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2.
Biosensors (Basel) ; 13(1)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36671946

RESUMO

A rapid and intuitive method for detecting Vibrio parahaemolyticus (VP) was established by a designed reaction vessel which coupled CRISPR/Cas12a with loop-mediated isothermal nucleic acid amplification (LAMP). There were two spaces in the vessel-holding LAMP reaction solution and CRISPR reaction solution, respectively, which were separated with a polyvinyl alcohol (PVA) membrane. The PVA membrane could be dissolved with a water solution. The thermolabile hemolysin (TLH) gene of VP was employed as the detection target. After the target sequence of the TLH gene was amplified with LAMP, the PVA membrane would be dissolved and the CRISPR reaction solution mixed with the LAMP reaction solution. In this way, amplicons could be detected with CRISPR/Cas12a in the reaction vessel. The fluorescent signals produced by the positive samples were clearly identified by the naked eye under a UV light, while the negative samples were dark. The whole detection procedure could be finished within 35 min with a detection limit of 100 copies/µL. The designed reaction vessel is easy to produce and can effectively prevent contamination due to the opening of the reaction vessel after the LAMP reaction. Thus, it will have the potential to provide a new solution for rapid detection in the field.


Assuntos
Álcool de Polivinil , Vibrio parahaemolyticus , Sistemas CRISPR-Cas , Técnicas de Amplificação de Ácido Nucleico/métodos , Vibrio parahaemolyticus/genética , Cateteres
3.
Biosensors (Basel) ; 13(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36671975

RESUMO

Given the possibility that food contaminated with SARS-CoV-2 might become an infection source, there is an urgent need for us to develop a rapid and accurate nucleic acid detection method for SARS-CoV-2 in food to ensure food safety. Here, we propose a sensitive, specific, and reliable molecular detection method for SARS-CoV-2. It has a mechanism to control amplicon contamination. Swabs from spiked frozen shrimps were used as detection samples, which were processed by heating at 95 °C for 30 s. These preprocessed samples served as the templates for subsequent amplification. A colorimetric LAMP reaction was carried out to amplify both the SARS-CoV-2 target and the MS2 phage simultaneously in one tube. MS2 phage was detected by colorimetric LAMP as the internal control, while SARS-CoV-2 was detected with a CRISPR/Cas12a system. The fluorescence results could be visually detected with an ultraviolet lamp. Meanwhile, uracil was incorporated during the LAMP reaction to provide an amplicon contamination proof mechanism. This test could detect as low as 20 copies of SARS-CoV-2 in one reaction. Additionally, the detection could be finished in 45 min. The test only needs a heating block and an ultraviolet lamp, which shows the potential for field detection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Sistemas CRISPR-Cas , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade
4.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675163

RESUMO

Neuroblastoma (NB) is characterized by several malignant phenotypes that are difficult to treat effectively without combination therapy. The therapeutic implication of mitochondrial ClpXP protease ClpP and ClpX has been verified in several malignancies, but is unknown in NB. Firstly, we observed a significant increase in ClpP and ClpX expression in immature and mature ganglion cells as compared to more malignant neuroblasts and less malignant Schwannian-stroma-dominant cell types in human neuroblastoma tissues. We used ONC201 targeting ClpXP to treat NB cells, and found a significant suppression of mitochondrial protease, i.e., ClpP and ClpX, expression and downregulation of mitochondrial respiratory chain subunits SDHB and NDUFS1. The latter was associated with a state of energy depletion, increased reactive oxygen species, and decreased mitochondrial membrane potential, consequently promoting apoptosis and suppressing cell growth of NB. Treatment of NB cells with ONC201 as well as the genetic attenuation of ClpP and ClpX through specific short interfering RNA (siRNA) resulted in the significant upregulation of the tumor suppressor alpha thalassemia/mental retardation X-linked (ATRX) and promotion of neurite outgrowth, implicating mitochondrial ClpXP proteases in MYCN-amplified NB cell differentiation. Furthermore, ONC201 treatment significantly decreased MYCN protein expression and suppressed tumor formation with the reactivation of ATRX expression in MYCN-amplified NB-cell-derived xenograft tumors. Taken together, ONC201 could be the potential agent to provide diversified therapeutic application in NB, particularly in NB with MYCN amplification.


