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1.
Environ Pollut ; 330: 121760, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37142210

RESUMO

Phthalates exposure is linked with cardiovascular disease. Decreased heart rate variability (HRV) is an early indicator of cardiac autonomic imbalance. We conducted a longitudinal panel study in 127 Chinese adults with 3 repeated visits to explore the associations of individual and mixtures of phthalates exposure with HRV. We quantified 10 urinary phthalate metabolites by gas chromatograph-tandem mass spectrometer (GC-MS/MS) and 6 HRV indices by 3-channel digital Holter monitors. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) models were separately implemented to evaluate the associations. After multivariate adjustments, we found that urinary mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MBP) at lag 0 day were inversely associated with low-frequency power (LF) or total power (TP) (all P-FDR <0.05). In mixture analysis, we observed negative overall associations of phthalate mixtures at lag 0 day with LF or TP, and MiBP was the major contributor. Moreover, stratified analysis suggested that the inverse relationships of MiBP at lag 0 day with LF and TP were more prominent in subjects aged >50 years (all Pinteraction < 0.01). Our findings revealed that exposure to individual and mixtures of phthalates, especially MiBP, were related to decreased HRV.

2.
Polymers (Basel) ; 15(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37177263

RESUMO

Understanding how to develop highly efficient and robust adsorbents for the removal of organic dyes in wastewater is crucial in the face of the rapid development of industrialization. Herein, d-Ti3C2Tx nanosheets (MXene) were combined with sodium alginate (SA), followed by electrospinning and successive Ca2+-mediated crosslinking, giving rise to a series of SA/MXene nanofiber membranes (NMs). The effects of the MXene content of the NMs on the adsorption performance for methylene blue (MB) were investigated systemically. Under the optimum MXene content of 0.74 wt.%, SA/MXene NMs possessed an MB adsorption capacity of 440 mg/g, which is much higher than SA/MXene beads with the same MXene content, pristine MXene, or electrospinning SA NMs. Furthermore, the optimum SA/MXene NMs showed excellent reusability. After the adsorbent was reused ten times, both the MB adsorption capacity and removal rate could remain at 95% of the levels found in the fresh samples, which indicates that the electrospinning technique has great potential for developing biomass-based adsorbents with high efficiency.

3.
J Autoimmun ; 138: 103048, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37216870

RESUMO

Metabolic reprogramming plays a pivotal role in the differentiation and function of immune cells including dendritic cells (DCs). Regulatory DCs can be generated in regional tissue niches like splenic stroma and act as an important part of stromal control of immune response for the maintenance of immune tolerance. However, the metabolic alterations during splenic stroma-driven regulatory DCs differentiation and the metabolic enzyme involved in regulatory DCs function remain poorly understood. By combining metabolomic, transcriptomic, and functional investigations of mature DCs (maDCs) and diffDCs (regulatory DCs differentiated from activated mature DCs through coculturing with splenic stroma), here we identified succinate-CoA ligase subunit beta Suclg2 as a key metabolic enzyme that reprograms the proinflammatory status of mature DCs into a tolerogenic phenotype via preventing NF-κB signaling activation. diffDCs downregulate succinic acid levels and increase the Suclg2 expression along with their differentiation from mature DCs. Suclg2-interference impaired the tolerogenic function of diffDCs in inducing T cell apoptosis and enhanced activation of NF-κB signaling and expression of inflammatory genes CD40, Ccl5, and Il12b in diffDCs. Furthermore, we identified Lactb as a new positive regulator of NF-κB signaling in diffDCs whose succinylation at the lysine 288 residue was inhibited by Suclg2. Our study reveals that the metabolic enzyme Suclg2 is required to maintain the immunoregulatory function of diffDCs, adding mechanistic insights into the metabolic regulation of DC-based immunity and tolerance.

