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1.
Anal Chem ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221578

RESUMO

Macrophages consist of a heterogeneous population of functionally distinct cells that participate in many physiological and pathological processes. They exhibit prominent plasticity by changing their different functional phenotypes represented by proinflammatory (M1) and anti-inflammatory (M2) in response to different environmental stimuli. Emerging evidence illustrates the importance of intracellular metabolic pathways in macrophage polarizations and functions. In the tumor microenvironment (TME), macrophages tend to M2 polarization, which promotes tumor growth and leads to adverse physiological effects. Due to the lack of highly specific antigens in M1 and M2 macrophages, significant challenges present in isolating these subtypes from clinical samples or in vitro coculture models of tumor-immune cells. In reverse, the single-cell technique provides the possibility to investigate the factors influencing macrophage polarization in the TME. In this research, we employed inertial microfluidic chip-mass spectrometry (IMC-MS) to conduct single-cell metabolomics analysis of macrophages polarized into the two major phenotypes, respectively, and 213 metabolites were identified in total. Subsequently, differential metabolites between macrophage phenotypes were analyzed using volcano plots and binary logistic regression models. Glutamine was pinpointed as a key metabolite for the M1 and M2 phenotypes. Experimental results from both monoculture and coculture cell models demonstrated that M1 polarization is more reliant on the presence of glutamine in the culture environment than M2 polarization. Glutamine deficiency resulted in failed M1 polarization, while its absence had a less pronounced effect on M2 polarization. Replenishing an appropriate amount of glutamine during the intermediate stages of coculture models significantly enhanced the proportion of M1 polarization and suppressed the growth of tumor cells. This research elucidated glutamine as a key factor influencing macrophage polarization in the TME via single-cell metabolomics based on IMC-MS, offering promising insights and targets for tumor therapies.

2.
Angew Chem Int Ed Engl ; : e202411794, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135198

RESUMO

The photoconversion of CO2 into valuable chemical products using solar energy is a promising strategy to address both energy and environmental challenges. However, the strongly adsorbed CO2 frequently impedes the seamless advancement of the subsequent reaction by significantly increasing the reaction activation energy. Here, we present a BiFeO3 material with lattice strain that collaboratively regulates the d/p-2π* orbitals hybridization between metal sites and *CO2 as well as *COOH intermediates to achieve rapid conversion of solidly adsorbed CO2 to critical *COOH intermediates, accelerating the overall CO2 reduction kinetics. Quasi in-situ X-ray photoelectron spectroscopy and in-situ Fourier Transform infrared spectroscopy combined with theoretical calculation reveals that the optimized Fe sites enhance the adsorption and activation effect of CO2, and continuous internal electrons are rapidly transferred to the reaction sites and injected into the surface *CO2 and *COOH under the condition of illumination, which promotes the rapid formation and stability of *COOH. Certainly, the performance of CO2 photoreduction to CO is improved by 12.81-fold compared with the base material. This work offers a new perspective for the rapid photoreduction process of strongly adsorbed CO2.

3.
Ecotoxicol Environ Saf ; 284: 116883, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39173222

RESUMO

Heavy metals (HMs) pollution is a globally emerging concern. It is difficult to cost-effectively combat such HMs polluted soil environments. The efficient remediation of HMs polluted soil is crucial to protect human health and ecological security that could be carried out by several methods. Amidst, biological remediation is the most affordable and ecological. This review focused on the principles, mechanisms, performances, and influential factors in bioremediation of HMs polluted soil. In microbial remediation, microbes can alter metallic compounds in soils. They transform these compounds into their metabolism through biosorption and bioprecipitation. The secreted microbial enzymes act as transformers and assist in HMs immobilization. The synergistic microbial effect can further improve HMs removal. In bioleaching, the microbial activity can simultaneously produce H2SO4 or organic acids and leach HMs. The production of acids and the metabolism of bacteria and fungi transform metallic compounds to soluble and extractable form. The key bioleaching mechanisms are acidolysis, complexolysis, redoxolysis and bioaccumulation. In phytoremediation, hyperaccumulator plants and their rhizospheric microbes absorb HMs by roots through absorption, cation exchange, filtration, and chemical changes. Then they exert different detoxification mechanisms. The detoxified HMs are then transferred and accumulated in their harvestable tissues. Plant growth-promoting bacteria can promote phytoremediation efficiency; however, use of chelants have adverse effects. There are some other biological methods for the remediation of HMs polluted soil environment that are not extensively practiced. Finally, the findings of this review will assist the practitioners and researchers to select the appropriate bioremediation approach for a specific soil environment.

