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2.
Plant Signal Behav ; : 1891769, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33818288

RESUMO

Late embryogenesis abundant (LEA) proteins play important roles in plant defense response to drought stress. However, genome-wide identification of the LEA gene family was not revealed in Salvia miltiorrhiza. In this study, 61 SmLEA genes were identified from S. miltiorrhiza and divided into 7 subfamilies according to their conserved domains and phylogenetic relationships. SmLEA genes contained the LEA conserved motifs and few introns. SmLEA genes of the same subfamilies had similar gene structures and predicted subcellular locations. Our results indicated that the promoters of SmLEA genes contained various cis-acting elements associated with abiotic stress response. In addition, RNA-seq and real-time PCR results suggested that SmLEA genes are specifically expressed in different tissue, and most SmLEA genes can be induced by drought stress. These results provide a valuable foundation for future functional investigations of SmLEA genes and drought stress-resistant breeding of S. miltiorrhiza.

3.
World J Urol ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725149

RESUMO

PURPOSE: To determine the incidence and risk factors of the venous thromboembolism (VTE) in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively reviewed the records of 896 consecutive cases receiving PCNL between July 2018 and August 2020 in our institution. Univariate analysis was performed to identify the risk factors of VTE, and multivariate logistic regression analysis was further performed to determine the independent risk factors. Furthermore, the corresponding nomogram was conducted to establish a predicted model for VTE. RESULTS: The overall incidence of VTE was 2.8%. The multivariate logistic regression analysis showed that discontinued anticoagulant or antiplatelet therapies (OR 4.505, 95% CI 1.410-14.401), increased postoperative 12-h D-dimer (OR 11.162, 95% CI 2.370-52.574), hydronephrosis (OR 3.303, 95% CI 1.303-8.375), higher Caprini risk assessment model (RAM) score (OR 3.233, 95% CI 1.207-8.659) and postoperative sepsis or septic shock (OR 3.784, 95% CI 1.163-12.306) were independent risk factors of VTE following PCNL. Moreover, the area under the curve of postoperative 12-h D-dimer, hydronephrosis and Caprini RAM score was 0.826, 0.621 and 0.660, respectively. Based on the identified independent risk factors, the well-calibrated nomogram showed a moderate discriminative ability with concordance index 0.731. CONCLUSIONS: 2.8% of patients developed VTE following PCNL. Regarding those patients who have independent risk factors in this study, due attention should be paid to the effective thromboprophylaxis and the early detection of VTE.

4.
Phytother Res ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724590

RESUMO

Erycibes are members of the Convolvulaceae family, including more than 10 species worldwide that are distributed in tropical Asia. Some Erycibes species have long been used as traditional remedies for rheumatoid arthritis, fever, hepatitis, and liver injury in China and Thailand. A total of 152 compounds from Erycibes plants have been isolated and identified, categorized as flavonoids, coumarins, quinic acid derivatives, lignans, and alkaloids. Coumarins are the characteristic and active constituents of this species, including scopoletin and scopolin. Modern pharmacological studies have shown that the extracts and bioactive components of Erycibes plants exhibit several biological activities, including antiinflammatory, analgesic, hepatoprotective, anti-gout, antitumor, antioxidation, and other therapeutic effects. However, in recent years, due to destructive exploitation and utilization, some Erycibes plants' natural resources have become rare or endangered. Developing substitutes is a strategy to alleviate the pressure on those endangered medicinal plant resources. To provide a scientific basis for the development and protection of those threatened Erycibes species, this review summarized the current status of the chemical compositions, pharmacological activities, quality control studies, and the development of substitutes for Erycibes plants. In particular, the rationale for use of Porana sinensis currently on the market is discussed.

