RESUMEN
Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-ß signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-ß signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles' heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.
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Células Madre Mesenquimatosas , Osteoporosis , Humanos , Proteínas Portadoras/metabolismo , Diferenciación Celular/genética , Células Cultivadas , Linfotoxina-alfa/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteogénesis/genética , Osteoporosis/genética , Proteína Smad2/metabolismoRESUMEN
We propose a design of the compact high-resolution photonic crystal (PhC) spectrometer with a wide working bandwidth based on both super-prism and local-super-collimation (LSC) effects. The optimizing methods, finding the ideal incident angle and oblique angle of PhC for a wider working bandwidth and ideal incident beam width and PhC size for a certain resolution requirement, are developed. Besides the theoretical work, for the first time, the experiment of such a PhC spectrometer is conducted in the microwave frequency range, and the beam-splitting effects for different frequencies in a wide working bandwidth agree very well with the theoretical predictions. According to the scalability, with the condition to control the deviations in the fabrication processes the design could be extended to optical frequency ranges, e.g., infrared, visible-light, and ultraviolet ranges. The spectrometer in optical frequencies can be implemented on silicon-on-insulator (SOI) chips as a thin-slab structure so that the operating bandwidth can be expanded further through the multi-layer design. Theoretically, the size of the ultra-high-resolution PhC spectrometer in optical frequency ranges based on our design could be two orders smaller than the traditional design.
RESUMEN
Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and embryonic trophoblasts during early pregnancy remains largely unknown. Here, we observed that enriched glutamine and activated glutaminolysis in dNK cells contribute to trophoblast invasion and embryo growth by insulin-like growth factor-1 (IGF-1) and growth differentiation factor-15 (GDF-15) secretion. Mechanistically, these processes are dependent on the downregulation of EGLN1-HIF-1α mediated by α-ketoglutarate (α-KG). Blocking glutaminolysis with the GLS inhibitor BPTES or the glutamate dehydrogenase inhibitor EGCG leads to early embryo implantation failure, spontaneous abortion and/or fetal growth restriction in pregnant mice with impaired trophoblast invasion. Additionally, α-KG supplementation significantly alleviated pregnancy loss mediated by defective glutaminolysis in vivo, suggesting that inactivated glutamine/α-ketoglutarate metabolism in dNK cells impaired trophoblast invasion and induced pregnancy loss.
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Aborto Espontáneo , Animales , Femenino , Ratones , Embarazo , Diferenciación Celular , Glutamina/farmacología , Factor 15 de Diferenciación de Crecimiento , Factor I del Crecimiento Similar a la Insulina , Ácidos Cetoglutáricos/farmacologíaRESUMEN
BACKGROUND: Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. RESULTS: We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. CONCLUSIONS: Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.
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Placenta , Células del Estroma , Embarazo , Humanos , Femenino , Factor I del Crecimiento Similar a la Insulina/genéticaRESUMEN
Uterine corpus endometrial carcinoma (UCEC) is one of the most common types of cancer in women, and the incidence is rapidly increasing. Studies have shown that various signaling pathways serve crucial roles in the tumorigenesis of UCEC, amongst which the Wnt/ß-catenin pathway is of great interest due to its crucial role in cell proliferation and the huge potential as a therapeutic target. In the present study, it was shown that FBXO17, which is a member of the F-box family, is abnormally downregulated in UCEC tissues compared with non-tumor endometrial tissues, and this was significantly associated with the clinical histological grade, as well as the abnormal proliferation of the UCEC cell line, Ishikawa, both in vitro and in vivo. Besides, the results suggested that FBXO17 may inhibit the Wnt/ß-catenin signaling pathway and influence the expression of adhesion molecules, such as E-cadherin and N-cadherin in Ishikawa cells. In conclusion, these findings indicate that FBXO17 is a novel inhibitor of endometrial tumor development and it likely exerts effects via regulation of the Wnt signaling pathway.
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Neoplasias Endometriales , Proteínas F-Box , Vía de Señalización Wnt , Línea Celular Tumoral , Proliferación Celular , Neoplasias Endometriales/patología , Proteínas F-Box/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , beta CateninaRESUMEN
BACKGROUND: Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. RESULTS: Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82-178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. CONCLUSIONS: Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.
