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Researchers in our laboratory have previously shown that ghrelin, a gastric peptide hormone, may regulate mesenchymal cell differentiation into adipocytes and myocytes. Here we show that ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defects in rats. Rats with a 9 mm full-thickness calvarial bone defect received either Bio-Oss ® (control group) or Bio-Oss ® mixed with 20 μg ghrelin (treatment group), followed by local administration of saline ordoi:10.1113/expphysiol.2007.041962 pmid:18562476 fatcat:mvxnp7cbkrea3gib4brzagr5iq
more »... hrelin (10 μg), respectively, on days 5, 10 and 15. After 6 and 12 weeks, new bone formation was assessed. Animals treated with ghrelin showed a significant increase in new bone formation as demonstrated by an increment in bone mineral density and fluorescence labelling of tetracycline relative to the control group. At 6 weeks, bone mineral density increased from 54 ± 7 (control group) to 78 ± 9 mg cm −2 in the treatment group, while the tetracycline fluorescence labelling increased by 61 ± 15%. A similar increment was observed at 12 weeks. Quantitative reverse transcriptase-polymerase chain reaction showed that expression of alkaline phosphatase (ALP), osteocalcin and collagen type I was elevated. Relative to the control animals, mRNAs for ALP, osteocalcin and collagen type I increased 2.4 ± 0.4-, 4.7 ± 1.9-and 4.0 ± 1.7-fold, respectively, in animals treated with ghrelin for 6 weeks (P < 0.05). At 12 weeks, mRNA levels of ALP, osteocalcin and collagen type I showed a decline relative to levels at 6 weeks but still remained significantly higher than in the control group, with fold changes of 2.4 ± 0.8, 2.4 ± 1.2 and 2.1 ± 0.7, respectively (P < 0.05). This study demonstrated that ghrelin stimulates intramembranous osteogenesis.
To conduct the clinical, genetic and molecular characterization of 494 Han Chinese subjects with Tic disorders (TD). In this study, we performed the mutational analysis of 22 mitochondrial tRNA genes in a large cohort of 494 Han Chinese subjects with TD via Sanger sequencing. These variants were then assessed for their pathogenic potential via phylogenetic, functional, and structural analyses. A total of 73 tRNA gene variants (49 known and 24 novel) on 22 tRNA genes were identified. Amongdoi:10.1042/bsr20201856 pmid:33289513 pmcid:PMC7755120 fatcat:wjp2l56r7vf4vd3cjdtvyrihgy
more »... 18 tRNA variants that were absent or present in <1% of 485 Chinese control patient samples were localized to highly conserved nucleotides, or changed the modified nucleotides, and had the potential structural to alter tRNA structure and function. These variants were thus considered to be TD-associated mutations. In total, 25 subjects carried one of these 18 putative TD-associated tRNA variants with the total prevalence of 4.96%. The phenotypic variability and incomplete penetrance of tic disorders in pedigrees carrying these tRNA mutations suggested the involvement of modifier factors, such as nuclear encoded genes associated mitochondrion, mitochondrial haplotypes, epigenetic and environmental factors. Our data provide the evidence that mitochondrial tRNA mutations are the important causes of tic disorders among Chinese population. These findings also advance current understanding regarding the clinical relevance of tRNA mutations, and will guide future studies aimed at elucidating the pathophysiology of maternal tic disorders.
Allergic diseases, such as asthma and allergic rhinitis, are common. Therefore, the discovery of therapeutic drugs for these conditions is essential. Methyleugenol (ME) is a natural compound with antiallergic, antianaphylactic, antinociceptive, and anti-inflammatory effects. This study examined the antiallergic effect of ME on IgE-mediated inflammatory responses and its antiallergy mechanism in the mast cell line, RBL-2H3. We found that ME significantly inhibited the release ofβ-hexosaminidase,doi:10.1155/2015/463530 pmid:25960618 pmcid:PMC4415531 fatcat:4pwxqxctrfhc5ivxc5ejipsea4
more »... tumor necrosis factor- (TNF-)α, and interleukin- (IL-) 4, and was not cytotoxic at the tested concentrations (0–100 μM). Additionally, ME markedly reduced the production of the proinflammatory lipid mediators prostaglandin E2(PGE2), prostaglandin D2(PGD2), leukotriene B4(LTB4), and leukotriene C4(LTC4). We further evaluated the effect of ME on the early stages of the FcεRI cascade. ME significantly inhibited Syk phosphorylation and expression but had no effect on Lyn. Furthermore, it suppressed ERK1/2, p38, and JNK phosphorylation, which is implicated in proinflammatory cytokine expression. ME also decreased cytosolic phospholipase A2(cPLA2) and 5-lipoxygenase (5-LO) phosphorylation and cyclooxygenase-2 (COX-2) expression. These results suggest that ME inhibits allergic response by suppressing the activation of Syk, ERK1/2, p38, JNK, cPLA2, and 5-LO. Furthermore, the strong inhibition of COX-2 expression may also contribute to the antiallergic action of ME. Our study provides further information about the biological functions of ME.
