Sulforaphane (SFN) is a dietary component with multiple bioactivities; however, its role in obesity-related metabolic derangement remains unclear. Here, the effect of SFN on the glucose intolerance ...of obese mice and the underlying mechanism were determined. C57B/6J male mice were randomly divided into two groups, having free access to water and a normal-fat diet (ND,
n
= 6) or a high-fat diet (HFD,
n
= 33) for 8 weeks; thereafter twelve mice having the greatest weight gain among the HFD-fed mice were considered as obese mice. These obese mice were randomly divided into two groups and treated orally for 6 weeks with or without SFN (100 μmol per kg bw, 3 times per week). During this period the animals were continuously maintained on a ND or a HFD. Blood glucose and serum insulin were examined; then glucose tolerance and insulin resistance were evaluated. In addition, the expression of insulin signaling pathway-related genes in the muscle was determined. Our data showed that the obese mice presented a marked insulin resistance and glucose intolerance as compared to the control group, while SFN treatment exerted a prominently protective effect. In addition, the SFN-treated obese mice had a significantly increased insulin receptor substrate 1 (IRS-1) protein level (
P
< 0.05), markedly elevated Akt activation, as well as dramatically enhanced phosphorylation of PDK-1 (
P
< 0.05) when compared with the SFN-untreated obese mice. Moreover, the SFN-treated obese mice exhibited a significantly enhanced translocation of GLUT4 (
P
< 0.05) to the plasma membrane in the muscle compared to the obese mice without SFN treatment. In conclusion, our results support the notion that SFN acts as a promising agent to improve glucose tolerance through the up-regulation of insulin signaling mainly involving the IRS-1/Akt/GLUT4 pathway in the muscle.
Sulforaphane (SFN) is a dietary component with multiple bioactivities; however, its role in obesity-related metabolic derangement remains unclear.
Functional constipation (FC) is a high morbidity gastrointestinal disease for which dysfunction in the enteric nervous system is a major pathogenesis mechanism. To enhance our understanding of the ...involvement of intestinal microbiota and its metabolites in the pathogenesis of FC, we conducted a shotgun metagenomic sequencing analysis of gut microbiota and serum short-chain fatty acids (SCFAs) analysis in 460 Chinese women with different defecation frequencies. We observed that the abundance of
, a butyric acid-producing bacterium, was positively correlated (
= 0.0096) with the frequency of defecation; however, the concentrations of serum butyric acid was negatively correlated (
= 3.51E-05) with defecation frequency. These results were verified in an independent cohort (6 patients with FC and 6 controls). To further study the effects of butyric acid on intestinal nerve cells, we treated mouse intestinal neurons
with various concentrations of butyrate (0.1, 0.5, 1, and 2.5 mM). We found that intestinal neurons treated with 0.5 mM butyrate proliferated better than those in the other treatment groups, with significant differences in cell cycle and oxidative phosphorylation signal pathways. We suggest that the decreased butyrate production resulting from the reduced abundance of
in gut microbiota affects the proliferation of intestinal neurons and the energy supply of intestinal cells. However, with FC disease advancing, the consumption and excretion of butyric acid reduce, leading to its accumulation in the intestine. Moreover, the accumulation of an excessively high amount of butyric acid inhibits the proliferation of nerve cells and subsequently exacerbates the disease.
To evaluate conventional ultrasonography (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) imaging in thyroid nodule malignancy prediction.
This prospective study was ...institutional review board approved; informed consent was obtained. Study included 375 patients (mean age, 51 years; range, 18-75 years) with 441 pathologically proven thyroid nodules. In 281 women (mean age, 50 years; range, 18-75 years) and 94 men (mean age, 53 years; range, 18-74 years), conventional US, EI, Virtual Touch tissue imaging (VTi; Siemens, Mountain View, Calif), and Virtual Touch tissue quantification (VTq; Siemens) of ARFI imaging were performed for each nodule. Multivariate logistic regression analysis was performed to assess 17 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis.
