Mitochondrial protein, TBRG4, modulates KSHV and EBV reactivation from latency.

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr (EBV) are gammaherpesviruses associated with multiple human malignancies. KSHV is the etiological agent of Kaposi's Sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). EBV is associated with Burkitt's lymphoma (BL), Hodgkin's lymphoma (HL), nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). KSHV and EBV establish life-long latency in the human host with intermittent periods of lytic reactivation. Here, we identified a cellular factor named transforming growth factor-beta regulator 4 (TBRG4) that plays a role in the gammaherpesvirus lifecycle. We find that TBRG4, a protein that is localized to the mitochondria, can regulate lytic reactivation from latency of both KSHV and EBV. Knockdown of TBRG4 in cells latently infected with KSHV or EBV induced viral lytic gene transcription and replication. TBRG4 deficiency causes mitochondrial stress and increases reactive oxygen species (ROS) production. Treatment with a ROS scavenger decreased viral reactivation from latency in TBRG4-depleted cells. These data suggest that TBRG4 serves as a cellular repressor of KSHV and EBV reactivation through the regulation of ROS production.

Quantitative and Fiber-Selective Evaluation for Central Poststroke Pain.

The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to explore the relationship between clinical features and lesion location in patients with CPSP using the current perception threshold (CPT) approach. Here, patients underwent the standardized CPT measure at five detection sites on both the contralesional and ipsilesional sides, using a constant alternating-current sinusoid waveform stimulus at three frequencies: 2000 Hz, 250 Hz, and 5 Hz. 57 CPSP patients were recruited in this cross-sectional study, including 13 patients with thalamic lesions and 44 patients with internal capsule lesions. Patients with a thalamic lesion had more frequent abnormal Aδ and C fibers than those with an internal capsule lesion (69.2% versus 36.4%, p value = 0.038; 53.8% versus 63.6%, p value = 0.038). The patients with internal capsule lesions had more frequent abnormal Aß fibers than those with thalamic lesions (53.8% versus 63.6%, p value < 0.001). The sensory dysfunction in the patients with thalamic lesions was more likely to occur in the upper limbs (i.e., the shoulder (p value = 0.027) and the finger (p value = 0.040)). The lower limbs (i.e., the knee (p value = 0.040) and the toe (p value = 0.005)) were more likely to experience sensory dysfunction in the patients with internal capsule lesions. Hyperesthesia was more likely to occur in the thalamic patients, and hypoesthesia was more likely to occur in the patients with internal capsule lesions (p value < 0.001). In patients with thalamic lesions, Visual Analogue Scale (VAS) had a positive correlation with 5 Hz CPT on the shoulder (r = 0.010, p value = 0.005), 250 Hz CPT on the finger (r = 0.690, p value = 0.009) from the contralesional side, and 2000 Hz CPT on the knee (r = 0.690, p value = 0.009). In patients with internal capsule lesions, VAS had a positive correlation with 2000 Hz CPT on the knee (r = 0.312, p value = 0.039) and foot (r = 0.538, p value < 0.001). In conclusion, the abnormal fiber types, sensory dysfunction territory, and clinical signs of CPSP in thalamic stroke differ from those in internal capsule stroke. Implementation of the portable and convenient CPT protocol may help clarify the locations of different stroke lesions in various clinical settings.

Estimation of Heart Rate and Energy Expenditure Using a Smart Bracelet during Different Exercise Intensities: A Reliability and Validity Study.

