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1.
Dis Markers ; 2021: 2148820, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659588

RESUMO

Parkinson's disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.

2.
World J Clin Cases ; 9(21): 5980-5987, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34368317

RESUMO

BACKGROUND: Caudate lobe hemangioma of the liver is relatively rare. Due to the unique anatomical location of the caudate lobe, the caudate lobectomy accounts for only 0.5% to 4% of hepatic resection, which is difficult to operate and takes a long time, and even has many postoperative complications. CASE SUMMARY: A 34-year-old female presented with a 1 year history of intermittent pain in the right side of the waist without obvious inducement. All laboratory blood tests were within normal limits. Indocyanine green 15 min retention was rated 2.9%, and Child-Pugh was rated A. Computed tomography and magnetic resonance imaging diagnosed giant hemangioma of the caudate lobe with hemangioma of left lobe of liver. After discussion, surgical treatment was performed, which lasted 410 min, with intraoperative bleeding of about 600 mL and postoperative pathological findings of cavernous hemangioma. There were no obvious postoperative complications, and the patient was discharged 10 d after surgery. CONCLUSION: Caudate lobectomy is difficult due to its special anatomical location. Under the condition of fully exposing the anatomy of the first porta hepatis, the second porta hepatis, the third porta hepatis, the fourth porta hepatis and middle hepatic vein and combining with the Pringle maneuver, caudate lobectomy can be performed in a precise and safe process.

3.
Int J Rheum Dis ; 24(10): 1247-1256, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314100

RESUMO

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

4.
World J Surg Oncol ; 19(1): 203, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229720

RESUMO

BACKGROUND: To evaluate the outcomes of pancreaticogastrostomy and pancreaticojejunostomy after pancreatoduodenectomy with the help of a meta-analysis. METHODS: Randomized controlled trials comparing pancreaticogastrostomy and pancreaticojejunostomy were searched electronically using PubMed, The Cochrane Library, and EMBASE. Fixed and random-effects were used to measure pooled estimates. Research indicators included pancreatic fistula, delayed gastric emptying, postoperative hemorrhage, intraperitoneal fluid collection, wound infection, overall postoperative complications, reoperation, and mortality. RESULTS: Overall, 10 randomized controlled trials were included in this meta-analysis, with a total of 1629 patients. The overall incidences of pancreatic fistula and intra-abdominal collections were lower in the pancreaticogastrostomy group than in the pancreaticojejunostomy group (OR=0.73, 95% CI 0.55~0.96, p=0.02; OR=0.59, 95% CI 0.37~0.96, p=0.02, respectively). The incidence of B/C grade pancreatic fistula in the pancreaticogastrostomy group was lower than that in the pancreaticojejunostomy group, but no significant difference was observed (OR=0.61, 95%CI 0.34~1.09, p=0.09). Postoperative hemorrhage was more frequent in the pancreaticogastrostomy group than in the pancreaticojejunostomy group (OR=1.52; 95% CI 1.08~2.14, p=0.02). No significant differences in terms of delayed gastric emptying, wound infection, reoperation, overall postoperative complications, mortality, exocrine function, and hospital readmission were observed between groups. CONCLUSION: This meta-analysis suggests that pancreaticogastrostomy reduces the incidence of postoperative pancreatic fistula and intraperitoneal fluid collection but increases the risk of postoperative hemorrhage compared with pancreaticojejunostomy.


Assuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia , Gastrostomia/efeitos adversos , Humanos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Am J Pathol ; 191(8): 1431-1441, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34294192

RESUMO

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Nefropatias/diagnóstico , Glomérulos Renais/patologia , Biópsia , Humanos , Nefropatias/patologia , Coloração e Rotulagem
6.
Nat Prod Bioprospect ; 11(5): 545-555, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34061296