4.
Retina ; 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37224445

RESUMO

PURPOSE: To report the clinical profile and outcomes of acute Vogt-Koyanagi-Harada (VKH) disease with a strict immunosuppression regimen and investigate the risk factors for a prolonged disease course. METHODS: A total of 101 patients with acute VKH (202 eyes) with more than 24 months of follow-up were recruited from January 2011 to June 2020. They were divided into two groups according to the interval between the onset of VKH and treatment. Oral prednisone was gradually tapered off by a diminished dose according to a relatively strict protocol. Patient responses to the treatment regimen were classified as long-term drug-free remission or chronic recurrent. RESULTS: Ninety-six patients (95.0%) achieved long-term drug-free remission without recurrence, while 5 (5.0%) had chronic recurrence. Most patients achieved good best-corrected visual acuity (90.6%≧20/25). A generalized estimation equation model demonstrated that time of visit, ocular complications, and cigarette smoking were independent risk factors for a longer disease course, and smokers required a higher drug dose and longer treatment course than non-smokers. CONCLUSIONS: An immunosuppressive regimen with an appropriate tapering speed can lead to long-term drug-free remission in patients with acute VKH. Cigarette smoking significantly affects ocular inflammation.

5.
J Med Virol ; 95(5): e28797, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37218584

RESUMO

The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T1 ), 180 days after the second dose (T2 ) and 35 days after the third dose (T3 ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T1 , T2 , and T3 time periods were analyzed, and the effects of age, vaccine brand, and CD4+ T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4+ T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.


Assuntos
Formação de Anticorpos , COVID-19 , Humanos , Vacinas contra COVID-19 , Estudos Soroepidemiológicos , COVID-19/prevenção & controle , Imunoglobulina G , Anticorpos Antivirais , Anticorpos Neutralizantes
6.
Molecules ; 28(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37175248

RESUMO

Low-density lipoprotein receptor-related protein 6 (LRP6), a member of the low-density lipoprotein receptor (LDLR) family, displays a unique structure and ligand-binding function. As a co-receptor of the Wnt/ß-catenin signaling pathway, LRP6 is a novel therapeutic target that plays an important role in the regulation of cardiovascular disease, lipid metabolism, tumorigenesis, and some classical signals. By using capillary electrophoresis-systematic evolution of ligands by exponential enrichment (CE-SELEX), with recombinant human LRP-6 as the target, four candidate aptamers with a stem-loop structure were selected from an ssDNA library-AptLRP6-A1, AptLRP6-A2, AptLRP6-A3, and AptLRP6-A4. The equilibrium dissociation constant KD values between these aptamers and the LRP6 protein were in the range of 0.105 to 1.279 µmol/L, as determined by CE-LIF analysis. Their affinities and specificities were further determined by the gold nanoparticle (AuNP) colorimetric method. Among them, AptLRP6-A3 showed the highest affinity with LRP6-overexpressed human breast cancer cells. Therefore, the LRP6 aptamer identified in this study constitutes a promising modality for the rapid diagnosis and treatment of LRP6-related diseases.


Assuntos
Aptâmeros de Nucleotídeos , Nanopartículas Metálicas , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Lipoproteínas LDL , Ouro , DNA de Cadeia Simples , Aptâmeros de Nucleotídeos/química
7.
J Radiat Res ; 2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37154561

RESUMO

Human skeletal dosimetry has experienced great developments in radiation protection in recent years by using the heterogeneous skeletal model. While for the rats experimentally used in radiation medicine, the investigation on skeletal dosimetry were mainly based on the homogeneous skeletal model, leading to inaccurate assessments of dose to radiosensitive tissues of red bone marrow (RBM) and bone surface. The purpose of this study is to develop a rat model with heterogeneous skeletal system and to investigate the dose difference in bone tissues for external photon irradiation. The high resolution of microCT images of a rat weighing 335 g were segmented into bone cortical, bone trabecular, bone marrow as well as other organs to construct the rat model. The absorbed dose to bone cortical, bone trabecular and bone marrow were calculated respectively by using Monte Carlo simulation for 22 external monoenergetic photon beams between 10 keV and 10 MeV under four different irradiation geometries conditions (left lateral [LL], right lateral [RL], dorsal-ventral [DV], ventral-dorsal [VD]). The calculated absorbed dose data were expressed as dose conversion coefficients and presented in this article, and the effect of irradiation conditions, photon energies and bone tissues density on the skeletal dose was discussed. The results showed that the dose conversion coefficients varying the photon energy for bone cortical, bone trabecular and bone marrow exhibit different trends and have the same sensitivity to irradiation conditions. The dose difference in bone tissues indicated that bone cortical and bone trabecular have significant attenuation effect on the energy deposition in bone marrow and bone surface for photon energies below 0.2 MeV. The set of dose conversion coefficients in this work can be used to determine the absorbed dose to skeletal system for external photon irradiation and to supplement the rat skeletal dosimetry.