Background. With wrist-worn wearables becoming increasingly available, it is important to understand their reliability and validity in different conditions. The primary objective of this study was to examine the reliability and validity of the Lexin Mio smart bracelet in measuring heart rate (HR) and energy expenditure (EE) in people with different physical activity levels exercising at different intensities. Methods. A total of 65 participants completed one maximal oxygen uptake test and two running exercise tests wearing the Mio smart bracelet, the Polar H10 HR band, and a gas-analysis system. Results. In terms of HR measurement reliability, the Mio smart bracelet showed good reliability in a left versus right test and good test−retest reliability (p > 0.05; mean absolute percentage error (MAPE) < 10%; intraclass correlation coefficient (ICC) > 0.4). For EE measurement, the Mio smart bracelet showed good reliability in a left versus right test, good test−retest reliability on the right (p > 0.05; MAPE > 10%; ICC > 0.4), and low test−retest reliability on the left (p > 0.05; MAPE > 10%; ICC < 0.4). Regarding validity, the Mio smart bracelet showed good validity for HR measurement (p > 0.05; MAPE < 10%; ICC > 0.4) and low validity for EE measurement (p < 0.05; MAPE > 10%; ICC < 0.4). Conclusion. The Lexin Mio smart bracelet showed good reliability and validity for HR measurement among people with different physical activity levels exercising at various exercise intensities in a laboratory setting. However, the smart bracelet showed good reliability and low validity for the estimation of EE.

Factors associated with public attitudes towards persons with disabilities: a systematic review.

OBJECTIVE: The aim of this review is to identify and summarize factors that are associated with public attitudes towards people with various disabilities systematically. METHODS: An electronic search of three databases was performed (Medline, EMBASE and Cochrane) covering the period from 1950 to present. A comprehensive search strategy was developed and the lists of citations were screened for potential eligible studies. Only quantitative studies using valid measurements were included, and the methodological quality of included studies was appraised based on three criteria (sample, measurement, analysis) by two independent reviewers. RESULTS: The initial electronic search yielded 995 articles after duplicates removed, and 27 studies met the eligibility criteria were included in the study. Three categories of the factors were found to be associated with the public attitudes, which are related to the attitude provider, disabled people, and society respectively. Specifically, the more people know about disabilities, the more likely they were to have positive attitude; and the frequency and quality of the contact with the disabled are also proved to be influential to the attitudes. Meanwhile, the type of disability is also closely correlated to the public's attitude towards the disabilities. CONCLUSION: People's knowledge of the disability and their contact with individuals with disabilities are the main influential factors in public attitudes towards persons with disabilities.

Penetrating glassy carbon neural electrode arrays for brain-machine interfaces.

This paper presents a fabrication method for glassy carbon neural electrode arrays that combines 3D printing and chemical pyrolysis technology. The carbon electrodes have excellent biological compatibility and can be used in neural signal recording. A pretreated Si wafer is used as the substrate for 3D printing, and then, stereolithography 3D printing technology is employed to print photosensitive resin into a cone shape. Next, chemical pyrolysis is applied to convert the 3D prints into glassy carbon electrodes and modify the electrochemical performance of the carbon electrodes. Finally, the glassy carbon electrodes are packed with conductive wires and PDMS. The proposed fabrication method simplifies the manufacturing process of carbon materials, and electrodes can be fabricated without the need of deep reactive ion etching (DRIE). The height of the carbon electrodes is 1.5 mm, and the exposure area of the tips is 0.78 mm2, which is convenient for the implantation procedure. The specific capacitance of the glassy carbon arrays is higher than that of a platinum electrode (9.18 mF/cm2 vs 3.32 mF/cm2, respectively), and the impedance at 1 kHz is lower (7.1 kΩ vs 8.8 kΩ). The carbon electrodes were tested in vivo, and they showed excellent performance in neural signal recording. The signal-to-noise ratio of the carbon electrodes is 50.73 ± 6.11, which is higher than that of the Pt electrode (20.15 ± 5.32) under the same testing conditions. The proposed fabrication method of glassy carbon electrodes provides a novel approach to manufacture penetrating electrodes for nerve interfaces in biomedical engineering and microelectromechanical systems.

Transcranial direct current stimulation improves the swallowing function in patients with cricopharyngeal muscle dysfunction following a brainstem stroke.

