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1.
iScience ; 27(5): 109547, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38660400

RESUMO

Circulating tumor cell clusters/micro-emboli (CTM) possess greater metastatic capacity and survival advantage compared to individual circulating tumor cell (CTC). However, the formation of CTM subtypes and their role in tumor metastasis remain unclear. In this study, we used a microfluidic Cluster-Chip with easy operation and high efficiency to isolate CTM from peripheral blood, which confirmed their correlation with clinicopathological features and identified the critical role of CTC-platelet clusters in breast cancer metastasis. The correlation between platelets and CTM function was further confirmed in a mouse model and RNA sequencing of CTM identified high-expressed genes related to hypoxia stimulation and platelet activation which possibly suggested the correlation of hypoxia and CTC-platelet cluster formation. In conclusion, we successfully developed the Cluster-Chip platform to realize the clinical capture of CTMs and analyze the biological properties of CTC-platelet clusters, which could benefit the design of potential treatment regimens to prevent CTM-mediated metastasis and tumor malignant progression.

2.
Sci Adv ; 10(17): eadk3852, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38657063

RESUMO

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.


Assuntos
Migração Animal , Genômica , Vento , Animais , Genômica/métodos , Hemípteros/genética , Genoma de Inseto , Genética Populacional
3.
Cell Death Differ ; 31(5): 558-573, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38570607

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Metionina , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares , Humanos , Metionina/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Linhagem Celular Tumoral , Animais , Oncogenes , Camundongos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Camundongos Nus
4.
Small ; : e2307033, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552219

RESUMO

Recently, aqueous zinc ion batteries (AZIBs) with the superior theoretical capacity, high safety, low prices, and environmental protection, have emerged as a contender for advanced energy storage. However, challenges related to cathode materials, such as dissolution, instability, and structural collapse, have hindered the progress of AZIBs. Here, a novel AZIB is constructed using an oxidized 2D layered MnBi2Te4 cathode for the first time. The oxidized MnBi2Te4 cathode with large interlayer spacing and low energy barrier for zinc ion diffusion at 240 °C, exhibited impressive characteristics, including a high reversibility capacity of 393.1 mAh g-1 (0.4 A g-1), outstanding rate performance, and long cycle stability. Moreover, the corresponding aqueous button cell also exhibits excellent electrochemical performance. To demonstrate the application in practice in the realm of flexible wearable electronics, a quasi-solid-state micro ZIB (MZIB) is constructed and shows excellent flexibility and high-temperature stability (the capacity does not significantly degrade when the temperature reaches 100 °C and the bending angle exceeds 150°). This research offers effective tactics for creating high-performance cathode materials for AZIBs.

5.
Phytomedicine ; 128: 155438, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537443

RESUMO

BACKGROUND: Yi-Qi-Huo-Xue Decoction (YQHXD), a traditional Chinese medicine formula, has demonstrated efficacy in the clinical treatment of intracerebral hemorrhage (ICH) for over a decade. Nevertheless, the precise pharmacotherapeutic compounds of YQHXD capable of penetrating into cerebral tissue and the pharmacological underpinnings of YQHXD remain ambiguous. METHODS: The active components of YQHXD in rat brains was analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential targets, pathways and biological progresses of YQHXD ameliorating ICH induced injury was predicted by network pharmacology. Moreover, collagenase-induced ICH rat model, primary cortex neurons exposed to hemin and molecular docking were applied to validate the molecular mechanisms of YQHXD. RESULTS: Eleven active components of YQHXD were identified within the brains. Employing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, our investigation concentrated on the roles of autophagy and the BDNF/TrkB signaling pathway in the pharmacological context. The pharmacological results revealed that YQHXD alleviated neurological dysfunction, brain water content, brain swelling, and pathological injury caused by ICH. Meanwhile, YQHXD inhibited autophagy influx and autophagosome in vivo, and regulated cortex neuronal autophagy and TrkB/BDNF pathway both in vivo and in vitro. Subsequently, N-acetyl serotonin (NAS), a selective TrkB agonist, was employed to corroborate the significance of the BDNF/TrkB pathway in this process. The combination of NAS and YQHXD did not further enhance the protective efficacy of YQHXD in ICH rats. Additionally, outcomes of molecular docking analysis revealed that nine compounds of YQHXD exhibited potential regulatory effects on TrkB. CONCLUSIONS: Ipsilateral neuronal autophagy and BDNF/TrkB pathway were activated 72 h after ICH. YQHXD effectively resisted injury induced by ICH, which was related with suppression of ipsilateral neuronal autophagy via BDNF/TrkB pathway. This study provides novel insights into the therapeutic mechanisms of traditional Chinese medicine in the context of ICH treatment.