RESUMO

One novel spirolactone, aquilarisinolide (1), three new sesquiterpenoids, (2R,4S,5R,7R)-2-hydroxyeremophila-9,11-dien-8-one (2), (1R,4S,5S,7R,11R)-13-hydroxyepidaphnauran-9-en-8-one (3), and (4R,5S,7R,8S,10S,13R)-8,13-dihydroxyrotunda-1,11-dien-3-one (4), together with 13 known compounds (5-17) were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). The structures of the new compounds were elucidated based on the analysis of NMR and MS data and theoretical calculations their ECD spectra. The isolated compounds were evaluated for their protective activities against PC12 cell injury induced by corticosterone (CORT) and 1-methyl-4-phenylpyridine ion (MPP+), as well as inhibitory activities against BACE1. Compound 4, 5,6-dihydroxy-2-(2-phenylethyl)chromone (5), daphnauranol B (7), 6-methoxy-2-[2-(3-methyoxyphenyl)ethyl]chromone (10), isoagarotetrol (14), and 1-hydroxy-1,5-diphenylpentan-3-one (16) showed significant protective effects on CORT-induced injury in PC12 cells at a concentration of 20 µM (P < 0.001). Isoagarotetrol (14) showed a significant protective effect on MPP+-induced injury in PC12 cells at a concentration of 20 µM (P < 0.001), while compound 4 showed a moderate activity (P < 0.01). The BACE1-inhibitory activities of all tested compounds were very weak with less than 30% inhibition at a concentration of 20 µM.

7.
Acupunct Med ; 39(6): 629-636, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34049443

RESUMO

BACKGROUND: Conventional therapy may be inadequate for many patients with axial spondyloarthritis (axSpA). Traditional Chinese medicine (TCM) may be a viable alternative, but its effectiveness for axSpA is unknown. We are currently conducting a pragmatic randomised controlled trial (RCT) to investigate the effectiveness of a TCM collaborative model of care (TCMCMC), which combines usual rheumatologic care with acupuncture for patients with axSpA. This nested qualitative sub-study aims to identify facilitators of and barriers to the implementation of the TCMCMC. METHODS: We conducted individual in-depth interviews with participants who had completed the acupuncture regimen to elicit opinions on the facilitators of and barriers to the implementation of the TCMCMC. The interviews were transcribed and analysed using thematic analysis. RESULTS: Twelve participants were included, with data saturation occurring after 10 interviews. The analysis revealed both a number of important 'facilitators' and 'barriers'. Facilitators to the implementation of the TCMCMC included effectiveness of TCM to relieve symptoms, inadequacy of conventional treatment and positive social perceptions of TCM. Barriers included scepticism towards TCM, inability of TCM to provide instant relief, needle-related discomfort, variable effectiveness of TCM influenced by physicians' skills and experience and the high cost of TCM. Recommendations to overcome barriers included further patient education about TCM. CONCLUSION: Policymakers should take into account the various feasibility factors identified in this study when developing and implementing a TCMCMC. TRIAL REGISTRATION NUMBER: NCT03420404 (ClinicalTrials.gov).

8.
Chin Med J (Engl) ; 134(12): 1457-1464, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34039871

RESUMO

BACKGROUND: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. METHODS: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. RESULTS: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. CONCLUSIONS: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. TRIAL REGISTRATION: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , China , Difosfonatos , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Tecnécio/uso terapêutico , Resultado do Tratamento
9.
BMC Nephrol ; 22(1): 148, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888083

