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1.
Talanta ; 279: 126639, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094531

RESUMO

In this paper, an ultra-small-sized CuOx/GDYO nanozyme in situ grown on ITO glass was rationally synthesized from mixed precursors of graphdiyne oxide (GDYO) and copper based infinite coordination polymer (Cu-ICP, consisting of Cu ions and two organic ligands 3,5-di-tert-butylcatechol and 1,4-bis(imidazole-1-ylmethyl)benzene) via mild and simple electrochemical strategy. On one hand, the preferential electro-reduction of Cu-ICP enabled the formation of ultra-small CuOx with Cu(I) as the main component and avoided the loss of oxygen-containing functional groups and defects on the surface of GDYO; on the other hand, GDYO can also serve as electroless reductive species to facilitate the electrochemical deposition of CuOx and turn itself to a higher oxidation state with more exposed functional groups and defects. This one-stone-two-birds electrochemical strategy empowered CuOx/GDYO nanozyme with superior peroxidase-mimicking activity and robust anchoring stability on ITO glass, thus enabled further exploration of the portable device with availability for point-of-use applications. Based on the organophosphorus pesticides (OPs) blocked acetylcholinesterase (AChE) activity, the competitive redox reaction was regulated to initiate the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by CuOx/GDYO peroxidase-like nanozyme, which laid out a foundation for the detection of OPs (with chlorpyrifos as an example). With a detection of limit low to 0.57 nM, the OPs residues during agricultural production can be directly monitored by the portable device we developed.

3.
Adv Mater ; : e2408550, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161077

RESUMO

Self-assembled graphene films at air-liquid interface have great potential for multiple applications. However, the large size and ultrathin thickness for graphene-based films are hardly achieved simultaneously because of poor assembly ability of graphene oxide (GO) and cautious film transfer process (FTP). Herein, the ethanol-based binary solution with supramolecular clusters and weak polarity is introduced to enhance the assembly performance of GO. In this regime, GO film is formed within 52 s, and its formation temperature can be as low as -20 °C. More importantly, the attractive force between the formed GO film and this binary solution is 62% lower than that between GO film and traditional aqueous solution. On this basis, for the first time a spontaneous separation of the self-assembled GO film from solution is reported, and the air‒floating graphene films (AGFs) with nanoscale thickness and centimeter-scale diameter are prepared without FTP. By means of this separation behavior, the in situ growth AGFs sensors are fabricated, and they express fast response and ultrahigh sensitivity to imperceptible change in temperature and disturbances that are hardly recognized by common sensors. Therefore, a new accessible strategy is demonstrated to prepare ultrathin graphene macrofilms, which can be the excellent candidates for multifunctional, ultrasensitive sensors.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39135383

RESUMO

Aging is a significant risk factor for the increased incidence of acute kidney injury and chronic kidney disease, posing significant challenges to global public health. The role of N6-methyladenosine (m6A) in the development of chronic kidney disease has been reported, but the regulatory mechanism of m6A in kidney aging remains unclear. In this study, we identified a long non-coding RNA (lncRNA), called TUG1, which exhibited a significantly decreased level of m6A modification in human aged kidney through the m6A-lncRNA epitranscriptome microarray. Bioinformatics analysis and machine learning predicted that TUG1 formed potentially strong interaction with PGC1-α. RIP and ChIP analysis supported that TUG1 promoted proliferator-activated receptor γ coactivator-1α (PGC1-α) expression by directly interact with its TBE region, thereby impacting mitochondrial quality control, cellular senescence and renal fibrosis. Silencing the RNA m6A methylase METTL14 or the reader protein IGF2BP2 resulted in the weakened stability of LncRNA TUG1, contributing to an imbalance in mitochondrial quality control. Our study demonstrated that Our study demonstrated that the m6A modification and stability of TUG1 was mediated by METTL14 in an IGF2BP2-dependent manner, and modulate the mitochondrial homeostasis in kidney aging by direct targeting PGC-1α. These findings provide a new perspective on potential therapeutic targets for kidney aging.

