Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 13.444
Filtrar
1.
J Cancer Res Clin Oncol ; 150(3): 109, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427078

RESUMO

BACKGROUND: Neuroblastoma (NB), a prevalent pediatric solid tumor, presents formidable challenges due to its high malignancy and intricate pathogenesis. The role of disulfidptosis, a novel form of programmed cell death, remains poorly understood in the context of NB. METHODS: Gaussian mixture model (GMM)-identified disulfidptosis-related molecular subtypes in NB, differential gene analysis, survival analysis, and gene set variation analysis were conducted subsequently. Weighted gene co-expression network analysis (WGCNA) selected modular genes most relevant to the disulfidptosis core pathways. Integration of machine learning approaches revealed the combination of the Least absolute shrinkage and selection operator (LASSO) and Random Survival Forest (RSF) provided optimal dimensionality reduction of the modular genes. The resulting model was validated, and a nomogram assessed disulfidptosis characteristics in NB. Core genes were filtered and subjected to tumor phenotype and disulfidptosis-related experiments. RESULTS: GMM clustering revealed three distinct subtypes with diverse prognoses, showing significant variations in glucose metabolism, cytoskeletal structure, and tumor-related pathways. WGCNA highlighted the red module of genes highly correlated with disulfide isomerase activity, cytoskeleton formation, and glucose metabolism. The LASSO and RSF combination yielded the most accurate and stable prognostic model, with a significantly worse prognosis for high-scoring patients. Cytological experiments targeting core genes (CYFIP1, EMILIN1) revealed decreased cell proliferation, migration, invasion abilities, and evident cytoskeletal deformation upon core gene knockdown. CONCLUSIONS: This study showcases the utility of disulfidptosis-related gene scores for predicting prognosis and molecular subtypes of NB. The identified core genes, CYFIP1 and EMILIN1, hold promise as potential therapeutic targets and diagnostic markers for NB.


Assuntos
Neuroblastoma , Criança , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Apoptose , Proliferação de Células/genética , Glucose , Aprendizado de Máquina , Neuroblastoma/genética , Prognóstico
2.
Heliyon ; 10(5): e26873, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434384

RESUMO

Objective: In recent decades, there has been a notable increase in the morbidity and mortality rates linked to bacteremia and candidemia. This study aimed to investigate the clinical significance of inflammatory markers in assessing the disease severity in critically ill patients suffering from mixed-bloodstream infections (BSIs) due to Enterococcus spp. and Candida spp. Methods: In this retrospective research, patients diagnosed with BSIs who were admitted to the intensive care unit (ICU) during the period of January 2019 to December 2022 were analyzed. The patients were divided into two groups: a mixed-pathogen BSI group with both Enterococcus spp. and Candida spp., and a single-pathogen BSI group with only Enterococcus spp. The study examined the differences in inflammatory marker levels and disease severity, including Acute Physiology and Chronic Health Evaluation (APACHE) II scores, duration of ICU stay, and 30-day mortality, between the two groups. Furthermore, we sought to scrutinize the potential associations among these aforementioned parameters. Results: The neutrophil-to-lymphocyte ratios (NLRs) and levels of plasma C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) in the mixed-pathogen BSI group were higher than those in the single-pathogen BSI group. Spearman's rank correlation analysis showed that NLRs and plasma CRP and IL-6 levels were positively correlated with disease severity in the mixed-pathogen BSI group. Further, the levels of plasma IL-8 and TNF-α were also positively correlated with ICU stay duration and 30-day mortality. In multivariate analysis, plasma CRP and IL-6 levels were independently associated with 30-day mortality. Conclusion: Mixed-pathogen BSIs caused by Enterococcus spp. and Candida spp. may give rise to increased NLRs and plasma CRP, IL-6, IL-8, and TNF-α levels in comparison to BSI caused by Enterococcus spp. only, thus leading to elevated disease severity in critically ill patients.

