Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.590
Filtrar
1.
Plant Physiol Biochem ; 207: 108424, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335888

RESUMO

Gibberellic acid (GA) plays important roles in diverse biological processes in plants. However, its function in rice (Oryza sativa) resistance to saline-alkaline (SAK) stress is unclear. This study showed that SAK stimuli changed GA signaling gene expression levels. Genetic analyses using the mutants of key GA signaling regulators, Slender rice 1 (SLR1) and Dwarf 1(D1), demonstrated that SLR1 negatively, while D1 positively regulated the resistance of rice to SAK stress, suggesting that the GA signaling positively regulates the resistance of rice to SAK. Further analyses revealed that SLR1 interacted with and inhibited the transcription activation activity of IDD10 and bZIP23. Furthermore, IDD10 interacted with bZIP23 to activate Ammonium transporter 1;2 (AMT1;2), and slr1, IDD10 OX and bZIP23 OX accumulated more ammonium (NH4+), while idd10 and bzip23 accumulated less NH4+ than the wild-type (WT). In addition, the bzip23 mutant was more sensitive to SAK, while bZIP23 OX was less sensitive compared with the WT, suggesting that bZIP23 positively regulates the resistance of rice to SAK. These findings demonstrate that GA signaling promoted rice's SAK resistance by regulating NH4+ uptake through the SLR1-IDD10-bZIP23 pathway.

2.
Transplant Proc ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336485

RESUMO

Crohn disease (CD) is one of the most common causes of short bowel syndrome and intestinal failure. Intestinal transplantation (IT) is sometimes needed for patients with CD who develop intestinal failure after multiple intestinal resections resulting from CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been few case reports concerning the endoscopic surveillance of patients with CD after IT. In this article, we present 2 patients with CD who underwent IT because of short bowel syndrome with intestinal failure. We administered posttransplantation immunosuppressants and conducted regular follow-up magnifying endoscopy with narrow-band imaging (ME-NBI). Both cases demonstrated favorable outcomes after surveillance with ME-NBI. In this report, we outline our post-IT follow-up strategies applying the VENCH scoring system, which is based on endoscopic features using ME-NBI to predict graft rejection. Our approach could effectively distinguish between acute cellular rejection and non-rejection, particularly disease recurrence of underlying CD. This study was approved by the institutional review board of Far Eastern Memorial Hospital (FEMH-105023-F). The patients provided written informed consent for publication.

3.
Hum Mol Genet ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340456

RESUMO

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.

4.
J Imaging Inform Med ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366294

RESUMO

Computed tomography (CT) is the most commonly used diagnostic modality for blunt abdominal trauma (BAT), significantly influencing management approaches. Deep learning models (DLMs) have shown great promise in enhancing various aspects of clinical practice. There is limited literature available on the use of DLMs specifically for trauma image evaluation. In this study, we developed a DLM aimed at detecting solid organ injuries to assist medical professionals in rapidly identifying life-threatening injuries. The study enrolled patients from a single trauma center who received abdominal CT scans between 2008 and 2017. Patients with spleen, liver, or kidney injury were categorized as the solid organ injury group, while others were considered negative cases. Only images acquired from the trauma center were enrolled. A subset of images acquired in the last year was designated as the test set, and the remaining images were utilized to train and validate the detection models. The performance of each model was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value based on the best Youden index operating point. The study developed the models using 1302 (87%) scans for training and tested them on 194 (13%) scans. The spleen injury model demonstrated an accuracy of 0.938 and a specificity of 0.952. The accuracy and specificity of the liver injury model were reported as 0.820 and 0.847, respectively. The kidney injury model showed an accuracy of 0.959 and a specificity of 0.989. We developed a DLM that can automate the detection of solid organ injuries by abdominal CT scans with acceptable diagnostic accuracy. It cannot replace the role of clinicians, but we can expect it to be a potential tool to accelerate the process of therapeutic decisions for trauma care.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38367094

