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1.
Infect Genet Evol ; : 104847, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823307

RESUMO

Emerging variant novel duck reovirus (NDRV) strains that cause spleen swelling and necrosis have seriously threatened the waterfowl industry since 2017. However, there is no report about the complete genomic sequence of emerging variant strains isolated from Cherry valley ducks. In this study, we acquired the complete genome sequences of two variant NDRV strains, SD19/6201 and SD19/6202, and analyzed their genetic and evolutionary relationship with other orthoreoviruses. The phylogenetic analysis of σC showed that all the Chinese NDRVs were clustered into two distinct branches. The SD19/6201 strain located in branch I with most of the Chinese NDRVs, while SD19/6202 was clustered in branch II with significantly different from the existing strains. Within the branch I, the NDRVs isolated in 2017 and thereafter clustered in a new subgroup. Comparison analysis of σC amino acid sequences indicated that ten amino acid differences were found between SD19/6201 and SD19/6202. Apart from the SD19/6201 and SD19/6202 strains, isolates in 2017 and thereafter had specific mutations at residues 132A, 138R, 158H, and 258A. These two NDRV strains showed different pathogenicity in SPF duck embryos and ducks. The viral loads in the spleen of infected ducks were significantly higher than those of other organs, which might be the reason why NDRV could cause obvious spleen necrosis in ducks. This study will help us to formulate effective prevention and control strategies against NDRV and enrich our understanding of the intra- and inter-species relationships of orthoreoviruses.

2.
Genes (Basel) ; 12(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809560

RESUMO

Tilletia controversa J. G. Kühn is a causal organism of dwarf bunt in wheat. Understanding the interaction of wheat and T. controversa is of practical and scientific importance for disease control. In this study, the relative expression of TaLHY and TaPR-4 and TaPR-5 genes was higher in a resistant (Yinong 18) and moderately resistant (Pin 9928) cultivars rather than susceptible (Dongxuan 3) cultivar at 72 h post inoculation (hpi) with T. controversa. Similarly, the expression of defensin, TaPR-2 and TaPR-10 genes was observed higher in resistant and moderately resistant cultivars after exogenous application of phytohormones, including methyl jasmonate, salicylic acid, and abscisic acid. Laser confocal microscopy was used to track the fungal hyphae in the roots, leaves, and tapetum cells, which of susceptible cultivar were infected harshly by T. controversa than moderately resistant and resistant cultivars. There were no fungal hyphae in tapetum cells in susceptible cultivar after methyl jasmonate, salicylic acid and abscisic acid treatments. Moreover, after T. controversa infection, the pollen germination was of 80.06, 58.73, and 0.67% in resistant, moderately resistant and susceptible cultivars, respectively. The above results suggested that the use using of resistant cultivar is a good option against the dwarf bunt disease.

4.
Thorac Cancer ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811475

RESUMO

Primary pulmonary Hodgkin's lymphoma (PPHL) is an extremely rare disease. The nonspecific clinical and radiological features render the diagnosis a great challenge. Here, we present a case of PPHL mimicking rheumatoid arthritis-associated organizing pneumonia.

5.
Artigo em Chinês | MEDLINE | ID: mdl-33794610

RESUMO

Objective:To explore the clinical features of cephalic and facial limited langerhans cell histiocytosis (LCH) in children for improving its diagnosis and treatment. Methods:Clinical data of 8 children with cephalic and facial limited LCH were retrospectively analyzed, including the onset time of disease, lesion location, imaging data, clinical manifestations and treatment strategies. Results:One case was preliminarily diagnosed as chronic inflammation with nasal back lesions, then conformed by repeated surgical pathology. Six cases were found to have simple cephalic and facial lumps without pain and swelling. One case was found to have temporal lump with suppurate in the lateral auditory canal. Five cases were treated with surgical excision of lesions. Three cases were treated with surgical excision of lesions, and continued with chemotherapy after confirmed pathological diagnosis. All cases were followed up for 2-3 years with good prognosis. Conclusion:Cephalic and facial limited LCH in children was easy to be misdiagnosed and should be regarded as animportant differential diagnosis of cephalic and facial lumps. Good outcome is achieved by treatment with surgical resection combined with adjuvant chemotherapy.


