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1.
Support Care Cancer ; 29(1): 203-211, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32337625

RESUMO

BACKGROUND: Postoperative fatigue (POF) is a common complication after gastrointestinal tumor surgery, and it also brings negative effect on prognosis and life quality. However, there are no prediction models for POF, and studies of risk factors are not comprehensive. Therefore, the aim of this study is to investigate the risk factors and pick out the best prediction model for POF and to validate it. METHODS: A prospective study was conducted for patients undergoing elective gastrointestinal tumor surgery. Physiological, psychological, and socioeconomic factors were collected. Logistic regression, back-propagation artificial neural networks (BP-ANNs), and classification and regression tree (CART) were constructed and compared. RESULTS: A total of 598 patients consisting of 463 derivation sample and 135 validation sample were included. The incidence of POF in derivation sample, validation sample, and total were 58.3%, 57.0%, and 58.7%, respectively. Logistic regression results showed age, higher degree of education, lower personal monthly income, advanced cancer, hypoproteinemia, preoperative anxiety or depression, and limited social support were risk factors for POF. Receiver operating characteristic curve (ROC) and performance indices were used to test three models. BP-ANN was the best by the comparison of models, and its strong predictive performance was also validated. CONCLUSIONS: More attention should be paid on specific patients after gastrointestinal tumor surgery. BP-ANN is a powerful mathematical tool that could predict POF exactly. It may be used as a noninvasive screening tool to guide clinicians for early identification of high-risk patients and grading interventions.

2.
Eur J Med Chem ; : 112970, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33153765

RESUMO

To discover novel anticancer agents with potent and low toxicity, we designed and synthesized a range of new thiosemicarbazone-indole analogues based on lead compound 4 we reported previously. Most compounds displayed moderate to high anticancer activities against five tested tumor cells (PC3, EC109, DU-145, MGC803, MCF-7). Specifically, the represented compound 16f possessed strong antiproliferative potency and high selectivity toward PC3 cells with the IC50 value of 0.054 µM, compared with normal WPMY-1 cells with the IC50 value of 19.470 µM. Preliminary mechanism research indicated that compound 16f could significantly suppress prostate cancer cells (PC3, DU-145) growth and colony formation in a dose-dependent manner. Besides, derivative 16f induced G1/S cycle arrest and apoptosis, which may be related to ROS accumulation due to the activation of MAPK signaling pathway. Furthermore, molecule 16f could effectively inhibit tumor growth through a xenograft model bearing PC3 cells and had no evident toxicity in vivo. Overall, based on the biological activity evaluation, analogue 16f can be viewed as a potential lead compound for further development of novel anti-prostate cancer drug.

3.
Arthritis Rheumatol ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33174383

RESUMO

OBJECTIVE: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (KOA). METHODS: In this multicenter randomized sham-controlled trial, participants with KOA were randomly assigned to receive electro-acupuncture (EA), manual acupuncture (MA) or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors and statisticians were masked to treatment group assignment. The primary outcome was the response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function at week 8. The primary analysis was analyzed by the Z-test for proportions with the modified intention-to-treat population, which included all randomized participants who have at least one post-baseline measurement. RESULTS: Out of 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91/151), 58.6% (85/145), and 47.3% (69/146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5%CI, 0.2% to 25.9%; P=0.0234) for EA vs SA and 11.3% (97.5%CI, -1.6% to 24.4%; P=0.0507) for MA vs SA. The response rates in EA and MA groups were both significantly higher than the SA group at weeks 16 and 26. CONCLUSION: Among patients with KOA, compared with SA, intensive EA resulted in less pain and better function at week 8 and these effects persisted though week 26. Intensive MA had no benefit for KOA at week 8, although it showed benefits during follow-up.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33166630