Assuntos
Autofagia , Fator Neurotrófico Derivado do Encéfalo , Hemorragia Cerebral , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Neurônios , Ratos Sprague-Dawley , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Autofagia/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Receptor trkB/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia
6.
Small ; : e2400477, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38402438

RESUMO

Utilizing the ionic flux to generate voltage output has been confirmed as an effective way to meet the requirements of clean energy sources. Different from ionic thermoelectric (i-TE) and hydrovoltaic devices, a new hydrothermal chemical generator is designed by amorphous FeCl3 particles dispersing in MWCNT and unique ferric chloride or water gate. In the presence of gate, the special ion behaviors enable the cell to present a constant voltage of 0.60 V lasting for over 96 h without temperature difference. Combining the differences of cation concentration, humidity and temperature between the right and left side of sample, the maximum short-circuit current and power output can be obtained to 168.46 µA and 28.11 µW, respectively. The generator also can utilize the low-grade heat to produce electricity wherein Seebeck coefficient is 6.79 mV K-1 . The emerged hydrothermal chemical generator offers a novel approach to utilize the low-grade heat, water and salt solution resources, which provides a simple, sustainable and low-cost strategy to realize energy supply.

7.
ACS Nano ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335299

RESUMO

Recently, the topological insulator MnBi2Te4 has aroused great attention owing to its exotic quantum phenomena and intriguing device applications, but the superior performances of MnBi2Te4 have not been researched in the field of electrochemistry. By theoretical calculations, it is found that MnBi2Te4 exhibits excellent Zn2+ storage and transport properties. Therefore, it is speculated that MnBi2Te4 has excellent electrochemical performance in zinc-ion batteries (ZIBs). In this research, MnBi2Te4 as a pioneer has been explored in ZIBs, showing surprising electrochemical properties. The MnBi2Te4 electrode displays a high average discharge specific capacity (264.8 mA h g-1 at 0.40 A g-1), a competitive cycle life (88.6% of initial capacity after 400 cycles at 4.00 A g-1), and an excellent rate performance (average capacity retention rate of 95.1% from 0.40 to 8.00 A g-1) owing to the fast ion transport of the conductive topological surface state and dissipationless channel of the edge state. Surprisingly, the quasi-solid-state (QSS) MnBi2Te4/Zn battery delivers excellent Zn2+ storage capability and possesses a capacity retention of 79.9% after 1000 cycles at 4.00 A g-1. In addition, the QSS MnBi2Te4/Zn battery can exhibit excellent performance and the GCD curves maintain stability without distortion deformation even at temperatures of 0 and 75 °C.

8.
Int Immunopharmacol ; 130: 111717, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38387193

RESUMO

Programmed cell death protein 1 (PD-1) binds to its ligand to help tumours evade the immune system and promote tumour progression. Although anti-PD-1/PD-L1 therapies show powerful effects in some patients, most patients are unable to benefit from this treatment due to treatment resistance. Therefore, it is important to overcome tumour resistance to PD-1/PD-L1 blockade. There is substantial evidence suggesting that the JAK/STAT signalling pathway plays a significant role in PD-1/PD-L1 expression and anti-PD-1/PD-L1 treatment. Herein, we describe the effects of the JAK/STAT signalling pathway on PD-1/PD-L1. Subsequently, the relationship between molecular mutations in the JAK/STAT signalling pathway and immune resistance was analysed. Finally, the latest advancements in drugs targeting the JAK/STAT pathway combined with PD1/PD-L1 inhibitors are summarised.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Neoplasias/tratamento farmacológico
9.
Small ; 20(13): e2305207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37963824