RESUMO

BACKGROUND: Membranous nephropathy (MN) is mainly classified into idiopathic MN (iMN) and secondary MN in etiology. In recent years, a new kind of membranous nephropathy, atypical membranous nephropathy (aMN) which shows "full house" in immunofluorescence but without definite etiology was paid more attention. In a single center cohort, the renal outcomes of iMN and aMN were compared. METHODS: iMN and aMN patients were selected from renal pathology databank from January 2006 to December 2015. Patients' demographics, laboratory values, induction regimens and patients' responses were recorded. Specially, creatinine, eGFR, albumin and 24 h urinary protein excretion were recorded at 6th month after the induction of immunosuppressive (IS) treatment and at the end of follow up. Complete proteinuria remission was defined as urinary protein < 0.3 g/d, partial proteinuria remission was defined as urinary protein between 0.3 g/d ~ 3.5 g/d and decreased > 50 % from the baseline. The primary outcome was worsening renal function, defined as a 30 % or more decrease in eGFR or end-stage renal disease (eGFR < 15ml/min/1.73m2). COX proportional hazard models were used to test if aMN was a risk factor of worsening renal function compared with iMN. RESULTS: There were 298 patients diagnosed with MN and followed in our center for 1 year or more, including 145 iMN patients with an average follow-up time of 4.5 ± 2.6 years, and 153 aMN patients with 4.1 ± 2.0 years (p = 0.109). The average age of iMN patients was older than aMN patients (56.1 ± 12.2 versus 47.2 ± 16.2 years old, p < 0.001). There were 99 iMN patients and 105 aMN patients with nephrotic range proteinuria and without previous immunosuppressive treatment. 93 (93.9 %) and 95 (90.5 %) patients underwent immunosuppressive treatment in iMN and aMN group, and there was no significant difference of the overall proteinuria remission rates at 6th month (59.1 % vs. 52.0 %, p = 0.334) and endpoint (73.7 % vs. 69.5 %, p = 0.505) between the two groups. 25 (25.3 %) patients in iMN group and 21 (20.0 %) patients in aMN group reached primary endpoint (X2 = 0.056, p = 0.812). Multivariate COX regression showed that after demographics, baseline laboratory values and remission status at 6th month were adjusted, aMN group had similar renal outcome compared with iMN group, the HR of primary outcome was 0.735 (95 % CI 0.360 ~ 1.503, p = 0.399). CONCLUSIONS: The proteinuria remission rates and renal outcomes were similar in iMN and aMN patients after covariables were adjusted.

10.
Zhongguo Zhen Jiu ; 41(3): 303-6, 2021 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-33798314

RESUMO

OBJECTIVE: To observe the imaging features of focus of knee joint tendon in patients with knee osteoarthritis (KOA) by musculoskeletal ultrasound (MSUS) technique. METHODS: One hundred KOA patients and 100 healthy subjects were included. All the KOA patients were palpated by the sequence of foot yangming meridian, foot shaoyang meridian, foot taiyang meridian and foot three yin-meridians, and the focus of knee tendon and its frequency were recorded by MSUS technique. The top-5 focus of knee tendon of KOA patients and the corresponding focus of knee tendon of healthy subjects were selected as the observation sites to compare the differences of thickness of ligament and tendon soft tissue in the extension and flexion positions of the knee joint. RESULTS: The top-5 focus of knee tendon of KOA patients were located in medial inferior patella, medial tibial condyle, inferior patella, Zusanlici and Hedingci. The thickness of ligaments and tendons in extension and flexion positions in KOA patients were thicker than that in healthy subjects (P<0.05). CONCLUSION: The focus of knee joint tendon in KOA patients shows significantly thickened musculoskeletal imaging features.


Assuntos
Osteoartrite do Joelho , Voluntários Saudáveis , Humanos , Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Tendões/diagnóstico por imagem , Ultrassonografia
11.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33673023

RESUMO

Botryosphaeria dothidea is a pathogen with worldwide distribution, infecting hundreds of species of economically important woody plants. It infects and causes various symptoms on apple plants, including wart and canker on branches, twigs, and stems. However, the mechanism of warts formation is unclear. In this study, we investigated the mechanism of wart formation by observing the transection ultrastructure of the inoculated cortical tissues at various time points of the infection process and detecting the expression of genes related to the pathogen pathogenicity and plant defense response. Results revealed that wart induced by B. dothidea consisted of proliferous of phelloderm cells, the newly formed secondary phellem, and the suberized phelloderm cells surrounding the invading mycelia. The qRT-PCR analysis revealed the significant upregulation of apple pathogenesis-related and suberification-related genes and a pathogen cutinase gene Bdo_10846. The Bdo_10846 knockout transformants showed reduced cutinase activity and decreased virulence. Transient expression of Bdo_10846 in Nicotiana benthamiana induced ROS burst, callose formation, the resistance of N. benthamiana to Botrytis cinerea, and significant upregulation of the plant pathogenesis-related and suberification-related genes. Additionally, the enzyme activity is essential for the induction. Virus-induced gene silencing demonstrated that the NbBAK1 and NbSOBIR1 expression were required for the Bdo_10846 induced defense response in N. benthamiana. These results revealed the mechanism of wart formation induced by B. dothidea invasion and the important roles of the cutinase Bdo_10846 in pathogen virulence and in inducing plant immunity.