OBJECTIVE: This study investigated the effects of transcranial direct current stimulation (tDCS) combined with conventional swallowing training on the swallowing function in brainstem stroke patients with cricopharyngeal muscle dysfunction (CPD). METHODS: Twenty-eight brainstem stroke patients with CPD were assigned randomly to an anodal tDCS group or a sham tDCS group. The patients received anodal tDCS or sham tDCS over the bilateral oesophageal cortical area combined with simultaneous catheter balloon dilatation and conventional swallowing therapy for 20 days. Swallowing function was assessed using the functional oral intake scale (FOIS) and the functional dysphagia scale (FDS) and by measuring the pharyngoesophageal Segment Opening (PESO) before and immediately after the intervention. RESULTS: Both groups showed a significant improvement in the FDS, FOIS and PESO scores immediately after the intervention (all p < .005). However, compared with the sham stimulation group, the anodal tDCS group showed greater improvements in the FDS, FOIS and PESO scores immediately after the intervention (all p < .005). CONCLUSION: The bihemispheric anodal tDCS combined with simultaneous catheter balloon dilatation and conventional swallowing therapy effectively improves the swallowing function in patients with CPD caused by a brainstem stroke. tDCS may be an effective adjuvant therapy in CPD rehabilitation.

Effect of an indwelling nasogastric tube on swallowing function in elderly post-stroke dysphagia patients with long-term nasal feeding.

BACKGROUND: In clinical practice, a large number of post-stroke survivors require nasogastric tube (NGT) placement and nasal feeding for a relatively long period. However, its impact on the swallowing function remains largely unknown. This study examines the impact of prolonged placement of an NGT on the swallowing function of elderly post-stroke patients. METHODS: The participants of this study were 30 elderly post-stroke patients who had been using an NGT for more than 2 months. A videofluoroscopic swallowing study (VFSS) was performed before and 5 h after removal of the NGT. The following parameters were analyzed and compared, the functional dysphagia scale (FDS), residue in the valleculae, residue in the pyriform sinuses, and the penetration-aspiration scale (PAS). In addition, prior to the VFSS, the pharynx and larynx were examined using a fiberoptic laryngoscope. RESULTS: Significant differences were observed between the total scores of the FDS, pharyngeal transit times (PTTs), the residue in the valleculae, and the residue in the pyriform sinuses before and after the NGT removal, suggesting an improved swallowing function following the removal of the NGT. A significantly lower penetration-aspiration degree was found after removing the NGT compared with that before its removal. In addition, examinations using the fiberoptic laryngoscope showed that laryngopharyngeal edema was present in three quarters of the patients. CONCLUSIONS: Our results demonstrate that prolonged placement of the NGT had a negative impact on the swallowing function of elderly post-stroke dysphagia patients, mainly on the pharyngeal phase.

miR-451 inhibits cell growth, migration and angiogenesis in human osteosarcoma via down-regulating IL 6R.

Osteosarcoma (OS) has become one of the most common primary malignant tumors in the children and adolescents with a poor prognosis owing to its high malignant and metastatic potential. Although increasing evidence indicates that miR-451 could inhibit the growth and metastasis of OS, its effect on angiogenesis in OS is still very poor. What is more, the mechanism by which miR-451 affects the OS has not been fully elucidated. In the present study, miR-451 was reduced in human osteosarcoma tissues compared with the adjacent bone tissues, and the introduction of miR-451 dramatically inhibited the growth, migration and angiogenesis in OS. Additionally, it was suggested that IL 6R is a direct target gene of miR-451. Silencing of IL 6R suppressed the growth, migration and angiogenesis of OS, which was consistent with the effect of overexpression of miR-451. In conclusion, our data demonstrate that miR-451 may function as a potential suppressor of tumor growth, migration and angiogenesis in OS via down-regulating IL 6R, suggesting a promising therapeutic avenue for managing OS.

Exercise affects biological characteristics of mesenchymal stromal cells derived from bone marrow and adipose tissue.

