Baculovirus holds great promise for the genetic modification of mesenchymal stem cells (MSCs). However, whether baculovirus transduction provokes undesired MSCs responses that might compromise their ...in vivo applications has yet to be examined. Hereby, we unraveled that baculovirus transduction of human MSCs upregulated the transcription of interleukin (IL)-1β, interferon (IFN)-α and IL-6, but not tumor necrosis factor (TNF)-α and IFN-γ. However, only IL-6 secretion was detectable by enzyme-linked immunosorbent assay (ELISA). Baculovirus transduction also stimulated transient, low level upregulation of human leukocyte antigen I (HLA-I) on the human MSCs surface, yet it did not either altered the HLA-II expression or impaired the MSCs ability to inhibit lymphocyte proliferation. After transplantation into allogeneic rats, the transduced rat MSCs elicited transient, mild macrophage responses, but the cells remained tolerant as judged by the persistence of transplanted cells and absence of CD8+ T cells infiltration. Besides, transplantation of the transduced MSCs did not provoke systemic induction of monocytes and CD8+ T cells. This study, for the first time, explores the responses of MSCs to virus transduction and confirms the safety of transplanting baculovirus-engineered MSCs into immunocompetent animals for cell-based gene therapy.
Edge morphology and lattice orientation of single-crystal molybdenum disulfide (MoS
) monolayers, a transition metal dichalcogenide (TMD), possessing a triangular shape with different edges grown by ...chemical vapor deposition are characterized by atomic force microscopy and transmission electron microscopy. Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic edges of MoS
monolayers with localized midgap electronic states, which result in greatly enhanced optical second-harmonic generation (SHG). Microscopic S-zigzag edge and S-Mo Klein edge (bare Mo atoms protruding from a S-zigzag edge) terminations and the edge-atom dependent resonance energies can therefore be deduced based on SHG images. Theoretical calculations based on density functional theory clearly explain the lower energy of the S-zigzag edge states compared to the corresponding S-Mo Klein edge states. Characterization of the atomic-scale variation of edge-enhanced SHG is a step forward in this full-optical and high-yield technique of atomic-layer TMDs.
Topological transitions between significantly different phases typically require extreme conditions to collectively break chemical bonds and overcome the stress caused to the original structure by ...altering its correlated bond environment. In this work, we present a case system that can achieve rapid rearrangement of the whole lattice of a metal–organic framework (MOF) through a ‘domino’ alteration of the bond connectivity under mild conditions. The system transforms from a disordered amorphous MOF with low porosity to a highly porous and crystalline isomer within 40 seconds upon activation (solvent exchange and desorption), resulting in a significant increase in surface area, from 725 to 2,749 m2/g–1. Spectroscopic measurements show that this counter-intuitive lattice rearrangement involves a metastable intermediate that results from solvent removal on coordinatively unsaturated metal sites. In conclusion, this amorphous–crystalline switch between two topological distinct MOFs is shown to be reversible over four cycles through activation and re-immersion in polar solvents.
Objectives:
This paper documents our experience and outcomes of using a relatively new endovascular rotational thrombectomy device for salvage of thrombosed vascular access.
Methodology:
A ...retrospective study reviewing patients with thrombosed native AVF or AVG who underwent endovascular declotting using a rotational thrombectomy device between November 2018 and May 2020 at a tertiary university hospital in Southeast Asia. We evaluated demographics, procedural data, technical and procedural success, patency rates and complications.
Results:
A total of 40 patients underwent single session endovascular declotting of thrombosed vascular access. The mean follow-up period was 21.6 months (range 13.4–31 months). The technical success was 92.5% and clinical success was 80%. About 50% of patients had concomitant thrombolysis for pharmacomechanical thrombectomy. One patient had a myocardial infarction during the post-operative period. There were no other major complications within 30 days. The primary patency was 45.5% at 6 months and 22.7% at 12 months. Assisted primary patency was 68.1% at 6 months and 61.6% at 12 months, which was maintained up to 2 years. The secondary patency was 84.1% at 6 and 12 months.
Conclusion:
Our study shows that rotational thrombectomy device for single session thrombectomy of thrombosed arteriovenous fistulas and grafts is safe and effective. A high technical and clinical success rate was achieved, with low complication rates and specific advantages compared to other techniques, including reduced length of hospital stay. Our reported mid-term outcomes are reasonable with an assisted primary patency of 62% at 12 and 24 months. The use of newer techniques and novel dedicated thrombectomy devices show promise.