Assuntos
Deficiência Intelectual , Neuroblastoma , Talassemia alfa , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Linhagem Celular Tumoral , Deficiência Intelectual/genética , Talassemia alfa/genética , Neuroblastoma/metabolismo , Mitocôndrias/metabolismo , Peptídeo Hidrolases/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo
5.
Heliyon ; 9(1): e12812, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36699279

RESUMO

In this paper, a direct numerical simulation (DNS) of dielectric fluid flow subjected to unipolar injection under an alternating current (AC) electric field is carried out. The effect of frequency f of pulsed direct current (PDC) and AC on the transient evolution of electroconvection and their subcritical bifurcations are investigated in details. Electroconvection under PDC or AC tends to exhibit oscillating flow due to the periodic boundary condition of charge density and potential compared to the direct current (DC) case. The results demonstrate that under the PDC field, the linear criterion T c decreases with increasing frequency, while the nonlinear stability criterion T f is hardly affected. Under the AC field, a critical frequency f c  = 0.0316 is found, which separates electroconvection into two typical flow regimes-periodic flow regime (f < f c ) and inhibited flow regime (f ≥ f c )-depending on whether free charges can reach the collector electrode before electric field inversion. AC-electrohydrodynamics (EHD) systems promote various flow patterns with relatively lower voltage regimes than DC-EHD systems. These mechanisms of electroconvection under the PDC/AC field offer unique possibilities for fluid flow control in biological EHD-driven flow and portable EHD applications.

6.
J Hazard Mater ; 446: 130715, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36603418

RESUMO

Neonicotinoids (NEOs) are widely applied in agricultural lands and are widespread in different environments, accelerating threats to ecosystems and human health. A number of in vitro/in vivo studies have reported adverse effects of NEOs on mammalian health, but the link between NEO exposure and toxic effects on human liver remains unclear. We randomly recruited 201 participants and quantified eight commercialized NEOs in bile. High frequency and concentration of detection indicate low degradation of human liver on NEOs. The main NEOs are nitenpyram and dinotefuran, which contribute to about 86% of the total residual levels of eight NEOs, due to the highest solubility in bile and are not degraded easily in liver. In contrast, imidacloprid and thiacloprid are major compounds in human blood, according to previous studies, suggesting that individual NEOs behave differently in blood and bile distribution. There was no statistical difference in NEO residues between cancer and non-cancer participants and among the different participant demographics (e.g., age, gender, and body mass index). The serum hematological parameters -bile acid, total bilirubin, cholesterol and alkaline phosphatase -were positively correlated with individual NEO concentrations, suggesting that NEO exposure affects liver metabolism and even enterohepatic circulation. The study first examined the NEO residues in human bile and provided new insights into their bioavailability and hepatoxicity risk.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Inseticidas , Animais , Humanos , Inseticidas/toxicidade , Inseticidas/análise , Bile/química , Ecossistema , Neonicotinoides/toxicidade , Nitrocompostos , Mamíferos
7.
J Agric Food Chem ; 71(3): 1291-1309, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36625507

RESUMO

Plant virus disease is the second most prevalent plant diseases and can cause extensive loss in global agricultural economy. Extensive work has been carried out on the development of novel antiplant virus agents for preventing and treating plant virus diseases. In this review, we summarize the achievements of the research and development of new antiviral agents in the recent five years and provide our own perspective on the future development in this highly active research field.


Assuntos
Antivirais , Vírus de Plantas , Plantas
8.
Plant Physiol ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36659854

