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1.
J Invertebr Pathol ; : 108115, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719180

RESUMO

To explore the relationship between the intestinal flora of Exopalaemon Carinicauda and infection by Enterocytozoo Hepatopenaei (EHP), we analyzed the species and richness of gut microbiota in infected individuals in different EHP load groups [i.e., control (C), high load (H), and low load (L)] using gene sequencing after infection. The results showed that the abundance of intestinal flora in the high-load EHP group was significantly lower than that in the healthy group. Based on the UPGMA cluster tree and PCoA analysis, with comparisons to healthy shrimp, the gut microbiota of the EHP high load and low load groups were clustered into one branch, which indicated that EHP infection changed the composition of the gut microbiota of infected shrimps. The heat map analysis of species abundance clustering revealed that the dominant bacteria in the low EHP load group and the control group were beneficial genera such as Lactococcus, Ligilactobacillius, and Bifidobacterium, but the dominant bacteria in the high EHP load group were harmful genera such as Pseudomonas, Photobacterium, and Candidatus hepatincola. The functions of the intestinal flora predicted that most genes related to metabolism were more abundant in healthy shrimp, most genes related to metabolism and the organisms' system were more abundant in the low EHP load group, and most genes related to diseases and environmental information processing were more abundant in the high EHP load group. After separation and purification, the dominant bacteria (Bifidobacterium animalis in healthy shrimp and Lactococcus garvieae in the low EHP load group) and the non-dominant bacteria (Macrococus caseolyticus in the low EHP load group) were obtained. Each of these isolated strains were used together with EHP to infect E. carinicauda, and the results showed that Bifidobacterium animali and Lactococcus garvieae significantly reduced the EHP load in EHP-infected individuals. At the same time, the morphology and structure of the hepatopancreas and intestinal tissue of EHP-infected E. carinicauda were improved. No improvement was seen in tissue that was infected with Macrococus caseolyticus.

2.
Cell Biochem Biophys ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722472

RESUMO

The activation, injury, and dysfunction of endothelial cells are considered to be the initial key events in the development of atherosclerosis. Di (2-ethylhexyl) phthalate (DEHP), a prevalent organic pollutant, can cause damage to multiple organs. Polysaccharide of Atractylodes macrocephala Koidz (PAMK) is a bioactive compound extracted from A. macrocephala Koidz with various biological activities. This study investigates the protective effects of PAMK on porcine aortic valve endothelial cells (PAVEC) damaged by DEHP. PAVECs treated with DEHP alone or with PAMK showed reduced cell apoptosis and death in PAMK-pretreated cells. PAMK up-regulated Bcl-2 expression and down-regulated Bax protein, suppressing apoptosis. Flow cytometry analysis demonstrated that PAMK protected PAVECs from DEHP-induced damage. These findings suggest that PAMK inhibits cell apoptosis and protects against DEHP damage in endothelial cells.

3.
J Clin Invest ; 134(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618952

RESUMO

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.


Assuntos
Adenina , Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Carcinogênese/genética , Carcinoma de Células Renais/genética , Transformação Celular Neoplásica , Expressão Gênica , Neoplasias Renais/genética , Metiltransferases/genética , Fosfatidilinositol 3-Quinases/genética
4.
Small ; : e2402108, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38586916

RESUMO

Lithium metal is a highly promising anode for next-generation high-energy-density rechargeable batteries. Nevertheless, its practical application faces challenges due to the uncontrolled lithium dendrites growth and infinite volumetric expansion during repetitive cycling. Herein, a composite lithium anode is designed by mechanically rolling and pressing a cerium oxide-coated carbon textile with lithium foil (Li@CeO2/CT). The in situ generated cerium dioxide (CeO2) and cerium trioxide (Ce2O3) form a heterojunction with a reduced lithium-ion migration barrier, facilitating the rapid lithium ions migration. Additionally, both CeO2 and Ce2O3 exhibit higher adsorbed energy with lithium, enabling faster and more distributed interfacial transport of lithium ions. Furthermore, the high specific surface area of 3D skeleton can effectively reduce local current density, and alleviate the lithium volumetric changes upon plating/stripping. Benefiting from this unique structure, the highly compact and uniform lithium deposition is constructed, allowing the Li@CeO2/CT symmetric cells to maintain a stable cycling for over 500 cycles at an exceptional high current density of 100 mA cm-2. When paired with LiNi0.91Co0.06Mn0.03O2 (NCM91) cathode, the cell achieves 74.3% capacity retention after 800 cycles at 1 C, and a remarkable capacity retention of 81.1% after 500 cycles even at a high rate of 4  C.

