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1.
J Headache Pain ; 25(1): 140, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192198

RESUMO

BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.


Assuntos
Núcleos Ventrais do Tálamo , Animais , Camundongos , Masculino , Neuralgia do Trigêmeo/fisiopatologia , Neuralgia/fisiopatologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Optogenética , Limiar da Dor/fisiologia
2.
J Med Virol ; 96(9): e29894, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39206838

RESUMO

A substantial body of literature, including our own, points to a connection between hepatitis B virus (HBV) infection and the development of drug resistance in hepatocellular carcinoma (HCC), particularly against sorafenib. However, the influence of HBV on resistance to regorafenib, another therapeutic agent, has been less studied. In this study, we used the GEO database (GSE87630) and clinical samples to demonstrate that C-C motif chemokine receptor 9 (CCR9) was highly expressed in HBV-related HCC and predicted poor overall survival. Its overexpression correlated with HBsAg-positive HCC patients. Both univariate and multivariable Cox regression analysis elucidated CCR9 was an independent risk factor for poor overall survival in HCC patients. Our in vitro findings further revealed that HBV structural proteins, small HBV surface antigen (SHBs), triggered an upregulation of CCR9. Functional assays showed that SHBs enhanced HCC cell proliferation, migration, and invasion, increased ABCB1 and ABCC1 expression, and promoted regorafenib resistance via CCR9. Intriguingly, overexpression of HBV plasmid and an AAV-HBV mouse model both exhibited a significant elevation in global N6-methyladenosine (m6A) levels. Further investigations revealed that SHBs elevated these m6A levels, upregulated CCR9 and stabilized CCR9 mRNA through KIAA1429-mediated m6A modification, with sites 1373 and 1496 on CCR9 mRNA being critical for modification. In conclusion, SHBs promoted HCC progression and regorafenib resistance via KIAA1429-mediated m6A modification of CCR9. Our findings suggested that CCR9 could be a potential prognostic biomarker and a valuable molecular therapeutic target of regorafenib resistance in HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Antígenos de Superfície da Hepatite B , Neoplasias Hepáticas , Compostos de Fenilureia , Piridinas , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Animais , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/metabolismo , Piridinas/farmacologia , Piridinas/uso terapêutico , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Camundongos , Masculino , Feminino , Receptores CCR/genética , Receptores CCR/metabolismo , Linhagem Celular Tumoral , Vírus da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Pessoa de Meia-Idade , Hepatite B/virologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Adenosina/análogos & derivados
3.
Ecotoxicol Environ Saf ; 281: 116678, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964067

RESUMO

The non-protein amino acid ß-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a 'double-edged sword' for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.


Assuntos
Diamino Aminoácidos , Doença Hepática Induzida por Substâncias e Drogas , Toxinas de Cianobactérias , Armadilhas Extracelulares , Estresse Oxidativo , Animais , Diamino Aminoácidos/toxicidade , Armadilhas Extracelulares/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Neurotoxinas/toxicidade , Transdução de Sinais/efeitos dos fármacos
4.
Animals (Basel) ; 14(14)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39061594

RESUMO

The liver of chickens is essential for maintaining physiological activities and homeostasis. This study aims to investigate the specific function and molecular regulatory mechanism of microRNA-122 (miR-122), which is highly expressed in chicken liver. A lentivirus-mediated overexpression vector of miR-122 was constructed and used to infect 12-day-old female Qingyuan Partridge chickens. Transcriptome sequencing analysis was performed to identify differentially expressed genes in the liver. Overexpression of miR-122 resulted in 776 differentially expressed genes (DEGs). Enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed associations with lipid metabolism, cellular senescence, cell adhesion molecules, and the MAPK signaling pathway. Eight potential target genes of miR-122 (ARHGAP32, CTSD, LBH, PLEKHB2, SEC14L1, SLC2A1, SLC6A14, and SP8) were identified through miRNA target prediction platforms and literature integration. This study provides novel insights into the molecular regulatory mechanisms of miR-122 in chicken liver, highlighting its role in key biological processes and signaling pathways. These discoveries enhance our understanding of miR-122's impact on chicken liver function and offer valuable information for improving chicken production performance and health.

