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The aim of this study is to develop a hybrid 3D printing platform integrating thermal-extrusion and electrospinning methods to fabricate bone scaffolds. The scaffolds made by mPEG–PCL–mPEG/HA biocomposite and their surface were enhanced by adding an electrospun fibre layer which improved adhesion and viability of osteoblastic cells. The scaffolds were evaluated by mechanical testing; biochemical analyses, SEM observation and their capabilities for supporting growth and adhesion of osteoblastic cells were also assessed in vitro. The 3D printing platform can manufacture the controllable and complicated shapes of bone scaffolds by controlling the thermal-extrusion and electrospinning equipment. It also can control the pore size, porosity and pore interconnectivity, and stack the scaffold structure by using different materials and different ways. Analyses showed that the bone scaffolds have a good mechanical strength and the scaffolds are suitable to support growth of MC3T3-E1 osteoblastic cells; and the electrospun fibres may increase the surface area of the fabricated scaffolds for the future application in modulating osteoblast response. Thus, it is feasible to produce bone tissue engineering scaffolds integrating thermal-extrusion and electrospinning techniques using our 3D printing platform. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between the fracture line distribution and the location of comminution in intra-articular distal radius fractures by building fracture mapping. Patients/methods: Forty cases with intra-articular fractures of distal radius were enrolled in the current prospective clinical study. Fracture lines and comminution zones were identified by reduced three-dimensional computed tomography reconstructions and then graphically superimposed onto a standard template to create two-dimensional fracture maps, followed by the conversion into heating maps. Based on qualitative descriptive fracture mapping analyses, the patterns of intra-articular distal radius fractures were determined. Results: It was observed that the highest fracture line intensity was located as an inverted "T" shape zone in the dorsal aspect of the joint with high incidence of fractures and the prominently intense color in heat mapping. The keystone projected area, the radial styloid process and the metacarpal radial side articular surface were found to be the least involved parts of the fracture. According to the mapping of the number and distribution of fracture lines, a new classification method for intra-articular fractures of the distal radius was redefined. Different surgical approaches and internal fixation techniques were proposed for different types. In this paper, we retrospectively compared the preoperative X-ray findings between different types. Based on the preoperative X-ray prediction, the distal intra-articular radius fractures were classified, so as to develop effective surgical strategies. In this study, a new surgical approach was attempted, but due to the lack of evidence-based evidence, long-term postoperative complications and hand function should be further evaluated. Conclusion: This study redefines a new method for the classification of intra-articular fractures of the distal radius, which allows doctors to have a clearer understanding of the characteristics of distal radius fractures. Moreover, the application value in fracture diagnosis is more significant, and the best surgical approach is selected for different types. [ABSTRACT FROM AUTHOR]

Opioids are widely administered to alleviate pain, including chronic pain in advanced cancer patients. Among opioids, morphine is one of the most clinically effective drugs for the palliative management of severe pain. In the last few decades, there has been a debate around the possible influence of opioids such as morphine on tumour growth and metastasis. Whilst several in vitro and in vivo studies suggest the possible modulatory effects of morphine on tumour cells, little is known about the impact of this analgesic drug on other mediators such as matrix metalloproteinases (MMPs) that play a key role in the control of cancer cell invasion and metastasis. MMP-9 has been considered as one of the principal mediators in regulation of not only the initial steps of cancer but during the invasion and spreading of cancer cells to distant organs. Herein, current studies regarding the direct and indirect effects of morphine on regulation of MMP-9 production are discussed. In addition, drawing from previous in vivo and in vitro studies on morphine action in regulating MMP-9 production, the potential roles of several underlying factors are summarised, including nuclear factor kappa-B and intracellular molecules such as nitric oxide. [ABSTRACT FROM AUTHOR]

Artificial abnormal microenvironment caused by microperfusion of L-glutamate (Glu) and Ca2+ in the hippocampus results in neuron damage, which is closely related to cerebral ischemia. Ginsenoside Rb1, a compound from Panax notoginseng, was previously used to counter the artificial abnormal hippocampal environment in a microperfusion model. In addition, while the Akt/mTOR/PTEN signaling pathway has been shown to mediate neuronprotection in cerebral ischemia, whether this pathway is involved in the neuroprotection of ginsenoside Rb1 is unknown. Here SH-SY5Y cells exposed to OGD/R injury in treated with LY294002, ginsenoside Rb1, ginsenoside Rb1+ LY294002. Expressions of phosphorylation (P-)Akt/P-mTOR/P-PTEN (24 h after OGD/R) were detected by Western blotting. Effects were examined via the memory function of rats (by Morris water maze test), morphological changes in pyramidal cell (by histology), and mRNA expression (by qRT-PCR) and phosphorylation (P-) (by Western blotting and immunohistochemical staining) of Akt, P-mTOR, and P-PTEN in the hippocampus. The memory deficit of rats and pyramidal cellular necrosis and apoptosis in the CA1 region of hippocampus after microperfusion of Glu and Ca2+ were dose dependently alleviated by ginsenoside Rb1.Moreover,Western blot showed that ginsenoside Rb1 increased the expressions of P-Akt, P-mTOR and reduced P-PTEN in vivo and vitro. Thus, the potent neuroprotection of ginsenoside Rb1 in artificial abnormal microenvironment is, at least partially, related to the activation of P-AKT/P-mTOR signaling pathway and inhibition of P-PTEN protein. [ABSTRACT FROM AUTHOR]

