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BACKGROUND: Pushing is a typical workplace activity that may result in musculoskeletal disorders (MSDs). A convenient method of assessing the risk of MSDs is to determine the association between the force applied and the subjective rating of force exertion. OBJECTIVES: This study aimed to determine the relationship between the subjective rating of force exertion and the force applied to both a fixed and a movable handle. It also aimed to confirm that the participants could apply a higher one-handed push force at shoulder height than at elbow height. METHODS: A one-handed pushing experiment was conducted. In the push-to-scale session, the participants pushed a handle fixed on a rig on four levels on the CR-10 scale. The push force was measured. In the force-rating session, the participants rated their force exertions when pushing a movable handle with metal blocks suspended on the two sides. The subjective ratings on the CR-10 were recorded. RESULTS: The one-handed push force at shoulder height was significantly higher than that at elbow height. More effort was needed to push on a movable handle than a fixed one. Two regression models were established to describe the relationship between the push force and the subjective ratings of pushing for each of the fixed and movable handles, respectively. The correlation coefficient results showed that these models are adequate to describe the relationship between the one-handed push force and the ratings of the CR-10 scale. CONCLUSION: Participants applied a higher one-handed push force at shoulder height than at elbow height was confirmed. Participants needed more efforts to push the movable handle under the same CR-10 level than the fixed handle. The predictive models developed in this study may be used to estimate the push force for one-handed pushing tasks when assessing the risk of MSDs. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with cognitive impairment (CI) in community-dwelling Chinese older adults, and to investigate whether this relationship is modified by the Apolipoprotein E (APOE) ε4 allele. Methods: The study is a secondary analysis of 703 participants aged ≥60 years randomly enrolled from the Beijing Longitudinal Study of Aging II prospective cohort. The education-adjusted Mini-Mental State Examination and the Clinical Dementia Rating Scale were used to measure the cognitive performance of the subjects. The main effects and interactions (additive and multiplicative) of the BDNF Met and the APOE ε4 alleles on CI were estimated by logistic regression models. Results: In total, 84 out of 703 older adults aged ≥60 years old had CI. No significant difference was observed in the risk of CI between participants with the BDNF Met allele and that of subjects without the BDNF Met allele (p = 0.213; p = 0.164). Individuals carrying both the BDNF Met and APOE ε4 alleles had an almost 1.5-fold increased odds of CI compared with carriers of the BDNF Met allele but without the APOE ε4 allele. The additive association indicated a positive interaction of both BDNF Met and APOE ε4 alleles with wide CIs (p = 0.021; p = 0.018). Conclusion: The results suggest that the APOE ε4 allele may be a potential modifier for the association of the BDNF Val66Met polymorphism with CI in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Background: Long-term nursing home (NH) care helps NH residents with their daily activities and improves their quality of life, but negatively affects their independent physical activities and increases the risk of dangerous events. Dangerous events in the elderly usually occur in the conversion of walking periods when forward striding has already happened, but the body has not yet entered a completely steady walking. Objectives: Compare the gait characteristics in Chinese long-term NH residents and community-living elderly during the walking Transitional Period (TP) and Stabilization Period (SP). Methods: 32 long-term NH residents and 33 age- and sex-matched community-living elderly were recruited. The 30-Second Chair Stand Test (30-s CST), Timed Up and Go Test (TUGT), and Modified Falls Efficacy Scale (MFES) were used to assess their body function. The Xsens MVN BIOMECH system was used to collect and analyze the gait parameters of participants. Results: Compared to community-living elderly, NH residents had fewer numbers of 30-s CST, took more time to complete TUGT, and lower MEFS scores. NH residents showed slower gait speed (P < 0.001), less peak hip flexion (P = 0.022) and extension (P = 0.003), knee internal rotation (P = 0.023), and ankle plantarflexion (P = 0.001) and internal rotation (P = 0.007) angles during walking. When walking progressed from TP to SP, NH residents showed increased ankle dorsiflexion (P < 0.001), decreased hip internal rotation (P < 0.001), and community-living elderly had increased hip extension (P = 0.005) angles. Conclusions: Chinese long-term NH residents had reduced lower extremities strength and postural balance, and higher fear of falling compared to community-living elderly. Their walking performance also showed high fall risk. Besides, long-term NH residents adopted a distal strategy to propel the body forward, which may be a compensatory measure to compensate for inadequate proximal joint control from forward walking to stable walking, and long-term NH residents have reduced postural stability during this process. [ABSTRACT FROM AUTHOR]

Objectives: At present, there is no effective method of evaluating the electrophysiological changes in cardiac myocytes during off-pump coronary artery bypass grafting (OPCAB). Therefore, we preliminarily explored the relationship between electrophysiological characteristics and the changes in cardiac function of 24 patients undergoing OPCAB. Methods: We used the CARTO3 system for epicardial electrophysiological mapping before surgery, during left anterior descending branch anastomosis, diagonal branch anastomosis and after surgery for 24 patients undergoing OPCAB. Data, including local activation time (LAT), bipolar voltage value (BV) and conduction velocity, were processed and analyzed by the system. Intraoperative invasive blood pressure, heart rate and arterial blood gas analysis data were recorded. Continuous electrocardiography (ECG) monitoring was performed three days after surgery. Routine resting myocardial perfusion imaging (MPI) and adenosine stress-gated MPI were performed before surgery. Patients were re-examined before discharge. Results: By analyzing the change in the LAT value, we found that the order of excitation of local myocardial cells changed after surgery. In addition, the LAT change in myocardial cells closer to the anastomosis was more significant. The earliest pacing point on the left anterior descending (LAD) coronary artery territory map was the third point (from the proximal to distal LAD) before OPCAB, but the earliest pacing point moved down to the fourth point (closer to the anastomosis) after the diagonal (DIA) anastomosis was complete. On the DIA territory map, the earliest pacing point was the fourth point before OPCAB; this moved up to the third point (closer to the anastomosis) after DIA bypass grafting. The voltages of all points were increased after myocardial revascularization. Compared with the preoperative period, the third, fourth and fifth points on the LAD territory map increased significantly after LAD anastomosis was complete (p=0.007, p=0.001, p=0.009, respectively). On the DIA territory map, the voltages of the first, second and third points were remarkably increased after completing the DIA anastomosis compared to before OPCAB and after LAD anastomosis completion (p=0.001, p=0.008, p<0.001 and p=0.006, p=0.032, p=0.002, respectively). The average conduction velocity (ACV) of all mapped points increased after OPCAB compared with before OPCAB (p<0.05). Postoperative resting MPI and adenosine stress-gated MPI showed that left ventricular global systolic function improved, the left ventricular ejection fraction (LVEF) increased significantly (p<0.05) and the left ventricular end systolic volume (LVESV) decreased significantly (p<0.05) compared to the preoperative MPI. Conclusions: Adequate surgical coronary revascularization could lead to more stable electrical activity of local cardiomyocytes, thus, illustrating the specific mechanism of coronary revascularization for improving the cardiac function from an electrophysiological perspective. [ABSTRACT FROM AUTHOR]

The central aim of this experiment was to compare acoustic parameters, formant frequencies and vowel space area (VSA), in adolescents with hearing-impaired (HI) and their normal-hearing (NH) peers; for kinematic parameters, the movements of vocal organs, especially the lips, jaw and tongue, during vowel production were analysed. The participants were 12 adolescents with different degrees of hearing impairment. The control group consisted of 12 age-matched NH adolescents. All participants were native Chinese speakers who were asked to produce the Mandarin vowels /a/, /i/ and /u/, with subsequent acoustic and kinematic analysis. There was significant difference between the two groups. Additionally, the HI group produced more exaggerated mouth and less tongue movements in all vowels, compared to their NH peers. Results were discussed regarding possible relationship between acoustic data, articulatory movements and degree of hearing loss to provide an integrative assessment of acoustic and kinematic characteristics of individuals with hearing loss. [ABSTRACT FROM AUTHOR]