5.
Water Res ; 265: 122307, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39180955

RESUMO

Ethanol feeding has been widely documented as an economical and effective strategy for establishing direct interspecies electron transfer (DIET) during anaerobic digestion. However, the mechanisms involved are still unclear, especially on correlation between intracellular electron transfer in electroactive bacteria and their gene expression for electrically conductive pili (e-pili), the most essential electrical connection component for DIET. Upon cooling from room temperature, the conductivity of digester aggregates with ethanol exponentially increased by an order of magnitude (from 45.5 to 125.4 µS/cm), whereas which with its metabolites (acetaldehyde [from 40.5 to 54.4 µS/cm] or acetate [from 32.1 to 50.4 µS/cm]) did not increase significantly. In addition, the digester aggregates only with ethanol were observed with a strong dependence of conductivity on pH. Metagenomic and metatranscriptomic analysis showed that Desulfovibrio desulfuricans was the most dominant and metabolically active bacterium that contained and highly expressed the genes for e-pili. Abundance of genes encoding the total type IV pilus assembly proteins (6.72E-04 vs 1.24E-03, P < 0.05), PilA that determined the conductive properties (2.22E-04 vs 2.44E-04, P > 0.05), and PilB that proceeded the polymerization of pilin (1.56E-04 vs 3.52E-03, P < 0.05) with ethanol was lower than that with acetaldehyde. However, transcript abundance of these genes with ethanol was generally higher than that with acetaldehyde. In comparison to acetaldehyde, ethanol increased the transcript abundance of genes encoding the key enzymes involved in NADH/NAD+ transformation on complex I and ATP synthesis on complex V in intracellular electron transport chain. The improvement of intracellular electron transfer in D. desulfuricans suggested that electrons were intracellularly energized with high energy to activate e-pili during DIET.

6.
J Extracell Vesicles ; 13(7): e12493, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39051750

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and chemotherapy is the cornerstone treatment for TNBC. Regrettably, emerging findings suggest that chemotherapy facilitates pro-metastatic changes in the tumour microenvironment. Extracellular vesicles (EVs) have been highly implicated in cancer drug resistance and metastasis. However, the effects of the EVs released from dying cancer cells on TNBC prognosis and corresponding therapeutic strategies have been poorly investigated. This study demonstrated that paclitaxel chemotherapy elicited CXCL1-enriched EVs from apoptotic TNBC cells (EV-Apo). EV-Apo promoted the chemoresistance and invasion of co-cultured TNBC cells by polarizing M2 macrophages through activating PD-L1 signalling. However, baohuoside I (BHS) remarkably sensitized the co-cultured TNBC cells to paclitaxel chemotherapy via modulating EV-Apo signalling. Mechanistically, BHS remarkably decreased C-X-C motif chemokine ligand 1 (CXCL1) cargo within EV-Apo and therefore attenuated macrophage M2 polarization by suppressing PD-L1 activation. Additionally, BHS decreased EV-Apo release by diminishing the biogenesis of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) of TNBC cells. Furthermore, BHS bound to the LEU104 residue of flotillin 2 (FLOT2) and interrupted its interaction with RAS oncogene family member 31 (RAB31), leading to the blockage of RAB31-FLOT2 complex-driven ILV biogenesis. Importantly, BHS remarkably chemosensitised paclitaxel to inhibit TNBC metastasis in vivo by suppressing EV-ApoCXCL1-induced PD-L1 activation and M2 polarization of tumour-associated macrophages (TAMs). This pioneering study sheds light on EV-ApoCXCL1 as a novel therapeutic target to chemosensitise TNBC, and presents BHS as a promising chemotherapy adjuvant to improve TNBC chemosensitivity and prognosis by disturbing EV-ApoCXCL1 biogenesis.


Assuntos
Apoptose , Quimiocina CXCL1 , Vesículas Extracelulares , Paclitaxel , Neoplasias de Mama Triplo Negativas , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Feminino , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Apoptose/efeitos dos fármacos , Quimiocina CXCL1/metabolismo , Linhagem Celular Tumoral , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos
7.
Ann Surg Oncol ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080137

