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1.
J Colloid Interface Sci ; 677(Pt B): 1061-1074, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39180841

RESUMO

The development of bacterial resistance significantly contributes to the persistence of infections. Although previous studies have highlighted the benefits of metal-doped positive carbon nanodots in managing bacterial wound infections, their mechanism of action is relatively simple and they may pose potential hazards to human cells. Therefore, it is essential to develop a one-stop carbon dot nanoplatform that offers high biocompatibility, antibacterial properties, and anti-inflammatory activities for wound infection management. This study explores the antibacterial efficacy, without detectable resistance, and wound-healing potential of nitrogen-doped (N-doped) negatively charged carbon dots (TPP-CDs). These carbon dots are synthesized using tannic acid (TA), polyethylene polyamine, and polyethylene glycol (PEG) as precursors, with a focus on their biocompatibility. Numerous systematic studies have shown that TPP-CDs can effectively destroy bacterial biofilms and deoxyribonucleic acid (DNA), while also inducing oxidative stress, leading to a potent antimicrobial effect. TPP-CDs also demonstrate the ability to scavenge excess free radicals, promote cellular proliferation, and inhibit inflammatory factors, all of which contribute to improved wound healing. TPP-CDs also demonstrate favorable cell imaging capabilities. These findings suggest that N-doped negatively charged TPP-CDs hold significant potential for treating bacterial infections and offer practical insights for their application in the medical field.


Assuntos
Antibacterianos , Anti-Inflamatórios , Materiais Biocompatíveis , Carbono , Testes de Sensibilidade Microbiana , Nitrogênio , Pontos Quânticos , Antibacterianos/farmacologia , Antibacterianos/química , Carbono/química , Carbono/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Humanos , Pontos Quânticos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nitrogênio/química , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Tamanho da Partícula , Animais , Propriedades de Superfície , Biofilmes/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Camundongos , Escherichia coli/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
2.
Anal Methods ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39351967

RESUMO

Cancer-associated extracellular vesicles (EVs) are crucial biomarkers for cancer diagnosis as they contain abundant tumor cell information. To efficiently and accurately detect cancer-associated EVs, an electrochemical hydrogen peroxide reduction reaction (HPRR)-based biosensor was developed, utilizing enzyme-linked immunosorbent and diatomic catalyst strategies for catalytic HPRR current amplification for specific identification and highly sensitive detection. The anti-CXCR4 antibody was immobilized on a Au-plated electrode to selectively capture EVs from the sample. Subsequently, Fe/Cu diatomic catalysts, modified with an anti-CD63 antibody, were bound to the CD63 on the EVs. Quantitative detection of EVs was achieved by measuring the electrical signals from the HPRR catalyzed by the labeled Fe/Cu diatomic catalysts. Under optimized conditions, the electrochemical signals exhibited a linear relationship with EV concentration in the range of 500 to 1 × 107 particles mL-1, with a detection limit of 117 particles mL-1, maintaining accuracy even in FBS. With its affordability, high sensitivity, and ease of use, this sensor holds significant potential for medication guidance and postoperative evaluation.

3.
World J Gastrointest Oncol ; 16(9): 4028-4036, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39350996

RESUMO

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and cases of GISTs tend to be of the disseminated type, with a global incidence of 10 to 15 cases/million each year. The rarer familial GISTs, which often represent a population, differ in screening, diagnosis, and treatment. Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs. However, whether the same genetic family has different phenotypes has not been reported. CASE SUMMARY: We report two cases of rare GISTs in the same family: A male patient with the V561D mutation in exon 12 of the PDGFRA gene, who has been taking the targeted drug imatinib since undergoing surgery, and a female patient diagnosed with wild-type GIST, who has been taking imatinib for 3 years since undergoing surgery. The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy, and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease. CONCLUSION: Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

5.
J Gene Med ; 26(10): e3741, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39357835

RESUMO

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.


