MiR-424 Inhibits neuronal apoptosis in rats with cerebral infarction through regulating TGF-ß1/Smad3 signaling pathway.

It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-ß (TGF-ß) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-ß1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-ß1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO.

Associations of depression with impaired glucose regulation, newly diagnosed diabetes and previously diagnosed diabetes in Chinese adults.

AIM: To examine the association between depression and impaired glucose regulation, newly diagnosed diabetes and previously diagnosed diabetes in middle-aged and elderly Chinese people, and whether depression was associated with different treatment regimens or durations of diabetes. METHODS: A cross-sectional study was performed among 229,047 adults living in the community aged ≥ 40 years from 25 centres in China. The self-reported depression rating scale Patient Health Questionnaire 9 (PHQ-9) was used to diagnose probable and sub-threshold depression. Glucose metabolism status was determined according to World Health Organization 1999 diagnostic criteria. RESULTS: The numbers of participants with normal glucose regulation, impaired glucose regulation, newly diagnosed diabetes and previously diagnosed diabetes were 120,458, 59,512, 24,826 and 24,251, respectively. The prevalence of sub-threshold depression in the total sample of participants was 4.8% (4.8%, 4.8%, 4.4% and 5.6% from normal glucose regulation to previously diagnosed diabetes, respectively), and the prevalence of probable depression was 1.1% (1.1%, 1.0%, 0.9% and 1.8% from normal glucose regulation to previously diagnosed diabetes, respectively). Compared with participants with normal glucose regulation, those with previously diagnosed diabetes had increased odds of probable depression [odds ratio (OR) = 1.61, 95% confidence interval (CI) 1.39-1.87] and sub-threshold depression (OR = 1.14, 95% CI 1.06-1.24), after adjustment for multiple confounding factors. Newly diagnosed diabetes or impaired glucose regulation was not associated with depression. Among those with previously diagnosed diabetes, insulin treatment was associated with greater odds of depression compared with no treatment or oral anti-diabetic medicine. CONCLUSION: Previously diagnosed diabetes, but not newly diagnosed diabetes or impaired glucose regulation, was associated with a higher prevalence of depression. Patients receiving insulin were more likely to have depression than those not receiving treatment or being treated with oral anti-diabetic medicine.

Unsteady aerodynamic analysis for offshore floating wind turbines under different wind conditions.

A free-vortex wake (FVW) model is developed in this paper to analyse the unsteady aerodynamic performance of offshore floating wind turbines. A time-marching algorithm of third-order accuracy is applied in the FVW model. Owing to the complex floating platform motions, the blade inflow conditions and the positions of initial points of vortex filaments, which are different from the fixed wind turbine, are modified in the implemented model. A three-dimensional rotational effect model and a dynamic stall model are coupled into the FVW model to improve the aerodynamic performance prediction in the unsteady conditions. The effects of floating platform motions in the simulation model are validated by comparison between calculation and experiment for a small-scale rigid test wind turbine coupled with a floating tension leg platform (TLP). The dynamic inflow effect carried by the FVW method itself is confirmed and the results agree well with the experimental data of a pitching transient on another test turbine. Also, the flapping moment at the blade root in yaw on the same test turbine is calculated and compares well with the experimental data. Then, the aerodynamic performance is simulated in a yawed condition of steady wind and in an unyawed condition of turbulent wind, respectively, for a large-scale wind turbine coupled with the floating TLP motions, demonstrating obvious differences in rotor performance and blade loading from the fixed wind turbine. The non-dimensional magnitudes of loading changes due to the floating platform motions decrease from the blade root to the blade tip.

[Linear correlation between tooth movement and facial profile change in patients with class â ¡ division 1 malocclusion].