3.
J Opt Soc Am A Opt Image Sci Vis ; 41(2): 311-322, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437344

RESUMO

In order to solve the problems of color shift and incomplete dehazing after image dehazing, this paper proposes an improved image self-supervised learning dehazing algorithm that combines polarization characteristics and deep learning. First, based on the YOLY network framework, a multiscale module and an attention mechanism module are introduced into the transmission feature estimation network. This enables the extraction of feature information at different scales and allocation of weights, and effectively improves the accuracy of transmission map estimation. Second, a brightness consistency loss based on the YCbCr color space and a color consistency loss are proposed to constrain the brightness and color consistency of the dehazing results, resolving the problems of darkened brightness and color shifts in dehazed images. Finally, the network is trained to dehaze polarized images based on the atmospheric scattering model and loss function constraints. Experiments are conducted on synthetic and real-world data, and comparisons are made with six contrasting dehazing algorithms. The results demonstrate that, compared to the contrastive dehazing algorithms, the proposed algorithm achieves PSNR and SSIM values of 23.92 and 0.94, respectively, on synthetic image samples. For real-world image samples, color restoration is more authentic, contrast is higher, and detailed information is richer. Both subjective and objective evaluations show significant improvements. This validates the effectiveness and superiority of the proposed dehazing algorithm.

4.
J Chromatogr A ; 1720: 464773, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38432106

RESUMO

Although the co-occurrences of isomeric chalcones and dihydroflavones widely appear in medicinal plants, the differentiation of such isomerism seldom succeeds using MS/MS, attributing to totally identical MS/MS spectra. Here, efforts were paid to pursue an eligible tool allowing to address the technical challenge. Being inspired by that one more proton signal is observed in 1H NMR spectrum of isoliquiritigenin than liquiritigenin when employing DMSO­d6 as solvent, hydrogen-deuterium exchange (HDX)-MS/MS was evaluated towards differentiating isomeric chalcones and dihydroflavones through replacing H2O with D2O to prepare the mobile phase. As a result, differences were observed for either MS1 or MS2 spectrum when comparing two pairs of isomers, such as liquiritigenin vs. isoliquiritigenin and liquiritin vs. isoliquiritin, because the isomeric precursor and fragment ion species owned different amounts of hydroxyl protons and those reactive protons could be partially or completely substituted by deuterium protons at the exposure in D2O to result in n × 1.006 mass increments. Moreover, utmost four hydrogen/deuterium exchanges occurred for a single glucosyl moiety. Thereafter, HDX-MS/MS was applied to characterize the flavonoids of Snow chrysanthemum, a precious edible herbal medicine that is rich in isomeric chalcones and dihydroflavones. Through paying special attention to the deuterium labeling styles of (de)protonated molecules as well as those featured fragment ions, five pairs of isomeric chalcones and dihydroflavones were confirmatively differentiated, in addition to that 28 flavonoids were structurally annotated by applying those well-defined mass fragmentation rules. Hence, this study offered an in-depth insight towards the flavonoids-focused characterization of Snow chrysanthemum, and more importantly, HDX-MS/MS is a superior tool to differentiate, but not limited to, isomeric chalcones and dihydroflavones.

5.
J Cell Mol Med ; 28(6): e18146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38426932

RESUMO

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1ß and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.


Assuntos
Acne Vulgar , Saponinas , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/efeitos adversos , Saponinas/farmacologia , Saponinas/uso terapêutico , Simulação de Acoplamento Molecular , Anti-Inflamatórios/uso terapêutico , NF-kappa B/metabolismo , Bactérias Gram-Negativas/metabolismo , Acne Vulgar/tratamento farmacológico , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Inflamação/metabolismo
6.
JCI Insight ; 9(5)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456502

RESUMO

Vascular calcification is a severe complication of cardiovascular diseases. Previous studies demonstrated that endothelial lineage cells transitioned into osteoblast-like cells and contributed to vascular calcification. Here, we found that inhibition of cyclin-dependent kinase (CDK) prevented endothelial lineage cells from transitioning to osteoblast-like cells and reduced vascular calcification. We identified a robust induction of CDK1 in endothelial cells (ECs) in calcified arteries and showed that EC-specific gene deletion of CDK1 decreased the calcification. We found that limiting CDK1 induced E-twenty-six specific sequence variant 2 (ETV2), which was responsible for blocking endothelial lineage cells from undergoing osteoblast differentiation. We also found that inhibition of CDK1 reduced vascular calcification in a diabetic mouse model. Together, the results highlight the importance of CDK1 suppression and suggest CDK1 inhibition as a potential option for treating vascular calcification.


