Melatonin mediates protective effects on inflammatory response induced by interleukin‐1 beta in human mesenchymal stem cells

Joint diseases like osteoarthritis usually are accompanied with inflammatory processes, in which pro‐inflammatory cytokines mediate the generation of intracellular reactive oxygen species (ROS) and compromise survival of subchondral osteoblasts. Melatonin is capable of manipulating bone formation and osteogenic differentiation of mesenchymal stem cells (MSCs). The aim of this work was to investigate the anti‐inflammatory effect of melatonin on MSC proliferation and osteogenic differentiation in the absence or presence of interleukin‐1 beta (IL‐1β), which was used to induce inflammation. Our data showed that melatonin improved cell viability and reduced ROS generation in MSCs in a dose‐dependent manner. When exposed to 10 ng/mL IL‐1β, various concentrations of melatonin resulted in significant reduction of ROS by 34.9% averagely. Luzindole as a melatonin receptor antagonist reversed the anti‐oxidant effect of melatonin in MSCs with co‐exposure to IL‐1β. Real‐time RT‐PCR data suggested that melatonin treatment up‐regulated the expression of CuZnSOD and MnSOD, while down‐regulated the expression of Bax. To investigate the effect of melatonin on osteogenesis, MSCs were cultured in osteogenic differentiation medium supplemented with IL‐1β, melatonin, or luzindole. After exposed to IL‐1β for 21 days, 1 μm melatonin treatment significantly increased the levels of type I collagen, ALP, and osteocalcin, and 100 μm melatonin treatment yielded the highest level of osteopontin. Our study demonstrated that melatonin maintained MSC survival and promoted osteogenic differentiation in inflammatory environment induced by IL‐1β, suggesting melatonin treatment could be a promising method for bone regenerative engineering in future studies.     

Endocrine Dysfunction Following Stroke

Endocrine dysfunction is known to occur after traumatic brain injury. The purpose of this study was to examine the incidence of various endocrine dysfunctions after a stroke. The Taiwan National Health Insurance Research Database (NHIRD) was searched from 2001 to 2011 for patients with a diagnosis of stroke. Stroke patients were matched by diagnosis date, age, and sex to patients without a stroke. Cox proportional hazards regression analyses were performed to compare the incidence of goiter, acquired hypothyroidism, thyroiditis, pituitary dysfunction, and disorders of the adrenal glands between stroke and non-stroke patients. There were 131,951 patients in the stroke group, and 131,951 in the matched non- stroke group (mean age 66.1 ± 14.9 years). Stroke patients had significantly higher risk of acquired hypothyroidism (crude hazard ratio [cHR] = 1.65, 95% confidence interval [CI]: 1.44, 1.90; adjusted hazard ratio [aHR] = 1.65, 95% CI: 1.42, 1.91), pituitary dysfunction (cHR = 2.32, 95% CI: 1.79, 2.99; aHR = 1.92, 95% CI: 1.46, 2.52), and disorders of the adrenal glands (cHR = 1.79, 95% CI: 1.52, 2.12; aHR =1.62, 95% CI: 1.36, 1.92) than non-stroke patients. Pituitary dysfunction and disorders of the adrenal glands were found in both hemorrhagic stroke and ischemic stroke patients, while hypothyroidism was seen in ischemic stroke patients only. No significant association was found for goiter and thyroiditis. In conclusions, stroke survivors have an approximately 2-fold increased risk of developing acquired hypothyroidism, pituitary dysfunction, or disorders of the adrenal glands. These risks should be taken into account in the management of patients who have ischemic or hemorrhagic strokes.