5.
Urolithiasis ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710365

RESUMO

To investigate how to administrate antibiotics for negative midstream urine culture (UC-) patients prior to percutaneous nephrolithotomy (PCNL), we retrospectively analyzed UC-patients receiving 0 or 3 days of cefuroxime prior to PCNL between July 2017 and May 2020. Patients were further divided into four groups (Group1A = urine with positive both nitrite and white blood cell (N + WBC +) and 0-day pre-operative cefuroxime; Group1B = N + WBC + and 3-day cefuroxime; Group2A = N - WBC + and 0-day cefuroxime; Group2B = N - WBC + and 3-day cefuroxime). All patients routinely received a dose of cefuroxime 30 min prior to the surgery. In addition, Group1B were matched to the Group1A; Group2B were matched to the Group2A at a 1:1 ratio regarding stone burden, the degree of hydronephrosis, stone hardness, age and sex in a sequential order. A total of 560 patients were included (Group1A = 72; Group1B = 72; Group2A = 208; Group2B = 208). The baseline characteristics were equally distributed between the matched-pair groups. Compared to Group1B, Group1A had a significantly higher incidence of SIRS, fever, urosepsis requiring only additional antibiotics, and an increased postoperative hospitalization stay. Compared to Group2B, Group2A had similar rate of infectious complications. In addition, Group1B was associated with a significantly lower rate of positive pelvic urine culture (PUC +) than that of Group1A; whereas, there was similar rate of PUC + between Group2A and Group2B. UC-patients with N + WBC + should be treated with extended period of antibiotic administration, and a single dose of prophylactic antibiotic was sufficient for UC-patients with N - WBC + prior to PCNL. Despite UC, it is suggested to stratify pre-operative antibiotics tailored to individual patients to optimize its application.

6.
Environ Res ; 194: 110671, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33385386

RESUMO

Biochar has attracted increased attention because of its potential benefits for carbon sequestration, soil fertility, and contaminant immobilization. However, mechanism of long-term successive biochar amendment affected crop yield by regulating soil properties and nitrogen (N) functional microbes is still unclear by now. A field fixed experiment was carried out from 2011 to 2018 that aimed to study the effects of successive biochar on soil properties, soil nitrogen functional microbial genes, and grain yield in wheat and maize rotation farmland in Northern China. Four straw biochar treatments were tested in this study: 0 (BC0, CK), 2.25 (BC2.25), 6.75 (BC6.75), and 11.25 (BC11.25) Mg ha-1. The results showed that, after seven wheat-maize rotations, the total organic carbon (TOC), total N (TN), NO3-, available potassium (AK), and the C/N ratio in 0-20 cm topsoil were increased significantly following biochar application; however, there were no obvious differences in available phosphorus (AP) and NH4+ among biochar treatments. Biochar also resulted in a significant increase in crop yield and NO3- accumulation in 0-200 cm soil layer, with the highest yield in BC6.75. Furthermore, a marked increase was found in the amoA gene abundance in topsoil; however, it decreased significantly with excessive biochar application (BC11.25). At wheat maturity, the nirS gene abundance consistently decreased following biochar application, whereas the nosZ gene abundance initially increased and then decreased (peaking in BC6.75); however, no obvious changes in the nirK gene were observed. At maize maturity, biochar significantly increased the nirS and nosZ gene abundance in topsoil, especially in BC6.75. In addition, redundancy analysis indicated that the soil moisture content, AP, AK, TN, TOC, NO3-, NH4+, pH, and C/N ratio had markedly effects on the abundance of the amoA, nirK, nirS, and nosZ genes. In general, biochar-induced alterations of soil properties resulted in changes of gene abundance of soil nitrifying and denitrifying bacteria, and eventually affecting crop yields.

7.
Sex Transm Dis ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33512899

RESUMO

ABSTRACT: Syphilitic spinal disease is a rare condition caused by the spirochete Treponema pallidum, either from direct spirochete involvement of the cord, or as a consequence of indirect spirochete involvement of the meninges, blood vessels, or the vertebral column. Following the introduction of penicillin therapy in the 1940s, it has become an increasingly rare condition. We report three challenging cases of syphilitic spinal disease presenting as myelopathy - one with an extra-axial gumma of tertiary syphilis causing cord compression, and two with tabes dorsalis complicated by tabetic spinal neuroarthropathy - each presenting a diagnostic dilemma to their treating physicians. We also review the literature for updates on modern investigative modalities, and discuss pitfalls physicians need to avoid in order to arrive at the diagnosis.

