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1.
BMC Genomics ; 25(1): 460, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38730330

RESUMO

BACKGROUND: Zingiber officinale Roscoe, colloquially known as ginger, is a crop of significant medicinal and culinary value that frequently encounters adversity stemming from inhospitable environmental conditions. The MYB transcription factors have garnered recognition for their pivotal role in orchestrating a multitude of plant biological pathways. Nevertheless, the enumeration and characterization of the MYBs within Z. officinale Roscoe remains unknown. This study embarks on a genome-wide scrutiny of the MYB gene lineage in ginger, with the aim of cataloging all ZoMYB genes implicated in the biosynthesis of gingerols and curcuminoids, and elucidating their potential regulatory mechanisms in counteracting abiotic stress, thereby influencing ginger growth and development. RESULTS: In this study, we identified an MYB gene family comprising 231 members in ginger genome. This ensemble comprises 74 singular-repeat MYBs (1R-MYB), 156 double-repeat MYBs (R2R3-MYB), and a solitary triple-repeat MYB (R1R2R3-MYB). Moreover, a comprehensive analysis encompassing the sequence features, conserved protein motifs, phylogenetic relationships, chromosome location, and gene duplication events of the ZoMYBs was conducted. We classified ZoMYBs into 37 groups, congruent with the number of conserved domains and gene structure analysis. Additionally, the expression profiles of ZoMYBs during development and under various stresses, including ABA, cold, drought, heat, and salt, were investigated in ginger utilizing both RNA-seq data and qRT-PCR analysis. CONCLUSION: This work provides a comprehensive understanding of the MYB family in ginger and lays the foundation for the future investigation of the potential functions of ZoMYB genes in ginger growth, development and abiotic stress tolerance of ginger.


Assuntos
Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Fatores de Transcrição , Zingiber officinale , Zingiber officinale/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
2.
Artigo em Inglês | MEDLINE | ID: mdl-38619963

RESUMO

Nonconvex optimization issues are prevalent in machine learning and data science. While gradient-based optimization algorithms can rapidly converge and are dimension-independent, they may, unfortunately, fall into local optimal solutions or saddle points. In contrast, evolutionary algorithms (EAs) gradually adapt the population of solutions to explore global optimal solutions. However, this approach requires substantial computational resources to perform numerous fitness function evaluations, which poses challenges for high-dimensional optimization in particular. This study introduces a novel nonconvex optimization algorithm, the niching-based gradient-directed evolution (NGDE) algorithm, designed specifically for high-dimensional nonconvex optimization. The NGDE algorithm generates potential solutions and divides them into multiple niches to explore distinct areas within the feasible region. Subsequently, each individual creates candidate offspring using the gradient-directed mutation operator we designed. The convergence properties of the NGDE algorithm are investigated in two scenarios: accessing the full gradient and approximating the gradient with mini-batch samples. The experimental studies demonstrate the superior performance of the NGDE algorithm in minimizing multimodal optimization functions. Additionally, when applied to train the neural networks of LeNet-5, NGDE shows significantly improved classification accuracy, especially in smaller training sizes.

3.
Nat Commun ; 15(1): 454, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212623

RESUMO

Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.


Assuntos
Ferroptose , Neoplasias , Humanos , Endocitose , Hemina , Hidrólise , Peptídeos/farmacologia , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Microambiente Tumoral
4.
Diabetol Metab Syndr ; 16(1): 5, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172976