There were 325 benign and 116 malignant nodules. Marked hypoechogenicity (odds ratio OR: 83.88; 95% confidence interval CI: 17.81, 394.99) was the strongest independent predictor for thyroid malignancy, followed by shape taller than wide (OR: 8.69; 95% CI: 2.87, 26.31), VTi (OR: 6.54; 95% CI: 3.61, 11.88), moderate hypoechogenicity (OR: 3.98; 95% CI: 1.13, 14.05), poorly defined margin (OR: 3.27; 95% CI: 1.22, 8.77), female sex (OR: 2.55; 95% CI: 1.33, 4.91), coarse background of surrounding thyroid tissue (OR: 2.01; 95% CI: 1.12, 3.62), and VTq (OR: 1.78; 95% CI: 1.28, 2.47) (all P < .05). EI was not significantly associated with thyroid malignancy (P = .855). Area under the ROC curve (Az) for VTq and VTi was higher than that with other significant independent variables. Az, sensitivity, and specificity were 0.91 (95% CI: 0.87, 0.94) and 0.86 (95% CI: 0.82, 0.90), 80% and 71.6%, and 93.8% and 83.4%, respectively, for VTi and VTq. VTq of at least 2.87 m/sec and VTi of at least grade IV were the best cutoff values for malignant thyroid nodules.
ARFI imaging is promising for malignant thyroid nodule prediction, with higher diagnostic performance than conventional US or EI. ARFI can be used to supplement conventional US to diagnose thyroid nodules in patients referred for surgery.
Large amounts of solid medium containing cordycepin, used in the industrial production of Cordyceps militaris through solid fermentation, are discarded as waste and contaminate the environment. We ...have developed a new column chromatographic extraction (CCE) method for the extraction of cordycepin from this waste and a preparation method for further separation and purification. Dried waste material was imbibed in four times its volume of water for 6h, transferred to columns and eluted with water. Eluates were directly separated with macroporous resin DM130 columns followed by purification steps, including precipitation, crystallization, and polyamide column chromatography. Extraction rates of more than 97% were obtained with 12 volumes of water for a single column and 4 volumes of water for eluates circulated through 3 different columns designed to concentrate cordycepin. Cordycepin (98% pure) was obtained following the separation and purification processes, with an overall recovery rate of more than 90%. The CCE method has high extraction efficiency, uses a minimum volume of solvent and can be used for both quantitative analysis and large preparations of cordycepin from waste. The preparation method is simple, highly efficient, energy-saving, environmentally friendly, and has been demonstrated to be effective for large preparations of cordycepin from waste with low equipment and operating costs.
Knowledge concerning the complicated changes of mass and heat transfer is desired to improve the performance and durability of unitized regenerative fuel cells (URFCs). In this study, a transient, ...non-isothermal, single-phase, and multi-physics mathematical model for a URFC based on the proton exchange membrane is generated to investigate transient responses in the process of operation mode switching from fuel cell (FC) to electrolysis cell (EC). Various heat generation mechanisms, including Joule heat, reaction heat, and the heat attributed to activation polarizations, have been considered in the transient model coupled with electrochemical reaction and mass transfer in porous electrodes. The polarization curves of the steady-state models are validated by experimental data in the literatures. Numerical results reveal that current density, gas mass fractions, and temperature suddenly change with the sudden change of operating voltage in the mode switching process. The response time of temperature is longer than that of current density and gas mass fractions. In both FC and EC modes, the cell temperature and gradient of gas mass fraction in the oxygen side are larger than that in the hydrogen side. The temperature difference of the entire cell is less than 1.5 K. The highest temperature appears at oxygen-side catalyst layer under the FC mode and at membrane under a more stable EC mode. The cell is exothermic all the time. These dynamic responses and phenomena have important implications for heat analysis and provide proven guidelines for the improvement of URFCs mode switching.
Objective:
People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. ...Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology.
