Blood cell count-derived inflammation indices as predictors of the osteoporotic risk of postmenopausal women.

OBJECTIVE: We investigated the associations between osteoporosis (OP) and systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in postmenopausal women. PATIENTS AND METHODS: This retrospective study included 966 postmenopausal women. Logistic regression and receiver operating characteristic curve (ROC) analyses were applied to explore the relationships between SII, NLR, MLR, and PLR with the bone mineral density (BMD) and risk of OP. RESULTS: Logistic regression analyses showed that SII, PLR, NLR, and MLR had independent negative associations with the OP risk. The ROC curve analysis showed that SII, NLR, and MLR predicted a low BMD, with NLR having the highest predictive value (area under the curve = 0.624). SII > 504.09, PLR > 131.87, NLR > 2.02, and MLR > 0.12 correlated with a particularly high OP risk. CONCLUSIONS: High levels of SII, PLR, NLR, and MLR were associated with a high OP risk. In particular, NLR > 2.02 strongly predicted the risk of OP, thereby representing a valuable and convenient inflammatory marker of the OP risk.

Serum CTRP3 concentrations are positively correlated with disease severity in women with postmenopausal osteoporosis: a population-based cross-sectional study.

OBJECTIVE: Osteoporosis is a leading public health problem that contributes to increasingly high rates of osteoporotic vertebral compression fractures among older adults. This study was developed with the goal of assessing serum C1q/TNF-related protein-3 (CTRP3) levels in postmenopausal osteoporosis (PMOP) patients and exploring the correlations between these levels and PMOP severity. PATIENTS AND METHODS: A population-based cross-sectional study of old women with osteoporosis was conducted. All women underwent both clinical and dual-energy X-ray absorptiometry examinations. Serum CTRP3, procollagen type I N propeptide (P1NP), and C-terminal telopeptide of type I collagen (CTX-1) concentrations in these patients were measured via ELISA. Bone tumor markers were additionally assessed. Receiver operating characteristic (ROC) analyses were utilized to assess the diagnostic performance of CTRP3 when identifying PMOP. RESULTS: This study included 54 PMOP patients, 62 patients with osteopenia, and 60 age-matched patients without PMOP. Serum CTRP3 concentrations in PMOP patients were significantly lower than in the other two groups. Bone mineral density (BMD) was positively correlated with serum CTRP3 levels in all study participants, whereas it was negatively correlated with levels of P1NP and CTX-1. ROC analyses also suggested that reductions in serum CTRP3 levels may offer value as a diagnostic indicator of PMOP. CONCLUSIONS: Present data highlight a close relationship between CTRP3 and PMOP, with lower serum CTRP3 levels being closely associated with BMD, such that they may represent a protective marker for PMOP.

Anion gap predicts the long-term neurological and cognitive outcomes of spontaneous intracerebral hemorrhage.

OBJECTIVE: To investigate whether anion gap (AG) can act as a potentially predictive biomarker in recoveries of neurological and cognitive functions. PATIENTS AND METHODS: A total of 89 patients with intracerebral hemorrhage (ICH) were recruited. Of these, 68 and 21 patients were categorized into screening cohort and validation cohort, respectively. In the screening cohort, patients were categorized into three groups, according to the serum AG levels at admission. We dynamically recorded AG levels. Neurological and cognitive functions were assessed using Glasgow coma scale (GCS), Glasgow outcome scale (GOS) and mini-mental state examination (MMSE) scale at different time points. Furthermore, in the validation cohort, 9 patients with increased AG level underwent interventions to rectify the electrolyte imbalance. RESULTS: In the screening cohort, statistical differences were observed for respiratory diseases (p=0.029) among the three groups. The number of patients in the ≥16 mmol/L group (59.3%) was higher than that in the other groups. The mean scores of GCS in the ≥16 mmol/L group were lower than those in the other groups. The AG levels at admission had significant associations with 180-day GOS (p=0.043) and 180-day MMSE (p=0.001). Among them, the mean scores of the 180-day GOS and 180-day MMSE were lower in the ≥16 mmol/L group than in the other groups. In the validation cohort, AG intervention promoted recoveries of neurological and cognitive functions when compared to those without AG interventions. CONCLUSIONS: AG is a potentially predictive biomarker for the long-term outcomes of ICH patients, and rectifying AG at admission improves the outcomes.