Assuntos
Osteogênese , Calcificação Vascular , Animais , Camundongos , Calcificação Fisiológica , Diferenciação Celular , Células Endoteliais/fisiologia , Osteogênese/fisiologia , Calcificação Vascular/etiologia
7.
Front Endocrinol (Lausanne) ; 15: 1361416, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469141

RESUMO

Background: Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal. Methods: A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis. Results: Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, P = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (ß = -0.086, standard error (SE) 0.036, P = 0.017). Conclusions: Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.


Assuntos
Aneurisma da Aorta Torácica , alfa-2-Glicoproteína-HS , Humanos , alfa-2-Glicoproteína-HS/genética , Análise da Randomização Mendeliana , Aneurisma da Aorta Torácica/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único
8.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469785

RESUMO

BACKGROUND: The aim was to analyze the serological and molecular genetic characteristics of a rare B(A) subtype pedigree, explore its pathogenesis, and discuss transfusion strategies. METHODS: ABO blood typing serological tests were conducted on a female subject and her family member using standard serological methods. Sequencing analysis of the ABO gene exons 6 and 7 was performed using PCR technique for the female subject and her family member to examine the blood types of the participants. RESULTS: The serological test results showed a discrepancy between the forward and reverse typings of the female subject. The forward typing was similar to that of AB subtype serological forward typing, while the reverse typing indicated AB blood type. Based on the sequencing results, it is inferred that the female subject and her son have 8 mutations on one BA.02 chain: 297A>G, 526C>G, 657C>T, 700C>G, 703G>A, 796C>A, 803G>C, and 930G>A. Comparing these eight mutation sites with the Blood Group Antigen Gene Mutation Database (BGMUT), it was found that the female subject had a heterozygous mutation at c.700C>G in the 7th exon of the B.01 gene, consistent with the characteristics of the BA.02 allele. The genotype of the female subject was determined as A1.02/ BA.02, while the genotype of her son was determined as O.01.01/BA.02. CONCLUSIONS: The serological presentation of the B(A) subtype for the female subject reported in this study was unique. It differed from previously reported cases, indicating that the determination of B(A) subtypes cannot solely rely on serological testing. It requires a comprehensive analysis combining the results of genetic testing and pedigree investigation.


Assuntos
Sistema ABO de Grupos Sanguíneos , Transfusão de Sangue , Humanos , Feminino , Sistema ABO de Grupos Sanguíneos/genética , Genótipo , Heterozigoto , Mutação , Alelos , Fenótipo
9.
Dev Neurosci ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471480

RESUMO

BACKGROUND: Upstream stimulating factor 2 (USF2) belongs to basic-Helix-Loop-Helix-Leucine Zipper transcription factor family, regulating expression of genes involved in immune response or energy metabolism network. Role of USF2 in neuropathic pain was evaluated. METHODS: Mice were intraspinally injected with adenovirus for knockdown of USF2 (Ad-shUSF2), and then subjected to spinal nerve ligation (SNL) to induce neuropathic pain. Distribution and expression of USF2 was detected by western blot and immunofluorescence. Mechanical and thermal pain sensitivity were examined by paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL). Chromatin immunoprecipitation (ChIP) and luciferase activity assays were performed to detect binding ability between USF2 and SNHG5. RESULTS: The expression of USF2 was elevated and colocalized with astrocytes and microglia in L5 dorsal root ganglion (DRG) of SNL-induced mice. Injection of Ad-shUSF2 attenuated SNL-induced decrease of PWT and PWL in mice. Knockdown of USF2 increased level of IL-10, but decreased TNF-α, IL-1ß, and IL-6 in SNL-induced mice. Silence of USF2 enhanced protein expression of CD206, while reduced expression of CD16 and CD32 in SNL-induced mice. USF2 bind to promoter of SNHG5, and weakened SNL-induced up-regulation of SNHG5. SNHG5 bind to miR-181b-5p, and miR-181b-5p to interact with CXCL5. CONCLUSION: Silence of USF2 ameliorated neuropathic pain, suppressed activation of M1 microglia and inhibited inflammation in SNL-induced mice through regulation of SNHG5/miR-181b-5p/CXCL5 axis. Therefore, USF2/SNHG5/miR-181b-5p/CXCL5 might be a promising target for neuropathic pain. However, the effect of USF2/SNHG5/miR-181b-5p/CXCL5 on neuropathic pain should also be investigated in further research.