Both bone marrow mesenchymal stromal cells (BMSCs) and adipose-derived mesenchymal stromal cells (ADSCs) are good sources for tissue engineering. To maximize therapeutic efficacy of MSCs, an appropriate source of MSCs should be selected according to their own inherent characteristics for future clinical application. Hence, this study was conducted to compare proliferative, differential and antiapoptosis abilities of both MSCs derived from exercised and sedentary rats under normal and hypoxia/serum deprivation conditions (H/SD). Our results showed that exercise may enhance proliferative ability and decrease adipogenic ability of BMSCs and ADSCs. However, positive effect of exercise on osteogenesis was only observed for BMSCs in either environment. Little effect was observed on the antiapoptotic ability of both MSC types. It was also suggested that biological characteristics of both types were partly changed. It is therefore believed that BMSCs derived from exercised rat on early passage may be a good cell source for bone tissue engineering.

Different responses of articular cartilage to strenuous running and joint immobilization.

OBJECTIVE: To compare the pathological changes in cartilage derived from rats that developed osteoarthritis either by joint immobilization or by strenuous treadmill running in order to better understand their respective pathomechanism. METHOD: A total of 24 male Wistar rats were randomly assigned to three groups: sedentary control (CON), immobilization (IM), and strenuous running (SR). For rats in the IM group, unilateral knee joint was immobilized in flexion. Rats in the SR group underwent treadmill running with high intensity. Eight weeks later, all animals were sacrificed. Femoral condyles were collected to take histological observation for cartilage characteristic and immunohistochemistry for collagen type II. In addition, cartilage samples were obtained to assess gene expression of aggrecan, collagen type II, biglycan, and fibromodulin by quantitative RT-PCR. RESULTS: Gross and histological observation showed osteoarthritic changes in groups SR and IM; however, more severe cartilage degradation was revealed in the latter. Proteoglycan and collagen II content decreased in groups SR and IM in comparison to group CON, with more loss in group IM. In group SR, mRNA levels in femoral cartilage were found to be unaltered for all the molecules measured. On the contrary, these molecules were significantly downregulated in group IM. CONCLUSION: Differences in gross observation, histological characteristics, and gene expression of proteoglycans and collagen II suggest that both knee immobilization and strenuous running would lead to degenerative change of cartilage, but at different stages of the degenerative process.

Strenuous Treadmill Running Induces a Chondrocyte Phenotype in Rat Achilles Tendons.

BACKGROUND Although tendinopathy is common, its underlying pathogenesis is poorly understood. This study aimed to investigate the possible pathogenesis of tendinopathy. MATERIAL AND METHODS In this study, a total of 24 rats were randomly and evenly divided into a control (CON) group and a strenuous treadmill running (STR) group. Animals in the STR group were subjected to a 12-week treadmill running protocol. Subsequently, all Achilles tendons were harvested to perform histological observation or biochemical analyses. RESULTS Histologically, hypercellularity and round cells, as well as disorganized collagen fibrils, were presented in rat Achilles tendon sections from the STR group. Furthermore, our results showed that the expression of aggrecan, collagen type II (Col II), and Sex-Determining Region Y Box 9 (Sox 9) were markedly increased in the STR group compared with that in the CON group. Additionally, the mRNA expression of bone morphogenetic protein-2 (BMP-2) and biglycan was significantly up-regulated in the STR group in contrast to that in CON group. CONCLUSIONS These results suggest that a 12-week strenuous treadmill running regimen can induce chondrocyte phenotype in rat Achilles tendons through chondrogenic differentiation of tendon stem cells (TSCs) by BMP-2 signaling.

Development and Prevention of Running-Related Osteoarthritis.

Studies investigating the effect of running on risk for developing osteoarthritis at weight-bearing joints have reported with conflicting results. Generally, moderate-level running is not likely detrimental to joint health. However, many factors may be associated with the increased risk of developing osteoarthritis in runners. Factors often implicated in the development of osteoarthritis comprise those that increase joint vulnerability and those which increase joint loading. It is therefore suggested that running has different effects on different people. Efforts should be made to identify those with joint vulnerability and joint loading, and measures should be taken to have those factors and/or their running programs modified to run safely. Further investigations are needed to examine the effect of running on joint health under different conditions to confirm the association between exposure to risk factors and development of osteoarthritis, as well as to validate the effectiveness of measures for preventing running-related osteoarthritis.