The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation. [ABSTRACT FROM AUTHOR]

Inflammatory and injury-induced skeletal pain are common conditions, and both conventional nonselective NSAIDs and the newer cyclo-oxygenase-2- specific inhibitors are widely used as post-traumatic and post-surgical analgesics. However, new research suggests that these drugs, particularly the cyclo-oxygenase-2 inhibitors, have a negative effect on the healing process in fractured bone and within orthopedic surgical sites, thus highlighting a need to develop new approaches for managing skeletal pain. Various experimental studies have revealed that locally upregulated neurotrophic factors, especially nerve growth factor, have a major role in mediating injury-induced or inflammatory pain. Nerve growth factor inhibitors, therefore, might be an effective alternative modality for post-traumatic and post-surgical analgesia, without impairing bone healing. [ABSTRACT FROM AUTHOR]

The expression and function of transforming growth factor alpha (TGF-α) in the kidney are not fully characterised. There exists controversy concerning the detection of renal TGF-α mRNA and the localisation of its immunoreactivity. In attempts to clarify the detection and localisation issue, the present study aimed to detect TGF-α mRNA in neonate and adult rat kidneys, to examine the specificity of two commonly used anti-TGF-α antibodies and finally to localise renal TGF-α immunoreactivity using a specific antibody. TGF-α mRNA of around 4.8 kb was readily detected with a sensitive non-radioactive northern analysis, with a similar abundance in neonatal and adult rat kidneys. Renal TGF-α peptide of the 6-kDa mature form was identified by western blotting. By using various controls, including specimens from TGF-α knock out mice in comparison with wild-type mice, the present study has confirmed the specificity of a polyclonal anti-human recombinant TGF-α antibody. With this antibody, TGF-α immunoreactivity was localised to the proximal tubules in renal cortex. In addition, the present study has also demonstrated a non-specificity in localising TGF-α in rodent kidneys by the most commonly used monoclonal anti-human TGF-α C-terminal peptide antibody, which stained collecting ducts in renal cortex and medulla. [ABSTRACT FROM AUTHOR]

Peripheral nerves are important pathways for receiving afferent sensory impulses and sending out efferent motor instructions, as carried out by sensory nerve fibers and motor nerve fibers. It has remained a great challenge to functionally reconnect nerve internal fiber bundles (or fascicles) in nerve repair. One possible solution may be to establish a 3D nerve fascicle visualization system. This study described the key technology of 3D peripheral nerve fascicle reconstruction. Firstly, fixed nerve segments were embedded with position lines, cryostat-sectioned continuously, stained and imaged histologically. Position line cross-sections were identified using a trained support vector machine method, and the coordinates of their central pixels were obtained. Then, nerve section images were registered using the bilinear method, and edges of fascicles were extracted using an improved gradient vector flow snake method. Subsequently, fascicle types were identified automatically using the multi-directional gradient and second-order gradient method. Finally, a 3D virtual model of internal fascicles was obtained after section images were processed. This technique was successfully applied for 3D reconstruction for the median nerve of the hand-wrist and cubital fossa regions and the gastrocnemius nerve. This nerve internal fascicle 3D reconstruction technology would be helpful for aiding peripheral nerve repair and virtual surgery. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop a hybrid 3D printing platform integrating thermal-extrusion and electrospinning methods to fabricate bone scaffolds. The scaffolds made by mPEG–PCL–mPEG/HA biocomposite and their surface were enhanced by adding an electrospun fibre layer which improved adhesion and viability of osteoblastic cells. The scaffolds were evaluated by mechanical testing; biochemical analyses, SEM observation and their capabilities for supporting growth and adhesion of osteoblastic cells were also assessed in vitro. The 3D printing platform can manufacture the controllable and complicated shapes of bone scaffolds by controlling the thermal-extrusion and electrospinning equipment. It also can control the pore size, porosity and pore interconnectivity, and stack the scaffold structure by using different materials and different ways. Analyses showed that the bone scaffolds have a good mechanical strength and the scaffolds are suitable to support growth of MC3T3-E1 osteoblastic cells; and the electrospun fibres may increase the surface area of the fabricated scaffolds for the future application in modulating osteoblast response. Thus, it is feasible to produce bone tissue engineering scaffolds integrating thermal-extrusion and electrospinning techniques using our 3D printing platform. [ABSTRACT FROM AUTHOR]