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1.
J Pharm Biomed Anal ; 245: 116146, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631069

RESUMO

Thymidine kinase 1 (TK1) is a marker of cell proliferation that can be used for early screening, treatment monitoring, and evaluating the prognosis of patients with tumors. The main purpose of this study was to develop clinically applicable TK1 antibodies, establish an appropriate detection method, and provide material and technical support for the research and clinical application for different types of tumors. Experimental mice were immunized with the C-terminal 31 peptide of human TK1 to screen monoclonal cell lines capable of stably secreting specific antibodies. Monoclonal antibodies were then prepared, purified and screened for optimal pairing following the identification of purity and isotype. Finally, based on the principles adopted by the double-antibody sandwich detection method, we constructed a lateral flow immunochromatographic assay (LFIA) to quantify the concentration of TK1 in serum samples when using a gold nanoparticle-labeled anti-TK1 monoclonal antibody as a probe. The limit of detection for TK1 in serum was 0.31 pmol/L with a detection range of 0.31-50 pmol/L. The spiked recoveries ranged from 97.7% to 109.0% with an analytical precision of 5.7-8.2%; there was no cross-reactivity with common proteins in the serum. The established LFIA also exhibited good consistency with commercially available chemiluminescent immunoassay kits for the detection of clinical samples. The LFIA developed in this study has the advantages of high sensitivity, accuracy, reproducibility and strong specificity, and provides a new technical tool for the quantitative detection of TK1.

2.
Analyst ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563739

RESUMO

Avian leukemia is an infectious tumorous disease of chickens caused by subgroup A of the avian leukemia virus (ALV-A), which mainly causes long-term viremia, slow growth, immune suppression, decreased production performance, multi-tissue tumors, and even death. The infection rate of this disease is very high in chicken herds in China, causing huge economic losses to the poultry industry every year. We successfully expressed the specific antigen protein of ALV (P27) through recombinant protein technology and screened a pair of highly sensitive monoclonal antibodies (mAbs) through mouse immunity, cell fusion, and antibody pairing. Based on this pair of antibodies, we established a dual antibody sandwich ELISA and gold nanoparticle immunochromatographic strip (AuNP-ICS) detection method. In addition, the parameters of the dual antibody sandwich ELISA and AuNP-ICS were optimized under different reaction conditions, which resulted in the minimum detection limits of 0.2 ng mL-1 and 1.53 ng ml-1, respectively. Commonly available ELISA and AuNP-ICS products on the market were compared, and we found that our established immune rapid chromatography had higher sensitivity. This established AuNP-ICS had no cross-reactivity with Influenza A (H1N1), Influenza A (H9N2), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), Listeria monocytogenes listeriolysin (LLO), and Staphylococcal enterotoxin SED or SEC. Finally, the established AuNP-ICS was used to analyze 35 egg samples, and the results showed 5 positive samples and 30 negative samples. The AuNP-ICS rapid detection method established by our group had good specificity, high sensitivity, and convenience, and could be applied to the clinical sample detection of ALV-A.

3.
Mater Today Bio ; 26: 101038, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38638704

RESUMO

The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasis-based regulatory implant biomaterials.

4.
Nat Commun ; 15(1): 3382, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643164

RESUMO

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Microambiente Tumoral , Organoides/patologia , Medicina de Precisão/métodos
5.
Cancer Cell Int ; 24(1): 119, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38553712

