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1.
ChemMedChem ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527731

RESUMO

Pancreatic lipase (PL), a key target for the prevention and treatment of obesity, plays crucial roles in the hydrolysis and absorption of in dietary fat. In this study, a series of pyrazolones was synthesized, and their inhibitory effects against PL were assayed by using 4-methylumbelliferyl oleate (4-MUO) as optical substrate for PL. Comprehensive structure-activity relationship analysis of these pyrazolones led us to design and synthesize a novel compound P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro-3H-pyrazol-3-one) as a potent mixed-competitive inhibitor of PL (IC50 =0.30 µM). In addition, P32 displayed some selectivity over other known serine hydrolases. A molecular docking study for P32 demonstrated that the inhibitory activity of P32 towards PL could be attributed to the π-π interactions of 2-naphthyl unit (R1 ) and hydrophobic interactions of phenyl moiety (R3 ) with the active site of PL. Thus, P32 could serve as promising lead compound for the development of more efficacious and selective pyrazolones-type PL inhibitors for biomedical applications.

2.
Acad Radiol ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33593702

RESUMO

RATIONALE AND OBJECTIVES: The study investigated the potential of the combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging in predicting the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) after two cycles of NAC. MATERIALS AND METHODS: Eighty-seven patients with breast cancer who underwent MR examination before and after two cycles of NAC were enrolled. The patients were randomly assigned to a training cohort and a validation cohort (3:1 ratio). MRI parameters including tumor longest diameter, time-signal intensity curve, early enhanced ratio (E90), maximal enhanced ratio and ADC value were measured, and percentage change in MRI parameters were calculated. Univariate analysis and multivariate logistic regression analysis were used to evaluate independent predictors of pCR in the training cohort. The validation cohort was used to test the prediction model, and the nomogram was created based on the prediction model. RESULTS: This study demonstrated that the ADC value after two cycles of NAC (OR = 1.041, 95% CI (1.002, 1.081); p = 0.037), percentage decrease in E90 (OR = 0.927, 95% CI (0.881, 0.977); p =0.004) and percentage decrease in tumor size (OR = 0.948, 95% CI (0.909, 0.988); p = 0.011) were significantly important for independently predicting pCR. The prediction model yielded AUC of 0.939 and 0.944 in the training cohort and the validation cohort, respectively. CONCLUSION: The combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging could accurately predict pCR after two cycles of NAC. The prediction model and the nomogram had strong predictive value to NAC.

3.
Environ Toxicol ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522686

RESUMO

INTRODUCTION: Prostate cancer has significant mortality and metastasis rate in the male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmacological properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the associated molecular mechanisms. MATERIALS AND METHODS: The human prostate cancer cell lines, Du-145 and PC-3, were treated with various concentrations of verbascoside (0.1, 1, 10 µM) for 24 h followed by the examination of cell viability using MTT and trypan blue exclusion assays. Cell migration and invasion capacities were assessed by wound healing assay and transwell system. Western blot and immunofluorescence staining were used to detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-ß)/Smad signaling, and high-mobility group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis. RESULTS: Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-ß pathway was suppressed, which was demonstrated by the diminished expression of type I and II TGF-ß receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-ß signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. CONCLUSION: Verbascoside mitigated the cell proliferation and aggressiveness of prostate cancer via downregulation of TGF-ß-associated EMT progression through HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.

4.
Biomed Res Int ; 2021: 6611244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506022

RESUMO

Liquid biopsy is conducted through minimally invasive or noninvasive procedures, and the resulting material can be subjected to genomic, proteomic, and lipidomic analyses for early diagnosis of cancers and other diseases. Extracellular vesicles (EVs), one kind of promising tool for liquid biopsy, are nanosized bilayer particles that are secreted by all kinds of cells and that carry cargoes such as lipids, proteins, and nucleic acids, protecting them from enzymatic degradation in the extracellular environment. In this review, we provide a comprehensive introduction to the properties and applications of EVs, including their biogenesis, contents, sample collection, isolation, and applications in diagnostics based on liquid biopsy.