Background: The critical shoulder angle (CSA) is the angle created between the superior and inferior bone margins of the glenoid and the most lateral border of the acromion. A few studies recently investigated the relation between CSA and functional outcomes after rotator cuff repair. However, there is a lack of research investigating the effect of CSA on postoperative tendon integrity after rotator cuff repair. Purpose: To assess the effects of the CSA on postoperative tendon integrity after rotator cuff repair. Study Design: Cohort study; Level of evidence, 3. Methods: All patients who underwent rotator cuff repair for full-thickness supraspinatus tears by 1 senior surgeon between January 2010 and January 2014 were included in this study. All patients had standardized anteroposterior shoulder radiographs the day before surgery. CSA and acromial index (AI) were measured. AI was derived by measuring the distance from the glenoid plane to the lateral border of the acromion and dividing it by the distance from the glenoid plane to the lateral aspect of the humeral head. Functional scores—including American Shoulder and Elbow Surgeons shoulder evaluation form, modified University of California at Los Angeles score, Constant-Murley score, and visual analog scale for pain—were used to evaluate shoulder function at a minimum follow-up of 2 years. Meanwhile, magnetic resonance imaging examinations were performed to evaluate rotator cuff integrity according to the Sugaya method and the signal/noise quotient (SNQ) of the rotator cuff tendon. Results: A total of 90 patients were included in this study: 42 patients with a single-row repair and 48 with a double-row repair. There was a significant positive correlation between CSA or AI and tendon SNQ. On the basis of CSA, the patients were divided into 2 groups: large CSA (>38°) and control (CSA ≤38°). At final follow-up, the large CSA group and the control CSA group demonstrated no significant differences in American Shoulder and Elbow Surgeons, University of California at Los Angeles, Constant, and visual analog scale scores. Postoperative magnetic resonance imaging revealed that the large CSA group had 9 cases of retear, with a significantly higher retear rate than the control group (15% vs 0%, P = .03). Furthermore, the tendon SNQ of the large CSA group was significantly greater than that of the control group. Conclusion: CSA did not appear to influence postoperative functional outcomes, while those in the large CSA group had poor tendon integrity after rotator cuff repair. These findings indicate that a large CSA is associated with an increased risk of rotator cuff tendon retear after repair. [ABSTRACT FROM AUTHOR]

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016-2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far. [ABSTRACT FROM AUTHOR]

Background: Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear.Aims: To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells.Methods: BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo.Results: BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo.Conclusions: BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC. [ABSTRACT FROM AUTHOR]

Background: The meniscus is one of the most commonly injured parts of the body, and meniscal healing is difficult. Hypothesis: Kartogenin (KGN) induces tendon stem cells (TSCs) to differentiate into cartilage cells in vitro and form meniscus-like tissue in vivo. A damaged meniscus can be replaced with a KGN-treated autologous tendon graft. Study Design: Controlled laboratory study. Methods: In the in vitro experiments, TSCs were isolated from rabbit patellar tendons and cultured with various concentrations of KGN, from 0 to 1000 µM. The effect of KGN on the chondrogenesis of TSCs in vitro was investigated by histochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The in vivo experiments were carried out on 6 New Zealand White rabbits by removing a meniscus from the rabbit knee and implanting an autologous tendon graft treated with KGN or saline. The meniscus formation in vivo was examined by histological analysis and immune staining. Results: The proliferation of TSCs was promoted by KGN in a concentration-dependent manner. Both histochemical staining and qRT-PCR showed that the chondrogenic differentiation of TSCs was increased with KGN concentration. After 3 months of implantation, the tendon graft treated with KGN formed a meniscus-like tissue with a white and glistening appearance, while the saline-treated tendon graft retained tendon-like tissue and appeared yellowish and unhealthy. Histochemical staining showed that after 3 months of implantation, the KGN-treated tendon graft had a structure similar to that of normal meniscus. Many cartilage-like cells and fibrocartilage-like tissues were found in the KGN-treated tendon graft. However, no cartilage-like cells were found in the saline-treated tendon graft after 3 months of implantation. Furthermore, the KGN-treated tendon graft was positively stained by both anti–collagen type I and type II antibodies, but the saline-treated tendon graft was not stained by collagen type II. Conclusion: The findings indicated that KGN can induce the differentiation of TSCs into cartilage-like cells in vitro and in vivo. The results suggest that KGN-treated tendon graft may be a good substitute for meniscal repair and regeneration. Clinical Relevance: This study revealed the direct effects of KGN on the chondrogenic differentiation of TSCs in vitro and in vivo. A KGN-treated autologous tendon graft induced formation of a meniscus-like tissue in vivo. This study provides a new cartilage regenerating technology for the treatment of damaged meniscus. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the clinical and molecular epidemiology and biofilm formation of Staphylococcus aureus (SA) isolated from pediatricians in China.Methods: SA strains were isolated from Beijing Children's hospital from February 2016 to January 2017. Isolates were typed by multilocus sequence typing (MLST), spa and SCCmec typing (for Methicillin-resistant SA [MRSA] only). Antimicrobial susceptibility testing was performed by agar dilution method except sulphamethoxazole/trimethoprim (E-test method). Biofilm formation and biofilm associated genes were detected.Results: Totally 104 children (41 females and 63 males; median age, 5.2 months) were enrolled in this study, in which 60 patients suffered from MRSA infection. Among the 104 cases, 54.8% were categorized as community associated SA (CA-SA) infections. The children under 3 years were more likely to occur CA-SA infections compared with older ones (P = 0.0131). ST59-SCCmec IV-t437 (61.7%) was the most prevalent genotype of MRSA, and ST22-t309 (18.2%), ST5-t002 (9.1%), ST6-t701 (9.1%), ST188-t189 (9.1%) were the top four genotypes of methicillin-sensitive SA (MSSA). All the present isolates were susceptible to linezolid, vancomycin, trimethoprim-sulfamethoxazole, mupirocin, tigecyclin, fusidic acid. No erythromycin-susceptible isolate was determined, and only a few isolates (3.8%) were identified as susceptible to penicillin. Multi-drug resistant isolates were reponsible for 83.8% of the ST59-SCCmec IV-t437 isolates. The isolates with strong biofilm formation were found in 85% of MRSA and 53.2% of MSSA, and in 88.7% of ST59-SCCmec IV-t437 isolates. Biofilm formation ability varied not only between MRSA and MSSA (P = 0.0053), but also greatly among different genotypes (P < 0.0001). The prevalence of the biofilm associated genes among ST59-SCCmec IV-t437 clone was: icaA (100.0%), icaD (97.3%), fnbpA (100.0%), fnbpB (0), clfA (100%), clfB (100%), cna (2.7%), bbp (0), ebpS (88.5%), sdrC (78.4%), sdrD (5.4%), and sdrE (94.5%).Conclusions: These results indicated strong homology of the MRSA stains isolated from Chinese children, which was caused by spread of multiresistant ST59-SCCmec IV-t437 clone with strong biofilm formation ability. The MSSA strains, in contrast, were very heterogeneity, half of which could produce biofilm strongly. [ABSTRACT FROM AUTHOR]

Some reports have shown that nicotinamide N-methyltransferase (NNMT) is associated with the body mass index (BMI) and energy metabolism. Here we explored the association between NNMT gene polymorphisms and obesity. The subjects were recruited from male Chinese Han college student. 289 of them (19 ≤ body fat percentage (BF%)) were selected as the high body fat group (HBFG), 494 of them (3 ≤ BF% < 13.5) were selected as the low body fat group (LBFG), and then a case-control study (fat versus thin) was carried out to explore the association between the NNMT gene polymorphism and the body composition using tagSNPs method. A tagSNP (rs10891644) in NNMT gene was found significantly associated with the body composition (P<0.0026). At this locus, the BF% for the genotype GT, TT, and GG were 14.56±8.35, 13.47±8.11, and 12.42±7.50, respectively, and the differences between the GT and the GG + TT were highly significant (P<0.01); the ORadjusted value of the GT versus (GG + TT) was 1.716 (Padjusted=0.002, 95% CI = 1.240–2.235). Therefore, the variation of the tagSNP, rs10891644, is significantly associated with obesity and the GT carriers are the susceptible population. [ABSTRACT FROM AUTHOR]

Objective To evaluate right ventricular function in patients with acute pulmonary embolism ( APE) using electrocardiogram-gated CTA and to discuss the clinical value of pulmonary artery CTA Patients and methods Based on death risk evaluation, 86 APE patients were divided into high-risk group (n=46) and non-high-risk group (n=40). The CT pulmonary embolism ( PE) index and parameters of right ventricular function were analyzed from the CTPA images and compared between the two groups. Potential correlation between the two was also discussed. Result CT PE index (median 24.69%) of the high-risk group was obviously higher than that of the non-high-risk group (median 8.58%) ( P<.05). Except the diameter of superior vena cava, all other parameters of right ventricular function were significantly different between the two groups ( P<.05). CT PE index was correlated with the parameters of right ventricular function. Conclusion ECG-gated pulmonary artery CTA is suitable for assessing the severity of APE and right ventricular function. [ABSTRACT FROM AUTHOR]

