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1.
Artigo em Inglês | MEDLINE | ID: mdl-38828494

RESUMO

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

2.
Small ; : e2402613, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850186

RESUMO

Methanol is not only a promising liquid hydrogen carrier but also an important feedstock chemical for chemical synthesis. Catalyst design is vital for enabling the reactions to occur under ambient conditions. This study reports a new class of van der Waals heterojunction photocatalyst, which is synthesized by hot-injection method, whereby carbon dots (CDs) are grown in situ on ZnSe nanoplatelets (NPLs), i.e., metal chalcogenide quantum wells. The resultant organic-inorganic hybrid nanoparticles, CD-NPLs, are able to perform methanol dehydrogenation through CH splitting. The heterostructure has enabled light-induced charge transfer from the CDs into the NPLs occurring on a sub-nanosecond timescale, with charges remaining separated across the CD-NPLs heterostructure for longer than 500 ns. This resulted in significantly heightened H2 production rate of 107 µmole·g-1·h-1 and enhanced photocurrent density up to 34 µA cm-2 at 1 V bias potential. EPR and NMR analyses confirmed the occurrence of α-CH splitting and CC coupling. The novel CD-based organic-inorganic semiconductor heterojunction is poised to enable the discovery of a host of new nano-hybrid photocatalysts with full tunability in the band structure, charge transfer, and divergent surface chemistry for guiding photoredox pathways and accelerating reaction rates.

3.
Sensors (Basel) ; 24(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38676140

RESUMO

The graph neural network (GNN) has shown outstanding performance in processing unstructured data. However, the downstream task performance of GNN strongly depends on the accuracy of data graph structural features and, as a type of deep learning (DL) model, the size of the training dataset is equally crucial to its performance. This paper is based on graph neural networks to predict and complete the target radio environment map (REM) through multiple complete REMs and sparse spectrum monitoring data in the target domain. Due to the complexity of radio wave propagation in space, it is difficult to accurately and explicitly construct the spatial graph structure of the spectral data. In response to the two above issues, we propose a multi-source domain adaptive of GNN for regression (GNN-MDAR) model, which includes two key modules: (1) graph structure alignment modules are used to capture and learn graph structure information shared by cross-domain radio propagation and extract reliable graph structure information for downstream reference signal receiving power (RSRP) prediction task; and (2) a spatial distribution matching module is used to reduce the feature distribution mismatch across spatial grids and improve the model's ability to remain domain invariant. Based on the measured REMs dataset, the comparative results of simulation experiments show that the GNN-MDAR outperforms the other four benchmark methods in accuracy when there is less RSRP label data in the target domain.

4.
Int Immunopharmacol ; 128: 111529, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244516

RESUMO

BACKGROUND: Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) plays a crucial role in DNA base excision repair, cell apoptosis, cell signaling, and the regulation of transcription factors through redox modulation and the control of reactive oxygen species (ROS). However, the connection between APE1 and acute liver injury (ALI) remains enigmatic. This study aims to unravel the molecular mechanisms underlying ALI and shed light on the role of APE1 in this context. METHOD: We induced acute liver injury (ALI) in mice by lipopolysaccharide/D-galactosamine (LPS/GalN) and intervened with the APE1 inhibitor E3330. We examined the expression of APE1 in ALI mice and ALI patient tissues after E3330 intervention, Additionally, we measured hepatic oxidative stress, ferroptosis, and autophagy marker proteins and genes. In establishing an AML-12 liver cell injury model, we utilized the Nrf2 activator tert-butylhydroquinone (TBHQ) as an intervention and examined APE1, Nrf2, ferroptosis-related proteins, and autophagy marker proteins and mRNA. RESULTS: Both ALI patients and ALI mice exhibited reduced APE1 expression levels. After E3330 intervention, there was a significant exacerbation of liver injury, oxidative stress, and a reduction in the expression of proteins, including GPX4, X-CT, ATG3, ATG5, and LC3 (LC3I/II). Consistent results were also observed in AML-12 cells. With TBHQ intervention, Nrf2 expression increased, along with the expression of proteins associated with iron death and autophagy. Mechanistically, APE1 activation regulates Nrf2 to inhibit ferroptosis and promote autophagy in hepatocytes. CONCLUSION: The data suggest that APE1 is a pivotal player in ALI, closely linked to its regulation of Nrf2. Strategies involving APE1 activation to modulate Nrf2, thereby inhibiting hepatocyte ferroptosis and promoting autophagy, may represent innovative therapeutic approaches for ALI. Additionally, tert-butylhydroquinone (TBHQ) holds significant promise in the treatment of acute liver injury.