Objective: To investigate the correlation between tooth movement and profile change in patients with class Ⅱ division 1 malocclusion. Methods: Pre- and post-treatment lateral cephalograms of 42 patients [10 males and 32 females, (23.8±6.3) years old, mean treatment time: 1.9 years] with class Ⅱ division 1 malocclusion were collected in Department of Oral & Cranio-Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from June 2012 to November 2017. The patients were treated with extraction of four first premolars or two maxillary first premolars. Cephalometric analysis was carried out before and after treatment. Thirty parameters were measured. The changes of soft and hard tissue after orthodontic treatment and their correlations were analyzed using bivariate linear regression. Related factors affecting the upper and lower lip, nasolabial angle (NLA) and mentolabial angle (MLA) were analyzed according to the standardized regression coefficient (Beta). Results: Among all the 30 parameters, 18 parameters were statistically different before and after treatment. After treatment, upper central incisor sagittal distance [(63.87±7.14) mm] and upper lip sagittal distance [(77.73±7.60) mm] were significantly decreased (P<0.05). The changes in 14 parameters after treatment showed linear relationship including strong positive correlation between upper lip sagittal retraction and upper central incisor sagittal retraction (r=0.649, P<0.01). There were moderate positive correlations between upper lip and upper central incisor vertical movement (r=0.544, P<0.01). While the sagittal change of gnathion and the Y-axis angle showed moderate negative correlations (r=0.537, P<0.01). The stepwise multiple linear regression showed that the retraction of upper lip process was correlated with the retraction of upper central incisor, the increase of occlusal plane angle and the increase of upper central incisor angle, which was most correlated with the retraction of upper central incisor (Beta=0.79). The downward displacement of upper lip process was correlated with the downward displacement of upper incisor, the decrease of upper central incisor angle, the decrease of the distance between maxillary first molar and palatal plane, and the increase of occlusal plane angle, which was more correlated with the downward displacement of upper incisor and the increase of occlusal plane angle (Beta=0.59). The downward displacement of lower lip process was correlated with the downward displacement of upper incisor and lower incisor, which was more correlated with the upper incisor (Beta=0.36). Conclusions: The relationship among nose, lips and chin was more coordinated. Incisor retraction had significant influence on lip prominence, and the lower lip position was highly related to the movement of upper incisor in sagittal and vertical dimension after orthodontic treatment in patients with class Ⅱ division 1 malocclusion. However, tooth movement had limited impact on the chin position.

Relationships between three potentiation effects of plyometric training and performance.

UNLABELLED: This study measured the potentiation effects of plyometric training [normalized electromyography (EMG) in triceps surae, stiffness and elastic energy utilization of the Achilles tendon] and investigated the correlations between these effects and performances [voluntary electromechanical delay (EMD) and jump height]. Twenty-one subjects were randomly assigned either to the control group (10 subjects: age 22.3+/-1.6 years) or to a training group (11 subjects: age 22.1+/-1.6 years) that performed 8 weeks of plyometric training. RESULTS: As compared with the performances before training, normalized EMG in the soleus were significantly (P

Allium vegetables and reduced risk of stomach cancer.

Interviews with 564 patients with stomach cancer and 1,131 controls in an area of China where gastric cancer rates are high revealed a significant reduction in gastric cancer risk with increasing consumption of allium vegetables. Persons in the highest quartile of intake experienced only 40% of the risk of those in the lowest. Protective effects were seen for garlic, onions, and other allium foods. Although additional research is needed before etiologic inferences can be made, the findings are consistent with recent reports of tumor inhibition following administration of allium compounds in experimental animals.

Diet and high risk of stomach cancer in Shandong, China.

A case-control investigation involving interviews with 564 stomach cancer patients and 1131 population-based controls was conducted to evaluate reasons for the exceptionally high rates of stomach cancer in Linqu, a rural county in Shandong Province in northeast China. Daily consumption of sour pancakes, a fermented indigenous staple, was associated with a 30% increase in risk. Risks of stomach cancer were also increased by 2- to 3-fold among persons with prior chronic gastritis or gastric ulcer, by 80% among those with stomach cancer in a family member, by 50% among men who smoked one or more packs of cigarettes/day, by 40% among those who preferred salty foods, and by 50% among families with moldy grain supplies. In contrast, risks tended to decrease in proportion to increasing consumption of fresh vegetables and fruits. This protective effect was more pronounced for vegetables, with those in the highest quartile of intake at less than one-half the risk of those in the lowest. Stomach cancer risks also declined with increasing dietary intake of carotene, vitamin C, and calcium, but not retinol. These findings provide leads to dietary factors that contribute to the high rates in Linqu, where stomach cancer is the leading cause of cancer and has not yet begun to decline as in other parts of the world.