10.
Huan Jing Ke Xue ; 45(2): 709-720, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471911

RESUMO

ITA and Beast methods were used to quantitatively analyze the nonlinear process of a PM2.5 concentration time series based on the PM2.5 concentration data of the three major urban agglomerations in China. The results showed that: ① the degree of the PM2.5 pollution in the three major urban agglomerations had decreased, and the high-concentration areas had noticeably shrunk. The degree of spatial polarization of PM2.5 concentration was reduced, and the spatial difference was narrowed. The PM2.5 concentration in most areas showed downward trends, but the degree of change was not the same. Compared with the YRD and PRD, the concentration of PM2.5 in the BTH was still at a relatively high level. ② The concentration of PM2.5 in the three major urban agglomerations had seasonal variation characteristics that were high in winter and spring and low in summer and autumn. There were obvious differences in PM2.5 concentration between winter and summer, and the convergence of PM2.5 concentration in summer was greater than that in winter. Areas with high PM2.5 concentration also had obvious downward trends, but the downward trends of PM2.5 concentration in the PRD were not obvious compared with those in the YRD and BTH. ③ The PM2.5 concentration time series of the three major urban agglomerations all had significant downward trends: Beijing-Tianjin-Hebei (BTH) > the Yangtze River Delta (YRD) > the Pearl River Delta (PRD). The PM2.5 concentration had the largest downward trends in winter. The higher the PM2.5 pollution level, the greater the downward trends. ④ The trend component of the PM2.5 concentration time series in the BTH had two change points, and there was one change point in the seasonal component. The trend and seasonal components of the PM2.5 concentration time series in the YRD had no change point. There was no change point in the seasonal component but one change point in the trend component of the PM2.5 concentration time series in the PRD. These results can provide scientific references for regional air pollution control.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38477843

RESUMO

OBJECTIVE: The relationship between skeletal muscle and adipose tissue compositions and risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) treatment needs to be investigated. METHODS: A total of 282 patients were collected from two medical centres. The median time of follow-up was 48.23 + 1.36 months and the first-year results of all patients after TIPS therapy were collected. The muscle and adipose tissue indices were quantified at the third lumbar vertebra level. Sarcopenia and myosteatosis were defined according to previous researches. Receiver operating characteristic curves, chi-square test, univariate and multivariate logistic regression analyses were employed to investigate the potential association between muscle and adipose indices, sarcopenia, myosteatosis and the risk of developing post-TIPS OHE. RESULTS: All skeletal muscle indices, adipose tissue indices and sarcopenia had limited associations with post-TIPS OHE. Myosteatosis (148 cases, 52.5%, 55 with OHE, 37.2%) was identified as an independent risk factor for post-TIPS OHE. with P < 0.001 in Chi-square test, P < 0.001, odds ratio (OR): 2.854, 95% confidence interval (CI): 1.632-4.993 in univariate logistic regression analyses, and P = 0.007, OR: 2.372, 95% CI: 1.268-4.438 in multivariate logistic regression analyses, respectively. CONCLUSION: Our results showed that myosteatosis was proven as an independent risk factor for the development of post-TIPS OHE.