Assuntos
Benzoquinonas , Ferroptose , Hidroquinonas , Leucemia Mieloide Aguda , Propionatos , Animais , Humanos , Camundongos , Autofagia/genética , Hepatócitos/metabolismo , Leucemia Mieloide Aguda/metabolismo , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo
5.
Sensors (Basel) ; 23(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37960582

RESUMO

In general, judging the use/idle state of the wireless spectrum is the foundation for cognitive radio users (secondary users, SUs) to access limited spectrum resources efficiently. Rich information can be mined by the inherent correlation of electromagnetic spectrum data from SUs in time, frequency, space, and other dimensions. Therefore, how to efficiently use the spectrum status of each SU implementation of reception multidimensional combination forecasting is the core of this paper. In this paper, we propose a deep-learning hybrid model called TensorGCN-LSTM based on the tensor data structure. The model treats SUs deployed at different spatial locations under the same frequency, and the spectrum status of SUs themselves under different frequencies in the task area as nodes and constructs two types of graph structures. Graph convolutional operations are used to sequentially extract corresponding spatial-domain and frequency-domain features from the two types of graph structures. Then, the long short-term memory (LSTM) model is used to fuse the spatial, frequency, and temporal features of the cognitive radio environment data. Finally, the prediction task of the spectrum distribution situation is accomplished through fully connected layers. Specifically, the model constructs a tensor graph based on the spatial similarity of SUs' locations and the frequency correlation between different frequency signals received by SUs, which describes the electromagnetic wave's dependency relationship in spatial and frequency domains. LSTM is used to capture the electromagnetic wave's dependency relationship in the temporal domain. To evaluate the effectiveness of the model, we conducted ablation experiments on LSTM, GCN, GC-LSTM, and TensorGCN-LSTM models using simulated data. The experimental results showed that our model achieves better prediction performance in RMSE, and the correlation coefficient R2 of 0.8753 also confirms the feasibility of the model.

6.
Neural Regen Res ; 18(1): 226-232, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799547

RESUMO

Previous studies have shown that berberine has neuroprotective effects against Alzheimer's disease, including antagonizing tau phosphorylation, and inhibiting acetylcholinesterase activity and neural cell apoptosis. However, its low bioavailability and adverse reactions with conventional administration limit its clinical application. In this study, we prepared berberine nanoliposomes using liposomes characterized by low toxicity, high entrapment efficiency, and biodegradability, and modified them with lactoferrin. Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency. We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer's disease established by injection of amyloid-beta 1-42 into the lateral ventricle. Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus, reduced tau over-phosphorylation in the cerebral cortex, and improved mouse behavior. These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer's disease.