RESUMO

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

6.
Front Pharmacol ; 15: 1299213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482054

RESUMO

Background: Despite the widespread adoption of COVID-19 vaccination, a comprehensive understanding of potential vaccine-induced adverse effects, particularly in the context of pregnancy, remains a critical area of investigation. Elevated concerns surround the maternal and neonatal outcomes subsequent to prenatal maternal COVID-19 vaccination. While existing studies have provided insights into the safety profile of COVID-19 mRNA vaccines, the extrapolation of these conclusions to inactivated COVID-19 vaccines poses uncertainties. Notably, limited data are available regarding the maternal and neonatal effects associated with inactivated COVID-19 vaccines. Objective: To evaluate the prenatal maternal inactivated COVID-19 vaccination and the impact on maternal and neonatal outcomes. Methods: This was a retrospective cohort study of women who delivered between January and June 2022 at a single university-affiliated hospital. Those who have completed at least one dose of inactivated vaccine before or during pregnancy were included in "vaccinated group," and those who were not vaccinated were included in "unvaccinated group," the maternal, pregnancy and neonatal outcomes were evaluated. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups. Results: A total of 1926 women were enrolled in this study, 827 (42.94%) women were prenatally vaccinated, and 1099 (57.06%) unvaccinated. The gestational week of delivery were slightly lower in the vaccinated group, 38.61 ± 1.89 weeks in the vaccinated group and 38.93 ± 1.49 weeks in the unvaccinated group. There was a higher rate of overall preterm delivery in the vaccinated group (aOR 1.61, 95% CI 1.07-2.42; p = 0.02), however, the probability of delivery before 34 weeks and before 32 weeks (early preterm delivery) were similar (p > 0.05). A total of 2009 infants were born, 851 in the vaccinated group and 1158 in the unvaccinated group. There were similar neonatal outcomes in the two groups. Conclusion: Although we found a slightly lower gestational week of delivery and a possible increased rate of late preterm birth in the vaccination group, there was no difference in mean neonatal weight, incidence of low birth weight infants and other neonatal adverse complications. Meanwhile, there was no difference in pregnancy and maternal outcomes between the two groups.

7.
J Agric Food Chem ; 72(10): 5307-5317, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426871

RESUMO

Many endeavors in expressing a heterologous gene in microbial hosts rely on simply placing the gene of interest between a selected pair of promoters and terminator. However, although the expression efficiency could be improved by engineering the host cell, how modifying the expression cassette itself systematically would affect heterologous gene expression remains largely unknown. As the promoter and terminator bear plentiful cis-elements, herein using the Aspergillus niger mannanase with high application value in animal feeds and the eukaryotic filamentous fungus workhorse Trichoderma reesei as a model gene/host, systematic engineering of an expression cassette was investigated to decipher the effect of its mutagenesis on heterologous gene expression. Modifying the promoter, signal peptide, the eukaryotic-specific Kozak sequence, and the 3'-UTR could stepwise improve extracellular mannanase production from 17 U/mL to an ultimate 471 U/mL, representing a 27.7-fold increase in expression. The strategies can be generally applied in improving the production of heterologous proteins in eukaryotic microbial hosts.


Assuntos
Hypocreales , Trichoderma , Regiões Promotoras Genéticas , Expressão Gênica , Trichoderma/metabolismo
8.
Adv Sci (Weinh) ; : e2400117, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477430

RESUMO

Ionic liquid salts (ILs) are generally recognized as additives in perovskite precursor solutions to enhance the efficiency and stability of solar cells. However, the success of ILs incorporation as additives is highly dependent on the precursor formulation and perovskite crystallization process, posing challenges for industrial-scale implementation. In this study, a room-temperature spin-coated IL, n-butylamine acetate (BAAc), is identified as an ideal passivation agent for formamidinium lead iodide (FAPbI3 ) films. Compared with other passivation methods, the room-temperature BAAc capping layer (BAAc RT) demonstrates more uniform and thorough passivation of surface defects in the FAPbI3 perovskite. Additionally, it provides better energy level alignment for hole extraction. As a result, the champion n-i-p perovskite solar cell with a BAAc capping layer exhibits a power conversion efficiency (PCE) of 24.76%, with an open-circuit voltage (Voc) of 1.19 V, and a Voc loss of ≈330 mV. The PCE of the perovskite mini-module with BAAc RT reaches 20.47%, showcasing the effectiveness and viability of this method for manufacturing large-area perovskite solar cells. Moreover, the BAAc passivation layer also improves the long-term stability of unencapsulated FAPbI3 perovskite solar cells, enabling a T80 lifetime of  3500 h when stored at 35% relative humidity at room temperature in an air atmosphere.