RESUMO

Atherosclerotic cardiovascular disease (ASCVD) consistently ranks as the primary mortality factor among diabetic people. A thorough comprehension of the pathophysiological routes and processes activated by atherosclerosis (AS) caused by diabetes mellitus (DM), together with the recognition of new contributing factors, could lead to the discovery of crucial biomarkers and the development of innovative drugs against atherosclerosis. Selenoprotein S (SELENOS) has been implicated in the pathology and progression of numerous conditions, including diabetes, dyslipidemia, obesity, and insulin resistance (IR)-all recognized contributors to endothelial dysfunction (ED), a precursor event to diabetes-induced AS. Hepatic-specific deletion of SELENOS accelerated the onset and progression of obesity, impaired glucose tolerance and insulin sensitivity, and increased hepatic triglycerides (TG) and diacylglycerol (DAG) accumulation; SELENOS expression in subcutaneous and omental adipose tissue was elevated in obese human subjects, and act as a positive regulator for adipogenesis in 3T3-L1 preadipocytes; knockdown of SELENOS in Min6 ß-cells induced ß-cell apoptosis and reduced cell proliferation. SELENOS also participates in the early stages of AS, notably by enhancing endothelial function, curbing the expression of adhesion molecules, and lessening leukocyte recruitment-actions that collectively reduce the formation of foam cells. Furthermore, SELENOS forestalls the apoptosis of vascular smooth muscle cells (VSMCs) and macrophages, mitigates vascular calcification, and alleviates inflammation in macrophages and CD4+ T cells. These actions help stifle the creation of unstable plaque characterized by thinner fibrous caps, larger necrotic cores, heightened inflammation, and more extensive vascular calcification-features seen in advanced atherosclerotic lesion development. Additionally, serum SELENOS could function as a potential biomarker, and SELENOS single nucleotide polymorphisms (SNPs) rs4965814, rs28628459, and rs9806366, might be effective gene markers for atherosclerosis-related diseases in diabetes. This review accentuates the pathophysiological processes of atherosclerosis in diabetes and amasses current evidence on SELENOS's potential therapeutic benefits or as predictive biomarkers in the various stages of diabetes-induced atherosclerosis.

5.
J Cell Mol Med ; 28(1): e18030, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37929884

RESUMO

Acetylshikonin (AS) is an active component of Lithospermum erythrorhizon Sieb. et Zucc that exhibits activity against various cancers; however, the underlying mechanisms of AS against oesophageal squamous carcinoma (ESCC) need to be elusive. The research explores the anti-cancer role and potential mechanism of AS on ESCC in vitro and in vivo, providing evidences for AS treatment against ESCC. In this study, we firstly demonstrated that AS treatment effectively inhibits cell viability and proliferation of ESCC cells. In addition, AS significantly induces G1/S phage arrest and promotes apoptosis in ESCC cell lines. Further studies reveal that AS induces ER stress, as observed by dose- and time-dependently increased expression of BIP, PDI, PERK, phosphorylation of eIF2α , CHOP and splicing of XBP1. CHOP knockdown or PERK inhibition markedly rescue cell apoptosis induced by AS. Moreover, AS treatment significantly inhibits ESCC xenograft growth in nude mice. Elevated expression of BIP and CHOP is also observed in xenograft tumours. Taken together, AS inhibits proliferation and induces apoptosis through ER stress-activated PERK/eIF2α /CHOP pathway in ESCC, which indicates AS represents a promising candidate for ESCC treatment.


Assuntos
Antraquinonas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Camundongos , Animais , Humanos , eIF-2 Quinase/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Camundongos Nus , Estresse do Retículo Endoplasmático , Apoptose , Fator de Transcrição CHOP/metabolismo
6.
Arch Microbiol ; 206(1): 45, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153526

RESUMO

An aerobic, haemolytic, Gram-negative and rod-shaped bacterial strain ZY171148T was isolated from the lung of a dead goat with respiratory disease in Southwest China. The strain grew at 24-39 °C, at pH 6.0-9.0 and in the presence of 0.5-2.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belongs to the genus Moraxella. The nucleotide sequence similarity analysis of the 16S rRNA gene showed that the strain has the highest similarity of 98.1% to Moraxella (M.) caprae ATCC 700019 T. Phylogenomic analysis of 800 single-copy protein sequences indicated that the strain is a member of the genus Moraxella and forms a separated branch on the Moraxella phylogenetic tree. The strain exhibited the highest orthologous average nucleotide identity (OrthoANI) and average amino acid identity (AAI) values of 77.0 and 77.9% to M. nasibovis CCUG 75921T and M. ovis CCUG 354T, respectively. The strain shared the highest digital DNA-DNA hybridization (dDDH) value of 26.2% to M. osloensis CCUG 350T. The genome G + C content of strain ZY171148T was 42.6 mol%. The strain had C18:1 ω9c (41.7%), C18:0 (11.2%), C16:0 (14.1%) and C12:0 3OH (9.7%) as the predominant fatty acids and CoQ-8 as the major respiratory quinone. The strain contained phosphatidylglycerol, phosphatidylethanolamine, cardiolipin, dilysocardiolipin, monolysocardiolipin and phosphatidic acid as the major polar lipids. ß-haemolysis was observed on Columbia blood agar. All results confirmed that strain ZY171148T represents a novel species of the genus Moraxella, for which the name Moraxella haemolytica sp. nov. is proposed, with strain ZY171148T = CCTCC AB 2021471T = CCUG 75920T as the type strain.