Authors' Contributions Xiao Ling and Yuqiang Xiang contributed equally to this work. ...doi:10.1155/2017/7146813 pmid:28947910 pmcid:PMC5602493 fatcat:wkdc4gecxzhljnwkoli3zc5puq
Radiotherapy, one of the clinical treatments of cancer, is accompanied by a high risk of damage to healthy tissues, such as bone loss and increased risk of fractures. The aim of the present study was to establish a rat model of local and systemic bone injury by focal irradiation, in order to study the etiological mechanism and intervention. The proximal metaphyseal region of the left hindlimb of male Sprague‑Dawley rats were exposed to a single 2 Gy or three 8 Gy doses delivered on days 1, 3doi:10.3892/ijmm.2019.4369 pmid:31638191 pmcid:PMC6844641 fatcat:5yidpu3vqnc2jc3lsqtbnlaydi
more »... 5 using a small animal irradiator, the changes in bone volume and microarchitecture were evaluated, and the mineral apposition rate (MAR) was assessed. Furthermore, bone marrow‑derived macrophages (BMMs) were isolated and induced to osteoclasts. It has been demonstrated that a single dose of 2 Gy may result in a significant loss of lumbar bone density at 3 days post‑irradiation, however this is restored at 30 days post‑irradiation. In the 3x8 Gy irradiation rat model, there was a rapid decrease in the aBMD of lumbar spine at 3 days and at 7 days post‑irradiation, and the aBMD decline persisted even at 60 days post‑irradiation. In addition, microCT analysis revealed a persistent decline in bone volume and damage in microarchitecture in the 3x8 Gy irradiation model, accompanied by a decrease in MAR, index of the decline in bone‑forming ability. In the cellular mechanism, a single 2 Gy local irradiation mainly manifested as an enhancement of the BMMs osteoclastogenesis potential, which was different from the osteoclastogenesis inhibition after high‑dose focal irradiation (3x8 Gy). In summary, the irradiation with simulated clinical focal fractionated radiotherapy exerts short‑ and long‑term systemic injury on bone tissue, characterized by different osteoclastogenesis potential between the high dose mode and a single 2 Gy focal irradiation. Physicians must consider the irreversibility of bone damage in clinical radiotherapy.
Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well established that STC is mostly caused by disorders of relevant nerves, especially the enteric nervous system (ENS). Colonic electrical stimulation (CES) has been regarded as a valuable alternative for the treatment of STC. However, little report focuses on the underlying nervous mechanism to normalize the delayed colonic emptying anddoi:10.1042/bsr20182405 pmid:31064818 pmcid:PMC6522827 fatcat:h7nnd3f6n5gzfknx5ppfxejj2m
more »... elieve symptoms. In the present study, the therapeutic effect and the influence on ENS triggered by CES were investigated in STC beagles. The STC beagle model was established by oral administration of diphenoxylate/atropine and alosetron. Histopathology, electron microscopy, immunohistochemistry, Western blot analysis and immunofluorescence were used to evaluate the influence of pulse train CES on myenteric plexus neurons. After 5 weeks of treatment, CES could enhance the colonic electromyogram (EMG) signal to promote colonic motility, thereby improving the colonic content emptying of STC beagles. HE staining and transmission electron microscopy confirmed that CES could regenerate ganglia and synaptic vesicles in the myenteric plexus. Immunohistochemical staining showed that synaptophysin (SYP), protein gene product 9.5 (PGP9.5), cathepsin D (CAD) and S-100B in the colonic intramuscular layer were up-regulated by CES. Western blot analysis and immunofluorescence further proved that CES induced the protein expression of SYP and PGP9.5. Taken together, pulse train CES could induce the regeneration of myenteric plexus neurons, thereby promoting the colonic motility in STC beagles.
