Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 519
Filtrar
1.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807010

RESUMO

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.

2.
J Immunol Res ; 2021: 6656121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763493

RESUMO

Anti-drug antibody (ADAb) development is associated with secondary therapeutic failure in biologic-treated rheumatoid arthritis (RA) patients. With a treat-to-target goal, we aimed to identify biomarkers for predicting ADAb development and therapeutic response in adalimumab-treated patients. Three independent cohorts were enrolled. In Cohort-1, 24 plasma samples (6 ADAb-positive and 6 ADAb-negative patients at baseline and week 24 of adalimumab therapy, respectively) were assayed with immune-related microarray containing 1,636 correctly folded functional proteins. Next, we executed statistically powered autoantibody profiling analysis of 50 samples in Cohort-2 (24 ADAb-positive and 26 ADAb-negative patients). Subsequently, immunofluorescence assay was performed on 48 samples in Cohort-3 to correlate with ADAb titers and drug levels. The biomarkers were identified for predicting ADAb development and therapeutic response using the immune-related microarray and machine learning approach. ADAb-positive patients had lower drug levels at week 24 (median = 0.024 µg/ml) compared with ADAb-negative patients (median = 6.38 µg/ml, p < 0.001). ROC analysis based on the ADAb status revealed the top 20 autoantibodies with AUC ≥ 0.7 in differentiating both groups in Cohort-1. Analysis of Cohort-2 dataset identified a panel of 8 biomarkers (TROVE2, SSB, NDE1, ZHX2, SH3GL1, CARD9, PTPN20, and KLHL12) with 80.6% specificity, 77.4% sensitivity, and 79.0% accuracy in discriminating poor from EULAR responders. Immunofluorescence assay validated that anti-TROVE2 antibody could highly predict ADAb development and poor EULAR response (AUC 0.79 and 0.89, respectively). Multivariate regression analysis proved anti-TROVE2 antibody to be an independent predictor for developing ADAb. Immune-related protein microarray and replication analysis identified anti-TROVE2 antibody as a useful biomarker for predicting ADAb development and therapeutic response in adalimumab-treated patients.

3.
J Transl Med ; 19(1): 94, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653375

RESUMO

BACKGROUND: This study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free ß-subunit of human chorionic gonadotropin (free ß-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP). MATERIALS AND METHODS: In this retrospective case-control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free ß-hCG levels for HDP. RESULTS: DD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free ß-hCG > DD > DD + AFP > DD + free ß-hCG > AFP + free ß-hCG > AFP > free ß-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free ß-hCG alone and AFP + free ß-hCG could reduce false positive rate and improve + LR. CONCLUSION: DD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free ß-hCG + AFP had the greatest diagnostic value for SPE.

4.
Pathogens ; 10(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671315

RESUMO

Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential cardiotoxicity in severe COVID-19 patients.

5.
J Endod ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33745945

RESUMO

External cervical resorption (ECR) is a relatively uncommon, yet aggressive form of dental hard tissue destruction. It is initiated at the cervical aspect of the root surface and extends apico-coronally and circumferentially inside the dentin. In spite of the large number of case reports and clinical studies that have investigated ECR, its etiology remains unclear. Recent advancements in clinical assessment measures, such as the use of cone-beam computed tomography (CBCT), have provided additional insights into the nature of this lesion. This has facilitated the continued development and improvement of treatment methods for this condition. In this article, we provide an overview of the latest research pertaining to the etiology, histopathology, predisposing factors, diagnosis, classification, and treatment of ECR. Furthermore, we provide a summary of the different classification schemes for ECR, and highlight the relevant therapeutic principles.

6.
Adv Mater ; 33(11): e2005569, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33538067

RESUMO

The rapid development of modern industry and excessive consumption of petroleum-based polymers have triggered a double crisis presenting a shortage of nonrenewable resources and environmental pollution. However, this has provided an opportunity to stimulate researchers to harness native biobased materials for novel advanced materials and applications. Nanocellulose-based aerogels, using abundant and sustainable cellulose as raw material, present a third-generation of aerogels that combine traditional aerogels with high porosity and large specific surface area, as well as the excellent properties of cellulose itself. Currently, nanocellulose aerogels provide a highly attention-catching platform for a wide range of functional applications in various fields, e.g., adsorption, separation, energy storage, thermal insulation, electromagnetic interference shielding, and biomedical applications. Here, the preparation methods, modification strategies, composite fabrications, and further applications of nanocellulose aerogels are summarized, with additional discussions regarding the prospects and potential challenges in future development.