RESUMO

PURPOSE: High fasting plasma glucose (HFPG) has been identified as a risk factor for drug-resistant tuberculosis incidence and mortality. However, the epidemic characteristics of HFPG-attributable multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) remain unclear. We aimed to analyze the global spatial patterns and temporal trends of HFPG-attributable MDR-TB and XDR-TB from 1990 to 2019. METHODS: Utilizing data from the Global Burden of Disease 2019 project, annual deaths and disability-adjusted life years (DALYs) of HFPG-attributable MDR-TB and XDR-TB were conducted from 1990 to 2019. Joinpoint regression was employed to quantify trends over time. RESULTS: From 1990 to 2019, the deaths and DALYs due to HFPG-attributable MDR-TB and XDR-TB globally showed an overall increasing trend, with a significant increase until 2003 to 2004, followed by a gradual decline or stability thereafter. The low sociodemographic index (SDI) region experienced the most significant increase over the past 30 years. Regionally, Sub-Saharan Africa, Central Asia and Oceania remained the highest burden. Furthermore, there was a sex and age disparity in the burden of HFPG-attributable MDR-TB and XDR-TB, with young males in the 25-34 age group experiencing higher mortality, DALYs burden and a faster increasing trend than females. Interestingly, an increasing trend followed by a stable or decreasing pattern was observed in the ASMR and ASDR of HFPG-attributable MDR-TB and XDR-TB with SDI increasing. CONCLUSION: The burden of HFPG-attributable MDR-TB and XDR-TB rose worldwide from 1990 to 2019. These findings emphasize the importance of routine bi-directional screening and integrated management for drug-resistant TB and diabetes.

6.
Ann Hematol ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381172

RESUMO

We aimed to describe the clinical characteristics, particularly the occurrence and risk factors of severe/critical illness, in allogeneic hematopoietic stem cell (allo-HSCT) recipients infected with coronavirus disease 2019 (COVID-19) caused by Omicron variant in an observational prospective study (n = 311). The median time from allo-HSCT to COVID-19 diagnosis was 8.5 months (range 0.8-106.1) months. Four patients (1.3%) were reported to be asymptomatic during Omicron variant infection, and 135 (43.4%) patients showed lower respiratory tract disease. Thirty-four (10.9%) patients were categorized into serious infection (severe illness n = 25; critical illness n = 9) and the median duration from COVID-19 diagnosis to serious infections was 6 days (range, 0-29) days. Thirteen (4.2%) and 6 (1.9%) patients required intensive care unit care and invasive mechanical ventilation, respectively. Receiving more than 1 type of immunosuppressive therapies at COVID-19 diagnosis was associated with severity and persistence of infection. Six patients (1.9%) died after diagnosis of COVID-19 infection. The 4-week probability of overall survival after COVID-19 diagnosis was 98.7%, which was 100% and 88.2% for non-serious and serious infection group (P < 0.001), respectively. Thus, we observed a relatively low serious infection and mortality rate in allo-HSCT recipients infected with COVID-19 caused by Omicron variant.

7.
Foods ; 13(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38338561

RESUMO

In this study, resveratrol-loaded nano-emulsions were added to yogurts, improving the physicochemical properties and functional factors and realizing the development of nutrient-fortified yogurt. Yogurts added with free resveratrol (Y-R), resveratrol-loaded emulsions stabilized by sodium caseinate (Y-NN), decaglycerol monooleate (Y-DN), and sodium caseinate-decaglycerol monooleate (Y-DND) were evaluated for their physicochemical properties, including pH, titratable acidity, syneresis, and textural parameters, with 5-day intervals for 15-day storage. The resveratrol retention rate was analyzed in the Y-R, Y-NN, Y-DN, and Y-NDN groups during 15 days of storage. The dynamic bioaccessibility of resveratrol and the NMR-based nutritional profile of yogurt in the Y-R, Y-NN, Y-DN, and the Y-NDN group were investigated after in vitro digestion. The results demonstrated that the addition of resveratrol emulsion decreased the hardness of yogurt while evaluating its titratable acidity and water-holding capacity, which were characterized by high stability. The stability of resveratrol added in the form of an emulsion was significantly higher than that of the free form. Compared with the other groups, the yogurt formulated with sodium caseinate/decaglycerol monooleate (NaCas/DGMO) emulsion showed the highest resveratrol retention rate, about 70%. In vitro digestion showed that encapsulation effectively and persistently improved the dynamic bioaccessibility of resveratrol. Additionally, NMR-based nutritional profile analysis before and after in vitro digestion demonstrated that resveratrol emulsion nutritional fortification promoted the release of nutrients, improving the nutritional value of yogurt. These findings offered theoretical guidance and technical support for the use of resveratrol nano-emulsions in yogurt.