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Epigenoma , Glycine max , Animales , Metilación de ADN , Perfilación de la Expresión Génica , Larva/genética , Glycine max/genéticaRESUMEN
The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of decidual stromal cells (DSCs), a series of cytokines and immune cells. Insulin-like growth factor 1 (IGF1) is a low molecular weight peptide hormone with similar metabolic activity and structural characteristics of proinsulin, which exerts its biological effects by binding with its receptor. Emerging evidence has shown that IGF1 is expressed at the maternal-fetal interface, but its special role in establishment and maintenance of pregnancy is largely unknown. Here, we found that the expression of IGF1 in the decidua was significantly higher than that in the endometrium. Additionally, decidua from women with normal pregnancy had high levels of IGF1 compared with that from women with unexplained recurrent spontaneous miscarriage. Estrogen and progesterone led to the increase of IGF1 in DSCs through upregulating the expression of WISP2. Recombinant IGF1 or DSCs-derived IGF1 increased the survival, reduced the apoptosis of DSCs, and downregulated the cytotoxicity of decidual NK cells (dNK) through interaction with IGF1R. These data suggest that estrogen and progesterone stimulate the growth of DSCs and impair the cytotoxicity of dNK possibly by the WISP2/IGF1 signaling pathway.
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Aborto Habitual/prevención & control , Proteínas CCN de Señalización Intercelular/metabolismo , Decidua/citología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células Asesinas Naturales/patología , Proteínas Represoras/metabolismo , Células del Estroma/citología , Aborto Habitual/metabolismo , Aborto Habitual/patología , Adulto , Apoptosis , Proteínas CCN de Señalización Intercelular/genética , Células Cultivadas , Decidua/efectos de los fármacos , Decidua/inmunología , Decidua/metabolismo , Estrógenos/farmacología , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Embarazo , Progesterona/farmacología , Progestinas/farmacología , Proteínas Represoras/genética , Células del Estroma/efectos de los fármacos , Células del Estroma/inmunología , Células del Estroma/metabolismoRESUMEN
BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment symptom in the peripheral nerves. High-frequency ultrasound (HFUS) is widely used in the diagnosis of CTS. Virtual Touch Tissue Imaging and Quantification (VTIQ), which provides more information about the hardness of organization, is used to diagnose CTS. However, the data of diagnostic value of them in various degrees of CTS are limited. Whether the combination of HFUS and VTIQ can improve the diagnostic efficiency also remains unknown. The study aimed to explore the diagnostic value of HFUS and VTIQ in various degrees of CTS and whether combination of HFUS and VTIQ could improve the diagnostic efficiency of CTS. METHODS: A collection and analysis of 133 CTS patients and 35 volunteers from January 2016 to January 2019 were performed. We compared the clinical characteristics, cross-sectional area (CSA) value and shear wave velocity SWVmean value of CTS group with volunteer group. RESULTS: The CSA value and SWVmean value of CTS cohort were significantly higher than volunteer group (10.79 ± 2.88 vs. 8.06 ± 1.39, p < 0.001, 4.36 ± 0.95 vs. 3.38 ± 1.09, p < 0.001, respectively). The area under the curve (AUC) of receiver operating characteristic (ROC) curve of CSA value and SWVmean value were 0.794 and 0.757, respectively. Hierarchical analysis of CSA value and SWVmean value showed that the AUC in the moderate and severe CTS group were higher than in mild CTS group. Furthermore, the CSA value combined with SWVmean value used to diagnose mild CTS was 0.758, which was higher than that of single CSA value or single SWVmean value. CONCLUSIONS: Both HFUS and VTIQ technology were feasible to evaluate CTS. HFUS was suitable for use in diagnosis of moderate and severe CTS. For mild CTS, combination of HFUS and VTIQ was relevant to improve the diagnostic efficiency of CTS.
