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1.
Sci Total Environ ; : 161665, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657672

RESUMO

Changes in lake area (water surface area) are often considered accurate and sensitive representations of climate change. However, the role that elevation plays in this dynamic is somewhat unclear; studies remain inconclusive as to whether lake responses are consistent across elevation gradients. Here, we used Landsat and keyhole satellite images to quantify lake area changes from the 1960s to 2020 at different elevations in Central Asia's Tianshan Mountains and relate them to both climatic and anthropogenic factors. The results revealed that all low-elevation lakes showed a decreasing trend, and the total area of all monitored low-elevation lakes was reduced by 18.50 %. The total area of the mid-elevation lakes decreased by 0.16 %, while the total area of the high-elevation glacial lakes increased by 4.35 %. Lakes are recharged by a variety of influxes including glacial meltwater and precipitation. Notably, human activities (urban and agricultural water consumption) were the dominant factors in the shrinkage of low-elevation lakes. Climatic factors were the main driving factors of mid-elevation lake changes, and these lakes appeared to be more sensitive to temperature changes than lakes at other elevations. In addition, significant warming dominated area changes in high-elevation proglacial and unconnected glacial lakes. Overall, those results emphasized that when using lakes to reconstruct paleoclimates or predict lake evolution, it is necessary to consider how elevation gradients and recharge types may affect lake sensitivity to variations in climatic and anthropogenic activity.

2.
Mikrochim Acta ; 190(2): 50, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629926

RESUMO

Poor selectivity and reusability of Au/Ag nanostructures are the main challenges for surface-enhanced Raman spectroscopy (SERS) in real sample detection. Herein, a novel specific and reusable three-dimensional (3D) SERS sensor with dual functions of selective trapping and photocatalytic degradation was designed. Firstly, Au-Ag bimetallic nanoparticles decorated silicon nanowires array (SiNWs-AuAg) were prepared as 3D SERS substrate. Then, silicon-based inorganic-framework molecularly imprinted TiO2 (TiO2@SiMIP) was synthesized and immobilized on SiNWs-AuAg by using rhodamine 6G (R6G) as template molecule. Owing to the excellent SERS performance of SiNWs-AuAg and the specific affinity of TiO2@SiMIP to template molecule, the prepared SERS sensor enables sensitive and selective detection of R6G in food samples with a limit of detection (LOD) of 0.27 nM. In addition, due to the photocatalysis of TiO2 and the stability of silicon-based inorganic framework, the residual templates in TiO2@SiMIP can be completely removed by UV irradiation, and the imprinted cavity of regenerated sensors still maintained good selectivity after regeneration by UV irradiation.


Assuntos
Nanopartículas Metálicas , Nanopartículas Metálicas/química , Silício/química , Análise Espectral Raman/métodos , Titânio/química
4.
Artigo em Inglês | MEDLINE | ID: mdl-36662448

RESUMO

PURPOSE: Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM. METHODS: A type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells. RESULTS: We showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects. CONCLUSION: Our data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.

5.
J Int Med Res ; 51(1): 3000605221147183, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36597409

RESUMO

OBJECTIVE: Endometriosis (EMS) is a chronic gynecological disorder with an urgent need of a reliable non-invasive diagnostic strategy. Recently, there has been increasing interest in using the contents of exosomes, especially exosomal microRNAs (miRNAs), as potential biomarkers for various types of diseases. In this study, we assessed the differentially expressed miRNAs in exosomes derived from primary normal and ectopic endometrial cells. METHODS: We used miRNA microarray analysis to identify differentially expressed exosomal miRNAs. Among the selected exosomal miRNAs, we focused on hsa-miR-202-3p and hsa-miR-202-5p and validated their expression levels using quantitative reverse transcription polymerase chain reaction analysis. We then further examined their expression in exosomes derived from vaginal discharge (leukorrhea) from patients with EMS and the negative control group. RESULTS: The data show that hsa-miR-202-3p and hsa-miR-202-5p were expressed significantly higher in leukorrhea-derived exosomes from EMS patients compared with the negative controls. CONCLUSION: Taken together, our results suggest that leukorrhea-derived exosomal hsa-miR-202 could serve as a potential useful biomarker for diagnosing EMS.