RESUMO

2D perovskites have attracted tremendous attention due to their superior optoelectronic properties and potential applications in optoelectronic devices. Especially, the larger bandgap of 2D perovskite means that they are suitable for UV photodetection. However, the layered structure of 2D perovskites hinders the interlayer carrier transport, which limits the improvement of device performance. Therefore, nanoscale structures are normally used to enhance the light absorption ability, which is an effective strategy to improve the photocurrent in 2D perovskite-based photodetectors. Herein, a template-assisted low-temperature method is proposed to fabricate 2D perovskite ((C6H5C2H4NH3)2PbBr4, (PEA)2PbBr4) grating single crystal films (GSCFs). The crystallinity of the (PEA)2PbBr4 GSCFs is significantly improved due to the slow evaporation of the precursor solution under low temperatures. Based on this high crystalline quality and extremely ordered microstructures, the metal-semiconductor-metal photodetectors are assembled. Finite-different time-domain (FDTD) simulation and experiment indicate that the GSCF-based photodetectors exhibit significantly improved performance in comparison with the plane devices. The optimized 2D perovskite photodetectors are sensitive to UV light and demonstrate a responsivity and detectivity of 28.6 mA W-1 and 2.4 × 1011 Jones, respectively. Interestingly, the photocurrent of this photodetector varies as the angle of the incident polarized light, resulting in a high polarization ratio of 1.12.

10.
Apoptosis ; 29(1-2): 66-85, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37943371

RESUMO

Pyroptosis is a gasdermin-mediated programmed cell death (PCD) pathway. It differs from apoptosis because of the secretion of inflammatory molecules. Pyroptosis is closely associated with various malignant tumors. Recent studies have demonstrated that pyroptosis can either inhibit or promote the development of malignant tumors, depending on the cell type (immune or cancer cells) and duration and severity of the process. This review summarizes the molecular mechanisms of pyroptosis, its relationship with malignancies, and focuses on current pyroptosis inducers and their significance in cancer treatment. The molecules involved in the pyroptosis signaling pathway could serve as therapeutic targets for the development of novel drugs for cancer therapy. In addition, we analyzed the potential of combining pyroptosis with conventional anticancer techniques as a promising strategy for cancer treatment.


Assuntos
Neoplasias , Piroptose , Humanos , Apoptose , Transdução de Sinais , Neoplasias/tratamento farmacológico , Neoplasias/genética
11.
J Control Release ; 365: 957-968, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38104776

RESUMO

Lipid nanoparticles (LNPs) hold great promise as carriers for developing drug delivery systems (DDSs) aimed at managing ischemic stroke (IS). Previous research has highlighted the vital role played by the lipid composition and biophysical characteristics of LNPs, influencing their interactions with cells and tissues. This understanding presents an opportunity to engineer LNPs tailored specifically for enhanced IS treatment. We previously introduced the innovative concept of reconstituted lipid nanoparticles (rLNPs), which not only retain the advantages of conventional LNPs but also incorporate lipids from the originating cell or tissue. Brain-derived rLNPs (B-rLNPs) exhibit significantly superior accumulation within the cerebral ischemic region when compared to liver-derived rLNPs (L-rLNPs). The homing effect of B-rLNPs was then employed to construct 3-n-butylphthalide (NBP) loaded DDS (B-rLNPs/NBP) for the treatment of IS. Our results demonstrated that compared with free NBP, B-rLNPs/NBP can significantly reduce infarct volume, neurological deficits, blood-brain barrier (BBB) leakage rate, brain water content, neutrophil infiltration, alleviate pathological structures, and improve the motor function in MCAO/R model. We also proved that B-rLNPs/NBP showed further reinforced protective effects on the same model than free NBP through the regulation of TLR4/MyD88/NF-κB (anti-inflammation) and Bax/Bcl-2 (anti-apoptosis) pathways. This study offers a promising tool towards improved IS treatment.


