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1.
J Gene Med ; 26(1): e3657, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282150

RESUMO

BACKGROUND: Natural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell-related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell-related genes for predicting thyroid cancer (THCA). METHODS: The single-cell RNA sequencing (scRNA-seq) data from seven THCA samples (GSE184362) and bulk-RNA-seq data of 502 THCA patients (TCGA-THCA) were included. The scRNA-seq data was analyzed using the "Seurat" R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package "ConsensusClusterPlus". The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta-cohort. In the TCGA-THCA cohort, the "glmnet" R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The "maftools" R package was used to examine the somatic mutation landscape of THCA in both low- and high-risk groups. RESULTS: One-hundred and eighty-five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA-THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low-risk H-TMB+ group had a better prognosis, while the high-risk L-TMB+ group had the worst prognosis. CONCLUSION: Natural killer cell-related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia , Imunoterapia , Células Matadoras Naturais , Algoritmos , Análise por Conglomerados , Microambiente Tumoral/genética
2.
Thromb J ; 22(1): 57, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951855

RESUMO

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

3.
Thromb J ; 22(1): 47, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840142

RESUMO

OBJECTIVE: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates. METHODS: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates. RESULTS: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality. CONCLUSIONS: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates.

4.
J Biochem Mol Toxicol ; 38(1): e23602, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38053484

RESUMO

Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.


Assuntos
Antioxidantes , Flavonas , Inibidores de Poli(ADP-Ribose) Polimerases , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Caspase 3/metabolismo , Lipopolissacarídeos/toxicidade , Estresse Oxidativo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Animais , Camundongos
5.
Environ Res ; 241: 117639, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37972811

RESUMO

In this study, CuFe2O4/CuS composite photocatalysts were successfully synthesized for the activation of peroxynomosulfate to remove ciprofloxacin from wastewater. The structural composition and morphology of the materials were analyzed by XRD, SEM, TEM, and Raman spectroscopy. The electrochemical properties of the samples were tested by an electrochemical workstation. The band gap of the samples was calculated by DFT and compared with the experimental values. The effects of different catalysts, oxidant PMS concentrations, and coexisting ions on the experiments were investigated. The reusability and stability of the photocatalysts were also investigated. The mechanism of the photocatalytic degradation process was proposed based on the free radical trapping experiment. The results show that the p-p heterojunction formed between the two contact surfaces of the CuFe2O4 nanoparticle and CuS promoted the charge transfer between the interfaces and inhibited the recombination of electrons and holes. CuFe2O4-5/CuS photocatalyst has the best catalytic activity, and the removal rate of ciprofloxacin is 93.7%. The intermediates in the degradation process were tested by liquid chromatography-mass spectrometry (LC-MS), and the molecular structure characteristics of ciprofloxacin were analyzed by combining with DFT calculations. The possible degradation pathways of pollutants were proposed. This study reveals the great potential of the photocatalyst CuFe2O4/CuS in the activation of PMS for the degradation of ciprofloxacin wastewater.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Peróxidos/química , Ciprofloxacina , Poluentes Químicos da Água/química , Oxidantes
6.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1221-1228, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856440

RESUMO

Twisted partially coherent light, characterized by its unique twist factor, offers novel control over the statistical properties of random light. However, the recognition of the twist factor remains a challenge due to the low coherence and the stochastic nature of the optical beam. This paper introduces a method for the recognition of twisted partially coherent beams by utilizing a circular aperture at the source plane. This aperture produces a characteristic hollow intensity structure due to the twist phase. A deep learning model is then trained to identify the twist factor of these beams based on this signature. The model, while simple in structure, effectively eliminates the need for complex optimization layers, streamlining the recognition process. This approach offers a promising solution for enhancing the detection of twisted light and paves the way for future research in this field.