7.
Int J Mol Sci ; 22(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572934

RESUMO

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.

8.
J Hum Hypertens ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594246

RESUMO

Whether the first trimester maternal mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) can predict hypertensive disorders of pregnancy (HDP) is unclear. We conducted a retrospective case-control study with the total population of 539 gravidas, of these 447 had normal pregnancy, 27 had gestational hypertension (GH), 36 had preeclampsia (PE), and 29 had preeclampsia with severe features (SPE). Prediction for HDP was determined by the area under curve (AUC). Compared to the healthy group, the multiple of the median (MoM) for MAP was increased in the study groups, while PlGF and PAPP-A were decreased. When the cutoff values for MAP, PlGF, and PAPP-A were 1.069, 0.769, and 0.673 MoM, respectively, the sensitivities for predicting HDP were 0.517, 0.446, and 0.500 and the specificities were 0.744, 0.826, and 0.769, respectively. To predict GH, the highest AUC was 0.755 (95% CI: 0.655-0.856, p < 0.001) based on MAP, PlGF, and PAPP-A. The combined PlGF and PAPP-A had the highest AUC (0.683 [95% CI: 0.584-0.782, p < 0.001] and 0.755 [95% CI: 0.682-0.829, p < 0.001]) for prediction of PE and SPE. We found that MAP, serum levels of PlGF, and PAPP-A in the first trimester pregnancy are markers that predict HDP in the third trimester. The combination of markers is far superior to single markers alone. To improve the diagnostic value, specific cutoff values should be applied to GH, PE, SPE in each condition.

9.
Nanoscale ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514980

RESUMO

Enabling stable lithium metal anodes is significant for developing electrochemical energy storage systems with higher energy density. However, safety hazards, infinite volume expansion, and low coulombic efficiency (CE) of lithium metal anodes always hinder their practical application. Herein, a nano-thickness lithiophilic Cu-Ni bimetallic coating was synthesized to prepare dendrite-free lithium metal anodes. The electron cloud migration effect caused by the different electronegativities of Cu and Ni can achieve lithiophobicity/lithiophilicity transformation and thus promote uniform Li deposition/dissolution. By changing the ratio of Cu to Ni, the electron cloud migration can be reasonably adjusted for obtaining dendrite-free lithium anodes. As a result, the as-obtained Cu-Ni bimetallic coating is able to guarantee dendrite-free lithium metal anodes with a stable long cycling time (>1500 hours) and a small voltage hysteresis (∼26 mV). In addition, full cells with LiFePO4 as a cathode present excellent cycling stability and high coulombic efficiency. This work can open a new avenue for optimizing the lithiophilicity of materials and realizing dendrite-free anodes.

10.
Food Funct ; 12(4): 1458-1468, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507202

RESUMO

BACKGROUND: Eccentric muscle contraction is an inherent component of numerous sporting movements but can result in muscle fatigue and injury, especially when engaging in unfamiliar exercise, which requires pharmacological intervention. Jilin ginseng root (GS) has been used to protect muscles and reduce the risk of exercise injury. AIM OF THE STUDY: In this study, we sought to examine and demonstrate the effectiveness of using GS in preventing muscle stiffness and reducing the risk of exercise injury in women. METHODS: Twenty females were randomly assigned to GS and placebo groups. Body composition, serum biochemistry index, kinematics, and endurance exercise tests were measured at two time point presupplementation and 6 weeks after supplementation. The major compounds of GS were characterized using a high-performance liquid chromatograph with a gradient delivery system (HPLC). RESULTS: After 6 weeks of supplementation, the GS group exhibited significant increases in the serum levels of free fatty acids and glucose as well as greater maximum oxygen consumption (VO2 max, mL min-1 kg-1) compared with the placebo group in an exhaustive biking test. Following drop jump tests, the jump height and reactive strength index were increased in the GS group after completing 70 DJs. In addition, subjects in the GS group also showed decreased knee and ankle stiffness in DJs, leading to reduced fatigue associated with eccentric movement. CONCLUSIONS: GS supplementation leads to ameliorates drop jump muscle stiffness and fatigue in females and is to be used as a nutrient supplement to reduce the risk of musculoskeletal system injuries when performing drop jumps.

