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1.
Stem Cells Int ; 2022: 5014895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571532

RESUMO

Autologous fat grafting has been widely used in plastic surgery in recent years, but the unstable retention of fat graft has always been a key clinical problem. Adipose tissue has poor tolerant to ischemia, so the transplanted adipose tissue needs to rebuild blood supply at an early stage in order to survive stably. Our previous study has found that comparing to human foreskin fibroblast exosome (HFF-Exo), human adipose-derived stem cells exosome (hADSC-Exo) can significantly improve the proliferation of vascular endothelial cells and the angiogenic effect of artificial dermal preconstructed flaps. Therefore, the ability of hADSC-Exo to improve the retention of adipose grafts and its potential regenerative mechanism aroused our strong interest. In this study, we applied hADSC-Exo and HFF-Exo to adipose grafts and explored the potential regeneration mechanism through various means such as bioinformatics, immunofluorescence, immunohistochemistry, and adipogenic differentiation. The results showed that hADSC-Exo can significantly promote grafts angiogenesis and adipogenic differentiation of ADSC to improve the retention of fat grafts and may downregulate the Wnt/ß-catenin signaling pathway to promote the adipogenic differentiation. In summary, our results provide a theoretical basis for the clinical translation of hADSC-Exo in fat grafting.

2.
Cells ; 11(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563795

RESUMO

Reverse transcriptase hTERT is essential to telomerase function in stem cells, as well as in 85-90% of human cancers. Its high expression in stem cells or cancer cells has made telomerase/hTERT an attractive therapeutic target for anti-aging and anti-tumor applications. In this study, we screened a natural product library containing 800 compounds using an endogenous hTERT reporter. Eight candidates have been identified, in which sanguinarine chloride (SC) and brazilin (Braz) were selected due to their leading inhibition. SC could induce an acute and strong suppressive effect on the expression of hTERT and telomerase activity in multiple cancer cells, whereas Braz selectively inhibited telomerase in certain types of cancer cells. Remarkably, SC long-term treatment could cause telomere attrition and cell growth retardation, which lead to senescence features in cancer cells, such as the accumulation of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells, the upregulation of p16/p21/p53 pathways and telomere dysfunction-induced foci (TIFs). Additionally, SC exhibited excellent capabilities of anti-tumorigenesis, both in vitro and in vivo. In the mechanism, the compound down-regulated several active transcription factors including p65, a subunit of NF-κB complex, and reintroducing p65 could alleviate its suppression of the hTERT/telomerase. Moreover, SC could directly bind hTERT and inhibit telomerase activity in vitro. In conclusion, we identified that SC not only down-regulates the hTERT gene's expression, but also directly affects telomerase/hTERT. The dual function makes this compound an attractive drug candidate for anti-tumor therapy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35467315

RESUMO

High levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We evaluated the effect of E2 concentration on survival endpoints among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints. 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR 1.79, 95% CI 1.17-2.75, P = 0.008) and OS in post-menopausal women (HR 1.35, 95% CI 1.04-1.74, P = 0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation ("L-shaped" and "U-shaped", respectively) with E2 levels. However, there was a linear relationship in post-menopausal women. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a "U-shaped" relationship with OS and PFS in pre-menopausal women. Pre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

4.
Colloids Surf B Biointerfaces ; 215: 112493, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35430486

RESUMO

Fluorine-19 magnetic resonance imaging (19F MRI) has been a technology of choice for in vivo cell tracking, in which perfluorocarbons (PFCs) nanoemulsions are the most used 19F MRI agents. However, the peculiar physicochemical properties of PFCs may lead to poor cell uptake and misleading cell tracking results. Herein, we employed partially fluorinated aromatic agents to formulate paramagnetic nanoemulsions as novel 19F MRI-fluorescence (FL) dual imaging agents for cell tracking. With the intramolecular π-π interaction, low density and fluorine content, the partially fluorinated agents enable considerable solubilities of functional agents and short relaxation times, which facilitates convenient preparation of stable, biocompatible, and multifunctional nanoemulsions with high 19F MRI sensitivity. Replacing PFCs in 19F MRI nanoemulsions with readily available partially fluorinated aromatic agents may address many issues associated with PFCs and provide a novel strategy for high-performance 19F MRI agents of broad biomedical applications.