Assuntos
Ascomicetos/genética , Hidrolases de Éster Carboxílico/genética , Proteínas Fúngicas/genética , Malus/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Ascomicetos/patogenicidade , Hidrolases de Éster Carboxílico/classificação , Hidrolases de Éster Carboxílico/metabolismo , Proteínas Fúngicas/classificação , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno/genética , Malus/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Virulência/genética
12.
J Asian Nat Prod Res ; : 1-9, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583279

RESUMO

Seven benzophenone compounds were synthesized in one or two steps, then their antitumor activity was evaluated. The total yields ranged from 9% to 44%. Compounds 3c-5c exhibited obvious antitumor activity. Among them, compounds 3c and 4c exhibited excellent and broad-spectrum antitumor activity. Compound 3c exhibited much stronger inhibitory activities against fourteen cancer cells than cisplatin. In particular, compound 3c exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than Taxol, with a half maximal inhibitory concentration (IC50) of approximately 0.111 µM. These results demonstrated that compounds 3c, 4c and 5c were very promising antitumor leads for further structural modification.

13.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430504

RESUMO

Fungal effectors play important roles in host-pathogen interactions. Botryosphaeria dothidea is an ascomycetous fungus that is responsible for the diseases of hundreds of woody plant species, including apple ring rot, which seriously affects apples worldwide. However, little is known about the effectors of B. dothidea. In this study, we analyzed the B. dothidea genome and predicted 320 candidate effector genes, 124 of which were successfully amplified and cloned. We investigated the effects of these genes on plant cell death in Nicotiana benthamiana while using a transient expression system. Twenty-four hours after initial inoculation with Agrobacterium tumefaciens cells carrying candidate effectors, the infiltrated leaves were challenged with A. tumefaciens cells carrying the BAX gene. In total, 116 candidate effectors completely inhibited, while one partially inhibited, the programmed cell death (PCD) of N. benthamiana induced by BAX, whereas seven candidate effectors had no effect. We then further tested seven candidate effectors able to suppress BAX-triggered PCD (BT-PCD) and found that they all completely inhibited PCD triggered by the elicitors INF1, MKK1, and NPK1. This result suggests that these effectors were activated in order to suppress pathogen-associated molecular pattern-triggered immunity. The signal peptides of these candidate effectors exhibited secretory activity in yeast (pSUC2 vector). Moreover, the respective deletion of Bdo_11198 and Bdo_12090 significantly reduced the virulence of B. dothidea. These results suggest that these effectors play important roles in the interaction of B. dothidea with its hosts.


Assuntos
Ascomicetos/genética , Interações Hospedeiro-Patógeno/genética , Malus/genética , Doenças das Plantas/genética , Agrobacterium tumefaciens/genética , Ascomicetos/patogenicidade , Malus/imunologia , Malus/microbiologia , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Tabaco/genética , Tabaco/microbiologia , Virulência/genética
14.
J Nephrol ; 34(4): 1169-1177, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33394345