Assuntos
AVC Isquêmico , Lipossomos , Nanopartículas , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , Barreira Hematoencefálica , NF-kappa B , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico
12.
ACS Appl Mater Interfaces ; 15(51): 59955-59963, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38085577

RESUMO

Metal halide-perovskite-based photodetectors have recently emerged as a class of promising optoelectronic devices in various fields. Meanwhile, nano/microstructuring perovskite-based photodetectors are a facile integration with complementary metal-oxide semiconductors for miniaturized imaging systems. However, there are still challenges to be overcome in reducing the losses caused by light reflection on the surface of microstructural perovskites. In this work, surface microstructure engineering is employed in MAPbBr3 microsheets for reducing light reflection and improving light absorption, resulting in high-performance perovskite photodetectors. MAPbBr3 microsheets, which possess different surface morphologies of flat, upright hemisphere arrays and inverted hemisphere arrays (IHAs), are fabricated by a simple microstructure template-assisted space confinement process. The light absorption capacity of IHA MAPbBr3 is significantly higher than that of the other two structures. Hence, IHA photodetectors with excellent figures of merit, including low dark current, decent responsivity, and fast speed, are achieved. Furthermore, the noise of the IHA photodetectors is only ∼10-13 A/Hz, which results in the superior sensitivity for weak light detection with a specific detectivity up to 1011 Jones. Our results demonstrate that surface engineering is a simple, low-cost, yet effective approach to improve the performance of nano-/micro-optoelectronic devices.

13.
Acta Pharm Sin B ; 13(11): 4621-4637, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37969730

RESUMO

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37278038

RESUMO

BACKGROUND: Osteosarcoma is a disease that primarily affects adolescents with skeletal immaturity. LncRNAs are abnormally expressed and correlated with osteosarcoma patients' prognosis. We identified aberrant expression of LncRNA SNHG25 (small nucleolar RNA host gene 25) in osteosarcoma and analyzed the molecular mechanisms by which it regulates osteosarcoma progression. METHODS: The expression levels of SNHG25 in tumour specimens and cells were measured by RT-qPCR. Loss-of-function assays were conducted to investigate the functional role of SNHG25 in vitro and in vivo. Bioinformatic predictions, dual-luciferase reporter assays, and western blotting were performed to explore the possible underlying mechanisms. RESULTS: SNHG25 was highly expressed in osteosarcoma cells and tissues. The Kaplan-Meier curve showed that the survival rate of patients with high SNHG25 expression was significantly lower than those with low SNHG25 expression. Functional studies have indicated that inhibition of SNHG25 suppresses cell proliferation, migration, and invasion, while promoting apoptosis. SNHG25 knockdown suppresses osteosarcoma tumour growth in vivo. SNHG25 functions as a sponge for miR-497-5p in osteosarcoma cells. The level of SNHG25 was negatively correlated with that of miR-497-5p. The proliferation, invasion, and migration of osteosarcoma cells were restored by transfection of the miR-497-5p inhibitor in the SNHG25 knockdown group. CONCLUSION: SNHG25 was determined to function as an oncogene by promoting osteosarcoma cell proliferation, invasion, and migration through the miR-497-5p/SOX4 axis. Upregulation of SNHG25 expression indicated poor prognosis in patients with osteosarcoma, which showed that SNHG25 may serve as a potential therapeutic target and prognostic biomarker in osteosarcoma.

15.
Int J Antimicrob Agents ; 62(1): 106841, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37160241

RESUMO

In the current study, a population pharmacokinetic (PPK) model was developed for biapenem in patients with febrile neutropenia (FN) and haematological malignancies. Through Monte Carlo simulation, optimal administration regimens were suggested based on the developed PPK model. In a prospective, single-centre, open-label study, 174 plasma samples from 120 Chinese patients with FN and haematological malignancies were analysed by chromatography, and PK parameters were analysed by NONMEM. The drug clearance process was influenced by crucial covariates, namely creatinine clearance (CLCR) and concomitant posaconazole (POS). The ultimate PPK model was as follows: CL (L/h)=29.81 × (CLCR/121.38)0.806 × (1-POS × 0.297); volume of distribution (L)=114. For the target of ≥40% fT>minimum inhibitory concentration (MIC) (duration that the plasma level exceeds the MIC of the causative pathogen) and achieving the probability of target attainment ≥90%, the PK/pharmacodynamic breakpoint was 2 mg/L for the 2.4 g/day dosing regimen consisting of 600 mg q6h and 800 mg q8h. The breakpoint was 1 mg/L for the 1.2 g/day dosing regimen consisting of 300 mg q6h and 600 mg q12h. Empirical therapy would benefit from utilizing higher dosages and extended infusion durations. Therefore, it is suggested that patients with symptoms that are strongly suggestive of Pseudomonas aeruginosa or Acinetobacter baumannii infection may be suitable for combined treatment with other antibacterial drugs.


