGFR) triggered tyrosine 211 (Y211) phosphorylation of PCNA, which in turn stabilized PCNA on chromatin to promote cell proliferation. Here we show that the phosphorylation can also be catalyzed by the non-receptor tyrosine kinase c-Abl. We further demonstrate that, in the absence of EGFR, signaling to PCNA can be attained through the activation of the Ron receptor tyrosine kinase and the downstream non-receptor tyrosine kinase c-Abl. We show that Ron and c-Abl form a complex, and that activation of Ron by its ligand, hepatocyte growth factor-like protein (HGFL), stimulates c-Abl kinase activity, which in turn directly phosphorylates PCNA at Y211 and leads to an increased level of chromatin-associated PCNA. Correspondingly, HGFL-induced Ron activation resulted in Y211 phosphorylation of PCNA while silencing of c-Abl blocked this effect. We show that c-Abl and Y211 phosphorylation of PCNA is an important axis downstream of Ron, which is required for cell proliferation. Treatment with a specific peptide that inhibits Y211 phosphorylation of PCNA or with the c-Abl pharmacological inhibitor imatinib suppressed HGFL-induced cell proliferation. Our findings identify the pathway of Ron-c-Abl-PCNA as a mechanism of oncogene-induced cell proliferation, with potentially important implications for development of combination therapy of breast cancer.
A marigold-like SiC@MoS2 nanoflower with a unique Z-scheme structure efficiently achieves the overall conversion of gas phase CO2 with H2O (CO2 (g) + 2H2O (g) = CH4 + 2O2) without any sacrificial ...reagents under visible light (λ ≥ 420 nm) irradiation. The CH4 and O2 evolution are 323 and 621 μL·g–1·h–1, and stable throughout 5 cycle reactions of total 40 h. This work demonstrates a breakthrough in artificial photosynthesis with the Z-scheme 1D heterojunction constructed by combining 2D semiconductor and 3D semiconductor based on the transfer balance of photogenerated electron and hole.
Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous cancers and involved in tumorigenesis, whereas their influences on pancreatic cancer (PC) still need further ...elucidation. The present research revealed that miR-494 was significantly decreased in PC cell lines and tissues. Functional study showed that overexpressed miR-494 could remarkably inhibit proliferation of PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1-phase arrest and senescence. Moreover, upregulated miR-494 significantly prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified as targets of miR-494 through dual luciferase assay and further confirmed by the reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore, co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and SIRT1 expression, and inhibited proliferation of PC, which simulated the effects of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1 effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical characteristics further revealed that low miR-494 correlated with larger tumor size, late tumor node metastasis stage, lymphatic invasion, distant metastasis and poor prognosis. In conclusion, the present study indicated that miR-494 might serve as predictor and inhibitor in PC by directy downregulating the loop of c-Myc and SIRT1.
In this study, 121 daily PM2.5 (aerosol particle with aerodynamic diameter less than 2.5 μm) samples were collected from an urban site in Beijing in four months between April 2009 and January 2010 ...representing the four seasons. The samples were determined for various compositions, including elements, ions, and organic/elemental carbon. Various approaches, such as chemical mass balance, positive matrix factorization (PMF), trajectory clustering, and potential source contribution function (PSCF), were employed for characterizing aerosol speciation, identifying likely sources, and apportioning contributions from each likely source. Our results have shown distinctive seasonality for various aerosol speciations associated with PM2.5 in Beijing. Soil dust waxes in the spring and wanes in the summer. Regarding the secondary aerosol components, inorganic and organic species may behave in different manners. The former preferentially forms in the hot and humid summer via photochemical reactions, although their precursor gases, such as SO2 and NOx, are emitted much more in winter. The latter seems to favorably form in the cold and dry winter. Synoptic meteorological and climate conditions can overwhelm the emission pattern in the formation of secondary aerosols. The PMF model identified six main sources: soil dust, coal combustion, biomass burning, traffic and waste incineration emission, industrial pollution, and secondary inorganic aerosol. Each of these sources has an annual mean contribution of 16, 14, 13, 3, 28, and 26%, respectively, to PM2.5. However, the relative contributions of these identified sources significantly vary with changing seasons. The results of trajectory clustering and the PSCF method demonstrated that regional sources could be crucial contributors to PM pollution in Beijing. In conclusion, we have unraveled some complex aspects of the pollution sources and formation processes of PM2.5 in Beijing. To our knowledge, this is the first systematic study that comprehensively explores the chemical characterizations and source apportionments of PM2.5 aerosol speciation in Beijing by applying multiple approaches based on a completely seasonal perspective.