7.
J Ethnopharmacol ; 301: 115837, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252875

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: During the Eastern Han Dynasty, Zhang Zhongjing first recorded the Gancao Fuzi decoction (GCFZD) formula in the "Synopsis of the Golden Chamber", which is reportedly an effective and safe treatment for rheumatoid arthritis (RA). However, the mechanism underlying the observed improvement in the T helper 17 (Th17)/regulatory T (Treg) cell imbalance in RA obtained with GCFZD has not been reported. AIM OF THE STUDY: This study aimed to demonstrate whether GCFZD ameliorated RA by modulating the Th17/Treg imbalance in RA mice. MATERIALS AND METHODS: Collagen was used to induce a model of collagen-induced arthritis (CIA) in mice. GCFZD was administered by gavage, and the arthritis index score, imaging and histopathological changes of the ankle joints, and the levels of the immunoglobulin G (IgG) class antibodies and proinflammatory factors in serum were determined. In addition, the frequencies of Th17 and Treg cells, the levels of relevant transcription factors and functional factors and the miR-34a gene in the spleen and the levels of interleukin-17A (IL-17A) and IL-10 in serum were determined. RESULTS: GCFZD significantly reduced the arthritis score, improved joint swelling and bone damage, reduced the pathological score, and decreased the serum levels of IgG class antibody (IgG and IgG2a) and proinflammatory factor [tumour necrosis factor-alpha (TNF-α), IL-1ß and IL-6]. Moreover, the Th17-cell proportion, the expression level of the Th17-specific transcription factor retinoic acid-related orphan receptor γt (RORγt) and functional factor IL-17A in the spleen, and the serum IL-17A level were decreased, whereas the Treg cell proportion, expression levels of the Treg-specific transcription factor forkhead box P3 (Foxp3) and functional factor IL-10 in the spleen, and the serum IL-10 level were increased. Furthermore, GCFZD inhibited miR-34a gene expression while promoting Foxp3 protein expression. CONCLUSIONS: The findings of this study demonstrate the therapeutic effect of GCFZD on mice with CIA, and the mechanism is related to an improvement in the Th17/Treg cell imbalance by targeting Foxp3 via miR-34a.


Assuntos
Artrite Experimental , Artrite Reumatoide , MicroRNAs , Camundongos , Animais , Linfócitos T Reguladores , Interleucina-17/metabolismo , Interleucina-10/metabolismo , Células Th17 , Artrite Reumatoide/patologia , Artrite Experimental/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Imunoglobulina G , Fatores de Transcrição/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
8.
BMC Cancer ; 22(1): 1128, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329394

RESUMO

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.


Assuntos
Neoplasias da Mama , Avaliação Nutricional , Humanos , Feminino , Prognóstico , Estudos Retrospectivos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Linfócitos/patologia , Neutrófilos/patologia , Inflamação/patologia
9.
Transl Neurosci ; 13(1): 369-378, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36304098

RESUMO

Oxidative stress is considered as an important mechanism underlying the pathology of neurodegenerative disorders. In this study, we utilized an in vitro model where oxidative stress process was evoked by exogenous hydrogen peroxide (H2O2) in HT22 murine hippocampal neurons and evaluated the neuroprotective effects of geissoschizine methyl ether (GME), a naturally occurring alkaloid from the hooks of Uncaria rhynchophylla (Miq.) Jacks. After a 24 h H2O2 (350 µM) insult, a significant decrease in cell survival and a sharp increase in intracellular reactive oxygen species were observed in HT22 cells. Encouragingly, GME (10-200 µM) effectively reversed these abnormal cellular changes induced by H2O2. Moreover, mechanistic studies using Western blot revealed that GME inhibited the increase of phospho-ERK protein expression, but not phospho-p38, caused by H2O2. Molecular docking simulation further revealed a possible binding mode that GME inhibited ERK protein, showing that GME favorably bound to ERK via multiple hydrophobic and hydrogen bond interactions. These findings indicate that GME provide effective neuroprotection via inhibiting ERK pathway and also encourage further ex vivo and in vivo pharmacological investigations of GME in treating oxidative stress-mediated neurological disorders.