RESUMO

OBJECTIVE: Light chain cast nephropathy is the most common form of renal lesion in multiple myeloma. Kidney impairment caused by light chain cast nephropathy can be reversed and survival can be improved if early diagnosis is available. It is thus of imperative importance to develop a non-invasive method to diagnose light chain cast nephropathy once the kidney biopsy is not always applicable. METHODS: We consecutively screened newly diagnosed multiple myeloma patients with kidney biopsies from 4 centers in China. Kidney pathologies were reviewed and clinical presentations were recorded. Then a diagnostic model was established by logistic regression and the predictive values were assessed. RESULTS: Between 1 June 1999 and 30 June 2019, a kidney biopsy was performed in 94 patients with newly diagnosed multiple myeloma, and light chain cast nephropathy was the most common pattern, seen in 52% of biopsied patients. The diagnostic model was established by multivariate logistic regression analysis as P(z) = 1/(1 + e-z) and z = - 0.093 Hemoglobin (g/L) + 0.421 Serum albumin (g/L) + 3.463 Acute kidney injury (0/1) - 9.207 High-density lipoprotein (mmol/L). If P(z) ≥ 0.55, the diagnosis pointed to light chain cast nephropathy; if P(z) < 0.55, the diagnosis favored non-light chain cast nephropathy. The area under the receiver operating characteristic curves was 0.981 (95% CI 0.959, 1.000). The model had a sensitivity of 93.9%, a specificity of 95.6%, a positive predictive value of 96.0%, a negative predictive value of 94.0%, and a total consistency of 95.0%. CONCLUSION: We built a novel, non-invasive diagnostic model through a multicenter study, which may be helpful in the diagnosis of light chain cast nephropathy in newly diagnosed multiple myeloma patients.


Assuntos
Injúria Renal Aguda , Mieloma Múltiplo , Humanos , Cadeias Leves de Imunoglobulina , Rim , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Albumina Sérica
15.
Phytochemistry ; 181: 112554, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33152579

RESUMO

Six undescribed compounds, including three sesquiterpenoids [(4S,5S,7S,8S,11R)-7-hydroxyguai-1(10)-en-8,12-olide, aquilarisinone, and 2Z,7(13),9E-humulatrien-12-ol-5-one], one diphenylpentanone [1-(2-hydroxyphenyl)-5-phenylpentan-3-one], and two 2-(2-phenylethyl)chromones (6-epiagarotetrol and triepoxyhexahydrochromone A), along with 15 known compounds, were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). Their structures were determined by mass (MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configuration of (4S,5S,7S,8S,11R)-7-hydroxyguai-1(10)-en-8,12-olide was confirmed by X-ray diffraction analysis, and the configurations of (4S,7S,8S,10R,11R)-7,10-epoxyguai-1(5)-en-8,12-olide, aquilarisinone, 6-epiagarotetrol, and triepoxyhexahydrochromone A were confirmed by electronic circular dichroism (ECD) calculations. The neuroprotective activities of the compounds were evaluated using models of BACE1 inhibition and PC12 cells with corticosterone- and 1-methyl-4-phenylpyridine ion (MPP+)-induced damage. At concentrations of 1, 2, and 5 µM, triepoxyhexahydrochromone A, (+)-(7R,10R)-selina-4,11(13)-diene-12,15-dial, (-)-(5R,7R,10R)-12,15-dioxo-α-selinene, and (+)-(1R,4S,5R)-1ß-hydroxyeremophila-7(11),9-dien-8-one exerted significant protective effects (p < 0.01) on PC12 cell injury induced by corticosterone, while triepoxyhexahydrochromone A and (-)-(5R,7R,10R)-12,15-dioxo-α-selinene exerted significant protective effects (p < 0.01) on MPP+-induced PC12 cell injury at concentrations of 1, 2, and 5 µM. No compounds produced significant inhibitory effects on BACE1, with inhibition rates of less than 20% observed at a concentration of 20 µM.


Assuntos
Secretases da Proteína Precursora do Amiloide , Thymelaeaceae , Animais , Ácido Aspártico Endopeptidases , Cromonas , Estrutura Molecular , Ratos
16.
Reprod Domest Anim ; 56(1): 142-152, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33174231