4.
J Pharm Anal ; 14(10): 100997, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39211791

RESUMO

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.

5.
Biology (Basel) ; 13(8)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39194531

RESUMO

Urban lakes commonly suffer from nutrient over-enrichment, resulting in water quality deterioration and eutrophication. Constructed wetlands are widely employed for ecological restoration in such lakes but their efficacy in water purification noticeably fluctuates with the seasons. This study takes the constructed wetland of Jinshan Lake as an example. By analyzing the water quality parameters at three depths during both summer and winter, this study explores the influence of the constructed wetland on the water quality of each layer during different seasons and elucidates the potential mechanisms underlying these seasonal effects. The results indicate that the constructed wetland significantly enhances total nitrogen (TN) concentration during summer and exhibits the capacity for nitrate-nitrogen removal in winter. However, its efficacy in removing total phosphorus (TP) is limited, and may even serve as a potential phosphorus (P) source for the lake during winter. Water quality test results of different samples indicated they belong to Class III or IV. Restrictive factors varied across seasons: nitrate-nitrogen and BOD5 jointly affected water quality in winter, whereas TP predominantly constrained water quality in summer. These results could provide a reference for water quality monitoring and management strategies of constructed wetlands in different seasons in Jiangsu Province.

6.
Theranostics ; 14(9): 3674-3692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948057

RESUMO

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants in multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, the rapid development of various Trop2-targeted therapies, notably marked by the advent of the antibody-drug conjugate (ADC), revolutionized the outcome for patients facing Trop2-positive tumors with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides a comprehensive summary of advances in Trop2-targeted therapies, including ADCs, antibodies, multispecific agents, immunotherapy, cancer vaccines, and small molecular inhibitors, along with in-depth discussions on their designs, mechanisms of action (MOAs), and limitations. Additionally, we emphasize the clinical research progress of these emerging Trop2-targeted agents, focusing on their clinical application and therapeutic efficacy against tumors. Furthermore, we propose directions for future research, such as enhancing our understanding of Trop2's structure and biology, exploring the best combination strategies, and tailoring precision treatment based on Trop2 testing methodologies.


Assuntos
Antígenos de Neoplasias , Moléculas de Adesão Celular , Imunoconjugados , Terapia de Alvo Molecular , Neoplasias , Humanos , Antígenos de Neoplasias/imunologia , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/metabolismo , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Imunoterapia/métodos , Animais , Vacinas Anticâncer/uso terapêutico
7.
Adv Sci (Weinh) ; : e2401142, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073752

RESUMO

Drug resistance after long-term use of Tyrosine kinase inhibitors (TKIs) has become an obstacle for prolonging the survival time of patients with clear cell renal cell carcinoma (ccRCC). Here, genome-wide CRISPR-based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied. Mechanically, HDAC8 deacetylated ETS1 at the K245 site to promote the interaction between ETS1 and HIF-2α and enhance the transcriptional activity of the ETS1/HIF-2α complex. However, the antitumor effect of inhibiting HDAC8 on sensitized TKI is not very satisfactory. Subsequently, inhibition of HDAC8 increased the expression of NEK1, and up-regulated NEK1 phosphorylated ETS1 at the T241 site to promote the interaction between ETS1 and HIF-2α by impeded acetylation at ETS1-K245 site is showed. Moreover, TKI treatment increased the expression of HDAC8 by inhibiting STAT3 phosphorylation in ccRCC cells is also found. These 2 findings highlight a potential mechanism of acquired resistance to TKIs and HDAC8 inhibitors in ccRCC. Finally, HDAC8-in-PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC-targeted therapies.

