RESUMO
Osteogenesis imperfecta (OI) is a group of clinically and genetically heterogeneous disorders characterized by decreased bone mass and recurrent bone fractures. Transmembrane protein 38B (TMEM38B) gene encodes trimeric intracellular cation channel type B (TRIC-B), mutations of which will lead to the rare form of autosomal recessive OI. Here we detected pathogenic gene mutations in TMEM38B and investigated its phenotypes in three children with OI from two non-consanguineous families of Chinese Han origin. The patients suffered from recurrent fractures, low bone mass, mild bone deformities and growth retardation, but did not have impaired hearing or dentinogenesis imperfecta. Next-generation sequencing and Sanger sequencing revealed a homozygous novel acceptor splice site variant (c.455-7T>G in intron 3, p.R151_G152insVL) in family 1 and a homozygous novel nonsense variant (c.507G>A in exon 4, p.W169X) in family 2. The parents of the probands were all heterozygous carriers of these mutations. We reported the phenotype and novel mutations in TMEM38B of OI for the first time in Chinese population. Our findings of the novel mutations in TMEM38B expand the pathogenic spectrum of OI and strengthen the role of TRIC-B in the pathogenesis of OI.
Assuntos
Genes Recessivos , Canais Iônicos/genética , Mutação , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/genética , Processamento Alternativo , Biomassa , Osso e Ossos/patologia , Pré-Escolar , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , RNA Mensageiro , RadiografiaRESUMO
OBJECTIVE: To study the effect of Tangshenkang Granule (TG) containing serum on renal mesangial cells' (RMCs) proliferation and TGF-ß1/Smad2/3 pathway in the high glucose condition. METHODS: Twelve SD rats were randomly divided into four groups, i.e., the low dose TG group, the middle dose TG group, the high dose TG group, and the blank control group, 3 in each group. After 7-day gastrogavage via portal vein blood, rats were sacrificed and their serum samples were collected. RMCs were cultured in common rat serum and TG containing serum respectively. The proliferation of mesangial cells was determined by methly thiazolyl tetrazolium (MTT) assay to determine the optimal TG containing serum concentration. Expression levels of TGF-ß1 mRNA and protein were determined by real time quantitative PCR and ELISA. Smad2/3 protein expression and phosphorylation were determined by Western blot and immunofluorescence. RESULTS: TG containing serum at different doses could inhibit high glucose induced RMC cells' proliferation, TGF-ß1 over-expression and Smad2/3 phosphorylation. CONCLUSION: TG containing serum could inhibit high glucose induced RMC cells' proliferation, and its mechanism might be possibly associated with inhibiting TGF-ß1/Smad2/3 signaling pathway.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Proliferação de Células , Glucose , Células Mesangiais , Fosforilação , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Soro , Transdução de Sinais , Proteína Smad2/metabolismoRESUMO
OBJECTIVE: To study effects of Chinese Herbal Compounds (CHC) for blood activating stasis removing (BASR), qi benefiting Shen invigorating (QBSI) on high glucose stimulated proliferation of renal mesangial cells (RMCs) and expressions of fibronectin (FN). METHODS: Rats' RMCs were dealt with high glucose and different concentrations of Chinese medicine for 24 and 48 h respectively. The proliferation of RMCs was detected with 4-A thiazolyl blue. mRNA expressions of FN was detected by real time quantitative PCR. The protein expression of FN was detected by ELISA. RESULTS: Compared with the control group, the proliferation obviously increased (P < 0.05, P < 0.01) after 24 and 48 h of treatment in the high glucose group, mRNA and protein expressions of FN also increased (P < 0.01). There was no statistical difference in the proliferation of RMCs or expressions of FN at 24 h between each CHC group and the high glucose group (P > 0.05). Compared with the high glucose group, the proliferation of RMCs and expressions of FN at 24 h each obviously decreased in the CHC group (P < 0.05, P < 0.01). CONCLUSIONS: High glucose could promote the proliferation of RMCs and induce expressions of FN. No obvious effect could be stimulated by CHC treatment for 24 h. The proliferation of RMCs, protein and mRNA expressions of FN could be reversed by CHC treatment for 48 h.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fibronectinas/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Animais , Células Cultivadas , Glucose/efeitos adversos , Túbulos Renais/citologia , Masculino , RNA Mensageiro/genética , RatosRESUMO
Here, we used glucocorticoid as an apoptosis inducer to study how glucocorticoid could accelerate cartilage degeneration and the responsible signal pathway. Human chondrocytes were isolated from knee joints gave glucocorticoid of different concentrations for 24 h, 48 h, 72 h, or 1 week, and cell viability was determined. Next, Sox9, Collagen type II, Aggrecan protein expression and mRNA transcription were detected by western blot analysis and quantitative real-time PCR, respectively. Glucocorticoid could suppress chondrocyte growth at the concentration of 100 µM. When cultured with glucocorticoid, the expressions of Sox9, Col II, and Aggrecan were depressed time-dependent and dose-dependent, as well as the mRNA transcription. The glucocorticoid-induced p38 inactivation was one mechanism that may response for the inhibition of extracellular matrix synthesis, and these influences appeared earlier than the apoptosis effect.