12.
J Inflamm Res ; 17: 1389-1396, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476469

RESUMO

Background: An unmet medical need for the treatment of inflammatory bowel disease (IBD) exists. A part of antidiabetic drugs had potential effects on IBD in various observational research. Objective: To investigate the potential of antidiabetic drugs on IBD. Methods: We undertook a summary-data-based Mendelian randomization (SMR) using the expression quantitative trait loci (eQTL) expressed in the blood or colon and a two sample Mendelian randomization (TSMR) utilizing single nucleotide polymorphism (SNP) of antidiabetic drug target genes mediated by blood glucose traits. Participants encompassed patients with IBD (25,042 cases/34,915 controls), UC (12,366 cases/33,609 controls), and CD (12,194 cases/28,072 controls). Data on eQTL in the blood or the colon were from the eQTLGen consortium (31,684 individuals) or GTEx Consortium V8, respectively. SMR was performed by SMR software (20,220,322); the primary method for TSMR was inverse-variance weighted (IVW) or Wald ratio through R studio (2023.06.0+421). Sensitivity analyses were carried out. Results: A 1-SD upper expression of the KCNJ11 gene (target gene of sulfonylureas) in the blood reduced the risk of CD (OR per 1-SD = 0.728, 95% CI = 0.586-0.903, P = 0.004) according to the result of SMR. ABCC8 (target gene of sulfonylureas) expressed in the colon did not affect CD, UC, or IBD. T2D-mediated KCNJ11 has a protective effect on CD (OR = 0.475, 95% CI = 0.297-0.761, P = 0.002). Gene predicted no relationship between T2D and CD. Conclusion: Sulfonylureas (SUs) may have side effects on CD. This work provides some suggestions for the selection of antidiabetic drugs in patients with CD.

13.
Ecotoxicol Environ Saf ; 274: 116210, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38479311

RESUMO

Thiosulfate influences the bioreduction and migration transformation of arsenic (As) and iron (Fe) in groundwater environments. The aim of this study was to investigate the impact of microbially-mediated sulfur cycling on the bioreduction and interaction of As and Fe. Microcosm experiments were conducted, including bioreduction of thiosulfate, As(V), and Fe(III) by Citrobacter sp. JH012-1, as well as the influence of thiosulfate input at different initial arsenate concentrations on the bioreduction of As(V) and Fe(III). The results demonstrate that Citrobacter sp. JH012-1 exhibited strong reduction capabilities for thiosulfate, As(V), and Fe(III). Improving thiosulfate level promoted the bioreduction of Fe(III) and As(V). When 0, 0.1, 0.5, and 1 mM thiosulfate were added, Fe(III) was completely reduced within 9 days, 3 days, 1 day, and 0.5 days, simultaneously, 72.8%, 82.2%, 85.5%, and 90.0% of As(V) were reduced, respectively. The products of As(III) binding with sulfide are controlled by the ratio of As-S. When the initial arsenate concentration was 0.025 mM, the addition of thiosulfate resulted in the accumulation of soluble thioarsenite. However, when the initial arsenate level increased to 1 mM, precipitates of orpiment or realgar were formed. In the presence of both arsenic and iron, As(V) significantly inhibits the bioreduction of Fe(III). Under the concentrations of 0, 0.025, and 1 mM As(V), the reduction rates of Fe(III) were 100%, 91%, and 83%, respectively. In this scenario, the sulfide produced by thiosulfate reduction tends to bind with Fe(II) rather than As(III). Therefore, the competition of arsenic-iron and thiosulfate concentration should be considered to study the impact of thiosulfate on arsenic and iron migration and transformation in groundwater.