11.
J Enzyme Inhib Med Chem ; 36(1): 425-436, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33445997

RESUMO

In discovery of HDAC inhibitors (HDACIs) with improved anticancer potency, structural modification was performed on the previous derived indole-3-butyric acid derivative. Among all the synthesised compounds, molecule I13 exhibited high HDAC inhibitory and antiproliferative potencies in the in vitro investigations. The IC50 values of I13 against HDAC1, HDAC3, and HDAC6 were 13.9, 12.1, and 7.71 nM, respectively. In the cancer cell based screening, molecule I13 showed increased antiproliferative activities in the inhibition of U937, U266, HepG2, A2780, and PNAC-1 cells compared with SAHA. In the HepG2 xenograft model, 50 mg/kg/d of I13 could inhibit tumour growth in athymic mice compared with 100 mg/kg/d of SAHA. Induction of apoptosis was revealed to play an important role in the anticancer potency of molecule I13. Collectively, a HDACI (I13) with high anticancer activity was discovered which can be utilised as a lead compound for further HDACI design.

12.
Life (Basel) ; 10(12)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297350

RESUMO

Apolipoprotein E (ApoE) polymorphism and adipokines are linked to atherosclerosis. We aimed to investigate the associations of apoE genotypes with adipokines, inflammatory parameters, and cardiovascular disease (CVD) risks in rheumatoid arthritis (RA) patients. We enrolled 152 RA patients and 49 healthy control (HC) subjects. The apoE genotyping was determined by a polymerase chain reaction, while plasma levels of adipokines and inflammatory cytokines were measured with ELISA. Although apoE genotypes distributions were indistinguishable between RA patients and HC, we found significantly higher levels of apoE and adipokines in RA patients compared with HC. RA patients with ε2ε3 genotype had lower levels of TNF-α, IL-6, resistin, and visfatin, but higher leptin levels compared with ε3ε3 genotype patients. Patients with ε3ε4 genotype had significantly higher low-density lipoprotein-cholesterol (LDL-C) levels and atherogenic index scores compared with ε2ε3 genotype carriers. Moreover, patients with ε2ε3 genotype had significantly lower 10-year CVD risk than ε3ε3 or ε3ε4 genotype patients. ε3ε4 genotype and adiponectin levels were independent predictors of a high 10-year CVD risk. RA patients with ε2ε3 genotype are associated with lower levels of TNF-α, IL-6, resistin, visfatin, and CVD risk, while RA patients with ε3ε4 genotype exhibited higher levels of LDL-C, insulin resistance, and higher CVD risks.

13.
BMC Pregnancy Childbirth ; 20(1): 776, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317474

RESUMO

BACKGROUND: To determine whether advanced maternal age (AMA) causes changes in the maternal serum markers of Trisomy 21, 18 and open neural tube defects (ONTD) during the second trimester of pregnancy. Our research aims to develop new cut-off values for AMA in order to reduce the need for further invasive testing. METHODS: This retrospective cohort study involved 12,739 pregnant women with AMA and 197,101 pregnant women with non-AMA. We then compared the two groups with respect to the positive rate and positive predictive value (PPV) of Trisomy 21, 18 and ONTD. Pregnant women with Trisomy 21, 18 and ONTD were diagnosed by karyotyping the amniotic fluid and by ultrasound diagnosis. RESULTS: Compared to the non-AMA group, the multiple of the median (MOM) of free beta- human chorionic gonadotropin (free ß-hCG), alpha-fetoprotein (AFP), and the risk value forTrisomy 21, were significantly higher in the AMA group (all P < 0.001). The positive rates of Trisomy 21, 18, and ONTD in the AMA group were significantly higher than those in the control group (all P < 0.001). In the AMA group, the PPVs for Trisomy 21 and other deformities were significantly higher (all P < 0.001), although the PPVs for Trisomy 18 and ONTD were similar to those of the non-AMA group. The area under the curve (AUC) values for the AMA group were higher than the non-AMA group, based on free ß-hCG MoM, AFP MoM, and the risk value of Trisomy 21. The cut-off value for the risk value of Trisomy 21 was 1/172 for the AMA, group and 1/780 for the non-AMA group. CONCLUSIONS: The positive rates for Trisomy 21, 18 and ONTD, and the PPV for Trisomy 21 and other deformities were significantly higher in the AMA group. It is essential for pregnant women with AMA to be tested using appropriate cut-off values of serum markers screening for Trisomy 21 during the second trimester of pregnancy to improve the efficacy of prenatal screening and reduce the need for further invasive testing.