5.
PeerJ ; 12: e17072, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525278

RESUMO

Sex determination in chickens at an early embryonic stage has been a longstanding challenge in poultry production due to the unique ZZ:ZW sex chromosome system and various influencing factors. This review has summarized the genes related to the sex differentiation of chicken early embryos (mainly Dmrt1, Sox9, Amh, Cyp19a1, Foxl2, Tle4z1, Jun, Hintw, Ube2i, Spin1z, Hmgcs1, Foxd1, Tox3, Ddx4, cHemgn and Serpinb11 in this article), and has found that these contributions enhance our understanding of the genetic basis of sex determination in chickens, while identifying potential gene targets for future research. This knowledge may inform and guide the development of sex screening technologies for hatching eggs and support advancements in gene-editing approaches for chicken embryos. Moreover, these insights offer hope for enhancing animal welfare and promoting conservation efforts in poultry production.


Assuntos
Galinhas , Diferenciação Sexual , Embrião de Galinha , Animais , Galinhas/genética , Diferenciação Sexual/genética , Processos de Determinação Sexual/genética , Cromossomos Sexuais
6.
IEEE Trans Image Process ; 33: 1883-1897, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451760

RESUMO

Self-supervised contrastive learning has proven to be successful for skeleton-based action recognition. For contrastive learning, data transformations are found to fundamentally affect the learned representation quality. However, traditional invariant contrastive learning is detrimental to the performance on the downstream task if the transformation carries important information for the task. In this sense, it limits the application of many data transformations in the current contrastive learning pipeline. To address these issues, we propose to utilize equivariant contrastive learning, which extends invariant contrastive learning and preserves important information. By integrating equivariant and invariant contrastive learning into a hybrid approach, the model can better leverage the motion patterns exposed by data transformations and obtain a more discriminative representation space. Specifically, a self-distillation loss is first proposed for transformed data of different intensities to fully utilize invariant transformations, especially strong invariant transformations. For equivariant transformations, we explore the potential of skeleton mixing and temporal shuffling for equivariant contrastive learning. Meanwhile, we analyze the impacts of different data transformations on the feature space in terms of two novel metrics proposed in this paper, namely, consistency and diversity. In particular, we demonstrate that equivariant learning boosts performance by alleviating the dimensional collapse problem. Experimental results on several benchmarks indicate that our method outperforms existing state-of-the-art methods.

7.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338942

RESUMO

Zoysia japonica (Zoysia japonica Steud.) is a kind of warm-season turfgrass with many excellent characteristics. However, the shorter green period and longer dormancy caused by cold stress in late autumn and winter are the most limiting factors affecting its application. A previous transcriptome analysis revealed that ethephon regulated genes in chlorophyll metabolism in Zoysia japonica under cold stress. Further experimental data are necessary to understand the effect and underlying mechanism of ethephon in regulating the cold tolerance of Zoysia japonica. The aim of this study was to evaluate the effects of ethephon by measuring the enzyme activity, intermediates content, and gene expression related to ethylene biosynthesis, signaling, and chlorophyll metabolism. In addition, the ethylene production rate, chlorophyll content, and chlorophyll a/b ratio were analyzed. The results showed that ethephon application in a proper concentration inhibited endogenous ethylene biosynthesis, but eventually promoted the ethylene production rate due to its ethylene-releasing nature. Ethephon could promote chlorophyll content and improve plant growth in Zoysia japonica under cold-stressed conditions. In conclusion, ethephon plays a positive role in releasing ethylene and maintaining the chlorophyll content in Zoysia japonica both under non-stressed and cold-stressed conditions.