5.
Cell Signal ; : 109877, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33296740

RESUMO

Tooth and bone are independent tissues with a close relationship. Both are composed of a highly calcified outer structure and soft inner tissue, and both are constantly under mechanical stress. In particular, the alveolar bone and tooth constitute an occlusion system and suffer from masticatory and occlusal force. Thus, mechanotransduction is a key process in many developmental, physiological and pathological processes in tooth and bone. Mechanosensitive ion channels such as Piezo1 and Piezo2 are important participants in mechanotransduction, but their functions in tooth and bone are poorly understood. This review summarizes our current understanding of mechanosensitive ion channels and their roles in tooth and bone tissues. Research in these areas may shed new light on the regulation of tooth and bone tissues and potential treatments for diseases affecting these tissues.

6.
PeerJ ; 8: e10374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282557

RESUMO

Background: Periosteum plays critical roles in de novo bone formation and fracture repair. Wnt16 has been regarded as a key regulator in periosteum bone formation. However, the role of Wnt16 in periosteum derived cells (PDCs) osteogenic differentiation remains unclear. The study goal is to uncover whether and how Wnt16 acts on the osteogenesis of PDCs. Methods: We detected the variation of Wnt16 mRNA expression in PDCs, which were isolated from mouse femur and identified by flow cytometry, cultured in osteogenic medium for 14 days, then knocked down and over-expressed Wnt16 in PDCs to analysis its effects in osteogenesis. Further, we seeded PDCs (Wnt16 over-expressed/vector) in ß-tricalcium phosphate cubes, and transplanted this complex into a critical size calvarial defect. Lastly, we used immunofluorescence, Topflash and NFAT luciferase reporter assay to study the possible downstream signaling pathway of Wnt16. Results: Wnt16 mRNA expression showed an increasing trend in PDCs under osteogenic induction for 14 days. Wnt16 shRNA reduced mRNA expression of Runx2, collage type I (Col-1) and osteocalcin (OCN) after 7 days of osteogenic induction, as well as alizarin red staining intensity after 21days. Wnt16 also increased the mRNA expression of Runx2 and OCN and the protein production of Runx2 and Col-1 after 2 days of osteogenic stimulation. In the orthotopic transplantation assay, more bone volume, trabecula number and less trabecula space were found in Wnt16 over-expressed group. Besides, in the newly formed tissue Brdu positive area was smaller and Col-1 was larger in Wnt16 over-expressed group compared to the control group. Finally, Wnt16 upregulated CTNNB1/ß-catenin expression and its nuclear translocation in PDCs, also increased Topflash reporter luciferase activity. By contrast, Wnt16 failed to increase NFAT reporter luciferase activity. Conclusion: Together, Wnt16 plays a positive role in regulating PDCs osteogenesis, and Wnt16 may have a potential use in improving bone regeneration.

7.
PLoS One ; 15(12): e0243373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296413

RESUMO

OBJECTIVES: Taiwan has implemented the Diagnosis Related Groups (DRGs) since 2010, and the quality of care under the DRG-Based Payment System is concerned. This study aimed to examine the characteristics, related factors, and time distribution of emergency department (ED) visits, readmission, and hospital transfers of inpatients under the DRG-Based Payment System for each Major Diagnostic Category (MDC). METHODS: We conducted a retrospective cohort study using data from the National Health Insurance Research Database (NHIRD) from 2012 to 2013 in Taiwan. Multilevel logistic regression analysis was used to examine the factors related to ED visits, readmissions, and hospital transfers of patients under the DRG-Based Payment System. RESULTS: In this study, 103,779 inpatients were under the DRG-Based Payment System. Among these inpatients, 4.66% visited the ED within 14 days after their discharge. The factors associated with the increased risk of ED visits within 14 days included age, lower monthly salary, urbanization of residence area, comorbidity index, MDCs, and hospital ownership (p < 0.05). In terms of MDCs, Diseases and Disorders of the Kidney and Urinary Tract (MDC11) conferred the highest risk of ED visits within 14 days (OR = 4.95, 95% CI: 2.69-9.10). Of the inpatients, 6.97% were readmitted within 30 days. The factors associated with the increased risk of readmission included gender, age, lower monthly salary, comorbidity index, MDCs, and hospital ownership (p < 0.05). In terms of MDCs, the inpatients with Pregnancy, Childbirth and the Puerperium (MDC14) had the highest risk of readmission within 30 days (OR = 20.43, 95% CI: 13.32-31.34). Among the inpatients readmitted within 30 days, 75.05% of them were readmitted within 14 days. Only 0.16% of the inpatients were transferred to other hospitals. CONCLUSION: The study shows a significant correlation between Major Diagnostic Categories in surgery and ED visits, readmission, and hospital transfers. The results suggested that the main reasons for the high risk may need further investigation for MDCs in ED visits, readmissions, and hospital transfers.

