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1.
Sleep Breath ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898189

RESUMO

OBJECTIVE: The endocannabinoid system (ECS) regulates bone turn-over and remodeling. Chronic intermittent hypoxia (CIH) occurring during obstructive sleep apnea (OSA) may lead to disorders of the ECS and bone metabolism abnormalities. This study aimed to investigate whether or not the cannabinoid receptor 1 (CB1R) antagonist rimonabant (Ri) alleviates bone metabolism abnormalities and bone destruction induced by chronic intermittent hypoxia (CIH). METHODS: Healthy male Sprague Dawley (SD) rats (n=48) were randomly divided into 6 groups of 8 rats: 2 normal control (NC) groups, 2 intermittent hypoxia (IH) groups, and 2 IH + Ri groups. Rats in NC groups breathed room air for 4 weeks (4w NC group) and 6 weeks (6w NC group). Rats in IH groups experienced IH environment for 4 weeks (4w IH group) and 6 weeks (6w IH group). In addition to the same IH exposure, rats in IH + Ri group were given daily intraperitoneal injection of Ri at the dosage of 1.5 mg/kg/d for 4 weeks (4w IH + Ri group) and 6 weeks (6w IH + Ri group). Levels of serum tartrate-resistant acid phosphatase (TRAP, a marker of bone resorption) were determined by ELISA. Hematoxylin and eosin (HE) staining was performed on bone sections to observe the changes in bone microstructure. Expression of CB1R in bone tissue was determined by immunohistochemistry. RESULTS: TRAP levels were higher in the 4w IH and 6w IH groups than in the 4w NC and 6w NC groups; TRAP levels were lower in the 4w IH + Ri and 6w IH + Ri groups than in the 4w IH and 6w IH groups. HE staining showed that the morphology of bone cells in the NC group was normal, but the 4w IH group had mild edema of bone cells, reduction in trabecular bone, and destruction of bone microstructure. Changes were more severe in the 6w IH group than 4w IH. The 4w IH + Ri group was slightly improved compared with the 4w IH group. The 6w IH + Ri group was improved compared with the 4w IH + Ri group. The results of immunohistochemistry showed that the expression of CB1R in IH group was significantly higher than that in NC group. The expression of CB1R in the IH + Ri group was lower than that in the IH group. With the prolongation of hypoxia, the expression of CB1R in bone cells of IH group increased. The expression level of CB1R in IH + Ri group decreased with the prolongation of intervention time. Correlation analysis showed that the expression rate of CB1R in bone cells was positively correlated with the level of TRAP in serum. CONCLUSION: CIH increases serum TRAP levels and triggers metabolic bone disorder by activating bone CB1R. Intervention with CB1R antagonist (rimonabant) reduces the bone dysmetabolism in the CIH rat model.

2.
Chin J Integr Med ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31903532

RESUMO

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

3.
Cereb Cortex ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907535

RESUMO

Angiogenesis in the developing cerebral cortex accompanies cortical neurogenesis. However, the precise mechanisms underlying cortical angiogenesis at the embryonic stage remain largely unknown. Here, we show that radial glia-derived vascular cell adhesion molecule 1 (VCAM1) coordinates cortical vascularization through different enrichments in the proximal and distal radial glial processes. We found that VCAM1 was highly enriched around the blood vessels in the inner ventricular zone (VZ), preventing the ingrowth of blood vessels into the mitotic cell layer along the ventricular surface. Disrupting the enrichment of VCAM1 surrounding the blood vessels by a tetraspanin-blocking peptide or conditional deletion of Vcam1 gene in neural progenitor cells increased angiogenesis in the inner VZ. Conversely, VCAM1 expressed in the basal endfeet of radial glial processes promoted angiogenic sprouting from the perineural vascular plexus (PNVP). In utero, overexpression of VCAM1 increased the vessel density in the cortical plate, while knockdown of Vcam1 accomplished the opposite. In vitro, we observed that VCAM1 bidirectionally affected endothelial cell proliferation in a concentration-dependent manner. Taken together, our findings identify that distinct concentrations of VCAM1 around VZ blood vessels and the PNVP differently organize cortical angiogenesis during late embryogenesis.