5.
Anal Chem ; 96(8): 3600-3608, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38372498

RESUMO

Peroxynitrite (ONOO-), as a short-term reactive biological oxidant, could lead to a series of effects in various physiological and pathological processes due to its subtle concentration changes. In vivo monitoring of ONOO- and relevant physiological processes is urgently required. Herein, we describe a novel fluorescent probe termed HBT-Fl-BnB for the ratiometric detection of ONOO- in vitro and in vivo. The probe consists of an HBT core with Fl groups at the ortho and para positions responding to the zwitterionic excited-state intramolecular proton-transfer (zwitterionic ESIPT) process and a boronic acid pinacol ester with dual roles that block the zwitterionic ESIPT and recognize ONOO-. Thanks to the specificity as well as low cytotoxicity, success in imaging of endogenous and exogenous ONOO- in living cells by HBT-Fl-BnB was obtained. Additionally, the applicability of HBT-Fl-BnB to tracking the abnormal expression of ONOO- in vivo induced by inactivated Escherichia coli was also explored. This is the first report of a fluorescent probe for ONOO- sensing via a zwitterionic ESIPT mechanism.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Humanos , Corantes Fluorescentes/toxicidade , Prótons , Imagem Óptica , Células HeLa
6.
Environ Toxicol ; 39(3): 1521-1530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38009637

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are associated with cancer progression. MiR-140-3p is a tumor suppressor. Nevertheless, its function in non-small cell lung cancer (NSCLC) is unclear. METHODS: MiR-140-3p expression in NSCLC clinical specimens was examined using the TCGA database and real-time PCR. NSCLC cell proliferation and apoptosis were investigated after the miRNA overexpression. Then, mineral dust-induced gene (MDIG) levels in NSCLC clinical specimens were monitored by real-time PCR and western blotting. Bioinformatics predicated the binding of miR-140-3p to MDIG, and their relationship was validated by luciferase reporter assay. The miR-140-3p/MDIG axis was further validated through rescue experiments. The involvement of STAT3 signaling in the actions of miR-140-3p/MDIG axis was investigated. RESULTS: MiR-140-3p was decreased in NSCLC tissues and negatively correlated with MDIG expression. Additionally, it was also lower in high-grade specimens than in low-grade ones. MiR-140-3p restrained cell proliferation, facilitated apoptosis, and inhibited STAT3 signaling in NSCLC. Interestingly, MDIG was a target of this miRNA. Furthermore, MDIG upregulation abolished miR-140-3p's effect on cell proliferation, apoptosis, and STAT3 pathway in NSCLC cells. CONCLUSION: MiR-140-3p restrained NSCLC development through the regulation of the STAT3 pathway by targeting MDIG. This axis may be a promising target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo
7.
Hum Brain Mapp ; 44(18): 6429-6438, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37909379

RESUMO

This study aims to explore the changes of the aspartate (Asp) level in the medial-prefrontal cortex (mPFC) of subjects with nicotine addiction (nicotine addicts [NAs]) using the J-edited 1 H MR spectroscopy (MRS), which may provide a positive imaging evidence for intervention of NA. From March to August 2022, 45 males aged 40-60 years old were recruited from Henan Province, including 21 in NA and 24 in nonsmoker groups. All subjects underwent routine magnetic resonance imaging (MRI) and J-edited MRS scans on a 3.0 T MRI scanner. The Asp level in mPFC was quantified with reference to the total creatine (Asp/Cr) and water (Aspwater-corr , with correction of the brain tissue composition) signals, respectively. Two-tailed independent samples t-test was used to analyze the differences in levels of Asp and other coquantified metabolites (including total N-acetylaspartate [tNAA], total cholinine [tCho], total creatine [tCr], and myo-Inositol [mI]) between the two groups. Finally, the correlations of the Asp level with clinical characteristic assessment scales were performed using the Spearman criteria. Compared with the control group (n = 22), NAs (n = 18) had higher levels of Asp (Asp/Cr: p = .005; Aspwater-corr : p = .004) in the mPFC, and the level of Asp was positively correlated with the daily smoking amount (Asp/Cr: p < .001; Aspwater-corr : p = .004). No significant correlation was found between the level of Asp and the years of nicotine use, Fagerstrom Nicotine Dependence (FTND), Russell Reason for Smoking Questionnaire (RRSQ), or Barratt Impulsivity Scale (BIS-11) score. The elevated Asp level was observed in mPFC of NAs in contrast to nonsmokers, and the Asp level was positively correlated with the amount of daily smoking, which suggests that nicotine addiction may result in elevated Asp metabolism in the human brain.