8.
Phys Eng Sci Med ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38361179

RESUMO

Hemodynamic parameters derived from pulse wave analysis have been shown to predict long-term outcomes in patients with heart failure (HF). Here we aimed to develop a deep-learning based algorithm that incorporates pressure waveforms for the identification and risk stratification of patients with HF. The first study, with a case-control study design to address data imbalance issue, included 431 subjects with HF exhibiting typical symptoms and 1545 control participants with no history of HF (non-HF). Carotid pressure waveforms were obtained from all the participants using applanation tonometry. The HF score, representing the probability of HF, was derived from a one-dimensional deep neural network (DNN) model trained with characteristics of the normalized carotid pressure waveform. In the second study of HF patients, we constructed a Cox regression model with 83 candidate clinical variables along with the HF score to predict the risk of all-cause mortality along with rehospitalization. To identify subjects using the HF score, the sensitivity, specificity, accuracy, F1 score, and area under receiver operating characteristic curve were 0.867, 0.851, 0.874, 0.878, and 0.93, respectively, from the hold-out cross-validation of the DNN, which was better than other machine learning models, including logistic regression, support vector machine, and random forest. With a median follow-up of 5.8 years, the multivariable Cox model using the HF score and other clinical variables outperformed the other HF risk prediction models with concordance index of 0.71, in which only the HF score and five clinical variables were independent significant predictors (p < 0.05), including age, history of percutaneous coronary intervention, concentration of sodium in the emergency room, N-terminal pro-brain natriuretic peptide, and hemoglobin. Our study demonstrated the diagnostic and prognostic utility of arterial waveforms in subjects with HF using a DNN model. Pulse wave contains valuable information that can benefit the clinical care of patients with HF.

9.
Diabetes Res Clin Pract ; 209: 111585, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364910

RESUMO

AIMS: This study explores the link between Vitamin D deficiency (VDD) and diabetic peripheral neuropathy (DPN) in elderly type 2 diabetes mellitus (T2DM) patients. METHODS: Involving 257 elderly T2DM patients, the study utilized propensity score matching to balance age, sex, and diabetes duration. VDD was defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 20 ng/ml. Large nerve fiber lesions were evaluated by electromyogram, while small nerve fiber lesions were assessed by measuring skin conductance. RESULTS: DPN patients had notably lower serum 25(OH)D levels than non-DPN patients [15.05 vs. 18.4 ng/ml, P = 0.018]. VDD was identified as an independent risk factor for DPN (odds ratio = 2.488, P = 0.008) in multivariate logistic regression analysis. Spearman's correlation showed negative correlations between serum 25(OH)D levels and specific nerve latencies, and positive correlations with specific nerve velocities and amplitudes. The VDD group exhibited longer median sensory nerve latencies and motor evoked potential latencies compared to the vitamin D-sufficient group. Further, VDD is associated with the prolongation of the median motor nerve latency (odds ratio = 1.362, P = 0.038). CONCLUSIONS: VDD is independently associated with a higher risk of DPN. VDD may promote the development of DPN by affecting large nerve fibers.

10.
Front Immunol ; 15: 1340224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348025

RESUMO

Purpose: To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. Design: Prospective, cross-sectional, observational study. Participants and controls: Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. Methods: Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. Main outcome measures: OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. Results: A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. Conclusion: Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.


Assuntos
Retinopatia Diabética , Lúpus Eritematoso Sistêmico , Doenças Retinianas , Humanos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Estudos Transversais , Estudos Prospectivos , Retinopatia Diabética/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Retina/diagnóstico por imagem , Doenças Retinianas/etiologia , Doenças Retinianas/patologia , Lúpus Eritematoso Sistêmico/patologia
11.
J Hazard Mater ; 467: 133738, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38350317

RESUMO

Little information is available on how boron (B) supplementation affects plant cell wall (CW) remodeling under copper (Cu) excess. 'Xuegan' (Citrus sinensis) seedlings were submitted to 0.5 or 350 µM Cu × 2.5 or 25 µM B for 24 weeks. Thereafter, we determined the concentrations of CW materials (CWMs) and CW components (CWCs), the degree of pectin methylation (DPM), and the pectin methylesterase (PME) activities and PME gene expression levels in leaves and roots, as well as the Cu concentrations in leaves and roots and their CWMs (CWCs). Additionally, we analyzed the Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectra of leaf and root CWMs. Our findings suggested that adding B reduced the impairment of Cu excess to CWs by reducing the Cu concentrations in leaves and roots and their CWMs and maintaining the stability of CWs, thereby improving leaf and root growth. Cu excess increased the Cu fractions in leaf and root pectin by decreasing DPM due to increased PME activities, thereby contributing to citrus Cu tolerance. FTIR and XRD indicated that the functional groups of the CW pectin, hemicellulose, cellulose, and lignin could bind and immobilize Cu, thereby reducing Cu cytotoxicity in leaves and roots.