Methods:
Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities.
Results:
290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways.
Conclusion:
Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.
•Substantial vasculogenic capacity can be induced in high-grade glioma cells but little in low-grade ones.•Glioblastoma cells possess weaker vasculogenic activity but higher sensitivity to angiogenic ...stimulation than normal endothelial cells.•Proangiogenic effect of hypoxia on glioblastoma cells is more potent that of proangiogenic growth factors.
Neovascularization is a histological feature of glioma, especially of glioblastoma (GBM), being associated with tumor invasiveness and poor prognosis. However, current anti-angiogenic therapies targeting vascular endothelial cells (ECs), has exhibited poor efficacy in some GBM cases. This may be at least partially attributed to the potential of glioblastoma cells to construct blood supply chain via vasculogenic mimicry or endothelial differentiation. This study aims to explore differences in vasculogenic activity and sensitivity to angiogenic stimulants between normal human ECs and glioma cells of different grades. We found that grade IV U87 GBM cells showed highly inducible vasculogenic activity either in the orthotopic xenograft model or under in vitro angiogenic stimulants as compared with grade II CHG5 glioma cells. The hypoxia mimetic more strongly induced in vitro vasculogenic capacity and endothelial marker expression of U87 GBM cells than the stimulation with multiple proangiogenic growth factors (vascular endothelial growth factor, basic fibroblast growth factor and epidermal growth factor). In contrast, proangiogenic effect of hypoxia on human umbilical vein endothelial cells (HUVECs) was weaker than on U87 GBM cells. In addition, it was also observed that the in vitro vasculogenic process of U87 cells started later but lasted longer than that of HUVECs. These results demonstrate that when compared with normal ECs, high-grade glioma cells basically possess weaker vasculogenic activity, but exhibit higher sensitivity and longer-lasting response to angiogenic stimulants, especially to hypoxia. This may be helpful to develop novel anti-angiogenic strategies targeting both vascular ECs and vasculogenic glioma cells.
In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) ...from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients D (HBsAg+)/R(HBsAg-) without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity.
We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients D(HBcAb+)/R(HBcAb-) were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint.
Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure.
D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Silk Road pattern (SRP), which is a teleconnection pattern along the Asian upper-tropospheric westerly jet in summer, exhibits both interannual and decadal variabilities. Through the nine-year ...Gaussian filtering method and regression analyses, this study compares the interannual and decadal components of the SRP. The results indicate that the interannual SRP corresponds to a well-organized wave train of alternate cyclonic and anticyclonic anomalies across the Eurasian continent along the Asian westerly jet, resulting in a similar wave-like pattern of cold and warm surface temperature anomalies. This pattern of temperature anomalies differs from that associated with the original SRP, which is characterized by warmer or cooler temperatures mainly over Europe-West Asia and Northeast Asia, depending on the phase of the SRP. On the other hand, the decadal SRP shows a similar pattern to the interannual one from Europe to Central Asia, but the meridional wind anomalies tend to be weak over East Asia. These circulation anomalies are responsible for the significant temperature anomalies over Europe-West Asia and Northeast Asia but weak anomalies between these two domains.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer malignancy worldwide and is known to have poor prognosis. The pathogenesis behind the development of HNSCC is not fully ...understood. Modifications on RNA are involved in many pathophysiological processes, such as tumor development and inflammation. Adenosine-related RNA modifications have shown to be linked to cancer and may play a role in cancer occurrence and development. To date, there are at least 170 different chemical RNA modifications that modify coding and non-coding RNAs (ncRNAs). These modifications affect RNA stability and transcription efficiency. In this review, we focus on the current understanding of the four major RNA adenosine modifications (N
-Methyladenosine, N
-Methyladenosine, Alternative Polyadenylation Modification and A-to-I RNA editing) and their potential molecular mechanisms related to HNSCC development and progression. We also touch on how these RNA modifications affect treatment of HNSCCs.
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