Assuntos
Endometriose , Exossomos , Leucorreia , MicroRNAs , Feminino , Humanos , Endometriose/diagnóstico , Endometriose/genética , Endometriose/metabolismo , Leucorreia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Exossomos/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-36642942

RESUMO

The main objective of this study was to compare the pharmacokinetic (PK) bioequivalence of two capecitabine tablets and explore the different PK profiles of various tumors in Chinese patients with cancer. All 76 patients with a confirmed cancer diagnosis were included in this study. A single dose of 2000 mg of test or reference capecitabine (Xeloda, Hoffmann-La Roche) was orally administered postprandially. After 24 hours of washout, the patients were administered the test or the reference capecitabine alternately. PK samples were taken at the time of predose up to 6 hours postdose. Bioequivalence evaluation was performed using the geometric mean ratios of peak concentration in plasma (Cmax) , area under the concentration-time curve from time 0 to 6 h (AUC0-t) , and area under the concentration-time curve from time 0 to infinity (AUC0-∞ ) for capecitabine and 5-fluorouracil (5-FU). In this study, 90% confidence intervals of test/reference mean ratios of Cmax , AUC0-t , AUC0-∞ of capecitabine and 5-FU were in the range of 80%-125%. Both the test and reference capecitabine regimens were well tolerated in this study. Furthermore, we found that patients with esophageal-gastrointestinal cancers had higher exposure to capecitabine and a shorter time to Cmax (Tmax) than those with breast cancer. In conclusion, a single oral dose of 2000 mg of test capecitabine tablets after postprandial administration was bioequivalent to the reference drug.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36683548

RESUMO

PURPOSES: The physiological and pathological conditions of individuals could influence the absorption and metabolism of drugs in vivo, so this study assessed the bioequivalence and pharmacokinetics of lenalidomide 25 mg capsules (test formulation) and Revlimid 25 mg capsules (reference formulation) in Chinese patients with multiple myeloma (MM). MATERIALS AND METHODS: A multicenter, open-label, randomized, two-period, crossover trial was established to evaluate a single capsule of test and reference formulations under fasting conditions. Pharmacokinetic parameters were assessed, and adverse events (AEs) were monitored throughout. RESULTS: Overall, 40 patients with MM completed the study. 17 AEs were reported, among which there was 1 serious event during the study. Geometric ratios for the maximum plasma concentration (Cmax) (98.50%; 90% confidence interval (CI), 91.89 - 105.60%), area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration (AUC(0-t)) (94.74%; CI, 92.07 - 97.50%), and AUC from time 0 to infinity (AUC(0-∞)) (95.55%; CI, 93.07 - 98.09%) all met bioequivalence criteria. Statistics of the data of 39 patients after oral administration of lenalidomide (both test and reference formulation) demonstrated that plasma exposure tends to increase with age. CONCLUSION: The two formulations of lenalidomide 25 mg displayed similar pharmacokinetic profiles and were bioequivalent. Age was verified to change the pharmacokinetics of lenalidomide, as increasing age was correlated with higher total exposure.

8.
Mar Pollut Bull ; 188: 114577, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36689872

RESUMO

In order to better understand the migration and accumulation behavior of polycyclic aromatic hydrocarbons (PAHs) in biological chains in the cold environment around the Ardley Island, a variety of biological and penguin manure samples during China's 36th Antarctic Scientific expedition have been collected and studied. A certain difference in PAHs concentration was observed in the environmental samples, and the order of size was as follows: fish > limpets > krill > manure > brown alga > mosses. The percentage of PAHs with different ring numbers in brown alga, moss, and krill was in the following order: three rings > two rings > four rings > five rings > six rings. The proportion of HMW-PAHs in limpets and fish samples was higher than that in brown alga, moss, manure, and krill samples. The main source of PAHs in environmental samples near Ardley Island is oil, which may be due to the development of tourism in Antarctica, the number of ships and human activities around the region. Therefore, it is imperative to strengthen the protection of the ecological environment in the area around Ardley Island.