Summary: This study evaluated the levels of bone turnover markers (BTMs) and investigated relationships between them and bone mineral density (BMD) in postmenopausal women in China suburban district. The prevalence of osteoporosis was 25.03 % at lumbar spine and 6.23 % at femoral neck, and BTMs were negatively correlated with BMDs. Introduction: The aims of this study were to evaluate the levels of bone turnover markers (BTMs), including serum N-terminal procollagen of type I collagen (P1NP), beta C-terminal cross-linked of type I collagen (β-CTX), 25-hydroxyvitamin D [25(OH)D], and parathyroid hormone (PTH), and to investigate relationships between these markers and bone mineral density (BMD) as well the prevalence of osteoporosis in postmenopausal women of suburban district. Methods: A population of 4822 postmenopausal women aged 55-69 years old (62.22 ± 6.75) from the suburban district was recruited voluntarily. BMD was measured at the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry; 2251 women in this group had the serum BTMs 25(OH)D and PTH tested. Results: The prevalence of osteoporosis was 25.03 % at lumbar spine and 6.23 % at femoral neck. The median (interquartile range) values of serum P1NP, β-CTX, 25(OH)D, and PTH were 59.3 ng/mL (44.7-75.52), 0.370 ng/mL (0.280-0.490), 23.0 ng/mL (17.1-30.5), and 31.4 pg/mL (24.9-39.7), respectively. Serum P1NP and β-CTX levels presented significantly negative correlations with BMDs at the all the sites (Beta = −0.098 to −0.208, respectively, P < 0.001), whereas PTH levels were negatively correlated with BMDs of the femoral neck and total hip (Beta = −0.062 and −0.054, P < 0.01, respectively). Serum 25(OH)D had positive associations with BMDs at total hip (Beta = 0.051, P < 0.01). Conclusions: The BMD of postmenopausal women in China suburban area is higher than that in downtown area, and over 60 % of the participants had their serum 25(OH)D level over 20 ng/mL. BTMs were negatively correlated with BMDs, suggesting that BTMs are reliable factors for early declines in BMD. [ABSTRACT FROM AUTHOR]

Background: An understudied component of the diet, branchedchain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs. Objective: We tested the hypotheses that concentrations of BCFAs in human milk differ between populations and are associated with maternal diet. Design: We surveyed the BCFA composition of samples collected as part of a standardized, prospective study of human-milk composition. Mothers were enrolled from 3 urban populations with differing diets: Cincinnati, Ohio; Shanghai, China; and Mexico City, Mexico. Enrollment was limited to healthy mothers of term singleton infants. We undertook a cross-sectional analysis of milk from all women with samples at postpartum week 4 (n = 359; ~ 120 women/site). Fatty acids were extracted from milk by using a modified Bligh-Dyer technique and analyzed by gas chromatography. Statistical analysis was performed by ANOVA and Tobit regression. For Cincinnati mothers, 24-h diet recalls were analyzed in relation to the individual BCFA concentrations measured in milk samples. Results: Total BCFAs in milk differed by site, with the highest concentration in Cincinnati followed by Mexico City and Shanghai (mean ± SE: 7.90 ± 0.41, 6.10 ± 0.36, and 4.27 ± 0.25 mg/100 mL, respectively; P < 0.001). Site differences persisted after delivery mode, maternal age, and body mass index were controlled for. The individual concentrations of iso-14:0, iso-16:0, iso-18:0, anteiso-15:0, and anteiso-17:0 also differed between sites. Milk concentrations of iso-14:0 and anteiso-15:0 were associated with maternal intake of dairy; iso-16:0 was associated with maternal intakes of dairy and beef. Conclusions: BCFA concentrations in milk at 4 wk postpartum differed between mothers from Cincinnati, Shanghai, and Mexico City. Variations in human-milk BCFAs are influenced by diet. The impact of BCFAs on infant health warrants investigation. [ABSTRACT FROM AUTHOR]

Background: Excessive iodine intake may have adverse effects on the thyroid, particularly in children, but the safe upper iodine intake concentration in children is unclear. Objective: We assessed the adverse effects of high iodine intake from iodine-rich drinking water on thyroid size in children by examining associations between thyroid volume (Tvol), total goiter rate (TGR), and iodine intake. Design: In a multistage cross-sectional survey, we collected two 24-h urine samples on 2 nonconsecutive days and determined 24-h urinary iodine excretion, then calculated habitual daily iodine intake. Ultrasonographic Tvol was measured, and TGR was calculated based on international and Chinese reference ranges for Tvol in children. Results: This study included 2089 children from Shandong province, where the median (IQR) drinking water iodine concentration was 183 mg/L (69-406 mg/L). The median (IQR) 24-h urinary iodine concentrations for the 2 collections were 381 mg/L (203-649 mg/L) and 398 mg/L (202-687 mg/L), respectively. The median (IQR) habitual daily iodine intake of children was 298 mg/d (186-437 mg/d). Tvols were slightly higher in boys than in girls (P = 0.035). The overall TGR was 9.7% and did not differ by sex. The TGR was ~5% for children aged 7-10 and 11-14 y at iodine intakes of 200-249 and 250-299 mg/d, respectively. With the use of logistic regression and 2-step linear regression, a nonlinear association was observed between Tvol, TGR, and iodine intake, with a threshold intake of 150 mg/d. Conclusions: Tvol begins to increase in children when iodine intake is $ 150 mg/d, and the TGR exceeds 5% when daily iodine intake is $250 mg/d for children aged 7-10 y and $300 mg/d for children aged 11-14 y. Our findings suggest that 150-249 and 150-299 mg/d seem to be safe upper iodine intake ranges for children aged 7-10 and 11-14 y, respectively. [ABSTRACT FROM AUTHOR]

This study investigated the effects of fingertip tactile sensitivity on the structural variability of thumb and index finger forces during stable precision grip. Thirty right-handed healthy subjects participated in the experiment. Transient perturbation of tactile afferents was achieved by wrapping up the distal pads of the thumb or index finger with transparent polyethylene films. The time-dependent structure of each digit force and the variability of interdigit force correlation were examined by detrended fluctuation analysis (DFA) and detrended cross-correlation analysis (DCCA), respectively. Results showed that the tactile sensitivity affected αDFA of the vertical shear force Fx (F3,239 = 6.814, p<0.001) and αDCCA of Fx (χ2 = 16.440, p<0.001). No significant difference was observed in αDFA or αDCCA of the normal forces produced by the thumb or index finger. These results suggested that with blurred tactile sensory inputs the central nervous system might decrease the vertical shear force flexibility and increase the interdigit shear force coupling in order to guarantee a stable grip control of an object against gravity. This study shed light on the feedback and feed-forward strategies involved in digit force control and the role of SA-II afferent fibers in regulation of vertical shear force variability for precision grip. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL) affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L) promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L) inhibited root elongation. There was a significant (P<0.05) positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes’ (superoxide dismutase, peroxidase, and catalase) activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots. [ABSTRACT FROM AUTHOR]

Background Being small for gestational age ( SGA), a foetal growth abnormality, has a long-lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid ( FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter-relationships among methylation levels of two imprinted genes [ H19 differentially methylated regions ( DMRs) and MEST DMRs], maternal FA supplementation and SGA. Methods We conducted a case-control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age ( AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. Results Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 ( P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites ( P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). Conclusions Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri-conception FA supplementation and also be sex-specific. [ABSTRACT FROM AUTHOR]

Introduction: According to the Traditional Chinese Medicine theory of acupuncture, Baihui (GV20) is applied to treat neurological and psychiatric disorders. However, the relationships between neural responses and GV20 remain unknown. Thus, the main aim of this study was to examine the brain responses induced by electroacupuncture stimulation (EAS) at GV20. Materials and Methods: Functional magnetic resonance imaging (fMRI) was performed in 33 healthy subjects. Based on the non-repeated event-related (NRER) paradigm, group differences were examined between GV20 and a sham acupoint using the regional homogeneity (ReHo) method. Results: Compared with the sham acupoint, EAS at GV20 induced increased ReHo in regions including the orbital frontal cortex (OFC), middle cingulate cortex (MCC), precentral cortex, and precuneus (preCUN). Decreased ReHo was found in the anterior cingulate cortex (ACC), supplementary motor area (SMA), thalamus, putamen, and cerebellum. Conclusions: The current findings provide preliminary neuroimaging evidence to indicate that EAS at GV20 could induce a specific pattern of neural responses by analysis of ReHo of brain activity. These findings might improve the understanding of mechanisms of acupuncture stimulation at GV20. [ABSTRACT FROM AUTHOR]