9.
Heliyon ; 10(5): e27351, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463805

RESUMO

Older adults with chronic illness, as well as their primary caregivers in multigenerational families, may experience a complex interplay of factors that affect their quality of life (QOL). However, this interplay is not yet well-characterized for Chinese multigenerational families in particular. In this study, we analyzed how family resilience and social support affect the QOL of both older adults and caregivers in multigenerational Chinese families specifically. We enrolled 258 pairs of older adults with chronic illness and their primary caregivers in a multicenter cross-sectional study conducted in southern China in December 2021. Using the Actor-Partner Interdependence Model (APIM), we then examined the correlation between family resilience, social support, and QOL in dyadic analysis and found that QOL, family resilience, and social support for primary caregivers were better than those of older adults with chronic illness (t = 3.66-16.3, p<0.01). These factors were found to be positively correlated (r = 0.22-0.60, p<0.05), except for the family resilience of primary caregivers and the QOL of older adults with chronic illness (r = -0.14, p = 0.04). Additionally, actor effect results showed that when a dyadic member has high family resilience and objective social support, they tend to have a better QOL (ß = 0.5-1.48, P < 0.01). However, partner effect results showed that when the primary caregiver has high family resilience, this is associated with a worse QOL for the older adult (ß = -1.06, P < 0.01). Furthermore, we found that objective social support of dyads does not significantly influence their partner's QOL (ß = 0.88/0.31, P>0.05) for any pair. This suggests that medical staff should pay attention to the impact of family resilience on the QOL of older adult and caregiver dyads and explore health management plans that focus on binary coping in multigenerational families.

10.
PLoS One ; 19(3): e0294758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427701

RESUMO

The multiple global environments have triggered changes in the international environment, leading to a sharp decline of foreign direct investment (FDI) compared to pre-pandemic level. To evaluate the investment risk of FDI and make optimal investment decision becomes the most important issue for investors. This paper focuses on the evaluation of investment risk for FDI. First, an index system for risk evaluation of FDI is constructed. Then, we introduce the probabilistic linguistic entropy and cross entropy measures, based on which, a programming model is developed to identify the objective attribute weights. A composite weight derivation method, which takes both the objective attribute weights and the subjective attribute weights into account, is further introduced. In view of attributes' uncertainty and fuzziness and the conflicting characteristics of some attributes, the VIKOR (the Serbian name: VlseKriterijumska Optimizacija I Kompromisno Resenje, means multi-criteria optimization and compromise solution) method is used to evaluate the risk of FDI under the probabilistic linguistic environment. Furthermore, a case study is presented to illustrate the proposed method. The comparative analysis and some further discussions verify the validity of the proposed method for the FDI risk evaluation.


Assuntos
Linguística , Incerteza , Entropia
11.
Environ Pollut ; 348: 123776, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38492750

RESUMO

The International Agency for Research on Cancer (IARC) classifies PFOA as a Class 1 carcinogen. Here, a new naked-eye PFOA immunochromographic strip was developed to recognize PFOA in domestic water and real human samples within 10 min based on a novel custom designed anti-PFOA monoclonal antibody (mAb) 2A3, which was firstly an immune rapid detection method for PFOA has been proposed. Using computer simulation techniques such as quantum computing to assist in designing the structural formula of PFOA semi antigen, which hapten was firstly proposed. The half maximal inhibitory concentration of PFOA monoclonal antibody (mAb) 2A3 was 2.4 µg/mL. Using mAb 2A3, we developed an immunochromatographic strip (ICS) for detecting PFOA in real samples. The developed method generated results in 10 min, with visual detection limits of 20, 20, and 200 µg/mL and limit of detection of 50, 200, and 500 µg/mL for water, blood and urine samples, respectively. The established ICS and indirect competitive enzyme-linked immunosorbent assay were used to analyze the actual samples, and the results were confirmed by LC-MS/MS. Our study findings showed that the ICS and ic-ELISA can quickly detect PFOA in actual samples.


