To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects ...of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment. We reviewed the pharmacological agents which reduced the risk of HT associated with delayed (beyond 4.5 hours post-stroke) tPA treatment in preclinical studies, which we classified into those that putatively preserve the blood-brain barrier (e.g., minocycline, cilostazol, fasudil, candesartan, and bryostatin) and/or enhance vascularization and protect the cerebrovasculature (e.g., coumarin derivate IMM-H004 and granulocyte colony-stimulating factor). Recently, other new therapeutic modalities (e.g., oxygen transporters) have been reported which improved delayed tPA-associated outcomes by acting through other mechanisms. While the above-mentioned interventions unequivocally reduced delayed tPA-induced HT in stroke models, the long-term efficacy of these drugs are not yet established. Further optimization is required to expedite their future clinical application. The findings from this review indicate the need to explore the most ideal adjunctive interventions that will not only reduce delayed tPA-induced HT, but also preserve neurovascular functions. While waiting for the next breakthrough drug in acute stroke treatment, it is equally important to allocate considerable effort to find approaches to address the limitations of the only FDA-approved stroke therapy.
This paper explains and discusses the concepts of ecological conservation and construction in China in three parts. The first part provides a brief description of the historical background of ...ecological activities in China and their major achievements in the past. The second part is a comprehensive review of various types of ecological control activity aimed at the improvement of natural and artificially established ecosystems at the landscape, regional (watershed) and higher levels. The scope of and differences between some ecological terms used in China such as ecological protection, conservation, remediation (rehabilitation), restoration as well as the reestablishment of new ecosystems are elaborated. The review suggests that the term "ecological conservation and construction" should be used to embrace all types of ecological control activity in China. Finally, five guidelines are proposed for promoting the implementation of ecological conservation and construction in China based on the two important governmental documents related to the development of ecological civilization in China.
This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared ...to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.
C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after ...hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.
Ischemic wounds are chronic wounds with poor blood supply that delays wound reconstruction. To accelerate wound healing and promote angiogenesis, adipose-derived stem cells (ADSCs) are ideal seed ...cells for stem cell-based therapies. Nevertheless, providing a favorable environment for cell proliferation and metabolism poses a substantial challenge. A highly sulfated heparin-like polysaccharide 2-N, 6-O-sulfated chitosan (26SCS)-doped poly(lactic-co-glycolic acid) scaffold (S-PLGA) can be used due to their biocompatibility, mechanical properties, and coagent 26SCS high affinity for growth factors. In this study, a nano-scaffold system, constructed from ADSCs seeded on electrospun fibers of modified PLGA, was designed to promote ischemic wound healing. The S-PLGA nanofiber membrane loaded with adipose stem cells ADSCs@S-PLGA was prepared by a co-culture
, and the adhesion and compatibility of cells on the nano-scaffolds were explored. Scanning electron microscopy was used to observe the growth state and morphological changes of ADSCs after co-culture with PLGA electrospun fibers. The proliferation and apoptosis after co-culture were detected using a Cell Counting Kit-8 kit and flow cytometry, respectively. An ischemic wound model was then established, and we further studied the ability of ADSCs@S-PLGA to promote wound healing and angiogenesis. We successfully established ischemic wounds on the backs of rats and demonstrated that electrospun fibers combined with the biological effects of adipose stem cells effectively promoted wound healing and the growth of microvessels around the ischemic wounds. Phased research results can provide a theoretical and experimental basis for a new method for promoting clinical ischemic wound healing.
Display omitted
•We developed a visuo-haptic surgical training simulator for bone-sawing procedure.•We validated the simulator’s face validity and construct validity.•This simulator was able to ...produce the effect of learning bone-sawing skill.•This simulator could provide a training alternative for novices.
Bone sawing or cutting is widely used for bone removal processes in bone surgery. It is an essential skill that surgeons should execute with a high level of experience and sensitive force perception. Surgical training simulators, with virtual and haptic feedback functions, can offer a safe, repeatable and cost-effective alternative to traditional surgeries. In this research, we developed a surgical training simulator with virtual and haptic force feedback for maxillofacial surgery, and we validated the effects on the learning of bone-sawing skills through empirical evaluation.
Omega.6 from Force Dimension was employed as the haptic device, and Display300 from SenseGraphices was used as the 3D stereo display. The voxel-based model was constructed using computed tomography (CT) images, and the virtual tools were built through reverse engineering. The multi-point collision detection method was applied for haptic rendering to test the 3D relationship between the virtual tool and the bone voxels. Bone-sawing procedures in maxillofacial surgery were simulated with a virtual environment and real-time haptic feedback. A total of 25 participants (16 novices and 9 experienced surgeons) were included in 2 groups to perform the bone-sawing simulation for assessing the construct validity. Each of the participants completed the same bone-sawing procedure at the predefined maxillary region six times. For each trial, the sawing operative time, the maximal acceleration, and the percentage of the haptic force exceeding the threshold were recorded and analysed to evaluate the validity. After six trials, all of the participants scored the simulator in terms of safe force learning, stable hand control and overall performance to confirm the face validity. Moreover, 10 novices in 2 groups indentified the transfer validity on rapid prototype skull models by comparing the operative time and the maximal acceleration.