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Síndrome del Túnel Carpiano , Área Bajo la Curva , Síndrome del Túnel Carpiano/diagnóstico por imagen , Pruebas Diagnósticas de Rutina , Humanos , Nervio Mediano/diagnóstico por imagen , Curva ROC , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
During gestation, excess palmitate (PA) is enriched in decidua. Both excess PA and decidual dysfunctions are associated with numerous adverse pregnancy outcomes such as gestational diabetes, preeclampsia and preterm birth and intrauterine growth restriction. Here, mRNA data about the effects of PA were collected from multiple databases and analyzed. Human decidual tissues were obtained from clinically normal pregnancies, terminated for non-medical reasons, during the first trimester, and decidual stromal cells (DSCs) were isolated and exposed to PA, alone or together with the inhibitors of Toll-like receptor 4 (TLR4), Jun N-terminal kinase (JNK), nuclear factor-kappa-gene binding (NF-kB) or glutamine (GLN) oxidation. Furthermore, DSCs were transfected with lentiviral particles overexpressing human TLR4. We demonstrate that excess PA interacting with its receptor TLR4 disturbs DSC hemostasis during the first trimester. Specifically, high PA signal induced DSC apoptosis and formed an inflammatory program (elevated interleukin-1 beta and decreased interleukin-10) via the activation of TLR4/JNK/NF-kB pathways. A complexed cross-talk was found between TLR4/JNK/NF-kB signals and PA deposition in DSCs. Besides, under an excess PA environment, GLN oxidation was significantly enhanced in DSCs and the suppression of GLN oxidation further augmented PA-mediated DSC apoptosis and inflammatory responses. In conclusion, excess PA induces apoptosis and inflammation in DSCs via the TLR4/JNK/NF-kB pathways, which can be augmented by the suppression of GLN oxidation.
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Apoptosis/efectos de los fármacos , Decidua/citología , Glutamina/metabolismo , Sistema de Señalización de MAP Quinasas , FN-kappa B/fisiología , Células del Estroma/efectos de los fármacos , Receptor Toll-Like 4/fisiología , Femenino , Ontología de Genes , Humanos , Oxidación-Reducción , Palmitatos/farmacología , Embarazo , Primer Trimestre del Embarazo , Proteínas Recombinantes/metabolismo , Células del Estroma/citología , Receptor Toll-Like 4/genética , TransfecciónRESUMEN
Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-ß led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis.
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Endometriosis/metabolismo , Interferón gamma/metabolismo , Interleucinas/metabolismo , Linfocitos T/metabolismo , Adulto , Líquido Ascítico/metabolismo , Endometriosis/inmunología , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Cultivo Primario de Células , Células del Estroma/fisiologíaRESUMEN
OBJECTIVE: To investigate the application value of dynamic intracavitary three-dimensional contrast-enhanced tomographic transrectal ultrasound imaging (3D-CETRUS TUI) in transperineal prostate biopsy for patients with different levels of PSA. METHODS: This prospective study included 180 patients with escalated levels of PSA (≥4 µg/L) or abnormal results of digital rectal examination. According to the level of PSA, the patients were divided into groups A (PSA ≤10 µg/L, n = 104) and B (PSA >10 µg/L, n = 76), and all underwent intracavitary 3D-CETRUS TUI followed by transperineal prostate biopsy under the guidance of two-dimensional gray-scale ultrasound, which involved a standard 12-core transperineal systematic prostate puncture by intracavitary biplane probe and then a 2-core puncture in the abnormal region displayed by 3D-CETRUS TUI. With the pathological results as the gold standard, comparisons were made between the diagnostic value of 3D-CETRUS TUI-guided biopsy and that of 12-core systematic biopsy. RESULTS: Prostate cancer was diagnosed in 69 (38.33%) of the 180 cases and in the specimens from 631 (25.03%) of the 2 520 punctures. The positive rates of prostate cancer were 37.5% (39/104) and 57.9% (44/76) in groups A and B, respectively. 3D-CETRUS TUI-guided prostate biopsy achieved a higher positive rate than 12-core systematic biopsy in both of the groups, with statistically significant difference in group A (P < 0.05), but not in B (P > 0.05). CONCLUSIONS: For patients with a PSA level ≤10 µg/L, dynamic intracavitary 3D-CETRUS TUI-guided transperineal prostate biopsy is more efficient than 12-core systematic biopsy in detecting the positive lesion, while for those with a PSA level > 10 µg/L, it effectively reduces the number of punctures.