Assuntos
Caprilatos , Metodologias Computacionais , Fluorocarbonos , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Simulação por Computador , Teoria Quântica , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática/métodos , Limite de Detecção
12.
Proc Natl Acad Sci U S A ; 121(13): e2310469121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38502692

RESUMO

The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. L-penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC50) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC50 values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.


Assuntos
COVID-19 , Coronavirus Humano OC43 , Humanos , Animais , Camundongos , SARS-CoV-2/genética , Anticorpos/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico
13.
J Colloid Interface Sci ; 662: 727-737, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377692

RESUMO

Improving the separation efficiency of photogenerated carriers plays an important role in photocatalysis. In this study, two-dimensional (2D)/2D zinc indium sulfide (ZnIn2S4)/bismuth titanate (Bi4Ti3O12) nanoplate heterojunctions were synthesized to alter the Bi4Ti3O12 morphology, modulate the bandgap of Bi4Ti3O12, and enhance the utilization of light. Meanwhile, the construction of the S-scheme heterojunction establishes an internal electric field at the ZnIn2S4/Bi4Ti3O12 heterojunctions interface and achieves the spatial separation of photogenerated charges. The hydrogen production rate of ZnIn2S4/Bi4Ti3O12 nanoplate with the optimal ratio reaches 27.50 mmol h-1 g-1, which is 1.5 times higher than that of ZnIn2S4/Bi4Ti3O12 nanoflower (18.28 mmol h-1 g-1) and 2.4 times higher than that of ZnIn2S4 (11.69 mmol h-1 g-1). The apparent quantum efficiency of ZnIn2S4/Bi4Ti3O12 nanoplate reached 57.9 % under a single wavelength of light at 370 nm. This work provides insights into the study of new materials for photocatalytic hydrogen production.

14.
Transl Pediatr ; 13(1): 26-37, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38323184

RESUMO

Background: There is no relevant study on landmarks detection, one of the Convolutional Neural Network algorithms, in the field of fetal echocardiography (FE). This study aimed to explore whether automatic landmarks detection could be used in FE correctly and whether the atrial length (AL) to ventricular length (VL) ratio (AVLR) could be used to diagnose atrioventricular septal defect (AVSD) prenatally. Methods: This was an observational study. Two hundred and seventy-eight four-chamber views in end diastole, divided into the normal, AVSD, and differential diagnosis groups, were retrospectively included in this study. Seven landmarks were labeled sequentially by the experts on these images, and all images were divided into the training and test sets for normal, AVSD, and differential diagnosis groups. U-net, MA-net, and Link-net were used as landmark prediction neural networks. The accuracy of the landmark detection, AL, and VL measurements, as well as the prenatal diagnostic effectiveness of AVLR for AVSD, was compared with the expert labeled. Results: U-net, MA-net, and Link-net could detect the landmarks precisely (within the localization error of 0.09 and 0.13 on X and Y axis) and measure AL and VL accurately (the measured pixel distance error of AL and VL were 0.12 and 0.01 separately). AVLR in AVSD was greater than in other groups (P<0.0001), but the statistical difference was not obvious in the complete, partial, and transitional subgroups (P>0.05). The diagnostic effectiveness of AVLR calculated by three models, area under receiver operating characteristic curve could reach 0.992 (0.968-1.000), was consistent with the expert labeled. Conclusions: U-net, Link-net, and MA-net could detect landmarks and make the measurements accurately. AVLR calculated by three neural networks could be used to make the prenatal diagnosis of AVSD.