RESUMO

Bud dormancy is an important trait in geophytes that largely affects their flowering process and vegetative growth after dormancy release. Compared with seed dormancy, the regulation of bud dormancy is still largely unclear. Abscisic acid (ABA) acts as the predominant hormone that regulates the whole dormancy process. In Gladiolus (Gladiolus hybridus), cold storage promotes corm dormancy release (CDR) by repressing ABA biosynthesis and signaling. However, the mechanisms governing ABA-related processes during CDR via epigenetics are poorly understood. Here, we show that class I BASIC PENTACYSTEINE2, (GhBPC2) directly binds to 9-CIS-EPOXYCAROTENOID DIOXYGENASE (GhNCED) and ABA INSENSITIVE5 (GhABI5) loci and down-regulates their expression to accelerate CDR. During CDR, histone modifications change dramatically at the GhBPC2-binding loci of GhABI5 with an increase in H3K27me3 and a decrease in H3K4me3. GhBPC2 is involved in both H3K27me3 and H3K4me3 and fine-tunes GhABI5 expression by recruiting Polycomb Repressive Complex 2 (PRC2) and the chromatin remodeling factor EARLY BOLTING IN SHORT DAYS (GhEBS). These results show GhBPC2 epigenetically regulates corm dormancy release in Gladiolus by mediating GhABI5 expression with PRC2 and GhEBS.

9.
Clin Med Insights Oncol ; 17: 11795549221147993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36685988

RESUMO

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

10.
ISA Trans ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36623993

RESUMO

The issue of decentralized adaptive safe tracking control for interconnected large-scale nonlinear systems (ILSNSs) with conflicted output constraints is discussed in this paper. By "conflicted output constraints", we mean that the output constraint functions conflict with reference signal, i.e., the reference signal is not completely constrained within the constraint range. In existing methods, it is always assumed that the reference signal is constrained within the constraint region. In practice, the constraints may be detected during system operation and conflict with the reference signal given in advance. In this particular case, the existing methods based on barrier Lyapunov function (BLF) or nonlinear transformation function (NTF) are invalid. From a new point of view, this article designs a new safety reference signal (SRS) which is completely restricted within the constraint range by using the boundary protection approach. Meanwhile, a prescribed performance function which can arbitrarily define the convergence time and tracking accuracy is introduced so that the system output can better track the SRS. Then, combining backstepping technique and radial basis function neural network (RBFNN), a new controller is constructed, under which a desired tracking trajectory can be obtained under the premise of ensuring safety performance. Furthermore, by adding a dynamic event triggering mechanism (DETM) between the actuator and the plant, the communication burden is effectively reduced. Simulation results verify the scheme developed.

11.
Antimicrob Agents Chemother ; : e0082122, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625569

RESUMO

Protein ubiquitination is an important posttranslational regulation mechanism that mediates Plasmodium development and modifies parasite responses to antimalarial drugs. Although mutations in several parasite ubiquitination enzymes have been linked to increased drug tolerance, the molecular mechanisms by which ubiquitination pathways mediate these parasite responses remain largely unknown. Here, we investigate the roles of a Plasmodium falciparum ring finger ubiquitin ligase (PfRFUL) in parasite development and in responses to antimalarial drugs. We engineered a transgenic parasite having the Pfrful gene tagged with an HA-2A-NeoR-glmS sequence to knockdown (KD) Pfrful expression using glucosamine (GlcN). A Western blot analysis of the proteins from GlcN-treated pSLI-HA-NeoR-glmS-tagged (PfRFULg) parasites, relative to their wild-type (Dd2) controls, showed changes in the ubiquitination of numerous proteins. PfRFUL KD rendered the parasites more sensitive to multiple antimalarial drugs, including mefloquine, piperaquine, amodiaquine, and dihydroartemisinin. PfRFUL KD also decreased the protein level of the P. falciparum multiple drug resistance 1 protein (PfMDR1) and altered the ratio of two bands of the P. falciparum chloroquine resistance transporter (PfCRT), suggesting contributions to the changed drug responses by the altered ubiquitination of these two molecules. The inhibition of proteasomal protein degradation by epoxomicin increased the PfRFUL level, suggesting the degradation of PfRFUL by the proteasome pathways, whereas the inhibition of E3 ubiquitin ligase activities by JNJ26854165 reduced the PfRFUL level. This study reveals the potential mechanisms of PfRFUL in modifying the expression of drug transporters and their roles in parasite drug responses. PfRFUL could be a potential target for antimalarial drug development.