Assuntos
Aspartato-Amônia Ligase , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Aspartato-Amônia Ligase/genética , Aspartato-Amônia Ligase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Prognóstico , Animais , Camundongos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida
6.
J Am Chem Soc ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361550

RESUMO

Membrane-free biphasic self-stratified batteries (MBSBs) utilizing aqueous/nonaqueous electrolyte systems have garnered significant attention owing to their flexible manufacturing and cost-effectiveness. In this study, we present an ultrastable high-voltage Mg MBSB based on an aqueous/nonaqueous electrolyte system. The engineered aqueous electrolyte had a wide electrochemical stability window of 3.24 V. The Mg metal anode features a Mg2+-conductive protective coating. Two metal-free redox compounds, 2,2,6,6-tetramethylpiperdinyl oxy (TEMPO) and N-propyl phenothiazine (C3-PTZ), were used as catholytes. The Mg||TEMPO and Mg||C3-PTZ MBSBs exhibited high cell voltages of 2.07 and 2.12 V, respectively, and were studied under static, stirred, and flow conditions. The Mg MBSBs were initially evaluated at different catholyte concentrations (0.1, 0.3, and 0.5 M) under static conditions. Notably, the Mg||TEMPO (0.5 M) and Mg||C3-PTZ (0.5 M) static batteries maintained exceptional performances over 500 cycles at 8 mA/cm2, with capacity retention rates of 97.84% and 98.87%, Coulombic efficiencies of 99.17% and 99.12%, and capacity utilization of 70.2% and 71.3%, respectively. Under stirred and flow conditions, the Mg||TEMPO (0.5 M) and Mg||C3-PTZ (0.5 M) batteries cycled 500 times at 12 mA/cm2 demonstrated capacity retention rates of 99.82% and 99.88% (stirred), 93.58% and 92.16% (flow), respectively. Under flow conditions, the Mg||TEMPO (0.5 M) and Mg||C3-PTZ (0.5 M) batteries demonstrated power densities of 195 and 191 mW/cm2, respectively, surpassing those of 139 and 144 mW/cm2 under static conditions. These cost-effective Mg MBSBs exhibit remarkable performance and advance the application of Mg chemistry in organic flow batteries.

7.
Int Immunopharmacol ; 143(Pt 1): 113299, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39362017

RESUMO

The purpose of this work was to investigate how curcumin (Cur) might enhance cognitive function and to gain a better understanding of the molecular mechanisms behind Cur's impacts on neurogenesis deficits brought on by intermittent hypoxia (IH). Using network pharmacology, we explored possible targets for Cur's obstructive sleep apnea (OSA) therapy. We established an IH model using C57BL/6 mice and c17.2 cells, and we assessed the influence of Cur on treatment outcomes as well as the effect of IH on cognitive function. Hippocampal damage and neurogenesis, as well as expression of core targets, were then examined. Network pharmacology analysis revealed that Cur has the potential for multi-target, multi-pathway therapy, with CTNNB1 and MYC as core target genes. The Morris water maze test showed that Cur (100 mg/kg, intragastrically) significantly improved cognitive dysfunction induced by IH. The hematoxylin and eosin (H&E) and Nissl staining indicated that Cur could alleviate damage to the hippocampus caused by IH. Immunohistochemistry, immunofluorescence, and western blotting results showed that Cur might promote neurogenesis and upregulate the expression of ß-catenin and c-myc. In vitro, Cur (0.5 µM) has a protective effect on IH-induced neural stem cells (NSCs) injury and apoptosis and can restore the Wnt/ß-catenin. Cur significantly increased the neurogenesis via the Wnt/ß-catenin pathway, providing the scientific groundwork for the development of new treatment strategies for neurological damage linked to OSA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39356200