RESUMO

BACKGROUND: Due to the deep location of the prostate within the pelvic cavity, procedures of robot-assisted radical prostatectomy (RARP) might be challenged by the prostate size and the limited pelvic cavity space. This study aimed to investigate the roles of bony pelvic and prostate dimensions in RARP procedures by an original study coupled with a meta-analysis. METHODS: In the original study, patients undergoing multiport RARP between 2021 and 2022 were consecutively assessed. The associations of anatomic features with operative time (OT), estimated blood loss (EBL), and positive surgical margin (PSM) were evaluated using linear and logistic regression analyses as well as restricted cubic spline (RCS) analysis. Based on machine-learning algorithms, this study established predictive models for surgical difficulty and interpreted the model using SHapley Additive exPlanation (SHAP). In the meta-analysis, three databases were searched for eligible studies. Quantitative syntheses were subsequently performed. RESULTS: Overall, 219 patients were enrolled in the original study. Prostate volume (PV) and the prostate volume-to-pelvic cavity index (PCI) ratio (PV-to-PCI ratio) were significantly associated with longer OT (P < 0.05). In the RCS models, U-shaped associations were observed between the prostate anteroposterior diameter (PAD) and OT, and between the prostate height (PH) and EBL, and an L-shaped association was observed between the anteroposterior diameter of the pelvic inlet (API) and EBL. The XGBoost model was superior to the logistic regression model in predicting prolonged OT. The meta-analysis demonstrated that greater PV was significantly associated with longer OT (ß = 0.20; 95% confidence interval [CI] 0.12-0.27; odds ratio [OR] = 1.05; 95% CI 1.00-1.11), and a smaller PV could increase the risk of PSM (OR = 0.82; 95% CI 0.77-0.88). CONCLUSIONS: A large prostate within a narrow and deep pelvis might suggest increased surgical difficulty of RARP. The size of the pelvic inlet also had a great impact on RARP. For PAD and PH, there seemed to be an optimal range with the lowest surgical difficulty. Machine-learning models based on the XGBoost algorithm could be successfully applied to predict the surgical difficulty of RARP.

8.
J Cell Mol Med ; 28(14): e18521, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39021279

RESUMO

In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imuno-Histoquímica , Antígeno Ki-67 , Neoplasias Pulmonares , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Prognóstico , Feminino , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Idoso , Nomogramas , Microambiente Tumoral/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal/genética , Estudos Retrospectivos
9.
Sci Rep ; 14(1): 16509, 2024 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019936

RESUMO

The negative effects of obesity and excess body fat on bone mineral density (BMD) have been widely reported. As opposed to waist circumference (WC) or body mass index (BMI), weight-adjusted waist index (WWI) is a superior method for assessing obesity. WWI also indicates centripetal obesity independently of the weight of the individual. An investigation of WWI and adolescents' BMD was conducted in this study. The National Health and Nutrition Examination Survey (NHANES) 2011-2018 provided the data for this cross-sectional investigation. In this study, weighted multivariate logit models were employed to assess the correlation between teenage BMD and WWI. Additionally, we conducted interaction tests and subgroup analysis. Through multivariate linear regression, we discovered that WWI was negatively linked with lumbar, trunk, and total BMD but not pelvis BMD in this study, which included 6828 subjects. We found that each unit increase in WWI resulted in a lumbar BMD decline of 0.04 g/cm2 (95%CI -0.04, -0.04), a trunk BMD decrease of 0.03 g/cm2 (95%CI -0.03, -0.02), and a total BMD decrease of 0.02 g/cm2 (95%CI -0.02, -0.02). In conclusion, in US teenagers, there were negative connections discovered between WWI and lumbar, trunk, and total BMD, but not pelvis BMD.


Assuntos
Densidade Óssea , Inquéritos Nutricionais , Circunferência da Cintura , Humanos , Adolescente , Masculino , Feminino , Estudos Transversais , Índice de Massa Corporal , Peso Corporal , Obesidade/fisiopatologia , Vértebras Lombares/diagnóstico por imagem
10.
Biomed Pharmacother ; 177: 117037, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38959602