Assuntos
Infecções por Acinetobacter , Neutropenia Febril , Neoplasias Hematológicas , Humanos , Método de Monte Carlo , Estudos Prospectivos , Antibacterianos/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Neutropenia Febril/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Testes de Sensibilidade Microbiana
16.
Front Med (Lausanne) ; 10: 1147782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122331

RESUMO

Purine adenosine pathway exists widely in the body metabolism, and is involved in regulating various physiological processes. It is one of the important pathways of environmental regulation in human body. CD73 is essentially a protease that catalyzes further dephosphorylation of extracellular adenine nucleotides, hydrolyzing extracellular AMP to adenosine and phosphate. CD73 is an important part of the adenosine signaling pathway. Studies have shown that CD73-mediated adenosine pathway can convert the inflammatory ATP into the immunosuppressant adenosine. This paper aims to summarize the relevant effects of CD73 in the occurrence, development and prognosis of liver diseases such as viral hepatitis, highlight the important role of CD73 in liver diseases, especially in viral hepatitis such as HBV and HCV, and explore new clinical ideas for future treatment targets of liver diseases.

17.
Phytomedicine ; 113: 154732, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933457

RESUMO

BACKGROUND: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear. PURPOSE: This study aimed to confirm the efficacy of SHSB against lung adenocarcinoma (LUAD), which is a major histological type of LC, unveil the downstream targets of this formula, and assess the clinical relevance and biological roles of the newly identified target. METHODS: An experimental metastasis mouse model and a subcutaneous xenograft mouse model were used to evaluate the anti-cancer activity of SHSB. Multi-omics profiling of subcutaneous tumors and metabolomic profiling of sera were performed to identify downstream targets, especially the metabolic targets of SHSB. A clinical trial was conducted to verify the newly identified metabolic targets in patients. Next, the metabolites and enzymes engaged in the metabolic pathway targeted by SHSB were measured in clinical samples. Finally, routine molecular experiments were performed to decipher the biological functions of the metabolic pathways targeted by SHSB. RESULTS: Oral SHSB administration showed overt anti-LUAD efficacy as revealed by the extended overall survival of the metastasis model and impaired growth of implanted tumors in the subcutaneous xenograft model. Mechanistically, SHSB administration altered protein expression in the post-transcriptional layer and modified the metabolome of LUAD xenografts. Integrative analysis demonstrated that SHSB markedly inhibited acetyl-CoA synthesis in tumors by post-transcriptionally downregulating ATP-citrate lyase (ACLY). Consistently, our clinical trial showed that oral SHSB administration declined serum acetyl-CoA levels of patients with LC. Moreover, acetyl-CoA synthesis and ACLY expression were both augmented in clinical LUAD tissues of patients, and high intratumoral ACLY expression predicted a detrimental prognosis. Finally, we showed that ACLY-mediated acetyl-CoA synthesis is essential for LUAD cell growth by promoting G1/S transition and DNA replication. CONCLUSION: Limited downstream targets of SHSB for LC treatment have been reported in previous hypothesis-driven studies. In this study, we conducted a comprehensive multi-omics investigation and demonstrated that SHSB exerted its anti-LUAD efficacy by actively and post-transcriptionally modulating protein expression and particularly restraining ACLY-mediated acetyl-CoA synthesis.