14.
Carcinogenesis ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347535

RESUMO

CircRNAs (circular RNAs), recently identified as a critical regulator in tumorigenesis, participate in colorectal cancer (CRC) growth. However, role of hsa_circRNA_002144 in CRC was poorly understood. Firstly, hsa_circRNA_002144 showed significantly elevation in both of CRC tissues and cell lines, and suggested closely associated with poor prognosis in patients. Secondly, data from functional assays revealed that silence of hsa_circRNA_002144 inhibited CRC progression with reduced cell viability, proliferation, migration and invasion, while enhanced cell apoptosis. In addition, in vivo CRC growth and metastasis were also suppressed by knockdown of hsa_circRNA_002144. However, CRC progression was promoted with over-expression of hsa_circRNA_002144. Thirdly, hsa_circRNA_002144 colocalized with miR-615-5p in the cytoplasm of CRC cells, and decreased miR-615-5p expression. Moreover, miR-615-5p could target LARP1 (La ribonucleoprotein 1, translational regulator). Lastly, the suppressive effects of hsa_circRNA_002144 knockdown on CRC progression was reversed by LARP1 over-expression. In conclusion, hsa_circRNA_002144 could sponge miR-615-5p to promote CRC progression through regulation of LARP1, providing a therapeutic target for cancer intervention.

15.
Int J Med Sci ; 17(17): 2888-2894, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162817

RESUMO

Background: Fidgetin (FIGN), a conserved ATP-dependent enzyme, is regarded as a hepatocellular carcinoma (HCC) risk gene, but the prognostic implication of FIGN in HCC remains obscure. In this study, we investigate the expression of FIGN in HCC and to evaluate its prognostic value. Methods: A total of 216 patients with HCC who experienced hepatectomy were recruited in this study. The expression of FIGN in HCC samples was evaluated by quantitative real-time PCR, immunohistochemistry and immunoblotting analysis. And Cox regression model was used to evaluate the prognostic value of all covariates. Results: Of the 216 HCC patients, 67 (31.0%) had tumors with high FIGN expression and 149 (69.0%) had tumors with low FIGN expression. FIGN expression was positively correlated with TNM stage (P = 0.039), tumor with incomplete capsule (P = 0.036), microvascular invasion (P = 0.023), and portal vein tumor thrombus (P = 0.003). High expression of FIGN indicated shorter overall survival (OS) (hazard ratio: 4.569, P = 0.036) and disease-free survival (DFS) (hazard ratio: 6.487, P = 0.001). Conclusion: Our results indicate that high Fidgetin expression is associated with tumor progression and suggest a worse prognosis in HCC. Fidgetin might serve as a potential target for therapy.

16.
Regul Toxicol Pharmacol ; 119: 104817, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171209

RESUMO

The production of soy leghemoglobin C2 (LegH) by Pichia pastoris (syn. K. phaffii) was developed by Impossible Foods to serve as a sustainable source of flavor and aroma in plant-based meats. The potential allergenicity and toxicity of a LegH from a new production process was analyzed using bioinformatics, proteomics and a pepsin digestion assay on leghemoglobin, and residual host proteins. LegH in the new preparation had the same proteoform as in the previous preparations as well as in soy root nodule extracts. Results of seven Pichia proteins, each representing ≥1% of the total protein content, showed no significant sequence matches to any known allergens with the exception of one, which matched the highly conserved wheat GAPDH, whose protein homolog is found in fungi and humans. Based on the data, it is unlikely that there is any risk of cross reactivity between LegH Prep and GAPDH. Pichia protein sequences showed very good alignment to homologous proteins from many common yeasts including Saccharomyces sp. In addition, LegH and Pichia proteins were all rapidly digested in a pepsin digest assay. In conclusion, LegH Prep from this P. pastoris production process is unlikely to pose a risk of food allergenicity.