RESUMO

BACKGROUND: Previous studies found different cut-offs of vena contracta area (VCA) to define severe tricuspid regurgitation (TR). The aim of this study was to investigate the factors associated with such variability through comparing technical variables and vendors. METHODS: Sixty-nine patients with scheduled tricuspid surgery were included in this prospective study. For each patient, TR data sets were obtained through three-dimensional (3D) color Doppler transthoracic echocardiography on at least two of the three systems: GE Vivid E95 (n=39), Siemens SC2000 prime (n=64) and Philips EPIQ 7C (n=60). The VCA was measured with default settings or with color baseline shifted on all three platforms, and with minimal color gain (10% to 20%) on GE. RESULTS: Color gain reduction and baseline shift caused significant change in VCA measurement ( -46% and 10% respectively). Inter-vendor comparison exhibited wide limits of agreement (the narrowest range, -74% to 167%), either with default or optimized settings. Different technical settings, platforms and reference methods all found different VCA cut-offs for severe TR. CONCLUSIONS: VCA measurement in TR is sensitive to technical factors and demonstrates inter-vendor variability. Technical variables in VCA measurement should be reported in detail for future research comparison. Same vendor and settings should be used for longitudinal analysis of TR VCA in the same patient in multi-vendor echocardiographic labs.

5.
J Mol Endocrinol ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151904

RESUMO

The aberrant histone methylation patterns contribute to the pathogenesis of endometriosis (EM). Mixed lineage leukemia 1 (MLL1), a histone methyltransferase, is crucial for gene expression by catalyzing the trimethylation of histone 3 lysine 4 (H3K4me3) in gene promoter. This study aimed to explore whether MLL1 is involved in EM-related infertility. The expressions of MLL1 and H3K4me3 were analyzed in the eutopic endometria from EM women with infertility (n=22) and the normal endometria from EM-free women (n=22). Mouse EM model was established. The MLL1 and H3K4me3 expression patterns in mice endometria of early pregnancy were also investigated. Immortalized human endometrial stromal cells (iESCs) were cultured and underwent in vitro decidualization. The chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to find the target gene of MLL1 during decidual process. Results showed that both MLL1 and H3K4me3 decreased in the eutopic endometrium from EM patients compared to that in the normal endometrium. During early pregnancy and the decidual process, MLL1 and H3K4me3 were significantly upregulated in stromal cells. ChIP-seq and ChIP-qPCR found that the cytochrome c oxidase subunit 4I 2 (COX4I2) was directly targeted by MLL1. The dominance of COX4I2-containing enzyme induced the expression of hypoxia-inducible factor-2α (HIF-2α), whose expression in the peri-implantation endometrium is essential for embryo implantation. Further results showed that MLL1 was directly regulated by progesterone (P4) - P4 receptors (PRs). Our study proved that MLL1 was involved in EM-related infertility, which may provide a novel approach to treat the nonreceptive endometrium in EM patients.

6.
Life Sci ; : 118786, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221346

RESUMO

AIMS: To assess the effects of three specific exercise training modes, aerobic exercise (A), resistance training (R) and autonomous climbing (AC), aimed at proposing a cross-training method, on improving the physical, molecular and metabolic characteristics of mice without many side effects. MATERIALS AND METHODS: Seven-week-old male mice were randomly divided into four groups: control (C), aerobic exercise (A), resistance training (R), and autonomous climbing (AC) groups. Physical changes in mice were tracked and analysed to explore the similarities and differences of these three exercise modes. Histochemistry, quantitative real-time PCR (RT-PCR), western blot (WB) and metabolomics analysis were performed to identify the underlying relationships among the three training modes. KEY FINDINGS: Mice in the AC group showed better body weight control, glucose and energy homeostasis. Molecular markers of myogenesis, hypertrophy, antidegradation and mitochondrial function were highly expressed in the muscle of mice after autonomous climbing. The serum metabolomics landscape and enriched pathway comparison indicated that the aerobic oxidation pathway (pentose phosphate pathway, galactose metabolism and fatty acid degradation) and amino acid metabolism pathway (tyrosine, arginine and proline metabolism) were significantly enriched in group AC, suggesting an increased muscle mitochondrial function and protein balance ability of mice after autonomous climbing. SIGNIFICANCE: We propose a new exercise mode, autonomous climbing, as a convenient but effective training method that combines the beneficial effects of aerobic exercise and resistance training.