The tissue transglutaminase: a potential target regulating MDR in breast cancer.

OBJECTIVE: Multi-drug resistance (MDR) is the main obstacle influencing the anti-tumor effect in breast cancer. To date, no proper potential targets are found to overcome MDR. Here, tTG was explored to show whether it is a potential target to regulate MDR in breast cancer. MATERIALS AND METHODS: tTG was silenced by small interfere siRNA. After that, the mRNA level of CD44, CD24, LRP, MRP and MDR1 were detected by RT-PCR. The Western blot analysis was used to detect the expression of LRP, P-gp and MRP. In addition, the impact of tTG on cell apoptosis, as well as cell proliferation were observed. Finally, to evaluate the role of tTG in BALB/c nude mice, the growth of tumor was performed, and the immunohistochemistry analysis was used to observe the expression of LRP, P-gp and MRP in vivo. RESULTS: In MCF-7/ADR, Compared to MCF-7, tTG expression was highly increased. After silencing tTG, the mRNA level and the protein level of P-gp, MRP, LRP were both differently decreased. The mRNA level of CD44 and CD24 was also down-regulated after silencing tTG. In addition, the cell proliferation was significantly inhibited in the ADR + tTG siRNA+Adriamycin group (p<0.05), and the tumor growth was prevented in a time-dependent situation. Cell apoptosis was significantly strengthened in the ADR+tTG siRNA+Adriamycin group (p<0.05). In vivo, the growth of tumors was reduced after silencing tTG, and the LRP, P-gp and MRP expression were significantly down-regulated in ADR + tTG SiRNA +adriamycin group (p<0.05). CONCLUSIONS: It is concluded that the tTG may be a potential target regulating the MDR by regulating LRP, P-gp and MRP expression as well as the expression of CD44CD24 to improve the MDR in breast cancer.

LncRNA NEAT1 facilitates the progression of sepsis through up-regulating TSP-1 via sponging miR-370-3p.

OBJECTIVE: Sepsis is a systemic inflammatory disease. LncRNA NEAT1 has been reported to be up-regulated in sepsis patients. Nevertheless, the modulatory network of NEAT1 in sepsis remains to be revealed. PATIENTS AND METHODS: The abundance of long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1), miR-370-3p, and thrombospondin-1 (TSP-1) were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in sepsis patients and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Enzyme-linked immunosorbent assay (ELISA) was performed to examine the concentration of cytokines in RAW 264.7 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry assay, and Western blot assay were conducted to detect the proliferation and apoptosis of RAW 264.7 cells. Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay were conducted to confirm the combination between miR-370-3p and NEAT1 or TSP-1 in RAW 264.7 cells. RESULTS: The enrichment of NEAT1 was enhanced in sepsis patients and LPS-stimulated RAW 264.7 cells. NEAT1 contributed to LPS-induced inflammation and apoptosis of RAW 264.7 cells. MiR-370-3p bound to NEAT1, and it was negatively regulated by NEAT1 in RAW 264.7 cells. LPS promoted the inflammation and apoptosis while restrained the proliferation of RAW 264.7 cells via NEAT1/miR-370-3p axis. TSP-1 was a target of miR-370-3p in RAW 264.7 cells, and miR-370-3p suppressed the inflammation and apoptosis while it facilitated the proliferation of LPS-induced RAW 264.7 cells via TSP-1. CONCLUSIONS: LncRNA NEAT1 promoted the inflammation and apoptosis while restrained the proliferation of LPS-stimulated RAW 264.7 cells through the miR-370-3p/TSP-1 axis.