Assuntos
Histiocitose de Células de Langerhans , Criança , Meato Acústico Externo , Face , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Humanos , Dor , Estudos Retrospectivos
6.
Eur J Pharmacol ; : 174077, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798601

RESUMO

This study investigated the hemodynamic effect of Bay 60-7550, a phosphodiesterase type 2 (PDE2) inhibitor, in healthy rat hearts both in vivo and ex vivo and its underlying mechanisms. In vivo rat left ventricular pressure-volume loop, Langendorff isolated rat heart, Ca2+ transient of left ventricular myocyte and western blot experiments were used in this study. The results demonstrated that Bay 60-7550 (1.5 mg/kg, i.p.) increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-diastolic volume, heart rate, and ejection fraction. The simultaneous aortic pressure recording indicated that the systolic blood pressure was increased and diastolic blood pressure was decreased by Bay 60-7550. Also, the arterial elastance which is proportional to the peripheral vessel resistance was significantly decreased. Bay 60-7550 (0.001, 0.01, 0.1, 1 µmol/l) also enhanced the left ventricular development pressure in non-paced and paced modes with a decrease of heart rate in non-paced model. Bay 60-7550 (1 µmol/l) increased SERCA2a activity and SR Ca2+ content and reduced SR Ca2+ leak rate. Furthermore, Bay 60-7550 (0.1 µmol/l) increased the phosphorylation of phospholamban at 16-serine without significantly changing the phosphorylation levels of phospholamban at 17-threonine and RyR2. Bay 60-7550 increased the rat heart contractility and reduced peripheral arterial resistance may be mediated by increasing the phosphorylation of phospholamban and dilating peripheral vessels. PDE2 inhibitors which result in a positive inotropic effect and a decrease in peripheral resistance might serve as a target for developing agents for the treatment of heart failure in clinical settings.

7.
Int J Nanomedicine ; 16: 2337-2356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790553

RESUMO

The development of monoclonal antibody treatments for successful tumor-targeted therapies took several decades. However, the efficacy of antibody-based therapy is still confined and desperately needs further improvement. Nanobodies are the recombinant variable domains of heavy-chain-only antibodies, with many unique properties such as small size (~15kDa), excellent solubility, superior stability, ease of manufacture, quick clearance from blood, and deep tissue penetration, which gain increasing acceptance as therapeutical tools and are considered also as building blocks for chimeric antigen receptors as well as for targeted drug delivery. Thus, one of the promising novel developments that may address the deficiency of monoclonal antibody-based therapies is the utilization of nanobodies. This article provides readers the significant factors that the structural and biochemical properties of nanobodies and the research progress on nanobodies in the fields of tumor treatment, as well as their application prospect.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33710495

RESUMO

A 67-year-old female patient was admitted due to "coughing and chest tightness" for more than 7 months. She had recurring chest tightness and shortness of breath after activities for more than 3 months, which worsened in the past 1 month. More than 7 months ago, the patient had a severe cough with a small amount of white sputum and chest tightness and discomfort, and visited a local hospital. The heart color Doppler ultrasound and other examinations were checked, and she was diagnosed with pulmonary embolism. Pulmonary artery CTA (CT angiography) showed the shadow of an intraluminal filling defect in the proximal main pulmonary artery. Therefore, a diagnosis of pulmonary embolism was made, with proximal tortuous stenosis of the left main pulmonary artery and distal expansion, which were considered to be congenital malformations.

9.
Sci Rep ; 11(1): 5773, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707584

RESUMO

Dwarf bunt of wheat, which is caused by Tilletia controversa J.G. Kühn, is a soil-borne disease which may lead up to an 80% loss of yield together with degradation of the quality of the wheat flour by production of a fishy smell. In this study, high-throughput sequencing technology was employed to characterize the microbial composition of wheat tissues (roots, spikes, first stem under the ear, and stem base) and rhizosphere soil of wheat varieties that are resistant and susceptible to T. controversa. We observed that the soil fungal community abundance and diversity were higher in resistant varieties than in susceptible varieties in both inoculated and uninoculated wheat, and the abundances of Sordariomycetes and Mortierellomycetes increased in the resistant varieties infected with T. controversa, while the abundances of Dothideomycetes and Bacteroidia increased in the susceptible varieties. Regarding the bacteria present in wheat tissues, the abundances of Chloroflexi, Bacteroidetes, Gemmatimonadetes, Verrucomicrobia and Acidobacteria in the ear and the first stem under the ear were higher than those in other tissues. Our results indicated that the abundances of Sordariomycetes, Mortierellomycetes, Leotiomycetes, Chryseobacterium and Massilia were higher in T. controversa-infected resistant varieties than in their controls, that Dothideomycetes, Bacteroidia, Nocardioides and Pseudomonas showed higher abundances in T. controversa-infected susceptible varieties, and that Curtobacterium, Exiguobacterium, Planococcus, and Pantoea may have higher abundances in both T. controversa-infected susceptible and resistant varieties than in their own controls.