Noncoding RNAs (ncRNAs) have been identified in many fungi. However, no genome-scale identification of ncRNAs has been inventoried for basidiomycetes. In this research, we detected 254 small noncoding RNAs (sncRNAs) in a genome assembly of an isolate (CCEF00389) of Pleurotus ostreatus, which is a widely cultivated edible basidiomycetous fungus worldwide. The identified sncRNAs include snRNAs, snoRNAs, tRNAs, and miRNAs. SnRNA U1 was not found in CCEF00389 genome assembly and some other basidiomycetous genomes by BLASTn. This implies that if snRNA U1 of basidiomycetes exists, it has a sequence that varies significantly from other organisms. By analyzing the distribution of sncRNA loci, we found that snRNAs and most tRNAs (88.6%) were located in pseudo-UTR regions, while miRNAs are commonly found in introns. To analyze the evolutionary conservation of the sncRNAs in P. ostreatus, we aligned all 254 sncRNAs to the genome assemblies of some other Agaricomycotina fungi. The results suggest that most sncRNAs (77.56%) were highly conserved in P. ostreatus, and 20% were conserved in Agaricomycotina fungi. These findings indicate that most sncRNAs of P. ostreatus were not conserved across Agaricomycotina fungi. [ABSTRACT FROM AUTHOR]

Background The present study evaluated the relationship between dietary fatty acid ( FA) intakes and human milk FA levels. Methods Healthy lactating women ( n = 514) from Northern China participated in the study. Dietary intake was assessed with a 24-h dietary recall questionnaire and evaluated using golden key maternal nutrition software (Wincome, Shanghai, China) and China Food Composition 2009. Human milk FA composition was determined by gas chromatography. Results The maternal daily median intakes of linoleic acid ( LA), α-linolenic acid ( ALA) and arachidonic acid ( AA) were 19.93 g, 3.08 g and 16.33 mg, respectively. Eicosapentaenoic acid ( EPA) and docosahexaenoic acid ( DHA) intakes were below the recommended levels. FA levels in 100 g of human milk were 0.363 g LA, 0.038 g γ-linolenic acid ( GLA), 0.052 g dihomo γ-linolenic acid ( DGLA), 0.144 g ALA, 0.079 g AA, 0.007 g EPA, 0.018 g docosatetraenoic acid ( DTA) and 0.048 g DHA. Multiple linear regression analysis revealed that human milk DGLA levels were negatively correlated with dietary LA intake (β = −0.223, P = 0.030), and human milk GLA and DTA levels were negatively correlated with dietary ALA intake (β = −2.189, P = 0.031; β = −2.252, P = 0.027) after adjusting for possible confounding factors. Conclusions The results of the present study suggest the presence of competitive interactions between n-3 fatty acids ( ALA) and n-6 fatty acids ( GLA and DTA). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effects of moderately increased maternal dietary energy intake during gestation on foetal skeletal muscle development and metabolism with pig as a model. Methods: Twelve primiparous purebred Large White sows (initial body weight 135.5 ± 1.6 kg) were allocated to one of two energy intake treatments: normal-energy-intake group (Con, 30.96 MJ DE/day) as recommended by the National Research Council (NRC; 2012) and high-energy-intake group (HE, 34.15 MJ DE/day). The nutritional treatments were introduced from mating to day 90 of gestation. On day 90 of gestation, foetuses were examined by morphological, biochemical and molecular analysis of the longissimus muscle. Umbilical vein serum hormones were measured. Results: Sow body weight was increased in HE group compared with Con group ( P < 0.05), whereas foetal myofibre density was decreased ( P < 0.05). Meanwhile, protein concentration, creatine kinase and lactate dehydrogenase activities and umbilical vein serum triiodothyronine (T3) concentration were decreased in HE foetuses ( P < 0.05). Maternal HE diets decreased the mRNA abundance of muscle growth-related genes, myosin heavy-chain (MYH/MyHC) genes (MYH2 and MYH1) and insulin-like growth factor 1 and insulin growth factor-binding protein 5 ( P < 0.05). Furthermore, the protein expressions of myogenic differentiation factor 1, myogenin and fast-MyHC isoforms were reduced in HE foetuses ( P < 0.05). Conclusion: Our results suggest that moderately increased maternal dietary energy intake delays the differentiation and maturation in skeletal muscle of the foetus on day 90 of gestation. [ABSTRACT FROM AUTHOR]

Objective FOXE1 plays an important role in craniofacial development. The aim of this study was to investigate associations between genetic variants of FOXE1 and risk of non-syndromic orofacial clefts in a Chinese population. Materials and Methods Three potentially functional SNPs of FOXE1 (rs3758250 and rs907577 in the 5′ upstream and rs7043516 in the 3′- UTR) were selected and their associations with non-syndromic orofacial cleft susceptibility were investigated in a case-control study from a Chinese population (602 cases and 605 controls). Genotyping was performed with double ligation and multiplex fluorescence PCR. Associations between the SNPs and risk of non-syndromic orofacial clefts and its subgroups were estimated from unconditional logistic regression analysis. Luciferase reporter assay was conducted to assess SNP function. Results Overall, we did not find any of the individual SNP or haplotype was associated with NSOC susceptibility. Nevertheless, in stratified analysis, we found rs7043516, locating in the 3′- UTR of FOXE1, was associated with risk of cleft lip only. Further in vitro luciferase assay indicated that this SNP could contribute to differential binding ability with mi RNA. Conclusions Taken together, this study showed that rs7043516 may be considered as a potentially susceptible marker of cleft lip only among Chinese Han populations. [ABSTRACT FROM AUTHOR]

This study assessed the effect of 1-year regular Tai Chi (TC) on neuromuscular reaction in elderly women. A total of 41 elderly women (55 years–68 years) completed the study. The TC group (n = 21) performed the 24-form TC, while the control group (C, n = 20) was instructed to read newspapers or watch television when the TC group practised. Electromyogram measurements were conducted before and after intervention. After a year-long intervention, the post-test results of between-group neuromuscular reaction time showed significant differences in the rectus femoris (t = 3.607, p = 0.001), semitendinosus (t = 2.678, p = 0.011), anterior tibialis (t = 3.455, p = 0.001), and gastrocnemius muscles (t = 4.061, p = 0.000). Within-group results showed that the TC group had significantly shorter neuromuscular reaction time compared to its baseline value in the rectus femoris (t = 3.066, p = 0.006), semitendinosus (t = 2.485, p = 0.022), anterior tibialis (t = 2.311, p = 0.032), and gastrocnemius muscles (t = 2.462, p = 0.023). Results suggested that year-long regular TC can improve neuromuscular reaction function in elderly women. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to investigate the protective effect of recombinant human EPO(rhEPO) on cerebral microvascular endothelial cells and the mechanisms by which rhEPO interacts with TJs proteins, claudin-5, Occludin and ZO-1 during the early period following traumatic brain injury. Research design: Rats (n = 81) were randomly divided into sham-operated group, TBI group and rhEPO+TBI group. Traumatic brain injury was induced by the Marmarou method. Methods and procedures: Rats were killed at 3, 24, 72 and 168 hours after TBI. The integrity of the blood–brain barrier was investigated by using a spectrophotometer to assess extravasation of Evans blue dye. The expression of Claudin-5, Occludin and ZO-1 were determined by immunohistochemistry and real-time fluorescence quantitative PCR. Results: From 3 hours to 3 days, rats in the TBI group demonstrated a remarkable increase in Evans blue content in the brain, relative to rats in the sham-operated group (p < 0.05). The expression of Claudin-5 and Occludin was significantly lower than those in the sham-operated group (p < 0.05). In contrast, rats in the TBI+rhEPO group demonstrated a significant decrease in brain levels. Conclusion: It was found that administration of rhEPO protected cerebral microvascular endothelial cells and reduced permeability of BBB and the mechanisms may be due to increasing the expression of TJs proteins. [ABSTRACT FROM AUTHOR]