Pre-thymic transcription of TCR genes by adult murine bone marrow cells.

In the adult mouse, the earliest thymocytes are derived from bone marrow-resident T lymphocyte precursor (pre-T) cells that immigrate to the thymus. There they undergo maturation through a series of developmental steps that include rearrangement and expression of the TCR genes, positive and negative selection, and functional maturation. Although these intrathymic processes have been extensively characterized, little is known about the T cell-specific events that take place in the bone marrow microenvironment. Of particular interest are the events surrounding transcription and rearrangement of the various TCR chains that are required for functional TCR expression. We have previously reported the transcription of incompletely rearranged TCR beta genes in pre-T cell-containing fractions of adult bone marrow. Here we demonstrate that the TCR gamma chain genes are also transcriptionally active in these cells. Like the TCR beta transcripts, TCR gamma transcripts are sterile, originating from unrearranged gamma loci. Interestingly, both RAG-1 and RAG-2 transcripts were also detected in this cell fraction, suggesting that sterile TCR transcription might be dependent upon the presence of a functional recombinase system. However, both C beta and C gamma sterile transcripts could be detected from the same bone marrow cell population isolated from RAG-1 gene deficient mice. Therefore, the expression of TCR genes can initiate at the earliest stages of T cell development, prior to exposure to the thymic microenvironment, and a functional recombinase system is not required for the production of these sterile TCR transcripts.

Interleukin 7 induces TCR gene rearrangement in adult marrow-resident murine precursor T cells.

Rearrangement of the T cell antigen receptor genes is a complex, highly regulated process. To gain a better understanding of the extracellular factors involved in the regulation of TCR beta and gamma gene rearrangement in adult murine bone marrow-resident precursor T cells, several cytokines were tested for their ability to induce gene recombination. A selected population of C58/J bone marrow cells (Thy 1(low), CD3, CD8, B220) that is enriched for pre-T cell activity was propagated in vitro in medium supplemented with IL-3 and mast cell growth factor (MGF, also referred to as stem cell factor, Steele factor and c-kit ligand). These cytokines were required for the maintenance of pre-T cell activity in culture, but had no effect on TCR gene expression. Several additional cytokines were added to the culture medium. Of all those tested, only IL-7 induced complete rearrangement of the TCR gamma locus. Complete rearrangement of the TCR beta locus was not induced under any of the culture conditions analysed here. The bone marrow cells cultured in IL-3, MGF and IL-7 did not begin to express mature T cell proteins and maintained their in vivo progenitor potential. Furthermore, IL-7 cultured bone marrow cells were capable of differentiation in vivo into all phenotypic subpopulations of T cells, without an apparent bias toward the gammadelta lineage. The data presented here suggest that TCR gamma gene rearrangement in adult pre-T cells is regulated by IL-7, but that the TCR beta locus requires additional or alternative signals for the induction of complete rearrangement.

Changes in Concentration and Distribution of Biomarkers in Biodegraded Oils from Dongying Depression, China.

The alkane fraction of 11 biodegraded oils and five non-biodegraded oils from the Dongying Depression, Bohai Bay Basin, eastern China, were analyzed by gas chromatography-mass spectrometry to investigate the biomarker alteration caused by biodegradation. Results indicated that the concentration of 25-norhopanes was correlated with increased biodegradation. The oil samples showed an increase in the C31 and C32 hopane 22S/(22S + 22R), C29 sterane C2920S/(20S + 20R), and C29ßß/(ßß + αα) thermal maturity parameters in the heavily biodegraded oils. Oleanane was preferentially biodegraded compared with C3017α-hopane, which was preferentially biodegraded compared with C2917α, 21ß-norhopane, C30 moretane, and C29 25-norhopane. The selective depletion of C27-C29 steranes followed the order ααα 20R > ααα 20S + αßß 20R > αßß 20S and C27 > C29 > C28, and the diasteranes and C20-C21 steranes were much more resistant to biodegradation than regular C27-C29 steranes. The steranes were generally preferentially biodegraded compared with the hopanes in this study.