10.
Health Qual Life Outcomes ; 19(1): 79, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750396

RESUMO

PURPOSE: Buyang Huanwu decoction (BHD) is a widely used traditional Chinese medicine for the rehabilitation of ischemic stroke patients in China, but its clinical efficacy and safety have not been adequately assessed. In this paper, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of BHD. METHODS: We searched seven electronic databases from inception to 31 March 2019. The language was limited to Chinese and English. Randomized controlled trials evaluating the efficacy and safety of BHD for the rehabilitation of ischemic stroke patients were included in the meta-analysis. Reviewers independently performed the screening, data extraction, bias assessment, and data analysis. The treatment efficacy was pooled in a meta-analysis using RevMan 5.3 software with a random-effect model. Any disagreement was resolved by discussion among all reviewers. The PRISMA statement was used in the review process. RESULTS: A total of 11 studies with 1084 patients were included in the meta-analysis. The results suggested that BHD was superior to other treatments in terms of clinical efficacy in symptoms and daily activities (n = 684, RR = 1.12, 95% CI: 0.99 to 1.27), clinical efficacy in TCM symptoms (n = 280, RR = 1.45, 95% CI: 1.03 to 2.03), National Institute of Health stroke scale (n = 192, MD = 1.66, 95% CI: -1.08 to 4.40), and activities of daily living (n = 200, MD = 8.20, 95% CI: -3.95 to 20.35). CONCLUSIONS: The results supported the clinical use of BHD for the rehabilitation of ischemic stroke patients. However, the methodological qualities of the included studies were relatively low, and there were limited reports on adverse events. The clinical efficacy and safety of BHD need to be further confirmed by more well-designed and high-quality randomized controlled trials to warrant the clinical recommendation of BHD for the rehabilitation of ischemic stroke patients.

11.
Ying Yong Sheng Tai Xue Bao ; 32(3): 1015-1022, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754568

RESUMO

The distribution pattern of biological soil crusts (biocrusts) is one of the main factors affecting runoff and sediment yield. The relationship between runoff and sediment yield and biocrusts' distribution pattern is not clear, which hinders understanding the mechanism underlying the effects of biocrusts on runoff and sediment from slopes. To fill the knowledge gap, we investigated the relationship between the landscape indices of three biocrusts' distribution patterns, i.e. zonation, chessboard and random, and the hydraulic parameters, using of simulated rainfall experiments and landscape ecology methods. The results showed that biocrust significantly affected the erosion force of slopes and that its distribution pattern could affect slope erosion dynamics. Compared to bare soil, the presence of biocrusts significantly reduced the runoff velocity (54.6%) and Froude number (67.0%), increased the runoff depth (86.2%) and Darcy-Weisbach resistance coefficient (10.68 times), but did not affect the Reynolds number and runoff power. Expect for the runoff depth, there were significant differences in the hydraulic parameters of the three biocrusts' distribution patterns, with the random pattern having the strongest impacts on the dynamics of slope erosion. Based on factor analysis and cluster analysis, five indices of percentage of patch to landscape area, patch density, landscape shape index, patch cohesion and splitting could be used as the indicators for the distribution characteristics of biocrust patches. The patch cohesion and splitting of biocrust patches were the main distribution pattern indices of the hydrodynamics of surface runoff. As the patches patch cohesion decreased, the splitting increased, which caused the surface runoff velocity increase, the resistance decrease, and the slope erosion became more severe.