5.
J Appl Microbiol ; 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35365856

RESUMO

AIMS: To characterize the functions of nitrilases of Variovorax boronicumulans CGMCC 4969 and evaluate flonicamid (FLO) degradation and ß-cyano-L-alanine (Ala(CN)) detoxification by this bacterium. METHODS AND RESULTS: Variovorax boronicumulans CGMCC 4969 nitrilases (NitA and NitB) were purified, and substrate specificity assay indicated that both of them degraded insecticide FLO to N-(4-trifluoromethylnicotinoyl)glycinamide (TFNG-AM) and 4-(trifluoromethyl)nicotinol glycine (TFNG). Ala(CN), a plant detoxification intermediate, was hydrolysed by NitB. Escherichia coli overexpressing NitA and NitB degraded 41.2 and 93.8% of FLO (0.87 mmol·L-1 ) within 1 h, with half-lives of 1.30 and 0.25 h, respectively. NitB exhibited the highest nitrilase activity towards FLO. FLO was used as a substrate to compare their enzymatic properties. NitB was more tolerant to acidic conditions and organic solvents than NitA. Conversely, NitA was more tolerant to metal ions than NitB. CGMCC 4969 facilitated FLO degradation in soil and surface water and utilized Ala(CN) as a sole nitrogen source for growth. CONCLUSIONS: CGMCC 4969 efficiently degraded FLO mediated by NitA and NitB; NitB was involved in Ala(CN) detoxification. SIGNIFICANCE AND IMPACT OF THE STUDY: This study promotes our understanding of versatile functions of nitrilases from CGMCC 4969 that is promising for environmental remediation.

6.
Front Immunol ; 13: 820891, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371004

RESUMO

Crohn's disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.


Assuntos
Doença de Crohn , Enterite , Ácido Tranexâmico , Tuberculose Gastrointestinal , Biomarcadores , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Humanos , Imunoglobulina A , Imunoglobulina G , Estudos Retrospectivos , Tuberculose Gastrointestinal/diagnóstico
7.
Org Biomol Chem ; 20(16): 3335-3341, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35352080

RESUMO

Dual-imaging agents with highly sensitive fluorescence (FL) imaging and highly selective fluorine-19 magnetic resonance imaging (19F MRI) are valuable for biomedical research. At the same time, photosensitizers with a high reactive oxygen species (ROS) generating capability are crucial for photodynamic therapy (PDT) of cancer. Herein, a series of tetra-trifluoromethylated aza-boron dipyrromethenes (aza-BODIPYs) were conveniently synthesized from readily available building blocks and their physicochemical properties, including ultraviolet-visible (UV-Vis) absorption, FL emission, photothermal efficacy, ROS generating efficacy, and 19F MRI sensitivity, were systematically investigated. An aza-BODIPY with 12 symmetrical fluorines was identified as a potent FL-19F MRI dual-imaging traceable photodynamic agent. It was found that the selective introduction of trifluoromethyl (CF3) groups into aza-BODIPYs may considerably improve their UV absorption, FL emission, photothermal efficacy, and ROS generating properties, which lays the foundation for the rational design of trifluoromethylated aza-BODIPYs in biomedical applications.