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have properties that make them promising for the treatment of chronic nonhealing wounds. The major challenge is ensuring an efficient, safe, and painless delivery of BMMSCs. Tissue-engineered skin substitutes have considerable benefits in skin damage resulting from chronic nonhealing wounds. Here, we have constructed a three-dimensional biomimetic scaffold known as collagen-chitosan sponge scaffolds (CCSS) using the cross-linking and freeze-drying method. Scanning electron microscopy images showed that CCSS had an interconnected network pore configuration about 100 μm and exhibited a suitable swelling ratio for maintaining morphological stability and appropriate biodegradability to improve biostability using swelling and degradation assays. Furthermore, BM-MSCs were seeded in CCSS using the two-step seeding method to construct tissueengineered skin substitutes. In addition, in this three-dimensional biomimetic CCSS, BM-MSCs secreted their own collagen and maintain favorable survival ability and viability. Importantly, BM-MSCs exhibited a significant upregulated expression of proangiogenesis factors, including HIF-1α, VEGF, and PDGF following hypoxia pretreatment. In vivo, hypoxia pretreatment of the skin substitute observably accelerated wound closure via the reduction of inflammation and enhanced angiogenesis in diabetic rats with hindlimb ischemia. Thus, hypoxia pretreatment of the skin substitutes can serve as ideal bioengineering skin substitutes to promote optimal diabetic skin wound healing. [ABSTRACT FROM AUTHOR]

Background Fetal interrupted aortic arch (IAA) is a rare cardiac anomaly and its prenatal diagnosis is challenging. The purpose of our report is to evaluate the use of two-dimensional echocardiography (2 DE) and 4D echocardiography with B-flow imaging and spatiotemporal image correlation (4D BF- STIC) in detecting IAA type A ( IAA-A). Materials & Methods Twenty-three cases of confirmed IAA-A identified by fetal echocardiography were involved in the study. The fetal echocardiography image data were reviewed to analyze the ratio of right ventricle to left ventricle ( RV/ LV) diameter, the ratio of main pulmonary artery to ascending aorta ( MPA/ AAO) diameter, and the correlation of RV/ LV diameter ratio and size of ventricular septal defect ( VSD). 4D BF- STIC was performed in 21 fetuses using the sagittal view (4D BF- STIC-sagittal) and the four-chamber view (4D BF- STIC-4 CV) as initial planes of view. An additional 183 normal fetuses were also included in our study. RV/ LV and MPA/ AAO ratios were calculated and compared with that of IAA-A fetuses. Fetal 2 DE, 4D BF- STIC-sagittal, and 4D BF- STIC-4 CV were used to visualize the aortic arch and its associated neck vessels. Six subgroups were evaluated according to gestational age. Results Fetal 2 DE, 4D BF- STIC-sagittal, and 4D BF- STIC-4 CV made the correct prenatal diagnosis of IAA-A in 19/23 (82.6%), 14/21 (66.7%), and 19/21 (90.5%) of patients, respectively. A significantly enlarged MPA combined with symmetric ventricles was found in the IAA-A fetuses, while the size of the VSD was negatively correlated with RV/ LV ratio. 4D BF- STIC-sagittal and 4D BF- STIC-4 CV were better than traditional 2D ultrasound in detecting the aortic arch and neck vessels between 17 and 28 gestational weeks and 29 to 40 gestational weeks in normal fetuses. Conclusion It is demonstrated that IAA-A could be diagnosed by traditional fetal echocardiography, while 4D technique could better display the anatomic structure and the spatial relationships of the great arteries. Use of volume reconstruction may promote its clinical usage and help prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Omge-3 polyunsaturated fatty acids (PUFAs) exhibited significant effect in inhibiting various tumors. However, the mechanisms of its anticancer role have not been fully demonstrated. The declination of 5-methylcytosine (5 mC) was closely associated with poor prognosis of tumors. To explore whether omega-3 PUFAs influences on DNA methylation level in tumors, colorectal cancer (CRC) rat model were constructed using N-methyl phosphite nitrourea and omega-3 PUFAs were fed to part of the rats during tumor induction. The PUFAs contents in the rats of 3 experimental groups were measured using gas chromatography and 5 mC level were detected by liquid chromatography tandem mass spectrometry. The results showed that tumor incidence in omega-3 treated rats was much lower than in CRC model rats, which confirmed significant antitumor role of omega-3 PUFAs. Six PUFA members categorized to omega-3 and omega-6 families were quantified and the ratio of omega-6/omega-3 PUFAs was remarkably lower in omega-3 PUFAs treatment group than in CRC model group. 5 mC content in omega-3 PUFAs treated rats was higher than in CRC model rats, suggesting omega-3 PUFAs promoted 5 mC synthesis. Therefore, omega-3 PUFAs probably inhibited tumor growth via regulating DNA methylation process, which provided a novel anticancer mechanism of omega-3 PUFAs from epigenetic view. [ABSTRACT FROM AUTHOR]

Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered. [ABSTRACT FROM AUTHOR]

Objective Neutrophil extracellular traps (NETs) have been shown to play an important role in systemic lupus erythematosus (SLE) pathogenesis by activating plasmacytoid dendritic cells (PDCs) and the type I interferon (IFN) pathway. NETs composed of self-DNA are considered to be of nuclear origin and are a major source of anti-DNA autoantibody generation. This study was undertaken to evaluate whether mitochondrial DNA (mtDNA) resides in NETs, to evaluate whether mtDNA and anti-mtDNA antibodies cause dysregulation of the PDC-IFNα pathway, and to investigate the clinical implication in SLE. Methods Patients with SLE (n = 102), patients with rheumatoid arthritis (n = 30), and healthy donors (n = 40) were enrolled in in vitro studies. NETs were generated from phorbol 12-myristate 13-acetate (PMA)-stimulated peripheral neutrophils. Immunofluorescence staining was used to detect NET formation ex vivo and in lupus nephritis renal biopsy samples. The mtDNA levels and type I IFN-inducible gene scores were measured by quantitative polymerase chain reaction. Anti-mtDNA antibodies, anti-double-stranded DNA (anti-dsDNA) antibodies, and IFNα were detected by enzyme-linked immunosorbent assay. Purified PDCs were stimulated by isolated NETs, mtDNA, or dsDNA, combined with anti-mtDNA or dsDNA IgG, or other culture conditions. Additional patients with SLE (n = 113) were enrolled in a proof-of-concept trial. We evaluated the efficacy and safety of metformin on a background of corticosteroids and conventional immunosuppressive agents in patients with mild or moderate lupus. The primary end point was the efficacy of metformin for reducing disease flare. Results We detected mtDNA in NETs, and anti-mtDNA antibody levels were elevated in SLE patients compared with controls and significantly correlated with IFN scores and the disease activity index. The presence of anti-mtDNA antibodies was disproportionately associated with lupus nephritis, and correlated better than anti-dsDNA antibody levels with the lupus nephritis activity index. Mitochondrial DNA was deposited in NETs in lupus nephritis renal biopsy specimens. In addition, mtDNA/anti-mtDNA were greater inducers of PDC IFNα production via Toll-like receptor engagement than dsDNA/anti-dsDNA. We assessed the effect of metformin on down-regulating the NET mtDNA-PDC-IFNα pathway. Metformin decreased PMA-induced NET formation and CpG-stimulated PDC IFNα generation. A proof-of-concept trial of metformin add-on treatment of mild or moderate SLE resulted in decreases in clinical flares, prednisone exposure, and body weight. Conclusion Our findings establish a link between mtDNA in NETs, anti-mtDNA antibodies, and PDC IFNα pathogenesis in SLE, and highlight that specific strategies to down-regulate this pathway, such as treatment with metformin, may be new approaches to treat SLE. [ABSTRACT FROM AUTHOR]