RESUMO

The inhibition of autophagy is a potential therapeutic strategy to improve the chemosensitivity of triple-negative breast cancer (TNBC). In this study, we demonstrated that a natural terpenoid tanshinone I (TAN) enhanced the effectiveness of paclitaxel (PTX), at least in part, through an autophagy-dependent mechanism against TNBC. In vitro validation demonstrated that the combined therapy resulted in a synergistic decrease in the growth of TNBC cells. The chemosensitizing impact of TAN might be attributed to its inhibition of PTX-induced autophagy in the late phase by obstructing the fusion of autophagosomes and lysosomes, rather than by inhibiting lysosomal function. The findings from KEGG pathway analysis and molecular docking suggested that TAN might impact breast cancer chemoresistance primarily through the PI3K-Akt and MAPK signaling pathways. The non-canonical AKT/p38 MAPK signaling was further validated as the primary mechanism responsible for the inhibition of autophagy by TAN. In vivo study showed that the combined administration of TAN and PTX demonstrated a more significant suppression of tumor growth and autophagic activity compared to PTX monotherapy in the MDA-MB-231 xenograft nude mouse model. The safety evaluation of TAN in a zebrafish model, along with in vitro and in vivo validation, provided experimental and pre-clinical data supporting its potential as a natural adjunctive therapy in TNBC. Overall, this study suggests that the combination of TAN with PTX could provide an effective treatment option for advanced breast cancer, and targeting the AKT/p38 MAPK/late-autophagy signaling axis may be a promising approach for developing therapeutic interventions against TNBC.


Assuntos
Abietanos , Autofagia , Camundongos Nus , Paclitaxel , Proteínas Proto-Oncogênicas c-akt , Neoplasias de Mama Triplo Negativas , Peixe-Zebra , Proteínas Quinases p38 Ativadas por Mitógeno , Autofagia/efeitos dos fármacos , Animais , Abietanos/farmacologia , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Feminino , Paclitaxel/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico
11.
Front Oncol ; 14: 1408972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974243

RESUMO

Background: The relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis. Methods: Genetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran's Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk. Results: IVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439-0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026-1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma. Conclusions: HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.

12.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832848

RESUMO

Magnetic fields provide a valuable method to manipulate atomic energy levels and interactions in quantum precision measurements, but achieving precise measurements requires collaboration between the magnetic field system and the optical detection system. We propose a magnetic field system that incorporates a fast-switching magnetic field and an alternating magnetic field. Specifically, we enhance the switching speed by making structural improvements during the switching operation. An independent control approach is employed to reduce the switching time caused by electromagnetic induction across the coil using multilayer coils. The results demonstrate an inverse correlation between the rise and fall times of the magnetic field switch and the number of independently stacked coil layers, indicating the possibility of achieving further improvements in switching speed through structural enhancements. The system developed here has considerable potential for application to diverse quantum systems.

13.
Sci Rep ; 14(1): 14290, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906992

RESUMO

To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.


Assuntos
Stents , Artéria Subclávia , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Artéria Subclávia/cirurgia , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento , Síndrome do Roubo Subclávio/terapia , Síndrome do Roubo Subclávio/cirurgia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Angioplastia/métodos , Angioplastia/efeitos adversos , Constrição Patológica/terapia , Angioplastia com Balão/métodos , Angioplastia com Balão/efeitos adversos , Arteriopatias Oclusivas/terapia , Arteriopatias Oclusivas/cirurgia
14.
J Am Chem Soc ; 146(25): 17201-17210, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38874405

RESUMO

As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.


Assuntos
Antioxidantes , Dissecção Aórtica , Cobalto , Catálise , Cobalto/química , Cobalto/farmacologia , Dissecção Aórtica/tratamento farmacológico , Dissecção Aórtica/patologia , Antioxidantes/química , Antioxidantes/farmacologia , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/síntese química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Nanopartículas Metálicas/química
15.
Chin J Nat Med ; 22(6): 501-514, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38906598

RESUMO

Prostate cancer (PCa) is the second most common malignancy among men globally. The Fu-Zheng-Yi-Liu (FZYL) Formula has been widely utilized in the treatment of PCa. This study investigates whether the FZYL Formula can inhibit PCa by targeting the TAMs/CCL5 pathway. We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their interaction. Results showed that the FZYL Formula significantly reduced the proliferation, colony formation, subpopulations of PCSCs, and sphere-formation efficacy of PCa cells, even in the presence of TAM co-culture. Additionally, the Formula markedly decreased the migration, invasion, and epithelial-mesenchymal transition (EMT) of PCa cells induced by TAMs. The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion, with minimal cytotoxicity observed. Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula, as the addition of exogenous CCL5 partially reversed the formula's inhibitory effects on PCSCs self-renewal in the co-culture system. Importantly, the Formula also significantly inhibited the growth of PCa xenografts, bone metastasis, and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway. Overall, this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.