12.
Cardiovasc Ultrasound ; 21(1): 2, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683065

RESUMO

BACKGROUND: Left ventricular (LV) myocardial work index (WI) and work efficiency (WE) have become the latest indicators for assessing LV function. Reference ranges for normal LV segmental WI and WE have not been established. METHODS: Four hundred eleven healthy Asian subjects (47% men, median age: 35 years) were enrolled prospectively. WI and WE were analysed using the LV pressure-strain loop (LVPSL) with specific software. RESULTS: WI and WE differed significantly between segments as well as between walls and levels of the left ventricle. The anteroseptal basal segment had the lowest WI and WE (1440 mmHg ± 324 and 92% [88-96], respectively) among the eighteen segments. Significant WI and WE differences were found between sexes and age groups. No correlation was observed between age groups and the average WI of any wall or level in men, while the average WI of several different walls and levels in women showed significant differences between age groups. The average WI of most walls and levels increased with age in women. No correlation was found between age groups and the average WE of any wall or level in either men or women. CONCLUSIONS: This study establishes the normal reference values of WI and WE of eighteen segments for clinical work and clinical experiments. There were significant differences in WI and WE between segments, levels, and walls of the normal left ventricle. Sex should be considered when analysing WI and WE. Age should be considered when analysing WI in women.


Assuntos
Ecocardiografia , Função Ventricular Esquerda , Masculino , Humanos , Feminino , Adulto , Valores de Referência , Ventrículos do Coração/diagnóstico por imagem , Miocárdio
13.
Diabetologia ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692509

RESUMO

AIMS/HYPOTHESIS: The mitochondrial chaperonin heat shock protein (HSP) 60 is indispensable in protein folding and the mitochondrial stress response; however, its role in nutrient metabolism remains uncertain. This study investigated the role of HSP60 in diet-induced non-alcoholic fatty liver disease (NAFLD). METHODS: We studied human biopsies from individuals with NAFLD, murine high-fat-diet (HFD; a diet with 60% energy from fat)-induced obesity (DIO), transgenic (Tg) mice overexpressing Hsp60 (Hsp60-Tg), and human HepG2 cells transfected with HSP60 cDNA or with HSP60 siRNA. Histomorphometry was used to assess hepatic steatosis, biochemistry kits were used to measure insulin resistance and glucose tolerance, and an automated home cage phenotyping system was used to assess energy expenditure. Body fat was assessed using MRI. Macrophage infiltration, the lipid oxidation marker 4-hydroxy-2-nonenal (4-HNE) and the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected using immunohistochemistry. Intracellular lipid droplets were evaluated by Nile red staining. Expression of HSP60, and markers of lipogenesis and fatty acid oxidation were quantified using RT-PCR and immunoblotting. Investigations were analysed using the two-way ANOVA test. RESULTS: Decreased HSP60 expression correlated with severe steatosis in human NAFLD biopsies and murine DIO. Hsp60-Tg mice developed less body fat, had reduced serum triglyceride levels, lower levels of insulin resistance and higher serum adiponectin levels than wild-type mice upon HFD feeding. Respiratory quotient profile indicated that fat in Hsp60-Tg mice may be metabolised to meet energy demands. Hsp60-Tg mice showed amelioration of HFD-mediated hepatic steatosis, M1/M2 macrophage dysregulation, and 4-HNE and 8-OHdG overproduction. Forced HSP60 expression reduced the mitochondrial unfolded protein response, while preserving mitochondrial respiratory complex activity and enhancing fatty acid oxidation. Furthermore, HSP60 knockdown enhanced intracellular lipid formation and loss of sirtuin 3 (SIRT3) signalling in HepG2 cells upon incubation with palmitic acid (PA). Forced HSP60 expression improved SIRT3 signalling and repressed PA-mediated intracellular lipid formation. SIRT3 inhibition compromised HSP60-induced promotion of AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferator-activated receptor α (PPARα levels), while also decreasing levels of fatty acid oxidation markers. CONCLUSION/INTERPRETATION: Mitochondrial HSP60 promotes fatty acid oxidation while repressing mitochondrial stress and inflammation to ameliorate the development of NAFLD by preserving SIRT3 signalling. This study reveals the hepatoprotective effects of HSP60 and indicates that HSP60 could play a fundamental role in the development of therapeutics for NAFLD or type 2 diabetes.