10.
Int J Mol Sci ; 23(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35163418

RESUMO

Damage to organs by trauma, infection, diseases, congenital defects, aging, and other injuries causes organ malfunction and is life-threatening under serious conditions. Some of the lower order vertebrates such as zebrafish, salamanders, and chicks possess superior organ regenerative capacity over mammals. The extracellular signal-regulated kinases 1 and 2 (ERK1/2), as key members of the mitogen-activated protein kinase (MAPK) family, are serine/threonine protein kinases that are phylogenetically conserved among vertebrate taxa. MAPK/ERK signaling is an irreplaceable player participating in diverse biological activities through phosphorylating a broad variety of substrates in the cytoplasm as well as inside the nucleus. Current evidence supports a central role of the MAPK/ERK pathway during organ regeneration processes. MAPK/ERK signaling is rapidly excited in response to injury stimuli and coordinates essential pro-regenerative cellular events including cell survival, cell fate turnover, migration, proliferation, growth, and transcriptional and translational activities. In this literature review, we recapitulated the multifaceted MAPK/ERK signaling regulations, its dynamic spatio-temporal activities, and the profound roles during multiple organ regeneration, including appendages, heart, liver, eye, and peripheral/central nervous system, illuminating the possibility of MAPK/ERK signaling as a critical mechanism underlying the vastly differential regenerative capacities among vertebrate species, as well as its potential applications in tissue engineering and regenerative medicine.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Organogênese/fisiologia , Regeneração/fisiologia , Vertebrados/fisiologia , Animais , MAP Quinases Reguladas por Sinal Extracelular/química , Humanos , Modelos Biológicos
11.
Transl Pediatr ; 10(9): 2298-2306, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733670

RESUMO

BACKGROUND: The molecular mechanism of Astragali Radix in the treatment of children with nephrotic syndrome (NS) is unclear. This study aimed to use network pharmacology to explore this potential mechanism. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to identify the main active ingredients of Astragali Radix. The PharmMapper, Online Mendelian Inheritance in Man (OMIM), and GeneCards databases were then used to identify the active ingredients of Astragali Radix. The String database and Cytoscape software were used to construct the protein-protein network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID Database. RESULTS: In the TCMSP Database, a total of 20 chemical constituents of Astragali Radix were screened. After removing the duplicates and false positive genes, 394 targets of these active ingredients were obtained from PharmMapper. By comparing the NS-related genes in the GeneCards and OMIM Databases, a total of 39 potential NS-related targets were ultimately identified. The protein-protein-interaction network included 39 nodes and 366 edges. The top 5 proteins were albumin (ALB), serine/threonine kinase (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), and matrix metallopeptidase 9 (MMP9). The GO analysis showed that the target genes were mainly involved in biological processes (e.g., signal transduction, the positive regulation of cell proliferation, and the positive regulation of migration). The cellular components included a plasma membrane, extracellular exosome, and extracellular space. The molecular functions included protein binding, zinc-ion binding, protein tyrosine kinase activity, and enzyme binding. The KEGG analysis showed that the treatment of NS by Astragali Radix mainly involved pathways in cancer, proteoglycans in cancer, the phosphatidylinositol 3-kinase and protein kinase B (PI3K-Akt) signaling pathway, the rennin-angiotensin-system (Ras) signaling pathways, and Forkhead box protein O1 (FoxO) signaling pathways. CONCLUSIONS: In the present study, the network pharmacology method was used to explore the potential targets and pathways of Astragali Radix in the treatment of NS. We also provided future research directions for the treatment of NS with a complex pathogenesis.

12.
Mater Sci Eng C Mater Biol Appl ; 130: 112469, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34702544

RESUMO

Tissue-engineered skin equivalent (TESE) is an optimized alternative for the treatment of skin defects. Designing and fabricating biomaterials with desired properties to load cells is critical for the approach. In this study, we aim to develop a novel TESE with recombinant human collagen (rHC) hydrogel and fibroblasts to improve full-thickness skin defect repair. First, the bioactive effect of rHC on fibroblast proliferation, migration and phenotype was assayed. The results showed that rHC had good biocompatibility and could stimulate fibroblasts migration and secrete various growth factors. Then, rHC was cross-linked with transglutaminase (TG) to prepare rHC hydrogel. Rheometer tests indicated that 10% rHC/TG hydrogel could reach a oscillate stress of 251 Pa and remained stable. Fibroblasts were seeded into rHC/TG hydrogel to prepare TESE. Confocal microscope and scanning electronic microscope observation showed that seeded fibroblasts survived well in the hydrogel. Finally, the therapeutic effect of the newly prepared TESE was tested in a mouse full-thickness skin defect model. The results demonstrated that TESE could significantly improve skin defect repair in vivo. Conclusively, TESE prepared from rHC and fibroblasts in this study exhibits great potential for clinical application in the future.