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Biopsia/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Ultrasonografía , Humanos , Masculino , Estudios Prospectivos , Antígeno Prostático Específico/sangreRESUMEN
BACKGROUND Spinal tuberculosis (STB) is the main cause of bone and joint tuberculosis. This study aimed to screen and analyze the susceptibility genes for STB using whole-exome sequencing (WES). MATERIAL AND METHODS All exon regions of peripheral blood DNA from 6 STB patients were captured and sequenced using WES and the sequencing data were analyzed by modern bioinformatics methods to identify disease-causing mutations. Sanger sequencing was then used to validate the mutation sites in normal controls (207) and STB patients (193). The mRNA expression of the mutant gene and the serum levels of IL-6 and TNF-α were detected using qPCR or ELISA assay, respectively. RESULTS A nonsynonymous single-nucleotide polymorphism (SNP) in the gene HLA-DQA1 (rs796778515, c.592delCinsG, CAG to GAG, p.Q198E) was identified and further validated by Sanger sequencing. The percentage of the 3 genotypes C/C, C/G and G/G in STB patients and normal controls were 37.3%, 32.1%, and 30.6% and 47.8%, 33.8%, and 18.4%, respectively. Furthermore, the C>G mutation was significantly associated with the occurrence of STB. In addition, the levels of HLA-DQA1 mRNA were significantly lower in blood cells from STB patients compared with normal controls, while the serum levels of IL-6 and TNF-α were significantly higher. CONCLUSIONS The C>G mutation in the HLA-DQA1 gene was associated with the occurrence of STB. This variation may result in the decreased level of HLA-DQA1 mRNA and increased serum levels of IL-6 and TNF-α, which finally led the STB susceptibility.
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Exoma/genética , Predisposición Genética a la Enfermedad , Cadenas alfa de HLA-DQ/genética , Análisis de Secuencia de ADN , Tuberculosis de la Columna Vertebral/genética , Anciano , Alelos , Secuencia de Aminoácidos , Secuencia de Bases , Quimiocinas/metabolismo , Cadenas alfa de HLA-DQ/sangre , Cadenas alfa de HLA-DQ/química , Humanos , Mediadores de Inflamación/metabolismo , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tuberculosis de la Columna Vertebral/sangreRESUMEN
Hydrogen sulphide (H2 S) serves as a vital gastric mucosal defence under acid condition. Non-steroidal anti-inflammatory drugs (NSAIDs) are among widely prescribed medications with effects of antipyresis, analgesia and anti-inflammation. However, their inappropriate use causes gastric lesions and endogenous H2 S deficiency. In this work, we reported the roles of a novel pH-controlled H2 S donor (JK-1) in NSAID-related gastric lesions. We found that JK-1 could release H2 S under mild acidic pH and increase solution pH value. Intragastrical administration of aspirin (ASP), one of NSAIDs, to mice elicited significant gastric lesions, evidenced by mucosal festering and bleeding. It also led to infiltration of inflammatory cells and resultant releases of IL-6 and TNF-α, as well as oxidative injury including myeloperoxidase (MPO) induction and GSH depletion. In addition, the ASP administration statistically inhibited H2 S generation in gastric mucosa, while up-regulated cyclooxygenase (COX)-2 and cystathionine gamma lyase (CSE) expression. Importantly, these adverse effects of ASP were prevented by the intragastrical pre-administration of JK-1. However, JK-1 alone did not markedly alter the property of mouse stomachs. Furthermore, in vitro cellular experiments showed the exposure of gastric mucosal epithelial (GES-1) cells to HClO, imitating MPO-driven oxidative injury, decreased cell viability, increased apoptotic rate and damaged mitochondrial membrane potential, which were reversed by pre-treatment with JK-1. In conclusion, JK-1 was proved to be an acid-sensitive H2 S donor and could attenuate ASP-related gastric lesions through reconstruction of endogenous gastric defence. This work indicates the possible treatment of adverse effects of NSAIDs with pH-controlled H2 S donors in the future.