Aseptic loosening of an implant after total joint arthroplasty is still a major complication that results from periprosthetic osteolysis. Fibroblasts in the interface membrane express receptor activator of nuclear factor kappa B ligand (RANKL) and stimulate osteoclast formation. Studies demonstrate that through the control of osteoclastic bone loss bisphosphonates inhibit wear particle-induced bone resorption around total hip arthroplasty. The majority of bisphosphonates studies have focused on their effects on osteoblasts and osteoclasts. Little attention has been paid to their action on fibroblasts.~Purpose~Objective~We isolated fibroblasts from the interface membrane that was obtained when revision hip arthroplasty was performed because of aseptic loosening. Fibroblasts were stimulated with alendronate. RANKL and osteoprotegerin (OPG) assays were performed using enzyme-linked immunosorbent assay kit and real time Reverse Transcription- Polymerase Chain Reaction (RT-PCR).~Methods~Methods~We found that alendronate stimulated OPG mRNA and protein expression in a time and dose dependent manner. By contrast, alendronate did not affect RANKL expression.~Results~Results~The results indicate that alendronate modulated OPG production by fibroblasts from periprosthetic membrane, which may prove helpful for the inhibition of bone loss during aseptic loosening following total joint arthroplasty.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Objective. Mesenchymal stem cells (MSCs) derived from patients with systemic lupus erythematosus (SLE) exhibit enhanced senescence. Cellular senescence has been reported to be induced by several inflammatory cytokines, including interferon-a (IFNα) and IFNγ, that are involved in the pathogenesis of SLE. We undertook this study to investigate whether the inflammatory environment in SLE could affect MSC senescence. Methods. Cellular senescence was measured by staining of senescence-associated β-galactosidase and by expression of the cell cycle inhibitors p53 and p21. Eighty cytokines and chemokines in serum from healthy controls and patients with SLE were identified by cytokine antibody array. Results. SLE serum promoted senescence of MSCs, which was reversed by the phosphatidylinositol 3-kinase (PI3K)/Akt signaling inhibitor LY294002 but not by the JAK/STAT inhibitor AG490 and not by the MEK/ERK inhibitor PD98059. Cytokine antibody array analysis revealed that leptin and neutrophil-activating peptide 2 (NAP-2) were the 2 factors most significantly elevated in SLE serum compared with normal serum. Blockade of leptin or NAP-2 in MSC cultures abolished SLE serum- induced senescence, while direct addition of these 2 factors could promote senescence in cultures of normal MSCs. Inhibition of PI3K/Akt signaling with LY294002 reduced leptin- and NAP-2-induced senescence in MSCs. Conclusion. Taken together, our data show that leptin and NAP-2 act synergistically to promote MSC senescence through enhancement of the PI3K/Akt signaling pathway in SLE patients. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacte-rially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gut microbiota and associations with cardiometabolic health have not been examined. Objective: The objective of this study was to identify associations between fecal menaquinone profiles, gut microbiota composition, and biomarkers of cardiometabolic health. Design: The menaquinone profile and gut microbiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gut microbiota composition and to improve cardiometabolic biomarkers. Results: Co variance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P < 0.05); and longitudinal changes in the relative abundance of > 100 OTUs were associated with altered fecal content of ≥ 1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation. Conclusions: These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gut microbiota and that diet-mediated alterations in gut microbiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese Clinical Trials Registry as ChiCTR-TRC-09000353. [ABSTRACT FROM AUTHOR]

Primary objective: Lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB) in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying disruption of the BBB in LPS-induced sepsis. Research design: Both in vitro and in vivo experiments were designed to test the role of AMP-activated protein kinase (AMPK) in LPS-induced BBB dysfunction. Methods and procedures: Human brain microvascular endothelial cells (HBMECs) were cultured. The protein expressions were detected by western blot. BBB integrity was determined by Evans Blue. Main outcomes and results: LPS (1 μg ml-1) dramatically increased the permeability of the BBB and the ROS productions, as well as reducing the expression levels of occludin and claudin-5 in cultured HBMECs. Inhibition of NAD(P)H oxidase by apocynin or up-regulation of AMPK reversed the LPS-induced abnormities in HBMECs. In LPS-induced sepsis in mice, it was found that LPS dramatically increased NAD(P)H oxidase protein expressions and ROS productions in the brain and disrupted BBB function assayed by Evans blue staining, which were abolished by AICAR treatment. Conclusions: It is concluded that AMPK activation improves the functions of the BBB impaired by LPS through suppression of NAD(P)H oxidase-derived ROS in mice. [ABSTRACT FROM AUTHOR]

Background: Cytokines secreted by adipose tissue macrophages (ATMs) significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. However, little relevant information is available regarding the role of microvesicles (MVs) derived from ATMs in macrophage-adipocyte crosstalk. Methods: MVs were generated by stimulation of M1 or M2 phenotype THP-1 macrophages and incubated with human primary mature adipocytes and differentiated adipocytes. Subsequently, insulin-stimulated phosphorylation of Akt (pAkt) and glucose uptake were determined. Glucose transporter 4 (GLUT4) translocation and nuclear translocation of nuclear factor (NF)-kappa B were also analyzed in treated adipocytes. Results: M1 macrophage-derived MVs (M1 MVs) significantly reduced protein abundance of insulin-induced Akt phosphorylation in human primary mature adipocytes and differentiated adipocytes, when compared with the same concentration of M2 macrophage-derived MVs (M2 MVs). In contrast to M2 MVs, which enhanced the insulin-induced glucose uptake measured by 2-NBDG, M1 MVs decreased this effect in treated adipocytes. M1 MVs treatment also brought about a significant increase in the nuclear translocation of nuclear factor (NF)-kappa B, coupled with a decrease in pAkt level and GLUT4 translocation compared with M2 MVs-treated adipocytes. These effects were reversed by BAY 11-7085, a NF- kappa B specific inhibitor. Conclusions: MVs derived from proinflammatory (M1) macrophages may, at least in part, contribute to the pathogenesis of obesity-induced insulin resistance, reducing insulin signal transduction and decreasing glucose uptake in human adipocytes, through NF-kappa B activation. Therefore, these MVs may be potential therapy candidates for the management of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

This study examined the effects of mechanical strain on osteogenic and adipogenic differentiation of cultured MSCs by stimulating MSCs cultured in general and adipogenic differentiation media using a mechanical strain device. Markers of osteogenic (Runx2, Osx, and I-collagen) and adipogenic (PPARγ-2, C/EBPα, and lipid droplets) differentiation were examined using real-time PCR, western blot, immunocytochemical, or histochemical stain analyses. Levels of Runx2 and Osx gradually increased in MSC groups in general medium subject to strain stimulation, as compared with in unstrained groups. After adding the stress signal, I-collagen protein levels of expression were obviously promoted in cells in comparison to the controls. The levels of PPARγ-2 and C/EBPα were decreased, and the emergence of lipid droplets was delayed in MSCs groups in adipogenic differentiation medium subject to strain stimulation, as compared with in unstrained groups. Mechanical strain can promote differentiation of MSCs into osteoblasts and can impede differentiation into adipocytes. These results clarify the mechanisms underlying the effects of exercise on bone repair and reconstruction and provide a more adequate scientific basis for the use of exercise therapy in the treatment of obesity and metabolic osteoporosis. [ABSTRACT FROM AUTHOR]

Objective. CD200/CD200R1 signalling has an immunoregulatory effect on the activation threshold of the inflammatory immune response and maintains immune homeostasis. In this study we evaluated the status of CD200/CD200R1 interaction in patients with RA. Methods. The expression of CD200 and CD200R1 was examined by immunohistochemistry and flow cytometry and was compared between RA patients and healthy controls (HCs). Sorted CD4+ T cells were stained with carboxyfluorescein succinimidyl ester (CFSE) and annexin V-propidium iodide to evaluate the effect of CD200 on cell proliferation and apoptosis. The effect of CD200 on Th17 differentiation, function and osteoclastogenesis was determined by flow cytometry, transwell migration assay and immunocytochemistry, respectively. Results. The proportion of CD200+ cells and CD200R1+ cells in peripheral blood mononuclear cells, peripheral CD14+ cells and CD4+ T cells was significantly lower in the RA patients than in HCs, whereas the number of CD200+ cells was higher in synovium from RA patients than in that from HCs. After treatment with infliximab and MTX we found increased expression of peripheral CD200/CD200R1 that correlated with a decrease in the 28-joint DAS. CD200Fc in vitro partially inhibited CD4+ T cell proliferation, promoted CD4+ T cell apoptosis, reduced CD4+ T cell differentiation into Th17 cells and down-regulated CCR6-mediated Th17 chemotaxis in cells from RA patients. In addition, the engagement of the CD200 receptors on CD14+ cells with CD200Fc in vitro reduced osteoclastogenesis and inhibited CD14+ celldriven Th17 differentiation. Conclusion. Abnormal CD200/CD200R1 expression in RA may contribute to abnormal Th17 cell differentiation, chemotaxis and osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Aim The implantation of bone marrow-derived mesenchymal stem cells ( MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal periodontal regeneration is still unknown. This in vivo study explored which differentiation approach is most suitable for periodontal regeneration. Materials and Methods Mesenchymal stem cells were obtained from Fischer rats and seeded onto poly(lactic-co-glycolic acid)/poly( ɛ-caprolactone) electrospun scaffolds, and then pre-cultured under different in vitro conditions: (i) retention of multilineage differentiation potential; (ii) osteogenic differentiation approach; and (iii) chondrogenic differentiation approach. Subsequently, the cell-scaffold constructs were implanted into experimental periodontal defects of Fischer rats, with empty scaffolds as controls. After 6 weeks of implantation, histomorphometrical analyses were applied to evaluate the regenerated periodontal tissues. Results The chondrogenic differentiation approach showed regeneration of alveolar bone and ligament tissues. The retention of multilineage differentiation potential supported only ligament regeneration, while the osteogenic differentiation approach boosted alveolar bone regeneration. Conclusion Chondrogenic differentiation of MSCs before implantation is a useful strategy for regeneration of alveolar bone and periodontal ligament, in the currently used rat model. [ABSTRACT FROM AUTHOR]