8.
Huan Jing Ke Xue ; 41(12): 5458-5469, 2020 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-33374062

RESUMO

As an important primary producer, diatoms play a key role in aquatic ecosystems. However, little is known about the geographical distribution characteristics and driving factors of diatoms in large rivers. In this study, based on a high-throughput sequencing dataset of microeukaryotes, we analyzed the diversities and community compositions of planktonic and sedimentary diatoms in the 1200 km mainstream of Lancang River, a typical large river in southwestern China. The results showed that the diversities of planktonic and sedimentary diatoms in Lancang River were higher in the upstream natural section, and the community compositions of both groups were significantly different among different river sections. Dam construction had a significant effect on the dominant genera. Variance partitioning analysis showed that dispersal limitation was a major driving factor for the distribution pattern of planktonic and sedimentary diatoms, with explanation proportions of 16.7% and 29.8%. Co-occurrence network analyses showed that the interspecific competition relationship and network connectivity of the planktonic diatom network were stronger than the sedimentary ones. The network connectivity of planktonic and sedimentary diatoms in the cascade reservoir section was higher than that of the upstream natural section. This study will help to better understand the biogeographical distribution of diatoms in large rivers and provide useful information for ecological responses of diatoms to dam construction in rivers.


Assuntos
Diatomáceas , Rios , China , Ecossistema , Monitoramento Ambiental , Plâncton
9.
J Affect Disord ; 280(Pt A): 156-166, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33212407

RESUMO

BACKGROUND: Women with threatened preterm labor (TPTL) resting at home face several life challenges, but their psychological well-being has been ignored. This study aimed to explore the status and related factors of the psychological status of women with TPTL resting at home, and to compare the psychological status differences between TPTL and healthy pregnant women. METHODS: A cross-sectional, multiple time-point study was conducted to repeatedly assess depression, perceived stress, and distress in 49 TPTL women and 62 healthy pregnant women during pregnancy in Taiwan. Mann-Whitney U tests were used to compare the psychological status differences between these women and the generalized estimating equation was used to identify the factors related to their psychological status. RESULTS: The TPTL women's perceived stress at 24-27 weeks (p=0.047) and 32-35 weeks (p=0.04) and distress at each time point was significantly greater than that of healthy pregnant women (p<0.001). The common distress experienced by TPTL women was the inability to provide self-care and family care, the baby's health and safety, and to request leave from work for bed rest. Positive personalities, gestational age, preterm birth history, follow-up status and employment have been shown to be related to the psychological status of TPTL women. LIMITATIONS: The major limitation of this study is the small sample size. CONCLUSION: This study contributed to a better understanding of the emotional burdens of women with TPTL resting at home. Such findings highlight the need for constructing effective interventions to alleviate the psychological burden of these women.

10.
Environ Health ; 19(1): 110, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153466

RESUMO

BACKGROUND: Evidence is limited on excess risks of cardiovascular diseases (CVDs) associated with ambient air pollution in diabetic populations. Survival analyses without considering the spatial structure and possible spatial correlations in health and environmental data may affect the precision of estimation of adverse environmental pollution effects. We assessed the association between air pollution and CVDs in type 2 diabetes through a Bayesian spatial survival approach. METHODS: Taiwan's national-level health claims and air pollution databases were utilized. Fine individual-level latitude and longitude were used to determine pollution exposure. The exponential spatial correlation between air pollution and CVDs was analyzed in our Bayesian model compared to traditional Weibull and Cox models. RESULTS: There were 2072 diabetic patients included in analyses. PM2.5 and SO2 were significant CVD risk factors in our Bayesian model, but such associations were attenuated or underestimated in traditional models; adjusted hazard ratio (HR) and 95% credible interval (CrI) or confidence interval (CI) of CVDs for a 1 µg/m3 increase in the monthly PM2.5 concentration for our model, the Weibull and Cox models was 1.040 (1.004-1.073), 0.994 (0.984-1.004), and 0.994 (0.984-1.004), respectively. With a 1 ppb increase in the monthly SO2 concentration, adjusted HR (95% CrI or CI) was 1.886 (1.642-2.113), 1.092 (1.022-1.168), and 1.091 (1.021-1.166) for these models, respectively. CONCLUSIONS: Against traditional non-spatial analyses, our Bayesian spatial survival model enhances the assessment precision for environmental research with spatial survival data to reveal significant adverse cardiovascular effects of air pollution among vulnerable diabetic patients.