Assuntos
Compostos de Boro , Fotoquimioterapia , Compostos de Boro/química , Imageamento por Ressonância Magnética , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio
9.
Inorg Chem ; 61(14): 5495-5501, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35289176

RESUMO

White light-emitting diodes provide widespread applications in lighting, electronic equipment, and high-tech displays. However, thermal quenching effect severely limits their practical application. Here, we developed an orange-red phosphor ß-KMg(PO3)3:Mn2+, which emits bright orange-red light when excited by ultraviolet light without the energy transfer of sensitizer, owing to the strong crystal field provided by ß-KMg(PO3)3 for Mn2+. The self-reduction of Mn4+ → Mn2+ and good thermal stability have been realized in an ambient atmosphere. The defect types were verified by X-ray photoelectron spectroscopy, and cationic vacancy plays a significant role in the self-reduction of Mn4+ → Mn2+. Furthermore, the properties of the trap energy levels were studied by thermoluminescence. The recombination luminescence of the detrapped carriers released from the deep trap levels at high temperatures suppresses the luminescence loss of thermal quenching. Moreover, the trap energy levels play an important role in the mechanoluminescence of ß-KMg(PO3)3:Mn2+. This work emphasizes the significance of the defects in the luminescent characteristics and opens up a new approach for the development of advanced optical functional materials.

10.
Antibiotics (Basel) ; 11(3)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35326859

RESUMO

Little attention has been paid to the problem of the combined toxicity of accumulated antibiotics on humans from food and clinical treatments. Therefore, we used human hepatocytes to study the joint toxicity of four common antibiotics. The cytotoxicity of enrofloxacin (ENR), combined with ciprofloxacin (CFX), florfenicol (FFC), or sulfadimidine (SMD) on THLE-2 cells was determined by CCK-8 assays; then their joint toxicity was evaluated using CalcuSyn 2.0. Dose-effect curves and median-effect plots established on large amounts of data and CI values were calculated to judge the nature of the combination's interaction. ED50, ED75, and ED90 were predicted to elucidate the changing trend of the concentration on the toxicity of each drug pair. The ENR-CFX and ENR-FFC pairs exhibited synergistic toxicity only at special concentration rates, while ENR and SMD synergistically induced cytotoxicity at almost all the concentration rates studied. The mixed ratio was a significant factor for synergistic toxicity and should be evaluated in all combined effect studies. These results suggested that the combined toxicity of these four drugs should be taken into account in their risk assessment.

11.
EClinicalMedicine ; 45: 101330, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35274091

RESUMO

Background: There is a strong connection between oral health and overall wellness. We aim to examine the association between poor oral health and the risk of developing or dying of cancer, and whether the association differs by residential area. Methods: Between 2004 and 2008, a total of 510,148 adults free of cancer were included from the China Kadoorie Biobank study and thereafter followed up to 2015. Poor oral health was assessed from a self-reported baseline questionnaire and defined as a combination of rarely brushing teeth and always gum bleeding. We used Cox proportional hazards models to estimate the hazard ratio (HR) of cancer risk and its associated 95% confidence interval (CI) according to oral health status. Findings: Overall, 14.9% of participants (19.7% in rural areas and 8.8% in urban areas) reported poor oral health at baseline. After 4,602,743 person-years of follow-up, we identified 23,805 new cancer cases and 11,973 cancer deaths, respectively. Poor oral health was associated with higher risks of total cancer incidence (HR: 1.08, 95% CI: 1.04-1.12) and death (HR: 1.10, 95% CI: 1.05-1.16). For the site-specific cancers, poor oral health was significantly associated with higher risk of stomach cancer incidence (cases: 2964, HR: 1.10, 95% CI: 1.00-1.22), esophageal cancer incidence (cases: 2119, HR: 1.19, 95% CI: 1.07-1.33), esophageal cancer death (cases: 1238, HR: 1.29, 95% CI: 1.12-1.49), liver cancer incidence (cases: 2565, HR: 1.18, 95% CI: 1.06-1.32), and liver cancer death (cases: 1826, HR: 1.20, 95% CI: 1.05-1.36). This positive association was stronger among rural residents compared to urban residents (interaction test P < 0.01). Interpretation: Our findings indicate that poor oral health is associated with higher risk for cancers, especially digestive system cancers. Promotion of oral health in the general population, especially for rural residents, could have valuable public health significance in preventing major systemic diseases. Funding: Supported by grants (2021YFC2500400, 2016YFC0900500, 2016YFC0900501, 2016YFC0900504) from the National Key Research and Development Program of China, grants from the Kadoorie Charitable Foundation in Hong Kong and grants grants (088158/Z/09/Z, 104085/Z/14/Z, 202922/Z/16/Z) from Wellcome Trust in the UK. CKB is supported by the Kadoorie Charitable Foundation (KCF) in Hong Kong.