Evidence of false-positive galactomannan enzyme immunoassay (GM-EIA) results associated with intravenous immunoglobulin (IVIG) administration is scarce. Here, we aimed to determine the false-positive ...rate of GM-EIA after IVIG administration and to identify the related factors.
Standard GM-EIA was performed using diluted and pure human IVIG samples with and without heat treatment. We also included adult patients who had at least one GM-EIA result within 1 week of IVIG administration for analysis. Those who had prior invasive aspergillosis within 1 year before IVIG therapy were excluded. The clinical characteristics and galactomannan index (GMI) kinetics between patients with false-positive and true-positive GMI were compared.
All diluted and pure IVIG samples tested positive for GM. Heat treatment resulted in the considerable elevation of GMI. Of 48 patients with positive GM-EIA results within 1 week of IVIG administration, 22 (45.8%) were considered to have false-positive antigenaemia (false-positive group, FPG). After the completion of IVIG administration, a decline in GMI was observed in all FPG patients but in only 18 out of 26 patients (69.2%) with true-positive results (true-positive group, TPG). By 7, 14, and 18 days of IVIG administration, GMI reverted to negative values in 7/15 (46.7%), 18/20 (90%) and 22/22 (100%) FPG patients, respectively, and 6/24 (25%), 14/24 (58.3%), and 16/26 (61.5%) of TPG patients, respectively. The TPG was more likely to have two or more consecutively positive GMIs after IVIG administration than the FPG (adjusted odds ratio, 9.01; 95% confidence interval, 1.99–40.9).
IVIG treatment may produce false-positive GM-EIA results. A positive GMI among patients receiving human IVIG should be interpreted with caution.
Objective
To investigate the risks of attempted and completed suicide in women who experienced a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally and compare this risk ...with that in women who experienced a live birth.
Design
A nested case–control study.
Setting
Linking three nationwide population‐based data sets in Taiwan: the National Health Insurance Research Database, the National Birth Registry and the National Death Registry.
Sample
In all, 485 and 350 cases of attempted and completed suicide, respectively, were identified during 2001–11; for each case, ten controls were randomly selected and matched to the cases according to the age and year of delivery.
Methods
Conditional logistic regression.
Main outcome measures
Attempted and completed suicidal statuses were determined.
Results
The rates of attempted suicide increased in the women who experienced fetal loss. The risk of completed suicide was higher in women who experienced a stillbirth adjusted odds ratio (aOR) 5.2; 95% CI 1.77–15.32, miscarriage (aOR 3.81; 95% CI 2.81–5.15), or termination of pregnancy (aOR 3.12; 95% CI 1.77–5.5) than in those who had a live birth. Furthermore, the risk of attempted suicide was significantly higher in women who experienced a miscarriage (aOR 2.1; 95% CI 1.66–2.65) or termination of pregnancy (aOR 2.5; 95% CI 1.63–3.82). In addition to marital and educational statuses, psychological illness increased the risk of suicidal behaviour.
Conclusions
The risk of suicide might increase in women who experience fetal loss within 1 year postnatally. Healthcare professionals and family members should enhance their sensitivity to care for possible mental distress, particularly for women who have experienced a stillbirth.
Tweetable
Suicide risk increased in women who had a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally.
Tweetable
Suicide risk increased in women who had a stillbirth or abortion within 1 year postnatally.
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