The analysed results of construct validity showed that the two groups significantly reduced their sawing operative times after six trials. Regarding maximal acceleration, the curve significantly descended and reached a plateau after the fifth repetition (novices) or third repetition (surgeons). Regarding safe haptic force, the novices obviously reduced the percentage of the haptic force exceeding the threshold, with statistical significance after four trials, but the surgeons did not show a significant difference. Moreover, the subjectively scored results demonstrated that the proposed simulator was more helpful for the novices than for the experienced surgeons, with scores of 8.31 and 7.22, respectively, for their overall performance. The experimental results on skill transference showed that the experimental group performed bone-sawing operation in lower maximal acceleration than control group with a significant difference (p<0.05). These findings suggested that the simulator training had positive effects on real sawing.
The evaluation results proved the construct validity, face validity and the transfer validity of the simulator. These results indicated that this simulator was able to produce the effect of learning bone-sawing skill, and it could provide a training alternative for novices.
Introduction
Corticotomy is widely used in clinical practice to accelerate tooth movement and shorten the duration of orthodontic treatment. It is effective, but an invasive surgery is needed to ...induce alveolar bone osteopenia that enable rapid tooth movement. In this study, we discovered the potential of 6-shogaol as a more patient-friendly non-invasive alternative to induce transient osteopenia and accelerate tooth movement.
Materials and methods
The effects of 6-shogaol on the bone marrow macrophages (BMM) proliferation and osteoclast differentiation, and bone resorption were determined in vitro. Sprague–Dawley rats were distributed into three groups: CON, IPinj or Localinj and euthanized at day 28. Micro-CT, histology, immunohistological, and TUNEL analysis were performed to evaluate the tooth movement acceleration effect of 6-shogaol.
Results
In vitro, 6-shogaol promotes osteoclast differentiation and functional demineralization of alveolar bone. RANKL-induced mRNA expression of osteoclastic-specific genes was significantly higher in the presence of 6-shogaol. A dose-dependent increase in the area of TRAP-positive cells was observed with 6-shogaol treatment. F-actin ring formation and increased bone resorption confirmed that osteoclasts treated with 6-shogaol were mature and functional. 6-shogaol stimulated JNK activation and NFATc1 expression during osteoclast differentiation. In vivo, 6-shogaol promotes alveolar bone transient osteopenia and accelerates orthodontic tooth movement. Alveolar bone mass was reduced, more osteoclasts were observed in bone resorption lacunae on the compression side, and the expression of RANKL and sclerostin were higher than the control group. In conclusion, our results suggest that 6-shogoal accelerates tooth movement by inducing osteopenia by a mechanism similar to surgically induced bone injury.
Cortical neurons oscillate between Up and Down states during slow wave sleep and general anesthesia. Recent studies show that Up/Down oscillations also occur during quiet wakefulness. Arousal ...eliminates Down states and transforms Up/Down oscillations to a persistent Up state. Further evidence suggests that Up/Down oscillations are crucial to memory consolidation, whereas their transition to a persistent Up state is essential for arousal and attention. We have shown that
D
-amphetamine promotes cortical Up state, and the effect depends on activation of central α
1A
adrenergic receptors. Here, we report that dopamine also plays a role in
D
-amphetamine’s effect. Thus, using local-field-potential recording in the prefrontal cortex in chloral hydrate-anesthetized rats, we showed that the Up-state promoting effect of
D
-amphetamine was attenuated by antagonists at either D1 or D2-like dopamine receptors. The effect was also partially mimicked by co-activation of D1 and D2-like receptors. These results are consistent with the fact that
D
-amphetamine increases the release of both norepinephrine and dopamine. They are also in agreement with studies showing that dopamine promotes wakefulness and mediates
D
-amphetamine-induced emergence from general anesthesia. The effect of
D
-amphetamine was not mimicked, however, by activation of either D1 or D2-like receptors alone, indicating an interdependence between D1 and D2-like receptors. The dopamine/norepinephrine precursor L-DOPA also failed to promote the Up state. While more studies are needed to understand the difference between L-DOPA and
D
-amphetamine, our finding may provide an explanation for why L-DOPA lacks significant psychostimulant properties and is ineffective in treating attention-deficit/hyperactivity disorder.
PDF