Background and Objective Lipopolysaccharide ( LPS) on the cell wall of periodontal pathogens is a major mediator of the inflammatory response and can enhance alveolar bone resorption in periodontitis. Bone sialoprotein is an early marker of osteoblast differentiation. The proinflammatory cytokine, interleukin-8 ( IL-8), induces osteoclast differentiation, maturation and maintenance of bone resorption activity. However, the effects of LPS from periodontal pathogens on the expression of bone sialoprotein and IL-8 in human osteoblasts and the mechanism of periodontal bone metabolism regulation are rather unclear. The objectives of this study were to determine the effects of Porphyromonas gingivalis LPS on the production of bone sialoprotein and IL-8 in human periodontal ligament fibroblasts ( hPDLFs), and to investigate whether toll-like receptor ( TLR) 2, TLR4 and MAPKs pathways are involved in the regulation of production of bone sialoprotein and IL-8 by P. gingivalis LPS. Material and Methods The third-generation of h PDLFs were cultured with mineralization-inducing culture medium. After h PDLFs were treated with P. gingivalis LPS, bone sialoprotein and IL-8 m RNA expression were detected using Real time PCR. Then h PDLFs were transiently transfected with si TLR2 or si TLR4 (20 n m) or inhibited by MAPK signaling pathways inhibitors, and then bone sialoprotein and IL-8 m RNA and protein expression were also detected using Real time PCR and western blotting. Results Treatments with 0.01 and 0.1 mg/L of P. gingivalis LPS for 8 h up-regulated bone sialoprotein mRNA expression, whereas 10 and 100 mg/L of P. gingivalis LPS induced a significant decrease in the expression of bone sialoprotein mRNA. In contrast, IL8 mRNA levels were increased significantly by 10 mg/L of P. gingivalis LPS. Interestingly, small interfering RNA (siRNA) knock down of the TLR2 and ERK1/2 inhibitor, PD98059, abolished the effects of P. gingivalis LPS on the bone sialoprotein mRNA level, whereas si RNA knock down of the TLR2 and p38 MAPK inhibitor, SB203580, blocked the effect of P. gingivalis LPS on IL-8 in hPDLFs. Conclusion This study suggests that in hPDLFs, P. gingivalis LPS suppresses bone sialoprotein and enhances IL-8 gene and protein expression via TLR2 and ERK1/2 or the p38 MAPK signaling pathway, respectively. [ABSTRACT FROM AUTHOR]

Background and Objective Human beta-defensins ( hBDs) are a group of antimicrobial peptides important in epithelial innate immunity, and their differential expression is associated with periodontal diseases. The aim of this study was to explore relationships among hBDs, total subgingival bacteria and periodontopathogens in healthy subjects and in patients with chronic periodontitis. Material and Methods The periodontal clinical parameters of 29 healthy subjects and 25 patients with chronic periodontitis were recorded. The relative expression of hBD1, hBD2 and hBD3 genes in gingival biopsies was measured using real-time PCR. The numbers of total bacteria and of Treponema denticola, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Tannerella forsythia in subgingival plaque were quantified by real-time PCR. Data were analyzed using the Mann-Whitney U-test and Spearman's rank correlation test. Results No significant differences in expression of the hBD genes were found between the group of healthy subjects and the group of patients with chronic periodontitis. Total bacteria and T. denticola were detected in all participants. F. nucleatum and T. forsythia were detected in all patients with chronic periodontitis and in 86.21% and 51.72%, respectively, of healthy volunteers. P. gingivalis and A. actinomycetemcomitans were detected in 24.14% and 17.24%, respectively, of the healthy group and in 84.00% and 12.00%, respectively, of the chronic periodontitis group. The prevalence of all bacteria, except A. actinomycetemcomitans, was significantly higher in the group of patients with chronic periodontitis than in the group of healthy subjects ( p < 0.05). A significant, negative correlation was observed between total bacteria and hBD-2 ( r = −0.384, p = 0.011). Upon analyzing the data in different groups, total bacteria and hBD-2 were significantly correlated ( r = −0.492, p = 0.026) only in the group of healthy subjects. Conclusion The negative correlations between hBD-2 and total bacteria, especially in the group of healthy subjects, indicate that hBDs may play an important role by limiting an increase of bacterial load at the initial stage of periodontitis. [ABSTRACT FROM AUTHOR]

Bone marrow derived mesenchymal stem cells (BM-MSCs) are considered as the most promising cells source for bone engineering. Cannabinoid (CB) receptors play important roles in bone mass turnover. The aim of this study is to test if activation of CB2 receptor by chemical agonist could enhance the osteogenic differentiation and mineralization in bone BM-MSCs. Alkaline phosphatase (ALP) activity staining and real time PCR were performed to test the osteogenic differentiation. Alizarin red staining was carried out to examine the mineralization. Small interference RNA (siRNA) was used to study the role of CB2 receptor in osteogenic differentiation. Results showed activation of CB2 receptor increased ALP activity, promoted expression of osteogenic genes, and enhanced deposition of calcium in extracellular matrix. Knockdown of CB2 receptor by siRNA inhibited ALP activity and mineralization. Results of immunofluorescent staining showed that phosphorylation of p38 MAP kinase is reduced by knocking down of CB2 receptor. Finally, bone marrow samples demonstrated that expression of CB2 receptor is much lower in osteoporotic patients than in healthy donors. Taken together, data from this study suggested that activation of CB2 receptor plays important role in osteogenic differentiation of BM-MSCs. Lack of CB2 receptor may be related to osteoporosis. [ABSTRACT FROM AUTHOR]

Objective: 2,3,7,8-Tetrachlorodibenzo-p-dioxin contributes to cleft palate, but the cellular and molecular mechanisms responsible for the deleterious effect on the developing palate are unclear. Because Wnt signaling is associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin in organ development, we wondered whether the malformation of the palate also results from altered Wnt signaling. Results: The 2,3,7,8-tetrachlorodibenzo-p-dioxin administration affected cell proliferation of the anteroposterior axis of the palatal shelf and delayed shelf elevation in mice. The activity of Wnt5a and lymphoid enhancing-binding factor 1 was inhibited by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the developing palate. Conclusions: Downregulated Wnt5a and lymphoid enhancing-binding factor 1 are associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate. Moreover, delayed shelf elevation by 2,3,7,8-tetrachlorodibenzo-p-dioxin is the crucial mechanism contributing to the high incidence of cleft palate. Our findings may help in elucidating the mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate. [ABSTRACT FROM AUTHOR]

Objectives. We aimed to investigate whether CD147 can up-regulate the chemotactic, adhesive and invasive properties of human neutrophils and to determine the mechanism underlying this process.Methods. Human promyelocytic leukaemia cells (HL-60) cells and peripheral blood or synovial fluid neutrophils were isolated from RA patients. Under cyclophilin A (CypA) stimulation, chemotaxis, adhesion potential and invasion ability were assessed using chemotaxis, adhesion and invasiveness assays. Lipid raft isolation and western blot were used to determine the mechanism underlying the effects of CypA stimulation.Results. CD147 up-regulates the calcium-induced chemotaxis, adhesion ability and invasiveness of human neutrophils in RA patients. Transient receptor potential melastatin 7 may be responsible for this phenomenon.Conclusion. These findings suggest that in RA patients, abundant CypA up-regulates the calcium-induced chemotactic, adhesive and invasive properties of neutrophils via direct binding to CD147. Cyclophilin–CD147 interactions might contribute to the destruction of cartilage and bone in RA. [ABSTRACT FROM PUBLISHER]