8.
Br J Cancer ; 131(3): 444-456, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38890443

RESUMO

BACKGROUND: The combined use of CDK4/6 inhibitors and mTOR inhibitors has achieved some clinical success in ccRCC. Exploring the underlying mechanism of the CDK4/6 pathway in cancer cells and the drug interactions of CDK4/6 inhibitors in combination therapy could help identify new therapeutic strategies for ccRCC. Notably, CDK4/6 inhibitors inactivate the mTOR pathway by increasing the protein levels of TSC1, but the mechanism by which CDK4/6 inhibitors regulate TSC1 is still unclear. METHODS: Mass spectrometry analysis, coimmunoprecipitation analysis, GST pull-down assays, immunofluorescence assays, Western blot analysis and RT‒qPCR analysis were applied to explore the relationships among CDK4, RNF26 and TSC1. Transwell assays, tube formation assays, CCK-8 assays, colony formation assays and xenograft assays were performed to examine the biological role of RNF26 in renal cancer cells.TCGA-KIRC dataset analysis and RT‒qPCR analysis were used to examine the pathways affected by RNF26 silencing. RESULTS: CDK4/6 inhibitors stabilized TSC1 in cancer cells. We showed that CDK4 enhances the interaction between TSC1 and RNF26 and that RNF26 activates the mTOR signaling pathway in ccRCC, contributes to ccRCC progression and angiogenesis, and promotes tumorigenesis. We then found that RNF26 functions as an E3 ligase of TSC1 to regulate CDK4-induced TSC1. This finding suggested that RNF26 promotes ccRCC progression and angiogenesis to some extent by negatively regulating TSC1. CONCLUSION: Our results revealed a novel CDK4/RNF26/TSC1 axis that regulates the anticancer efficacy of CDK4/6 inhibitors and mTOR inhibitors in ccRCC.


Assuntos
Carcinoma de Células Renais , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Neoplasias Renais , Serina-Treonina Quinases TOR , Proteína 1 do Complexo Esclerose Tuberosa , Ubiquitina-Proteína Ligases , Humanos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Proteína 1 do Complexo Esclerose Tuberosa/genética , Ubiquitina-Proteína Ligases/metabolismo , Camundongos , Animais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/genética , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Fosforilação/efeitos dos fármacos
9.
J Environ Manage ; 363: 121336, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850915

RESUMO

Sulfur-siderite autotrophic denitrification (SSAD) has been proved to solve the key problem of low nitrogen removal efficiency caused by the shortage of carbon source in constructed wetlands (CWs). In this study, five vertical flow constructed wetlands (VFCWs) were constructed with different Fe/S ratios (0/0, 0/1, 1/1, 2/1 and 1/2) to optimizing SSAD process, labeled S.0, S.1, S.2, S.3 and S.4. The results showed that the best NO3--N and TN removal rates were achieved with a Fe/S ratio of 2:1 (S.3), which were 96.26 ± 1.40% and 93.63 ± 3.12%, respectively. The abundance of denitrification genes (nirS, nirK and nosZ) in S.3 was significantly increased. Illumina high-throughput sequencing analysis indicated that the abundance and diversity of microorganisms involved in the "Sulfur-Iron-Nitrogen" cycle were enriched in S.3. The current study provided that the "Sulfur-Iron-Nitrogen" cycle in CWs was optimized by adjusting Fe/S ratio, and more types of denitrifying bacteria could be enriched, thereby enhancing nitrogen removal.


Assuntos
Desnitrificação , Ferro , Nitrogênio , Enxofre , Áreas Alagadas , Nitrogênio/metabolismo , Enxofre/metabolismo , Ferro/metabolismo
10.
J Hazard Mater ; 474: 134740, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38805821

RESUMO

Construction of air filter membranes bearing prominent collecting and transferring capability is highly desirable for detecting airborne pathogens but remains challenging. Here, a hyaluronic acid air filter membrane (HAFM) with tunable heterogeneous micro-nano porous structures is straightforwardly constructed through the ethanol-induced phase separation strategy. Airborne pathogens can be trapped and collected by HAFM with high performance due to the ideal trade-off between removal efficiency and pressure drop. By exempting the sample elution and extraction processes, the HAFM after filtration sampling can not only directly disperse on the agar plate for colony culture but also turn to an aqueous solution for centrifugal enrichment, which significantly reduces the damage and losses of the captured microorganisms. The following combination with ATP bioluminescence endows the HAFM with a real-time quantitative detection function for the captured airborne pathogens. Benefiting from high-efficiency sampling and non-traumatic transfer of airborne pathogens, the real-world bioaerosol concentration can be facilely evaluated by the HAFM-based ATP assay. This work thus not only provides a feasible strategy to fabricate air filter membranes for efficient microbial collection and enrichment but also sheds light on designing advanced protocols for real-time detection of bioaerosols in the field.