Assuntos
Etilenos , Compostos Organofosforados , Poaceae , Clorofila A/metabolismo , Poaceae/genética , Etilenos/metabolismo , Clorofila/metabolismo
8.
Cell Biosci ; 13(1): 213, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990254

RESUMO

BACKGROUND: Abnormalities in the 5-HT system and synaptic plasticity are hallmark features of schizophrenia. Previous studies suggest that the human endogenous retrovirus W family envelope (ERVWE1) is an influential risk factor for schizophrenia and inversely correlates with 5-HT4 receptor in schizophrenia. To our knowledge, no data describes the effect of ERVWE1 on 5-HT neuronal plasticity. N6-methyladenosine (m6A) regulates gene expression and impacts synaptic plasticity. Our research aims to systematically investigate the effects of ERVWE1 on 5-HT neuronal plasticity through m6A modification in schizophrenia. RESULTS: HTR1B, ALKBH5, and Arc exhibited higher levels in individuals with first-episode schizophrenia compared to the controls and showed a strong positive correlation with ERVWE1. Interestingly, HTR1B was also correlated with ALKBH5 and Arc. Further analyses confirmed that ALKBH5 may be an independent risk factor for schizophrenia. In vitro studies, we discovered that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ERVWE1 induced HTR1B upregulation by improving its mRNA stability in ALKBH5-m6A-dependent epigenetic mechanisms. Importantly, ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1. CONCLUSIONS: Overall, HTR1B, Arc, and ALKBH5 levels were increased in schizophrenia and positively associated with ERVWE1. Moreover, ALKBH5 was a novel risk gene for schizophrenia. ERVWE1 impaired 5-HT neuronal plasticity in ALKBH5-m6A dependent mechanism by the HTR1B-ERK-ELK1-Arc pathway, which may be an important contributor to aberrant synaptic plasticity in schizophrenia.

9.
Front Oncol ; 13: 1067246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37823052

RESUMO

Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed through immunohistochemistry. In total, 655 patients with breast cancer who underwent surgery after biopsy at Sir Run Run Shaw Hospital between January 2019 to December 2021 were evaluated. The concordance rates (CRs) of malignant surgical specimens with CassiII needle biopsy was significantly high compared with core needle biopsy. Moreover, CassiII needle biopsy had about 20% improvement in sensitivity and about 5% improvement in positive predictive value compared to Core needle biopsy. The characteristics including age and tumor size were identified the risk factors for pathological inconsistencies with core needle biopsies. However, CassiII needle biopsy was associated with tumor diameter only. The CRs of ER, PgR, HER2, and Ki67 using Cassi needle were 98.08% (kappa, 0.941; p<.001), 90.77% (kappa, 0.812; p<.001), 69.62% (kappa, 0.482; p<.001), and 86.92% (kappa, 0.552; p<.001), respectively. Post-biopsy complications with CassiII needle biopsy were also collected. The complications of CassiII needle biopsy including chest stuffiness, pain and subcutaneous ecchymosis are not rare. The underlying mechanism of subcutaneous congestion or hematoma after CassiII needle biopsy might be the larger needle diameter and the effect of temperature on coagulation function. In summary, CassiII needle biopsy is age-independent and has a better accuracy than CNB for distinguishing carcinoma in situ and invasive carcinoma.

10.
Biomimetics (Basel) ; 8(3)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37504164

RESUMO

At present, the packing method of "plastic bag-buffer packing-packing paper box" is adopted for bearing packaging. However, the common packing method has a poor packing effect and poor versatility. In this study, a new biomimetic cobweb cushion is proposed to solve the problem of insufficient cushioning capacity of high-precision bearing cushion packaging pads. First, according to the nature of cobweb form, the cobweb cushion structure configuration is determined. Next, based on the structure of the cushion and the relationship between the parameters of radial thread and spiral thread, a mechanical and target optimization model is established. The stress nephogram of bearing and the cobweb cushion are analyzed under three drop heights of 381, 610, and 700 mm, in the finite element simulation software to ensure that the maximum bearings stress is not beyond the material yield strength. Via the 3D printing technology, a cobweb cushion shell cast is made. Drop tests of the bearing were performed, and the results were verified with the finite element simulation analysis. This research can provide technical support for the protection of high-precision bearings from accidental drops during transportation.

