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1.
J Obstet Gynaecol ; 44(1): 2360547, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38904638

RESUMO

BACKGROUND: MiR-381 can regulate the expression of cyclin A2 (CCNA2) to inhibit the proliferation and migration of bladder cancer cells, but whether miR-381 has the same function in breast cancer is not well know. METHODS: The over express or silence miR-381 expressing cell lines were constructed by lentivirus infection to reveal the biological functions of miR-381 in vitro. The expression of miR-381 and CCNA2 in 162 breast cancer patients were detected to further reveal their impact and predictive value on progression-free survival (PFS) and overall survival (OS). RESULTS: After transfection of MDA-MB-231 and MCF-7 cells with miR-381 mimics, the expression of miR-381 was effectively up-regulated and CCNA2 was effectively down-regulated, while the opposite results were observed in tumour cell which transfected with miR-381 inhibitors. After transfection of cell lines with miR-381 mimics, tumour cell activity was significantly reduced, while the opposite results were observed in tumour cell which transfected with miR-381 inhibitors. The area under curves (AUCs) of miRNA-381 and CCNA2 for predicting PFS and OS were 0.711, 0.695, 0.694 and 0.675 respectively. Cox regression analysis showed that miRNA-381 ≥ 1.65 2-ΔΔCt and CCNA ≥ 2.95 2-ΔΔCt were the influence factors of PFS and OS, the hazard ratio (HR) values were 0.553, 2.075, 0.462 and 2.089, respectively. CONCLUSION: miR-381 inhibitors breast cancer cells proliferation and migration by down-regulating the expression of CCNA2, both of them can predict the prognosis of breast cancer.


miR-381 can regulate the expression of cyclin A2 and inhibit the proliferation and migration of bladder cancer cells, but whether miR-381 has the same function in breast cancer is not well know. We analysed the levels of miR-381 and cyclin A2 in breast cancer patients and breast cancer cells to reveal the mechanism of miR-381 affecting the expression of cyclin A2. We found miRNA-381 affects the proliferation and migration of breast cancer cells by down-regulating the expression of cyclin A2. The expression of serum miR-381 and cyclin A2 have important values in predicting the prognosis of breast cancer. Our findings provide mechanistic insights into how miR-381 regulates the proliferation and migration of breast cancer, as well as a new target for clinical treatment. Future research may focus on how to improve patient prognosis by up-regulating expression of miR-381 and down-regulating the expression of cyclin A2.


Assuntos
Neoplasias da Mama , Proliferação de Células , Ciclina A2 , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Proliferação de Células/genética , Ciclina A2/genética , Ciclina A2/metabolismo , Prognóstico , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Células MCF-7 , Adulto
2.
Ann Rehabil Med ; 48(3): 220-227, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830633

RESUMO

OBJECTIVE: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. METHODS: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. RESULTS: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. CONCLUSION: Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

3.
Nature ; 631(8020): 307-312, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898280

RESUMO

Spin accumulation in semiconductor structures at room temperature and without magnetic fields is key to enable a broader range of optoelectronic functionality1. Current efforts are limited owing to inherent inefficiencies associated with spin injection across semiconductor interfaces2. Here we demonstrate spin injection across chiral halide perovskite/III-V interfaces achieving spin accumulation in a standard semiconductor III-V (AlxGa1-x)0.5In0.5P multiple quantum well light-emitting diode. The spin accumulation in the multiple quantum well is detected through emission of circularly polarized light with a degree of polarization of up to 15 ± 4%. The chiral perovskite/III-V interface was characterized with X-ray photoelectron spectroscopy, cross-sectional scanning Kelvin probe force microscopy and cross-sectional transmission electron microscopy imaging, showing a clean semiconductor/semiconductor interface at which the Fermi level can equilibrate. These findings demonstrate that chiral perovskite semiconductors can transform well-developed semiconductor platforms into ones that can also control spin.