Assuntos
Cabras , Doenças Respiratórias , Animais , Ovinos , Filogenia , RNA Ribossômico 16S/genética , Moraxella/genética , DNA
7.
Front Immunol ; 14: 1230766, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035096

RESUMO

Objective: Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil-to-lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS). Methods: Utilizing a nationally representative, multistage cross-sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all-cause mortality, with Kaplan-Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte-based inflammatory markers and mortality. The analysis was conducted in 2023. Results: Our analysis included 1,715 COPD participants, representing 6,976,232 non-institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40-85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow-up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non-ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all-cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04-1.16, p < 0.001], 0.83 (95% CI, 0.71-0.98; p = 0.03), and 1.10 (95% CI, 1.05-1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/µL), neutrophil count (≥3,800 cells/µL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/µL). Conclusion: Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all-cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management.


Assuntos
Eosinófilos , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Adulto , Idoso , Neutrófilos , Inquéritos Nutricionais , Estudos Transversais , Administração por Inalação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Corticosteroides , Linfócitos , Biomarcadores
8.
Am J Nucl Med Mol Imaging ; 13(5): 230-244, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023818

RESUMO

The earlier identification of EGFR mutation status in lung adenocarcinoma patients is crucial for treatment decision-making. Radiomics, which involves high-throughput extraction of imaging features from medical images for quantitative analysis, can quantify tumor heterogeneity and assess tumor biology non-invasively. This field has gained attention from researchers in recent years. The aim of this study is to establish a model based on 18F-FDG PET/CT radiomic features to predict the epidermal growth factor receptor (EGFR) mutation status of lung adenocarcinoma and evaluate its performance. 155 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT scans and EGFR gene detection before treatment were retrospectively analyzed. The LIFEx packages was used to perform 3D volume of interest (VOI) segmentation manually on DICOM images and extract 128 radiomic features. The Wilcoxon rank sum test and least absolute shrinkage and selection operator (LASSO) regression algorithm were applied to filter the radiomic features and establish models. The performance of the models was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Among the models we have built, the radiomic model based on 18F-FDG PET/CT has the best prediction performance for EGFR gene mutation status, with an AUC of 0.90 (95% CI 0.84~0.96) in the training set and 0.79 (95% CI 0.64~0.94) in the test set. In conclusion, we have established a radiomics model based on 18F-FDG PET/CT, which has good predictive performance in identifying EGFR gene mutation status in lung adenocarcinoma patients.

9.
MedComm (2020) ; 4(6): e403, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37881785

RESUMO

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα-positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα-positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression-induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse-free survival and overall survival in ERα-positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial-mesenchymal transition in BC.

10.
Biomed Pharmacother ; 167: 115440, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37683595

RESUMO

The discovery of new therapeutic strategies for diseases is essential for drug research. Deoxyhypusine synthase (DHPS) is a critical enzyme that modifies the conversion of the eukaryotic translation initiation factor 5A (eIF5A) precursor into physiologically active eIF5A (eIF5A-Hyp). Recent studies have revealed that the hypusine modifying of DHPS on eIF5A has an essential regulatory role in human diseases. The hypusination-induced DHPS/eIF5A pathway has been shown to play an essential role in various cancers, and it could regulate immune-related diseases, glucose metabolism-related diseases, neurological-related diseases, and aging. In addition, DHPS has a more defined substrate and a well-defined structure within the active pocket than eIF5A. More and more researchers are focusing on the prospect of advanced development of DHPS inhibitors. This review summarizes the regulatory mechanisms of the hypusination-induced DHPS/eIF5A pathway in a variety of diseases in addition to the inhibitors related to this pathway; it highlights and analyzes the structural features and mechanisms of action of DHPS inhibitors and expands the prospects of future drug development using DHPS as an anticancer target.