Assuntos
Nicotina , Tabagismo , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Nicotina/metabolismo , Ácido Aspártico/metabolismo , Tabagismo/diagnóstico por imagem , Creatina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Inositol/metabolismo , Córtex Pré-Frontal/metabolismo , Água/metabolismo
8.
Sci Adv ; 9(47): eadi1867, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37992175

RESUMO

Adaptation to low levels of oxygen (hypoxia) is a universal biological feature across metazoans. However, the unique mechanisms how different species sense oxygen deprivation remain unresolved. Here, we functionally characterize a novel long noncoding RNA (lncRNA), LOC105369301, which we termed hypoxia-induced lncRNA for polo-like kinase 1 (PLK1) stabilization (HILPS). HILPS exhibits appreciable basal expression exclusively in a wide variety of human normal and cancer cells and is robustly induced by hypoxia-inducible factor 1α (HIF1α). HILPS binds to PLK1 and sequesters it from proteasomal degradation. Stabilized PLK1 directly phosphorylates HIF1α and enhances its stability, constituting a positive feed-forward circuit that reinforces oxygen sensing by HIF1α. HILPS depletion triggers catastrophic adaptation defect during hypoxia in both normal and cancer cells. These findings introduce a mechanism that underlies the HIF1α identity deeply interconnected with PLK1 integrity and identify the HILPS-PLK1-HIF1α pathway as a unique oxygen-sensing axis in the regulation of human physiological and pathogenic processes.


Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Oxigênio , Transdução de Sinais , Hipóxia/genética
9.
Cell Cycle ; 22(18): 2038-2056, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37902305

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor in the head and neck, the 5-year relative survival rate of patients diagnosed with laryngeal cancer was estimated to be 61% from 2012 to 2018. An increasing number of studies have shown that circular RNAs (circRNAs) play a key role in the occurrence and development of cancer and may function as cancer biomarkers and new therapeutic targets. At present, the research on the relationship between circRNAs and LSCC is still in its infancy and needs further exploration. In this study, we found a circRNA (hsa_circ_0001445) associated with LSCC based on bioinformatics analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) assay indicated that the expression of hsa_circ_0001445 was down-regulated in LSCC tissues and cell lines. Notably, the expression of hsa_circ_0001445 was negatively correlated with aggressive clinicopathological features and poor prognosis. Then, functional experiments found that overexpression of hsa_circ_0001445 inhibited the proliferation, migration and invasion of LSCC cells and tumor growth in vivo. Mechanistically, RNA immunoprecipitation (RIP), biotin-labeled probe pull-down, luciferase reporter assay and western blot experiments were employed and found that EIF4A3 reduced the expression of hsa_circ_0001445, and the direct binding of hsa_circ_0001445 to hsa-miR-432-5p attenuated the inhibitory effect of hsa-miR-432-5p on RGMA. In summary, our research suggests that hsa_circ_0001445 may be used as a potential prognostic biomarker and therapeutic target for LSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , MicroRNAs , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Regulação para Cima/genética , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Fator de Iniciação 4A em Eucariotos/genética , RNA Helicases DEAD-box/metabolismo
10.
Anal Chem ; 95(26): 10096-10104, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37351925

RESUMO

In this work, a potential-resolved electrochemiluminescence (ECL) multiplex immunoassay (MIA) was developed using zirconium-based metal-organic framework (MOF) nanoparticles with intense self-ECL as an anodic ECL tag and CdTe nanocrystals (NCs) as a cathodic ECL tag. ECL luminophore 5,5'-(anthracene-9,10-diyl)diisophthalic acid (H4ADIP) and coreactant hexamethylenetetramine (HMT) bound to zirconium nodes in the MOF, giving Zr-ADIP-HMT nanoparticles. Benefiting from the intrareticular charge transfer (ICT) between the oxidized ligands of H4ADIP and HMT via hydrogen bonds, the intense self-ECL from Zr-ADIP-HMT was applied to the potential-resolved ECL MIA without an exogenous anodic coreactant, which can eliminate detrimental effects of multiplex coreactants and anodic ECL emission from CdTe NCs. The ICT within Zr-ADIP-HMT nanoparticles could shorten the electron transport path and reduce the complexity of radical intermediate transport. The ECL intensity from Zr-ADIP-HMT was 18.6-fold that from the mixture of H4ADIP and HMT. In potential-resolved ECL MIA, two lung cancer biomarkers, carcinoembryonic antigen and neuron-specific enolase, were adopted as model analytes, with detection limits of 18 and 5.3 fg·mL-1, respectively. The dual-ligand Zr-ADIP-HMT nanoparticles provide a proof of concept using ICT-based self-ECL luminophores for potential-resolved ECL MIAs with isolated coreactants.