Assuntos
Compostos de Cálcio , Óxidos , Semicondutores , Temperatura , Titânio , Compostos de Cálcio/química , Titânio/química , Óxidos/química , Espectroscopia Fotoeletrônica
4.
Adv Sci (Weinh) ; : e2309264, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828782

RESUMO

Se alloying has enabled significantly higher carrier lifetimes and photocurrents in CdTe solar cells, but these benefits can be highly dependent on CdSexTe1-x processing. This work evaluates the optoelectronic, chemical, and electronic properties of thick (3 µm) undoped CdSexTe1-x of uniform composition and varied processing conditions (CdSexTe1-x evaporation rate, CdCl2 anneal, Se content) chosen to reflect various standard device processing conditions. Sub-bandgap defect emission is observed, which increased as Se content increased and with "GrV-optimized CdCl2" (i.e., CdCl2 anneal conditions used for group-V-doped devices). Low carrier lifetime is found for GrV-optimized CdCl2, slow CdSexTe1-x deposition, and low-Se films. Interestingly, all films (including CdTe control) exhibited n-type behavior, where electron density increased with Se up to an estimated ≈1017 cm-3. This behavior appears to originate during the CdCl2 anneal, possibly from Se diffusion leading to anion vacancy (e.g., VSe, VTe) and ClTe generation.

5.
Front Pharmacol ; 15: 1362150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903985

RESUMO

Introduction: Diabetes mellitus (DM) is a common endocrine disease resulting from interactions between genetic and environmental factors. Type II DM (T2DM) accounts for approximately 90% of all DM cases. Current medicines used in the treatment of DM have some adverse or undesirable effects on patients, necessitating the use of alternative medications. Methods: To overcome the low bioavailability of plant metabolites, all entities were first screened through pharmacokinetic, network pharmacology, and molecular docking predictions. Experiments were further conducted on a combination of antidiabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS), along with in vitro evaluation (α-amylase inhibition assay) and diabetic mice tests (oral glucose tolerance test, OGTT; oral starch tolerance test, OSTT) for maximal responses to validate starch digestion and glucose absorption while facilitating insulin sensitivity. Results: The results revealed that the combination of metabolites achieved all required criteria, including ADMET, drug likeness, and Lipinski rule. To determine the mechanisms underlying diabetic hyperglycemia and T2DM treatments, network pharmacology was used for regulatory network, PPI network, GO, and KEGG enrichment analyses. Furthermore, the combined metabolites showed adequate in silico predictions (α-amylase, α-glucosidase, and pancreatic lipase for improving starch digestion; SGLT-2, AMPK, glucokinase, aldose reductase, acetylcholinesterase, and acetylcholine M2 receptor for mediating glucose absorption; GLP-1R, DPP-IV, and PPAR-γ for regulating insulin sensitivity), in vitro α-amylase inhibition, and in vivo efficacy (OSTT versus acarbose; OGTT versus metformin and insulin) as nutraceuticals against T2DM. Discussion: The results demonstrate that the combination of RA, Lut, and RS could be exploited for multitarget therapy as prospective antihyperglycemic phytopharmaceuticals that hinder starch digestion and glucose absorption while facilitating insulin sensitivity.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38795366

RESUMO

CONTEXT: Low bone mineral density (BMD) has been linked to elevated risks of mortality and infections in the general population; however, its association with these outcomes in stroke patients remains unclear. OBJECTIVE: This study aims to investigate the correlation between low BMD and risks of mortality and infections among stroke patients in a Taiwanese cohort. METHODS: In this single-centered retrospective cohort study, 905 stroke patients from a Taiwanese database (2000-2022) were analyzed. Patients were divided based on BMD measurements of the femur and spine. The primary outcome was all-cause mortality, and secondary outcomes included urinary tract infection (UTI) and pneumonia. Accelerated failure time regression model analyses evaluated the association between BMD and these outcomes, while the Kaplan-Meier method and log-rank test assessed survival differences between groups. RESULTS: Among the participants (average age 76.1 years, 70.5% female), 33.82% had osteopenia and 55.25% had osteoporosis. Stroke patients with lower spine and right femur BMD had significantly reduced survival rates, especially when the BMD value fell below 0.842 g/cm2 (spine), and 0.624 g/cm2 (right femur), respectively. Regarding secondary outcomes, lower spine BMD was significantly associated with an increased risk of UTI. CONCLUSION: Low BMD, particularly in the femur and spine, is a significant predictor of mortality and UTI in stroke patients. These findings highlight the importance of assessing and managing BMD in stroke patients to improve outcomes and reduce complications.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38738556