11.
Viruses ; 15(8)2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37632087

RESUMO

Enterovirus G (EV-G) is prevalent in pig populations worldwide, and a total of 20 genotypes (G1 to G20) have been confirmed. Recently, recombinant EV-Gs carrying the papain-like cysteine protease (PLCP) gene of porcine torovirus have been isolated or detected, while their pathogenicity is poorly understood. In this study, an EV-G17-PLCP strain, 'EV-G/YN23/2022', was isolated from the feces of pigs with diarrhea, and the virus replicated robustly in numerous cell lines. The isolate showed the highest complete genome nucleotide (87.5%) and polyprotein amino acid (96.6%) identity in relation to the G17 strain 'IShi-Ya4' (LC549655), and a possible recombination event was detected at the 708 and 3383 positions in the EV-G/YN23/2022 genome. EV-G/YN23/2022 was nonlethal to piglets, but mild diarrhea, transient fever, typical skin lesions, and weight gain deceleration were observed. The virus replicated efficiently in multiple organs, and the pathological lesions were mainly located in the small intestine. All the challenged piglets showed seroconversion for EV-G/YN23/2022 at 6 to 9 days post-inoculation (dpi), and the neutralization antibody peaked at 15 dpi. The mRNA expression levels of IL-6, IL-18, IFN-α, IFN-ß, and ISG-15 in the peripheral blood mononuclear cells (PBMCs) were significantly up-regulated during viral infection. This is the first documentation of the isolation and pathogenicity evaluation of the EV-G17-PLCP strain in China. The results may advance our understanding of the evolution characteristics and pathogenesis of EV-G-PLCP.


Assuntos
Enterovirus Suínos , Torovirus , Animais , Suínos , Papaína/genética , Leucócitos Mononucleares , Virulência , China , Calpaína , Diarreia
13.
Front Cell Infect Microbiol ; 13: 1140548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424777

RESUMO

Background: The impact of COVID-19 on the world is still ongoing, and it is currently under regular management. Although most infected people have flu-like symptoms and can cure themselves, coexisting pathogens in COVID-19 patients should not be taken lightly. The present study sought to investigate the coexisting pathogens in SARS-CoV-2 infected patients and identify the variety and abundance of dangerous microbes to guide treatment strategies with a better understanding of the untested factors. Methods: We extracted total DNA and RNA in COVID-19 patient specimens from nasopharyngeal swabs to construct a metagenomic library and utilize Next Generation Sequencing (NGS) to discover chief bacteria, fungi, and viruses in the body of patients. High-throughput sequencing data from Illumina Hiseq 4000 were analyzed using Krona taxonomic methodology for species diversity. Results: We studied 56 samples to detect SARS-CoV-2 and other pathogens and analyzed the species diversity and community composition of these samples after sequencing. Our results showed some threatening pathogens such as Mycoplasma pneumoniae, Klebsiella pneumoniae, Streptococcus pneumoniae, and some previously reported pathogens. SARS-CoV-2 combined with bacterial infection is more common. The results of heat map analysis showed that the abundance of bacteria was mostly more than 1000 and that of viruses was generally less than 500. The pathogens most likely to cause SARS-CoV-2 coinfection or superinfection include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Klebsiella pneumoniae, and Human gammaherpesvirus 4. Conclusions: The current coinfection and superinfection status is not optimistic. Bacteria are the major threat group that increases the risk of complications and death in COVID-19 patients and attention should be paid to the use and control of antibiotics. Our study investigated the main types of respiratory pathogens prone to coexisting or superinfection in COVID-19 patients, which is valuable for identifying and treating SARS-CoV-2.


Assuntos
COVID-19 , Coinfecção , Superinfecção , Vírus , Humanos , SARS-CoV-2/genética , Coinfecção/microbiologia , Vírus/genética , Bactérias/genética , Streptococcus pneumoniae , Klebsiella pneumoniae , Nasofaringe/microbiologia
15.
Biomed Eng Online ; 22(1): 54, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37237394