8.
Psychol Health Med ; : 1-16, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37227800

RESUMO

Fluid-control adherence was important for hemodialysis (HD) patients, and while significant correlations between treatment adherence and illness perceptions have been found, there is limited research that explored the relationship between illness perceptions and fluid-control adherence. We sought to assess illness perceptions and fluid-control adherence and to explore the relationship between them among Chinese hemodialysis patients. A cross-sectional study of 253 Chinese HD patients was conducted. We recorded sociodemographic and disease characteristics, Revised Illness Perception Questionnaire (IPQ-R) responses, Fluid Control in Hemodialysis Patients Scale (FCHPS) scores and the interdialytic weight gain (IDWG). The total FCHPS score of hemodialysis patients was of a moderate level, and 45.85% hemodialysis patients' IDWG exceeded 3.0 kg. Regression analysis revealed that sex, academic level, marital status, treatment control dimension and causal (physical) factors of illness perceptions explained 12.7% variance in the total FCHPS score. Age, normalized whole-body urea clearance (Kt/V), dry weight (DW) residual urine volume (mL/24 h) and consequence dimension of illness perceptions explained 29.0% variance in IDWG. About mediating effect analysis, positive indirect effects on IDWG were found for identity, consequences and emotional representations through the attitude dimension of FCHPS, and negative indirect effects on IDWG were found for treatment control and illness coherence through the attitude dimension of FCHPS. The results demonstrated that some sociodemographic and clinical characteristics and illness perceptions were associated with fluid-control adherence, and the patient's attitude toward fluid control is an important mediator between illness perceptions and IDWG, implying that attitude can be a focus of intervention programs based on illness perceptions to improve Chinese HD patients' fluid-control adherence.

9.
Aging (Albany NY) ; 152023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37227816

RESUMO

BACKGROUND: T cell plays a crucial role in the occurrence and progression of Skin cutaneous melanoma (SKCM). This research aims to identify the actions of T cell proliferation-related genes (TRGs) on the prognosis and immunotherapy response of tumor patients. METHOD: The clinical manifestation and gene expression data of SKCM patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. T cell proliferation-related molecular subtypes were identified utilizing consensus clustering. Subsequently, Cox and Lasso regression analysis was conducted to identify six prognostic genes, and a prognostic signature was constructed. A series of experiments, such as qRT-PCR, Western blotting and CCK8 assay, were then conducted to verify the reliability of the six genes. RESULTS: In this study, a grading system was established to forecast survival time and responses to immunotherapy, providing an overview of the tumoral immune landscape. Meanwhile, we identified six prognostic signature genes. Notably, we also found that C1RL protein may inhibit the growth of melanoma cell lines. CONCLUSION: The scoring system depending on six prognostic genes showed great efficiency in predicting survival time. The system could help to forecast prognosis of SKCM patients, characterize SKCM immunological condition, assess patient immunotherapy response.