Assuntos
Condrócitos/efeitos dos fármacos , Dexametasona/farmacologia , Matriz Extracelular/efeitos dos fármacos , Glucocorticoides/farmacologia , Fatores de Transcrição SOX9/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Cartilagem Articular/citologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Relação Dose-Resposta a Droga , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Articulação do Joelho/citologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição SOX9/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (ß-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with ß-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.
Assuntos
Densidade Óssea , Absorciometria de Fóton , Bile , Biomarcadores , Remodelação Óssea , Colágeno Tipo I , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa , Pós-MenopausaRESUMO
BACKGROUND: Osteogenesis imperfecta (OI), a heritable bone fragility disorder, is mainly caused by mutations in COL1A1 gene encoding α1 chain of type I collagen. This study aimed to investigate the COL1A1 mutation spectrum and quantitatively assess the genotype-phenotype relationship in a large cohort of Chinese patients with OI. METHODS: A total of 161 patients who were diagnosed as OI in Department of Endocrinology of Peking Union Medical College Hospital from January 2010 to December 2017 were included in the study. The COL1A1 mutation spectrum was identified by next generation sequencing and confirmed by Sanger sequencing. A new clinical scoring system was developed to quantitatively assess the clinical severity of OI and the genotype-phenotype relationship was analyzed. The independent sample t-test, analysis of variance, Mann-Whitney U-test, Chi-squared test, Pearson correlation, and multiple linear regression were applied for statistical analyses. RESULTS: Among 161 patients with OI, 32.9% missense mutations, 16.8% non-sense mutations, 24.2% splice-site mutations, 24.8% frameshift mutations, and 1.2% whole-gene deletions were identified, of which 38 variations were novel. These mutations led to 53 patients carrying qualitative defects and 67 patients carrying quantitative defects in type I collagen. Compared to patients with quantitative mutations, patients with qualitative mutations had lower alkaline phosphatase level (296 [132, 346] U/L vs. 218 [136, 284] U/L, Pâ=â0.009) and higher clinical score (12.2â±â5.3 vs. 7.4â±â2.4, Pâ<â0.001), denoting more severe phenotypes including shorter stature, lower bone mineral density, higher fracture frequency, more bone deformity, vertebral compressive fractures, limited movement, and dentinogenesis imperfecta (DI). Patients would not present with DI if the glycine substitutions happened before the 79th amino acid in triple helix of α1 chains. CONCLUSIONS: This presented distinctive COL1A1 mutation spectrum in a large cohort of Chinese patients with OI. This new quantitative analysis of genotype-phenotype correlation would be helpful to predict the prognosis of OI and genetic counseling.
Assuntos
Colágeno Tipo I/genética , Mutação/genética , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. OI patients of autosomal recessive inheritance are extremely rare, of which OI type XIII is attributable to mutation in BMP1 gene. CASE REPORT: Here, we detect the pathogenic mutations and analyze their relation to the phenotypes in a Chinese family with OI using next-generation sequencing (NGS) and Sanger sequencing. We also evaluate the efficacy of alendronate treatment in the patient with OI type XIII. The clinical phenotypes of the patient included recurrent fractures, muscle weakness, bone deformity, macrocephaly and elbow contractures, but no blue sclera or dentinogenesis imperfecta. High-resolution peripheral quantitative computed tomography revealed high bone mineral density and bone volume, but reduced trabecular numbers, increased porosity and comprised strength in this patient. Novel heterozygous mutations of c.1324Gâ¯>â¯T (p.Asp442Tyr) and c.148â¯+â¯1Gâ¯>â¯A in BMP1 gene were found in the proband, which would affect the CUB2 domain and the prodomain of mutant proteins. The parents were heterozygous carriers for the two mutations respectively, but with normal phenotype. CONCLUSIONS: We report for the first time that the novel pathogenic mutations in BMP1 can lead to the extremely rare OI type XIII, which exhibit unique characters of high bone mass, but with impaired bone microstructure and comprised bone strength. Alendronate is beneficial in increasing bone mineral density and decreasing bone resorption biomarkers, but concerns still remain whether it can reduce fracture incidence in this rare type of OI.