RESUMO

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models. METHODS: Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3-related inflammatory factors. Subsequently, the effects of 4-OI on the IRG1-itaconic acid-NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP-1 cells) via in vitro experiments. RESULTS: Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4-OI inhibited the activation of the IRG1-itaconic acid-NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. INTERPRETATION: 4-OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD-derived PBMCs and in a human macrophage model. Thus, 4-OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

8.
Foot Ankle Surg ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38811273

RESUMO

PURPOSE: The purpose of this systematic review and network meta-analysis was to compare the efficacy of different surgical treatments, including open and arthroscopic modified Broström procedures (MB), anatomical reconstructions, and suture tape augmentations (STA), for chronic lateral ankle instability (CLAI). METHODS: We conducted a systematic search for comparative studies that included adult patients with CLAI who underwent open MB, arthroscopic MB, reconstruction with autografts or allografts, and STA. We used a random-effects model to present the NMA results, with mean differences and 95 % confidence intervals (CI) for continuous measures and relative ratios with 95 % CI for dichotomous variables. Surface under the cumulative ranking curve analysis (SUCRA) was used for treatment ranking. RESULTS: The results, based on surface under the cumulative ranking curve analysis, showed that arthroscopic MB likely improves functional outcomes the most as measured by change in American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores. Anatomical graft reconstructions with allografts or autografts demonstrated greater reduction in anterior talar translation (ATT) and talar tilt angle (TTA). Arthroscopic MB and STA were associated with fewer complications. CONCLUSIONS: Arthroscopic MB may be associated with better functional outcomes, while anatomical reconstructions appear to provide greater improvements in stability for CLAI. Additionally, arthroscopic techniques seem to have lower complication risks compared to open procedures. These potential differences in outcomes and risks between techniques could help guide surgical decision-making.

9.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1809-1817, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812193

RESUMO

The content of 15 total amino acids(TAAs) in Bambusae Concretio Silicea was determined by HPLC with phenyl-isothiocyanate(PITC) for pre-column derivatization. The results showed that the content of TAA was 0.61-12.25 mg·g~(-1), and aspartic acid(Asp), glutamic acid(Glu), proline(Pro), glycine(Gly), and valine(Val) were the top five amino acids in terms of the average content. The content of essential amino acids(EAAs), conditionally essential amino acids(CEAAs), non-essential amino acids(NEAAs), and medicinal amino acids(MAAs) was 0.24-4.75, 0.30-4.73, 0.40-7.50, and 0.36-6.51 mg·g~(-1), respectively. Among the delicious amino acids, sweet amino acids(SAA), bitter amino acids(BAA), fresh-taste amino acids(FAAs), and odourless amino acids(OAAs) had the content of 0.22-4.70, 0.19-4.03, 0.13-2.26, and 0.06-1.26 mg·g~(-1), respectively. The 21 batches of Bambusae Concretio Silicea samples presented the same composition but significant differences in the content of amino acids. Among the three producing areas, Guangdong was the area where the samples had the highest content of TAAs, EAAs, CEAAs, NEAAs, MAAs, and delicious amino acids. Furthermore, the ratio of amino acid(RAA), ratio coefficient of amino acid(RCAA), and score of ratio coefficient of amino acid(SRCAA) were calculated to evaluate the nutritional value of Bambusae Concretio Silicea. The results showed that the Bambusae Concretio Silicea samples from Guangdong had better nutritional value. The nutritional value evaluation based on the content of 15 amino acids was proposed to provide data support for the quality grading of Bambusae Concretio Silicea and lay a foundation for the development and utilization of the medicinal material resources.


Assuntos
Aminoácidos , Valor Nutritivo , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão
10.
Angew Chem Int Ed Engl ; : e202403333, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787684