Background and Objective Lipopolysaccharide ( LPS)-mediated signaling in host cells involves Toll-like receptor 4 ( TLR4) accessory molecules, including LPS-binding protein ( LBP), cluster of differentiation 14 ( CD14) and lymphocyte antigen 96 ( MD-2). However, expression of these innate defense molecules in various compartments of the human periodontium is unclear. The aim of this study was to investigate the expression profile of TLR4 in human gingiva. Material and Methods Human gingival biopsies were collected from healthy gingival or chronic periodontitis tissue. Primary gingival keratinocytes and fibroblasts were cultured. Immunohistochemical analysis for TLR4 was performed. Transcripts of TLR4, MD-2, CD14 and LBP, and their protein products, were examined using RT- PCR, immunoprecipitation and immunoblotting. The interactions between these molecules in keratinocytes and fibroblasts were investigated by co-immunoprecipitation. Results TLR4 immunoreactivity was found in healthy gingival epithelium and periodontitis tissue, and appeared to be lower in junctional epithelium ( p ≤ 0.01). Fibroblasts and inflammatory cells stained more strongly for TLR4 in diseased periodontal tissues ( p < 0.001). Three TLR4 splicing variants, two MD-2 splicing variants and one CD14 mRNA were expressed by gingival keratinocytes and fibroblasts. Expression of TLR4, CD14 and MD-2 proteins was detected in keratinocytes and fibroblasts in vitro. TLR4 protein from gingival keratinocytes and fibroblasts could be co-immunoprecipitated with CD14 or MD-2, suggesting an association between the related molecules in vivo. LBP transcript was detected in gingival biopsies, but not in primary cultures of gingival keratinocytes or fibroblasts. Conclusion TLR4, CD14 and MD-2, but not LBP, are expressed in human gingival keratinocytes and fibroblasts. The TLR4 expression level in the junctional epithelium appeared to be lowest within the periodontal epithelial barrier. [ABSTRACT FROM AUTHOR]

To elucidate the effects of maternal dietary betaine supplementation on hepatic expression of cholesterol metabolic genes in newborn piglets and the involved epigenetic mechanisms, we fed gestational sows with control or betaine-supplemented diets (3 g/kg) throughout pregnancy. Neonatal piglets born to betaine-supplemented sows had higher serum methionine concentration and hepatic content of betaine, which was associated with significantly up-regulated hepatic expression of glycine N-methyltransferase. Prenatal betaine exposure increased hepatic cholesterol content and modified the hepatic expression of cholesterol metabolic genes in neonatal piglets. Sterol regulatory element-binding protein 2 was down-regulated at both mRNA and protein levels, while 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) was down-regulated at the mRNA level, but up-regulated at the protein level, in betaine-exposed piglets. The transcriptional repression of HMGCR was associated with CpG island hypermethylation and higher repressive histone mark H3K27me3 (histone H3 lysine 27 trimethylation) on the promoter, whereas increased HMGCR protein content was associated with significantly decreased expression of miR-497. Furthermore, LDL receptor was significantly down-regulated at both mRNA and protein levels in the liver of betaine-exposed piglets, which was associated with promoter CpG hypermethylation. In addition, the expression of cholesterol-27α-hydroxylase (CYP27α1) was up-regulated at both mRNA and protein levels, while the expression of cholesterol-7α-hydroxylase (CYP7α1) was increased at the mRNA level, but unchanged at the protein level associated with increased expression of miR-181. These results indicate that maternal betaine supplementation increases hepatic cholesterol content in neonatal piglets through epigenetic regulations of cholesterol metabolic genes, which involve alterations in DNA and histone methylation and in the expression of microRNA targeting these genes. [ABSTRACT FROM PUBLISHER]

The article discusses a study which hypothesized that combined magnetic field (CMF) technology can enhance bone-tendon junction repair through endochondral ossification for regeneration of the fibrocartilage zone. Results show that the newly formed bone and regenerated fibrocartilage zone in the those treated with CMF increased by 99.2%. It concluded that CMF is associated with enhanced healing after bone-tendon junction injuries in a rabbit model.

Objective Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. Methods The effects of allogeneic umbilical cord-derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC-mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation. Results Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow-derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients. Conclusion We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients. [ABSTRACT FROM AUTHOR]

Objective To study the relationship between the human secreted protein stabilin-1−interacting chitinase-like protein (SI-CLP) and rheumatoid arthritis (RA). Methods The expression of SI-CLP in peripheral blood mononuclear cells (PBMCs) and synovial fluid from patients with RA and the effects of cytokines on SI-CLP expression were examined by Western blotting. Fluorescence-activated cell sorting analysis was performed to investigate the binding between SI-CLP and cells. Bone marrow-derived macrophages were isolated from wild-type and SI-CLP−/− mice, and real-time quantitative polymerase chain reaction was performed to detect the levels of messenger RNA for cytokines or SI-CLP in SI-CLP− or cytokine-treated macrophages. Histologic studies were conducted to evaluate inflammation and the expression of interleukin-12 (IL-12), IL-13, and SI-CLP in lesions. Enzyme-linked immunosorbent assays were used to detect the cytokine levels in bone marrow-derived macrophages. Rats or mice with collagen-induced arthritis (CIA) and SI-CLP−/− mice were used to study the function of SI-CLP in RA. Results SI-CLP expression was increased in PBMCs and detectable in synovial fluid from patients with RA. Administration of SI-CLP to rats with CIA aggravated arthritis-associated inflammation. SI-CLP was specifically attached to the surface protein of macrophages, which elevated the expression of IL-1β, IL-6, IL-12, and IL-13 in macrophages and mouse bone marrow-derived macrophages, up-regulating ERK phosphorylation. Moreover, SI-CLP was up-regulated by both IL-12 and IL-13 through JNK and JAK/STAT signaling, respectively. Knockout of SI-CLP resulted in a decrease in the expression of IL-1β, IL-6, IL-12, and IL-13 and lower susceptibility to CIA compared with wild-type mice. SI-CLP treatment also aggravated arthritis-related inflammation in wild-type and SI-CLP−/− mice. Conclusion SI-CLP functions as a regulator of the inflammatory response by macrophages. The decrease in inflammation-associated cytokine levels resulting from SI-CLP knockout may explain the lower susceptibility to CIA in SI-CLP−/− mice. [ABSTRACT FROM AUTHOR]

Background and Objective Glycosylated extracellular matrix metalloproteinase inducer ( EMMPRIN) is specifically associated with caveolin-1 and influences its ability to induce matrix metalloproteinases ( MMPs) production. This study investigated EMMPRIN glycosylation and caveolin-1 expression in healthy and inflamed human gingival tissues, analyzed the relationship between EMMPRIN glycosylation and caveolin-1 expression, and assessed how this interaction influenced MMP-1 production. Material and Methods Gingival tissues were collected from 10 healthy subjects and 15 chronic periodontitis ( chronic periodontitis) subjects. EMMPRIN, caveolin-1 and MMP-1 expressions were analyzed by immunohistochemistry. EMMPRIN and caveolin-1 co-localization was detected by immunofluorescence. EMMPRIN glycosylation, caveolin-1, active MMP-1 and pro MMP-1 expression was assessed by Western blot. Results EMMPRIN was expressed in gingival epithelial cells, inflammatory cells, endothelial and fibroblast-like cells. Strong caveolin-1 immunoreactivity was detected in gingival epithelial and endothelial cells. Double immunofluorescence studies revealed EMMPRIN and caveolin-1 co-localization in gingival epithelium, endothelial and fibroblast-like cells. Compared with healthy subjects, the chronic periodontitis group had increased high-glycoform EMMPRIN ( HG- EMMPRIN) and active MMP-1 expression ( p < 0.05). Active MMP-1 and pro MMP-1 protein levels were positively correlated with HG- EMMPRIN levels ( p < 0.05). Conclusion EMMPRIN and caveolin-1 colocalize in periodontal tissues. The increased active MMP-1 and pro MMP-1 production may be associated with elevated HG- EMMPRIN levels. [ABSTRACT FROM AUTHOR]