14.
Phytomedicine ; 109: 154548, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610154

RESUMO

BACKGROUND: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. OBJECTIVE: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. METHODS: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aß-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. RESULTS: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aß, α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice. CONCLUSION: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Camundongos , alfa-Sinucleína/metabolismo , Caenorhabditis elegans , Doenças Neurodegenerativas/tratamento farmacológico , Animais Geneticamente Modificados , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Autofagia , Doença de Alzheimer/tratamento farmacológico
15.
Anal Chim Acta ; 1239: 340670, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628703

RESUMO

Currently, some on-site nucleic acid detection platforms have been developed. However, these platforms still need to be improved in device integration and multiple detection capability. In this work, an integrated dual nucleic acid analysis platform was developed by slip valve-assisted fluidic chip coupled with CRISPR/Cas12a system. All the reagents, including nucleic acid extraction, air-dried loop-mediated isothermal amplification (LAMP) and CRISPR/Cas12a detection reagents, were preloaded on the fluidic chip. Liquids transfer and stirring could be controlled by a slip valve and a syringe. By combining duplex LAMP reaction with two CRISPR detection units, CRISPR/Cas12a-based dual nucleic acid analysis was successfully constructed. Benefiting from high-quality nucleic acid extraction on the chip, as low as 30 copies/reaction of Vibrio parahaemolyticus (V. parahaemolyticus) and 20 copies/reaction of Salmonella typhimurium (S. typhimurium) could be simultaneously detected. Detection results could be observed by the naked eye under a portable ultraviolet lamp. The whole detection procedure was finished within 60 min. This method with integrated nucleic acid analysis, dual detection capability and fluorescence visualized results provides a new solution for on-site nucleic acid analysis.


Assuntos
Sistemas CRISPR-Cas , Ácidos Nucleicos , Técnicas de Amplificação de Ácido Nucleico/métodos , Salmonella typhimurium
16.
J Clin Med ; 12(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675568

RESUMO

BACKGROUND: Few studies have explored the correlation between asthma medication and features on HRCT images. We aim to analyse the differences and temporal changes of lung function and airway resistance in asthma with diverse HRCT phenotypes in a short period after inhalation of budesonide/formoterol. METHOD: This observational study recruited 55 adult patients with varying severities of asthma. We performed detailed airway metrics measurements of chest CT scans, such as airway wall thickness (WT), wall area percentage (WA%), wall thickness percentage (T/OR), and airways with an inner perimeter of 10 mm (Pi10). The effect of lung structural features on asthma medication response was explored according to the WA% and T/OR twelve hours post-drug administration. Using multivariable regression models, we then assessed the influence of WA% on lung function. RESULTS: WA% (p < 0.001) and T/OR (p < 0.001) significantly increased in asthma than in healthy control subjects. Compared to mild asthma, airway walls were further thickened (WA%, p = 0.023; T/OR: p = 0.029) and associated with lumen narrowing (Pi10, p = 0.055) in moderate to severe asthma. WA% and T/OR correlated well with lung function (FEV1, FVC, MMEF, and PEF) and airway resistance (R5, R20, Rp, and Fres). Regression analysis showed that MEF25 decreased with increasing age and WA% (R2 = 0.58, p < 0.001). Patients with thickened airway walls experienced a maximal increase in FVC, FEV1, and PEF at 2 h (p < 0.001) and a maximal decrease of R5, Z5, and Rp at 2 h (p < 0.001) in those with a thickened airway pattern. CONCLUSIONS: Asthma patients with different bronchial wall thicknesses exhibited variable lung function changes. Specifically, patients with thick airway wall patterns were more sensitive to inhaled budesonide in the short term.