9.
Sci Rep ; 11(1): 2169, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500507

RESUMO

To evaluate the predictive effect of T-lymphoid subsets on the conversion of common covid-19 to severe. The laboratory data were collected retrospectively from common covid-19 patients in the First People's Hospital of Zaoyang, Hubei Province, China and the Third People's Hospital of Kunming, Yunnan Province, China, between January 20, 2020 and March 15, 2020 and divided into training set and validation set. Univariate and multivariate logistic regression was performed to investigate the risk factors for the conversion of common covid-19 to severe in the training set, the prediction model was established and verified externally in the validation set. 60 (14.71%) of 408 patients with common covid-19 became severe in 6-10 days after diagnosis. Univariate and multiple logistic regression analysis revealed that lactate (P = 0.042, OR = 1097.983, 95% CI 1.303, 924,798.262) and CD8+ T cells (P = 0.010, OR = 0.903, 95% CI 0.835, 0.975) were independent risk factors for general type patients to turn to severe type. The area under ROC curve of lactate and CD8+ T cells was 0.754 (0.581, 0.928) and 0.842 (0.713, 0.970), respectively. The actual observation value was highly consistent with the prediction model value in curve fitting. The established prediction model was verified in 78 COVID-19 patients in the verification set, the area under the ROC curve was 0.906 (0.861, 0.981), and the calibration curve was consistent. CD8+ T cells, as an independent risk factor, could predict the transition from common covid-19 to severe.


Assuntos
Linfócitos T CD8-Positivos/virologia , Progressão da Doença , Corticosteroides/administração & dosagem , Adulto , Algoritmos , China , Feminino , Humanos , Hipóxia/metabolismo , Lopinavir/administração & dosagem , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Oxigênio/química , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Ritonavir/administração & dosagem
10.
ACS Omega ; 5(47): 30348-30355, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33283082

RESUMO

Large quantities of Triassic solid asphaltite were discovered in the Guangyuan area, northwest Sichuan. The asphaltite is formed in layers with a vertical thickness between 0.3 and 2.8 m and is stably distributed with intrusive contact with surrounding rocks. This study aims on the genesis and distribution of asphaltite through trace element, biomarker, and Re-Os isotope analyses. Trace element analysis shows the enrichment of V and Cr in the asphaltite, indicating that it is derived from relatively deep hydrocarbon sources. The carbon isotope and biomarker results suggest that the asphaltite originates from Cambrian paleo reservoir. The Re-Os isotope analysis determines a formation age of 220 ± 6 Ma, which corresponds to the late Triassic, indicating the cracking of paleo reservoirs in late Triassic. Therefore, the origin of asphaltite is epigenetic-reservoir asphaltite. The generation of oil from Cambrian source rocks began at the end of Silurian and ended after Caledonian orogeny. At the end of Permian, the fracture system was well developed due to the influence of the Hercynian movement, which provided favorable conditions for the migration of Cambrian oil. By the end of Triassic, hydrocarbons generated from Cambrian source rocks were mainly distributed in fractures and reservoirs, thus forming paleo oil reservoirs. Afterward, the paleo reservoirs were adjusted to the surface or near the surface during the Indosinian movement and thus have cracked into asphaltite. The distribution of asphaltite is closely related to the tectonic activities, and the asphaltite is preferentially stored in the anticline axes, fissures, and some interlayer fracture zones.