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Aspirina/toxicidad , Mucosa Gástrica/efectos de los fármacos , Sulfuro de Hidrógeno/metabolismo , Organotiofosfonatos/farmacología , Sustancias Protectoras/farmacología , Animales , Antiinflamatorios no Esteroideos/toxicidad , Línea Celular , Ciclooxigenasa 2/metabolismo , Cistationina gamma-Liasa/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Concentración de Iones de Hidrógeno , Interleucina-6/metabolismo , Masculino , Ratones , Estructura Molecular , Organotiofosfonatos/química , Organotiofosfonatos/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: To determine the associations of single nucleotide polymorphism (SNP) in leptin (LEP) genes and environmental factors with cholesterol gallstone in southeast Han populations. METHODS: A 1:2 matched case-control study was conducted involving 200 patients with cholesterol gallstone. Genotyping of the SNP was examined on the LightCycler480 PCR platform using in-house high resolution melting (HRM) approaches. Detection correctness was validated through direct sequencing. Multifactor dimensionality reduction (MDR) analysis was applied to examine the effects of potential gene-environment interactions. RESULTS: Three genotypes of LEP G2548A were obtained by HRM genotyping, including 52 cases of GG wild type, 192 cases of GA mutant heterozygosity and 356 cases of AA mutation homozygous type. The genotype distribution of the SNP locus in the control group was in line with the Hardy-Weinberg genetic balance (P>0.05). The AA genotype carriers of LEP G2548A had significantly higher serum leptin than the GA/GG genotype carriers (H=6.83, P<0.05). The conditional logistic regression revealed that high serum leptin [odds ratio (OR)=5.012, 95% confidence interval (CI): 3.248-7.734], AA genotype of LEP G2548A site (OR=2.292, 95%CI: 1.012-5.193), family history of gallstones (OR=2.984, 95%CI: 1.329-6.700), high SBP (OR=1.927, 95%CI: 1.140-3.255) and smoking (OR=1.717, 95%CI: 1.006-2.928) were predictors of cholesterol gallstone. However, regular drinking of strong tea (OR=0.552, 95%CI: 0.336-0.907) and exercise (OR=0.591, 95%CI: 0.395-0.882) were protecting factors for cholesterol gallstone. The results of MDR analysis indicated that tea drinking, genotype of LEP G2548A site and serum leptin formed the optimal gene-environment interaction model. CONCLUSIONS: Individuals who drink less tea, carry AA genotype and have high serum leptin are more susceptible to cholesterol gallstone.
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Cálculos Biliares/genética , Leptina/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Colesterol , Predisposición Genética a la Enfermedad , Genotipo , HumanosRESUMEN
BACKGROUND: To investigate the association and magnitude of risk between JIA, its associated treatment and cancer development in Taiwanese children. METHODS: Nationwide population-based 1:4 age- and gender-matched retrospective cohort study was designed using the National Health Insurance Research Database of Taiwan. A cohort of 2,892 children <16 years old with JIA was formed as well as a non-JIA cohort of 11,568 in year 2003 to 2005. They were followed up till a diagnosis of malignancy or up to 8 years until 2010. Relative risk (RR), incidence rate ratio (IRR), and adjusted hazard ratio (aHR) of developing malignancy were calculated. RESULTS: The female to male ratio was 0.79:1. There were 3 cases of incident cancer in the "MTX use, biologics-naïve" group, only 1 in the anti-TNF biologics-containing group and 29 in the "both MTX- and biologics-naïve" group, in comparison, there were 50 cases of cancer in the non-JIA comparator group. During a 16114.16 patient-years follow-up, the RR and IRR for developing a malignancy in both methotrexate- and anti-tumor necrosis factor (TNF) biologics-naïve JIA children were 2.75 (95% confidence interval, 1.75 - 4.32) and 3.21 (2.01 - 5.05), respectively. For leukemia, the IRR was 7.38 (2.50 - 22.75); lymphoma, 8.30 (1.23 - 69.79); and soft tissue sarcoma, 11.07 (0.84 - 326.4). The IRR of other cancers was 2.08 (1.11 - 3.71). The aHR on cancer risk was 3.14 (1.98 - 4.98) in methotrexate- and biologics-naïve group. There were no statistically significant increased risk in JIA patients treated with methotrexate and/or anti-TNF biologics. CONCLUSIONS: Compared with children without JIA, children with JIA have 3-fold increase of risk on malignancy in East Asia. Seemingly neither methotrexate nor anti-TNF biologics increases the risk further.