4.
Chin J Integr Med ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31919749

RESUMO

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

5.
Obes Facts ; : 1-18, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935731

RESUMO

OBJECTIVE: To investigate the anorexigenic and anti-obesity effectiveness of electroacupuncture (EA) on high-fat-diet-induced (HFDI) obese rats with insulin resistance (IR) and to reveal the possible mechanisms of EA affecting SIRT1 (silent mating type information regulation 2 homolog 1) in the central nervous system (CNS). METHODS: We divided 60 rats into 6 groups. All interventions, including EA and intracerebroventricular administration, were performed after 8 weeks of model establishment. We tested obesity phenotypes like body weight (BW) gain; food intake; and IR levels including glucose infusion rate, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) during treatment. We detected protein expression and microscopic locations in hypothalamic SIRT1, the transcription factor FOXO1 (forkhead box protein O1), acetylated FOXO1 (Ac-FOXO1), pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) via Western blotting and immunofluorescence, and monitored gene expression by real-time polymerase chain reaction. RESULTS: Like the SIRT1 agonist, EA suppressed BW gain and IR levels in obese rats, but this was only partially blocked by the SIRT1 antagonist. EA could upregulate protein expression of hypothalamic SIRT1 and downregulate the acetylation level of FOXO1 in the hypothalamic arcuate nucleus (ARC), which decreased gene expression of NPY and increased that of POMC. The agonist targeted the hypothalamic SIRT1 gene, unlike EA, which targeted posttranscriptional regulation. CONCLUSION: EA could improve obesity in HFDI rats with IR via its anorectic effect. This effect targeted posttranscriptional regulation of the SIRT1 gene, which induced upregulation of ARC FOXO1 deacetylation and mediated the gene expression of POMC and NPY.

6.
Insect Biochem Mol Biol ; : 103315, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31945452

RESUMO

Melanin and cuticular proteins are vital cuticle components in insects. Cuticular defects caused by mutations in cuticular protein-encoding genes can obstruct melanin deposition. The effects of changes in melanin on the expression of cuticular protein-encoding genes, the cuticular and morphological traits, and the origins of these effects are unknown. We found that the cuticular physical characteristics and the expression patterns of larval cuticular protein-encoding genes markedly differed between the melanic and non-melanic integument regions. By using four p multiple-allele color pattern mutants with increasing degrees of melanism (+p, pM, pS, and pB), we found that the degree of melanism and the expression of four RR1-type larval cuticular protein-encoding genes (BmCPR2, BmLcp18, BmLcp22, and BmLcp30) were positively correlated. By modulating the content of melanin precursors and the expression of cuticular protein-encoding genes in cells in tissues and in vivo, we showed that this positive correlation was due to the induction of melanin precursors. More importantly, the melanism trait introduced into the BmCPR2 deletion strain Dazao-stony induced up-regulation of three other similar chitin-binding characteristic larval cuticular protein-encoding genes, thus rescuing the cuticular, morphological and adaptability defects of the Dazao-stony strain. This rescue ability increased with increasing melanism levels. This is the first study reporting the induction of cuticular protein-encoding genes by melanin and the biological importance of this induction in affecting the physiological characteristics of the cuticle.