RESUMO

The aims of the present study were to determine uterine, vaginal and placental blood flows by Doppler ultrasound cross-buffalo gestation and to evaluate the relationships among reproductive Doppler parameters and serum metabolic parameters as well as oxidative stress. Uterine (UA) and vaginal (VA) arteries were scanned every month, and placentome was scanned from month 4 till 8 in gestation. Time-averaged maximum velocity (TAMV), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (SD) and arterial diameter (AD) were used for accessing UA and VA hemodynamics. Time-averaged maximum velocity positively correlated with and AD, and both negatively correlated with their PI, RI and SD in UA and VA. TAMV and AD increased constantly in pregnancy, with maximum increase in months 4 and 9. Pulsatility index, RI and AD of UA decreased between months 4 and 9, while PI, RI and AD of VA decreased between months 5 and 9 and then increased in month 10 in pregnancy. Time-averaged maximum velocity of placentome blood flow increased exponentially from months 4 to 8, but decreased at the last two months in pregnancy. Serum lipids were significantly higher in the first month compared to all other months, while glucose was significantly lower in months 9 and 10. Malondialdehyde increased from month 3 till term, but peaked in month 5 and 10. Glutathione and catalase were highest in the first month and remained after. Time-averaged maximum velocity and AD for both UA and VA negatively correlated with serum lipids, glucose, catalase and glutathione, while positively correlated with malondialdehyde and total protein. Thus, increases in uterine blood flow (UtBF), vaginal blood flow (VaBF) and placental blood flow (PaBF) are associated with increased metabolism and oxidative stress in buffalo pregnancy.

17.
Bioorg Med Chem Lett ; 31: 127682, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33207281

RESUMO

One new sesquineolignan, piperneolignan A (1), four new neolignans, piperneolignans B-E (2-5), and eight known compounds were isolated from the leaves of Piper betle (Piperaceae) collected from Myanmar. These new structures were determined by analysis of MS and NMR data, and the absolute configuration of piperneolignan A was elucidated by electronic circular dichroism (ECD) calculations. Piperneolignan A (1), piperneolignan B (2), hydroxychavicol (6), p-hydroxycinnamaldehyde (10), and diallylcatechol (13) possessed anti-inflammatory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells with IC50 values of 9.87, 45.94, 4.80, 26.40, and 40.45 µM, respectively, compared with the positive control NG-monomethyl-l-arginine (l-NMMA, IC50 = 33.84 µM). The two hydroxy groups in the structure of hydroxychavicol are essential for activity, and dimerization or trimerization of hydroxychavicol decreases activity.

19.
J Asian Nat Prod Res ; : 1-11, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33334137

RESUMO

Five polyhydroxybenzophenones were synthesized, then their antitumor and antioxidant activities were evaluated. Compounds 1-3 and 5 exhibited obvious antitumor activity. Among them, compounds 1 and 2 exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than cisplatin, with half maximal inhibitory concentrations (IC50) of approximately 3.86 and 5.32 µM, respectively. Compounds 1, 2, and 3 exhibited stronger antioxidant activity than trolox, with IC50 values of 11.15, 10.15, and 8.91 µM, respectively, and the antioxidant mechanism and strength of all compounds were further verified using computational chemistry. These results demonstrated that compounds 1-3 and 5 were very promising leads for further structural modification.

20.
Antioxidants (Basel) ; 9(11)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202933

RESUMO

Opening of large conductance calcium-activated and voltage-dependent potassium (BKCa) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H2S) has been recently identified as a new UA vasodilator, yet the mechanism underlying H2S-induced UA dilation is unknown. Here, we tested whether H2S activated BKCa channels in human UA smooth muscle cells (hUASMC) to mediate UA relaxation. Multiple BKCa subunits were found in human UA in vitro and hUASMC in vitro, and high ß1 and γ1 proteins were localized in SM cells in human UA. Baseline outward currents, recorded by whole-cell and single-channel patch clamps, were significantly inhibited by specific BKCa blockers iberiotoxin (IBTX) or tetraethylammonium, showing specific BKCa activity in hUASMC. H2S dose (NaHS, 1-1000 µM)-dependently potentiated BKCa currents and open probability. Co-incubation with a Ca2+ blocker nifedipine (5 µM) or a chelator (ethylene glycol-bis (ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), 5 mM) did not alter H2S-potentiated BKCa currents and open probability. NaHS also dose-dependently relaxed phenylephrine pre-constricted freshly prepared human UA rings, which was inhibited by IBTX. Thus, H2S stimulated human UA relaxation at least partially via activating SM BKCa channels independent of extracellular Ca2+.

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