Assuntos
Filtros de Ar , Microbiologia do Ar , Membranas Artificiais , Filtros de Ar/microbiologia , Filtração/instrumentação , Aerossóis/análise , Monitoramento Ambiental/métodos , Trifosfato de Adenosina/análise , Bactérias/isolamento & purificação
11.
J Colloid Interface Sci ; 670: 417-427, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38772258

RESUMO

Air filtration has become a desirable route for collecting airborne microbes. However, the potential biotoxicity and sterilization of current air filtration membranes often lead to undesired inactivation of captured microbes, which greatly limits microbial non-traumatic transfer and recovery. Herein, we report a gel-confined phase separation strategy to rationally fabricate a fully bio-based filtration membrane (SGFM) using soluble soybean polysaccharide and gelatin. The versatile SGFM features fascinating honeycomb micro-nano architecture and hierarchical interconnected porous structures for microbial capture, and achieves a lower pressure drop, higher interception efficiency (99.3%), and superior microbial survivability than commercial gelatin filtration membranes. Particularly, the water-dissolvable SGFM can greatly simplify the elution and extraction process after bioaerosol sampling, thereby bringing about maximum sample transfer and vigorous recovery of collected microbes. Meanwhile, green capture coupled with ATP bioluminescence endows the SGFM with rapid and quantitative detection capability for airborne microbes. This work may pave the way for designing green protocols for the detection of bioaerosols.


Assuntos
Microbiologia do Ar , Filtração , Membranas Artificiais , Gelatina/química , Glycine max/química , Glycine max/microbiologia , Tamanho da Partícula , Géis/química , Química Verde , Propriedades de Superfície , Porosidade
12.
J Environ Qual ; 53(3): 340-351, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595076

RESUMO

The primary drivers of eutrophication in lakes following the reduction of external nutrient inputs are the release of N and P from sediments. Constructed wetlands play a pivotal role in ameliorating N, P, and other biogenic element levels. However, the presence of large vegetation in these wetlands also substantially contributes to nutrient accumulation in sediments, a phenomenon influenced by seasonal variations. In this study, a typical constructed wetland was selected as the research site. The research aimed to analyze the forms of N and P in sediments during both summer and winter. Simultaneously, a comprehensive pollution assessment and analysis were conducted within the study area. The findings indicate that elevated summer temperatures, together with the presence of wetland vegetation, promote the release of N through the nitrification process. Additionally, seasonal variations exert a significant impact on the distribution of P storage. Furthermore, the role of constructed wetlands in the absorption and release of N and P is primarily controlled by the influence of organic matter on nitrate-nitrogen, nitrite-nitrogen, and available phosphorus, and is also subject to seasonal fluctuations. In summary, under the comprehensive influence of constructed wetlands, vegetation types, and seasons, sediments within the lake generally exhibit a state of mild or moderate pollution. Therefore, targeted measures should be adopted to optimally adjust vegetation types, and human intervention is necessary, involving timely sediment harvesting during the summer to reduce N and P loads, and enhancing sediment adsorption and retention capacity for N and P during the winter.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Nitrogênio , Fósforo , Estações do Ano , Poluentes Químicos da Água , Áreas Alagadas , Lagos/química , Fósforo/análise , Nitrogênio/análise , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , Poluentes Químicos da Água/análise , Eutrofização , Inundações
13.
Cell Death Differ ; 31(5): 592-604, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514847

RESUMO

RB transcriptional corepressor 1 (RB) deletion is the most important genomic factor associated with the prognosis of castration-resistant prostate cancer (CRPC) patients receiving androgen receptor (AR) signaling inhibitor therapy. Loss of RB could support prostate cancer cell growth in a hormone-independent manner, but the underlying mechanism by which RB regulates tumor progression extends far beyond the cell cycle pathway. A previous study indicated that RB inactivates AKT signaling but has no effect on mTOR signaling in cancer cells. Here, we found that the S249/T252 site in RB is key to regulating the transcriptional activity of the tumor-promoting factor TRIM24 in CRPC, as identified through FXXXV mapping. The RB/TRIM24 complex functions through DUSP2, which serves as an intermediate bridge, to activate the mTOR pathway and promote prostate cancer progression. Accordingly, we designed RB-linker-proteolysis-targeting chimera (PROTAC) molecules, which decreased TRIM24 protein levels and inactivated the mTOR signaling pathway, thereby inhibiting prostate cancer. Therefore, this study not only elucidates the novel function of RB but also provides a theoretical basis for the development of new drugs for treating prostate cancer.