7.
Zhongguo Zhen Jiu ; 40(1): 59-66, 2020 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-31930901

RESUMO

OBJECTIVE: To explore the mechanism of catgut embedding at back-shu points on nonalcoholic steatohepatitis (NASH) in rats based on IKK/IKB/NF-κB signaling pathway and downstream inflammatory factors. METHODS: Eighty SPF SD rats were selected, among them 10 rats were selected divided into a normal group (group A), and the remaining 70 rats were fed with high-fat diet to establish NASH model. At the end of 12 weeks, 10 rats were randomly selected to verify whether the model establishment was successful. Then the remaining 60 rats were randomly divided into a model group (group B), a catgut embedding at back-shu points group (group C), a catgut embedding at abdominal points group (group D), an acupuncture at back-shu points group (group E), a sham catgut embedding group (group F) and a western medication group (group G), 10 rats in each group. The rats in the group C were treated with catgut embedding at "Ganshu" (BL 18), "Pishu" (BL 20), "Weishu" (BL 21) and "Shenshu" (BL 23); the rats in the group D were treated with catgut embedding at "Daheng" (SP 15), "Fujie" (SP 14), "Huaroumen" (ST 24) and "Tianshu" (ST 25); the rats in the group E were treated with acupuncture at the same acupoints as the group C; the rats in the group F were treated with catgut embedding at back-shu points but the needle did not enter subcutaneous tissue gamma; the rats in the group G were treated with intragastric administration of vitamin E capsule. All the treatment was given for 4 weeks. The rats in the group A were fed with normal diet until the end of 16 weeks without any intervention. The rats in the group B continued to be fed with high-fat diet until the end of 16 weeks. After the intervention, the liver index was calculated; the liver histomorphology was observed by HE staining; the liver function [alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GGT), alkaline phosphatase (ALP)] and blood lipid [serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL)] were measured by serum biochemistry. The serum levels of TNF-α, IL-6 and IL-1ßwere detected by ELISA, and the expressions of IKK-α, NF-κBp65, IL-6, IL-1ß and TNF-α proteins in liver tissue were detected by Western blot. The temperature of the conception vessel and the governor vessel was measured by infrared thermography. RESULTS: Compared with the group A, the obvious steatosis and inflammatory cell infiltration were observed in the group B, and the body weight, liver wet-weight and liver index were all increased (P<0.01). Compared with the group B, the liver tissue morphology in the group C, the group D, the group E and the group G was improved in varying degrees, and the liver index was decreased (P<0.05), which was the most significant in the group C (P<0.05). Compared with the group A, the ALT, γ-GGT, ALP, TG, TC, LDL, TNF-α, IL-6 and IL-1ß were all increased in the group B (P<0.01); compared with the group B, the ALT, γ-GGT, ALP, TG, TC, LDL, TNF-α, IL-6 and IL-1ß in all intervention groups were all decreased in varying degrees (P<0.01, P<0.05), which was the most significant in the group C (P<0.01). Compare with the group A, the expressions of IKK-α, NF-κBp65, TNF-α, IL-6 and IL-1ßproteins in the group B were all increased (P<0.01); compared with the group B, the expressions of IKK-α, NF-κBp65, TNF-α, IL-6 and IL-1ßproteins in all intervention groups were decreased in varying degrees (P<0.05), which was the most significant in the group C (P<0.01). Compared with the group A, the temperature of the conception vessel and governor vessel was decreased in the group B (P<0.01). Compared with the group B, the temperature of the conception vessel and governor vessel was all increased in the group C, the group D and the group E (P<0.01); the temperature of the conception vessel in the group C was similar to that in the group D (P>0.05), while the temperature of the governor vessel in the group C was superior to that in the group D (P<0.05). CONCLUSION: The catgut embedding at back-shu points might inhibit the activation of IKK/IKB/NF-κB signaling pathway to interrupt the inflammatory cascade, and reduce the "second hit" of inflammatory factors on liver, which could slow down NASH progress and prevent and treat NASH.

8.
EBioMedicine ; 51: 102583, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31901866

RESUMO

BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear. METHODS: The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models. FINDINGS: In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3'-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA. INTERPRETATION: Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments.

9.
Aging (Albany NY) ; 12(1): 543-570, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31905173

RESUMO

Ligands of nicotinic acetylcholine receptors (nAChRs) are widely considered as potential therapeutic agents. The present study used primary hippocampus cells and APPswe/PSEN1dE9 double-transgenic mice models to study the possible therapeutic effect and underlying mechanism of the specific activation of α7 nAChR by PNU-282987 in the pathogenesis of Alzheimer's disease. The results indicated that activation of α7 nAChR attenuated the Aß-induced cell apoptosis, decreased the deposition of Aß, increased the expression of synaptic-associated proteins, and maintained synaptic morphology. Furthermore, in the APP/PS1_DT mice model, activation of α7 nAChR attenuated Aß-induced synaptic loss, reduced the deposition of Aß in the hippocampus, maintained the integral structure of hippocampus-derived synapse, and activated the calmodulin (CaM)-calmodulin-dependent protein kinase II (CaMKII)-cAMP response element-binding protein signaling pathway by upregulation of its key signaling proteins. In addition, activation of α7 nAChR improved the learning and memory abilities of the APP/PS1_DT mice. Collectively, the activation of α7 nAChR by PNU-282987 attenuated the toxic effect of Aß in vivo and in vitro, which including reduced deposition of Aß in the hippocampus, maintained synaptic morphology by partially reversing the expression levels of synaptic-associated proteins, activation of the Ca2+ signaling pathway, and improvement of the cognitive abilities of APP/PS1_DT mice.