Assuntos
Proteína Morfogenética Óssea 1/genética , Mutação , Osteogênese Imperfeita/genética , Adolescente , Seguimentos , Heterozigoto , Humanos , Masculino , FenótipoRESUMO
BACKGROUNDS: SERPINF1 mutations caused deficiency of pigment epithelium-derived factor (PEDF) and would lead to osteogenesis imperfecta (OI) type VI. However, serum PEDF levels were unclear in Chinese OI patients who had clear molecular diagnosis. OBJECTIVE: To assess PEDF levels in different genotypes of OI, to evaluate the influencing factors of PEDF in Chinese OI patients with clear molecular diagnosis. METHODS: Known candidate genes of OI were examined by a targeted next generation sequence. Serum PEDF levels were measured by ELISA in 6 OI patients with SERPINF1 mutations, 6 carriers of one copy of the SERPINF1 mutation, 88 OI patients with COL1A1, CLO1A2, IFITM5 and other pathogenic mutations of OI and 24 healthy controls. We compared the differences in serum PEDF levels among different OI patients and normal controls. RESULTS: Serum PEDF levels were extremely low in OI patients with SERPINF1 mutations (0.66±1.60µg/ml) than in OI patients with other pathogenic mutations (4.88±1.43-7.07±2.43µg/ml), carriers of one copy of SERPINF1 mutation (4.94±2.35µg/ml), and normal controls (7.29±2.31µg/m) (P<0.001). No significant differences in serum PEDF concentrations were found among patients with OI type I, III or IV, and between patients with or without bisphosphonate treatment. Serum PEDF level was positively correlated with Z-score of weight (r=0.310, P=0.004), BMI (r=0.253, P=0.020) and alanine aminotransferase (r=0.291, P=0.007). CONCLUSIONS: Extremely low level of PEDF was demonstrated as a specific, convenient, and inexpensive diagnostic biomarker for OI patients with SERPINF1 mutations, but it could not provide information regarding the clinical severity of OI and the efficacy of bisphosphonates treatment.
Assuntos
Proteínas do Olho/sangue , Mutação , Fatores de Crescimento Neural/sangue , Osteogênese Imperfeita/genética , Serpinas/sangue , Adulto , Povo Asiático , Biomarcadores/sangue , Estudos de Casos e Controles , Difosfonatos/uso terapêutico , Proteínas do Olho/genética , Humanos , Fatores de Crescimento Neural/deficiência , Fatores de Crescimento Neural/genética , Osteogênese Imperfeita/sangue , Osteogênese Imperfeita/classificação , Serpinas/deficiência , Serpinas/genética , Adulto JovemRESUMO
Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disorder with poorly known etiology, pathophysiology, and therapy. We aimed to investigate the clinical characteristics of PLO and evaluate the effectiveness and safety of bisphosphonates on it. A total of 12 patients were diagnosed with PLO on the basis of medical history, bone mineral density (BMD), and/or fragility fractures during pregnancy and lactation. We investigated the clinical, biochemical, and radiological characteristics of patients. We assessed the effects of alendronate or zoledronic acid through observing the changes of bone turnover biomarkers and BMD during the treatment. Secondary osteoporosis was excluded by comprehensive differential diagnosis. The mean age of these patients was 31 ± 5 years old. All of these patients presented severe back pain. Multiple vertebral compression fractures (VCFs) were found in 10 patients, and the median (P25th, P75th) number of compressed vertebra was 3 (3, 5). Ten patients had vitamin D insufficiency or deficiency. Serum level of bone resorption marker (ß-CTX with mean of 0.68 ± 0.41 ng/ml) was moderately higher than the normal range. BMD at lumbar spine, femoral neck, and total hip were low as 0.894 ± 0.153 g/cm2, 0.728 ± 0.090 g/cm2, and 0.728 ± 0.080 g/cm2, respectively. Either alendronate or zoledronic acid could effectively relieve bone pain, reduce ß-CTX level, and increase BMD. PLO is a rare type of osteoporosis, which was characterized by increased bone resorption and decreased BMD, even VCFs. Bisphosphonate therapy was well tolerated and effective in management of PLO, but needed to be further verified in randomized controlled trial.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Lactação , Osteoporose/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Alendronato/uso terapêutico , Dor nas Costas/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Feminino , Fraturas por Compressão/etiologia , Humanos , Osteoporose/etiologia , Gravidez , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Deficiência de Vitamina D , Ácido Zoledrônico/uso terapêuticoRESUMO