7.
Eur Spine J ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007983

RESUMO

PURPOSE: To investigate the impact of preoperative compensatory curve on the postoperative curve progression in congenital scoliosis (CS) patients following thoracolumbar hemivertebra (HV) resection and short fusion. METHODS: This study retrospectively reviewed a consecutive cohort of patients with CS who underwent thoracolumbar HV resection and short fusion with a minimum of 2 years follow-up. According to the preoperative curve pattern, patients were divided into compensatory curve group non-compensatory curve group. Based on the postoperative coronal curve evolution, patients were further divided into the progressed group (Group P, with curve decompensation ≥ 20°) and the non-progressed group (Group NP, characterized by well-compensated curves). RESULTS: A total of 127 patients were included in this study, with 31 patients in the compensatory curve group and 96 patients in the non-compensatory curve group. The incidence of postoperative coronal curve progression was significantly higher in the compensatory curve group than that in non-compensatory curve group (35.5% vs. 13.5%, p = 0.007). In the compensatory curve group, patients who experienced postoperative curve progression showed fewer fusion segments (p = 0.001), greater preoperative UIV translation (p = 0.006), greater preoperative LIV tilt (p = 0.017), and larger postoperative UIV tilt (p < 0.001) compared with patients in group NP. Multiple logistic regression demonstrated that the shorter fusion segments and greater postoperative UIV tilt were two independent risk factors for postoperative curve progression. CONCLUSION: The presence of the compensatory curve was associated with a higher incidence of postoperative curve progression in patients with CS who underwent thoracolumbar HV resection and short fusion. Shorter fusion segments and greater postoperative UIV tilt were found to be the risk factors for postoperative curve progression.

8.
Zygote ; 32(1): 21-27, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38047349

RESUMO

Our previous studies have suggested that spastin, which aggregates on spindle microtubules in oocytes, may promote the assembly of mouse oocyte spindles by cutting microtubules. This action may be related to CRMP5, as knocking down CRMP5 results in reduced spindle microtubule density and maturation defects in oocytes. In this study, we found that, after knocking down CRMP5 in oocytes, spastin distribution shifted from the spindle to the spindle poles and errors in microtubule-kinetochore attachment appeared in oocyte spindles. However, CRMP5 did not interact with the other two microtubule-severing proteins, katanin-like-1 (KATNAL1) and fidgetin-like-1 (FIGNL1), which aggregate at the spindle poles. We speculate that, in oocytes, due to the reduction of spastin distribution on chromosomes after knocking down CRMP5, microtubule-kinetochore errors cannot be corrected through severing, resulting in meiotic division abnormalities and maturation defects in oocytes. This finding provides new insights into the regulatory mechanisms of spastin in oocytes and important opportunities for the study of meiotic division mechanisms.


Assuntos
Cinetocoros , Fuso Acromático , Camundongos , Animais , Cinetocoros/metabolismo , Espastina/genética , Espastina/metabolismo , Fuso Acromático/fisiologia , Microtúbulos/metabolismo , Meiose , Oócitos/fisiologia
9.
Chaos ; 34(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38976800

RESUMO

Networked Turing patterns often manifest as groups of nodes distributed on either side of the homogeneous equilibrium, exhibiting high and low density. These pattern formations are significantly influenced by network topological characteristics, such as the average degree. However, the impact of clustering on them remains inadequately understood. Here, we investigate the relationship between clustering and networked Turing patterns using classical prey-predator models. Our findings reveal that when nodes of high and low density are completely distributed on both sides of the homogeneous equilibrium, there is a linear decay in Turing patterns as global clustering coefficients increase, given a fixed node size and average degree; otherwise, this linear decay may not always hold due to the presence of high-density nodes considered as low-density nodes. This discovery provides a qualitative assessment of how clustering coefficients impact the formation of Turing patterns and may contribute to understanding why using refuges in ecosystems could enhance the stability of prey-predator systems. The results link network topological structures with the stability of prey-predator systems, offering new insights into predicting and controlling pattern formations in real-world systems from a network perspective.

10.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1564-1569, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621940

RESUMO

Various separation methods in combination with spectral data analysis, X-ray single crystal diffraction analysis, and litera-ture data comparison were employed to clarify the chemical constituents of Itea yunnanensis. Seven compounds were obtained from I. yunnanensis, which were identified as(S)-3-[1-(4-hydroxyphenyl)propane-2-yl]-4-methoxybenzoate methyl ester(1), iteafuranal B(2), syringaresinol(3), dihydrokaempferol(4), trimethoxybenzene(5), eicosane(6), and nonacosane(7), respectively. Among them, compound 1 was a new nor-neolignan compound named iteanorneoligan A, and the rest of the compounds were identified from I. yunnanensis for the first time. The anti-hepatocellular carcinoma effect of the compound was evaluated based on Sk-hep-1 cells model via MTT assay, and compound 2 showed a significant inhibitory effect on the proliferation of Sk-hep-1 cells with an IC_(50) of 9.4 µmol·L~(-1). The antioxidant capacity was determined via DPPH, ABTS~(·+), and O■ radical scavenging ability, and compound 1 exhibited a significant ABTS~(·+) radical scavenging effect with an IC_(50) of 0.178 mg·mL~(-1).