Assuntos
Colágeno , Hidrogéis , Animais , Materiais Biocompatíveis/farmacologia , Fibroblastos , Humanos , Hidrogéis/farmacologia , Camundongos , Pele , Engenharia Tecidual
13.
Front Cell Dev Biol ; 9: 649656, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422792

RESUMO

Phosphatidylinositol 3-kinase (PI3K) signaling plays a central role in various biological processes, and its abnormality leads to a broad spectrum of human diseases, such as cancer, fibrosis, and immunological disorders. However, the mechanisms by which PI3K signaling regulates the behavior of stem cells during regeneration are poorly understood. Planarian flatworms possess abundant adult stem cells (called neoblasts) allowing them to develop remarkable regenerative capabilities, thus the animals represent an ideal model for studying stem cells and regenerative medicine in vivo. In this study, the spatiotemporal expression pattern of Djpi3k, a PI3K ortholog in the planarian Dugesia japonica, was investigated and suggests its potential role in wound response and tissue regeneration. A loss-of-function study was conducted using small molecules and RNA interference technique, providing evidence that PI3K signaling is required for blastema regrowth and cilia maintenance during planarian regeneration and homeostasis. Interestingly, the mitotic and apoptotic responses to amputation are substantially abated in PI3K inhibitor-treated regenerating animals, while knockdown of Djpi3k alleviates the mitotic response and postpones the peak of apoptotic cell death, which may contribute to the varying degrees of regenerative defects induced by the pharmacological and genetic approaches. These observations reveal novel roles for PI3K signaling in the regulation of the cellular responses to amputation during planarian regeneration and provide insights for investigating the disease-related genes in the regeneration-competent organism in vivo.

14.
J Cell Physiol ; 236(7): 4973-4984, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33615474

RESUMO

Cervical cancer (CC) has caused numerous cancer-related deaths in women. Recent years, circular RNAs have been reported as vital factors in CC tumorigenesis. Our current study focused on the role of hsa_circ_0102171 (called circ_0102171 subsequently) in CC. At first, we applied reverse transcription polymerase chain reaction to detect the expression of circ_0102171 in CC tissues and cells. Subsequently, we silenced circ_0102171 to conduct loss-of-function assays, including cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, Transwell assay, and flow cytometry analysis. Interestingly, we discovered that circ_0102171 expressed at a high level in CC tissues and cells. Functionally, silencing circ_0102171 prohibited cell proliferation, migration and invasion, and strengthened cell apoptosis in CC in vitro. Mechanistic investigations revealed that circ_0102171 could act as a sponge for miR-4465. Gain-of-function assays demonstrated that miR-4465 hindered the growth and migration of CC cells. Moreover, circ_0102171 enhanced the level of CREB3 regulatory factor (CREBRF) which was the downstream target of miR-4465. Rescue assays suggested that CREBRF and miR-4465 could involve in circ_0102171-mediated CC progression. Finally, in vivo data supported that silencing circ_0102171 hindered CC cell growth. In conclusion, circ_0102171 aggravates CC progression via targeting miR-4465/CREBRF axis.


Assuntos
Transformação Celular Neoplásica/patologia , MicroRNAs/genética , RNA Circular/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/patologia , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Feminino , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Transplante de Neoplasias , Transplante Heterólogo , Proteínas Supressoras de Tumor/genética , Neoplasias do Colo do Útero/genética
15.
Chin Med ; 16(1): 18, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549148

RESUMO

BACKGROUND: Shende'an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson's disease (PD) in vitro and in vivo. METHODS: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively. RESULTS: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson's disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway. CONCLUSIONS: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