11.
Sensors (Basel) ; 23(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37177720

RESUMO

The secondary-phase grating-based tomographic microscopy system, which is widely used in the biological and life sciences, can observe all the sample multilayer image information simultaneously because it has multifocal points. However, chromatic aberration exists in the grating diffraction, which seriously affects the observation of the image. To correct the chromatic aberration of the tomographic microscope system, this paper proposes a system that adopts blazed gratings and angle-variable reflectors as chromatic aberration correction devices according to the principle of dispersion compensation and Fourier phase-shift theory. A reflector-separated light dispersion-compensated 3D microscopy system is presented to achieve chromatic aberration correction while solving the problem of multilayer image overlap. The theoretical verification and optical design of the system were completed using ZEMAX software. The results show that the proposed system reduced the chromatic aberration of ordinary tomographic microscopy systems by more than 90%, retaining more wavelengths of light information. In addition, the system had a relatively wide range in the color difference compensation element installation position, reducing the difficulty of dispersion compensation element installation. Overall, the results indicate that the proposed system is effective in reducing chromatic aberration in grating diffraction.

12.
Appl Opt ; 62(11): 2766-2775, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37133117

RESUMO

To suppress the mid-high-frequency error of small optical tungsten carbide aspheric molds, it is proposed to quickly select the critical process parameters by simulating the residual error after convolution of the tool influence function (TIF). After polishing for 10.47 min by the TIF, two simulation optimizations, RMS and Ra, converge to 9.3 and 5.347 nm, respectively. Their convergence rates are improved by 40% and 7.9%, respectively, compared to ordinary TIF. Then, a faster and more high-quality multi-tool combination smoothing suppression method is proposed, and the corresponding polishing tools are designed. Finally, the global Ra of the aspheric surface converges from 5.9 to 4.5 nm after smoothing for 5.5 min with a disc-shaped polishing tool with a fine microstructure and maintains an excellent low-frequency error (PV 0.0781 µm).

13.
Sensors (Basel) ; 23(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36679691

RESUMO

To address the shortcomings in many traditional spectral feature extraction algorithms in practical application of low modeling accuracy and poor stability, this paper introduces the "Boruta algorithm-based local optimization process" based on the traditional simulated annealing algorithm and proposes the "two-step simulated annealing algorithm (TSSA)". This algorithm combines global optimization and local optimization. The Boruta algorithm ensures that the feature extraction results are all strongly correlated with the dependent variable, reducing data redundancy. The accuracy and stability of the algorithm model are significantly improved. The experimental results show that compared with the traditional feature extraction method, the accuracy indexes of the inversion model established by using the TSSA algorithm for feature extraction were significantly improved, with the determination coefficient R2 of 0.9654, the root mean square error (RMSE) of 3.6723 µg/L, and the mean absolute error (MAE) of 3.1461 µg/L.


Assuntos
Algoritmos
14.
EMBO J ; 42(6): e112039, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36715460

RESUMO

Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of the intestinal epithelium. However, how ISC self-renewal is regulated still remains unclear. Here we identified a circular RNA, circBtnl1, that is highly expressed in ISCs. Loss of circBtnl1 in mice enhanced ISC self-renewal capacity and epithelial regeneration, without changes in mRNA and protein levels of its parental gene Btnl1. Mechanistically, circBtnl1 and Atf4 mRNA competitively bound the ATP-dependent RNA helicase Ddx3y to impair the stability of Atf4 mRNA in wild-type ISCs. Furthermore, ATF4 activated Sox9 transcription by binding to its promoter via a unique motif, to enhance the self-renewal capacity and epithelial regeneration of ISCs. In contrast, circBtnl1 knockout promoted Atf4 mRNA stability and enhanced ATF4 expression, which caused Sox9 transcription to potentiate ISC stemness. These data indicate that circBtnl1-mediated Atf4 mRNA decay suppresses Sox9 transcription that negatively modulates self-renewal maintenance of ISCs.