15.
Int Immunopharmacol ; 130: 111719, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38377854

RESUMO

Stress-induced immunosuppression (SIIS) can weaken the immune response effect of poultry vaccination, and bring huge hidden dangers and economic losses to the poultry industry. However, the detailed molecular mechanisms are still not fully understood. Unveiling the common mechanism of SIIS affecting the immune response to different vaccines is critical for detecting and minimizing the losses caused by SIIS. This study used glucocorticoid dexamethasone (Dex) to simulate SIIS, and three classic avian vaccines (including avian influenza virus (AIV), Newcastle disease virus (NDV), and infectious bursal disease virus (IBDV)) were used to induce immune responses in chicken. Quantitative real-time PCR (qRT-PCR) revealed the expression characteristics and functions of circMYO1B and miR-155 in the processes of SIIS affecting the immune response to the aforementioned avian vaccines, as well as their targeted regulatory relationship. Subsequent bioinformatics analysis predicted FOS, one of the potential target genes of miR-155. The results showed that circMYO1B/miR-155 pathway served as a key common mechanism by which SIIS affected the immune response to the three vaccines. Both heart and proventriculus appeared to be the crucial tissues for this process, with five days post immunization (dpi) emerging as the primary time of interest. Moreover, mitogen-activated protein kinase (MAPK) signaling system played a key role in modulating the immune response subsequent to SIIS administration. Our findings provide new insights into the immune function of competitive endogenous RNA (ceRNA), which have important function in the detection and treatment of SIIS affecting vaccine immunity.


Assuntos
Vacinas contra Influenza , MicroRNAs , Doenças das Aves Domésticas , Vacinas Virais , Animais , Galinhas , Terapia de Imunossupressão , Vírus da Doença de Newcastle , Imunidade , MicroRNAs/genética
16.
Food Chem ; 444: 138599, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38310776

RESUMO

As a widely used fungicide in agriculture, bitertanol (BIT) significantly affects hormone regulation leading to imbalance of homeostasis in vivo, which makes it necessary to monitor BIT residues in foods. In this research, a novel hapten derivation scheme was designed by analyzing the chemical structure of BIT to prepare an anti-BIT monoclonal antibody with high affinity, specificity and sensitivity (half inhibitory concentration of 4.78 ng/mL). Subsequently, a visualized gold immunochromatographic assay (GICA) platform was established based on antigen-antibody specific recognition, with a limit of detection of 0.06 mg/kg and 0.18 mg/kg in cucumber and tomato, respectively. GICA has spiked recoveries of 84.3 %-114.1 %, determines results are not significantly different from those of LC-MS/MS, and the complex purification treatments can be reduced during the detection process. Therefore, the developed GICA is a reliable, rapid, and sensitive method for on-site rapid monitoring of BIT in foods.


Assuntos
Compostos de Bifenilo , Ouro , Espectrometria de Massas em Tandem , Triazóis , Cromatografia Líquida , Imunoensaio/métodos , Cromatografia de Afinidade/métodos , Limite de Detecção
17.
Adv Healthc Mater ; : e2304125, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38301194

RESUMO

Disturbance in the mitochondrial electron transport chain (ETC) is a key factor in the emerging discovery of immune cell activation in inflammatory diseases, yet specific regulation of ETC homeostasis is extremely challenging. In this paper, a mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial "VI" complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis is creatively developed. MCBN is composed of bovine serum albumin (BSA), polyethylene glycol (PEG), and triphenylphosphine (TPP) hierarchically encapsulating MnO2 polycrystalline particles. It has nanoscale size and biological properties like natural complexes. In vivo and in vitro experiments confirm that MCBN can target the mitochondrial complexes of inflammatory macrophages, absorb excess electrons in ETC, and convert the electrons to decompose H2 O2 . By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF-κB signaling pathway, MCBN effectively suppresses macrophage M1 activation and inflammatory factor secretion. It also demonstrates good inflammation control and significantly alleviates alveolar bone loss in a mouse model of ligation-induced periodontitis. This is the first nanozyme that mimics the mitochondrial complex and regulates ETC, demonstrating the potential application of MCBN in immune diseases.

