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Ossification of the spinal ligaments (OSL) is characterized by the appearance of pathologic bone tissue within the spinal ligamentous tissue. OSL tends to occur in the cervical and thoracic segments with important cause of spinal stenosis. Compression of the spinal cord or nerve roots by ossified masses can lead to severe neurological dysfunction, which has a tremendous impact on the quality of life of patients. However, the exact etiology and pathogenesis of OSL are still unclear. Epigenetic regulation is widespread in organisms and refers to the appearance of heritable changes in gene expression without alteration in genomic DNA sequence. As an important form of biodiversity regulation, epigenetic regulation plays an important role in development of several diseases. Epigenetic regulation has multiple manifestations in OSL, including DNA methylation, histone modifications, and non-coding RNA regulation. Sequencing tools, such as gene microarrays, have revealed significant differences in DNA methylation profiles and non-coding RNA expression between ossified and normal spinal ligaments. These differences can cause abnormal expression of osteogenesis-related target genes through direct or indirect pathways, thus affecting the ossification process of spinal ligaments. In addition, interactions between these epigenetic regulatory mechanisms constitute a large and complex regulatory network. Consequently, an in-depth understanding of the role of different epigenetic regulatory mechanisms and the linkages between them in the initiation and progression stages of OSL is expected to provide a valuable reference for the clinical diagnosis and treatment of OSL-related diseases.
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OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments, but its side effects often limit the clinical usage. Metabolic disorders are one of the side effects induced by cisplatin, which closely relate to the onset of chemotherapy-induced anorexia (CIA) in cancer patients but lacks effective controls. Liujunzi decoction (LJZD) is a traditional Chinese formula that has a promising effect in treating CIA. However, whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow. The present study evalu?ated the mechanism of cisplatin-induced metabolic disorders, and the effect of LJZD in ameliorating these disturbances. METHODS 42 male Sprague-Dawley (SD) rats (180-220 g) were randomly divided into 3 groups:normal control group (distilled water+saline), model group (distilled water+cisplatin), LJZD group (4.8 g·kg-1 Liujunzi decoction ingredients+cisplatin). Intragastrical administered each drug twice a day (7:00-19:00) since day 0 for 4 d, animals were intraperito?neal injected with cisplatin 6 mg·kg-11 h after administration while normal control groups were injected with same volume of saline. On day 3, each group was anesthetized with pentobarbital sodium 45 mg · kg-1 (ip), and blood samples were collected from aorta abdominalis. Then the samples were analyzed using an LC-ESI-MS/MS system. Significantly regu?lated metabolites between groups were determined by VIP≥1 and absolute Log2FC (fold change)≥1. Identified metabo?lites were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Metaboanalyst 5.0 (https://www.metaboanalyst.ca/). RESULTS A total of 133, 77 and 32 differential metabolites were filtrated in control vs model, control vs LJZD and model vs LJZD groups respectively. Comparing to control, the levels of hexadecanoic acid (Log2FC=6.3153), linoleic acid (Log2FC=5.3478), and 8, 11-icosadienoic acid (Log2FC=5.2342) significantly increased, and the levels of N-acetyl-L-tyrosine (Log2FC = -2.6283), cinnamic acid (Log2FC = -2.3381), N-acetylphenylalanine (Log2FC = -2.2501) significantly decreased in model group. The KEGG pathway enrichments of these metabolites indi?cated that, cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid, unsaturated fatty acids, and phenylalanine. Compared to control, treatment of LJZD significantly increased the levels of 4-hydroxytryptamine (Log2FC =12.0186), hexadecanoic acid (Log2FC = 5.7412), linoleic acid (Log2FC = 5.1877) and significantly decreased the levels of N-acetylmethionine (Log2FC=-1.7317), 2-aminoethanesulfinic acid (Log2FC=-1.6578), N-acetyl-L-tyrosine (Log2FC=-1.5355). And com?paring to the model group, 4-hydroxytryptamine (Log2FC = 12.0186), 7, 12-diketocholic acid (Log2FC = 2.0998), N-acetylneuraminic acid (Log2FC = 2.0560) markedly increased, and 3-hydroxy-3-methylpentane-1 (Log2FC = -1.9202), 5-dioic acid (Log2FC = -1.7166), N-isovaleroylglycine, hexanoyl glycine (Log2FC = -1.4958) markedly decreased in LJZD group. It was worth noting that, there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups, which were the key metabolites of LJZD in treating CIA. Among these 23 common metabolites, there were 16 metabolites excluding the control vs LJZD group, that was, LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites. Cisplatin-induced downregula?tion of 11 metabolites such as hydrocinnamic acid, (±)12(13)epoxy-9Z-octadecenoic acid, cinnamic acid were upregulated after LJZD treatment, and cisplatin-induced upregulation of imidazoleacetic acid, 2'-deoxycytidine-5'-monophosphate and other 5 metabolites were downregulated by LJZD. The KEGG pathway analysis indicated that the linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism were the most enriched metabolic pathway. Thus, cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism, and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA. CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabo?lism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments, relating to the regulation of linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism.