Assuntos
Proteína do Retinoblastoma , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Humanos , Masculino , Camundongos , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Nus , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Proteína do Retinoblastoma/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatase 2 de Especificidade Dupla/metabolismo
14.
Angew Chem Int Ed Engl ; 63(15): e202400857, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38356122

RESUMO

Photocatalytic oxygen reductive H2O2 production is a promising approach to alternative industrial anthraquinone processes while suffering from the requirement of pure O2 feedstock for practical application. Herein, we report a spaced double hydrogen bond (IC-H-bond) through multi-component Radziszewski reaction in an imidazole poly-ionic-liquid composite (SI-PIL-TiO2) and levofloxacin hydrochloride (LEV) electron donor for highly efficient and selective photocatalytic air reductive H2O2 production. It is found that the IC-H-bond formed by spaced imino (-NH-) group of SI-PIL-TiO2 and carbonyl (-C=O) group of LEV can switch the imidazole active sites characteristic from a covered state to a fully exposed one to shield the strong adsorption of electron donor and N2 in the air, and propel an intenser positive potential and more efficient orbitals binding patterns of SI-PIL-TiO2 surface to establish competitive active sites for selectivity O2 chemisorption. Moreover, the high electron enrichment of imidazole as an active site for the 2e- oxygen reduction ensures the rapid reduction of O2. Therefore, the IC-H-bond enables a total O2 utilization and conversion efficiency of 94.8 % from direct photocatalytic air reduction, achieving a H2O2 production rate of 1518 µmol/g/h that is 16 and 23 times compared to poly-ionic-liquid composite without spaced imino groups (PIL-TiO2) and TiO2, respectively.

15.
Mater Today Bio ; 24: 100918, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38223459

RESUMO

The development of skin substitutes aims to replace, mimic, or improve the functions of human skin, regenerate damaged skin tissue, and replace or enhance skin function. This includes artificial skin, scaffolds or devices designed for treatment, imitation, or improvement of skin function in wounds and injuries. Therefore, tremendous efforts have been made to develop functional skin substitutes. However, there is still few reports systematically discuss the relationship between the advanced function and design requirements. In this paper, we review the classification, functions, and design requirements of artificial skin or skin substitutes. Different manufacturing strategies for skin substitutes such as hydrogels, 3D/4D printing, electrospinning, microfluidics are summarized. This review also introduces currently available skin substitutes in clinical trials and on the market and the related regulatory requirements. Finally, the prospects and challenges of skin substitutes in the field of tissue engineering are discussed.

16.
Pharmacol Ther ; 253: 108577, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38081519

RESUMO

Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include 111In-DTPA-BC-2, 131I-BC-2, 131I-BC-4, 90Y-BC4, 131I81C6, 131I-ch81C6, 211At-ch81C6, F16124I, 131I-tenatumomab, ST2146biot, FDC 131I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and 125I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.


Assuntos
Imunoconjugados , Tenascina , Humanos , Matriz Extracelular , Peptídeos , Imunoconjugados/uso terapêutico , Linhagem Celular Tumoral
17.
Front Immunol ; 14: 1323670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143761

RESUMO

Growth differentiation factor 11 (GDF11) is one of the important factors in the pathophysiological process of animals. It is widely expressed in many tissues and organs of animals, showing its wide biological activity and potential application value. Previous research has demonstrated that GDF11 has a therapeutic effect on various diseases, such as anti-myocardial aging and anti-tumor. This has not only sparked intense interest and enthusiasm among academics but also spurred some for-profit businesses to attempt to develop GDF11 as a medication for regenerative medicine or anti-aging application. Currently, Sotatercept, a GDF11 antibody drug, is in the marketing application stage, and HS-235 and rGDF11 are in the preclinical research stage. Therefore, we believe that figuring out which cells GDF11 acts on and its current problems should be an important issue in the scientific and commercial communities. Only through extensive, comprehensive research and discussion can we better understand the role and potential of GDF11, while avoiding unnecessary risks and misinformation. In this review, we aimed to summarize the role of GDF11 in different cells and its current controversies and challenges, providing an important reference for us to deeply understand the function of GDF11 and formulate more effective treatment strategies in the future.