Assuntos
Chuva , Solo , Sedimentos Geológicos , Hidrodinâmica
12.
Biomed Pharmacother ; 137: 111375, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761601

RESUMO

Anthracyclines are highly effective chemotherapeutics for antineoplastic treatment. However, cumulative cardiotoxicity is the main side effect with poor prognosis. No mechanism-based therapy is currently available to reverse chronic anthracycline-induced cardiotoxicity (AIC) after the deterioration of cardiac function. Calycosin (CA) is the main compound extracted from the traditional Chinese medicine Astragalus, and it has diverse beneficial effects, including autophagy modulation, anti-inflammatory and anti-tumor effects. Autophagy dysregulation is an important pathological event in AIC. Our study demonstrated a cardioprotective effect of CA in a zebrafish embryonic AIC model. To assess the effect of CA on late-onset chronic AIC, adult zebrafish were treated with CA 28 days after doxorubicin (DOX) injection, at which point heart function was obviously impaired. The results demonstrated that DOX blocked autophagic activity in adult zebrafish 8 weeks post-injection, and CA treatment improved heart function and restored autophagy. Further in vitro experiments demonstrated that atg7, which encodes an E1-like activating enzyme, may play an essential role in the CA regulation of autophagy. In conclusion, we used a rapid pharmacological screening system in embryo-adult zebrafish in vivo and elucidated the mechanism of gene targeting in vitro.

13.
Water Res ; 195: 116957, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711745

RESUMO

To fully understand the economic viability and implementation strategy of the emerging algae-based desalination technology, this study investigates the economic aspects of algae-based desalination system by comparing the life-cycle costs of three different scenarios: (1) a multi-stage microalgae based desalination system; (2) a hybrid desalination system based on the combination of microalgae and low pressure reverse osmosis (LPRO) system; and (3) a seawater reverse osmosis (SWRO) desalination system. It is identified that the capital expenditure (CAPEX) and operational expenditure (OPEX) of scenario 1 are significantly higher than those of scenarios 2 and 3, when algal biomass reuse is not taken into consideration. If the revenues obtained from the algal biomass reuse are taken into account, the OPEX of scenario 1 will decrease significantly, and scenarios 2 and 3 will have the highest and lowest OPEX, respectively. However, due to the high CAPEX of scenario 1, the total expenditure (TOTEX) of scenario 1 is still 27% and 33% higher than those of scenarios 2 and 3, respectively. A sensitivity study is undertaken to understand the effects of six key parameters on water total cost for different scenarios. It is suggested that the electricity unit price plays the most important role in determining the water total cost for different scenarios. An uncertainty analysis is also conducted to investigate the effects and limitations of the key assumptions made in this study. It is suggested that the assumption of total dissolved solids (TDS) removal efficiency of microalgae results in a high uncertainty of life-cycle cost analysis (LCCA). Additionally, it is estimated that 1.58 megaton and 0.30 megaton CO2 can be captured by the algae-based desalination process for scenarios 1 and 2, respectively, over 20 years service period, which could result in approximately AU $18 million and AU $3 million indirect financial benefits for scenarios 1 and 2, respectively. When algal biomass reuse, CO2 bio-fixation and land availability are all taken into account, scenario 2 with hybrid desalination system is considered as the most economical and environmentally friendly option.


Assuntos
Purificação da Água , Animais , Custos e Análise de Custo , Filtração , Osmose , Água do Mar
14.
Urol Oncol ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33685800

RESUMO

BACKGROUND: Reported 4Kscore thresholds used to differentiate between patients with and without high-grade prostate cancer (CaP) were variable. Patients with 4Kscore results <7.5% have been proven to be at low risk of carrying high-grade CaP. This study employed a meta-analysis approach in order to assess the diagnostic accuracy of the 4Kscore as a means of detecting high-grade CaP in prostate biopsy samples using cutoff values of 7.5% to 10%. METHODS: Relevant studies published as of December 2019 were identified via searching PubMed, Embase, and Cochrane Library. Data pertaining to 4Kscore diagnostic accuracy were then extracted from these studies and utilized for the calculation of pooled sensitivity , specificity , diagnostic odds ratio , and area under the curve values relating to high-grade CaP diagnosis. RESULTS: In total, 9 studies incorporating 1,689 high-grade CaP patients were included in our meta-analysis. Following the exclusion of 1 outlier study, the pooled sensitivity, specificity , diagnostic odds ratio , and area under the curve values for 4Kscore diagnostic accuracy with corresponding 95% confidence intervals (CIs) were 0.90 (95%CI: 0.86-0.92), 0.44 (95%CI: 0.36-0.52), 7 (95%CI: 5-8), and 0.81 (95%CI: 0.77-0.84), respectively. CONCLUSION: These findings indicate that 4Kscore can be used as a model for the diagnosis of high-grade CaP. However, we detected significant heterogeneity among studies that was not explained by subgroup or meta-regression analysis, thus lowering our confidence in these results. It is therefore essential that future large, well-designed studies be conducted so as to confirm whether the 4Kscore can be used with cutoff values of 7.5% to 10% to reliably detect high-grade CaP.