12.
J Ovarian Res ; 15(1): 30, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227296

RESUMO

BACKGROUND: Accumulating evidence suggests a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism remains unclear. In this study, we identified previously unrecognized genes that are significantly correlated with PCOS and OC via bioinformatics. MATERIALS AND METHODS: Multiple bioinformatic analyses, such as differential expression analysis, univariate Cox analysis, functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction, survival analysis, and immune infiltration analysis, were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. RESULTS: TCGA-OC, GSE140082 (for OC) and GSE34526 (for PCOS) datasets were downloaded. Twelve genes, including RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were identified as signature genes. Drug sensitivity analysis showed that OGN might represent a hub gene in the progression of PCOS and OC. Experimental analysis found that OGN could increase FSHR expression, indicating that OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that OGN function might be closely related to m6A and ferroptosis. CONCLUSIONS: Our study identified a 12-gene signature that might be involved in the prognostic significance of OC. Furthermore, the hub gene OGN represent a significant gene involved in OC and PCOS progression by regulating the hormonal response.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Ovarianas/genética , Síndrome do Ovário Policístico/genética , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Quimiocina CXCL11/genética , Biologia Computacional , Células Dendríticas , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Ferroptose/genética , Humanos , Fatores Reguladores de Interferon/genética , Glicoproteínas de Membrana/metabolismo , Metilação , N-Acetilgalactosaminiltransferases/genética , Proteínas do Tecido Nervoso/metabolismo , Neutrófilos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/patologia , Prognóstico , RNA Mensageiro/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Receptores do FSH/genética , Receptores de Interleucina/genética , Receptores de Ácidos Lisofosfatídicos/genética , Fator de Transcrição STAT1/genética , Transcriptoma , Ubiquitina-Proteína Ligases/genética
13.
Front Oncol ; 12: 827171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223508

RESUMO

BACKGROUND: In the past few decades, nanomaterial-mediated phototherapy has gained significant attention as an alternative antitumor strategy. However, its antitumor success is majorly limited to the treatment of subcutaneous tumors in nude mice. In fact, no studies have been previously conducted in this area/field on clinically-relevant big animal models. Therefore, there is an urgent need to conduct further investigation in a typical big animal model, which is more closely related to the human body. RESULTS: In this study, niobium carbide (NbC) was selected as a photoactive substance owing to the presence of outstanding near-infrared (NIR) absorption properties, which are responsible for the generation of NIR-triggered hyperthermia and reactive oxygen species that contribute towards synergetic photothermal and photodynamic effect. Moreover, the present study utilized macrophages as bio-carrier for the targeted delivery of NbC, wherein phagocytosis by macrophages retained the photothermal/photodynamic effect of NbC. Consequently, macrophage-loaded NbC ensured/allowed complete removal of solid tumors both in nude mice and big animal models involving rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) were used to monitor physiological evolution in tumor in vivo post-treatment, which clearly revealed the occurrence of the photoablation process in tumor and provided a new strategy for the surveillance of tumor in big animal models. CONCLUSION: Altogether, the use of a large animal model in this study presented higher clinical significance as compared to previous studies.