11.
J Neurol Sci ; 419: 117216, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33171389

RESUMO

BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) and anti-voltage-gated potassium channel (VGKC) encephalitis are the commonest antibody-associated autoimmune encephalitides (AIE). Acute clinical features have been well-described, but data on the role of radiological findings in diagnosis and prognosis of AIE are limited. METHODS: Anti-NMDAR and anti-VGKC encephalitis patients from the National Neuroscience Institute were identified. We compared clinical and paraclinical features, at acute presentation and on follow-up between and within groups. RESULTS: Twenty-six anti-NMDAR and 11 anti-VGKC encephalitis patients were reviewed. At acute presentation, dysautonomia (57.7%) and impairment of consciousness (84.6%) occurred exclusively in anti-NMDAR encephalitis. Cerebrospinal fluid pleocytosis was more common in anti-NMDAR encephalitis (88.5% vs 20.0%, p = 0.003), while ictal electroencephalography abnormalities were more frequent in anti-VGKC encephalitis (11.5% vs 45.5%, p = 0.022). On acute imaging, leptomeningeal enhancement was seen only in anti-NMDAR encephalitis (37.5%), while hippocampal T2 hyperintensities supported the diagnosis of anti-VGKC encephalitis (63.6% vs 12.5%, p = 0.002). At follow-up (median 53.0 months, range 13.0-119.0), anti-NMDAR encephalitis patients had better modified Rankin scale scores (median 0.0 vs 3.0, p = 0.023). Relapses occurred equally in both groups. Anti-VGKC encephalitis patients with abnormal acute MRI were more likely to have poor outcomes compared to those with normal imaging (100% vs 25%, p = 0.008), whereas acute imaging features in anti-NMDAR encephalitis did not predict long-term outcomes. CONCLUSIONS: Acute MRI findings can aid in early diagnosis and prognostication in suspected AIE. Leptomeningeal enhancement in anti-NMDAR encephalitis and hippocampal lesions in anti-VGKC encephalitis, together with typical clinical features, may allow distinction between these antibody subtypes, and specific abnormal imaging features in anti-VGKC encephalitis may be used as a prognostic marker.

12.
Transl Androl Urol ; 9(5): 2082-2093, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209671

RESUMO

Background: The aim of this stay was to determine the effect of calcium ions in promoting osteogenic-like differentiation in human renal interstitial fibroblasts (hRIFs). The role of miRNA-410-3p in upregulating Msh homeobox 2 (MSX2) level in hRIFs was also investigated. Methods: Quantitative polymerase chain reaction (qPCR) analysis was used to assess the expression levels of miRNA-410-3p in Randall's plaque (RP) and normal renal papillary (nRP) tissues. Furthermore, the expression levels of osteogenesis-related protein in the RP and nRP tissues were assessed with qPCR and immunohistochemistry (IHC). hRIFs were cultured from isolated human kidney papilla before treatment with calcium chloride or osteogenic medium, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed at 1, 5, 9, and 14 days post-treatment. Alizarin red staining was used to estimate the deposits of calcium aggregates. After the overexpression or knockdown of miRNA-410-3p, we evaluated the changes in the osteogenic-like differentiation and osteogenesis-related protein by alizarin red staining and qPCR, respectively. A binding relationship between miRNA-410-3p and MSX2 was established through a dual-luciferase reporter gene assay. Rescue experiments demonstrated that miRNA-410-3p regulated the osteogenic-like differentiation by targeting MSX2. Results: miRNA-410-3p levels were lower in RP tissue than in control nRP tissues. qPCR and IHC showed that the level of runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) were higher in RP tissues. The calcium deposition of hRIFs showed a time-dependent trend when treated with osteogenic medium or calcium chloride. The overexpression of miRNA-410-3p downregulated the levels of osteogenesis-related expression and attenuated mineralization. The knockdown of miRNA-410-3p yielded the opposite trend. Dual-luciferase reporter gene assay and rescue experiments indicated that miRNA-410-3p could target MSX2, while the overexpression of MSX2 reversed the effects of miRNA-410-3p on osteogenic-like differentiation. Conclusions: The current findings suggest that calcium ions could promote the osteogenic-like differentiation of hRIFs and miRNA-410-3p regulates hRIFs osteogenic-like differentiation by inhibiting MSX2.