9.
Curr Med Sci ; 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680686

RESUMO

OBJECTIVE: Cardiac fibroblasts (CFs) proliferation and extracellular matrix deposition are important features of cardiac fibrosis. Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases. This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway. METHODS: MTT and 5-ethynyl-2'-deoxyuridine assays were performed to determine cell viability. Western blotting was performed to detect the expression of proliferating cell nuclear antigen (PCNA) and integrin signaling pathway. The fibronectin was observed by ELISA. Immunohistochemical staining was employed to evaluate the expression of integrin ß3. RESULTS: The PCNA expression in the CFs was enhanced after isoproterenol (ISO) stimulation accompanied by an elevated expression of integrin beta-3 (ß3). The blockade of the integrin ß3 with a specific integrin ß3 antibody reduced the PCNA expression induced by the ISO. Decreasing the integrin ß3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt. Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs. Calcitriol (CAL), an active form of vitamin D, attenuated the ISO-induced CFs proliferation by downregulating the integrin ß3 expression, and phosphorylation of FAK and Akt. Moreover, CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO. The administration of calcitriol decreased the integrin ß3 expression in the ISO-induced myocardial injury model. CONCLUSION: These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrin ß3/FAK/Akt pathway.

10.
Sci Adv ; 9(3): eadd3867, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662861

RESUMO

Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Peptídeo Hidrolases/metabolismo , Proteólise , Metaloproteases/metabolismo , Internalização do Vírus
11.
J Virol ; : e0171922, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688655

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

12.
Antiviral Res ; 209: 105491, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36526073

RESUMO

In an effort to develop safe and innovative in vitro models for Ebola virus (EBOV) research, we generated a recombinant Ebola virus where the glycoprotein (GP) gene was substituted with the Cre recombinase (Cre) gene by reverse genetics. This defective virus could multiply itself in a complementary permissive cell line, which could express GP and reporter protein upon exogenous Cre existence. The main features of this novel model for Ebola virus are intact viral life cycle, robust virus multiplication and normal virions morphology. The design of this model ensures its safety, excellent stability and maneuverability as a tool for virology research as well as for antiviral agent screening and drug discovery, and such a design could be further adapted to other viruses.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Humanos , Ebolavirus/genética , Ebolavirus/metabolismo , Linhagem Celular , Glicoproteínas/genética , Replicação Viral , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
13.
J Colloid Interface Sci ; 634: 601-609, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36549208

RESUMO

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure(Au-star@PB)as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging(PAI) and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , Fototerapia/métodos , Nanopartículas/química , Ferrocianetos/química , Imageamento por Ressonância Magnética/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Meios de Contraste/química , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Ouro/química
14.
Oral Oncol ; 136: 106278, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36525782

RESUMO

OBJECTIVES: Artificial intelligence could enhance the use of disparate risk factors (crude method) for better stratification of patients to be screened for oral cancer. This study aims to construct a meta-classifier that considers diverse risk factors to identify patients at risk of oral cancer and other suspicious oral diseases for targeted screening. MATERIALS AND METHODS: A retrospective dataset from a community oral cancer screening program was used to construct and train the novel voting meta-classifier. Comprehensive risk factor information from this dataset was used as input features for eleven supervised learning algorithms which served as base learners and provided predicted probabilities that are weighted and aggregated by the meta-classifier. Training dataset was augmented using SMOTE-ENN. Additionally, Shapley additive explanations (SHAP) values were generated to implement the explainability of the model and display the important risk factors. RESULTS: Our meta-classifier had an internal validation recall, specificity, and AUROC of 0.83, 0.86, and 0.85 for identifying the risk of oral cancer and 0.92, 0.60, and 0.76 for identifying suspicious oral mucosal disease respectively. Upon external validation, the meta-classifier had a significantly higher AUROC than the crude/current method used for identifying the risk of oral cancer (0.78 vs 0.46; p = 0.001) Also, the meta-classifier had better recall than the crude method for predicting the risk of suspicious oral mucosal diseases (0.78 vs 0.47). CONCLUSION: Overall, these findings showcase that our approach optimizes the use of risk factors in identifying patients for oral screening which suggests potential clinical application.