Assuntos
Quimiocina CCL5 , Medicamentos de Ervas Chinesas , Células-Tronco Neoplásicas , Neoplasias da Próstata , Microambiente Tumoral , Macrófagos Associados a Tumor , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Masculino , Humanos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Quimiocina CCL5/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Metástase Neoplásica , Movimento Celular/efeitos dos fármacos , Técnicas de Cocultura , Camundongos Nus
16.
Food Chem ; 455: 139773, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38833856

RESUMO

A molecularly imprinted polymer (MIP) based microfiber differential demodulation sensing system for sodium benzoate (SB) concentration detection is proposed. The specific binding of MIP on the surface of microfibers with SB can lead to changes in local refractive index (RI). RI change induces a drift in the interference wavelength, which can be monitored by the power difference between two fiber Bragg gratings (FBGs). The sensing system can detect SB in the concentration range of 0.1-50 µg/ml, and interference wavelength and FBG power difference sensitivities are 0.55 nm/(µg/ml) and 2.64 dB/(µg/ml) in the low concentration range of 0.1-1 µg/ml, respectively, with a limit of detection (LOD) of 0.1 µg/ml. This microfiber differential demodulation sensing system is not only simple to fabricate, but also simplifies the demodulation equipment to reduce the cost, which providing a simple, reliable and low-cost technique for the quantitative detection of SB concentration in beverages and flavoured foods.


Assuntos
Polímeros Molecularmente Impressos , Benzoato de Sódio , Benzoato de Sódio/análise , Benzoato de Sódio/química , Polímeros Molecularmente Impressos/química , Fibras Ópticas , Limite de Detecção , Contaminação de Alimentos/análise , Impressão Molecular , Polímeros/química
17.
Nat Commun ; 15(1): 4982, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862504

RESUMO

Various noncollinear spin textures and magnetic phases have been predicted in twisted two-dimensional CrI3 due to competing ferromagnetic (FM) and antiferromagnetic (AFM) interlayer exchange from moiré stacking-with potential spintronic applications even when the underlying material possesses a negligible Dzyaloshinskii-Moriya or dipole-dipole interaction. Recent measurements have shown evidence of coexisting FM and AFM layer order in small-twist-angle CrI3 bilayers and double bilayers. Yet, the nature of the magnetic textures remains unresolved and possibilities for their manipulation and electrical readout are unexplored. Here, we use tunneling magnetoresistance to investigate the collective spin states of twisted double-bilayer CrI3 under both out-of-plane and in-plane magnetic fields together with detailed micromagnetic simulations of domain dynamics based on magnetic circular dichroism. Our results capture hysteretic and anisotropic field evolutions of the magnetic states and we further uncover two distinct non-volatile spin textures (out-of-plane and in-plane domains) at ≈1° twist angle, with a different global tunneling resistance that can be switched by magnetic field.

18.
Inflamm Res ; 73(9): 1425-1434, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38907743

RESUMO

BACKGROUND: In recent years, there has been a growing interest in the utilization of biologic therapies for the management of asthma. Both TSLP and IgE are important immune molecules in the development of asthma, and they are involved in the occurrence and regulation of inflammatory response. METHODS: A comprehensive search of PubMed and Web of Science was conducted to gather information on anti-TSLP antibody and anti-IgE antibody. RESULTS: This investigation elucidates the distinct mechanistic roles of Thymic Stromal Lymphopoietin (TSLP) and Immunoglobulin E (IgE) in the pathogenesis of asthma, with a particular emphasis on delineating the therapeutic mechanisms and pharmacological properties of monoclonal antibodies targeting IgE and TSLP. Through a meticulous examination of clinical trials involving paradigmatic agents such as omalizumab and tezepelumab, we offer valuable insights into the potential treatment modalities for diseases with shared immunopathogenic pathways involving IgE and TSLP. CONCLUSION: The overarching objective of this comprehensive study is to delve into the latest advancements in asthma therapeutics and to provide guidance for future investigations in this domain.