7.
Vet Microbiol ; : 108919, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33191002

RESUMO

Marek's disease virus serotype 1 (MDV-1) is an important oncogenic α-herpesvirus that induces immunosuppressive and rapid-onset T-cell lymphomatous disease in poultry commonly referred to as Marek's disease (MD). As an excellent biomodel for the study of virally-induced cancers in natural hosts, MDV-1 encoded microRNAs (miRNAs) have been previously demonstrated with the potential roles to act as critical regulators in virus replication, latency, pathogenesis and especially in oncogenesis. Similar to the oncogenic γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), miR-M4-5p, the cellular microRNA-155 (miR-155) ortholog encoded by MDV-1, is also involved in MD oncogenesis. In lymphoblastoid cell lines derived from MDV-induced T-cell lymphomas, miR-M4-5p has been shown to be highly expressed and participate in inducing MD lymphomagenesis by regulating multiple signal pathways. Herein we report the new identification of the host WW domain-containing oxidoreductase (WWOX) as a biological target for miR-M4-5p. Further experiments revealed that as a critical oncomiRNA, miR-M4-5p promotes the proliferations of both chicken embryo fibroblast (CEF) and MSB-1 cells via suppressing cell apoptosis by targeting WWOX, a well-known tumor suppressor. Our data presents a novel insight in elucidating the regulatory mechanisms mediated by the viral analog of miR-155 that potentially contribute to MD tumorigenesis.

8.
Patient Educ Couns ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33191060

RESUMO

OBJECTIVE: To assess the effect of a patient decision aid on the quality of decision-making for patients with age-related cataracts. METHODS: 773 patients with cataracts aged 50-80 years were randomly assigned to receive either the intervention decision aid (including standard information, quantitative information on the possible outcomes of cataract surgery and a value clarification exercise) or the control booklet (including standard information). The primary outcome was informed choice (defined as adequate knowledge and congruency between attitudes and surgical intentions), which was assessed at 2 weeks after intervention via a telephone interview. RESULTS: The decision aid increased the proportion of participants making an informed choice, from 5.68 % in the control group to 27.7 % in the intervention group (P < 0.001). Compared with controls, more participants in the intervention group had adequate overall knowledge about cataract surgery (36.8 % vs. 8.79 % in controls; P < 0.001), and fewer participants intended to undergo surgery (22.5 % vs. 34.1 % in controls; P < 0.001). CONCLUSION: Use of the patient decision aid may increase the proportion of patients making informed choices. Importantly, it might also reduce the acceptance of operations. PRACTICE IMPLICATIONS: Patient decision aids represent a simple and low-cost tool to facilitate informed choice among patients with cataracts.

9.
Br J Ophthalmol ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243828

RESUMO

PURPOSE: To estimate the disease burden due to intraocular foreign bodies (IOFBs) and evaluate contributions of various risk factors to IOFB-associated disability-adjusted life-years (DALYs). METHODS: Global, regional and country-level number, rate and age-standardised rate of DALYs due to IOFBs were acquired from the Global Burden of Disease Study 2017 database. The Human Development Index (HDI) and other region and country-level data were obtained from open databases. Time trends for number, rate and age-standardised rate of DALYs due to IOFBs were calculated. Regression analysis was used to evaluate associations between age-standardised rate of DALYs and potential predictors. RESULTS: Global DALYs due to IOFBs rose by 43.7% between 1990 (139 (95% CI 70.8 to 233) thousand) and 2017 (202 (95% CI 105 to 335) thousand). The DALY rate remained stable while the age-standardised rate decreased during this period. Higher disease burden due to IOFBs was associated with higher glaucoma prevalence (ß=0.006, 95% CI 0.003 to 0.09, p<0.001), lower refractive error prevalence (ß=-0.0005, 95% CI -0.0007 to -0.0002, p<0.001), and lower income (ß=-0.020, 95% CI -0.035 to -0.006, p=0.007). CONCLUSION: Predictors of a greater burden of IOFB disability generally point to lower socioeconomic level. The association with glaucoma may reflect a complication of IOFB, increasing risk of vision loss and disability.