Assuntos
Fator 4 Ativador da Transcrição , Mucosa Intestinal , Estabilidade de RNA , RNA Circular , RNA Mensageiro , Regeneração , Células-Tronco , Células-Tronco/citologia , Células-Tronco/fisiologia , Organoides/citologia , Camundongos Endogâmicos C57BL , Animais , Camundongos , RNA Circular/genética , RNA Circular/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/fisiologia , Regeneração/genética , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , RNA Mensageiro/metabolismo , Ativação Transcricional , Fatores de Transcrição SOX9/genética , Antígenos de Histocompatibilidade Menor/metabolismo , RNA Helicases DEAD-box/metabolismo
15.
Asian J Surg ; 46(7): 2682-2688, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36283878

RESUMO

OBJECTIVE: Patients undergoing percutaneous transforaminal endoscopic discectomy (PTED) often complain of unbearable intraoperative pain. This study is to observe clinical effectiveness and safety of intradiscal local anesthetic injection for intraoperative pain relief. METHODS: Total 268 patients who underwent PTED were analyzed. Patients were divided into intradiscal saline injection group (group C) and intradiscal local anesthetic injection group (group L). Intradiscal mixture was consisted of saline or local anesthetic + methylene blue, the amount of injected mixture was 3 mL. Demographic data, visual analog scale (VAS) and Quebec Back Pain Disability Scale (QBPDS) scores, mean arterial pressure (MAP) and heart rate (HR), total dosage of fentanyl, satisfaction rate of anesthesia and complications were collected at different timepoints. RESULTS: Compared with group C (3.94 ± 0.57), there was a significant reduction of VAS in group L (2.83 ± 0.28) during fibrous annular operation phase (T2). Group L had a lower total dosage of fentanyl (71 [63, 78] µg) and a higher anesthesia satisfaction rate (95.3%) than group C (82 [70, 132] µg and 73.6%, respectively) (P < 0.001). MAP and HR were lower in group L than in group C at T2 (P < 0.001). Baseline characteristics and QBPDS scores showed no meaningful intergroup differences. Four cases of complications were reported in this study. CONCLUSION: Intradiscal local anesthetic injection significantly alleviated intraoperative back pain and increased the satisfaction rate of anesthesia, without severe complications, indicating that this technique is a feasible method for intraoperative back pain relief for patients undergoing PTED.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Anestésicos Locais , Estudos Retrospectivos , Deslocamento do Disco Intervertebral/cirurgia , Discotomia Percutânea/métodos , Resultado do Tratamento , Dor nas Costas/cirurgia , Fentanila
16.
J Immunother Cancer ; 10(12)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36543379

RESUMO

BACKGROUND: Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer. METHODS: We measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues. RESULTS: PLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1. CONCLUSIONS: Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Antígeno B7-H1/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Imunoterapia , Imunidade , Proliferação de Células , Proteínas/uso terapêutico
17.
Eur J Pharmacol ; 936: 175363, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36343694

RESUMO

PRE: and post-conditioning of sevoflurane attenuate cardiomyocyte death and protects against myocardial ischemia/reperfusion (I/R) injury, and this process is considered to be associated with cell autophagy and pyroptosis, but the detailed molecular mechanisms regarding to this issue have not been fully studied. In this study, we verified that sevoflurane exerted its protective effects in myocardial I/R injury by synergistically regulating the AMPK/ULK1 pathway-mediated autophagy and NLRP3-mediated pyroptotic cell death, and the interplays between cell autophagy and pyroptosis were also preliminarily investigated. Specifically, sevoflurane conditioning suppressed NLRP3 and cleaved caspase-1 expressions to inactivate cell pyroptosis, upregulated LC3B-II/I ratio, facilitated autophagosome formation and accelerated p62 degradation to trigger autophagy, and promoted the expressions of CDK2, CDK6 and Cyclin D1 to recover cell cycle in I/R mouse myocardial tissues in vivo and hypoxic/re-oxygenated (H/R) cardiomyocytes in vitro. Further experiments validated that sevoflurane promoted the phosphorylation of both AMPK (p-AMPK) and ULK1 (p-ULK1) to activate the AMPK/ULK1 pathway, and the promoting effects of sevoflurane on cell autophagy in H/R cardiomyocytes were abrogated by co-treating cells with AMPK inhibitor (compound C) and ULK1 inhibitor (SBI-0206965). Moreover, it was verified that compound C, SBI-0206965 and autophagy blocker chloroquine reversed H/R-induced cell death and pyroptosis in cardiomyocytes. Taken together, we concluded that sevoflurane activated the AMPK/ULK1 pathway to trigger autophagic flux and suppress NLRP3-mediated pyroptotic cell death in I/R or H/R-treated cardiomyocytes, which further ameliorated myocardial I/R injury.