Assuntos
Antiasmáticos , Anticorpos Monoclonais , Asma , Citocinas , Imunoglobulina E , Linfopoietina do Estroma do Timo , Asma/tratamento farmacológico , Asma/imunologia , Humanos , Imunoglobulina E/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Anticorpos Monoclonais/uso terapêutico , Animais , Antiasmáticos/uso terapêutico , Antiasmáticos/farmacologia , Omalizumab/uso terapêutico
19.
Lipids Health Dis ; 23(1): 181, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867213

RESUMO

INTRODUCTION: Although there has been abundant evidence of the association between dyslipidemia as a single factor and osteoporosis, the non-linear relationship between osteoporosis and the Atherogenic Index of Plasma (AIP) has not yet been thoroughly investigated. This study aimed to investigate the complex relationship between AIP and bone mineral density (BMD) to elucidate their interrelationship. METHODS: An analysis of 2007-2018 National Health and Nutrition Survey (NHANES) data was conducted for this study. The study enrolled 5,019 participants. Logarithmically multiplying triglycerides and high-density lipoprotein cholesterol yields the AIP (base 10). The measured variables consisted of BMD in the total femur (TF), femoral neck (FN), and lumbar spine (LS). The association between AIP and BMD was examined using a range of statistical models, such as weighted multivariable logistic regression, generalized additive model, etc. RESULTS: It was found that AIP was positively associated with BMD after adjusting for age, gender, race, socioeconomic status, degree of education, income, Consuming alcoholic beverages, osteoporosis status (Yes or No), ALT, AST, serum creatinine, and total calcium levels. Further studies supported the association link between elevated BMD and AIP. Furthermore, compared to men, females had a higher positive connection between AIP and BMD. In general, there was a curve in the reverse L-shape seen, with a point of change around 0.877, indicating a relationship between AIP and TF BMD. Moreover, a curve exhibiting an L-formed pattern, with a point of inflection at around 0.702, was seen between AIP and FN BMD. In addition, a J-shaped curve was seen, with a point of inflection at 0.092, which demonstrates the association between AIP and LS BMD. CONCLUSION: The AIP and TF BMD curves resemble inverted L shapes, as do the AIP and FN BMD curves. The relationship between AIP and LS BMD was further demonstrated by a J-shaped curve. The results indicate a possible association between AIP and bone mineral density, which should be explored in more detail.


Assuntos
Aterosclerose , Densidade Óssea , Osteoporose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Aterosclerose/sangue , Osteoporose/sangue , Adulto , HDL-Colesterol/sangue , Triglicerídeos/sangue , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Colo do Fêmur/diagnóstico por imagem , Idoso , Inquéritos Nutricionais , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia
20.
Front Vet Sci ; 11: 1426377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872794

RESUMO

Excessive fat deposition due to impaired fat metabolism in chickens is a major problem in the poultry industry. Nutritional interventions are effective solutions, but current options are limited. A safe phytochemical, rutin, has shown positive effects in animals, but its effect on lipid metabolism in poultry remains unknown. Hence, this study is to investigate the effects of rutin on egg quality, serum biochemistry, fat deposition, lipid peroxidation and hepatic lipid metabolism in post-peak laying hens. A total of 360 Taihang laying hens (49-week-old) were randomly divided into five groups and fed a basal diet (control group, 0%) and a basal diet supplemented with 300 (0.03%), 600 (0.06%), 900 (0.09%), and 1,200 (0.12%) mg rutin/kg feed, respectively. The results showed that eggshell strength was significantly (p < 0.05) higher in the dietary rutin groups, whereas yolk percentage (p < 0.05), total cholesterol (TC) (p < 0.01) and yolk fat ratio (p < 0.01) decreased linearly (p < 0.05) in the dietary rutin groups. Importantly, dietary rutin reduced serum triglyceride (TG) and TC levels, decreased abdominal lipid deposition and liver index (p < 0.05), and which concomitantly decreased hepatic lipid (TG, TC, and free fatty acid) accumulation (p < 0.05). An increase (p < 0.05) in total antioxidant capacity and superoxide dismutase activity and a decrease (p < 0.05) in malondialdehyde levels were also found. At the same time, the activities of hepatic lipase, acetyl-CoA carboxylase and malic enzyme in the liver were decreased (p < 0.05). Dietary rutin also increased (p < 0.05) the expression of fatty acid oxidation-related genes (carnitine palmitoyl transferase 1, peroxisome proliferator-activated receptor α, farnesoid X receptor). Additionally, it decreased fatty acid synthesis genes (sterol regulatory element binding protein-1c, acetyl-CoA carboxylase α, stearoyl-CoA desaturase 1) (p < 0.05). In conclusion, the addition of rutin (0.06-0.12%) to the diet improved the fat metabolism and increased liver antioxidant capacity in post-peak laying hens, and these positive changes improved egg quality to some extent.

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