16.
Brachytherapy ; 20(3): 519-526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33485809

RESUMO

BACKGROUND: The recommended external beam radiotherapy (EBRT) dose for cervical cancer is 40-50 Gy, but there is no consensus. In this study, 45-Gy and 50.4-Gy treatment groups were compared for fused doses to target tumor areas and organs at risk (OARs), clinical efficacy, and quality of life. METHODS: Seventy-nine cases receiving radical radiotherapy within the past 3 years were retrospectively analyzed. EBRT and three-dimensional brachytherapy dose fusion values were calculated for target areas and OARs using Elastix V5.0. Clinical efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST), adverse events using Common Terminology Criteria for Adverse Events v4.03 (CTCAE4.03), and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RESULTS: Minimum fused dose delivered to 90% of the high-risk clinical target volume (HRCTV D90) did not differ significantly between 45-Gy and 50.4-Gy groups, whereas D2cc values of rectum and bladder (OARs) were significantly lower in the 45-Gy group (both p < 0.05). Further analysis showed that these D2cc differences resulted primarily from EBRT. No grade III-IV adverse events were observed in either group during follow up. Short-term clinical efficacy, adverse events, and EORTC QLQ-C30 functional and symptom scales also did not differ significantly between groups (all p > 0.05). However, quality of life was markedly higher in the 45-Gy group (p < 0.05). CONCLUSION: Appropriate EBRT dose reduction can reduce OAR irradiation without compromising total target area dose or clinical efficacy. Dose fusion can facilitate the judicious choice of EBRT to limit OAR exposure, reduce adverse events, and enhance the quality of life.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Braquiterapia/métodos , Feminino , Humanos , Órgãos em Risco , Qualidade de Vida , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Reto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/radioterapia
17.
J Cell Physiol ; 235(10): 7592-7603, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32324262

RESUMO

Cervical cancer (CC) is one of the commonest malignant cancers among women with high morbidity and mortality. Despite encouraging advances had been found in diagnostic and therapeutic strategies, effective therapeutic strategy and further exploration of the mechanism underlying in CC is still needed. We searched The Cancer Genome Atlas database and found that long noncoding RNA LINC02535 was highly expressed in CC. LINC02535 has not been studied in CC, and its molecular regulation mechanism remains unknown. Based on starBase database, LINC02535 could potentially bind poly (rC) binding protein 2 (PCBP2). In the present study, we discovered a significant increase of the LINC02535 and PCBP2 expression in CC tissues and cells as compared with the adjacent normal tissues and normal cervical epithelial cells. LINC02535 and PCBP2 can bind with each other and were colocated in cytoplasm. LINC02535 and PCBP2 promoted cell proliferation, migration, invasion, and suppressed apoptosis in CC. LINC02535 and PCBP2 facilitated the repair of DNA damage to promote CC progression. LINC02535 cooperated with PCBP2 to enhance the stability of RRM1 messenger RNA (mRNA). RRM1 promoted the repair of DNA damage and epithelial-to-mesenchymal transition (EMT) process in CC cells. LINC02535 regulated tumorigenesis in vivo. In conclusion, LINC02535 cooperated with PCBP2, regulated stability of RRM1 mRNA to promote cell proliferation and EMT process in CC cells by facilitating the repair of DNA damage, providing a potential biomarker for CC.


Assuntos
Dano ao DNA/genética , Reparo do DNA/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Ribonucleosídeo Difosfato Redutase/genética , Neoplasias do Colo do Útero/genética , Animais , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias do Colo do Útero/patologia
18.
Sci Immunol ; 5(44)2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060144