RESUMO

OBJECTIVES: Use of an AI system based on deep learning to investigate whether the system can aid in distinguishing malignant from benign calcifications on spot magnification mammograms, thus potentially reducing unnecessary biopsies. METHODS: In this retrospective study, we included public and in-house datasets with annotations for the calcifications on both craniocaudal and mediolateral oblique vies, or both craniocaudal and mediolateral views of each case of mammograms. All the lesions had pathological results for correlation. Our system comprised an algorithm based on You Only Look Once (YOLO) named adaptive multiscale decision fusion module. The algorithm was pre-trained on a public dataset, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), then re-trained and tested on the in-house dataset of spot magnification mammograms. The performance of the system was investigated by receiver operating characteristic (ROC) analysis. RESULTS: We included 1872 images from 753 calcification cases (414 benign and 339 malignant) from CBIS-DDSM. From the in-house dataset, 636 cases (432 benign and 204 malignant) with 1269 spot magnification mammograms were included, with all lesions being recommended for biopsy by radiologists. The area under the ROC curve for our system on the in-house testing dataset was 0.888 (95% CI 0.868-0.908), with a sensitivity of 88.4% (95% CI 86.9-8.99%), specificity of 80.8% (95% CI 77.6-84%), and an accuracy of 84.6% (95% CI 81.8-87.4%) at the optimal cutoff value. Using the system with two views of spot magnification mammograms, 80.8% benign biopsies could be avoided. CONCLUSION: The AI system showed good accuracy for classification of calcifications on spot magnification mammograms which were all categorized as suspicious by radiologists, thereby potentially reducing unnecessary biopsies.


Assuntos
Neoplasias da Mama , Calcinose , Humanos , Feminino , Mamografia/métodos , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Calcinose/diagnóstico por imagem , Inteligência Artificial
16.
Curr Mol Med ; 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37076961

RESUMO

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammatory fibrosis usually involving the whole biliary tree. However, there are very limited treatment options to treat this disease. Our previous study found a lipid-protein rCsHscB from a liver fluke - Clonorchis sinensis, which had full capacities of immune regulation. Therefore, we investigated the role of rCsHscB in a mouse model of sclerosing cholangitis induced by xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to explore whether this protein had potential therapeutic value for PSC. METHODS: Mice were fed 0.1% DDC for 4 weeks and treated with CsHscB (30 µg/mouse, intraperitoneal injection, once every 3 days); the control group was given an equal amount of PBS or CsHscB under normal diet conditions. All the mice were sacrificed at 4 weeks for the evaluation of biliary proliferation, fibrosis, and inflammation. RESULTS: rCsHscB treatment attenuated DDC-induced liver congestion and enlargement and significantly decreased the upregulation of serum AST and ALT levels. The administration of rCsHscB to DDC-fed mice significantly decreased cholangiocyte proliferation and pro-inflammatory cytokine production compared to mice fed with DDC alone. Also, rCsHscB treatment showed a decreased expression of α-SMA in the liver and other markers of liver fibrosis (Masson staining, Hydroxyproline content, and collagen deposit). More interestingly, DDC-fed mice treated with rCsHscB showed a significant up-regulation of PPAR-γ expression, which was similar to control mice, indicating the involvement of PPAR-γ signaling in the protective action of rCsHscB. CONCLUSION: Overall, our data show that rCsHscB attenuates the progression of cholestatic fibrosis induced by DDC and supports the potential for manipulating the parasite-derived molecule to treat certain immune-mediated disorders.

17.
Huan Jing Ke Xue ; 44(4): 1873-1881, 2023 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-37040938

RESUMO

The dry deposition of heavy metals in atmospheric particulates is one of the important sources of heavy metals in agricultural areas, but there are few observational studies on the atmospheric deposition of heavy metals in agricultural areas. In this study, the concentrations of atmospheric particulates with different particle sizes and ten kinds of metal elements in them were analyzed by sampling a typical rice-wheat rotation area in the suburb of Nanjing for one year, and the dry deposition fluxes were estimated using the big leaf model, so as to understand the input characteristics of particulates and heavy metals. The results showed that the particulate concentrations and dry deposition fluxes were high in winter and spring but low in summer and autumn. In winter and spring, coarse particulates (2.1-9.0 µm) and fine particulates (<2.1 µm) had dual effects on particulate pollution, whereas in summer and autumn, particulate pollution was mainly attributed to the fine particulates. The concentrations of metal elements were the lowest in giant particulates (>9.0 µm) and were similar in coarse particulates and fine particulates, whereas Pb, Mn, As, and Cd elements were relatively high in fine particulates. The average annual dry deposition fluxes[g·(m2·a)-1] of particulates was giant particulates (8.31)>coarse particulates (5.99)>fine particulates (0.629). The order of average annual dry deposition fluxes[mg·(m2·a)-1] of the 10 metals was Ca(2096.4)>Al(1710.4)>Zn(855.0)>Fe(256.1)>Pb(40.35)>Cu(31.93)>V(26.21)>Mn(9.10)>As(2.48)>Cd(0.28). The average annual dry deposition fluxes of the 10 metal elements in fine particulates, coarse particulates, and giant particulates were 179.03, 2124.97, and 2724.18 mg·(m2·a)-1, respectively. These results will provide a reference for a more comprehensive understanding of the impact of human activities on the quality and safety of agricultural products and soil ecological environment.