13.
Med Sci Monit ; 26: e923448, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159032

RESUMO

BACKGROUND The aim of this study was to investigate the effects of red blood cell (RBC) storage duration on the outcomes of adult isolated traumatic brain injury (iTBI) patients after transfusion. MATERIAL AND METHODS A total of 1252 adult iTBI patients who received the fresh RBCs (stored for £14 days) or old RBCs (stored for >14 days) were finally enrolled in this study. The primary outcome was 90-day mortality. The secondary outcomes were in-hospital mortality, nosocomial infection, and complications. RESULTS By 90 days after RBC transfusion, 89 patients (17.0%) had died in the fresh RBC group, and 107 had died (14.7%) in the old RBC group, with no significant difference in 90-day mortality between the 2 groups (OR=1.192, 95% CI: 0.877-1.620, P=0.261). According to ISS score, no differences were discovered in mild injury (OR=1.079, 95% CI: 0.682-1.707, P=0.746), severe injury (OR=1.055, 95% CI: 0.634-1.755, P=0.838), and more severe injury (OR=1.940, 95% CI: 0.955-3.943, P=0.064). For GCS score, there were no differences in mild injury (OR=1.546, 95% CI: 0.893-2.676, P=0.118), moderate injury (OR=0.965, 95% CI: 0.616-1.513, P=0.877), and severe injury (OR=1.332, 95% CI: 0.677-2.620, P=0.406). We also observed no significant differences in secondary outcomes. CONCLUSIONS Use of old RBCs did not increase the 90-day mortality in adult iTBI patients.

15.
J Neuroophthalmol ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33136679

RESUMO

We present the first reported case of facial nerve involvement accompanying an optic neuritis in myelin oligodendrocyte glycoprotein antibody-associated disorder.

16.
Lancet Infect Dis ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031750

RESUMO

BACKGROUND: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

17.
Pain ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33021564

RESUMO

Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7. Colorectal distension did not activate L4 DRG neurons. TNBS-treated mice exhibited more Evans blue extravasation than did control mice, and developed mechanical hypersensitivity in low-back skin and hind paws, which are innervated by L6 and L4 DRG neurons, respectively, suggesting that colonic inflammation induced mechanical hypersensitivity in both homo-segmental and hetero-segmental somatic regions. Importantly, the percentage of L4 DRG neurons activated by hind-paw pinch and brush stimulation, and calcium responses of L6 DRG neurons to low-back brush stimulation were higher at day 7 post-TNBS than those in control mice. Visceral irritation from intracolonic capsaicin instillation also increased Evans blue extravasation in hind paws and low-back skin, and acutely increased the percentage of L4 DRG neurons responding to hind-paw pinch and the response of L6 DRG neurons to low-back brush stimulation. These findings suggest that TNBS-induced colitis and capsaicin-induced visceral irritation may sensitize L6 DRG neurons to colorectal and somatic inputs, and also increase the excitability of L4 DRG neurons that do not receive colorectal inputs. These changes may represent a potential peripheral neuronal mechanism for visceral pain sensitization and referred somatic hypersensitivity.

18.
Pain ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33110031

RESUMO

Agonists to subtype C of the Mas-related G-protein-coupled receptors (MrgC) induce pain inhibition after intrathecal (i.t.) administration in rodent models of nerve injury. Here, we investigated whether tolerance develops after repeated MrgC agonist treatments and examined the underlying mechanisms. In animal behavior studies conducted in male rats at 4-5 weeks after an L5 spinal nerve ligation (SNL), the ability of dipeptide MrgC agonist JHU58 (0.1 mM, 10 µL, i.t.) to inhibit mechanical and heat hypersensitivity decreased after 3 days of treatment with a tolerance-inducing dose (0.5 mM, 10 µL, i.t., twice/day). In HEK293T cells, acute treatment with JHU58 or BAM8-22 (a large peptide MrgC agonist) led to MrgC endocytosis from the cell membrane, and later sorting to the membrane for reinsertion. However, chronic exposure to JHU58 increased the coupling of MrgC to ß-arrestin-2 and led to the ubiquitination and degradation of MrgC. Importantly, pretreatment with TAK-243 (0.2 mM, 5 µL, i.t.), a small-molecule inhibitor of the ubiquitin activating enzyme, during tolerance induction attenuated the development of tolerance to JHU58-induced inhibition of mechanical and heat hypersensitivity in SNL rats. Interestingly, morphine analgesia was also decreased in SNL rats that had become tolerant to JHU58, suggesting a cross-tolerance. Furthermore, intrathecal pretreatment with TAK-243, which reduced JHU58 tolerance, also attenuated the cross-tolerance to morphine analgesia. These findings suggest that tolerance can develop to MrgC agonist-induced pain inhibition after repeated intrathecal administrations. This tolerance development to JHU58 may involve increased coupling of MrgC to ß-arrestin-2 and ubiquitin-mediated receptor degradation.