Magnesium with micro-arc oxidation coating and polymeric membrane: an in vitro study on microenvironment.

Numerous modification methods have been reported to enhance the corrosion resistance of magnesium with positive results. However, little attention has been paid on their impact on micro-environment, particularly the ion concentration and local pH value. In this study, two different coatings were prepared on magnesium, one with porous micro-arc oxidation (MAO) coating alone, and the other with additional polymer polyhydroxybutyrate (PHB) membrane using spinning technique. Their in vitro corrosional and biological behaviors were investigated and compared. Both coatings were found to reduce the degradation rate of magnesium, but an additionally deposited PHB membrane was superior to MAO-coated magnesium since it could produce a micro-environment with preferable local pH value and ion concentration for osteoblast proliferation. Our study suggests that micro-environment should be another critical issue in evaluation of a modification method for orthopaedic implants.

Cell-laden photocrosslinked GelMA-DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering.

To effectively repair or replace damaged tissues, it is necessary to design three dimensional (3D) extracellular matrix (ECM) mimicking scaffolds with tunable biomechanical properties close to the desired tissue application. In the present work, gelatin methacrylate (GelMA) and dextran glycidyl methacrylate (DexMA) with tunable mechanical and biological properties were utilized to prepared novel bicomponent polymeric hydrogels by cross-linking polymerization using photoinitiation. We controlled the degree of substitution (DS) of glycidyl methacrylate in DexMA so that they could obtain relevant mechanical properties. The results indicated that copolymer hydrogels demonstrated a lower swelling ratio and higher compressive modulus as compared to the GelMA. Moreover, all of the hydrogels exhibited a honeycomb-like architecture, the pore sizes decreased as DS increased, and NIH-3T3 fibroblasts encapsulated in these hydrogels all exhibited excellent viability. These characteristics suggest a class of photocrosslinkable, tunable mechanically copolymer hydrogels that may find potential application in tissue engineering and regenerative medicine applications.

Controlled oxidative nanopatterning of microrough titanium surfaces for improving osteogenic activity.

To further enhance the biological properties of acid-etched microrough titanium surfaces, titania nanotextured thin films were produced by simple chemical oxidation, without significantly altering the existing topographical and roughness features. The nanotextured layers on titanium surfaces can be controllably varied by tuning the oxidation duration time. The oxidation treatment significantly reduced water contact angles and increased the surface energy compared to the surfaces prior to oxidation. The murine bone marrow stromal cells (BMSCs) were used to evaluate the bioactivity. In comparison, oxidative nanopatterning of microrough titanium surfaces led to improved attachment and proliferation of BMSCs. The rate of osteoblastic differentiation was also represented by the increased levels of alkaline phosphatase activity and mineral deposition. These data indicated that oxidative nanopatterning enhanced the biological properties of the microrough titanium surfaces by modulating their surface chemistry and nanotopography. Based on the proven mechanical interlocking ability of microtopographies, enhancement of multiple osteoblast functions attained by this oxidative nanopatterning is expected to lead to better implant osseointegration in vivo.

O-linked ß-N-acetylglucosaminylation may be a key regulatory factor in promoting osteogenic differentiation of bone marrow mesenchymal stromal cells.

Cumulative evidence suggests that O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) plays an important regulatory role in pathophysiological processes. Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated, the potential mechanisms of O-GlcNAcylation in bone metabolism, particularly, in the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) remains unexplored. In this study, the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed, assuming that it could trigger more scholars to focus on research related to O-GlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.

Evaluation of Quantitative and Selective Sensory Fiber Dysfunction in Patients with Cirrhosis.

BACKGROUND: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values. METHODS: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed. RESULTS: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators. CONCLUSION: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aß fiber neuropathy.

Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis.

BACKGROUND: Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM: To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS: 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS: Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION: Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.