14.
Front Med (Lausanne) ; 9: 831337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223927

RESUMO

OBJECTIVE: To evaluate the clinical features and inflammatory cytokines of dry eye disease (DED) in patients with schizophrenia. METHODS: This is a case-control study. The modified self-rating depression scale (M-SDS) and the ocular surface disease index (OSDI) were used to evaluate the symptoms of depression and DED, respectively. Lipid layer thickness (LLT), partial blink rate (PBR), meibomian gland loss (MGL), tear break-up time (TBUT), corneal fluorescein staining, Schirmer I-test, and eyelid margin abnormalities were also measured. A multiplex ELISA Quantibody array was used to detect the inflammatory cytokines in the tears of all participants. RESULTS: Forty schizophrenic patients and 20 control subjects were included. The mean age was 45.0 ± 9.5 years (range, 22-63 years) in schizophrenic patients and 45.4 ± 16.2 years (range, 23-76 years) in controls (P = 0.914). The ratio of male to female was 1.1 in schizophrenic patients and 1.0 in controls (P = 0.914). Ten women (52.6%) with schizophrenia and 2 (20%) in the control group (P = 0.096) were menopausal or post-menopausal. The OSDI [0.0 (0.0-4.2) vs. 7.3 (2.1-14.6)] and TBUT [4.5 (3.0-6.0) vs. 10.0 (3.5-11.0)] were significantly lower in patients with schizophrenia than in controls (P = 0.003 and P = 0.009, respectively). The rate of MGL [36.5 (17.5-47.5) vs. 8.5 (0.0-17.5)] increased in schizophrenic patients (P < 0.001). Among pro-inflammatory cytokines, the levels of interleukin (IL)-1α, IL-6, IL-11, IL-12A, IL-15, IL-17A, and granulocyte colony-stimulating factor (G-CSF) in tears were elevated in the schizophrenia group (all P < 0.01). Most of the chemokines examined were at increased levels in the tears of schizophrenics (all P < 0.05). The levels of matrix metalloproteinases-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) were also higher in the schizophrenic patients (all P < 0.001). The concentrations of IL-1Ra, tissue-inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in the schizophrenia group were decreased (all P < 0.001). In schizophrenic patients, the level of CCL2 in tears was positively correlated with OSDI (R = 0.34, P = 0.03). The increasing TIMP-1 and decreasing IL-5 were correlated with increasing LLT (R = 0.33, P = 0.035; R = -0.35, P = 0.027, respectively). The level of ICAM-1 was then positively correlated with partial blink rate (PBR) (R = 0.33, P = 0.035). There was a negative correlation between IL-8 and the Schirmer I-test (R = -0.41, P = 0.009). CONCLUSIONS: Patients with schizophrenia were more likely to experience asymptomatic DED, with mild symptoms and obvious signs. The inflammatory cytokines in the tears of schizophrenic patients differed greatly from that of non-schizophrenic patients.

15.
Eur Heart J ; 43(18): 1702-1711, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35195259

RESUMO

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.


Assuntos
Doença da Artéria Coronariana , China/epidemiologia , Estudos de Coortes , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Herança Multifatorial/genética , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
16.
Soft Matter ; 18(9): 1885-1895, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35175271

RESUMO

In this investigation, transient crosslinking was constructed to obtain a hydrogel with excellent mechanical and self-healing properties. Firstly, core-shell particles with hydrophilic amino groups were prepared by emulsion polymerization and subsequently dispersed into hydrophobic association polyacrylamide hydrogels. Transient crosslinking was constructed through hydrogen bonding between core-shell particles and polyacrylamide. As a result, the hydrogels exhibited a tensile strength of 1.4 MPa and self-healing efficiency of 98% at 24 h. Furthermore, reconstruction of the transient crosslinking was confirmed from rheological measurements. Therefore, the essential reinforcement principle based on transient crosslinking would open a novel strategy to obtain hydrogels with superior toughness and self-healing properties.