RESUMO

High-/medium-entropy materials have been explored as promising electrocatalysts for water splitting due to their unique physical and chemical properties. Unfortunately, state-of-the-art materials face the dilemma of explaining the enhancement mechanism, which is now limited to theoretical models or an unclear cocktail effect. Herein, a medium-entropy NiCoFeMnP with an advanced hierarchical particle-nanosheet-tumbleweed nanostructure has been synthesized via simple precursor preparation and subsequent phosphorization. Evaluated as the electrocatalyst for oxygen evolution reaction (OER), the medium-entropy NiCoFeMnP displays a lower overpotential of 272 mV at a current density of 10 mA cm-2, and more favorable kinetics than the binary NiFeP, ternary NiCoFeP, quaternary NiCoFeCuP and NiCoFeCrP counterparts, and other reported high-/medium-entropy electrocatalysts. Careful experimental analyses reveal that the incorporation of Mn can significantly regulate the electronic structure of Ni, Co, and Fe sites. More importantly, the Mn introduction and entropy stabilization effect in the reconstructed metal (oxy)hydroxide simultaneously promote the lattice oxygen mechanism, improving the activity. This work sheds new light on the design of high-/medium-entropy materials from an in-depth understanding of the underlying mechanism for improving energy conversion efficiency.

9.
Plant Biotechnol J ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364753

RESUMO

Monitoring and localizing molecules on living plants is critical for understanding their growth, development and disease. However, current techniques for molecular imaging of living plants often lack spatial information or require tedious pre-labelling. Here, we proposed a novel molecular imaging platform that combines sliver nanowire-doped Ti3C2 MXene (Ag NWs@MXene) flexible film substrate with laser desorption/ionization mass spectrometry imaging (AMF-LDI-MSI) to study the spatial distribution of biomolecules on the surface of living plants. This platform overcomes the MSI challenges posed by difficult-to-slice plant tissues (e.g., tough or water-rich roots and fragile flowers) and enables precisely transfer and visualize the molecule. Comparisons of the measurement results to those from matrix-assisted LDI-MSI (MALDI-MSI) technology demonstrate the accuracy and reliability of the platform. Biocompatibility evaluations indicated that the platform without observable adverse effects on the health of living plants. The distribution of growth and disease-associated signalling molecules, such as choline, organic acids and carbohydrates, can be in situ non-destructively detected on the surfaces of living plants, which is important for tracking the health of plants and their diseased areas. AMF-LDI-MSI platform can serve as a promising tool for label-free, in situ and non-destructive monitoring of functional biomolecules and plant growth from a spatial perspective.

10.
Discov Oncol ; 15(1): 519, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361158

RESUMO

Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients' disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa.

11.
Nat Commun ; 15(1): 8555, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39362864

RESUMO

Boron-doped acenes have attracted attention due to their unique structures and intriguing luminescent properties. However, the hitherto known boron-doped acenes have only one or two boron atoms, limiting the chemical space of this unique family of compounds and the capability to tune their optical properties. Herein, we report the synthesis of quadruply boron-doped acenes, including pentacene, heptacene, and nonacene. The importance of the boron doping level on the luminescent properties of acenes is demonstrated. The title compounds manifest enhanced Lewis acidity as compared with dihydrodiboraacenes, leading to Lewis-base-responsive emission in the solid state. Moreover, quadruply boron-doped nonacene displays mechanochromic luminescence in addition to Lewis-base-responsive properties, realizing high-contrast solid-state multicolor emission. This work greatly expands the chemistry of boron-doped acenes and offers opportunities for developing boron-based luminescent materials.