15.
Clin Respir J ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686798

RESUMO

INTRODUCTION AND OBJECTIVES: Pulmonary infarction (PI) shares similar symptoms and imaging presentations with community-acquired pneumonia (CAP), which might delay diagnosis and lead to devastating consequences. Noncontrast computed tomography (CT) is the first-line examination for the patients with the respiratory symptoms. This study aimed to investigate a radiomics method to differentiate PI from CAP using noncontrast-enhanced CT. METHODS: Noncontrast-enhanced CT images of 54 patients with PI and 64 patients with CAP were retrospectively selected. All patients were confirmed using computed tomography pulmonary angiography (CTPA). A radiomics model was built with 18 texture features that showed significant differences between PI and CAP patients. For comparison, a clinical model using clinical biomarkers and an integrated model combining the radiomics and clinical biomarkers were also generated. An experienced radiologist performed diagnoses using the noncontrast-enhanced CT images. The parameters of the models were generated using a training dataset of 61 patients, whereas the performance of the models was evaluated using receiver operating characteristic (ROC) analysis and Harrell's concordance index (C-index) applied to a separate validation dataset of 57 patients. RESULTS: The integrated model achieved the best performance (C-index 0.760, sensitivity 0.703, specificity 0.867, positive predictive value [PPV] 0.826, and negative predictive value [NPV] 0.765). The radiomics model was better than both the clinical model and the radiologist's interpretations (C-index 0.721, 0.707, 0.665, respectively; sensitivity 0.667, 0.630, 0.593; specificity 0.800, 0.785, 0.733; PPV 0.750, 0.739, 0.667; and NPV 0.727, 0.706, 0.667). CONCLUSIONS: Radiomics features generated from noncontrast-enhanced CT images allow PI to be differentiated from CAP with considerable accuracy. The radiomics-based method could provide useful information in clinical practice.

16.
Am J Ophthalmol ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737032

RESUMO

PURPOSE: To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population. DESIGN: Cross-sectional study METHODS: : The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines. RESULTS: The study included 7719 participants (mean age:60.5±8.1years; range:50-97years). The prevalence of any, early, intermediate and late AMD was 1607/7719 (20.8%;95% confidence interval (CI):20.1,21.9%), 832/7719 (10.8%;95%CI:10.1,11.5%), 733/7719 (9.5%;95%CI:8.9,10.2%), and 42/7719 (0.50%;95%CI:0.40,0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio (OR):3.49;95%CI:2.26,5.38;P<0.001;), after adjusting for older age (OR:1.06;95%CI:1.05,1.07;P<0.001), higher serum concentration of calcium (OR:2.52;95%CI:1.32,4.84;P=0.005), high-density lipoproteins (OR:1.39;95%CI:1.19,1.61;P<0.001), and lower lipoprotein a (OR:0.99;95%CI:0.98,0.99;P=0.02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD:OR:4.35,P<0.001; intermediate and late AMD:OR:6.14,P<0.001). Individuals with a monocyte count of ≥0.5 × 109/L as compared to participants with a monocyte of 0.1-0.4 × 109/L had a 1.45 fold increased risk for any AMD (OR:1.45;95%CI:1.27,1.64;P<0.001), and 1.58 fold increase risk for intermediate/late AMD (OR:1.58;95%CI:1.33,1.87;P<0.001). CONCLUSION: A higher prevalence of early, intermediate AMD, late AMD and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD.