10.
Oral Dis ; 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31957176

RESUMO

OBJECTIVES: FOXA2 gene methylation links to the progression of cancers, but has not been documented in oral cancer. Herein, we explore the role of FOXA2 in the migration of oral cancer cells. MATERIAL AND METHODS: Methylation-specific PCR was applied for gene methylation. Wound healing and transwell experiments were tested for cell migration. FOXA2 expression in oral cancer tissues was addressed by immunohistochemistry, followed by statistical analysis of its association with clinical manifestations and patient survival. RESULTS: FOXA2 bound to the promoter of CDH1 and enhanced the expression of its gene product E-cadherin, and decreased the cancer cell migration activity. High FOXA2 expression in oral cancer tissues was associated with high E-cadherin expression, decreased lymph node metastasis, and increased patient survival. CONCLUSION: FOXA2-E-cadherin link is involved in regulation of oral cancer cell metastasis and provides a new insight for the tumor suppressor activity of FOXA2 in oral cancer.

11.
Anticancer Drugs ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31789624

RESUMO

Hepatocellular carcinoma (HCC) is a complicated and poor prognosis cancer, necessitating the development of a potential treatment strategy. In this study, we initially revealed that LukS-PV belonged to leukocidin family performs an anti-HCC action. Then, we used liquid chromatography-mass spectrometry (LC/MS) to compare protein expression profiles of the LukS-PV-treated human HCC cell lines HepG2 and the control cells. GO annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out of differential expression followed by protein-protein interactome, to explore the underlying cancer suppressor mechanisms of LukS-PV for human HCC. A total of 88 upregulated proteins and 46 downregulated proteins were identified. The top 10 proteins identified by the MCC method are FN1, APP, TIMP1, nucleobindin-1, GOLM1, APLP2, CYR61, CD63, ENG, and CD9. Our observation on protein expression indicated that LukS-PV produces a signature affecting central carbon metabolism in cancer, galactose metabolism, and fructose and mannose metabolism pathways. The results give a functional effects and molecular mechanism insight, following LukS-PV treatment.

12.
Chin J Integr Med ; 25(12): 902-910, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31802424

RESUMO

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION: PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

13.
Patient Prefer Adherence ; 13: 2039-2046, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824139

RESUMO

Background: An increasing number of surgeries are performed as ambulatory surgeries, and mobile health applications (m-health apps) have therefore been designed to help provide patients with more convenient health-care services and improve the working efficiency of health-care professionals (HCPs). To find an effective approach to design such m-health apps, a study to evaluate ambulatory surgery patients' preferences is necessary. Methods: A structured questionnaire was distributed to 360 patients undergoing ambulatory surgery to understand their demographic characteristics, preferences regarding the features and functions of m-health apps and willingness to engage with m-health apps. Results: In total, 84.16% of ambulatory surgery patients stated that they would be willing to engage with an m-health app during the perioperative period. In addition, their top 10 necessary features and functions of m-health apps were related mainly to ambulatory surgery and communication with HCPs. Furthermore, younger age (χ 2=10.42, p<0.01), employment (χ 2=9.04, p<0.01), higher education (χ 2=13.67, p<0.01), longer daily use of phones (χ 2=11.84, p<0.01) and more frequent usage of m-health apps (χ 2=23.23, p<0.01) were associated with patients' willingness to engage with m-health apps, but only more frequent usage of m-health apps (OR=2.97, 95% CI=1.54-5.71, p<0.01) was found to be a predictor. Conclusion: This study presents an initial evaluation of ambulatory surgery patients' preferences regarding m-health apps. Gaining these insights will be useful to help us design an evidence-based, highly functional m-health app that best meets the needs of patients undergoing ambulatory surgery.

14.
J Cell Mol Med ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876386

RESUMO

The interaction between Axin and DVL2 is critical for the breaking down of the beta-catenin destruction complex and the activation of the Wnt/beta-catenin cascade. However, this biological process remains poorly understood. In the present study, TM4SF1 was identified as the interacting partner of DVL2 and positively regulated as Wnt/beta-catenin signalling by strengthening the DVL2-Axin interaction. The expression levels of TM4SF1 were elevated in hepatocellular carcinoma (HCC) and were induced by Kras signalling. The overexpression of TM4SF1 promoted the growth and motility of HCC cells, and up-regulated the target genes (Axin2 and cyclin D1). The down-regulation of TM4SF1 impaired the capability of HCC cells for growth, migration and metastasis. In addition, the down-regulation of TM4SF1 promoted the ubiquitination of beta-catenin. In summary, these results reveal the oncogenic functions of TM4SF1 in HCC progression and suggest that TM4SF1 might be a target for treatment.