14.
Int J Biol Macromol ; : 130736, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38479672

RESUMO

The manuscript aimed to study the immune function maintenance effect of Achyranthes bidentata polysaccharides (ABPs). The mice were divided into the control group, cyclophosphamide-induced (CTX) group, and ABPs-treated (ABP) group. The results showed that, compared with the CTX group, ABPs could significantly improve the spleen index and alleviate the pathological changes in immune organs. Ex vivo study of whole spleen cells, the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were increased. The proliferation of lymphocytes and the proportion of CD3+CD4+ Th cells in peripheral blood mononuclear cells were increased. The transcription of GATA-3, Foxp3, and ROR γ t were decreased, while the transcription of T-bet was increased. The transcriptome sequencing analysis showed that the differentially expressed genes (DEGs) caused by ABPs-treated were mostly downregulated in CTX-induced mice. The Th2-related genes were significantly enriched in DEGs, with representative genes, including Il4, II13, Il9, etc., while increasing the expression of immune effector genes simultaneously, including Ccl3, Ccr5, and Il12rb2. It was suggested that ABPs possibly regulated the balance of cytokines in helper T cells to ameliorate the immune function of CTX-induced mice.

15.
Int J Biol Macromol ; 264(Pt 2): 130568, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38447822

RESUMO

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.

16.
Front Neurol ; 15: 1334000, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487325

RESUMO

Background: The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized treatment outcomes in patients with lymphoid malignancies. However, several studies have reported a relatively high rate of infection in adult patients following CD19-targeting CAR T-cell therapy, particularly in the first 28 days. Notably, acute human herpesvirus 6 B (HHV6B) reactivation occurs in up to two-thirds of allogeneic hematopoietic stem cell transplantation patients. Case presentations: Herein, we describe a report of HHV6B encephalitis/myelitis in three patients with relapsed/refractory diffuse large B-cell lymphoma post CAR T-cell therapy. All three patients received multiple lines of prior treatment (range: 2-9 lines). All patients presented with fever that persisted for at least 2 weeks after CAR-T cell infusion (CTI). Both the onset time and duration were similar to those of the cytokine release syndrome (CRS); nevertheless, the CRS grades of the patients were low (grade 1 or 2). Delirium and memory loss after CTI were the earliest notable mental presentations. Neurological manifestations progressed rapidly, with patients experiencing varying degrees of impaired consciousness, seizures, and coma. Back pain, lumbago, lower limb weakness and uroschesis were also observed in Patient 3, indicating myelitis. High HHV6B loads were detected in all Cerebral spinal fluid (CSF) samples using metagenomic next-generation sequencing (mNGS). Only one patient required high-activity antivirals and IgG intravenous pulse treatment finally recovered, whereas the other two patients died from HHV6B encephalitis. Conclusion: Considering its fatal potential, HHV6B encephalitis/myelitis should be urgently diagnosed post CAR-T cell-based therapy. Furthermore, hematologists should differentially diagnose these conditions from CRS or other immunotherapy-related neurotoxicities as early as possible. The results of this study demonstrate the potential of mNGS in the early diagnosis of HHV6B infection, particularly when the organism is difficult to culture.

17.
Front Oncol ; 14: 1346413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487724

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelial cells. Common treatment methods for NPC include radiotherapy, chemotherapy, and surgical intervention. Despite these approaches, the prognosis for NPC remains poor due to treatment resistance and recurrence. Hence, there is a crucial need for more comprehensive research into the mechanisms underlying treatment resistance in NPC. Long non coding RNAs (LncRNAs) are elongated RNA molecules that do not encode proteins. They paly significant roles in various biological processes within tumors, such as chemotherapy resistance, radiation resistance, and tumor recurrence. Recent studies have increasingly unveiled the mechanisms through which LncRNAs contribute to treatment resistance in NPC. Consequently, LncRNAs hold promise as potential biomarkers and therapeutic targets for diagnosing NPC. This review provides an overview of the role of LncRNAs in NPC treatment resistance and explores their potential as therapeutic targets for managing NPC.

