Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events involved in the pathophysiology of vascular diseases. Sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), has ...been reported to have the function of antiatherosclerosis, but its role in neointima formation remains unknown.
The present study was designed to investigate the role of SIRT1 in the regulation of neointima formation and to elucidate the underlying mechanisms.
A decrease in SIRT1 expression was observed following carotid artery ligation. smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) mice were generated. SIRT1 overexpression substantially inhibited neointima formation after carotid artery ligation or carotid artery wire injury. In the intima of injured carotid arteries, VSMC proliferation (proliferating cell nuclear antigen (PCNA)-positive cells) was significantly reduced. SIRT1 overexpression markedly inhibited VSMC proliferation and migration and induced cell cycle arrest at G1/S transition in vitro. Accordingly, SIRT1 overexpression decreased the induction of cyclin D1 and matrix metalloproteinase-9 (MMP-9) expression by treatment with serum and TNF-α, respectively, whereas RNAi knockdown of SIRT1 resulted in the opposite effect. Decreased cyclin D1 and MMP-9 expression/activity were also observed in injured carotid arteries from SMC-SIRT1 Tg mice. Furthermore, 2 targets of SIRT1, c-Fos and c-Jun, were involved in the downregulation of cyclin D1 and MMP-9 expression.
Our findings demonstrate the inhibitory effect of SIRT1 on the VSMC proliferation and migration that underlie neointima formation and implicate SIRT1 as a potential target for intervention in vascular diseases.
Aims
The aim of this study was to evaluate its feasibility of a non-symbiotic nitrogen-fixing strain, Ac63 (
Azotobacter chroococcum
), to promote biomass of common vegetable crops and its ...colonization mechanisms in their roots.
Methods
Root exudates of common vegetables, including
Amaranthus tricolor
(AT),
Willow amaranth
(WA),
Chrysanthemum coronarium
(CC), cabbage, and lettuce, were collected, and a chemotaxis assay with Ac63 was performed. Components in exudates for the most differential chemotaxis effect crops (AT and lettuce) were determined with GC-MS. Then, the traditional screening strategies of chemotaxis, swarming, and in vitro were utilized to find the signal molecule for this strain. Finally, the colonization effects of Ac63 in roots of these two crops were verified with a soil pot experiment.
Results
Chemotaxis effects of root exudates on Ac63 follow the lists of AT > WA > CC > cabbage ≈ control (water) ≈ lettuce. With a 30-μM concentration of
l
-glutamic acid, bacterial amount of Ac63 in chemotaxis and in vitro was observed with 2.9- and 7.4-times enhancement compared with that in the control. Laser confocal microscopy indicated that
l
-glutamic acid induced Ac63 to form a robust biofilm in roots, suggesting that
l
-glutamic acid is a signal molecule for the colonization of this strain. Soil pot assay showed that the biomass, chlorophyll, and available nitrogen of AT significantly increased than those of lettuce after Ac63 inoculation, resulting from this strain was substantially increased in roots of AT with
l
-glutamic acid secretion.
Conclusion
l
-Glutamic acid induced the colonization of high-efficiency nitrogen-fixing strain Ac63 in AT roots, which provides a practical information for its agricultural applications.
Cadmium (Cd) re-mobilize by phosphate-solubilizing bacteria (PSB) from immobilization contaminated soil has drawn great attention due to its serious threat to human health through food chain. ...However, Cd binding with weathered coal (WC), an effective Cd immobilization material, will be re-mobilized by PSB or not is still unclear. In this study, the soil and sand pots with Cd were respectively mixed with the weight fractions of 0‰, 2‰, and 3‰ WC, inoculated with or without PSB, and planted with
Amaranthus mangostanus
L. The experimental results indicated that: (i) Cd in soil was transformed into organic fraction with WC, which has been led to the Cd accumulation concentrations in roots and shoots reduced by 38.8% and 20.5%, respectively; (ii) PSB could promote the concentration of exchangeable-Cd fraction and soil Cd uptake by amaranth in all treatments; and (iii) WC application in sand pot respectively reduced the Cd accumulation by 47.5% in roots and 24.1% in shoots, but PSB inoculation showed no significant effect on Cd accumulation in plants under WC application. SEM, zeta potential, and FT-IR results showed that PSB inoculation after Cd immobilized by WC had no influence on the microstructure, amount of negative charge, type, and content of functional groups in WC, indicating that organic fraction Cd in WC was not re-mobilized by PSB. Therefore, the application of WC in contaminated soil was conducive to transforming Cd in organic-bound forms and intensifying Cd immobilization effects.
Iugisporipsathyra
, a new psathyrelloid genus from tropical red soil of China, is established with
I. reticulopilea
as the type species. The new genus is characterised by basidiomata psathyrelloid, ...pileus rugose to appearing reticulate ridged, covered by persistent, but inconspicuous villus, pleurocystidia absent and ridge-ornamented spores with an obvious suprahilar plage. The genus is unique amongst Psathyrellaceae in producing ridge-ornamented spores with an obvious suprahilar plage and forms a distinct lineage within Psathyrellaceae, based on the Maximum Likelihood and Bayesian Inference analyses of a combined three-gene sequence dataset (ITS, LSU and β-
tub
). Full descriptions and photographs of the new genus and species are presented.