12.
Opt Express ; 32(3): 3379-3393, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297560

RESUMO

In contrast to conventional emitters fashioned from traditional materials, tunable thermal emitters exhibit a distinct propensity to fulfill the demands of diverse scenarios, thereby engendering an array of prospects within the realms of communications, military applications, and control systems. In this paper, a tunable thermal emitter without continuous external excitation is introduced using Ge2Sb2Te5 (GST) and high-temperature-resistant material Mo. It is automatically optimized by inverse design with genetic algorithm (GA) to switch between different functions according to the object temperature to adapt to diverse scenarios. In "off" mode, the emitter orchestrates a blend of infrared (IR) stealth and thermal management. This is evidenced by average absorptivity values of 0.08 for mid-wave infrared (MIR, 3-5 µm), 0.19 for long-wave infrared (LIR, 8-14 µm), and 0.68 for the non-atmospheric window (NAW, 5-8 µm). Conversely, when confronted with high-temperature entities, the emitter seamlessly transitions to "on" mode, instigating a process of radiative cooling. This transformation is reflected in the augmented emissivity of the dual-band atmospheric window including MIR and LIR, attaining peak values of 0.96 and 0.97. This transition yields a cooling potential, quantified at 64 W/m2 at the ambient temperature of 25°C. In addition, our design employs a layered structure, which avoids complex patterned resonators and facilitates large-area fabrication. The emitter in this paper evinces robust insensitivity to polarization variations and the angle of incidence. We believe that this work will contribute to the development in the fields of dynamic tunability for IR stealth, dynamic radiative cooling systems, and thermal imaging.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38298177

RESUMO

CONTEXT: Dysthyroid optic neuropathy (DON) is a serious vision-threatening complication of thyroid-associated ophthalmopathy (TAO). Exploration of the underlying mechanisms of DON is critical for its timely clinical diagnosis. OBJECTIVE: We hypothesized that TAO patients with DON may have altered brain functional networks. We aimed to explore the alterations of static and dynamic functional connectomes in patients with and without DON using resting-state functional MRI with graph theory method. DESIGN: A cross-sectional study. SETTING: Grade A tertiary hospital. PARTICIPANTS: Sixty-six TAO patients (28 DON and 38 non-DON) and 30 healthy controls (HCs). MAIN OUTCOME MEASURES: Topological properties of functional networks. RESULTS: For static properties, DON patients exhibited lower global efficiency (Eg), local efficiency, normalized clustering coefficient, small-worldness (σ), and higher characteristic path length (Lp) than HCs. Both DON and non-DON patients exhibited varying degrees of abnormalities in nodal properties. Meanwhile, compared with non-DON, DON patients exhibited abnormalities in nodal properties in orbitofrontal cortex and visual network (VN). For dynamic properties, DON group exhibited higher variance in Eg and Lp than non-DON and HC groups. A strengthened subnetwork with VN as the core was identified in DON cohort. Significant correlations were found between network properties and clinical variables. For distinguishing DON, the combination of static and dynamic network properties exhibited optimal diagnostic performance. CONCLUSION: Functional network alterations were observed in both DON and non-DON patients, providing novel insights into the underlying neural mechanisms of disease. Functional network properties may be potential biomarkers for reflecting the progression of TAO from non-DON to DON.

14.
Heliyon ; 10(2): e24394, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38312638

RESUMO

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

15.
Cell Commun Signal ; 22(1): 95, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308318

RESUMO

BACKGROUND: The remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration. METHODS: The model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1). RESULTS: Tet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly. CONCLUSION: Our findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Regeneração Hepática/fisiologia , Carcinoma Hepatocelular/metabolismo , Ativação de Macrófagos , Neoplasias Hepáticas/metabolismo , Hepatectomia , Fígado/metabolismo , Hepatócitos/metabolismo , Proliferação de Células
16.
Adv Mater ; : e2307454, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299428

RESUMO

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2 ) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.