Author Contributions Jingen Hu, Yang Lu, Ling Cai, Kwabena Gyabaah Owusu-Ansah, Gewen Xu, Feilong Han, Junjie Bao, collected the patient's data and drafted the manuscript. ...doi:10.1038/s41598-017-02497-3 pmid:28539658 pmcid:PMC5443820 fatcat:lwbwms5vrreetf7j2zrvrhb7lm
Sauce-flavor baijiu is a popular Chinese baijiu. To avoid adulteration and market cheating, this study aims to develop a new, reliable, and accurate traceability system for characterization of the geographical origins. Totally, 100 samples collected from seven regions in Guizhou Province of China are analyzed, involving 13 trace elements, 5 organic acids, and stable carbon isotope composition of acetic acid. Based on these data, a geographical classification model is established. The origindoi:10.1155/2019/7525201 fatcat:dad4hy6udvht3hvksxb3rnv4su
more »... racy is found to reach as high as 83%, thus providing a useful technique for authentication of the sauce-flavor baijiu and contributing to the healthy development of the baijiu industry in China.
Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A3 G mutation in mitochondrial tRNA Met . The m.4435A3 G mutation affected a highly conserved adenosine at position 37, 3 adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition anddoi:10.1074/jbc.ra117.000317 pmid:29222331 fatcat:ebdwfh6v3bgjngvevp3eiclspe
more »... We hypothesized that the m.4435A3 G mutation introduced an m 1 G37 modification of tRNA Met , altering its structure and function. Primer extension and methylation activity assays indeed confirmed that the m.4435A3 G mutation created a tRNA methyltransferase 5 (TRMT5)-catalyzed m 1 G37 modification of tRNA Met . We found that this mutation altered the tRNA Met structure, indicated by an increased melting temperature and electrophoretic mobility of the mutated tRNA compared with the wildtype molecule. We demonstrated that cybrid cell lines carrying the m.4435A3 G mutation exhibited significantly decreased efficiency in aminoacylation and steadystate levels of tRNA Met , as compared with those of control cybrids. The aberrant tRNA Met metabolism resulted in variable decreases in mitochondrial DNA (mtDNA)-encoded polypeptides in the mutant cybrids. Furthermore, we found that the m.4435A3 G mutation caused respiratory deficiency, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in mutant cybrids. These results demonstrated that an aberrant m 1 G37 modification of mitochondrial tRNA Met affected the structure and function of its tRNA and consequently altered mito-chondrial function. Our findings provide critical insights into the pathophysiology of maternally inherited hypertension, which is manifested by the deficient tRNA nucleotide modification. Defects in nucleotide modifications of mitochondrial tRNAs have been associated with several clinical abnormalities including cancer, diabetes, neurological disorders, deafness, and hypertension (1-4). These nucleotide modifications of human 22 mitochondrial tRNAs encoded by its own genome were catalyzed by tRNA-modifying enzymes encoded by nuclear genome (5-8). To date, 15 types of modifications have been identified in 118 positions in different mammalian mitochondrial tRNAs (9, 10). These nucleotide modifications play a vital role in the structure and function of tRNAs (11) (12) (13) (14) . Core modifications including pseudouridinylation at position 55 at the T⌿C loop primarily contributed to structural stability of tRNAs and in some cases, may affect the aminoacylation (2, 3). These were exemplified by our recent discovery that the loss of pseudouridinylation at position 55 at the T⌿C loop of tRNA Glu caused the maternally inherited deafness and diabetes (4). Indeed, the anticodon loop modifications including nucleotides at positions 34 and 37 regulate the stabilization of anticodon structure, fidelity, and efficiency of translation (2, 3, 11, 15-17). The defective 5-taurinomethyluridine (m 5 U) at U34 of tRNA Leu(UUR) was associated with mitochondrial encephalopathy lactic acidosis and stroke-like episodes, whereas the lack of 5-taurinomethyl-2-thiouridine (m 5 s 2 U) at U34 of tRNA Lys was responsible for myoclonus epilepsy associated with ragged red fibers (MERRF) (18 -20). Furthermore, mutations in tRNA modifying enzymes TRMU, MTO1, GTPBP3, and NSUN3 involved in nucleotide modifications at position 34 of mitochondrial tRNAs have been associated several clinical phenotypes including deafness (21-25).