Assuntos
Células , Fatores de Diferenciação de Crescimento , Humanos , Animais , Fatores de Diferenciação de Crescimento/metabolismo , Fatores de Diferenciação de Crescimento/uso terapêutico , Células/metabolismo , Biomarcadores , Neoplasias/terapia , Cardiomiopatias/terapia , Inflamação/terapia
18.
Front Immunol ; 14: 1292839, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954614

RESUMO

Human epithelial growth factor receptor-2 (HER2) plays an oncogenic role in numerous tumors, including breast, gastric, and various other solid tumors. While anti-HER2 therapies are approved for the treatment of HER2-positive tumors, a necessity persists for creating novel HER2-targeted agents to resolve therapeutic resistance. Utilizing a synthetic nanobody library and affinity maturation, our study identified four anti-HER2 nanobodies that exhibited high affinity and specificity. These nanobodies recognized three distinct epitopes of HER2-ECD. Additionally, we constructed VHH-Fc and discovered that they facilitated superior internalization and showed moderate growth inhibition. Compared to the combination of trastuzumab and pertuzumab, the VHH-Fc combos or their combination with trastuzumab demonstrated greater or comparable antitumor activity in both ligand-independent and ligand-driven tumors. Most remarkably, A9B5-Fc, which targeted domain I of HER2-ECD, displayed significantly enhanced trastuzumab-synergistic antitumor efficacy compared to pertuzumab under trastuzumab-resistant conditions. Our findings offer anti-HER2 nanobodies with high affinity and non-overlapping epitope recognition. The novel nanobody-based HER2-targeted antibody, A9B5-Fc, binding to HER2-ECD I, mediates promising receptor internalization. It possesses the potential to serve as a potent synergistic partner with trastuzumab, contributing to overcoming acquired resistance.


Assuntos
Neoplasias , Anticorpos de Domínio Único , Humanos , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Receptor ErbB-2 , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/uso terapêutico , Ligantes , Neoplasias/patologia , Epitopos
19.
J Control Release ; 363: 180-200, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37739014

RESUMO

Wound healing is a crucial process that restores the integrity and function of the skin and other tissues after injury. However, external factors, such as infection and inflammation, can impair wound healing and cause severe tissue damage. Therefore, developing new drugs or methods to promote wound healing is of great significance. Photothermal therapy (PTT) is a promising technique that uses photothermal agents (PTAs) to convert near-infrared radiation into heat, which can eliminate bacteria and stimulate tissue regeneration. PTT has the advantages of high efficiency, controllability, and low drug resistance. Hence, nanomaterial-based PTT and its related strategies have been widely explored for wound healing applications. However, a comprehensive review of PTT-related strategies for wound healing is still lacking. In this review, we introduce the physiological mechanisms and influencing factors of wound healing, and summarize the types of PTAs commonly used for wound healing. Then, we discuss the strategies for designing nanocomposites for multimodal combination treatment of wounds. Moreover, we review methods to improve the therapeutic efficacy of PTT for wound healing, such as selecting the appropriate wound dressing form, controlling drug release, and changing the infrared irradiation window. Finally, we address the challenges of PTT in wound healing and suggest future directions.


Assuntos
Nanocompostos , Fototerapia , Fototerapia/métodos , Cicatrização , Temperatura Alta , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
20.
Mater Today Bio ; 21: 100710, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37545561

RESUMO

Electrospinning as a versatile, simple, and cost-effective method to engineer a variety of micro or nanofibrous materials, has contributed to significant developments in the biomedical field. However, the traditional electrospinning of single material only can produce homogeneous fibrous assemblies with limited functional properties, which oftentimes fails to meet the ever-increasing requirements of biomedical applications. Thus, multi-material electrospinning referring to engineering two or more kinds of materials, has been recently developed to enable the fabrication of diversified complex fibrous structures with advanced performance for greatly promoting biomedical development. This review firstly gives an overview of multi-material electrospinning modalities, with a highlight on their features and accessibility for constructing different complex fibrous structures. A perspective of how multi-material electrospinning opens up new opportunities for specific biomedical applications, i.e., tissue engineering and drug delivery, is also offered.

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