18.
Pak J Pharm Sci ; 36(1): 205-210, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36967513

RESUMO

This work aimed to clarify the potential regulating effects of Qufeng Xuanfei formula (QFXF) on airway neurogenic inflammation and its underlying target signal pathway. Guinea pig model of airway hyperergy (AHR) was used. The relative susceptibility of major proteins to airway neurogenic inflammation was assessed using Western blot immunoassay followed by being separated by SDS-PAGE. Compared to the model group, QFXF of all concentrations effectively depressed the capsaicin enhanced cough in guinea pigs and the peak values of airway resistance significantly decreased. The results illustrated that QFXF alleviated cough symptom in guinea pigs and reduced airway neurogenic inflammation when compared to AHR model group. Airway inflammation and damage, as well as the levels of NGF, SP and c-Fos in QFXF decreased the most in the high-dose group. The mechanism of antitussive activity may be associated with reducing airway inflammation. QFXF displayed effect on chronic cough through reducing the levels of neuropeptides, attenuating airway inflammation and promoting recovery from disease to decrease the airway neuro sensitivity, suggesting that the potential mechanism may be related to Ras/ERK/c-Fos pathway.


Assuntos
Tosse , Inflamação Neurogênica , Cobaias , Animais , Tosse/tratamento farmacológico , Inflamação Neurogênica/metabolismo , Pulmão , Inflamação/metabolismo
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 281-286, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36949686

RESUMO

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.


Assuntos
Esquizofrenia , Humanos , Encéfalo , Mapeamento Encefálico , Lobo Temporal , Imageamento por Ressonância Magnética
20.
BMC Cardiovasc Disord ; 23(1): 72, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750929

RESUMO

BACKGROUND: Postoperative delirium (POD) complicates the postoperative course. There is limited information on POD-related risk factors (RFs) and prognosis in patients with acute type A aortic dissection (ATAAD) after modified triple-branched stent graft implantation (MTBSG) surgery. METHODS: We retrospectively examined consecutive ATAAD patients who received MTBSG surgery in our hospital between January 2013 and December 2019. We employed univariate and multivariate analyses to identify stand-alone RFs for POD. A nomogram was next generated to estimate POD occurrence. The primary outcome was the development of POD, and the secondary outcomes were intensive care unit (ICU) and hospital stays, hospitalization costs, and in-hospital and follow-up mortality. RESULTS: We selected 692 patients, of whom 220 experienced POD (31.8%). Based on our analysis, the following factors enhanced the likelihood of POD development: alcohol consumption (p < 0.001), acute physiology and chronic health evaluation II score (p = 0.023), serum total bilirubin (p = 0.007), stage 3 acute kidney injury (p < 0.001), serum interleukin-6 (p = 0.031), post-operative analgesics usage (p = 0.015), and ventilation duration (p = 0.008). POD patients had significantly longer ventilator times (p = 0.003), ICU stays (p < 0.001), and hospital stays (p = 0.038), together with increased hospitalization costs (p < 0.001) and in-hospital mortality (p = 0.019). However, POD was not a RF for mortality during follow-up (log-rank p = 0.611). CONCLUSIONS: We demonstrated a strong link between POD and poor prognosis in ATAAD patients. We also constructed a prognosis estimator model which will benefit early management guidance to minimize the incidence of POD.


Assuntos
Dissecção Aórtica , Delírio , Delírio do Despertar , Humanos , Delírio do Despertar/complicações , Nomogramas , Estudos Retrospectivos , Delírio/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
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