EURO-MUSCULUS/USPRM Basic Scanning Protocols for shoulder.

In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned shoulder structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers.

EURO-MUSCULUS/USPRM Basic Scanning Protocols for elbow.

In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned elbow structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers.

EURO-MUSCULUS/USPRM. Basic Scanning Protocols for Ankle and foot.

In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned ankle/foot structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers.

EURO-MUSCULUS/USPRM. Basic scanning protocols for knee.

In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned knee structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers.

EURO-MUSCULUS/USPRM. Basic scanning protocols for hip.

In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned hip structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers.

In vitro cellular tropism of human T cell leukemia virus type 2.

Human T cell leukemia virus type 1 (HTLV-1) and 2 (HTLV-2) are distinct oncogenic retroviruses that infect several cell types, but display their biologic/pathogenic activity only in T lymphocytes. HTLV-1 is associated with adult T cell leukemia, a malignancy of mature CD4(+) T cells, and a chronic neurological disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 is less pathogenic and has been associated with a few cases of a variant of hairy cell leukemia and neurological disease. Previous studies have indicated that in vivo HTLV-1 has a preferential tropism for CD4(+) T cells, whereas HTLV-2 in vivo tropism is less clear, but appears to favor CD8(+) T cells. The molecular mechanism that determines the cellular tropism of HTLV-1 and HTLV-2 has not been precisely determined. However, one study by our group has provided evidence that HTLV-1-enhanced viral transcription in CD4(+) T cells may be responsible for its tropism. In an effort to understand HTLV-2 tropism we tested the ability of HTLV-2 to infect, replicate in, and transform purified CD4(+) or CD8(+) T cells in cell culture. After cocultures of purified primary human CD4(+) and CD8(+) T cells with an HTLV-2-producer cell line we measured viral transcription by reverse transcription PCR analysis, virus production by p19(gag) ELISA, proviral integration by DNA slot-blot analysis, surface phenotype by FACS analysis, and cellular transformation. We also measured HTLV-2 long terminal repeat-directed transcription in the presence and absence of Tax in purified CD4(+) and CD8(+) T cells, using transient transfection assays. Our data indicate that CD4(+) and CD8(+) T cells are equally susceptible to HTLV-2 infection. We observed no significant difference in viral transcription based on mRNA and virus production in CD4(+) and CD8(+) T cell cocultures. Although LTR transcription was enhanced 12- to 16-fold in the presence of Tax, there was no significant difference in CD4(+) or CD8(+) T cells. Interestingly, we show that HTLV-2 preferentially transforms CD8(+) T cells in culture. Together, our data indicate that, unlike HTLV-1, HTLV-2 cell tropism is not due to inhibition of viral infection and inefficient gene expression in CD4(+) versus CD8(+) T cells, and likely involves unique interactions with viral and CD8(+) T cell-specific proteins.

Purification of polymers used for fabrication of an immunoisolation barrier.

A multistep extraction procedure has been tested for purification of natural and semi-synthetic polymers used for fabrication of an immunoisolation barrier for implanting animal cells. This procedure, originally described by Klock et al. for alginates, has been adapted for other gelling polymers to remove pyrogens (endotoxins) and mitogens. Several other steps have also been tested, resulting in a new and simple procedure for polymer purification, giving satisfactory levels of contamination. Endotoxin levels have been quantified by means of chromogenic and gelclot LAL methods. A simple calculation of the endotoxin permissible levels shows that the quality of purified polymers exceeds FDA specifications for implantable polymers.

Permeability assessment of capsules for islet transplantation.