RESUMO

Numerous studies have shown a fact that phase transformation and/or reconstruction are likely to occur and play crucial roles in electrochemical scenarios. Nevertheless, a decisive factor behind the diverse photoelectrochemical activity and selectivity of various copper/silicon photoelectrodes is still largely debated and missing in the community, especially the possibly dynamic behaviors of metal catalyst/semiconductor interface. Herein, through in situ X-ray absorption spectroscopy and transmission electron microscope, a model system of Cu nanocrystals with well-defined facets on black p-type silicon (BSi) is unprecedentedly demonstrated to reveal the dynamic phase transformation of forming irreversible silicide at Cu nanocrystal-BSi interface during photoelectrocatalysis, which is validated to originate from the atomic interdiffusion between Cu and Si driven by light-induced dynamic activation process. Significantly, the adaptive junction at Cu-Si interface is activated by an expansion of interatomic Cu-Cu distance for CO2 electroreduction, which efficiently restricts the C-C coupling pathway but strengthens the bonding with key intermediate of *CHO for CH4 yield, resulting in a remarkable 16-fold improvement in the product ratio of CH4/C2 products and an intriguing selectivity switch. This work offers new insights into dynamic structural transformations of metal/semiconductor junction and design of highly efficient catalysts toward photosynthesis.

11.
Phys Chem Chem Phys ; 26(15): 11738-11745, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563831

RESUMO

High-performance sodium-ion batteries (SIBs) require anode materials with high capacity and fast kinetics. Based on first-principles calculations, we propose BC3N2 and BC3N2/graphene (B/G) heterostructure as potential SIB anode materials. The BC3N2 monolayer exhibits intrinsic metallic behavior. In addition, BC3N2 possesses a low Na+ diffusion barrier (0.15 eV), a high storage capacity (777 mA h g-1), a low open-circuit voltage (0.72 V), and a tiny axial expansion (0.36%). Compared with the BC3N2 monolayer, the B/G heterostructure exhibits a lower diffusion barrier of 0.027 eV, suggesting a much faster diffusion. More importantly, although the B/G heterostructure possesses heavier molar weight, its theoretical capacity (689 mA h g-1) is comparable to that of the BC3N2 monolayer. Based on the above-mentioned properties, we hope both the BC3N2 monolayer and the B/G heterostructure would be promising anodes for SIBs.

12.
Phys Chem Chem Phys ; 26(17): 13395-13404, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647031

RESUMO

Carbonaceous materials are promising candidates as anode materials for non-lithium-ion batteries (NLIBs) due to their appealing properties such as good electrical conductivity, low cost, and high safety. However, graphene, a classic two-dimensional (2D) carbon material, is chemically inert to most metal atoms, hindering its application as an electrode material for metal-ion batteries. Inspired by the unique geometry of a four-penta unit, we explore a metallic 2D carbon allotrope C5-10-16 composed of 5-10-16 carbon rings. The C5-10-16 monolayer is free from any imaginary frequencies in the whole Brillouin zone. Due to the introduction of a non-sp2 hybridization state into C5-10-16, the extended conjugation of π-electrons is disrupted, leading to the enhanced surface activity toward metal ions. We investigate the performance of C5-10-16 as the anode for sodium/potassium-ion batteries by using first-principles calculations. The C5-10-16 sheet has high theoretical specific capacities of Na (850.84 mA h g-1) and K (743.87 mA h g-1). Besides, C5-10-16 exhibits a moderate migration barrier of 0.63 (0.32) eV for Na (K), ensuring rapid charging/discharging processes. The average open-circuit voltages of Na and K are 0.33 and 0.62 V, respectively, which are within the voltage acceptance range of anode materials. The fully sodiated (potassiated) C5-10-16 shows tiny lattice expansions of 1.4% (1.3%), suggesting the good reversibility. Moreover, bilayer C5-10-16 significantly affects both the adsorption strength and the mobility of Na or K. All these results show that C5-10-16 could be used as a promising anode material for NLIBs.

13.
Br J Pharmacol ; 181(16): 2774-2793, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38644540

RESUMO

BACKGROUND AND PURPOSE: White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. EXPERIMENTAL APPROACH: WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. KEY RESULTS: Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. CONCLUSION AND IMPLICATIONS: Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.


Assuntos
Tecido Adiposo Branco , Artrite Experimental , Artrite Reumatoide , PPAR gama , Animais , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Humanos , Ratos , Artrite Experimental/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Masculino , Artrite Reumatoide/metabolismo , Artrite Reumatoide/tratamento farmacológico , PPAR gama/metabolismo , PPAR gama/agonistas , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Feminino , Ratos Endogâmicos Lew , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Adipocinas/metabolismo
14.
Strahlenther Onkol ; 200(6): 535-543, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453699

RESUMO

PURPOSE: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues. METHODS: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated. RESULTS: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells. CONCLUSION: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.