Long non-coding RNA FTX alleviates hypoxia/reoxygenation-induced cardiomyocyte injury via miR-410-3p/Fmr1 axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are involved in the development of myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the roles and underlying mechanisms of five prime to Xist (FTX) in myocardial I/R injury using cardiomyocyte hypoxia/reoxygenation (H/R) model. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine the expression of FTX, microRNA-410-3p (miR-410-3p) and fragile X mental retardation 1 (Fmr1) mRNA. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to evaluate cell proliferation and apoptosis, respectively. Western blot assay was conducted to examine the protein levels of apoptosis-associated factors and Fmr1. Specific kits were used to detect the levels of oxidative stress-associated factors. Dual-luciferase reporter assay was performed to verify the association between miR-410-3p and FTX or Fmr1. RESULTS: FTX was reduced in myocardial I/R injury patients' serum and H/R-stimulated H9c2 cells. FTX overexpression relieved cell damage caused by H/R treatment through inducing cell proliferation and repressing cell apoptosis and oxidative stress in H9c2 cells. FTX was a sponge for miR-410-3p and the impact of FTX overexpression on H/R-induced cell injury was abolished by miR-410-3p elevation in H9c2 cells. Fmr1 was identified as a target of miR-410-3p and Fmr1 knockdown reversed the effect on H/R-induced cell damage mediated by miR-410-3p inhibition in H9c2 cells. Moreover, FTX positively regulated Fmr1 expression through sponging miR-410-3p in H9c2 cells. CONCLUSIONS: FTX regulated H/R-induced cardiomyocyte damage by upregulating Fmr1 via sponging miR-410-3p.

Anatomical study of the anterior neurovascular interval approach to the elbow: observation of the neurovascular interval and relevant branches.

BACKGROUND: The aim of the study was to investigate the anatomy of the anterior nerve and artery of the elbow joint to provide reference on the relevant surgical approach to the elbow joint, and determine a simple better surgical approach for the treatment of part of the fractures of the elbow joint. MATERIALS AND METHODS: The upper extremities of 10 adult cadavers fixed by formaldehyde and perfused with red latex in the artery were observed to investigate the anatomic structure of the anterior approach to the elbow joint. From the clearance of the brachioradialis and pronator teres muscle to the approach of the neurovascular interval, we observed the states of the median nerve, the brachial, radial and ulnar arteries, and its branches through anatomical layers and measurement methods. RESULTS: Through the anterior neurovascular interval approach to the elbow, nerve and artery can be protected, and the anterior structures of the elbow, such as the ulna coronoid process, humeroulnar joint and trochlea of the humerus, can be exposed. CONCLUSIONS: This study demonstrates that the anterior anatomical structure of the elbow joint including the trochlea of the humerus, coronoid process of the ulna and the front capsule of the elbow can be exposed through the anterior neurovascular approach to the elbow.

SIRT3 retards intervertebral disc degeneration by anti-oxidative stress by activating the SIRT3/FOXO3/SOD2 signaling pathway.

OBJECTIVE: The objective of this paper is to determine whether SIRT3 could retard intervertebral disc degeneration and study the mechanism. MATERIALS AND METHODS: We chose the 3-month mice to establish intervertebral disc degeneration model and study the effect of SIRT3 on the intervertebral disc by Western blotting, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), immunohistochemistry. Mouse nucleus pulposus cells were cultured to study the exact mechanism. RESULTS: The expression of SIRT3 was decreased in degenerated human nucleus pulposus. Intervertebral discs of mice treated with theacrine expressed more collagen II and less collagen X. In addition, nucleus pulposus cells stimulated with interleukin-1ß (IL-1ß) expressed less SIRT3 than that in the control group and nucleus pulposus cells with SIRT3 overexpress vectors expressed more collagen II FOXO3a and superoxide dismutase 2 (SOD2), indicating that SIRT3 could improve the intervertebral disc degeneration by anti-oxidative stress. CONCLUSIONS: SIRT3 is a protective factor for intervertebral discs and can reduce oxidative stress in the intervertebral disc.

Effects of SIRT1/Akt pathway on chronic inflammatory response and lung function in patients with asthma.