Assuntos
Anestésicos , Traumatismo por Reperfusão Miocárdica , Animais , Camundongos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Sevoflurano/farmacologia , Piroptose , Miócitos Cardíacos , Proteínas Quinases Ativadas por AMP , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hipóxia , Autofagia , Inflamação
18.
Front Genet ; 13: 1005522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246634

RESUMO

Systemic therapy is one of the most significant cancer treatments. However, drug resistance often appears and has become the primary cause of cancer therapy failure. Regulation of drug target, drug metabolism and drug efflux, cell death escape (apoptosis, autophagy, et al.), epigenetic changes, and many other variables are complicatedly involved in the mechanisms of drug resistance. In various types of cancers, long non-coding RNA H19 (lncRNA H19) has been shown to play critical roles in tumor development, proliferation, metastasis, and multiple drug resistance as well. The efficacy of chemotherapy, endocrine therapy, and targeted therapy are all influenced by the expression of H19, especially in breast cancer, liver cancer, lung cancer and colorectal cancer. Here, we summarize the relationship between lncRNA H19 and tumorigenesis, and illustrate the drug resistance mechanisms caused by lncRNA H19 as well. This review may provide more therapeutic potential targets for future cancer treatments.

19.
Biomark Res ; 10(1): 58, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962400

RESUMO

Circulating tumor cells (CTCs) are cells that shed from a primary tumor and travel through the bloodstream. Studying the functional and molecular characteristics of CTCs may provide in-depth knowledge regarding highly lethal tumor diseases. Researchers are working to design devices and develop analytical methods that can capture and detect CTCs in whole blood from cancer patients with improved sensitivity and specificity. Techniques using whole blood samples utilize physical prosperity, immunoaffinity or a combination of the above methods and positive and negative enrichment during separation. Further analysis of CTCs is helpful in cancer monitoring, efficacy evaluation and designing of targeted cancer treatment methods. Although many advances have been achieved in the detection and molecular characterization of CTCs, several challenges still exist that limit the current use of this burgeoning diagnostic approach. In this review, a brief summary of the biological characterization of CTCs is presented. We focus on the current existing CTC detection methods and the potential clinical implications and challenges of CTCs. We also put forward our own views regarding the future development direction of CTCs.

20.
Plants (Basel) ; 11(3)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35161421

RESUMO

Zoysia japonica is a warm-season turfgrass with a good tolerance and minimal maintenance requirements. However, its use in Northern China is limited due to massive chlorophyll loss in early fall, which is the main factor affecting its distribution and utilization. Although ethephon treatment at specific concentrations has reportedly improved stress tolerance and extended the green period in turfgrass, the potential mechanisms underlying this effect are not clear. In this study, we evaluated and analyzed chlorophyll changes in the physiology and transcriptome of Z. japonica plants in response to cold stress (4 °C) with and without ethephon pretreatment. Based on the transcriptome and chlorophyll content analysis, ethephon pretreatment increased the leaf chlorophyll content under cold stress by affecting two processes: the stimulation of chlorophyll synthesis by upregulating ZjMgCH2 and ZjMgCH3 expression; and the suppression of chlorophyll degradation by downregulating ZjPAO, ZjRCCR, and ZjSGR expression. Furthermore, ethephon pretreatment increased the ratio of chlorophyll a to chlorophyll b in the leaves under cold stress, most likely by suppressing the conversion of chlorophyll a to chlorophyll b due to decreased chlorophyll b synthesis via downregulation of ZjCAO. Additionally, the inhibition of chlorophyll b synthesis may result in energy redistribution between photosystem II and photosystem I.

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