19.
Mol Biol Rep ; 47(10): 8159-8168, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32979165

RESUMO

Colorectal cancer (CRC) is one of the leading causes of tumor morbidity and mortality worldwide. Endoscopy is currently the main screening method, but the invasiveness and high cost hamper the application of endoscopy in asymptomatic patients with a risk of CRC and lead to a low diagnostic rate for early CRC. In recent years, the progress of transcriptomics, epigenetics, immunomics and metabolomics has greatly contributed to the identification of novel molecular markers for the noninvasive screening of CRC, and many molecules in various biological processes have been identified and evaluated for CRC detection. However, individual molecules always have insufficient diagnostic performance as biomarkers for the detection of CRC; therefore, a frequent strategy to overcome this deficiency is the use of molecule signatures as biomarker panels to improve the diagnostic power. Here, we reviewed the diagnostic performance of blood-derived molecular signatures (mRNAs, microRNAs, autoantibodies, and metabolites) as biomarker panels for CRC detection, particularly for early detection, and discussed their limitations and prospects.

20.
Ecotoxicol Environ Saf ; 205: 111339, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961491

RESUMO

Famoxadone-cymoxanil is a new protective and therapeutic fungicide, but little research has been done on it or its toxicity in aquatic organisms. In this study, we used zebrafish to investigate the cardiotoxicity of famoxadone-cymoxanil and the potential mechanisms involved. Zebrafish embryos were exposed to different concentrations of famoxadone-cymoxanil until 72 h post-fertilization (hpf), then changes of heart morphology in zebrafish embryos were observed. We also detected the levels of oxidative stress, myocardial-cell proliferation and apoptosis, ATPase activity, and the expression of genes related to the cardiac development and calcium-signaling pathway. After famoxadone-cymoxanil exposure, pericardial edema, cardiac linearization, and reductions in the heart rate and cardiac output positively correlated with concentration. Although myocardial-cell apoptosis was not detected, proliferation of the cells was severely reduced and ATPase activity significantly decreased, resulting in a severe deficiency in heart function. In addition, indicators of oxidative stress changed significantly after exposure of the embryos to the fungicide. To better understand the possible molecular mechanisms of cardiovascular toxicity in zebrafish, we studied the transcriptional levels of cardiac development, calcium-signaling pathways, and genes associated with myocardial contractility. The mRNA expression levels of key genes in heart development were significantly down-regulated, while the expression of genes related to the calcium-signaling pathway (ATPase [atp2a1], cardiac troponin C [tnnc1a], and calcium channel [cacna1a]) was significantly inhibited. Expression of klf2a, a major endocardial flow-responsive gene, was also significantly inhibited. Mechanistically, famoxadone-cymoxanil toxicity might be due to the downregulation of genes associated with the calcium-signaling pathway and cardiac muscle contraction. Our results found that famoxadone-cymoxanil exposure causes cardiac developmental toxicity and severe energy deficiency in zebrafish.


Assuntos
Acetamidas/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Coração/efeitos dos fármacos , Estrobilurinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Cardiotoxicidade , Regulação para Baixo , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Coração/embriologia , Frequência Cardíaca/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
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