doi:10.1109/igarss.2010.5653328 dblp:conf/igarss/LingLCTBW10 fatcat:iuynifywmfbrdctfs6qjpvmivm
We propose a long-term parameterization scheme for two critical parameters, zero-plane displacement height (d) and aerodynamic roughness length (z 0m ), that we further use in the Surface Energy Balance System (SEBS). A sensitivity analysis of SEBS indicated that these two parameters largely impact the estimated sensible heat and latent heat fluxes. First, we calibrated regression relationships between measured forest vertical parameters (Lorey's height and the frontal area index (FAI)) anddoi:10.3390/rs71215806 fatcat:p2ybr76bijgulkpkopgny7d5b4
more »... st aboveground biomass (AGB). Next, we derived the interannual Lorey's height and FAI values from our calibrated regression models and corresponding forest AGB dynamics that were converted from interannual carbon fluxes, as simulated from two incorporated ecological models and a 2009 forest basis map These dynamic forest vertical parameters, combined with refined eight-day Global LAnd Surface Satellite (GLASS) LAI products, were applied to estimate the eight-day d, z 0m , and, thus, the heat roughness length (z 0h ). The obtained d, z 0m and z 0h were then used as forcing for the SEBS model in order to simulate long-term forest evapotranspiration (ET) from 2000 to 2012 within the Qilian Mountains (QMs). As compared with MODIS, MOD16 products at the eddy covariance (EC) site, ET estimates from the SEBS agreed much better with EC measurements (R 2 = 0.80 and RMSE = 0.21 mm¨day´1).
One of the objectives of Forest Dragon 2 project is the generation of a forest cover change map between 1990s and 2000s for Northeast China based on ERS-1/2 tandem data and ENVISAT ASAR data. For the 1990s' map, an automatic and seasonal-adaptive retrieval of forest biomass method was used to produce a forest biomass map based on the ERS tandem interferometric coherence. The biomass map was integrated into two categories (forest and nonforest). For the 2000s' map, an object-based classificationdoi:10.5167/uzh-77355 fatcat:xrfj7eh25jdipdbud2fjidpmx4
more »... method was developed for ASAR HH/HV images acquired on a single date. Post-classification comparison method for change detection was adopted based on the two forest/nonforest maps. Abstract -One of the objectives of Forest Dragon 2 project is the generation of a forest cover change map between 1990s and 2000s for Northeast China based on ERS-1/2 tandem data and ENVISAT ASAR data. For the 1990s' map, an automatic and seasonal-adaptive retrieval of forest biomass method was used to produce a forest biomass map based on the ERS tandem interferometric coherence. The biomass map was integrated into two categories (forest and nonforest). For the 2000s' map, an object-based classification method was developed for ASAR HH/HV images acquired on a single date. Post-classification comparison method for change detection was adopted based on the two forest/nonforest maps.
The European contribution to the Forest DRAGON 2 focused on the evaluation of multitemporal, multi-sensor and multi-scale Earth Observation images and data products within the vegetation ecosystem of Northeast China. The forest growing stock volume (GSV) map produced with ERS-1/2 coherence images for 1995-1998 and two GSV maps produced from Envisat ASAR ScanSAR data for 2005 and 2010 were inter-compared with respect to several datasets (in situ, EO images and EO data products) to assess thedoi:10.5167/uzh-77312 fatcat:lhjzisuklfavhap6n6xazvq47a
more »... sibility of the GSV estimates, the contribution to land cover mapping and the dynamics over time. For this purpose, a multi-source database was set up including in situ data and EO data products. Land use / land cover (LULC) datasets identified mis-classification of GSV in the ERS dataset primarily for cropland. An a posteriori correction of the GSV resulted in an increase of overall accuracy up to 7%. LULC products can also support the fine tuning of the algorithm to estimate GSV from ASAR data particularly in transition regions between forest and shrubland. The ASAR-based GSV estimates were consistent and highlighted areas of change. From the two ASAR maps, slight loss of volume from 2005 to 2010 was estimated. ABSTRACT The European contribution to the Forest DRAGON 2 focused on the evaluation of multi-temporal, multisensor and multi-scale Earth Observation images and data products within the vegetation ecosystem of Northeast China. The forest growing stock volume (GSV) map produced with ERS-1/2 coherence images for 1995-1998 and two GSV maps produced from Envisat ASAR ScanSAR data for 2005 and 2010 were inter-compared with respect to several datasets (in situ, EO images and EO data products) to assess the plausibility of the GSV estimates, the contribution to land cover mapping and the dynamics over time. For this purpose, a multi-source database was set up including in situ data and EO data products. Land use / land cover (LULC) datasets identified mis-classification of GSV in the ERS dataset primarily for cropland. An a posteriori correction of the GSV resulted in an increase of overall accuracy up to 7%. LULC products can also support the fine tuning of the algorithm to estimate GSV from ASAR data particularly in transition regions between forest and shrubland. The ASAR-based GSV estimates were consistent and highlighted areas of change. From the two ASAR maps, slight loss of volume from 2005 to 2010 was estimated.
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