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Molecular target anticancer drugs are commonly used in various forms of cancers. It is a concern that the risk of serious adverse events (SAEs) and fatal adverse events (FAEs) of molecular target drugs are increasing. An up-to-date meta-analysis of all Phase II/III/IV randomized trials of molecular target anticancer drugs was conducted to calculate the increased risk of SAEs and FAEs. A systematic search of PubMed, Web of Science, and Cochrane Library up to April 6, 2017, was conducted. The study enrolled Phase II/III/IV randomized trials of cancer that compared molecular target drugs alone versus placebo or performed single-arm analysis of molecular target drugs. Data on SAEs and FAEs were extracted from the included studies and pooled to compute risk ratio (RR), the overall incidence, and 95% confidence interval (CI). In this meta-analysis, a total of 19,965 and 26,642 patients in randomized 53 and 65 Phase II/II/IV trials were included in the analysis of SAEs and FAEs associated with molecular target anticancer drug, respectively. There were significant differences in the relationship of molecular target anticancer drugs with SAEs (RR = 1.57, 95% CI = 1.35–1.82, P < 0.01, I2 = 81%) and FAEs (RR = 1.51, 95% CI = 1.19–1.91, P < 0.01, I2 = 0%) compared to placebo. The overall incidence of SAEs and FAEs was 0.269 (95% CI = 0.262–0.276, P < 0.01) and 0.023 (95% CI = 0.020–0.025, P < 0.01), respectively. Molecular target anticancer drugs significantly increased the risk of SAEs and FAEs. For patients taking molecular target drugs, efforts are needed to prevent the occurrence of SAEs and FAEs
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OBJECTIVE@#To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD).@*METHODS@#The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05).@*CONCLUSIONS@#As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.
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Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). Conclusions As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.
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<p><b>OBJECTIVE</b>To investigate the structure, mechanical and low temperature aging properties of colored dental zirconia ceramics.</p><p><b>METHODS</b>5 graded colored dental zirconia ceramics were made by adding colorants and their combinations into a 3Y-TZP (tetragonal zirconia stabilized by 3mol% yttrium) powder, the green body were compacted at 200 MPa, pre-sinter at 1,050 degrees C and maintained for 2 h, then densely sintered at 1,500 degrees C for 2 h. Specimens were cut from each of the 5 graded colored blocks. Physical, mechanical properties as well as chemical stability were tested, microstructure were observed, crystalline phase were identified by X-ray diffraction (XRD), aging properties were assessed by measurement of the relative content of monoclinic phase and bending strength testing.</p><p><b>RESULTS</b>The overall density of colored zirconia ceramics was over 99.7%, linear shrinkage was about 20%, while thermal expansion coefficient was about 11 x 10(-6) x degrees C(-1), the crystalline phase was tetragonal, bending strength was over 900 MPa which was slightly lowered than that of the uncolored zirconia, fracture toughness was slightly higher. Good chemical stability in acetic acid was observed. After aging treatment, tetragonal-to-monoclinic phase transformation was detected up to 40%, while bending strength was not significantly degraded.</p><p><b>CONCLUSION</b>The results showed that colored 3Y-TZP ceramics presented good mechanical properties even after aging treatments, and was suitable for dental clinical use.</p>
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Cerámica , Ensayo de Materiales , Difracción de Rayos X , Itrio , CirconioRESUMEN
Objective: To investigate the influence of allogeneic spleen tissue transplantation with low-dose FK506 on allograft tolerance in rats receiving orthotopic liver transplant and the related mechanism. Methods: Female Brown Norway (BN) rats were divided into 5 groups (eight rats in each group). Rats in Group 1 received orthotopic allogeneic liver transplantation using inbred Lewis rats as donors. Rats in Group 2 received Lewis liver transplantation+low-dose FK-506 (0.25 mg/kg FK-506 was orally given after transplantation). Rats in Group 3 received Lewis liver transplantation+Lewis spleen transplantation. Rats in Group 4 received Lewis liver transplantation+Lewis spleen transplantation+low-dose FK-506. Rats in Group 5 received Lewis liver+SD spleen transplantation+low-dose FK-506. The survival periods were recorded for each group. The forming of chimerism, the responsiveness of T cells to alloantigen and the pathological changes of transplanted liver were analyzed after treatment. Results: Compared with rats in other groups, rats in Group 4 had an obviously longer survival time, an obviously reduced T cell responsiveness to alloantigen, and obviously increased donor-positive cells (remained for 60 days after transplantation) (P<0.05). There was no significant pathological evidence of rejection. Conclusion: Allogeneic spleen transplantation combined with low-dose FK506 treatment can induce graft immune tolerance in orthotopic allogeneic liver transplant recipients through promoting the formation of chimerism and T cells hyporesonsiveness to alloantigen.
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<p><b>OBJECTIVE</b>To evaluate the value of EBNA1-IgA and EA-IgG in serological diagnosis of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>The serum EBNA1-IgA and EA-IgG of 56 patients with NPC and 58 healthy adults were detected by ELISA. The sensitivity, specificity, positive predictive value, accuracy rate and odds ratio of the two tests used singly or in combination were compared with each other.</p><p><b>RESULTS</b>The sensitivity of EBNA1-IgA (91.07%) was higher than that of EA-IgG (87.50%), while the specificity of EA-IgG (87.93%) was higher than that of EBNA1-IgA (84.48%). The combination of EBNA1-IgA and EA-IgG could enhance the specificity (94.83%), positive predictive value (0.9375), likelihood ratio (15.5435) and odds ratio (75.0000) for serological diagnosis of NPC. Forty-five patients showed both positive EBNA1-IgA and positive EA-IgG. A positive EA-IgG was detected in 4 out of 5 patients with negative EBNA1-IgA and a positive EBNA1-IgA was founded in 6 out of 7 patients with negative EA-IgG.</p><p><b>CONCLUSION</b>Although relatively high sensitivity and specificity could be obtained by either EBNA1-IgA or EA-IgG test alone, the combination of these two tests with a complementary effect is able to enhance the reliability of serological diagnosis of NPC as most patients have positive ENBA1-IgA and EA-IgG concurrently.</p>