Assuntos
Lignanas , Estrutura Molecular , Benzotiazóis , Ácidos Sulfônicos , Antioxidantes/farmacologia , Antioxidantes/química
11.
Zhongguo Zhong Yao Za Zhi ; 49(4): 912-923, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621898

RESUMO

With the promotion of chemical fertilizer and pesticide reduction and green production of traditional Chinese medicines, microbial fertilizers have become a hot way to achieve the zero-growth of chemical fertilizers and pesticides, improve the yield and qua-lity of medicinal plants, maintain soil health, and promote the sustainable development of the planting industry of Chinese herbal medicines. Soil conditions and microenvironments are crucial to the growth, development, and quality formation of medicinal plants. Microbial fertilizers, as environmentally friendly fertilizers acting on the soil, can improve soil quality by replenishing organic matter and promoting the metabolism of beneficial microorganisms to improve the yield and quality of medicinal plants. In this regard, understanding the mechanism of microbial fertilizer in regulating the quality formation of medicinal plants is crucial for the development of herbal eco-agriculture. This study introduces the processes of microbial fertilizers in improving soil properties, participating in soil nutrient cycling, enhancing the resistance of medicinal plants, and promoting the accumulation of medicinal components to summarize the mechanisms and roles of bacterial fertilizers in regulating the quality formation of medicinal plants. Furthermore, this paper introduces the application of bacterial fertilizers in medicinal plants and makes an outlook on their development, with a view to providing a scientific basis for using microbial fertilizers to improve the quality of Chinese herbal medicines, improve the soil environment, promote the sustainable development of eco-agriculture of traditional Chinese medicine, and popularize the application of microbial fertilizers.


Assuntos
Praguicidas , Plantas Medicinais , Fertilizantes , Agricultura , Solo/química , Bactérias/genética , Extratos Vegetais , Microbiologia do Solo
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 325-330, 2024 Apr 15.
Artigo em Zh | MEDLINE | ID: mdl-38660894

RESUMO

Medicine is a continuously advancing science, characterized by the integration of multiple disciplines, ultimately focusing on the "human" aspect. Over the past half-century, there has been a global surge in efforts to reshape the humanistic spirit of medicine. Narrative medicine, a field that highly integrates medical professionalism with universal humanistic values, has developed rapidly in China from scratch over the past decade or so. This article introduces the development of narrative medicine both domestically and internationally, explains how to correctly understand the connotation of China's narrative medicine system and the significance of practicing narrative medicine. It analyzes current challenges in clinical practice, education and teaching, scientific research, doctor-patient consensus, and social recognition. Furthermore, it proposes directions for effort, namely, in the context of "greater health" and "new medical science", narrative medicine is empowered to help construct a harmonious medical narrative ecosystem, promote high-quality development in pediatrics, contribute to the innovation in medical education and talent training with humanistic strength and wisdom.


Assuntos
Medicina Narrativa , Pediatria , Pediatria/educação , Humanos
13.
Mol Biol Evol ; 39(1)2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34730826

RESUMO

Colonization of land from marine environments was a major transition for biological life on Earth, and intertidal adaptation was a key evolutionary event in the transition from marine- to land-based lifestyles. Multicellular intertidal red algae exhibit the earliest, systematic, and successful adaptation to intertidal environments, with Porphyra sensu lato (Bangiales, Rhodophyta) being a typical example. Here, a chromosome-level 49.67 Mb genome for Neoporphyra haitanensis comprising 9,496 gene loci is described based on metagenome-Hi-C-assisted whole-genome assembly, which allowed the isolation of epiphytic bacterial genome sequences from a seaweed genome for the first time. The compact, function-rich N. haitanensis genome revealed that ancestral lineages of red algae share common horizontal gene transfer events and close relationships with epiphytic bacterial populations. Specifically, the ancestor of N. haitanensis obtained unique lipoxygenase family genes from bacteria for complex chemical defense, carbonic anhydrases for survival in shell-borne conchocelis lifestyle stages, and numerous genes involved in stress tolerance. Combined proteomic, transcriptomic, and metabolomic analyses revealed complex regulation of rapid responses to intertidal dehydration/rehydration cycling within N. haitanensis. These adaptations include rapid regulation of its photosynthetic system, a readily available capacity to utilize ribosomal stores, increased methylation activity to rapidly synthesize proteins, and a strong anti-oxidation system to dissipate excess redox energy upon exposure to air. These novel insights into the unique adaptations of red algae to intertidal lifestyles inform our understanding of adaptations to intertidal ecosystems and the unique evolutionary steps required for intertidal colonization by biological life.