OBJECTIVE: Asthma is the most common chronic airway inflammatory disease. Sirtuin 1 (SIRT1) exerts a crucial effect on regulating chronic inflammatory responses. Therefore, this study aims to explore the effect of SIRT1 on the pathogenesis of asthma. MATERIALS AND METHODS: Serum level of SIRT1 in asthma patients and healthy controls was detected by Western blot. Correlation between SIRT1 level and pulmonary function in asthma patients was analyzed. Subsequently, asthma model in mouse was established. Primary airway epithelial cells were extracted from asthma mice and control mice to detect SIRT1 level. Furthermore, relative levels of Akt and interleukin 6 (IL-6) were detected in 16HBE cells. Regulatory effects of Akt on SIRT1 in 16HBE cells were determined as well. RESULTS: SIRT1 was highly expressed in serum of asthma patients, which was negatively correlated with FEV1/FVC (r=-0.27, **p<0.01). Both mRNA and protein levels of SIRT1 were downregulated in primary airway epithelial cells extracted from asthma mice compared with those from controls. SIRT1 knockdown in 16HBE cells upregulated IL-6 expression, which was reversed by Akt inhibitors. CONCLUSIONS: SIRT1 regulates IL-6 level via Akt pathway, thereafter affecting pulmonary function in asthma patients.

Investigating and analyzing three cohorts of mushroom poisoning caused by Amanita exitialis in Yunnan, China.

Amanita exitialis is a lethal mushroom found in China. Knowledge regarding taxonomic characterization, toxin detection, general poisoning conditions, clinical manifestations, laboratory examinations, and clinical treatments for this species is currently lacking. We investigated three A. exitialis mushroom poisoning cohorts in Yunnan Province in 2014 and 2015, involving 10 patients. Mushroom samples were identified by morphological and molecular studies. Ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry was used to detect the peptide toxins in the mushroom samples. Epidemiological information, clinical data, and results of laboratory examinations were collected and analyzed. The mushroom samples were all identified as A. exitialis. The average toxin concentration decreased from the cap to the stipe to the volva, and the average concentration of the peptide toxins decreased in the order of α-amanitin > phallacidin > ß-amanitin > γ-amanitin. The latency period between ingestion and the onset of symptoms was 13.9 ± 2.1 h, and the time from ingestion to hospitalization was 49.6 ± 8.5 h. The most common symptoms were nausea and vomiting (100%). Four patients died from fulminant hepatic failure. Laboratory examinations showed that the alanine transaminase, aspartate transaminase, prothrombin time, and activated partial thromboplastin time levels peaked on the third day post-ingestion. Total bilirubin and direct bilirubin values peaked on day 7. The death group and the survival group had a similar variation trend of serological indexes, but the death group had a greater change. A. exitialis is an extremely dangerous mushroom and there is a need to educate the public to avoid picking and eating wild mushrooms that have not been definitively identified.

Effect of miR-212 targeting TCF7L2 on the proliferation and metastasis of cervical cancer.

OBJECTIVE: MicroRNAs (miRs) function as either oncogenes or tumor suppressors in the progression of various human cancers, including cervical cancer. This study aimed to explore the role of miR-212 in cervical cancer and the mechanisms underlying this role. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (RT-PCR) and Western blot assays were used to determine the expression levels of miR-212 and TCF7L2 in the cervical cancer cells. Cell proliferation invasion was examined using BrdU assays and transwell, respectively. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation. RESULTS: In our study, we demonstrated that miR-212 expression was significantly downregulated in cervical cancer tissues and cell lines. Moreover, the increased expression of miR-212 suppressed cell proliferation and invasion of cervical cancer cell lines in vitro. On the contrary, the decreased expression of miR-212 promoted cell proliferation and invasion of cervical cancer cell lines. Finally, the results of Western blot showed that overexpression of miR-212 dramatically suppressed the protein expression of TCF7L2. The knockdown of miR-212 showed the contrary effect. Luciferase reporter assay identified TCF7L2 as a novel direct target of miR-212. CONCLUSIONS: Our results revealed that miR-212 inhibited cervical cancer metastasis and progression by targeting TCF7L2 expression.