17.
Mol Neurobiol ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33733293

RESUMO

Ketamine is a widely used analgesic and anesthetic in obstetrics and pediatrics. Ketamine is known to promote neuronal death and cognitive dysfunction in the brains of humans and animals during development. Monosialotetrahexosyl ganglioside (GM1), a promoter of brain development, exerts neuroprotective effects in many neurological disease models. Here, we investigated the neuroprotective effect of GM1 and its potential underlying mechanism against ketamine-induced apoptosis of rats. Seven-day-old Sprague Dawley (SD) rats were randomly divided into the following four groups: (1) group C (control group: normal saline was injected intraperitoneally); (2) group K (ketamine); (3) group GM1 (GM1 was given before normal saline injection); and (4) GM1+K group (received GM1 30 min before continuous exposure to ketamine). Each group contained 15 rats, received six doses of ketamine (20 mg/kg), and was injected with saline every 90 min. The Morris water maze (MWM) test, the number of cortical and hippocampal cells, apoptosis, and AKT/GSK3ß pathway were analyzed. To determine whether GM1 exerted its effect via the PI3K/AKT/GSK3ß pathway, PC12 cells were incubated with LY294002, a PI3K inhibitor. We found that GM1 protected against ketamine-induced apoptosis in the hippocampus and cortex by reducing the expression of Bcl-2 and Caspase-3, and by increasing the expression of Bax. GM1 treatment increased the expression of p-AKT and p-GSK3ß. However, the anti-apoptotic effect of GM1 was eliminated after inhibiting the phosphorylation of AKT. We showed that GM1 lessens ketamine-induced apoptosis in the hippocampus and cortex of young rats by regulating the PI3K/AKT/GSK3ß pathway. Taken together, GM1 may be a potential preventive treatment for the neurotoxicity caused by continuous exposure to ketamine.

18.
J Ethnopharmacol ; 274: 114043, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33753143

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen Injection (CKI) is a widely used TCM formula for treatment of carcinomatous pain and tumors of digestive system including hepatocellular carcinoma (HCC). However, the potential mechanisms of CKI for treatment of HCC have not been systematically and deeply studied. AIM OF STUDY: A metabolic data-driven systems pharmacology approach was utilized to investigate the potential mechanisms of CKI for treatment of HCC. MATERIALS AND METHODS: Based on phenotypic data generated by metabolomics and genotypic data of drug targets, a propagation model based on Dijkstra program was proposed to decode the effective network of key genotype-phenotype of CKI in treating HCC. The pivotal pathway was predicted by target propagation mode of our proposed model, and was validated in SMMC-7721 cells and diethylnitrosamine-induced rats. RESULTS: Metabolomics results indicated that 12 differential metabolites, and 5 metabolic pathways might be involved in the anti-HCC effect of CKI. A total of 86 metabolic related genes that affected by CKI were obtained. The results calculated by propagation model showed that 6475 shortest distance chains might be involved in the anti-HCC effect of CKI. According to the results of propagation mode, EGFR was identified as the core target of CKI for the anti-HCC effect. Finally, EGFR and its related pathway EGFR-STAT3 signaling pathway were validated in vivo and in vitro. CONCLUSION: The proposed method provides a methodological reference for explaining the underlying mechanism of TCM in treating HCC.

19.
J Pathol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33660264

RESUMO

IgA nephropathy (IgAN) is the most common type of glomerulonephritis worldwide, which follows a chronic but nonetheless highly variable course of progression. IgA immune complexes are the primary source of renal deposits in IgAN. Apart from the presence of granular IgA1 deposits in the glomerular mesangium and mesangial hypercellularity as common features, the detailed process of IgA1 deposition and clearance in the kidney remains unclear. We sought to examine the dynamics of IgA deposition and tissue plasticity in response to deposits including their intrarenal clearance. We followed a synthetic approach to produce a recombinant fusion between IgA Fc (rIgA) and a biotin tag, which was subsequently induced with streptavidin (SA) to form an oligomeric poly-IgA mimic. Both uninduced rIgA (mono-rIgA) and polymeric SA-rIgA (poly-rIgA) were injected intravenously into Wistar rats. Plasma IgA levels and renal and liver histology were examined in a time series. In contrast to mono-rIgA, this synthetic poly-rIgA analog formed renal deposits exclusively in the glomerulus and were mostly cleared in 3 h. However, repeated daily injections for 12 days caused long-lasting and stronger glomerular IgA deposition together with IgG and complement C3, in association with mesangial cell proliferation, matrix expansion, and variable degrees of albuminuria and hematuria that phenocopied IgAN. Ex vivo, poly-rIgA bound cultured mesangial cells and elicited cytokine production, in addition to activating plasma C3 that was consistent with the actions of IgA immune complexes in IgAN pathogenesis. Remarkably, the kidneys were able to reverse all pathologic manifestations and restore normal glomerular histology 2 weeks after injections were halted. The synthetic model showed the kinetics between the intricate balance of renal deposition and clearance, as well as glomerular plasticity towards healing. Together, the results revealed a priming effect of existing deposits in promoting stronger and longer-lasting IgA deposition to cause renal damage. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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