11.
Front Microbiol ; 11: 583194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193223

RESUMO

Tuberculosis (TB) is an infectious respiratory disease caused by Mycobacterium tuberculosis and one of the top 10 causes of death worldwide. Treating TB is challenging; successful treatment requires a long course of multiple antibiotics. Rifampicin (RIF) is a first-line drug for treating TB, and the development of RIF-resistant M. tuberculosis makes treatment even more difficult. To determine the mechanism of RIF resistance in these strains, we searched for novel mutations by sequencing. Four isolates, CDC-1, CDC-2, CDC-3, and CDC-4, had high-level RIF resistance and unique mutations encoding RpoB G158R, RpoB V168A, RpoB S188P, and RpoB Q432insQ, respectively. To evaluate their correlation with RIF resistance, plasmids carrying rpoB genes encoding these mutant proteins were transfected into the H37Rv reference strain. The plasmid complementation of RpoB indicated that G158R, V168A, and S188P did not affect the MIC of RIF. However, the MIC of RIF was increased in H37Rv carrying RpoB Q432insQ. To confirm the correlation between RIF resistance and Q432insQ, we cloned an rpoB fragment carrying the insertion (encoding RpoB Q432insQ) into H37Rv by homologous recombination using a suicide vector. All replacement mutants expressing RpoB Q432insQ were resistant to RIF (MIC > 1 mg/L). These results indicate that RpoB Q432insQ causes RIF resistance in M. tuberculosis.

12.
Food Chem Toxicol ; : 111837, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212213

RESUMO

Toll-like receptor 4 (TLR4) is an important mediator of hypertension and AngII induced cardiac inflammation and remodelling. In this study, the potential of nerolidol to ameliorate hypertension induced cardiac injuries and the underlying mechanism of action was explored by using in vitro and in vivo models. The in vitro analysis was performed on AngII challenged H9c2 cells and their ability to overcome cardiac inflammation and cardiac remodelling effects was determined by evaluating TLR4/NF-κB signalling cascade using Western blot analysis and immunofluorescence. The results were further ascertained using in vivo experiments. Eighteen week old male rats were randomly allocated into different groups i.e. Wistar Kyoto (WKY) rats, hypertensive SHRs, SHRs treated with a low-dose (75 mg/kg b.w) and high-dose of nerolidol (150 mg/kg b.w) and SHRs treated with captopril (50 mg/kg b.w) through oral gauge and finally analysed through echocardiography, histopathological techniques and molecular analysis. The results show that nerilodol target TLR4/NF-κB signalling and thereby attenuate hypertension associated inflammation and oxidative stress thereby provides effective cardioprotection. Echocardiography analysis showed that nerolidol improved cardiac functional characteristics including Ejection Fraction and Fractional Shortening in the SHRs. Collectively, the data of the study demonstrates nerolidol as a cardio-protective agent against hypertension induced cardiac remodelling.