OBJECTIVE: Investigating the antioxidant activities of water and ethanol extracts of natural Cordyceps sinensis and Cordyceps militaris and their fermentation preparations. METHOD: The samples were tested through 6 assays: inhibition ability of linoleic acid oxidation; scavenging activity of DPPH, hydrogen peroxide, hydroxyl radical and superoxide anion; and metal chelating activity. RESULT: Samples showed different antioxidant ability, and there was not an extract that exhibited high activity in all assays; however, water extract of natural C. militaris could be regarded as the most powerful antioxidant among 8 samples. It had high activity in inhibition of linoleic acid oxidation, chelating metal ions, and scavenging DPPH and hydroxyl radical. The research also indicated that the contents of phenolic compounds in water and ethanol extracts of natural and cultured Cordyceps sp. had huge difference. CONCLUSION: Natural Cordyceps sp. and its fermentation preparations could be used as potential natural antioxidants. The fermented process affected the antioxidant ability of cultured Cordyceps sp., and the antioxidant activity of both natural and cultured Cordyceps sp. did not significantly related with the quantity of phenolics.
Assuntos
Antioxidantes/farmacologia , Cordyceps/química , Sequestradores de Radicais Livres/farmacologia , Materia Medica/farmacologia , Antioxidantes/isolamento & purificação , Quelantes/isolamento & purificação , Quelantes/farmacologia , Cordyceps/crescimento & desenvolvimento , Cordyceps/metabolismo , Etanol , Fermentação , Flavonoides/análise , Flavonoides/metabolismo , Sequestradores de Radicais Livres/isolamento & purificação , Ácido Linoleico/metabolismo , Materia Medica/isolamento & purificação , Oxirredução/efeitos dos fármacos , Fenóis/análise , Fenóis/metabolismo , PolifenóisRESUMO
BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive autonomic and sensory neuropathy. CIPA is associated with various mutations in NTRK1. CASES: Two unrelated Chinese patients presented separately with symptoms of insensitivity to pain, inability to sweat, repeated painless fractures, and Charcot arthropathy were recruited. Both of them were clinically diagnosed with CIPA. Increased serum bone resorption marker (ß-CTX) levels and decreased BMD were observed in both patients. X-ray films revealed enlarged bony calli in the fracture sites, Charcot arthropathy, and bilateral lower limb osteomyelitis. Sanger sequencing demonstrated compound heterozygous mutations in NTRK1 for proband 1 (IVS7-33T>A in intron 7 and c. 2281C>T in exon 17) and for proband 2 (IVS7-33T>A in intron 7 and c.1652delA in exon 14), of which the variation in exon 14 in NTRK1 was a novel mutation. CONCLUSIONS: We report the detailed phenotypes, as well as both recurrent and novel mutations in NTRK1 in 2 Chinese patients with CIPA. The genetic findings of our study expand the gene mutation spectrum of CIPA.
Assuntos
Povo Asiático/genética , Neuropatias Hereditárias Sensoriais e Autônomas/enzimologia , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Mutação , Receptor trkA/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Criança , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Receptor trkA/química , Adulto JovemRESUMO
BACKGROUND: Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. Most OI cases follow an autosomal dominant pattern of inheritance and are attributed to mutations in genes encoding type I collagen (COL1A1/COL1A2). Genomic structural variations involving type I collagen genes are extremely rare in OI. CASE REPORT: In this study, we characterized a de novo balanced translocation of t(5;7)(q32;q21.3) that caused an extremely rare type of OI in a patient from a non-consanguineous family. The clinical phenotypes of this OI included recurrent fractures, low bone mass, macrocephaly, blue sclera and failure to thrive. Next-generation sequencing was used to identify the translocation, and Sanger sequencing was used to validate and map the breakpoints. The breakpoint on chromosome 7 disrupted the COL1A2 gene in the 17th exon, presumed to affect type I collagen production and give rise to OI. The breakpoint on chromosome 5 disrupted the protein phosphatase 2 regulatory subunit B, beta gene (PPP2R2B) within the first intron. CONCLUSIONS: This is the first report of a copy-neutral structural variant involving COL1A2 that leads to a rare type of OI. This study expands the genotypic spectrum of OI and demonstrates the effectiveness of targeted sequencing for breakpoint mapping.