10.
J Dairy Sci ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33246628

RESUMO

Rapid and sensitive detection technology is the key to preventing food-borne disease outbreaks. In this study, a low-field nuclear magnetic resonance (NMR) biosensor based on polyamidoamine dendrimers was prepared for the rapid detection of Salmonella in milk. The polyamidoamine dendrimer was biotinylated by amide reaction and chelated to diethylene triamine pentacetate acid and gadolinium to form magnetic complexes. The antibody and magnetic complexes were combined through a streptavidin-biotin system using streptavidin as an intermediate bridge to obtain the immunoprobe. Salmonella was captured by the immunoprobe via antigen-antibody interaction and then separated from the mixture by membrane filtration. Finally, the longitudinal relaxation signal of the filtrate was obtained by NMR. The biosensor had excellent anti-interference capability and could detect Salmonella within 1.5 h at a sensitivity of 103 cfu mL-1. This method based on NMR can realize detection in complex samples and has the potential to be a quick and nondestructive method for detecting target bacteria.

11.
J Cell Physiol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33090488

RESUMO

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-ß, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.

12.
BMJ Open ; 10(10): e040196, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122324

RESUMO

OBJECTIVES: To investigate the clinical validity of using a handheld fundus camera to detect diabetic retinopathy (DR) in China. DESIGN AND SETTINGS: Prospective comparison study of the handheld fundus camera with a standard validated instrument in detection of DR in hospital and a community screening clinic in Guangdong Province, China. PARTICIPANTS: Participants aged 18 years and over with diabetes who were able to provide informed consent and agreed to attend the dilated eye examination with handheld tests and a standard desktop camera. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the proportion of those with referable DR (R2 and above) identified by the handheld fundus camera (the index test) compared with the standard camera. Secondary outcome was the comparison of proportion of gradable images obtained from each test. RESULTS: In this study, we examined 304 people (608 eyes) with each of the two cameras under mydriasis. The handheld camera detected 119 eyes (19.5%) with some level of DR, 81 (13.3%) of them were referable, while the standard camera detected 132 eyes (21.7%) with some level of DR and 83 (13.7%) were referable. It seems that the standard camera found more eyes with referable DR, although McNemar's test detected no significant difference between the two cameras.Of the 608 eyes with images obtained by desktop camera, 598 (98.4%) images were of sufficient quality for grading, 12 (1.9%) images were not gradable. By the handheld camera, 590 (97.0%) were gradable and 20 (3.2%) images were not gradable.The two cameras reached high agreement on diagnosis of retinopathy and maculopathy at all the levels of retinopathy. CONCLUSION: Although it could not take the place of standard desktop camera on clinic fundus examination, the handheld fundus camera showed promising role on preliminary DR screening at primary level in China. To ensure quality images, mydriasis is required.

13.
Curr Med Sci ; 40(5): 910-916, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123905

RESUMO

We aimed to explore the anti-inflammatory activity of mollugin extracted from Rubia cordifolia L, a traditional Chinese medicine, on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Thirty C57BL/6 mice were divided into a control group (n=6), a model group (n=6), and three experimental groups (40, 20, 10 mg/kg of mollugin, n=6 each). DSS solution (3%) was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model. Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10. Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3. The changes in colon pathology were detected by hematoxylin and eosin (HE) staining. Interleukin-1ß (IL-1ß) in the serum, and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN) in the tissues were measured by enzyme linked immunosorbent assay. Expression levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry. Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model. HE examinations demonstrated that mollugin treatment effectively improved the histological damage (P<0.05). The overproduction of IL-1ß and TNF-α was remarkably inhibited by mollugin treatment at doses of 20 and 40 mg/kg (P<0.05). Additionally, the levels of TLR4 in colon tissues were significantly reduced in mollugin-treated groups compared with the DSS group. Our findings demonstrated that mollugin ameliorates DSS-induced UC by inhibiting the production of pro-inflammatory chemocytokines.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33128532