Despite considerable progress in the development of immunoisolation devices, the optimal permeability of such devices is not known. This limitation stems partly from deficits in knowledge about which molecules should be allowed to traverse the semipermeable membrane and which molecules should be excluded, and also partly from experimental obstacles that have prevented a systematic study of permeability. To determine the optimal permeability of immunoisolation devices, we have created a series of microcapsules (800 microM diameter) that span a broad range of molecular exclusion limits yet are identical in wall thickness and chemical composition. Capsule permeability was precisely defined by two complementary methods--size exclusion chromatography (SEC) and a newly developed methodology to assess permeability of biologically relevant proteins. The entry of interleukin-1 beta-125I was significantly delayed, but not prevented, when the capsule exclusion limit was decreased from 230 kD to 3.2 kD, as determined by SEC with dextran standards. The influx of IgG was as predicted, based on the viscosity radius R eta of IgG and the capsule exclusion limit defined by SEC. Glucose-stimulated insulin secretion by encapsulated pancreatic islets did not differ as capsule permeability was decreased from a molecular exclusion limit of 230 kD to 120 kD. These studies should assist in the design of immunoisolation devices by defining the permeability optimal for cell function and also should be applicable to any cell type or immunoisolation device.

Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra.

Cyclooxygenases (COX), key enzymes in prostanoid biosynthesis, may represent important therapeutic targets in various neurodegenerative diseases. In the present study, we explored the role of COX in Parkinson's disease (PD) by using 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine (MPTP) as a tool to create a rodent Parkinsonian model. MPTP (20 mg/kg, subcutaneously) was injected daily into COX-1- and COX-2-deficient mice and wild-type (WT) controls for five consecutive days. Immunocytochemical analysis of tissues collected 7 days after the final MPTP treatment showed that MPTP significantly decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNc) of WT (40% decrease) and COX-1(-/-) (45% decrease) mutants. However, a much smaller loss of TH-ir neurons in COX-2(-/-) mutants (20% decrease) was observed. Furthermore, electrochemical analysis revealed a more than 70% decrease in the levels of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the striatum of the WT control COX-1(-/-) and COX-2(-/-) mutant mice. These results indicate that loss of COX-2 activity reduces MPTP-induced damage to the dopaminergic neurons of the SNc, but does not alter the levels of dopamine and its metabolites in the striatum. Interestingly, MPTP caused the same degree of loss of dopaminergic neurons in both COX-2(+/-) and COX-2(-/-) mice (20% loss). The results of this study indicate an important role of COX-2 in MPTP-induced neuronal degeneration and suggest the possibility that manipulation of the COX-2 could be an important target for therapeutic interventions in PD.

[General introduction to the clinical application of non-invasive respiratory aids].

Intermittent positive pressure ventilation via tracheostomy has been the most common method of providing ventilatory support for patients with respiratory failure since the late 1950s. It is the standard procedure for individuals who suffer from acute respiratory failure, impaired consciousness, and severe restrictive lung disease. However, numerous adverse complications from these invasive techniques have been reported in those who are long-term ventilator users. This paper describes the evolution and current application of non-invasive respiratory aids in both acute and long-term settings. The respiratory function can be aided by applying forces to the body or intermittent pressure to the air ways. The devices are negative pressure body ventilators which act on the body by creating negative pressure around the thorax and abdomen such devices effectively maintain the ventilation of individuals with respiratory failure, but have the shortcomings of bulkiness, high expense, and limitation on the users' activities. The non-invasive positive pressure ventilator applies intermittent pressure directly to the airway by a non-invasive interface; namely mouthpiece, nasal, or face masks. In this way, it can prevent patients from requiring either tracheostomy or endotracheal tube, but is not effective enough to ventilate patients with markedly decreased lung compliance because the high airway resistance provides air leakage from the non-invasive interface. Non-invasive respiratory aids should be the first choice to maintain ventilation for patients with respiratory failure secondary to neuromuscular disorder, because of their benefits of easy application, satisfactory results, fewer complications and early active rehabilitation. Increased understanding of non-invasive respiratory aids should assist in the management of patients with chronic respiratory failure.