15.
Huan Jing Ke Xue ; 40(9): 3949-3961, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854857

RESUMO

The characteristics of volatile organic compound (VOCs) species from various production procedures of wood-based panel production and other industrial processes in Chengdu were analyzed through gas chromatography-mass spectrometry (GC-MS) and other methods specified in national standards after the emissions of typical enterprises of wood-based panel production, pharmaceutical manufacturing, chemical production and other industrial processes in Chengdu had been sampled using sampling bottles and SUMMA canisters. Generally, the process of wood-based panel production includes glue making, glue mixing, sorting, and hot pressing, whereas the process of pharmaceutical manufacturing includes workshop production and wastewater treatment. The results showed that the main contribution species of VOCs in wood-based panel production and pharmaceutical manufacturing is oxygenated VOCs (OVOCs), accounting for more than 50% of the total VOCs emitted. The species from organized and unorganized emissions of formaldehyde manufacturing differed significantly. The main species of organized emissions was OVOCs, and that of unorganized emissions was halohydrocarbons. Emissions of VOCs from coating manufacturing were strongly correlated with the raw materials, and the corresponding emission species were composed mainly of aromatics and OVOCs. Except for glue mixing, the main species of VOCs in other process procedures of wood-based panel production was formaldehyde, with emission proportion of more than 50%. The primary species of VOCs in various processes of pharmaceutical manufacturing was ethanol; however 1,4-dioxane, ethyl acetate, and toluene were also important species. Moreover, the main VOCs from formaldehyde manufacturing were composed mainly of acetone and ethanol, and those of coating manufacturing were aromatic hydrocarbons such as p-xylene. The ozone formation potential was to characterize the reactivity of pollution sources in VOCs from wood-based panel production, pharmaceutical manufacturing, and chemical production. The results showed that the species of VOCs in different industries contributed similarly to the reactivity and that these species were mainly high-activity species such as formaldehyde, ethanol, and other OVOCs as well as some aromatic hydrocarbons. Therefore, supervision and regulation of enterprises of industrial processes is required with a focus on species with relatively large ozone formation potential. In addition, it is necessary to analyze the emission characteristics and chemical mechanism of various industries and to control O3 generation from the sources.

16.
Cancer Imaging ; 19(1): 87, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31849340

RESUMO

OBJECTIVE: The present study aimed to evaluate the short-term clinical performance and safety of percutaneous microwave ablation (MWA) techniques for the treatment of bone tumors. METHODS: This single-institution retrospective study investigated 47 cases of bone tumors treated by MWA from June 2015 to June 2018. The study included 26 patients (55.3%) with benign bone tumors and 21 patients (44.7%) with malignant bone tumors. The tumors were located in the spine or sacrum (15, 31.9%), the upper extremities (6, 12.8%), the lower extremities (17, 36.2%) and the pelvis (9, 19.1%). Outcomes regarding clinical efficacy, including pain relief, quality of life, and intervention-related complications, were evaluated before and after MWA using the visual analog scale (VAS) and the 36-item Short-Form Health Survey (SF-36) scoring system. RESULTS: Of the 47 patients included in this study, all of them completed follow-up examinations, with a mean follow-up duration of 4.8 ± 1.6 months (range, 2-9 months). Significantly improved VAS and SF-36 scores were recorded after the initial treatment (P<0.001), suggesting that almost 100% of patients experienced pain relief and an improved quality of life following surgery. No major intervention-related complications (e.g., serious neurovascular injury or infection) occurred during or after the treatment. We recorded only three minor posttreatment complications (6.4%, 3/47), which were related to thermal injury that caused myofasciitis and affected wound healing. CONCLUSION: In our study, the short-term efficacy of MWA was considerably favorable, with a relatively low rate of complications. Our results also showed that MWA was effective for pain relief and improved patients' quality of life, making it a feasible treatment alternative for bone tumors.