13.
Langmuir ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39383054

RESUMO

In this work, a water droplet impacting superhydrophobic flexible cantilever beams is systematically studied via experimental methods, aimed at recognizing the significance of the system dynamics that arises from the interplay between substrate oscillation and droplet impact. Influences of the substrate stiffness and the impact Weber number on the substrate oscillation and droplet impact dynamic are the focus particularly. For substrate oscillations, the beam deflection increases with the Weber number but decreases with the beam stiffness, while the oscillation period of the beam is not affected by the impact dynamic. For the droplet impact dynamic, the spreading dynamic is independent of beam oscillation, while the retraction dynamic is closely related to the surface elasticity. The effect of the cantilever beams on the droplet (i.e., promoting or inhibiting the rebound behavior) is dependent on the coupling movement of the water drop and the cantilever beam, which is varied by changing the stiffness of the cantilever beam. The findings of this work will provide a theoretical reference for the application of flexible substrates in the fields of anti-icing and self-cleaning.

14.
Front Plant Sci ; 15: 1442618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39391771

RESUMO

Background: In recent years, more severe droughts have occurred frequently in many parts of the world, drought stress is the primary abiotic stress factor restricting the growth and quality of flue-cured tobacco. Therefore, screening dryland cultivation-compatible flue-cured tobacco varieties will help reduce the negative impact of drought. Methods: Tobacco varieties were selected: Qinyan 96 (Q96), Zhongyan 101 (Z101), Yunyan 87 (Y87), and Yunyan 116 (Y116). A pot experiment was conducted with four water supply gradients: sufficient, mild stress, moderate stress, and severe stress. The aim was to analyze inter-varietal differences in agronomic traits, photosynthetic traits, reactive oxygen species (ROS) metabolism, and antioxidant enzyme system under drought stress. Additionally, the drought resistance of four flue-cured tobacco varieties was evaluated using principal component analysis and membership function analysis. Results: The results showed that drought intensification inhibited seedling growth and development across all varieties, with Q96 showing the least decrease and Y116 the greatest. With the increasing degree of drought stress, photosynthetic rates (Pn), transpiration rate (Tr), and stomatal conduction (Gs) have shown gradually decreasing trends, while substomatal cavity CO2 concentration (Ci) showed a growing trend. Severe drought corresponded with lower chlorophyll content and decreased the maximal photochemical efficiency (Fv/Fm), photosystem II (PSII), and photochemical quenching coefficient (qP) in all varieties, while steady-state non-photochemical quenching (NPQ) increased. Increased drought stress led to significantly higher reactive oxygen species (ROS) and malondialdehyde (MDA) content accumulation in tobacco seedlings. The antioxidant enzyme activities in, Q96, Z101, and Y87 increased under mild drought stress, whereas Y116 showed decreased activity. Conclusion: The drought resistance ranking among the four varieties is as follows: Q96 > Z101 > Y87 > Y116. Therefore, Q96 is a promising drought-tolerant breeding material that can be used as a reference for dryland cultivation of flue-cured tobacco.

15.
J Am Chem Soc ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392614

RESUMO

Single-crystalline covalent organic frameworks (COFs) are highly desirable toward understanding their pore chemistry and functions. Herein, two 50-100 µm single-crystalline three-dimensional (3D) COFs, TAM-TFPB-COF and TAPB-TFS-COF, were prepared from the condensation of 4,4',4″,4‴-methanetetrayltetraaniline (TAM) with 3,3',5,5'-tetrakis(4-formylphenyl)bimesityl (TFPB) and 3,3',5,5'-tetrakis(4-aminophenyl)bimesityl (TAPB) with 4,4',4″,4‴-silanetetrayltetrabenzaldehyde (TFS), respectively, in 1,4-dioxane under the catalysis of acetic acid. Single-crystal 3D electron diffraction reveals the triply interpenetrated dia-b networks of TAM-TFPB-COF with atom resolution, while the isostructure of TAPB-TFS-COF was disclosed by synchrotron single-crystal X-ray diffraction and synchrotron powder X-ray diffraction with Le Bail refinements. The nitrogen sorption measurements at 77 K disclose the microporosity nature of both activated COFs with their exceptionally high Brunauer-Emmett-Teller surface areas of 3533 and 4107 m2 g-1, representing the thus far record high specific surface area among imine-bonded COFs. This enables the activated COFs to exhibit also the record high methane uptake capacities up to 28.9 wt % (570 cm3 g-1) at 25 °C and 200 bar among all COFs reported thus far. This work not only presents the structures of two single-crystalline COFs with exceptional microporosity but also provides an example of atom engineering to adjust permanent microporous structures for methane storage.