RESUMO

Marchantia polymorpha L. (MPL), a common type of liverwort, has been used as herbal medicine to improve liver function in China for many years. Although modern studies revealed that MPL contains various polyphenols, terpenoids, and bis[bibenzyls], its biological effects on liver function have never been systemically studied in any animal model. In this study, flavonoids were extracted from MPL and the components in the MPL flavonoids as well as the antioxidant capacity of MPL flavonoids were analysed. A rat model of liver injury was induced by intraperitoneal injection of 10% carbon tetrachloride (CCl4). MPL flavonoids were administered daily at a dose of 50, 100, and 200 mg/kg body weight to the rats for 2 weeks prior to injection of CC14. Treatment with MPL flavonoids, especially at a dose of 200 mg/kg, attenuated CCl4-induced increases in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, nitric oxide, malondialdehyde, tumour necrosis factor-α, interleukin-1ß, and interleukin-6, as well as reductions in superoxide dismutase and glutathione peroxidase. Microarray analyses showed that co-treatment with MPL flavonoids and CCl4 up-regulated many antioxidant and anti-apoptotic genes, but down-regulated several pro-inflammatory genes, compared to treatment with CCl4 alone. PCR and western blot assays further identified that MPL flavonoids increased GPX1, TMX1, TXN, and XIAP expression, but decreased IL-1 and IL1RAP expression and inhibited Jak/stat3 signalling. In conclusion, MPL flavonoids exerted hepatoprotective effects via antioxidant and gene regulatory mechanisms. (Altern Ther Health Med.

15.
Life Sci ; 262: 118546, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035580

RESUMO

Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways.

16.
Vet Microbiol ; 250: 108860, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33045632

RESUMO

Pseudorabies virus (PRV), a porcine alphaherpesvirus, causes neurological disorders and reproductive failure in swine. It is capable of avoiding host antiviral responses, resulting in viral latency in infected animals. The mechanisms by which many PRV proteins help the virus to evade immune surveillance are poorly understood. In this study, we found that the PRV protein kinase, UL13, inhibits the IFN-ß signaling pathway by targeting interferon regulatory factor 3 (IRF3) for ubiquitination and degradation. PRV with mutant of UL13 is impaired in its ability to hinder IRF3 and interferon-ß (IFN-ß) activation, and has significantly less pathogenesis in mice that wild-type PRV. Our findings reveal an as yet undescribed mechanism utilized by PRV to evade host immune responses. PRV UL13 is a potential target for attenuated vaccines and antiviral drugs.

17.
Immunotherapy ; 12(18): 1313-1324, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33012209

RESUMO

Aim: This study aimed to evaluate the relationship between smoking status and efficacy of PD-1/PD-L1 inhibitors compared with conventional agents. Materials & methods: We reviewed Phase II/III trials of PD-1/PD-L1 inhibitors that reported hazard ratio (HR) in current/former and never smoking patients. Results: 15 qualifying trials comprising 9073 patients were eligible in this study. Compared with conventional agents, PD-1/PD-L1 inhibitors correlated with prolonged progression-free survival (HR: 0.73; 0.58-0.92) and overall survival (HR: 0.75; 0.71-0.80) in current/former smoker patients but not in never-smoker patients (HR: 1.15 and 0.86 for progression-free survival and overall survival, respectively; both p > 0.05) irrespective of cancer type, target of experimental agents and treatment strategy. Conclusion: There exit smoking status-based efficacy difference in anti-PD-1/PD-L1 immunotherapy.