Assuntos
Técnicas Biossensoriais , Compostos de Cádmio , Nanopartículas Metálicas , Estruturas Metalorgânicas , Nanopartículas , Pontos Quânticos , Estruturas Metalorgânicas/química , Zircônio , Compostos de Cádmio/química , Técnicas Eletroquímicas , Medições Luminescentes , Telúrio/química , Nanopartículas/química , Imunoensaio , Nanopartículas Metálicas/química , Limite de Detecção
11.
Front Genet ; 14: 1067172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37007952

RESUMO

Introduction: Prostate cancer (PCa) is the second most common malignancy in men. Despite multidisciplinary treatments, patients with PCa continue to experience poor prognoses and high rates of tumor recurrence. Recent studies have shown that tumor-infiltrating immune cells (TIICs) are associated with PCa tumorigenesis. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to derive multi-omics data for prostate adenocarcinoma (PRAD) samples. The CIBERSORT algorithm was used to calculate the landscape of TIICs. Weighted gene co-expression network analysis (WGCNA) was performed to determine the candidate module most significantly associated with TIICs. LASSO Cox regression was applied to screen a minimal set of genes and construct a TIIC-related prognostic gene signature for PCa. Then, 78 PCa samples with CIBERSORT output p-values of less than 0.05 were selected for analysis. WGCNA identified 13 modules, and the MEblue module with the most significant enrichment result was selected. A total of 1143 candidate genes were cross-examined between the MEblue module and active dendritic cell-related genes. Results: According to LASSO Cox regression analysis, a risk model was constructed with six genes (STX4, UBE2S, EMC6, EMD, NUCB1 and GCAT), which exhibited strong correlations with clinicopathological variables, tumor microenvironment context, antitumor therapies, and tumor mutation burden (TMB) in TCGA-PRAD. Further validation showed that the UBE2S had the highest expression level among the six genes in five different PCa cell lines. Discussion: In conclusion, our risk-score model contributes to better predicting PCa patient prognosis and understanding the underlying mechanisms of immune responses and antitumor therapies in PCa.

12.
Biomacromolecules ; 24(5): 2301-2313, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37067047

RESUMO

The aggregation-caused quenching, premature drug release, and hypoxia-caused resistance of photodynamic therapy (PDT) are challenges in the design and preparation of novel porphyrin-containing photosensitizers. In this work, a series of block copolymers consisting of a hydrophilic glycopolymer block and a porphyrin-containing hydrophobic block were prepared via reversible addition-fragmentation chain transfer polymerization. The polymeric photosensitizers generate singlet oxygen and excellent PDT against HepG2, which can be strengthened by the addition of cholic acid. To combine with chemotherapy, doxorubicin (Dox) was successfully loaded into copolymers, which were observed to be more phototoxic, indicating that the therapeutic benefit of the synergistic effect of PDT and chemotherapy is better than their simple combination. The sugar-cell-specific interaction of galactose-containing photosensitizers results in a stronger mean fluorescent index (MFI) intracellular uptake in HepG2 cells in vitro compared to L929 and MCF-7 cells. These polymeric nanoplatforms present a versatile and effective avenue for developing synergistic therapy for cancer treatment.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Ácido Cólico/farmacologia , Nanopartículas/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Polímeros/farmacologia , Polímeros/química , Porfirinas/química , Linhagem Celular Tumoral
13.
Open Med (Wars) ; 18(1): 20230665, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910848