Assuntos
Detecção Precoce de Câncer , Neoplasias Bucais , Humanos , Inteligência Artificial , Estudos Retrospectivos , Fatores de Risco , Aprendizado de Máquina
15.
Int J Cancer ; 152(1): 7-14, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362560

RESUMO

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P < .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Programas de Rastreamento , China/epidemiologia
16.
J Environ Sci (China) ; 127: 431-440, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36522075

RESUMO

Direct discharge of aquaculture wastewater may have toxic effects, due to the presence of heavy metals, antibiotics, and even resistant pathogens, but little attention has been given. Here, tanks simulating a wild ecosystem were built to study the effects of long-term exposure to duck wastewater containing oxytetracycline (OTC) and/or arsenic (As) on the growth, physiological function, and gut microbiota evolution of Xenopus tropicalis. The results showed that duck wastewater had no apparent impact on X. tropicalis, but the impact increased significantly (P < 0.05) with exposure to OTC and/or As, especially the impact on body weight and growth rate. Biochemical indicators revealed varying degrees of oxidative stress damage, hepatotoxicity (inflammation, necrosis, and sinusoids), and collagen fibrosis of X. tropicalis in all treated groups after 72 days of exposure, which indirectly inhibited X. tropicalis growth. Moreover, 16S rDNA amplicon sequencing results showed that the gut microbiota structure and metabolic function were perturbed after chronic exposure, which might be the leading cause of growth inhibition. Interestingly, the abundance of intestinal resistance genes (RGs) increased with exposure time owing to the combined direct and indirect effects of stress factors in duck wastewater. Moreover, once the RGs were expressed, the resistance persisted for at least 24 days, especially that conferred by tetA. These results provide evidence of the toxic effects of DW containing OTC (0.1-4.0 mg/L) and/or As (0.3-3.5 µg/L) on amphibians and indicate that it is vital to limit the usage of heavy metals and antibiotics on farms to control the biotoxicity of wastewater.


Assuntos
Arsênio , Oxitetraciclina , Animais , Oxitetraciclina/toxicidade , Patos , Arsênio/toxicidade , Xenopus , Ecossistema , Antibacterianos/toxicidade
17.
Vaccine ; 41(2): 555-563, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36503858

RESUMO

Antigens expressed during the sexual development of malaria parasites are transmission-blocking vaccine (TBV) targets. Pb22, a protein expressed and localized to the plasma membrane of gametes and ookinetes in Plasmodium berghei, is an excellent TBV candidate. Here, we evaluated the TB potential of the Plasmodium vivax ortholog Pv22 using a transgenic P. berghei parasite line and P. vivax clinical isolates. The full-length recombinant Pv22 (rPv22) protein was produced and used to immunize mice and rabbits to obtain antibodies. We generated a transgenic P. berghei line (TrPv22Pb) by inserting the pv22 gene into the pb22 locus and showed that Pv22 expression completely rescued the defects in male gametogenesis of the pb22 deletion parasite. Since Pv22 in the transgenic parasite showed similar expression and localization patterns to Pb22, we used the TrPv22Pb parasite as a surrogate to evaluate the TB potential of Pv22. In mosquito feeding assays, mosquitoes feeding on rPv22-immunized mice infected with TrPv22Pb parasites showed a 49.3-53.3 % reduction in the oocyst density compared to the control group. In vitro assays showed that the rPv22 immune sera significantly inhibited exflagellation and ookinete formation of the TrPv22Pb parasites. In a direct membrane feeding assay using three clinical P. vivax isolates, the rabbit anti-rPv22 antibodies also significantly decreased the oocyst density by 53.7, 30.2, and 26.2 %, respectively. This study demonstrated the feasibility of using transgenic P. berghei parasites expressing P. vivax antigens as a potential tool to evaluate TBV candidates. However, the much weaker TB activity of Pv22 obtained from two complementary assays suggest that Pv22 may not be a promising TBV candidate for P. vivax.