17.
Biotechnol Lett ; 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31865476

RESUMO

OBJECTIVE: L-methionine is an important sulfur-containing amino acid essential for humans and animals. Its biosynthesis pathway is complex and highly regulated. This study aims to explore the bottleneck limiting the improvement of L-methionine productivity and apply efficient strategies to increase L-methionine production in engineered E. coli. RESULTS: The enzyme O-succinylhomoserine sulfhydrylase involved in thiolation of OSH to form homocysteine was overexpressed in the engineered strain E. coli W3110 IJAHFEBC/PAm, resulting in L-methionine production increased from 2.8 to 3.22 g/L in shake flask cultivation. By exogenous addition of L-glycine as the precursor of one carbon unit, the titer of L-methionine was increased to 3.68 g/L. The glycine cleavage system was further strengthened for the efficient one carbon unit supply and a L-methionine titer of 3.96 g/L was obtained, which was increased by 42% compared with that of the original strain. CONCLUSIONS: Insufficient supply of one carbon unit was found to be the issue limiting the improvement of L-methionine productivity and its up-regulation significantly promoted the L-methionine production in the engineered E. coli.

18.
J Pharm Pharmacol ; 2019 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-31867739

RESUMO

OBJECTIVES: Neuroprotective potential of 7-methoxyflavanone (7MF) and its underlying mechanism was investigated. METHODS: Inhibitory effects of 7MF on microglial activation and neuroinflammation were evaluated by employment of lipopolysaccharide (LPS)-induced BV2 microglial cells. Changes in expression of genes and proteins of interest were investigated by RT-qPCR analysis and Western blot analysis. Inhibitory effects of 7MF on microglial overactivation were verified in LPS-treated C57BL/6J mice using ionized calcium-binding adaptor molecule-1 (Iba1) in the brain and interleukin-6 (IL-6) in serum as indicators. KEY FINDINGS: In BV2 cells, pretreatment with 7MF antagonized LPS-induced production of inflammatory factors IL-6, tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Mechanistic studies revealed reduced expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88), phosphorylated forms of c-Jun N-terminal kinase (p-JNK) and extracellular signal-regulated kinases 1/2 (p-ERK) but increased nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and cellular expression of NAD(P)H quinone dehydrogenase-1 (NQO-1) by 7MF. In LPS-treated mice, pretreatment with 7MF reduced the brain level of Iba1 and serum level of IL-6. CONCLUSIONS: 7-methoxyflavanone inhibited LPS-stimulated TLR4/MyD88/MAPK signalling and activated Nrf2-mediated transcription of antioxidant protein NQO-1, showing antineuroinflammatory effect, so it is a potential neuroprotective agent.

19.
Mol Ther Nucleic Acids ; 18: 533-545, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31671346

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as key regulators of cell differentiation and development. However, potential roles for lncRNAs in chondrogenic differentiation have remained poorly understood. Here we identify lncRNA ADAMTS9 antisense RNA 2, ADAMTS9-AS2, which controls the chondrogenic differentiation by acting as a competing endogenous RNA (ceRNA) in human mesenchymal stem cells (hMSCs). We screen out ADAMTS9-AS2 of undifferentiated and differentiated cells during chondrogenic differentiation by microarrays. Suppression or overexpression of lncRNA ADAMTS9-AS2 correlates with inhibition and promotion of hMSC chondrogenic differentiation, respectively. We find that ADAMTS9-AS2 can sponge miR-942-5p to regulate the expression of Scrg1, a transcription factor promoting chondrogenic gene expression. Finally, we confirm the function of ADAMTS9-AS2 to cartilage repair in the absence of transforming growth factor ß (TGF-ß) in vivo. In conclusion, ADAMTS9-AS2 plays an important role in chondrogenic differentiation as a ceRNA, so that it can be regarded as a therapy target for cartilage repair.

20.
Ann Transl Med ; 7(18): 489, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31700925

RESUMO

Background: Hypertension is a leading cause of stroke and the significance of blood pressure lowering treatment strategies for prevention of stroke has been well established. Despite the established and widespread use of BP lowering drugs, which one is better for stroke prevention is still debated. This study aimed to determine the most effective and safest blood pressure lowering treatments for stroke prevention among various single and combined therapies. Methods: A systematic search will be performed in PubMed and the Cochrane Library to identify RCTs and meta analyses of different pharmacological interventions for stroke prevention from January 01, 1966 to December 01, 2018. Primary efficacy outcome will be reduction of stroke incidence and safety outcome will be drug-related side effects withdraw. Study quality will be critically appraised based on the seven-point tool for assessing risk of bias by Cochrane collaboration. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. Discussion: This network meta-analysis will summarize the direct and indirect evidence aiming to provide a ranking of various blood pressure lowering strategies for prevention of stroke. The results of this meta-analysis may help the physicians in determining the best treatments for their patients in stroke prevention. Trial registration: CRD42018118454.

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