17.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649504

RESUMO

BACKGROUND: Several biomarkers could be intercalated with traditional measures to improve ARDS diagnostics. METHODS: There were 211 ICU patients enrolled in this retrospective, nested case-control study. Participants were divided into an ARDS (n = 79) and non-ARDS (n = 132) groups, according to the Berlin criteria. Patient characteristics, vital signs, and laboratory tests were collected within three hours of admission. CC16, Ang-2, sRAGE, HMGB1, and SPD were measured within three hours and again at 24 hours, after admission to ICU. Receiver Operating Characteristic curves and multivariate logistic regression analyses were applied for predictive purposes. RESULTS: C-reactive protein (CRP), NT-proBNP, and pH values were intercalated with five established ARDS indicators, and the PaO2/FiO2 ratio. Only four potential indicators were analyzed, with CRP having high diagnostic value. Areas under curve (AUC) were as follows: CC16 (AUC: 0.752; 95% CI 0.680 - 0.824), Ang-2 (AUC: 0.695; 95% CI 0.620 - 0.770), HMGB1 (AUC: 0.668; 95% CI 0.592 - 0.744), sRAGE (AUC: 0.665; 95% CI 0.588 - 0.743), CRP (AUC: 0.701; 95% CI 0.627 - 0.776). No single indicator improved upon the PaO2/FiO2 ratio which had an AUC: 0.844 (95% CI 0.789 - 0.898). However, when the binary logistic model was transformed and the model was constructed, the AUC increased from 0.647 (95% CI 0.568 - 0.726) to 0.911 (95% CI 0.864 - 0.946). Among the combinations tested, PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1 resulted in the highest AUC of 0.910 (95% CI 0.863 - 0.945), although there are other factors which must be considered. CONCLUSIONS: A combination of biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we tentatively recommend PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1. This is because of the cost implications in contrast with benefit involved in utilizing the more elaborate model. Further health economics research is required to consider the opportunity cost for emergency care policy.


Assuntos
Proteína HMGB1 , Síndrome do Desconforto Respiratório , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Síndrome do Desconforto Respiratório/diagnóstico , Biomarcadores , Prognóstico , Proteína C-Reativa , Curva ROC
18.
Artigo em Inglês | MEDLINE | ID: mdl-36627498

RESUMO

PURPOSE: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. METHODS: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. RESULTS: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. CONCLUSIONS: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains.

19.
Hepatol Int ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645648

RESUMO

BACKGROUND AND PURPOSE: The clinical role of postoperative adjuvant therapy in hepatocellular carcinoma (HCC) is still unclear. The purpose of our study was to explore the clinical value of postoperative adjuvant anti-programed cell death 1 antibody (PA-PD-1) on the prognosis of HCC patients with high relapse risks after surgery. PATIENTS AND METHODS: Data of consecutive HCC patients with high recurrence risks treated with liver resection at our center during January 2019 and March 2021 were prospectively collected. Baseline differences were balanced between HCC patients with (PA-PD-1 group) or without PA-PD-1 (non-PD-1 group) after hepatectomy by propensity-score matching (PSM). Between these two groups, we compared overall survival (OS) and recurrence-free survival (RFS). Independent prognostic risk factors for OS and RFS were confirmed by Cox regression analysis, and subgroup analysis was also performed. RESULTS: 47 pairs of patients with or without PD-1 treatment after hepatectomy were matched. After PSM, the 1-year and 2-year RFS was 58.4% and 44.1% in the PA-PD-1 group, and 34.0% and 21.3% in the non-PD-1 group (p = 0.008). The OS at 1 year and 2 years was 91.2% and 91.2% in the PA-PD-1 group, compared with 85.1% and 61.7% in the non-PD-1 group (p = 0.024). Multivariable analyses demonstrated that PA-PD-1 was an independent protective predictor associated with RFS and OS. Through subgroup analysis, we concluded that HCC patients with portal venous tumor thrombus (PVTT) or tumor size ≥ 5 cm significantly benefited from PA-PD-1 therapy in RFS and OS. CONCLUSIONS: Adjuvant anti-PD-1 antibody can effectively improve the survival outcomes of HCC patients with high relapse risks after hepatectomy in this prospective observational study. This finding should be confirmed by results of the ongoing phase 3 randomized controlled trials.

20.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614259

RESUMO

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.


Assuntos
Materiais Biocompatíveis , Traumatismos da Medula Espinal , Humanos , Materiais Biocompatíveis/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal , Medicina Regenerativa , Transplante de Células-Tronco , Regeneração Nervosa
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