Assuntos
Colágeno Tipo I/genética , Osteogênese Imperfeita/genética , Translocação Genética , Pré-Escolar , Pontos de Quebra do Cromossomo , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 7/genética , Humanos , Masculino , Osteogênese Imperfeita/etiologia , LinhagemRESUMO
Based on the biomass data of 276 sampling trees of Pinus koraiensis, Abies nephrolepis, Picea koraiensis and Larix gmelinii, the mono-element and dual-element additive system of biomass equations for the four conifer species was developed. The model error structure (additive vs. multiplicative) of the allometric equation was evaluated using the likelihood analysis, while nonlinear seemly unrelated regression was used to estimate the parameters in the additive system of biomass equations. The results indicated that the assumption of multiplicative error structure was strongly supported for the biomass equations of total and tree components for the four conifer species. Thus, the additive system of log-transformed biomass equations was developed. The adjusted coefficient of determination (Ra 2) of the additive system of biomass equations for the four conifer species was 0.85-0.99, the mean relative error was between -7.7% and 5.5%, and the mean absolute relative error was less than 30.5%. Adding total tree height in the additive systems of biomass equations could significantly improve model fitting performance and predicting precision, and the biomass equations of total, aboveground and stem were better than biomass equations of root, branch, foliage and crown. The precision of each biomass equation in the additive system varied from 77.0% to 99.7% with a mean value of 92.3% that would be suitable for predicting the biomass of the four natural conifer species.
Assuntos
Biomassa , Árvores/crescimento & desenvolvimento , Abies/crescimento & desenvolvimento , China , Larix/crescimento & desenvolvimento , Modelos Teóricos , Picea/crescimento & desenvolvimento , Pinus/crescimento & desenvolvimentoRESUMO
OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Densidade Óssea , Bile , Biomarcadores , Absorciometria de Fóton , Osteoporose Pós-Menopausa , Estudos Transversais , Remodelação Óssea , Pós-Menopausa , Colágeno Tipo IRESUMO
Fibrosarcoma is a malignant soft tissue tumor of mesenchymal origin. Despite advances in medical and surgical treatment, patient survival rates have remained poor. According to the cancer stem cell hypothesis, tumors are comprised of heterogeneous cell populations that have different roles in tumor formation and growth. Cancer stem cells are a small cell subpopulation that exhibits stem-like properties to gain aggressiveness and recurrence. These cells have been identified in a variety of cancerous tumors, but not in human fibrosarcoma. In this study, we observed that HT1080 cells and primary fibrosarcoma cells formed spheres and showed higher self-renewal capacity, invasiveness and drug resistance compared with their adherent counterparts. Moreover, we demonstrated that the cells showed higher expression of the embryonic stem cell-related genes Nanog, Oct3/4, Sox2, Sox10 and their encoding proteins, as well as greater tumorigenic capacity in nude mice. In conclusion, our data suggest the presence of a stem-like cell population in human fibrosarcoma tumors, which provides more evidence for the cancer stem cell hypothesis and assistance in designing new therapeutic strategies against human fibrosarcoma.
RESUMO
The nascent CaH product in the reaction Ca(4s4p1P1) + H2 --> CaH(X2Sigma+) + H is obtained using a pump-probe technique. The CaH(v = 0,1) distributions, with a population ratio of CaH(v = 0)/CaH(v = 1) = 2.7+/-0.2, may be characterized by low Boltzmann rotational temperature. According to Arrhenius theory, the temperature dependence measurement yields a potential barrier of 3820+/-480 cm(-1) for the current reaction. As a result of the potential energy surfaces (PES) calculations, the reaction pathway favors a Ca insertion into the H2 bond along a (near) C2v geometric approach. As the H2 bond is elongated, the configurational mixing between the orbital components of the 4p and nearby low-lying 3d state with the same symmetry makes significant the nonadiabatic transition between the 5A' and 2A' surface in the repulsive limbs. Therefore, the collision species are anticipated to track along the 5A' surface, then undergo nonadiabatic transition to the inner limb of the 2A' surface, and finally cross to the reactive 1A' surface. The observed energy barrier probably accounts for the energy requirement to surmount the repulsive hill in the entrance. The findings of the nascent CaH product distributions may be reasonably interpreted from the nature of the intermediate structure and lifetime after the 2A'-1A' surface transition. The distinct product distributions between the Ca(4 1P1) and Mg(3 1P1) reactions with H2 may also be realized with the aid of the PES calculations.