18.
J Ethnopharmacol ; : 113422, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007391

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Gentiana dahurica Fisch (called Qin-Jiao in China), a traditional Chinese medicine, is used in China to treat alcoholic liver disease (ALD), but there has been no scientific report on the treatment of ALD. AIM OF THE STUDY: To investigate the therapeutic effects of Gentiana dahurica Fisch ethanol extract (GDEE) on ALD and to reveal its possible mechanism of action using RNA sequencing. MATERIALS AND METHODS: The model of ALD was established by continuous gavage with alcohol in mice, and GDEE was used to treat ALD. Pathological observation (HE staining, oil red O staining) and biochemical indicators were performed to evaluate liver tissue lesions and efficacy of GDEE. RNA sequencing analysis of liver tissues was carried out to elucidate the pathogenesis of ALD and the mechanism of hepatoprotective effect by GDEE. The RNA sequencing results were verified by detecting mRNA and protein expressions of acetyl coenzyme A carboxylase α (Acacα), fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1A (Cpt1a) by quantitative real-time polymerase chain reaction (PCR) and Western blot. RESULTS: Measurements of biochemical parameters showed that GDEE could inhibit the increased transaminase activities in the serum and lipid levels in the liver caused by alcohol. It was observed that GDEE could alleviate fatty degeneration, edema and cell necrosis caused by alcohol in the liver tissue. RNA sequencing analysis of liver tissues found that 719 genes and 1137 genes were significantly changed by alcohol and GDEE, respectively. GDEE reversed most of the changes in triglycerides synthesis-related genes up-regulated by alcohol. GDEE up-regulated most of the genes involved in the fatty acid degradation in ALD mice, while alcohol had little effect on them. In addition, GDEE suppressed most of the genes involved in cholesterol synthesis that were up-regulated by alcohol. GDEE up-regulated genes related to bile acid synthesis in ALD mice, and down-regulated genes related to bile acid reabsorption, while alcohol had no significant effect on genes related to bile acid metabolism. In the validation experiments, the Acacα, Fasn and Cpt1a expressions quantified by real-time PCR and Western blot were consistent with the RNA sequencing results. CONCLUSIONS: GDEE can alleviate liver damage and steatosis in ALD mice, and its mechanism of action may be related to the process of regulating triglycerides and cholesterol.

19.
Phytother Res ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006176

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.

20.
BMC Cardiovasc Disord ; 20(1): 435, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028234

RESUMO

BACKGROUND: To evaluate the coronary plaque characteristics of coronary arteries using computed tomography angiography (CTA) in order to assess the risk of coronary artery disease and the relevance of high sensitivity C reactive protein (hs-CRP) in patients with Diabetes Mellitus (DM). METHODS: The clinical data of 400 DM patients and 400 non-DM patients from January 2017 to December 2019 were collected, including the results of coronaryCTA. The plasma hs-CRP level of the two groups were divided into three groups: CRP ≤ 1, 1 < CRP ≤ 2, CRP > 2. The correlation of the degree of stenosis, the number of plaques, the nature of plaques and hs-CRP value between the two groups was evaluated. RESULTS: Compared with non-DM patients, the incidence of coronary artery plaques and lumen stenosis in DM patients was more higher than that in non-DM patients. DM patients were more likely to have more diseased vessels, especially diffuse vascular disease (12.00% vs 1.75%; P < 0.001). Subjects with high hs-CRP levels were more likely to have any plaque compared with individuals showing normal hs-CRP levels (p<0.01). There was no statistical significance in non calcified plaque with high level of hs-CRP, but the occurrence of plaque types in DM group was statistically significant compared with other hs-CRP levels in non DM group. Subjects with high hs-CRP were observed to be at increased risk for the presence of calcified plaque and severe narrowing in the unadjusted values. CONCLUSIONS: Coronary CTA combined with hs-CRP can accurately detect the characteristics of coronary artery stenosis and plaque in DM patients, which has an important clinical value in the risk assessment of coronary heart disease in DM patients.

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