Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 ...(LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding. The phosphorylated LARS1 showed decreased leucine binding, which may inhibit protein synthesis and help save energy. Leucine that is not used for anabolic processes may be available for catabolic pathway energy generation. The LARS1-mediated changes in leucine utilization might help support cell survival under glucose deprivation. Thus, depending on glucose availability, LARS1 may help regulate whether leucine is used for protein synthesis or energy production.
Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell ...lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.
To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model.
Human breast cancer ...cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment IA-T, intravenous treatment IV-T, IA saline injection IA-S, and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured.
Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 interquartile range 8.48-16.05 vs. 25.69 mm3 IQR 20.39-30.29, p = 0.005), control group (IA-S, 33.83 mm3 IQR 32.00-36.30, p<0.01), and sham control (39.71 mm3 IQR 26.60-48.26, p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 IQR 7.23-8.20 vs. IA-S, 6.77 IQR 6.48-6.87, p = 0.044 and vs. sham control, 6.89 IQR 4.93-7.48, p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 IQR 20.39-30.29 vs. 39.71 mm3 IQR 26.60-48.26, p = 0.27); there was no significant change in the MRI parameters.
IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.
Despite their potential in various fields of bioapplications, such as drug/cell delivery, tissue engineering, and regenerative medicine, hydrogels have often suffered from their weak mechanical ...properties, which are attributed to their single network of polymers. Here, supertough composite hydrogels are proposed consisting of alginate/polyacrylamide double‐network hydrogels embedded with mesoporous silica particles (SBA‐15). The supertoughness is derived from efficient energy dissipation through the multiple bondings, such as ionic crosslinking of alginate, covalent crosslinking of polyacrylamide, and van der Waals interactions and hydrogen bondings between SBA‐15 and the polymers. The superior mechanical properties of these hybrid hydrogels make it possible to maintain the hydrogel structure for a long period of time in a physiological solution. Based on their high mechanical stability, these hybrid hydrogels are demonstrated to exhibit on‐demand drug release, which is controlled by an external mechanical stimulation (both in vitro and in vivo). Moreover, different types of drugs can be separately loaded into the hydrogel network and mesopores of SBA‐15 and can be released with different speeds, suggesting that these hydrogels can also be used for multiple drug release.
The mesoporous‐silica‐embedded, supertough hybrid hydrogel shows enhanced mechanical stability in both normal conditions and physiological conditions under mechanical stimulation. Furthermore, multiple drugs can be loaded into this hybrid hydrogel; these drugs are subject to on‐demand release at different times via stimulation with a mechanical force. These supertough hybrid hydrogels have great potential for a variety of bioapplications.
Aim
To study the role of sclerostin in periodontal ligament (PDL) as a homeostatic regulator in biophysical‐force‐induced tooth movement (BFTM).
Materials and Methods
BFTM was performed in rats, ...followed by microarray, immunofluorescence, in situ hybridization, and real‐time polymerase chain reaction for the detection and identification of the molecules. The periodontal space was analysed via micro‐computed tomography. Effects on osteoclastogenesis and bone resorption were evaluated in the bone‐marrow‐derived cells in mice. In vitro human PDL cells were subjected to biophysical forces.
Results
In the absence of BFTM, sclerostin was hardly detected in the periodontium except in the PDL and alveolar bone in the furcation region and apex of the molar roots. However, sclerostin was up‐regulated in the PDL in vivo by adaptable force, which induced typical transfiguration without changes in periodontal space as well as in vitro PDL cells under compression and tension. In contrast, the sclerostin level was unaffected by heavy force, which caused severe degeneration of the PDL and narrowed periodontal space. Sclerostin inhibited osteoclastogenesis and bone resorption, which corroborates the accelerated tooth movement by the heavy force.
Conclusions
Sclerostin in PDL may be a key homeostatic molecule in the periodontium and a biological target for the therapeutic modulation of BFTM.
The pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a public health emergency, and research on the development of various types of vaccines is rapidly progressing ...at an unprecedented development speed internationally. Some vaccines have already been approved for emergency use and are being supplied to people around the world, but there are still many ongoing efforts to create new vaccines. Virus-like particles (VLPs) enable the construction of promising platforms in the field of vaccine development. Here, we demonstrate that non-infectious SARS-CoV-2 VLPs can be successfully assembled by co-expressing three important viral proteins membrane (M), envelop (E) and nucleocapsid (N) in plants. Plant-derived VLPs were purified by sedimentation through a sucrose cushion. The shape and size of plant-derived VLPs are similar to native SARS-CoV-2 VLPs without spike. Although the assembled VLPs do not have S protein spikes, they could be developed as formulations that can improve the immunogenicity of vaccines including S antigens, and further could be used as platforms that can carry S antigens of concern for various mutations.
The study examined predictors of male nurse turnover intention in Korea using data collected from Korean hospitals. The results were obtained based on a secondary analysis of data previously ...collected from 306 male nurses in 16 regions of Korea from December 2014 to February 2015. Our findings suggest that male nurse turnover intention is predicted by (1) individual factors: single (B = 0.93, p = 0.008); (2) organizational factors: organizational commitment (B = −0.36, p < 0.001), job satisfaction (B = −0.27, p = 0.001), and job stress (B = 0.24, p < 0.001); and (3) social factors: hospital location in medium-categorized cities (B = 0.70, p = 0.012) and kinship responsibility (B = 0.13, p = 0.026). These factors accounted for 56.9% of the total variance. To lower the rate of turnover intention among male nurses, strategic interventions should be implemented based on the factors identified in this study.
Mixed matrix membranes (MMMs) with a thermally rearranged (TR) polymer and zeolitic imidazolate framework-8 (ZIF-8) were prepared in this study. ZIF-8 contributed to not only enhancing gas ...permeability, but also promoting thermal conversion of TR polymer membranes. As a result, TR ZIF-8 MMMs can be prepared at lower temperatures compared to the original TR polymers. The thermal rearrangement process also increased gas separation properties as it contributes to a tunable cavity size and hour-glass shape cavity distributions. Moreover, interfacial voids between the polymer phase and ZIF crystals which usually occur in most MMMs disappeared during thermal rearrangement of the TR polymer. As a result, the TR ZIF-8 MMMs showed excellent hydrogen separation properties with a H2 permeability of 1,206 Barrer, H2/N2 selectivity of 22.3, and H2/CH4 selectivity of 25.7.
TR conversion percent change of HPI and HPI ZF-8 MMMs with dwell time at 400 °C (left), conceptual images of HPI ZIF-8 MMMs (middle-top) TR ZIF-8 MMMs (middle-bottom), and the H2 permeability H2/N2 selectivity (right) of HPI ZIF-8 MMMs and TR ZIF-8 MMMs. Display omitted
•Thermally stable ZIF-8 nanoparticles were introduced into TR polymers.•The introduction of ZIF-8 into TR polymers enabled TR conversion under mild conditions.•The interfacial voids between TR polymer and ZIF-8 were alleviated during the TR process.•The resulting membranes presented enhanced hydrogen permeability and selectivity.
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