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is an aggressive and lethal malignant neoplasm with extremely poor prognoses. Accumulating evidence has indicated that preferentially expressed antigen in melanoma (PRAME) is correlated with several kinds of cancers. However, there is little direct evidence to substantiate the biological function of PRAME in LSCC. The purpose of the current study is to explore the oncogenic role of PRAME in LSCC. PRAME expression was analyzed in 57 pairs of LSCC tumor tissue samples through quantitative real-time PCR, and the correlation between PRAME and clinicopathological features was analyzed. The result indicated that PRAME was overexpressed in the LSCC patients and correlated with the TNM staging and lymphatic metastasis. The biological functions and molecular mechanism of PRAME in LSCC progression were investigated through in vitro and in vivo assays. Functional studies confirmed that PRAME facilitated the proliferation, invasion, migration, and epithelial-mesenchymal transition of LSCC cells, and PRAME also promoted tumor growth in vivo. HDAC5 was identified as an upstream regulator that can affect the expression of PRAME. Moreover, PRAME played the role at least partially by activating PI3K/AKT/mTOR pathways. The above findings elucidate that PRAME may be a valuable oncogene target, contributing to the diagnosis and therapy of LSCC.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36981809

RESUMO

The ongoing COVID-19 pandemic has imposed greater challenges and more stringent requirements on higher education institutions (HEIs). However, limited empirical research has been devoted to identifying external and internal factors that may promote individual preventive behaviors during the COVID-19 pandemic within the higher education context. This study proposed and examined an extended norm activation model (NAM) concerning the relationships among cultural tightness, original NAM components, and COVID-19 preventive behaviors. An online survey was conducted with a sample of 3693 university students from 18 universities in Beijing, China. The results showed that cultural tightness was positively associated with respondents' COVID-19 preventive behaviors. Three original NAM variables, namely, awareness of consequences, the ascription of responsibility, and personal norms, played a chain mediating role in the relationship between cultural tightness and COVID-19 preventive behaviors. Theoretical and practical implications regarding the findings of this study and suggestions for future research are discussed.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Universidades , Pandemias/prevenção & controle , Pequim/epidemiologia , Estudantes , China/epidemiologia
15.
Arch Toxicol ; 97(3): 635-650, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36773078

RESUMO

The phosphatidylinositol 3-kinase (PI3K) signalling pathway regulates cell survival, proliferation, migration, metabolism and other vital cellular life processes. In addition, activation of the PI3K signalling pathway is important for cancer development. As a result, a variety of PI3K inhibitors have been clinically developed to treat malignancies. Although several PI3K inhibitors have received approval from the Food and Drug Administration (FDA) for significant antitumour activity, frequent and severe adverse effects have greatly limited their clinical application. These toxicities are mostly on-target and immune-mediated; nevertheless, the underlying mechanisms are still unclear. Current management usually involves intervention through symptomatic treatment, with discontinuation if toxicity persists. Therefore, it is necessary to comprehensively understand these adverse events and ensure the clinical safety application of PI3K inhibitors by establishing the most effective management guidelines, appropriate intermittent dosing regimens and new combination administration. Here, the focus is on the development of PI3K inhibitors in cancer therapy, with particular emphasis on isoform-specific PI3K inhibitors. The most common adverse effects of PI3K inhibitors are also covered, as well as potential mechanisms and management approaches.


Assuntos
Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases , Inibidores de Fosfoinositídeo-3 Quinase/toxicidade , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Neoplasias/induzido quimicamente , Transdução de Sinais , Antineoplásicos/farmacologia
16.
J Mater Chem B ; 11(7): 1416-1433, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36734612

RESUMO

Although chemotherapy and photodynamic therapy (PDT) have been developed for fighting cancer, the complex and heterogeneous nature of tumors makes it difficult for a single therapy to completely inhibit tumor growth. In order to reduce multidrug resistance of cancer cells to chemotherapeutic drugs and overcome low PDT efficiency in the hypoxic tumor microenvironment (TME), chemo/PDT synergistic treatment has received much attention in recent years. Depending on the characteristic signals of TME, various drug delivery systems can be constructed to target tumors and improve the therapeutic efficacy and the pharmacokinetic profile of anticancer drugs. This review highlights the synergistic strategies, treatment protocols, and design of chemo/PDT co-therapy in recent years to explore its scope and limitations. Taking advantage of stimuli-responsive materials and active cancer-targeting agents, cancer-targeting synergistic therapy is presented and discussed, providing ideas and suggestions for the construction of chemo/PDT co-therapy "smart" nanocarriers.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Nanopartículas/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Microambiente Tumoral
17.
Cell Transplant ; 32: 9636897231154574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36852700

RESUMO

Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo. Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2'-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Decitabina , Regulação para Baixo/genética , Guanilato Quinases , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço
18.
Int J Biol Macromol ; 226: 510-524, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36509203