Graphical Abstract

     

KA1表达再分布对神经元兴奋毒性的影响

背景:特异的兴奋性神经递质受体过度活化时便发生细胞的兴奋性中毒,有关NMDA受体和AMPA受体活化致细胞兴奋性中毒死亡通路较为明确,但关于红藻氨酸(Kainate,KA)受体的功能到目前为止仍未明了。目的:探究小鼠海马内注射KA之后KA1受体的再分布状况对中枢神经元兴奋性中毒的影响。方法:成年雄性C57BL6小鼠海马内注射KA或PBS,2h后进行Bederson体征评分、全脑切片免疫组化分析和死亡神经元检测。结果与结论:海马内注射KA2h后,Bederson体征评分表明中枢神经功能出现明显损伤;KA1受体表达的变化主要出现在海马CA1和CA3区,在CA1区的表达上调明显,并开始出现神经元死亡,4~6h后可见大量神经元死亡。结果表明KA促使KA1受体亚单位在海马神经元CA区重新分布,增加神经元对兴奋性氨基酸毒性的敏感性,导致神经细胞死亡,中枢神经功能缺失。     

Nano-engineered microcapsules boost the treatment of persistent pain

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.     

Spatial attention modulates early face processing

It is widely reported that inverting a face dramatically affects its recognition. Previous studies have shown that face inversion increases the amplitude and delays the latency of the face-specific N170 component of the event-related potential (ERP) and also enhances the amplitude of the occipital P1 component (latency 100–132 ms). The present study investigates whether these effects of face inversion can be modulated by visual spatial attention. Participants viewed two streams of visual stimuli, one to the left and one to the right of fixation. One stream consisted of a sequence of alphanumeric characters at 6.67 Hz, and the other stream consisted of a series of upright and inverted images of faces and houses presented in randomized order. The participants’ task was to attend selectively to one or the other of the streams (during different blocks) in order to detect infrequent target stimuli. ERPs elicited by inverted faces showed larger P1 amplitudes compared to upright faces, but only when the faces were attended. In contrast, the N170 amplitude was larger to inverted than to upright faces only when the faces were not attended. The N170 peak latency was delayed to inverted faces regardless of attention condition. These inversion effects were face specific, as similar effects were absent for houses. These results suggest that early stages of face-specific processing can be enhanced by attention, but when faces are not attended the onset of face-specific processing is delayed until the latency range of the N170.     

Clinical outcomes of open treatment of old condylar head fractures in adults

The aim of this study was to classify the clinical feasibility and outcomes of open reduction treatment of old condylar head fractures (CHFs).This was a retrospective case series study of patients with old CHFs that were treated with open reduction and internal fixation, with anatomic reduction and sutured fixation of the articular disc. Preoperative and postoperative examinations were recorded and analyzed, including temporomandibular joint (TMJ) symptoms, occlusion, maximum interincisal opening (MIO), and mandibular deviation. Computed tomography (CT) was used to assess condylar morphology and position.Eleven patients with old CHFs were included (nine unilateral and two bilateral). The mean period from condylar fracture to operation was 8.9 months (ranging from 6 to 14 months). The mean follow-up period after surgery was 16.1 months (ranging from 12 to 22 months). At the end of follow-up period, no malocclusion was found, and the MIO had expanded considerably to 37.4 ± 3.8 mm. Postoperative CT showed that all fragments were properly reduced and the condyles were in the normal position. All patients showed apparently improved TMJ function, occlusion, and facial appearance.Our results showed that open reduction treatment could be an effective method for the treatment of old CHFs.     

A Prenatal Ultrasound Scanning Approach: One-Touch Technique in Second and Third Trimesters

This study was aimed at evaluating the performance of the innovative technique Smart Fetus (SF) developed to recognize the planes and obtain the basic biometric measurements of fetuses automatically. This prospective study included 1005 uncomplicated singleton pregnancies undergoing routine examinations. For every pregnancy, planes, including the transverse section of the thalami, transverse section of the abdomen and longitudinal section of the femur, were acquired, and standard biometric measurements, including biparietal diameter, head circumference, abdominal circumference and femur length, were obtained using SF and traditional ultrasound technique (TUT). The accuracy, reproducibility and time required for the analysis of SF were compared with those of TUT. In 998 of 1005 cases (99.30%), SF successfully acquired the sections and made all measurements. The agreement between the techniques was high for all measurements. The time to obtain sections and measure biometric parameters or solely measure biometric parameters was significantly shorter with SF than with TUT. No significant differences were found in SF repeated measurements obtained by two independent observers. The SF technique helped in the acquisition of reliable standard sections and biometric measurements and saved time. It might serve as a novel ultrasound scanning approach and improve workflow efficiency.