16.
Inorg Chem ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39385599

RESUMO

A B-site ordered double perovskite oxide Cd2CrSbO6 was synthesized under high-pressure and high-temperature conditions. The compound crystallizes to a monoclinic structure with a space group of P21/n. The charge configuration is confirmed to be that of Cd2+/Cr3+/Sb5+. The magnetic Cr3+ ions form a tetrahedral structural frustrated lattice, while a long-range ferromagnetic phase transition is found to occur at TC = 16.5 K arising from the superexchange interaction via the Cr-O-Cd-O-Cr pathway. Electrical transport measurements indicate that Cd2CrSbO6 is an insulator that can be described by the Mott 3D variable range hopping mechanism. First-principles calculations reproduce well the ferromagnetic and insulating ground state of Cd2CrSbO6 with an energy band gap of 1.55 eV. The intrinsic ferromagnetic insulating nature qualifies Cd2CrSbO6 as a promising candidate for possible spintronics applications.

17.
Int Immunopharmacol ; 143(Pt 1): 113193, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39368132

RESUMO

BACKGROUND: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown. PURPOSE: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms. METHODS: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/ß-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC. RESULTS: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/ß-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/ß-catenin pathway. CONCLUSIONS: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG.

18.
Colloids Surf B Biointerfaces ; 245: 114279, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39368423

RESUMO

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and drug resistance. To overcome these challenges, we developed a bismuth-based nanomaterial (BOS) for thermal injury-assisted continuous targeted therapy in HCC. Initially, the mesoporous nanomaterial was loaded with SOR, forming the BOS@SOR nano-carrier system for drug delivery and controlled release. Notably, compared to targeted or photothermal therapy alone, the combination therapy using this nano-carrier system significantly impaired cell proliferation and increased apoptosis. In vivo efficacy evaluations demonstrated that BOS@SOR exhibited excellent biocompatibility, confirmed through hemolysis and biochemical analyses. Additionally, BOS@SOR enhanced contrast in computed tomography, aiding in the precise identification of HCC size and location. The photothermal therapeutic properties of bismuth further contributed to the synergistic anti-tumor activity of BOS@SOR, significantly reducing tumor growth in an orthotopic xenograft HCC model. Taken together, encapsulating SOR within a bismuth-based mesoporous nanomaterial creates a multifunctional and environmentally stable nanocomposite (BOS@SOR), enhancing the therapeutic effect of SOR and presenting an effective strategy for HCC treatment.

19.
Cell Rep Med ; : 101758, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39368479

RESUMO

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation mediates genomic instability by inducing transcription-replication conflicts. Strikingly, CDK12-mutant organoids and patient-derived xenografts are sensitive to inhibition or degradation of the paralog kinase, CDK13. We therein establish CDK12 as a bona fide tumor suppressor, mechanistically define how CDK12 inactivation causes genomic instability, and advance a therapeutic strategy for CDK12-mutant mCRPC.

20.
Exp Ther Med ; 28(6): 439, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39355518

RESUMO

Prostate cancer poses a serious threat to the well-being of men worldwide, with the leading cause of mortality being primarily through metastasis. Prostate cancer metastasis is dependent on cell communication, which is an essential component of this process; yet its exact mechanism remains obscure. Nonetheless, cell-to-cell communication plays a critical part in prostate cancer metastasis. Exosomes play an indispensable role in the development of metastatic growth by promoting intercellular communication. They are pivotal regulatory agents for both prostate cancer cells as well as their microenvironment. The present study investigated the makeup and function of exosomes in the tumor microenvironment, highlighting their significance to prostate cancer metastasis.

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