RESUMO

The DRB1*15:01-DQB1*06:02 (DR1501-DQ6) haplotype is linked to dominant protection from type 1 diabetes, but the cellular mechanism for this association is unclear. To address this question, we identified multiple DR1501- and DQ6-restricted glutamate decarboxylase 65 (GAD65) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific T cell epitopes. Three of the DR1501/DQ6-restricted epitopes identified were previously reported to be restricted by DRB1*04:01/DRB1*03:01/DQB1*03:02. We also used specific class II tetramer reagents to assess T cell frequencies. Our results indicated that GAD65- and IGRP-specific effector and CD25+CD127-FOXP3+ regulatory CD4+ T cells were present at higher frequencies in individuals with the protective haplotype than those with susceptible or neutral haplotypes. We further confirmed higher frequencies of islet antigen-specific effector and regulatory CD4+ T cells in DR1501-DQ6 individuals through a CD154/CD137 up-regulation assay. DR1501-restricted effector T cells were capable of producing interferon-γ (IFN-γ) and interleukin-4 (IL-4) but were more likely to produce IL-10 compared with effectors from individuals with susceptible haplotypes. To evaluate their capacity for antigen-specific regulatory activity, we cloned GAD65 and IGRP epitope-specific regulatory T cells. We showed that these regulatory T cells suppressed DR1501-restricted GAD65- and IGRP-specific effectors and DQB1*03:02-restricted GAD65-specific effectors in an antigen-specific fashion. In total, these results suggest that the protective DR1501-DQ6 haplotype confers protection through increased frequencies of islet-specific IL-10-producing T effectors and CD25+CD127-FOXP3+ regulatory T cells.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Haplótipos , Células Secretoras de Insulina/imunologia , Diabetes Mellitus Tipo 1/patologia , Epitopos de Linfócito T/imunologia , Voluntários Saudáveis , Humanos
19.
J Clin Lab Anal ; 34(5): e23191, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31901184

RESUMO

BACKGROUND: The differential diagnoses of patients hospitalized for respiratory infections due to influenza virus vs other pathogens are challenging. Our study investigated whether hematological parameters such as neutrophil (N), lymphocyte (L), platelet (PLT), and neutrophil-to-lymphocyte ratio (NLR) contributed in diagnosing influenza virus infections and in discriminating other respiratory infections. METHODS: We retrospectively analyzed the laboratory characteristics of 307 patients with respiratory infections caused by influenza/non-influenza virus and bacteria. The diagnostic abilities of hematological indexes were evaluated in the patients compared with 100 healthy people. RESULTS: The hematological parameters in patients with influenza virus infection were dramatically altered compared with those in the controls. Additionally, among the systemic inflammatory markers, the sensitivity of NLR for influenza detection was higher than that of N and L. PLT was significantly lower in influenza virus-positive infection than in influenza virus-negative infection. Moreover, when patients with influenza virus infection were cured, PLT returned to a normal level. The red blood cell (RBC) and hemoglobin (Hb) levels of influenza virus infection were higher than those of bacterial infection. Compared with traditional N and L, NLR and platelet-to-neutrophil (PNR) showed greater significance between influenza virus and bacterial infection (P < .01). CONCLUSION: Neutrophil-to-lymphocyte ratio with high sensitivity is a preferable diagnostic tool to screen influenza virus-infected patients than N and L. PLT accounts in the differential diagnoses of respiratory infections due to influenza virus and other pathogens among patients. In addition, RBC, Hb, NLR, and PNR can significantly differentiate between influenza virus infections and bacterial infections.


Assuntos
Contagem de Células Sanguíneas , Influenza Humana/sangue , Influenza Humana/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/sangue , Infecções Bacterianas/diagnóstico , Feminino , Hospitalização , Humanos , Influenza Humana/etiologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
20.
Front Oncol ; 9: 696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31448225

RESUMO

Gas signaling molecules (GSMs), composed of oxygen, carbon monoxide, nitric oxide, hydrogen sulfide, etc., play critical roles in regulating signal transduction and cellular homeostasis. Interestingly, through various administrations, these molecules also exhibit potential in cancer treatment. Recently, hydrogen gas (formula: H2) emerges as another GSM which possesses multiple bioactivities, including anti-inflammation, anti-reactive oxygen species, and anti-cancer. Growing evidence has shown that hydrogen gas can either alleviate the side effects caused by conventional chemotherapeutics, or suppress the growth of cancer cells and xenograft tumor, suggesting its broad potent application in clinical therapy. In the current review, we summarize these studies and discuss the underlying mechanisms. The application of hydrogen gas in cancer treatment is still in its nascent stage, further mechanistic study and the development of portable instruments are warranted.

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