Hollow mesoporous silica (HMS) composed of a hollow cavity and mesoporous shell available for drug storage. The MgAl-LDH as a gatekeeper coated on the HMS outer surface by the layer-by-layer ...selfassembly method, encapsulated the anticancer drug 5-Fluorouracil (5-FU) within the HMS cavities and pores to get the pH-controlled drug release system (FU/HMS@LDH) for minimizing premature release of 5-FU. The structures, morphology, texture and 5-FU release behavior were characterized and investigated with various techniques. The kinetic data revealed that the targeted 5-FU release by the LDH-gated HMS release system (FU/HMS@LDH) stemmed from the dissolution of the LDH nanosheets upon decrease in pH and cleavage of the hydrogen bonds, indicating that the pH-responsive controlled release of 5-FU could be stimulated by acidic environments. These results suggested that the FU/HMS@LDH release system had the potential as an anticancer drug delivery system in targeted drug release for tumor chemotherapy.
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•Hydrotalcite-gated hollow mesoporous silica delivery system (FU/HMS@LDH) with pH-sense was successfully prepared.•The drug-loading pore channels can be closed and opened at will due to the pH-sense of the FU/HMS@LDH.•The FU/HMS@LDH can release sustainedly at pH 4.6, basically completely release at pH 2.4, and had ‘‘almost zero release’’ property (pH 7.4).
Due to invasion and intrahepatic metastasis, the prognosis for patients with hepatocellular carcinoma (HCC) is poor. However, the mechanisms underlying these processes of HCC remain unclear. Cancer ...stem cells may be involved in early systemic dissemination and metastasis formation and side population (SP) cells isolated from diverse cancer cells possess stem cell-like properties. However, the mechanisms involved in migration and invasion of cancer stem cells are not well understood. In this study, we identified and isolated populations of SP cells from HCC cell lines using flow cyto-metry. SP cells showed higher levels of migration and invasion capability. Higher expression of miR-21 was observed in SP cells. Silencing of miR-21 led to a reduction in the migration and invasion of these cells and overexpression of miR-21 can increase in cell migration and invasion. Overexpression of miR-21 did not cause degradation of PTEN or RECK or PDCD4 mRNA but drastically inhibited its protein expression. Consistent with these results, silencing miR-21 increased the levels of PTEN, RECK and PDCD4 protein, respectively. The role of silencing miR-21 was partially attenuated by silencing of PTEN or RECK or PDCD4 mRNA. The results of this study revealed the aberrant expression of miR-21 in SP cells and showed that miR-21 regulates the expression of multiple target proteins that are associated with tumor dissemination. MiR-21 is a pro-metastatic miRNA in SP cells and raises the possibility that therapy of HCC may be improved by pharmaceutical strategies directed towards miR-21.
Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. ...As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified.
HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration.
As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence.
HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.
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•Gegen Qinlian Decoction abated nonalcoholic steatohepatitis associated liver injuries.•Gegen Qinlian Decoction could improve lipid metabolism.•Gegen Qinlian Decoction had ...anti-oxidative stress effect.•Gegen Qinlian Decoction had anti-inflammatory effect.•Anti-inflammatory effect involved inhibition of TLR4 signaling pathways.
Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.
Temperature plays a major role in Cr(VI) adsorption although the underlying mechanisms are still unclear. The aim of this study was to determine the relationship among the temperature, adsorption ...properties and microstructure characteristics. In this work, the calcined Mg/Al hydrotalcites (MMO) as adsorbents were investigated for the Cr(VI) removal in aqueous solution. The effect of calcination and adsorption temperatures on the Cr(VI) removal of the MMO was studied based on the aspects of the microstructure characteristics and adsorption properties. The results showed that the sample calcined at 500°C (MMO500) had the largest adsorption capacity of 94.64mg·g−1 for Cr(VI). For MMO500 as an adsorbent, the experiment data were fitted well into Langmuir isotherm model and pseudo-second-order kinetic model. Combined with thermodynamic analysis, the activation energy (22.42kJ·mol−1) suggested that the adsorption process was chemisorption nature and diffusion was the rate limiting step. The further research showed that the film diffusion was more dominant than the intra-particle diffusion. The results demonstrated that the MMO500 was a promising adsorbent in the Cr(VI) pollution control.
•Calcination temperature strongly affected the microstructure of Mg/Al LDH.•Adsorption mechanism of Mg/Al LDH calcined at different temperatures was changing.•Mg/Al LDH calcined at 500°C had the highest adsorption capacity.•Film diffusion played a key role in the Cr(VI) adsorption process of the MMO500.
In the last few decades, the incidences of obesity and related metabolic disorders worldwide have increased dramatically. Major pathophysiology of obesity is termed "lipotoxicity" in modern western ...medicine (MWM) or "dampness-heat" in traditional Chinese medicine (TCM). "Dampness-heat" is a very common and critically important syndrome to guild clinical treatment in TCM. However, the pathogenesis of obesity in TCM is not fully clarified, especially by MWM theories compared to TCM. In this review, the mechanism underlying the action of TCM in the treatment of obesity and related metabolic disorders was thoroughly discussed, and prevention and treatment strategies were proposed accordingly. Hypoxia and inflammation caused by lipotoxicity exist in obesity and are key pathophysiological characteristics of "dampness-heat" syndrome in TCM. "Dampness-heat" is prevalent in chronic low-grade systemic inflammation, prone to insulin resistance (IR), and causes variant metabolic disorders. In particular, the MWM theories of hypoxia and inflammation were applied to explain the "dampness-heat" syndrome of TCM, and we summarized and proposed the pathological path of obesity: lipotoxicity, hypoxia or chronic low-grade inflammation, IR, and metabolic disorders. This provides significant enrichment to the scientific connotation of TCM theories and promotes the modernization of TCM.
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