RESUMO

(E)-ß-farnesene (EBF) is a typical and ecologically important infochemical in tri-trophic level interactions among plant-aphid-natural enemies. However, the molecular mechanisms by which parasitoids recognize and utilize EBF are unclear. In this study, we functionally characterized 8 AgifOBPs in Aphidifus gifuensis, one dominant endo-parasitoid of wheat aphid as well as peach aphid in China. Among which, AgifOBP6 was the only OBP upregulated by various doses of EBF, and it showed a strong binding affinity to EBF in vitro. The lack of homology between AgifOBP6 and EBF-binding proteins from aphids or from other aphid natural enemies supported that this was a convergent evolution among insects from different orders driven by EBF. Molecular docking of AgifOBP6 with EBF revealed key interacting residues and hydrophobic forces as the main forces. AgifOBP6 is widely expressed among various antennal sensilla. Furthermore, two bioassays indicated that trace EBF may promote the biological control efficiency of A. gifuensis, especially on winged aphids. In summary, this study reveals an OBP (AgifOBP6) that may play a leading role in aphid alarm pheromone detection by parasitoids and offers a new perspective on aphid biological control by using EBF. These results will improve our understanding of tri-trophic level interactions among plant-aphid-natural enemies.


Assuntos
Afídeos , Animais , Simulação de Acoplamento Molecular , Odorantes , Feromônios/metabolismo , China
19.
J Affect Disord ; 320: 751-761, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36174788

RESUMO

OBJECTIVE: A comprehensive meta-analysis using correlated coordinate data to explore abnormalities in white matter (WM) microarchitecture and changes in gray matter volume (GMV) in patients with obsessive-compulsive disorder (OCD). METHODS: We reviewed 23 reported studies of diffusion tensor imaging (DTI) in OCD patients. The differences in WM fractional anisotropy (FA) between OCD patients and healthy controls (HCs) were investigated using tract-based spatial statistics (TBSS) and voxel-based analysis (VBA), respectively, and the results of the two methods were compared. In addition, we will explore changes in OCD GMV by analyzing studies (n = 21) using the voxel-based morphometry (VBM) approach and comparing the difference between adults and adolescents. RESULTS: In the pooled meta-analysis, WM study results presented that compared with HCs, OCD patients had higher FA in right lenticular nucleus (putamen), and lower FA in corpus callosum (CC), left insula, right cerebellum (hemispheric lobule), right gyrus rectal and left inferior parietal gyri. However, in subgroup analysis, there was a significant difference in FA changes between TBSS and VBA in OCD patients compared with HCs. In addition, we found that the GMV of OCD patients was significantly increased in left striatum and left precentral gyrus, and significantly decreased in right inferior frontal gyrus triangular part, right superior temporal gyrus and right hippocampus. Compared with adolescents, adult patients have increased GMV in left lenticular nucleus putamen. CONCLUSION: The meta-analysis showed that OCD patients had abnormal WM microarchitecture and altered GMV. These changes may be closely related to the pathophysiological mechanism of the disease.


Assuntos
Transtorno Obsessivo-Compulsivo , Substância Branca , Humanos , Adulto , Adolescente , Imagem de Tensor de Difusão/métodos , Substância Branca/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Imageamento por Ressonância Magnética
20.
Pak J Pharm Sci ; 35(4(Special)): 1169-1172, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36218094

RESUMO

The study was carried out to observe the effect of combination drug therapy during cesarean section in preventing postpartum hemorrhage for women with hypertensive disorder complicating pregnancy (HDCP). The 180 women who had been treated in our hospital for HDCP were enrolled and randomly divided into observation group (sublingual administration of carboprost combined with oxytocin treatment (20IU oxytocin and small pot drip of 10IU oxytocin after delivery) and control group (1mg of carboprost when the fetal head came out and then applied with intramuscular injection of 20IU oxytocin), each containing 90. The comparison of postpartum hemorrhage situation between two groups was carried out. Compared with control group, the observation group had significantly lower intraoperative blood loss and postoperative 1h blood loss, p<0.0, but similar postoperative 2-24h blood loss, p>0.05; in observation, there were 6 cases of postpartum hemorrhage, while the number in control group was 20 cases. The two groups had no difference in blood pressure after treatment, p>0.05.The combination drug therapy during cesarean section is effective and reliable in preventing postpartum hemorrhage for women with HDCP.


Assuntos
Carboprosta , Hemorragia Pós-Parto , Carboprosta/uso terapêutico , Cesárea/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Ocitocina/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Parto/tratamento farmacológico , Hemorragia Pós-Parto/prevenção & controle , Gravidez
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