17.
Front Oncol ; 10: 592385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178617

RESUMO

In discovery of HDAC inhibitors with improved activity and selectivity, fluorine substitution was performed on our previously derived lead compound. The synthesized molecules N-(2-amino-4-fluorophenyl)-4-[bis-(2-chloroethyl)-amino]-benzamide (FNA) exhibited class I (HDAC1, 2, and 3) selectivity in the in vitro enzymatic assay and especially potent against HDAC3 activity (IC50: 95.48 nM). The results of in vitro antiproliferative assay indicated that FNA exhibited solid tumor cell inhibitory activities with IC50 value of 1.30 µM against HepG2 cells compared with SAHA (17.25 µM). Moreover, the in vivo xenograft model study revealed that FNA could inhibit tumor growth with tumor growth inhibition (TGI) of 48.89% compared with SAHA (TGI of 48.13%). Further HepG2 cell-based apoptosis and cell cycle studies showed that promotion of apoptosis and G2/M phase arrest make contributions to the antitumor activity of FNA. In addition, drug combination results showed that 0.5 µM of FNA could improve the anticancer activity of taxol and camptothecin. The present studies revealed the potential of FNA utilized as a high potent lead compound for further discovery of isoform selective HDAC inhibitors.

18.
BMC Surg ; 20(1): 282, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183289

RESUMO

BACKGROUND: Gardner syndrome is a subtype of familial adenomatous polyposis (FAP), characterized by a combination of adenomatous intestinal polyps and extracolonic lesions such as multiple osteomas, dental abnormalities, and soft tissue tumors. Although 12% of patients with intestinal polyposis of FAP may occur intra-abdominal desmoid tumors, pregnancy complicating with giant abdominal desmoid tumors is a relatively rare case. CASE PRESENTATION: A 28-year-old pregnant woman was diagnosed with Gardner syndrome in whom an intra-abdominal tumor was found a year after undergoing a laparoscopic total colectomy due to family adenomatous polyposis. At 32 weeks' gestation, she presented to our department for the third time complaining upper abdominal pain caused by the giant abdominal mass about 21 × 12 cm2 in size. After multidisciplinary consultation and discussion, the decision of fetal preservation treatment was made. After the delivery of a baby girl, abdominal mass resection was performed, and pathological examination revealed a fibrous adenoma. The patient was discharged after a week and was uneventful in the follow-up for half a year. CONCLUSIONS: Gardner syndrome is characterized by typical syndrome including family adenomatous polyposis and extra-intestinal tissue tumor. Were desmoid tumors rarely as large as fetus and local aggressively. In our case, we selected surgery to remove the intra-abdominal desmoid tumor after the natural delivery of the fetus and no abnormalities were observed during the 6 months follow-up. Women during pregnancy have an increased risk for the development of desmoid tumors, likely with the sex hormone to be one of the triggers. Therefore, we suggested that when a patient with Gardner syndrome desire to conceive again, they should go to the hospital for a regular review at least once every 3 months.

19.
Patterns (N Y) ; 1(2): 100013, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33205091

RESUMO

Analyzing coordination environments using X-ray absorption spectroscopy has broad applications in solid-state physics and material chemistry. Here, we show that random forest models trained on 190,000 K-edge X-ray absorption near-edge structure (XANES) spectra can identify the main atomic coordination environment with a high accuracy of 85.4% and all associated coordination environments with a high Jaccard score of 81.8% for 33 cation elements in oxides, significantly outperforming other machine-learning models. In a departure from prior works, the coordination environment is described as a distribution over 25 distinct coordination motifs with coordination numbers ranging from 1 to 12. More importantly, we show that the random forest models can be used to predict coordination environments from experimental K-edge XANES with minimal loss in accuracy. A drop-variable feature importance analysis highlights the key roles that the pre-edge and main-peak regions play in coordination environment identification.

20.
Medicine (Baltimore) ; 99(41): e22504, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031288

RESUMO

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Herpes Zoster/epidemiologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Linfócitos T , Idoso , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Interferon gama/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...