18.
Animals (Basel) ; 14(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38254394

RESUMO

Lipid metabolism plays an important role in maintaining lipid homeostasis and regulating immune functions. However, the regulations and mechanisms of lipid metabolism on the regional immune function of avian adipose tissue (AT) have not been reported. In this study, qRT-PCR was used to investigate the changes and relationships of different lipid metabolism pathways in chicken AT during stress-induced immunosuppression (SIIS) inhibiting immune response to Newcastle disease virus vaccine, then the miRNA regulation patterns of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene and its potential applications were further identified. The results showed that AT actively responded to SIIS, and ATGL, CPT1A and HMGCR were all the key genes involved in the processes of SIIS inhibiting the immune responses. SIIS significantly inhibited the natural and specific immune phases of the primary immune response and the initiation phase of the secondary immune response in AT by suppressing T cells by up-regulating steroid anabolism. Moreover, steroid metabolism could play dual roles in regulating the regional immune functions of AT. The miR-29a/c-3p-HMGCR network was a potential regulation mechanism of steroid metabolism in AT, and serum circulating miR-29a/c-3p had the potential as molecular markers. The study can provide valuable references for an in-depth investigation of the regional immune functions regulated by lipid metabolism in AT.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38281369

RESUMO

Imatinib is the tyrosine kinase inhibitor of choice for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. However, imatinib has drawbacks such as drug resistance and significant differences in pharmacokinetics within patients. Therefore, a colloidal gold-based immunochromatographic assay (CG-IA) was developed for measuring and monitoring imatinib in human serum. An imatinib derivative containing carboxyl groups was used for the synthesis of the immunogen, and 4-(4-methyl-1-piperazinylmethyl) benzoic acid was selected as the hapten for the heterologous coating antigen. Next, a highly sensitive and specific monoclonal antibody (mAb), 2F7 was screened for the construction of a CG-IA, with an IC50 value of 0.091 ng/mL. For the qualification of imatinib in human serum, the visual limit of detection (vLOD) and cut-off values of the CG-IA were 2 and 20 ng/mL, respectively. For quantitative detection, the calculated LOD value of the CG-IA was 0.068 ng/mL, with a linearity range of 1.004 and 23.087 ng/mL. The recovery rate of spiked serum samples was between 88.24 % and 104.75 %. In addition, the concentration of imatinib in the serum samples from 10 patients was detected by CG-IA and revealed a good correlation with those from LC-MS/MS. These results indicated that the developed gold-based paper sensor could become an effective tool for the rapid monitoring of imatinib in human serum samples.


Assuntos
Inibidores de Proteínas Quinases , Espectrometria de Massas em Tandem , Humanos , Mesilato de Imatinib , Cromatografia Líquida , Imunoensaio/métodos , Coloide de Ouro/química , Limite de Detecção , Cromatografia de Afinidade/métodos
20.
Environ Sci Technol ; 58(6): 2672-2682, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38290497

RESUMO

Flubendiamide (FLU), a widely used diamide insecticide, has been observed to potentiate adipogenesis in 3T3-L1 preadipocytes in vitro. Whether exposure to FLU disrupts hepatic lipid homeostasis in mammals and induces visceral obesity, however, remains unclear. The aim of this study was to assess the effects of FLU when administered orally to male C57BL/6J mice under normal diet (ND) and high-fat diet (HFD) conditions. FLU accumulated at higher levels in the tissues of the HFD group than those of the ND group, indicating that an HFD contributed to the accumulation of lipophilic pesticides in vivo. Notably, FLU (logP = 4.14) is highly lipophilic and easily accumulates in fat. Exposure to FLU had opposing effects on the lipid metabolism of the liver in the ND and HFD groups. Liver triacylglycerol levels in the ND group were reduced, while those in the HFD group were increased, resulting in more severe hepatic steatosis. More lipid accumulation was also observed in HepG2 cells exposed to FLU. Changes in hepatic lipid deposition in vivo occurred as the enhanced transcriptional regulation of the genes involved in lipid uptake, de novo lipogenesis, and fatty acid ß-oxidation (FAO). Moreover, an excessive increase in FAO caused oxidative stress, which in turn exacerbated the inflammation of the liver. This study revealed the disruptive effect of FLU exposure on hepatic lipid homeostasis, which may facilitate the triggering of nonalcoholic fatty liver disease in HFD-fed mice.


Assuntos
Fluorocarbonos , Hepatopatia Gordurosa não Alcoólica , Ftalimidas , Sulfonas , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Metabolismo dos Lipídeos , Lipídeos , Mamíferos
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