Assuntos
Proteômica , Rodófitas , Aclimatação/genética , Adaptação Fisiológica/genética , Ecossistema , Rodófitas/genética
14.
Am J Gastroenterol ; 118(2): 243-255, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563321

RESUMO

INTRODUCTION: Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis. METHODS: A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index. RESULTS: Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs. DISCUSSION: For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques.


Assuntos
Cisto Pancreático , Neoplasias Pancreáticas , Humanos , Metanálise em Rede , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/patologia
15.
Small ; 19(46): e2304031, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37455347

RESUMO

Amyloid fibrils-nanoscale fibrillar aggregates with high levels of order-are pathogenic in some today incurable human diseases; however, there are also many physiologically functioning amyloids in nature. The process of amyloid formation is typically nucleation-elongation-dependent, as exemplified by the pathogenic amyloid-ß peptide (Aß) that is associated with Alzheimer's disease. Spider silk, one of the toughest biomaterials, shares characteristics with amyloid. In this study, it is shown that forming amyloid-like nanofibrils is an inherent property preserved by various spider silk proteins (spidroins). Both spidroins and Aß capped by spidroin N- and C-terminal domains, can assemble into macroscopic spider silk-like fibers that consist of straight nanofibrils parallel to the fiber axis as observed in native spider silk. While Aß forms amyloid nanofibrils through a nucleation-dependent pathway and exhibits strong cytotoxicity and seeding effects, spidroins spontaneously and rapidly form amyloid-like nanofibrils via a non-nucleation-dependent polymerization pathway that involves lateral packing of fibrils. Spidroin nanofibrils share amyloid-like properties but lack strong cytotoxicity and the ability to self-seed or cross-seed human amyloidogenic peptides. These results suggest that spidroins´ unique primary structures have evolved to allow functional properties of amyloid, and at the same time direct their fibrillization pathways to avoid formation of cytotoxic intermediates.


Assuntos
Fibroínas , Aranhas , Humanos , Animais , Seda/química , Fibroínas/química , Polimerização , Amiloide , Peptídeos beta-Amiloides/metabolismo , Aranhas/metabolismo
16.
Mol Carcinog ; 62(5): 676-684, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36789975

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy with a high relapse rate. We previously found that C-X-C motif chemokine receptor 4 (CXCR4) was highly expressed in DLBCL and associated with poor prognosis. This study focused on the effect of hypoxia-inducible factor-1α (HIF-1α) on CXCR4 expression and the DLBCL progression. Two activated B cell-like DLBCL cell lines Ly-3 and SUDHL2 were transfected with overexpression and knockdown plasmids or HIF-1α. The viability and migration of DLBCL cells were significantly increased under hypoxic conditions, or upon HIF-1α overexpression under normoxic conditions, but the HIF-1α downregulation led to inverse trends. However, the promoting effects of HIF-1α overexpression on DLBCL cells were suppressed by Plerixafor (a CXCR4 inhibitor). The luciferase and chromatin immunoprecipitation assays revealed that HIF-1α bound to the functional site HRE1 on CXCR4 promoter to activate its transcription. HIF-1α-mediated CXCR4 activation further led to increased phosphorylation of AKT/mTOR under hypoxic conditions. Taken together, this work reports that HIF-1α promotes viability and migration of activated B cell-like cells under hypoxia, which might involve the transcription of CXCR4 and the activation of the AKT/mTOR pathway. The finding may provide novel lights in the management of DCBCL.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Linfoma Difuso de Grandes Células B , Receptores CXCR4 , Humanos , Hipóxia Celular , Linhagem Celular Tumoral , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linfoma Difuso de Grandes Células B/genética , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
17.
BMC Infect Dis ; 23(1): 25, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639649