18.
Med Image Anal ; 94: 103136, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38489895

RESUMO

Decoding brain states under different cognitive tasks from functional magnetic resonance imaging (fMRI) data has attracted great attention in the neuroimaging filed. However, the well-known temporal dependency in fMRI sequences has not been fully exploited in existing studies, due to the limited temporal-modeling capacity of the backbone machine learning algorithms and rigid training sample organization strategies upon which the brain decoding methods are built. To address these limitations, we propose a novel method for fine-grain brain state decoding, namely, group deep bidirectional recurrent neural network (Group-DBRNN) model. We first propose a training sample organization strategy that consists of a group-task sample generation module and a multiple-scale random fragment strategy (MRFS) module to collect training samples that contain rich task-relevant brain activity contrast (i.e., the comparison of neural activity patterns between different tasks) and maintain the temporal dependency. We then develop a novel decoding model by replacing the unidirectional RNNs that are widely used in existing brain state decoding studies with bidirectional stacked RNNs to better capture the temporal dependency, and by introducing a multi-task interaction layer (MTIL) module to effectively model the task-relevant brain activity contrast. Our experimental results on the Human Connectome Project task fMRI dataset (7 tasks consisting of 23 task sub-type states) show that the proposed model achieves an average decoding accuracy of 94.7% over the 23 fine-grain sub-type states. Meanwhile, our extensive interpretations of the intermediate features learned in the proposed model via visualizations and quantitative assessments of their discriminability and inter-subject alignment evidence that the proposed model can effectively capture the temporal dependency and task-relevant contrast.

19.
Cancer Lett ; : 216761, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490326

RESUMO

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with limited treatment options and poor prognosis. In this study, we reveal the pivotal role of Stratifin (SFN), also recognized as 14-3-3σ, in driving HCC progression. Our investigation underscores a substantial upregulation of SFN within HCC tissues, manifesting a significant association with worse prognostic outcomes among HCC patients. In vitro and in vivo experiments reveal that SFN overexpression significantly amplifies proliferation, mitigates sorafenib-induced effects on HCC cells, and enhances tumorigenesis. While SFN silencing exerts converse effects on HCC progression. Additionally, we unveil a critical interaction between SFN and AKT, where SFN boosts AKT kinase activity by disrupting the binding of PHLPP2 and AKT, thereby intensifying the malignant progression of HCC cells. In conclusion, this study identifies the oncogenic role of SFN and elucidates the regulatory mechanism of the SFN/AKT axis in HCC, which may provide valuable insights into the mechanisms of HCC progression and potential targets for therapeutic intervention.

20.
BMJ Open ; 14(3): e082770, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38479743

RESUMO

OBJECTIVES: This study aimed to evaluate the effectiveness of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) in predicting 24-hour in-hospital mortality among patients aged 65 years and older with isolated traumatic brain injury (TBI). DESIGN: A retrospective, single-centre cohort study. SETTING: This study was conducted at a government-run tertiary comprehensive hospital. PARTICIPANTS: This study included 982 patients aged 65 years or older with isolated TBI, who were admitted to the emergency department between 1 January 2020 and 31 December 2021. INTERVENTIONS: None. PRIMARY OUTCOME: 24-hour in-hospital mortality was the primary outcome. RESULTS: Among the 982 patients, 8.75% died within 24 hours of admission. The non-survivors typically had higher TRIAGES and lower GCS scores. Logistic regression showed significant associations of both TRIAGES and GCS with mortality; the adjusted ORs were 1.98 (95% CI 1.74 to 2.25) for TRIAGES and 0.72 (95% CI 0.68 to 0.77) for GCS. Receiver operating characteristic (ROC) analysis indicated an area under the ROC curve of 0.86 for GCS and 0.88 for TRIAGES, with a significant difference (p=0.012). However, precision-recall curve (PRC) analysis revealed an area under the PRC of 0.38 for GCS and 0.47 for TRIAGES, without a significant difference (p=0.107). CONCLUSIONS: The TRIAGES system is a promising tool for predicting 24-hour in-hospital mortality in older patients with TBI, demonstrating comparable or slightly superior efficacy to the GCS. Further multicentre studies are recommended for validation.


Assuntos
Lesões Encefálicas Traumáticas , Triagem , Humanos , Idoso , Escala de Coma de Glasgow , Estudos Retrospectivos , Estudos de Coortes , Pressão Sanguínea/fisiologia , Taxa Respiratória , Lesões Encefálicas Traumáticas/diagnóstico , Prognóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...