Phenotype transformation of vascular smooth muscle cells (VSMCs) is known to be modulated by mechanical strain. The present study was designed to investigate how different frequencies of mechanical strain affected VSMC phenotype. VSMCs were subjected to the strains of 10% elongation at 0, 0.5, 1 and 2 Hz for 24 h using a Flexercell strain unit. VSMC phenotype was assessed by cell morphology, measurement of two-dimensional cell area, Western blotting for protein and RT-PCR for mRNA expression of differentiation markers. Possible protein kinases involved were evaluated by Western blotting with their specific antibodies. The strains at certain frequencies could induce a contractile morphology in VSMC with almost perpendicular alignment to the strain direction. The strains also regulated protein and mRNA expression of several differentiation markers, as well as the activation of extracellular signal-regulated kinases (ERKs), p38 MAP kinase and protein kinase B (Akt) in a frequency-dependent manner. Furthermore, the inhibition of the p38 pathway could block the frequency-induced phenotype modulation of VSMCs, but not inhibition of ERK or Akt pathways. These results indicate that the frequency of cyclic strain can result in the differentiated phenotype of VSMCs, and it is mediated at least partly by the activation of the p38 pathway.
Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian cancer, thus molecular characterization may provide an important tool for this purpose. On a molecular level, proviral-integration site for Moloney-murine leukemia virus (PIM) kinases are over expressed in ovarian cancer and play a vital role in the regulation of different proteins responsible for this tumorigenesis. Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer. Interestingly, recent research has linked the PIM kinases to the PI3K/AKT/mTOR pathway in several types of cancers, but their connection in ovarian cancer has not been studied yet. Once the exact relationship of PIM kinases with the PI3K/AKT/mTOR pathway is acquired in ovarian cancer, it will hopefully provide effective treatments on a molecular level. This review mainly focuses on the role of PIM kinases in ovarian cancer and their interactions with proteins involved in its progression. In addition, this review suggests a connection between the PIM kinases and the PI3K/AKT/mTOR pathway and their parallel mechanism in the regulation of ovarian cancer.
Pim-3 is a member of proto-oncogene Pim family that encodes serine/threonine kinases. Pim proteins regulate both apoptosis and cellular metabolism by phosphorylating their substrates. Here, we report for the first time that Pim-3 is highly expressed at mRNA and protein levels in endothelial cells (ECs). We found that Pim-3 is concentrated at the cellular lamellipodia and co-localized with focal adhesion kinase (FAK). Pim-3 was dispersed from lamellipodia when ECs were treated with cytochalasin D, an inhibitor of actin polymerization. In addition, small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired EC spreading, migration, and proliferation, leading to a reduction in tube-like structure formation in a Matrigel assay. These results provide the novel evidence that Pim-3 plays an essential role in EC spreading and migration, suggesting that Pim-3 may be an important molecular target for the development of small-molecule inhibitors of angiogenesis.
This
work placed an emphasis that constructing segregated boron
nitride (BN)/carbon nanotube (CNT) hybrid network brought an immense
benefit to enhance the thermal conductivity (TC) of poly(vinylidene
fluoride) (PVDF) composites. The segregated composites ((CNT + BN)@PVDF)
showed a high TC of 1.8 W/mK at the total filler fraction of 25 vol
%, outperforming PVDF composites with random structure (CNT/BN/PVDF)
and segregated BN structure (BN@PVDF) by 169% and 50%, respectively.
Infrared thermal images further demonstrated that (CNT + BN)@PVDF
exhibited superior capability to dissipate heat compared to BN/PVDF.
The segregated architecture increased the effective utilization of
fillers and interfacial thermal resistance between neighboring BN
platelets was reduced by the bridging effect of CNTs. Molding pressure
and temperature governed the integration of segregated networks and
thus the enhancement efficiency of TC. The design of hybrid segregated
structure holds promise in a broad range of the preparation of thermal
management materials.
Objective:
To evaluate therapeutic efficacy of different combined antimicrobial treatments against
Acinetobacter baumannii
ventilator-associated pneumonia (VAP).
Methods:
Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth dilution methods determined the minimum inhibitory concentrations (MICs) of four antiseptic drugs singly used and combined two drugs against 36 isolates of multidrug-resistant (MDR)
A. baumannii
.
Results:
The incidence of VAP was approximately 6.9% (237/3424) between January 1, 2015 and December 31, and 35.9% (85/237) of the cases were caused by
A. baumannii
. Among these cases, 60 belonged to AB-VAP, for whom antimicrobial treatment plan was centralized and clinical data was complete. Moreover, all 60 strains of
A. baumannii
were MDR bacteria from reports microbiological laboratory. Resistance rate was lowest for amikacin (68.3%) and ampicillin sulbactam (71.7%). Resistance rate for imipenem increased from 63.2 to 90.9% during the 3 years. However, in these 60 cases of AB-VAP, the combination between 4 antibiotics was effective in most cases: the effective rate was 75% (18/24) for sulbactam combined with etilmicin, 71.4% (10/14) for sulbactam combined with levofloxacin, 72.7% (8/11) for meropenem combined with etilmicin, and 63.6% (7/11) for meropenem combined with levofloxacin. There was no statistical difference between four regimens (
P
> 0.05). Sulbactam combined with etilmicin decreased 1/2 of MIC
50
and MIC
90
of sulbactam while the decreases in etilmicin were more obviously than single drug. When adopting meropenem combined with levofloxacin or etilmicin, the MIC of meropenem reduced to 1/2 of that in applying single drug. As for sulbactam or meropenem combined with levofloxacin, it also lessened the MIC
50
of levofloxacin to 1/2 of that for single drug. FIC results suggested that the effects of four combined antimicrobial regimens were additive or unrelated. When sulbactam was combined with etimicin, the additive effect was 63.89%.
Conclusion:
Drug combination sensitivity test
in vitro
may be helpful for choosing antimicrobial treatment plans. Sulbactam or meropenem as the basis of treatment regimens can function as the alternatives against AB-VAP. Sulbactam combined with etimicin has been regarded as a recommended regimen in Suizhou, Hubei, China.
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