13.
Bioorg Chem ; 105: 104367, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33080495

RESUMO

Human Carboxylesterase 2A (hCES2A), one of the most important serine hydrolases, plays crucial roles in the hydrolysis and the metabolic activation of a wide range of esters and amides. Increasing evidence has indicated that potent inhibition on intestinal hCES2A may reduce the excessive accumulation of SN-38 (the hydrolytic metabolite of irinotecan with potent cytotoxicity) in the intestinal tract and thereby alleviate the intestinal toxicity triggered by irinotecan. In this study, more than sixty natural alkaloids have been collected and their inhibitory effects against hCES2A are assayed using a fluorescence-based biochemical assay. Following preliminary screening, seventeen alkaloids are found with strong to moderate hCES2A inhibition activity. Primary structure-activity relationships (SAR) analysis of natural isoquinoline alkaloids reveal that the benzo-1,3-dioxole group and the aromatic pyridine structure are beneficial for hCES2A inhibition. Further investigations demonstrate that a steroidal alkaloid reserpine exhibits strong hCES2A inhibition activity (IC50 = 0.94 µM) and high selectivity over other human serine hydrolases including hCES1A, dipeptidyl peptidase IV (DPP-IV), butyrylcholinesterase (BChE) and thrombin. Inhibition kinetic analyses demonstrated that reserpine acts as a non-competitive inhibitor against hCES2A-mediated FD hydrolysis. Molecular docking simulations demonstrated that the potent inhibition of hCES2A by reserpine could partially be attributed to its strong σ-π and S-π interactions between reserpine and hCES2A. Collectively, our findings suggest that reserpine is a potent and highly selective inhibitor of hCES2A, which can be served as a promising lead compound for the development of more efficacious and selective alkaloids-type hCES2A inhibitors for biomedical applications.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1433-1439, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067933

RESUMO

OBJECTIVE: To study the difference of long non coding RNA (lncRNA) expression profile in bone marrow specimens of children with acute leukemia (AL) and other hematological disease children with normal bone marrows as controls, to screen the lncRNA related with childhood hematological diseases, and to explore the expression of lncRNA AC002454.1 and its clinical significance in AL children. METHODS: The microarray gene chip technology was used to statistically analyze the lncRNA in bone marrow cells of newly diagnose AL children and control children. Ninty-seren differentially expressed lncRNAs were selected. The bone marrow specimens of ALL children (21 cases), AML children (22 cases) and control children (21 cases) were verified and compared by using qRT-PCR; then the lncRNA with maximum differential expression-lncRNA AC002454.1 was selected and used to analyze the relation of relative expression level with clinical indicators. RESULTS: The microarray gene chip detection showed that 1 884 differentially expressed lncRNA were found in ALL children, and 4 289 differentically expressed lncRNA were found in AML children. The results confirming these differentically expressed lncRNA by qRT-PCR showed that 9 lncRNA expression were significantly up-regulated in ALL children, and 12 lncRNA expression were significantly up-regulated in AML children. Among these up-regulated lncRNA, the difference of AC002454.1 expression was most significant in ALL and AML children (P<0.05, P<0.01). The detection showed that there was a significant difference, in AC002454.1 relative expression level of newly diagnosed T-ALL and B-ALL children (P<0.01), moreover, this difference also was found in ALL and AML children (P<0.05). The detection analysis showed that there was no statistical difference in AC002454.1 relative expression level among the different sex, age, WBC count at initial diagnosis, chromosome, fusion gene, and risk stratification (P>0.05 for all). CONCLUSION: The lncRNA expression profile of AL children has been gained by using the lncRNA microarray gene chip technicology. AC002454.1 the significantly high expression exist in AL children, which relates with immunotyping and prognosis of AL children in a certain degree.


Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Doença Aguda , Criança , Humanos , Leucemia Mieloide Aguda/genética , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Longo não Codificante/genética
15.
Injury ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33059925

RESUMO

INTRODUCTION: The effect of using closed suction drainage system with the proximal femoral nail antirotation (PFNA) system fixation on outcomes in treating intertrochanteric fractures (ITFs) is still unknown. This prospective randomized controlled trial aimed to examine whether routine drainage is useful for PFNA fixation in ITFs. METHODS: A total of 80 patients with acute ITFs were treated with closed or mini-open reduction with PFNA fixation at the National Cheng Kung University Hospital and 60 eligible patients were randomized for whether to receive suction drainage. In clinical outcomes, the visual analog scale (VAS), morphine equivalent dosage, injured thigh width, body temperature, wound condition and wound infection were measured on postoperative day 1, 2, 4, 10, and 90. In laboratory outcomes, we evaluated hemoglobin and hematocrit levels postoperatively at different time points. Blood transfusion and total blood loss (TBL) were measured by Mercuriali's formula in millimeter. RESULTS: The results revealed that the amount of blood transfusion received by the drained group (543.3 mL) was more than that by the undrained group (367.8 mL; p = 0.0074), and similarly, TBL in the drained group (750.1 mL) was more than that in the undrained group (537.4 mL; p = 0.0067). Regarding clinical and laboratory outcomes, compared with the undrained group, the drained group had a higher VAS score on postoperative day 2 (p = 0.0216). No difference was observed between the 2 groups for morphine equivalent dosage, thigh swelling, wound infection and hematoma, hospitalization period, or total number of complications at every time point after index procedure. CONCLUSIONS: Blood transfusion requirement and TBL were higher in the drained group than in the undrained group of PFNA fixation for ITFs. In addition, the closed drainage system may have manifested no short-term benefit for wound condition postoperatively.