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Artritis Juvenil/tratamiento farmacológico , Productos Biológicos/efectos adversos , Metotrexato/efectos adversos , Neoplasias/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Artritis Juvenil/epidemiología , Productos Biológicos/uso terapéutico , Niño , Preescolar , Asia Oriental/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Metotrexato/uso terapéutico , Neoplasias/inducido químicamente , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: There is currently a trend toward minimally invasive total knee arthroplasty (TKA) to decrease the morbidity related to the standard approach. The aim of our study was to clarify whether the mini-subvastus surgical had an advantage over the standard in term of pain level, blood loss, and postoperative recovery, whether the mini-subvastus surgical was prone to radiographic malalignment, prolonged operative time, and increased complications. METHODS: In a prospective randomized study, we compared the clinical and radiological results of primary TKA using a mini-subvastus approach or a standard approach in 68 patients. The mini-subvastus approach was used on 35 patients (group I) and the standard approach on 33 patients (group II). RESULTS: The mean follow-up was 28 months (range 24-36 months). Patients in group I had less blood loss and better visual analogue scale score at 1 day postoperatively. They achieved active straight leg raise earlier and underwent less lateral retinacular releases. The mean Knee Society function score, Oxford knee score, and range of movement were significantly better in group I up to 9 months after surgery (all, p < 0.05). However, there were no significant differences in these parameters between the groups at final follow-up. Reduced access and visibility in group I prolonged tourniquet time by an average of 22 min and resulted in five technical errors on radiographic evaluation. CONCLUSIONS: Patients can receive marked but temporary benefits from the mini-subvastus technique, with a definite cost: that of component malposition and prolongation of operative time.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Tempo Operativo , Osteoartritis de la Rodilla/cirugía , Estudios Prospectivos , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.
RESUMEN
The management of epilepsy during pregnancy presents particular challenges for neurologists worldwide. Currently, there are no clear recommendations for oxcarbazepine (OXC) specific target concentration during pregnancy. We conducted this retrospective observational cohort study on pregnant women with epilepsy (WWE) who received OXC monotherapy or polytherapy, at the epilepsy outpatient clinic of a tertiary hospital in eastern China. Sixteen pregnancies of 16 WWE were split into the seizure-free group or the non-seizure-free group, according to whether they had been seizure free for more than one year prior to conception or not. There was a significantly decrease in OXC concentration throughout pregnancy, as indicated by the concentration/dose ratio and the ratio of target concentration (RTC). The second trimester of pregnancy was the period when seizure deterioration occurred the most, particularly in the non-seizure-free group. Lower RTC_OXC was identified to be a risk factor for increasing seizure frequency in both the total group and the non-seizure-free group in both univariate and multivariate analysis, with a threshold of 0.575 for differentiating patients at high-risk and low-risk for seizure deterioration. In conclusion, this study suggested an OXC concentration threshold of 0.575 during pregnancy for assisting neurologists in OXC drug monitoring and dose adaptation.
RESUMEN
The effect of BayK 8644 on cytosolic Ca²âº concentrations ([Ca²âº]i) and viability in PC3 human prostate cancer cells was explored. Fura-2 was applied to measure [Ca²âº]i. BayK 8644 at 1-50 µM induced a [Ca2²âº]i rise concentration-dependently. The response was reduced by removing extracellular Ca²âº. BayK 8644-evoked Ca²âº entry was inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators. In Ca²âº-free medium, incubation with the endoplasmic reticulum Ca²âº pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished BayK 8644-induced [Ca²âº]i rise. Inhibition of phospholipase C did not alter BayK 8644-induced [Ca²âº]i rise. BayK 8644 killed cells in a concentrationdependent manner, which was not reversed by chelating cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Collectively, in PC3 human prostate cancer cells, BayK 8644 induced a [Ca²âº]i rise by evoking phospholipase C-independent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via protein kinase C-sensitive store-operated Ca²âº channels (and/or T-type Ca²âº channels). At high concentrations, BayK 8644 caused cell death.