Assuntos
Culicidae , Vacinas Antimaláricas , Malária Vivax , Malária , Masculino , Animais , Camundongos , Coelhos , Malária/prevenção & controle , Plasmodium vivax/genética , Plasmodium berghei/genética , Vacinas Antimaláricas/genética , Proteínas de Protozoários , Malária Vivax/prevenção & controle , Proteínas Recombinantes , Anticorpos Antiprotozoários
18.
Proteomics ; 22(5-6): e2100041, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34545670

RESUMO

Posttranslational modifications (PTMs) affect protein function/dysfunction, playing important roles in the occurrence and development of tauopathies including Alzheimer's disease. PTM detection is significant and still challenging due to the requirements of high sensitivity to identify the subtle structural differences between modifications. Herein, in terms of the unique geometry of the aerolysin (AeL) nanopore, we elaborately engineered a T232K AeL nanopore to detect the acetylation and phosphorylation of Tau segment (Pep). By replacing neutral threonine (T) with positively charged lysine (K) at the 232 sites, the T232K and K238 rings of this engineered T232K AeL nanopore corporately work together to enhance electrostatic trapping of the acetylated and phosphorylated Tau peptides. Translocation speed of the monophosphorylated Pep-P was decelerated by up to 46 folds compared to the wild-type (WT) AeL nanopore. The prolonged residences within the T232K AeL nanopore enabled to simultaneously identify the monoacetylated Pep-Ac, monophosphorylated Pep-P, di-modified Pep-P-Ac and non-modified Pep. The tremendous potential is demonstrated for PTM sensing by manipulating non-covalent interactions between nanopores and single analytes.


Assuntos
Nanoporos , Proteínas Citotóxicas Formadoras de Poros , Proteínas tau/química , Acetilação , Toxinas Bacterianas , Fosforilação , Proteínas Citotóxicas Formadoras de Poros/química , Engenharia de Proteínas , Processamento de Proteína Pós-Traducional
19.
J Magn Reson Imaging ; 55(6): 1864-1874, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34545977

RESUMO

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Animais , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Imagem de Difusão por Ressonância Magnética , Modelos Animais de Doenças , Fibrose , Humanos , Inflamação/diagnóstico por imagem , Imageamento por Ressonância Magnética , Camundongos , Estudos Prospectivos
20.
Front Genet ; 13: 1031589, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457745

RESUMO

Objective: Sepsis is a common disease in internal medicine, with a high incidence and dangerous condition. Due to the limited understanding of its pathogenesis, the prognosis is poor. The goal of this project is to screen potential biomarkers for the diagnosis of sepsis and to identify competitive endogenous RNA (ceRNA) networks associated with sepsis. Methods: The expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) were derived from the Gene Expression Omnibus (GEO) dataset. The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened by bioinformatics analysis. DEmRNAs were analyzed by protein-protein interaction (PPI) network analysis, transcription factor enrichment analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Set Enrichment Analysis (GSEA). After the prediction of the relevant database, the competitive ceRNA network is built in Cytoscape. The gene-drug interaction was predicted by DGIgb. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm five lncRNAs from the ceRNA network. Results: Through Venn diagram analysis, we found that 57 DElncRNAs, 6 DEmiRNAs and 317 DEmRNAs expressed abnormally in patients with sepsis. GO analysis and KEGG pathway analysis showed that 789 GO terms and 36 KEGG pathways were enriched. Through intersection analysis and data mining, 5 key KEGG pathways and related core genes were revealed by GSEA. The PPI network consists of 247 nodes and 1,163 edges, and 50 hub genes are screened by the MCODE plug-in. In addition, there are 5 DElncRNAs, 6 DEmiRNAs and 28 DEmRNAs in the ceRNA network. Drug action analysis showed that 7 genes were predicted to be molecular targets of drugs. Five lncRNAs in ceRNA network are verified by qRT-PCR, and the results showed that the relative expression of five lncRNAs was significantly different between sepsis patients and healthy control subjects. Conclusion: A sepsis-specific ceRNA network has been effectively created, which is helpful to understand the interaction between lncRNAs, miRNAs and mRNAs. We discovered prospective sepsis peripheral blood indicators and proposed potential treatment medicines, providing new insights into the progression and development of sepsis.

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