16.
Biochem Biophys Res Commun ; 533(3): 257-261, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33010888

RESUMO

The alginate lyase AlyQ from Persicobacter sp. CCB-QB2 is a three-domained enzyme with a carbohydrate-binding module (CBM) from family 32. The CBM32 domain, AlyQB, binds enzymatically cleaved but not intact alginate. Co-crystallisation of AlyQB with the cleaved alginate reveals that it binds to the 4,5-unsaturated mannuronic acid of the non-reducing end. The binding pocket contains a conserved R248 that interacts with the sugar's carboxyl group, as well as an invariant W303 that stacks against the unsaturated pyranose ring. Targeting specifically the non-reducing end is more efficient than the reducing end since the latter consists of a mixture of mannuronic acid and guluronic acid. AlyQB also seems unable to bind these two saturated sugars as they contain OH groups that will clash with the pocket. Docking analysis of YeCBM32, which binds oligogalacturonic acid, shows that the stacking of the pyranose ring is shifted in order to accommodate the sugar's axial C1-OH, and its R69 is accordingly elevated to bind the sugar's carboxyl group. Unlike AlyQB, YeCBM32's binding pocket is able to accommodate both saturated and unsaturated galacturonic acid.

17.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3812-3818, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893575

RESUMO

The current study was conducted to explore the effects of light intensity in cultivating environment on the cleaning away heat property of Viola yedoensis. In the present study, we established the acute inflammation model of ICR mice by injecting carrageenan. We compared the effects of V. yedoensis grown under different light intensities(100%, 80%, 50%, 35% and 5% of full sunlight) on mice body temperature, thermal radiation and the swelling degree of foot tissue before and after modeling observing by thermal infrared imaging technique and weighing method. The changes of energy metabolism related enzymes in liver were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the effects of V. yedoensis grown under different light intensities on human lung cancer cell A549 proliferation were explored with MTT method. The results showed that the body temperature of all groups of mice in V. yedoensis group were significantly lower than that of the blank group, except 5% full sunlight group, and the body temperature declined in positive proportion to light intensity. V. yedoensis group could alleviate foot swelling, reduce SDH activity in liver tissue(especially 100% full sunlight group and 80% full sunlight group were significantly lower than model group), and the degree of alleviating and reducing was positively correlated with light intensity. There was no significant difference in the activity of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase in liver tissue among treatments. The contents of IL-1ß, IL-6, TNF-α, PGE_2 in foot tissue of mice in V. yedoensis groups were significantly lower than those in model group. Among them, the lowest levels of IL-1ß, IL-6, TNF-α, PGE_2 were found in 80% full sunlight group, and there was no significant difference in TNF-α among different groups. The effects of V. yedoensis aqueous extract on A549 cell line proliferation inhibition rate increased with the light intensities of V. yedoensis cultivating environment. And the effects of V. yedoensis grown under 100% of full sunlight showed significantly higher A549 cell line proliferation inhibition rate compared with other groups(P<0.05). In summary, the light intensity of V. yedoensis cultivating environment is positively correlated with the cleaning away heat property of V. yedoensis, which conforms to the "light-cold and heat property" hypothesis,The V. yedoensis should be planted under full light according.


Assuntos
Viola , Animais , Temperatura Alta , Inflamação , Camundongos , Camundongos Endogâmicos ICR , Fator de Necrose Tumoral alfa
18.
Ulus Travma Acil Cerrahi Derg ; 26(5): 829-832, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32946106