10.
J Psychosom Res ; 170: 111344, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37178472

RESUMO

OBJECTIVE: To identify longitudinal trajectories of illness perception (IP) regarding breast cancer-related lymphedema (BCRL) in the first six months after surgery among women with breast cancer and to explore the predictive effects of demographics and clinical factors on IP trajectories. METHODS: From August 2019 to August 2021, a total of 352 patients participated in this study, 328 of whom were included in the data analysis. Demographic and clinical characteristics were collected at baseline (1-3 days after surgery). The BCRL-specific revised illness perception questionnaire was used to measure IP regarding BCRL at baseline and 1 month, 3 months and 6 months post-surgery. A multilevel model was conducted to analyze the data. RESULTS: Over the first six months post-surgery, the "timeline acute/chronic" and "illness coherence" dimensions showed positive growth trajectories; the "personal control" and "treatment control" dimensions presented negative growth trajectories; and the trajectories of identity, consequences, cyclicality and emotional influence perceptions regarding BCRL showed no significant changes. Age, education level, marital status, employment status, family monthly income per person, cancer stage and status of removed lymph nodes were indicated to be predictive factors of IP trajectories. CONCLUSIONS: The present study determined significant changes over the first six months post-surgery in four IP dimensions and predictive effects of some demographics and clinical details on IP trajectories. These findings may help healthcare providers know more about the dynamic characteristics of IPs regarding BCRL in patients with breast cancer and assist them in identifying patients with a tendency toward improper IP regarding BCRL.

11.
Front Immunol ; 14: 1153042, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37020548

RESUMO

Respiratory infections are a major public health concern caused by pathogens that colonize and invade the respiratory mucosal surface. Nasal vaccines have the advantage of providing protection at the primary site of pathogen infection, as they induce higher levels of mucosal secretory IgA antibodies and antigen-specific T and B cell responses. Adjuvants are crucial components of vaccine formulation that enhance the immunogenicity of the antigen to confer long-term and effective protection. Saponins, natural glycosides derived from plants, shown potential as vaccine adjuvants, as they can activate the mammalian immune system. Several licensed human vaccines containing saponins-based adjuvants administrated through intramuscular injection have demonstrated good efficacy and safety. Increasing evidence suggests that saponins can also be used as adjuvants for nasal vaccines, owing to their safety profile and potential to augment immune response. In this review, we will discuss the structure-activity-relationship of saponins, their important role in nasal vaccines, and future prospects for improving their efficacy and application in nasal vaccine for respiratory infection.


Assuntos
Adjuvantes de Vacinas , Infecções Respiratórias , Saponinas , Vacinas , Humanos , Adjuvantes de Vacinas/farmacologia , Saponinas/farmacologia , Vacinação
12.
Appl Microbiol Biotechnol ; 107(11): 3817-3828, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37074383

RESUMO

Biofilms inhabiting pipeline walls are critical to drinking water quality and safety. With massive pipeline replacement underway, however, biofilm formation process in newly built pipes and its effects on water quality are unclear. Moreover, differences and connections between biofilms in newly built and old pipes are unknown. In this study, early succession (≤ 120 days) of biofilm bacterial communities (abundance and diversity) in upper, middle and bottom areas of a newly built cement-lined ductile iron pipeline were evaluated using improved Propella™ biofilm reactor and multi-area analysis. A comparison with old pipelines (grey cast iron, 10 years) was performed. In the newly built pipeline, the abundance of biofilm bacteria did not change significantly between 40 and 80 days, but increased significantly between 80 and 120 days. The biofilm bacterial abundance (per unit area) in the bottom area was always higher than that in the upper and middle areas. Based on alpha diversity index and PCoA results, biofilm bacterial community richness, diversity and composition did not change significantly during the 120-day operation. Besides, biofilm shedding from the walls of newly built pipeline significantly increased bacterial abundance in the outlet water. Opportunistic pathogen-containing genera, such as Burkholderia, Acinetobacter and Legionella, were identified in both water and biofilm samples from newly built pipelines. The comparison between new and old pipelines suggested a higher bacterial abundance per unit area at the middle and bottom areas in old pipelines. Moreover, the bacterial community composition of biofilms in old pipelines was similar to that of newly built pipelines. These results contribute to accurate prediction and management of biofilm microbial communities in drinking water pipelines, ensuring the biosafety of drinking water. KEY POINTS: • Biofilm bacterial communities in different areas of pipe wall were revealed. • The abundance of biofilm bacteria increased significantly between 80 and 120 days. • Biofilm bacterial community compositions of newly built and old pipes were similar.