Assuntos
Apigenina , Glioma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Nus , MicroRNAs , PTEN Fosfo-Hidrolase , Tolerância a Radiação , Animais , MicroRNAs/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Apigenina/farmacologia , Apigenina/uso terapêutico , PTEN Fosfo-Hidrolase/genética , Camundongos , Glioma/radioterapia , Glioma/patologia , Glioma/genética , Glioma/tratamento farmacológico , Tolerância a Radiação/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Radiossensibilizantes/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C
15.
J Transl Med ; 22(1): 220, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429732

RESUMO

BACKGROUND: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. METHODS: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. RESULTS: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. CONCLUSION: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.


Assuntos
Antígeno CD47 , Neoplasias , Animais , Humanos , Neoplasias/patologia , Fagocitose , Macrófagos/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Modelos Animais de Doenças , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação/farmacologia , Antígenos de Diferenciação/uso terapêutico
17.
Langmuir ; 40(9): 4852-4859, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38382061

RESUMO

Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.

18.
J Phys Chem Lett ; 15(9): 2485-2492, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38408427

RESUMO

We propose a two-dimensional carbon allotrope (named KT-graphene) by incorporating kagome and tetragonal lattices consisting of trigonal, quadrilateral, octagonal, and dodecagonal rings. The introduction of non-hexagonal rings can give rise to the localized electronic states that improve the chemical reactivity toward potassium, making KT-graphene a high-performance anode material for potassium-ion batteries. It shows a high theoretical capacity (892 mAh g-1), a low diffusion barrier (0.33 eV), and a low average open-circuit voltage (0.51 V). The presence of electrolyte solvents is propitious to boost the K-ion adsorption and diffusion capabilities. Moreover, one-dimensional nanotubes (KT-CNTs), rolled up by the KT-graphene sheet, are metallic regardless of the tube diameter. As the curvature increases, KT-CNTs exhibit significantly increased surface activity, which can promote the electron-donating ability of K. Furthermore, the curvature effect greatly enhances the efficiency of K diffusion on the inner surface compared to that on the outer surface.

19.
Phys Chem Chem Phys ; 26(5): 4589-4596, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38250962

RESUMO

Multivalent-ion batteries have garnered significant attention due to their high energy density, low cost, and superior safety. Calcium-ion batteries (CIBs) are regarded as the next-generation energy storage systems for their abundant natural resources and bivalent characteristics. However, the absence of high-performance anode materials poses a significant obstacle to the progress of battery technology. Two-dimensional (2D) Dirac materials have excellent conductivity and abundant active sites, rendering them promising candidates as anode materials. A novel 2D Dirac material known as "graphene+" has been theoretically reported, exhibiting prominent properties including good stability, exceptional ductility, and remarkable electronic conductivity. By using first-principles calculations, we systematically investigate the performance of graphene+ as an anode material for CIBs. Graphene+ exhibits an ultra-high theoretical capacity (1487.7 mA h g-1), a small diffusion barrier (0.21 eV), and a low average open-circuit voltage (0.51 V). Furthermore, we investigate the impact of the electrolyte solvation on the performance of Ca-ion adsorption and migration. Upon contact with electrolyte solvents, graphene+ exhibits strong adsorption strength and rapid migration of Ca-ions on its surface. These results demonstrate the promising potential of graphene+ as a high-performance anode material for CIBs.

20.
Int J Oncol ; 64(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063241

RESUMO

Following the publication of the above article, a concerned reader drew to the Editor's attention that, regarding the western blots featured in Fig. 3B on p. 670, the bands featured in the U251 and U251­MC lanes for the miR­21 and U6 experiments appeared to be duplicates of each other. Moreover, certain of these data were strikingly similar to data that appeared in another article published at around the same time featuring some of the same authors (again, with apparent duplications of bands within the same gel slices, as they were presented). After having conducted an internal investigation of this matter, the Editor of International Journal of Oncology has judged that the apparently anomalous grouping of the data could not have been attributed to pure coincidence. Therefore, the Editor has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any incovenience caused, and we thank the reader for bringing this matter to our attention. [International Journal of Oncology 36: 665­672, 2010; DOI: 10.3892/ijo_00000542].

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