Assuntos
Hidrogéis , Nanopartículas , Hidrogéis/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Polimerização , Resistência à Tração
17.
Materials (Basel) ; 15(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35160803

RESUMO

The pick-up, migration, deposition, and clogging behaviors of fine particles are ubiquitous in many engineering applications, including contaminant remediation. Deposition and clogging are detrimental to the efficiency of environmental remediation, and their mechanisms are yet to be elucidated. Two-dimensional microfluidic models were developed to simulate the pore structure of porous media with unified particle sizes in this study. Kaolin and bentonite suspensions were introduced to microfluidic chips to observe their particle deposition and clogging behaviors. Interactions between interparticle forces and particle velocity profiles were investigated via computational fluid dynamics and discrete element method simulations. The results showed that (1) only the velocity vector toward the micropillars and drag forces in the reverse direction were prone to deposition; (2) due to the negligible weight of particles, the Stokes number implied that inertia was not the controlling factor causing deposition; and (3) the salinity of the carrying fluid increased the bentonite deposition because of the shrinkage of the diffused electrical double layer and an increase in aggregation force, whereas it had little effect on kaolin deposition.

18.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35048121

RESUMO

Advancement in single-cell RNA sequencing leads to exponential accumulation of single-cell expression data. However, there is still lack of tools that could integrate these unlimited accumulations of single-cell expression data. Here, we presented a universal approach iSEEEK for integrating super large-scale single-cell expression via exploring expression rankings of top-expressing genes. We developed iSEEEK with 11.9 million single cells. We demonstrated the efficiency of iSEEEK with canonical single-cell downstream tasks on five heterogenous datasets encompassing human and mouse samples. iSEEEK achieved good clustering performance benchmarked against well-annotated cell labels. In addition, iSEEEK could transfer its knowledge learned from large-scale expression data on new dataset that was not involved in its development. iSEEEK enables identification of gene-gene interaction networks that are characteristic of specific cell types. Our study presents a simple and yet effective method to integrate super large-scale single-cell transcriptomes and would facilitate translational single-cell research from bench to bedside.


Assuntos
Análise de Célula Única , Transcriptoma , Animais , Análise por Conglomerados , Redes Reguladoras de Genes , Camundongos , Análise de Célula Única/métodos , Sequenciamento Completo do Exoma
19.
Eur J Hum Genet ; 30(3): 349-362, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35027648

RESUMO

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Teorema de Bayes , Carcinoma Epitelial do Ovário/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco
20.
Org Biomol Chem ; 20(6): 1299-1305, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35072680

RESUMO

The synergistic chemotherapy and photodynamic therapy (PDT) may significantly improve the cancer therapeutic efficacy, in which fluorinated nanoemulsions are highly advantageous for their ability to deliver oxygen to hypoxic tumors and provide fluorine-19 magnetic resonance imaging (19F MRI). The low solubility of chemotherapy drugs and photosensitizers in current perfluorocarbon (PFC)-based 19F MRI agents usually leads to complicated formulations or chemical modifications and low nanoemulsion stability and performance. Herein, we employ readily available partially fluorinated ethyl 2-(3,5-bis(trifluoromethyl)phenyl)acetate as the 19F MRI agent and the solvent to dissolve the cancer stem cell inhibitor salinomycin and the photosensitizer ICG for the convenient preparation of 19F MRI-fluorescence dual imaging and synergistic chemotherapy, photothermal and photodynamic therapy nanoemulsions. The chemotherapy drug salinomycin has a high solubility in the partially fluorinated reagent, facilitating its high loading and efficient delivery. Paramagnetic iron(III) (Fe3+) is incorporated into the nanoemulsion through the dissolved chelator to significantly improve the 19F MRI sensitivity. Furthermore, the dissolved fluorinated 2-pyridone enables the efficient capture and sustained release of singlet oxygen in the dark for high PDT efficacy. The multifunctional nanoemulsions show sensitive 19F MRI and fluorescence dual imaging capability and high synergistic chemotherapy, photothermal and photodynamic therapy efficacy in cancer cells, which may be valuable oxygen delivery, sustained ROS generating and release, dual imaging and multimodal therapy agents for hypoxic tumors. This study provided a convenient co-solubilization strategy for the rapid construction of multifunctional theranostics for hypoxic tumors.


Assuntos
Fotoquimioterapia
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