The strategy of phase control has been playing an important role in optimizing the electromagnetic wave (EMW) absorption properties. Here, Ni nanoparticles (NPs) with two phases, hexagonal ...close-packed Ni (HCP-Ni) and face-centered cubic (FCC-Ni), coated by C shells are synthesized by metal-organic chemical vapor deposition. The average size of the Ni nanocores and thickness of C shells are about 10 and 4 nm, respectively. After blended with paraffin wax at a mass ratio of 1:5, the Ni-C core-shell NPs exhibit excellent EMW absorption properties with an optimal reflection loss of −52.6 dB and a large effective bandwidth ( B W e f f ) of 9.3 GHz. The core-shell NPs annealed in vacuum to remove the metastable HCP-Ni exhibit degraded EMW absorption properties. Comparative analyses reveal that the HCP-Ni phase in the core-shell NPs can enhance the dielectric loss and thus improve the impedance matching, suggesting that phase control should be a practicable strategy for optimizing the properties of Ni-based EMW absorption materials.
Doxorubicin is a widely used chemotherapy drug for the treatment of a variety of cancers, however it also has serious side effects such as anaphylaxis and heart damage. Therefore, it's very important ...to understand the downstream molecular pathways that are essential for Doxorubicin function in cancer treatment.
HeLa S3 cells were treated with different concentrations of Doxorubicin for 24 hours. Then, the mRNA levels of Notch pathway components in the Doxorubicin treated cells were determined by Real-Time qRT-PCR. Lentiviral transfection was used to up-regulate and down-regulate HES1 expression. Cell proliferation and apoptosis were measured with MTT assay and flow cytometry. Finally, immunofluorescence was used to detect protein subcellular location.
Doxorubicin treatment strongly increases the expression of multiple Notch pathway components in cancer cells. The Notch target HES1 is activated by Doxorubicin and is required for the Doxorubicin driven apoptosis. In addition, over-expression of HES1 can further enhances Doxorubicin's role in promoting apoptosis. Mechanistically, HES1 activates PARP1 and regulates the subcellular location of AIF to mediate the apoptosis response under Doxorubicin treatment.
Our results provided novel insights into the downstream molecular pathways underlying Doxorubicin treatment and suggested that manipulation of Notch signaling pathway could have synergistic effect with Doxorubicin for cancer treatment.
Internal disk disruption (IDD), an early event of lumbar disk degeneration, is the most common cause of low back pain. Since increased intradiskal pressure (IDP) is associated with symptoms and ...progression of disk degeneration, unloading a painful disk with an interspinous process device (IPD) is a rational treatment option. The goal of this study was to evaluate the effectiveness of dynamic stabilization with an IPD in the treatment of symptomatic IDD of the lumbar spine.
Patients with symptomatic IDD were treated with implantation of an IPD, the device for intervertebral assisted motion (DIAM). Diagnosis of IDD was based on typical MRI finding of posterior annular high-intensity zone and positive provocative test on discography. IDP was analyzed intraoperatively. Axial back and leg pain was evaluated with visual analog scale, functional status with Oswestry Disability Index, and final clinical outcomes with Odom criteria. Data from 34 patients followed up for at least 3 years were collected.
DIAM implantation significantly reduced IDP (n=11,
<0.0001). All 34 patients reported symptom relief. Thirty-one patients (91%) remained symptom free until the last followups. Three patients (9%) experienced recurrence of pain, of which the causes were unrelated to the IDD or surgery. Disk status at the DIAM-implanted segments remained stable. Segmental flexion/extension mobility was preserved in 27 of 30 patients with preoperative mobility. No proximal or distal adjacent segment degeneration was observed. The final clinical outcomes were excellent/good in 31 and fair/poor in three patients.
For patients with symptomatic IDD, dynamic stabilization with DIAM provides pain relief and functional improvement. The implantation maintains disk status and prevents progression of disk degeneration, without compromising segmental flexion/extension mobility or causing adjacent segment degeneration.
Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism ...could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0.001), had poor progression-free survival rates (p = 0.01) as compared with patients exhibiting lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence interval: 0.70-5.85). In cell lines, PKM2 inhibitor significantly inhibited the glycolytic rate according to cellular glucose consumption (p < 0.001). We also utilized Seahorse assays to assess metabolism-related cell-specific factors and the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed attenuation of the extracellular acidification rate (p < 0.05) and no significant difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2 inhibitor suppressed ovarian cancer growth and cell migration in vitro and inhibited tumor growth without significant toxicity in a xenograft study. PKM2 inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth. Targeting PKM2 may constitute a promising therapy for patients with ovarian cancer, and clinical trials involving shikonin are warranted.
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