Assuntos
Água Potável , Abastecimento de Água , Bactérias , Biofilmes , Ferro , Microbiologia da Água
13.
Mar Pollut Bull ; 191: 114972, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37119587

RESUMO

The Water-Sediment Regulation Scheme (WSRS) will deliver large amounts of water and sand to the Yellow River basin within a short period of time. This will significantly change the physicochemical environment of the Yellow River estuary and the surrounding marine ecosystem. Its effects on the spatial and temporal distribution patterns of ichthyoplankton are still unknown. In this study, six surface horizontal trawl surveys of ichthyoplankton were conducted during the WSRS in 2020 and 2021 using plankton nets. The results were as follows: (1) the estuarine sedentary fish Cynoglossus joyeri was the main species controlling the succession pattern of summer ichthyoplankton communities in the Yellow River estuary. (2) The WSRS influenced the ichthyoplankton community structure by changing the runoff, salinity, and suspension environment in the estuary. (3) The northern and southeastern parts of the estuary near Laizhou Bay were the main aggregation areas of the ichthyoplankton community.


Assuntos
Ecossistema , Água , Animais , Rios/química , Peixes , Plâncton , Estuários , China
14.
Br J Ophthalmol ; 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055157

RESUMO

AIM: To evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals. METHODS: This study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy. RESULTS: Incomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively. CONCLUSION: Peripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis.

15.
Diabetes ; 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37058417

RESUMO

Monocyte activation plays an important role in diabetic complications such as diabetic retinopathy (DR). However, the regulation of monocyte activation in diabetes remains elusive. Fenofibrate, an agonist of peroxisome proliferator-activated receptor-alpha (PPARα), has shown robust therapeutic effects on DR in type 2 diabetic patients. Here we found that PPARα levels were significantly down-regulated in monocytes from diabetic patients and animal models, correlating with monocyte activation. Fenofibrate attenuated monocyte activation in diabetes, while PPARα knock-out alone induced monocyte activation. Furthermore, monocyte-specific PPARα overexpression ameliorated, while monocyte-specific PPARα knock-out aggravated, monocyte activation in diabetes. PPARα knock-out impaired mitochondrial function, while increasing glycolysis in monocytes. PPARα knock-out increased cytosolic mitochondrial DNA release and activation of the cGAS-STING pathway in monocytes under diabetic conditions. STING knock-out or STING inhibitor attenuated monocyte activation induced by diabetes or by PPARα knock-out. These observations suggest that PPARα negatively regulates monocyte activation through metabolic reprogramming and interaction with the cGAS-STING pathway.

16.
Int J Mol Sci ; 24(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37047817

RESUMO

A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-γ. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance.


Assuntos
Receptores de Antígenos Quiméricos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Receptor de Morte Celular Programada 1/metabolismo , Recidiva Local de Neoplasia/metabolismo , Células Matadoras Naturais , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Imunoterapia Adotiva
17.
Toxicol Appl Pharmacol ; 467: 116492, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36977438

RESUMO

Guanine nucleotide exchange factor T (GEFT), which is frequently overexpressed in cancers, is closely related to tumorigenicity and metastasis. Up to now, little is known about the relationship between GEFT and cholangiocarcinoma (CCA). The work explored the expression and function of GEFT in CCA and revealed the underlying mechanisms. Both CCA clinical tissues and cell lines expressed higher levels of GEFT than normal controls. High GEFT levels were correlated with a low overall survival rate in CCA patients. A decrease in GEFT by RNA interference caused remarkable anticancer effects in CCA cells, including retarded proliferation, delayed cell cycle progression, subdued metastatic potential and enhanced chemosensitivity. Mechanistically, GEFT mediated the Wnt-GSK-3ß-ß-catenin cascade associated with the regulation of Rac1/Cdc42. The inhibition of Rac1/Cdc42 markedly diminished the enhancing effect of GEFT on the Wnt-GSK-3ß-ß-catenin and reversed GEFT-mediated cancer-promoting effects in CCA. Moreover, the reactivation of ß-catenin diminished GEFT-reduction-induced anticancer effects. Critically, CCA cells with decreasing GEFT had a weakened ability to form xenografts in mouse models. Collectively, this work illustrates that GEFT-mediated Wnt-GSK-3ß-ß-catenin cascade represents a novel mechanism underlying CCA progression and propose a decrease in GEFT as a potential path for treatment in CCA patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Camundongos , Animais , Humanos , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Proliferação de Células , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
18.
Nanoscale Horiz ; 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36988068