RESUMO

Myelolipomas are rare benign tumors comprised of mature adipose tissue and hematopoietic elements. Adrenal myelolipomas associated with traumatic adrenal injury are relatively rare and less common on the left due to the limited size and well-protected position of the gland. A 59-year-old female admitted to the emergency department with intermittent left flank pain radiating to the left abdomen after falling from the bed six hours earlier. Her vital signs were stable, and she had tenderness over the left flank area and left abdomen. Her initial hemoglobin level was 12.9 g/dL. Bedside focused assessment with sonography for trauma revealed unclear left kidney margins. Contrast abdominal computed tomography (CT) revealed a space-occupying mass, 11.6×10.4×8.8 cm in dimension, in the left suprarenal region with active bleeding in the lower pole. Angiography did not reveal any active contrast medium extravasation. The CT-guided biopsy, was well performed concomitantly with angiography. Pathological assessment of the biopsy specimen revealed the presence of mostly adipose tissue with few erythrocytes and leukocytes. She was diagnosed with adrenal myelolipoma and admitted to the urology ward for left adrenalectomy with tumor resection. Traumatic adrenal injury, an unusual presentation of adrenal myelolipoma incidentally found in less than 5% of all abdominal blunt injuries, should be considered in cases of bleeding with trauma to the flank for prompt treatment.

19.
Food Funct ; 11(10): 8680-8693, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32940318

RESUMO

Human carboxylesterase 1A1 (hCES1A) is a promising target for the treatment of hyperlipidemia and obesity-associated metabolic diseases. To date, the highly specific and efficacious hCES1A inhibitors are rarely reported. This study aims to find potent and highly specific hCES1A inhibitors from herbs, and to investigate their inhibitory mechanisms. Following large-scale screening of herbal products, Styrax was found to have the most potent hCES1A inhibition activity. After that, a practical bioactivity-guided fractionation coupling with a chemical profiling strategy was used to identify the fractions from Styrax with strong hCES1A inhibition activity and the major constituents in these bioactive fractions were characterized by LC-TOF-MS/MS. The results demonstrated that seven pentacyclic triterpenoid acids (PTAs) in two bioactive fractions from Styrax potently inhibit hCES1A, with IC50 values ranging from 41 nM to 478 nM. Among all the identified PTAs, epibetulinic acid showed the most potent inhibition activity and excellent specificity towards hCES1A. Both inhibition kinetic analyses and in silico analysis suggested that epibetulinic acid potently inhibited hCES1A in a mixed inhibition manner. Collectively, our findings demonstrate that some PTAs in Styrax are potent and highly specific inhibitors of hCES1A and these constituents can be used as promising lead compounds for the development of more efficacious hCES1A inhibitors.

20.
Clin Pharmacol Ther ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978779

RESUMO

This study explored heterogeneous treatment effects (HTEs) of the real-world use of dipeptidyl peptidase-4 inhibitors (DPP-4is) vs. sulfonylureas (SUs) on cardiovascular diseases (CVDs) and mortality in patients with type 2 diabetes. Utilizing Taiwan's National Health Insurance Research Database, 19,853 propensity score-matched pairs of DPP-4i and SU stable users were identified. Classification and regression tree analyses and Cox models were applied to explore HTEs, according to various patient characteristics, on the composite CVDs, three-point major adverse cardiovascular event (MACE), and all-cause mortality. The absolute risk difference (ARD), hazard ratio (HR), and 95% confidence interval (CI) were estimated for comparing treatment effects. CVD history, ischemic stroke, or transient ischemic attack (IS/TIA) history, and age at treatment initiation were significant treatment effect modifiers. Patients with prior IS/TIA but without any other prior CVDs benefited most in reduced risks of composite CVDs from using DPP-4i vs. SU (ARD -4.31%, 95% CI -7.48% to -1.14%, HR 0.81, 95% CI 0.69 ~ 0.95), followed by those without prior IS/TIA and CVDs and initiated with DPP-4i at age < 69.3 years (ARD -0.90%, 95% CI -1.47% to -0.32%, HR 0.86, 95% CI 0.77 ~ 0.97). Patients with prior IS/TIA benefited most in reduced risks of three-point MACE from using DPP-4i vs. SU (ARD -4.22%, 95% CV -6.66% to -1.78%, HR 0.80, 95% CI 0.69 ~ 0.93), followed by those without prior IS/TIA and initiated with DPP-4i at age < 69.3 years (ARD -0.68%, 95% CI -1.08% to -0.29%, HR 0.81, 95% CI 0.70 ~ 0.93). Consideration of CVD and IS/TIA histories and age could facilitate individualized diabetes management of using DPP-4i vs. SU. Future studies are warranted given the hypothesis-generating nature in this exploratory research.

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