Assuntos
Adenocarcinoma de Pulmão , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Humanos , Camundongos , Animais , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Acetilcoenzima A/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico
18.
Stem Cells Int ; 2023: 3827999, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818162

RESUMO

Background: Pyroptosis is closely related to the programmed death of cancer cells as well as the tumor immune microenvironment (TIME) via the host-tumor crosstalk. However, the role of pyroptosis-related genes as prognosis and TIME-related biomarkers in skin cutaneous melanoma (SKCM) patients remains unknown. Methods: We evaluated the expression profiles, copy number variations, and somatic mutations (CNVs) of 27 genes obtained from MSigDB database regulating pyroptosis among TCGA-SKCM patients. Thereafter, we conducted single-sample gene set enrichment analysis (ssGSEA) for evaluating pyroptosis-associated expression patterns among cases and for exploring the associations with clinicopathological factors and prognostic outcome. In addition, a prognostic pyroptosis-related signature (PPRS) model was constructed by performing Cox regression, weighted gene coexpression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score SKCM patients. On the other hand, we plotted the ROC and survival curves for model evaluation and verified the robustness of the model through external test sets (GSE22153, GSE54467, and GSE65904). Meanwhile, we examined the relations of clinical characteristics, oncogene mutations, biological processes (BPs), tumor stemness, immune infiltration degrees, immune checkpoints (ICs), and treatment response with PPRS via multiple methods, including immunophenoscore (IPS) analysis, gene set variation analysis (GSVA), ESTIMATE, and CIBERSORT. Finally, we constructed a nomogram incorporating PPRS and clinical characteristics to improve risk evaluation of SKCM. Results: Many pyroptosis-regulated genes showed abnormal expression within SKCM. TP53, TP63, IL1B, IL18, IRF2, CASP5, CHMP4C, CHMP7, CASP1, and GSDME were detected with somatic mutations, among which, a majority displayed CNVs at high frequencies. Pyroptosis-associated profiles established based on pyroptosis-regulated genes showed markedly negative relation to low stage and superior prognostic outcome. Blue module was found to be highly positively correlated with pyroptosis. Later, this study established PPRS based on the expression of 8 PAGs (namely, GBP2, HPDL, FCGR2A, IFITM1, HAPLN3, CCL8, TRIM34, and GRIPAP1), which was highly associated with OS, oncogene mutations, tumor stemness, immune infiltration degrees, IC levels, treatment responses, and multiple biological processes (including cell cycle and immunoinflammatory response) in training and test set samples. Conclusions: Based on our observations, analyzing modification patterns associated with pyroptosis among diverse cancer samples via PPRS is important, which can provide more insights into TIME infiltration features and facilitate immunotherapeutic development as well as prognosis prediction.

19.
J Colloid Interface Sci ; 629(Pt A): 628-639, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36095898

RESUMO

With WO3/BiVO4/MXene ternary composite layers as a working electrode, a smart volumetric photoelectrochemical system using electrostatic bias voltage inducted by atmospheric electric field was developed. Under single sun illumination and 0.8 V hardwired bias, the current response of the ternary electrode is 1.15 mA cm-2, which is 1.31 times higher than that of the WO3/BiVO4 electrode, mainly due to the higher charge transfer rate between the MXene layer and the BiVO4 structure. Further, the response of the ternary electrode increases to 1.39 mA cm-2 at an extra atmospheric electric field of 1100 V m-1. It can be demonstrated that the effect of the atmospheric electric field can be regarded as an extra hardwired bias of 0.101 V in the system. The experimental results reveal that the native carriers, including inducted electron/holes in MXene and BiVO4, and carriers in the electrolyte, are all effectively excited by the electrostatic induction of atmospheric electric field.

20.
Scand J Immunol ; 98(4): e13312, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38441348

RESUMO

Myeloid-derived suppressor cells (MDSCs) refer to a group of immature myeloid cells with potent immunosuppressive capacity upon activation by pathological conditions. Because of their potent immunosuppressive ability, MDSCs have garnered extensive attention in the past few years in the fields of oncology, infection, chronic inflammation and autoimmune diseases. Research on MDSCs in liver diseases has gradually increased, and their potential therapeutic roles will be further explored. This review presents a summary of the involvement and the role played by MDSCs in liver diseases, thus identifying their potential targets for the treatment of liver diseases and providing new directions for liver disease-related research.


Assuntos
Doenças Autoimunes , Hepatopatias , Células Supressoras Mieloides , Humanos , Hepatopatias/terapia , Células Mieloides , Doenças Autoimunes/terapia , Imunossupressores
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