17.
Chin Med Sci J ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38384000

RESUMO

Objective To explore the influence of extracellular matrix protein ABI3BP on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway. Methods The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels. Results The VSV-GFP-infected BJ-5ta cell model was successfully established. Efficient knockdown of ABI3BP on BJ-5ta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 - 3.5 times (P<0.01) and 2.2 - 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expressions of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, were significantly decreased in ABI3BP knockdown cells after VSV-GFP infection. Conclusion Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 125-131, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387910

RESUMO

OBJECTIVE: To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase (BTK) inhibitor in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL). METHODS: The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively. The clinical characteristics of patients and effect of chemotherapy regimen on efficacy, overall survival (OS) and progression-free survival (PFS) were observed. RESULTS: The median age of the patients was 58(56-61) years old, and male to female ratio was about 2.9∶1. Patients with Ann Arbor stage III-IV accounted for 77.6%, extranodal involvement > 2 for 43.3%, bone marrow involvement for 60.4%, gastrointestinal involvement for 24.6%, and hepatosplenomegaly for 38.1%. The median follow-up time was 30 (2-103) months, overall response rate (ORR) was 41.8%, 3-year PFS was not reached, and 3-year and 5-year OS rate was 62.7% and 53.8%, respectively. The ORR of BTK inhibitor group was 56.9%, which was higher than 32.5% of non-BTK inhibitor group (P =0.006). The difference was statistically significant in PFS between the two groups (P =0.002), but was not in OS (P>0.05). The difference was statistically significant in OS between classical and special morphology (P < 0.001), but was not in PFS (P >0.05). Ki-67 was an influencing factor for OS and PFS. Multivariate analysis showed that Ki-67, B symptoms, MIPI score, and Ann Arbor stage were independent prognostic factors affecting patients' OS. The second-line treatment regimen was an independent prognostic factor affecting patients' PFS. CONCLUSIONS: The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients. Ki-67, B symptoms, MIPI score, and Ann Arbor stage are independent prognostic factors for R/R MCL patients.

19.
Microb Pathog ; 187: 106535, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176463

RESUMO

Tuberculosis remains a threat to public health. The only approved vaccine, Bacillus Calmette-Guérin (BCG), is administered intradermally and provides limited protection, and its effect on innate immunity via the respiratory route has not been fully elucidated. A mouse model with genetically depleted TREM1 and seven-color flow cytometry staining were used to characterize the comprehensive immune response induced by respiratory BCG, through evaluating organ bacterial loads, lung histopathology, and lung immunohistochemistry. During respiratory BCG infection, the murine lungs displayed effective bacterial clearance. Notably, marked differences in neutrophils were observed between thymus and bone marrow cells, characterized by a significant increase in the expression of the triggering receptor expressed on myeloid cells 1 (TREM1). Subsequently, upon depletion of TREM1, a reduction in pulmonary neutrophils was observed, which further exacerbated bacterial loads and resulted in worsened pathology following respiratory BCG infection. In summary, up-regulated expression of TREM1 in rapidly increasing circulating neutrophil by pulmonary BCG is required for an efficient host response to BCG infection, and suggests the important role of TREM1 in neutrophil-related pulmonary bacteria clearance and pathology.


Assuntos
Bacillus , Mycobacterium bovis , Animais , Camundongos , Vacina BCG , Pulmão/patologia , Neutrófilos , Receptor Gatilho 1 Expresso em Células Mieloides
20.
Int J Biol Macromol ; 259(Pt 2): 129208, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185298

RESUMO

The Staphylococcus aureus clumping factor A (ClfA) is a fibrinogen (Fg) binding protein that plays an important role in the clumping of S. aureus in blood plasma. The current anti-infective approaches targeting ClfA are mainly based on monoclonal antibodies but showed less impressive efficacy for clinical applications. Nanobodies offer advantages in enhanced tissue penetration and a propensity to bind small epitopes. However, there is no report on generating specific nanobodies for ClfA. Here, we constructed a synthetic nanobody library based on yeast surface display to isolate nanobodies against the Fg binding domain ClfA221-550. We firstly obtained a primary nanobody directed to ClfA221-550, and then employed error-prone mutagenesis to enhance its binding affinity. Finally, 18 variants were isolated with high affinities (EC50, 1.1 ± 0.1 nM to 4.8 ± 0.3 nM), in which CNb1 presented the highest inhibition efficiency in the adhesion of S. aureus to fibrinogen. Moreover, structural simulation analysis indicated that the epitope for CNb1 partially overlapped with the binding sites for fibrinogen, thus inhibiting ClfA binding to Fg. Overall, these results indicated that the specific nanobodies generated here could prevent the adhesion of S. aureus to fibrinogen, suggesting their potential capacities in the control of S. aureus infections.


Assuntos
Anticorpos de Domínio Único , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Saccharomyces cerevisiae/metabolismo , Anticorpos de Domínio Único/metabolismo , Sítios de Ligação , Fibrinogênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...