RESUMO

Since the discovery of graphene in an atomic thin layer format, many investigations have been conducted to search for two-dimensional (2D) layered materials, in which 3d-transition metals offer much new physics and great freedom of tunability. In this work, through electron-beam irradiation, we enable the manufacture of a new 2D Ti nanosheet from a suspension of Ti0.91O2 nanosheets. In state-of-the-art density functional theory (DFT), both empirical and linear response theory predicted that Hubbard Ueff values would be imposed, resulting in unstable phonon dispersion curves. In the end, the newly found Ti monolayer is confirmed to be a non-magnetic superconductor, with a medium level of electron-phonon coupling. The newly established Ti layer is quite robust under strain, and the evolution of local Dirac points in electronic bands is also analyzed in terms of linearity and energetic shift near the Fermi energy. As suggested by the Fermi surface, this metal monolayer experiences an electronic topological transition under strain. Our findings will encourage many more explorations of pure d metal-based isotopic monolayers with diverse structures and open a new playground for 2D superconductors and ultra-thin sensoring components.

19.
Nutrients ; 15(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36904197

RESUMO

Epidemiological evidence regarding the possible link between multiple essential metals levels and all-cause mortality and cardiovascular disease (CVD) mortality among type 2 diabetes (T2D) patients is sparse. Here, we aimed to evaluate the longitudinal associations between 11 essential metals levels in plasma and all-cause mortality and CVD mortality among T2D patients. Our study included 5278 T2D patients from the Dongfeng-Tongji cohort. LASSO penalized regression analysis was used to select the all-cause and CVD mortality-associated metals from 11 essential metals (iron, copper, zinc, selenium, manganese, molybdenum, vanadium, cobalt, chromium, nickel, and tin) measured in plasma. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With a median follow-up of 9.8 years, 890 deaths were documented, including 312 deaths of CVD. LASSO regression models and the multiple-metals model revealed that plasma iron and selenium were negatively associated with all-cause mortality (HR: 0.83; 95%CI: 0.70, 0.98; HR: 0.60; 95%CI: 0.46, 0.77), whereas copper was positively associated with all-cause mortality (HR: 1.60; 95%CI: 1.30, 1.97). Only plasma iron has been significantly associated with decreased risk of CVD mortality (HR: 0.61; 95%CI: 0.49, 0.78). The dose-response curves for the association between copper levels and all-cause mortality followed a J shape (Pfor nonlinear = 0.01). Our study highlights the close relationships between essential metals elements (iron, selenium, and copper) and all-cause and CVD mortality among diabetic patients.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Selênio , Humanos , Cobre , Metais , Ferro , Fatores de Risco
20.
Genomics ; 115(2): 110590, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36868326

RESUMO

The role of peptidoglycan-associated lipoprotein (Pal) in A. baumannii pathogenesis remains unclear. Here, we illustrated its role by constructing a pal deficient A. baumannii mutant and its complementary strain.Transcriptome analysis of the WT and pal mutant revealed a total of 596 differentially expressed genes. Gene Ontology analysis revealed that pal deficiency caused the downregulation of genes related to material transport and metabolic processes. The pal mutant showed a slower growth and was sensitive to detergent and serum killing compared to WT strain, whereas, the complemented pal mutant showed rescued phenotype. The pal mutant caused decreased mortality in mice pneumonia infection compared to WT strain, while the complemented pal mutant showed increased mortality. Mice immunized with recombinant Pal showed 40% protection against A. baumannii-mediated pneumonia. Collectively, these data indicate Pal is a virulence factor of A. baumannii and may serve as a potential target for preventive or therapeutic interventions.


Assuntos
Acinetobacter baumannii , Pneumonia , Vacinas , Animais , Camundongos , Virulência/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Peptidoglicano/genética , Peptidoglicano/metabolismo , Vacinas/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismo
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