RESUMO

BACKGROUND: The ongoing coronavirus 2019 (COVID-19) pandemic has emerged and caused multiple pandemic waves in the following six countries: India, Indonesia, Nepal, Malaysia, Bangladesh and Myanmar. Some of the countries have been much less studied in this devastating pandemic. This study aims to assess the impact of the Omicron variant in these six countries and estimate the infection fatality rate (IFR) and the reproduction number [Formula: see text] in these six South Asia, Southeast Asia and Oceania countries. METHODS: We propose a Susceptible-Vaccinated-Exposed-Infectious-Hospitalized-Death-Recovered model with a time-varying transmission rate [Formula: see text] to fit the multiple waves of the COVID-19 pandemic and to estimate the IFR and [Formula: see text] in the aforementioned six countries. The level of immune evasion and the intrinsic transmissibility advantage of the Omicron variant are also considered in this model. RESULTS: We fit our model to the reported deaths well. We estimate the IFR (in the range of 0.016 to 0.136%) and the reproduction number [Formula: see text] (in the range of 0 to 9) in the six countries. Multiple pandemic waves in each country were observed in our simulation results. CONCLUSIONS: The invasion of the Omicron variant caused the new pandemic waves in the six countries. The higher [Formula: see text] suggests the intrinsic transmissibility advantage of the Omicron variant. Our model simulation forecast implies that the Omicron pandemic wave may be mitigated due to the increasing immunized population and vaccine coverage.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Ásia , Oceania
18.
J Math Biol ; 87(5): 71, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848667

RESUMO

Cholera is an environmentally driven disease where the human hosts both ingest the pathogen from polluted environment and shed the pathogen to the environment, generating a two-way feedback cycle. In this paper, we propose a bidirectionally linked immuno-epidemiological model to study the interaction of within- and between-host cholera dynamics. We conduct a rigorous analysis for this multiscale model, with a focus on the stability and bifurcation properties of each feasible equilibrium. We find that the parameter that represents the bidirectional connection is a key factor in shaping the rich dynamics of the system, including the occurrence of the backward bifurcation and Hopf bifurcation. Numerical results illustrate a practical application of our model and add new insight into the prevention and intervention of cholera epidemics.


Assuntos
Cólera , Epidemias , Humanos , Cólera/epidemiologia , Cólera/prevenção & controle , Modelos Biológicos , Modelos Epidemiológicos , Epidemias/prevenção & controle
19.
J Math Biol ; 88(1): 5, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38017080

RESUMO

Turing patterns arising from reaction-diffusion systems such as epidemic, ecology or chemical reaction models are an important dynamic property. Parameter identification of Turing patterns in spatial continuous and networked reaction-diffusion systems is an interesting and challenging inverse problem. The existing algorithms require huge account operations and resources. These drawbacks are amplified when apply them to reaction-diffusion systems on large-scale complex networks. To overcome these shortcomings, we present a new least squares algorithm which is rooted in the fact that Turing patterns are the stationary solutions of reaction-diffusion systems. The new algorithm is time independent, it translates the parameter identification problem into a low dimensional optimization problem even a low order linear algebra equations. The numerical simulations demonstrate that our algorithm has good effectiveness, robustness as well as performance.


Assuntos
Algoritmos , Modelos Biológicos , Análise dos Mínimos Quadrados , Ecologia , Modelos Químicos , Difusão
20.
J Math Biol ; 87(2): 29, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37452969

RESUMO

As there are no targeted medicines or vaccines for newly emerging infectious diseases, isolation among communities (villages, cities, or countries) is one of the most effective intervention measures. As such, the number of intercommunity edges ([Formula: see text]) becomes one of the most important factor in isolating a place since it is closely related to normal life. Unfortunately, how [Formula: see text] affects epidemic spread is still poorly understood. In this paper, we quantitatively analyzed the impact of [Formula: see text] on infectious disease transmission by establishing a four-dimensional [Formula: see text] edge-based compartmental model with two communities. The basic reproduction number [Formula: see text] is explicitly obtained subject to [Formula: see text] [Formula: see text]. Furthermore, according to [Formula: see text] with zero [Formula: see text], epidemics spread could be classified into two cases. When [Formula: see text] for the case 2, epidemics occur with at least one of the reproduction numbers within communities greater than one, and otherwise when [Formula: see text] for case 1, both reproduction numbers within communities are less than one. Remarkably, in case 1, whether epidemics break out strongly depends on intercommunity edges. Then, the outbreak threshold in regard to [Formula: see text] is also explicitly obtained, below which epidemics vanish, and otherwise break out. The above two cases form a severity-based hierarchical intervention scheme for epidemics. It is then applied to the SARS outbreak in Singapore, verifying the validity of our scheme. In addition, the final size of the system is gained by demonstrating the existence of positive equilibrium in a four-dimensional coupled system. Theoretical results are also validated through numerical simulation in networks with the Poisson and Power law distributions, respectively. Our results provide a new insight into controlling epidemics.


Assuntos
Doenças Transmissíveis , Epidemias , Humanos , Doenças Transmissíveis/epidemiologia , Modelos Biológicos , Redes Comunitárias , Epidemias/prevenção & controle , Simulação por Computador , Número Básico de Reprodução
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