Parathyroid hormone(1-34) exhibits more comprehensive effects than celecoxib in cartilage metabolism and maintaining subchondral bone micro-architecture in meniscectomized guinea pigs.

OBJECTIVE: To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). METHOD: Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1-34) (24 µg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. CONCLUSIONS: Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture.

Prognostic significance of DLL4 expression in papillary thyroid cancer.

OBJECTIVE: Delta-like ligand 4 (DLL4)-Notch signaling has an important role in tumor neovascular development and angiogenesis during tumor growth. However, the clinical significance of DLL4 expression in papillary thyroid cancer remains unclear to date. PATIENTS AND METHODS: 207 papillary thyroid cancer patients were in the present study. DLL4 expression in papillary thyroid cancer was analyzed and evaluated immunohistochemically. The correlation between DLL4 and clinicopathological factors was also evaluated. RESULTS: DLL4 expression was showed in the cytoplasm of papillary thyroid cancer cells by immunohistochemical staining. DLL4 positivity in papillary thyroid cancer was found in 112 (54%) of the 207 papillary thyroid cancer patients. Papillary thyroid cancer DLL4 expression was significantly correlated with thyroid tumour invasion and metastasis. CONCLUSIONS: Overexpression of DLL4 is associated with thyroid tumour invasion and metastasis and it may be an effective target of anti-DLL4 treatment in papillary thyroid cancer.

Genetic polymorphism at the KIR gene locus: determination of gene, genotype, and haplotype frequencies in the Xinjiang Han population.

The aim of this study was to explore the genetic polymorphism, genotype, and haplotype characteristics of the KIR locus in the Xinjiang Han population in order to establish a foundation for future analysis of the relationship between KIR genes and disease. KIR genes were detected by sequence-specific primer-polymerase chain reaction in 184 randomly selected, healthy individuals from the Han population in Xinjiang, China. Standard genotype and haplotype analyses were conducted using Hsu's standards classified for analysis. Sixteen KIR genes were detected: 3DL3, 2DL4, 3DL2, and 3DL2 (100%); 2DL1 and 2DP1 (99.46%); 2DL3 (98.91%); and so on. The 2DS2 gene frequency was the lowest at 21.74%. Twenty-one genotypes were detected: AJ (2, 2) was relatively common (42.39%), followed by AH (5, 2), AE (2, 8) and H (2, 4), with frequencies of 17.39, 11.96, and 8.15%, respectively. In addition, six novel genotypes were identified in 11 Han individuals as well as in other populations in China, which could not be classified for analysis. These results indicated that the Xinjiang Han population shares KIR gene, genotype, and haplotype frequency distributions with the Chinese Han population, but also has unique genotypes and haplotypes.

Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats.

UNLABELLED: We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae. INTRODUCTION: The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats. METHODS: We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression. RESULTS: At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats. CONCLUSIONS: Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.

DNA barcoding of common soft scales (Hemiptera: Coccoidea: Coccidae) in China.

The soft scales (Hemiptera: Coccoidea: Coccidae) are a group of sap-sucking plant parasites, many of which are notorious agricultural pests. The quarantine and economic importance of soft scales necessitates rapid and reliable identification of these taxa. Nucleotide sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene (barcoding region) and 28S rDNA were generated from 340 individuals of 36 common soft scales in China. Distance-based [(best match, Automated Barcode Gap Discovery (ABGD)], tree-based (neighbor-joining, Bayesian inference), Klee diagrams, and general mixed Yule coalescent (GMYC) models were used to evaluate barcoding success rates in the data set. Best match showed that COI and 28S sequences could provide 100 and 95.52% correct identification, respectively. The average interspecific divergences were 19.81% for COI data and 20.38% for 28S data, and mean intraspecific divergences were 0.56 and 0.07%, respectively. For COI data, multiple methods (ABGD, Klee, and tree-based methods) resulted in general congruence with morphological identifications. However, GMYC analysis tended to provide more molecular operational taxonomic units (MOTUs). Twelve MOTUs derived from five morphospecies (Rhodococcus sariuoni, Pulvinaria vitis, Pulvinaria aurantii, Parasaissetia nigra, and Ceroplastes rubens) were observed using the GMYC approach. In addition, tree-based methods showed that 28S sequences could be used for species-level identification (except for Ceroplastes ceriferus - Ceroplastes pseudoceriferus), even with low genetic variation (<1%). This report demonstrates the robustness of DNA barcoding for species discrimination of soft scales with two molecular markers (COI and 28S) and provides a reliable barcode library and rapid diagnostic tool for common soft scales in China.

Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

Improved biological performance of magnesium by micro-arc oxidation

Magnesium and its alloys have recently been used in the development of lightweight, biodegradable implant materials. However, the corrosion properties of magnesium limit its clinical application. The purpose of this study was to comprehensively evaluate the degradation behavior and biomechanical properties of magnesium materials treated with micro-arc oxidation (MAO), which is a new promising surface treatment for developing corrosion resistance in magnesium, and to provide a theoretical basis for its further optimization and clinical application. The degradation behavior of MAO-treated magnesium was studied systematically by immersion and electrochemical tests, and its biomechanical performance when exposed to simulated body fluids was evaluated by tensile tests. In addition, the cell toxicity of MAO-treated magnesium samples during the corrosion process was evaluated, and its biocompatibility was investigated under in vivo conditions. The results of this study showed that the oxide coating layers could elevate the corrosion potential of magnesium and reduce its degradation rate. In addition, the MAO-coated sample showed no cytotoxicity and more new bone was formed around it during in vivo degradation. MAO treatment could effectively enhance the corrosion resistance of the magnesium specimen and help to keep its original mechanical properties. The MAO-coated magnesium material had good cytocompatibility and biocompatibility. This technique has an advantage for developing novel implant materials and may potentially be used for future clinical applications.

Detection of Wolbachia genes in a patient with non-Hodgkin's lymphoma.

Wolbachia 16S rRNA and fbpA genes were twice detected over 5 days in the blood of a patient with high fever. The patient was given fluoroquinolones and the fever resolved. Four weeks later, he was diagnosed with non-Hodgkin's lymphoma and received R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) treatment resulting in complete remission. This is the first report of detection of Wolbachia genes from the blood of human patients with non-Hodgkin's lymphoma.

Parathyroid hormone (1-34) prevents cartilage degradation and preserves subchondral bone micro-architecture in guinea pigs with spontaneous osteoarthritis.

OBJECTIVE: To assess whether parathyroid hormone (PTH) (1-34) could improve the micro-structure of subchondral bone, and retard cartilage degradation in a naturally occurring Osteoarthritis (OA) model. DESIGN: Forty-eight 1-month-old guinea pigs were divided into two groups: 32 were treated by normal saline (NS) and sacrificed at 1, 3, 6 and 9 months of age; the other 16 received PTH (1-34) from 3 months, and were sacrificed at 6 and 9 months. Masson staining and the Osteoarthritis Research Society International (OARSI) grade scores were used to assess cartilage degradation. Immunohistochemistry analyses of type-II collagen, matrix metalloproteinases-13 (MMP-13) and sclerostin (SOST) in the cartilage, osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) and PTH receptor (PTH1R) in the cartilage and subchondral bone were performed. Subchondral bone micro-architecture was assessed by micro-computed tomography (micro-CT). RESULTS: Histological analyses revealed OA occurred at 3 months of age and was more severe with increasing age, and PTH (1-34) reduced the OARSI scores at 6 and 9 months of age. Micro-CT analysis indicated that PTH (1-34) treatment increased the bone volume ratio and bone mineral density (BMD), while retarding the subchondral trabecular bone micro-architectural changes from rod-like to plate-like. Immunohistochemical staining demonstrated that PTH (1-34) treatment increased type-II collagen expression and decreased SOST and MMP-13 expression in the cartilage, while elevating the PTH1R, OPG/RANKL expression ratio in the cartilage and subchondral trabecular bone when compared with the control groups. CONCLUSIONS: PTH (1-34) can prevent cartilage damage progression and retard the deterioration of subchondral trabecular bone in guinea pigs.