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1.
J Exp Clin Cancer Res ; 43(1): 123, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654325

RESUMO

BACKGROUND: Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. METHODS: A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. RESULTS: We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. CONCLUSIONS: NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Fucose , Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Neoplasias Pulmonares , MicroRNAs , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Glicosilação , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Exossomos/metabolismo , MicroRNAs/sangue , MicroRNAs/metabolismo , Genes Supressores de Tumor , Fucose/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Regulação para Baixo , Animais , Camundongos , Camundongos Nus , Proliferação de Células , Pontos de Checagem do Ciclo Celular , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Prognóstico , Transdução de Sinais , Progressão da Doença , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue
2.
PeerJ ; 12: e17141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529301

RESUMO

Background: Effective discrimination of lung adenocarcinoma (LUAD) in situ (AIS) from benign pulmonary nodules (BPN) is critical for the early diagnosis of AIS. Our pilot study in a small cohort of 90 serum samples has shown that serum interleukin 6 (IL-6) detection can distinguish AIS from BPN and health controls (HC). In this study, we intend to comprehensively define the diagnostic value of individual and combined detection of serum IL-6 related to the traditional tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) for AIS. Methods: The diagnostic performance of serum IL-6 along with CEA and CYFRA21-1 were evaluated in a large cohort of 300 serum samples by a chemiluminescence immunoassay and an electrochemiluminescence immunoassay. A training set comprised of 65 AIS, 65 BPN, and 65 HC samples was used to develop the predictive model for AIS. Data obtained from an independent validation set was applied to evaluate and validate the predictive model. Results: In the training set, the levels of serum IL-6 and CEA in the AIS group were significantly higher than those in the BPN/HC group (P < 0.05). There was no significant difference in serum CYFRA21-1 levels between the AIS group and the BPN/HC group (P> 0.05). Serum IL-6 and CEA levels for AIS patients showed an area under the curve (AUC) of 0.622 with 23.1% sensitivity at 90.7% specificity, and an AUC of 0.672 with 24.6% sensitivity at 97.6% specificity, respectively. The combination of serum IL-6 and CEA presented an AUC of 0.739, with 60.0% sensitivity at 95.4% specificity. The combination of serum IL-6 and CEA showed an AUC of 0.767 for AIS patients, with 57.1% sensitivity at 91.4% specificity in the validation set. Conclusions: IL-6 shows potential as a prospective serum biomarker for the diagnosis of AIS, and the combination of serum IL-6 with CEA may contribute to increased accuracy in AIS diagnosis. However, it is worth noting that further research is still necessary to validate and optimize the diagnostic efficacy of these biomarkers and to address potential sensitivity limitations.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Antígenos de Neoplasias , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma de Pulmão/diagnóstico , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/química , Interleucina-6/sangue , Interleucina-6/química , Queratina-19 , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Projetos Piloto , Estudos Prospectivos
3.
BMC Urol ; 24(1): 55, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454397

RESUMO

BACKGROUND: In the past few years, there has been a continuous rise in the occurrence of renal cell carcinoma (RCC), with RCC recurrence becoming the primary factor behind fatalities. Despite numerous clinical trials, the impact of different medications on the long-term survival of patients with RCC after surgery remains uncertain. This network meta-analysis aimed to evaluate the impact of various medications on the survival and safety of drugs in individuals with RCC following nephrectomy. METHODS: We conducted a thorough search in various databases, including CNKI, WAN FANG DATA, VIP, Web of Science, Cochrane Library (CENTRAL), PubMed, Scopus, and Embase, for articles published prior to June 2, 2023. This meta-analysis incorporated randomized controlled trials (RCTs). RESULTS: The analysis included 17 studies with 14,298 participants. The findings from the disease-free survival (DFS) analysis indicated that pembrolizumab demonstrated efficacy in enhancing DFS among patients with RCC following nephrectomy when compared to the placebo group (HR = 0.83, 95%CI 0.70 to 0.99). None of the drugs included in the study significantly improved overall survival (OS) and recurrence-free survival (RFS) after nephrectomy. For adverse events (AEs), sorafenib, pazopanib, sunitinib, and nivolumab plus ipilimumab interventions showed a higher incidence of adverse events compared with placebo. CONCLUSION: The network meta-analysis yielded strong evidence indicating that pembrolizumab could potentially enhance DFS in patients with RCC following nephrectomy, surpassing the effectiveness of a placebo.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Metanálise em Rede , Quimioterapia Adjuvante , Recidiva Local de Neoplasia/cirurgia , Nefrectomia
4.
J Int Med Res ; 52(3): 3000605241232946, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456648

RESUMO

OBJECTIVE: We aimed to investigate the impacts of prolonged mask use on patients with hypertension or diabetes during the COVID-19 pandemic. METHODS: This study included patients with hypertension or diabetes who visited the outpatient department of Nanjing Yimin Hospital between 1 February 2022 and 31 January 2023. We compared the change in blood pressure (BP) and fasting plasma glucose in patients with hypertension or diabetes and adjustments to treatment between the group with prolonged mask-wearing group (≥20 hours/week) and the control group (<20 hours/week). RESULTS: Compared with the control group of hypertensive patients, the prolonged mask-wearing group had significantly higher diastolic blood pressure (DBP) and mean arterial pressure (MAP). These two groups had had similar DBP and MAP 1 year earlier. Likewise, the prolonged mask-wearing group of patients with diabetes had a greater need than the control group for upgraded treatment to reach their therapeutic goals. CONCLUSIONS: This study suggests that prolonged mask use by patients with hypertension or diabetes has negative effects on hypertension and plasma glucose control. BP and plasma glucose monitoring should be improved in these patient populations and their treatment should be adjusted in a timely manner.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia , Máscaras , Pandemias , Automonitorização da Glicemia
5.
Sci Rep ; 14(1): 4985, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424293

RESUMO

Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.


Assuntos
Diazometano/análogos & derivados , Dipeptídeos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/patologia , Fosforilação Oxidativa , Projetos Piloto , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Movimento Celular
7.
Cell Signal ; 117: 111108, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38369266

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a severe malignancy with high incidence and mortality rate in China, while the application of standard chemotherapeutic drugs for ESCC meets the barriers of high toxicity and multiple drug resistance (MDR). In recent years, the anticancer effects of artesunate (ART), a Chinese medicine monomer have gained extensive attentions due to its characteristics of low toxicity, high potency, and reversal of MDR. In this study, we develop the artesunate-loaded solid lipid nanoparticles (SLNART) to overcome the poor water solubility and bioavailability of ART, further improving the efficiency of ART on ESCC treatment. Especially mentioned, SLNART is shown to present marked inhibitory effects on ESCC development based on the induction of ferroptosis by two pathways included upregulating TFR to increase Fe2+ ions and inhibiting the AKT/mTOR signaling to downregulate GPX4. Collectively, this study is the first to pave a promising approach for ESCC therapy based on a strategy of developing SLNART to induce ferroptosis by mediating Fe2+ ions and AKT/mTOR signaling.


Assuntos
Artesunato , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Lipossomos , Nanopartículas , Humanos , Artesunato/administração & dosagem , Artesunato/farmacologia , Artesunato/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
8.
IEEE J Biomed Health Inform ; 28(3): 1412-1423, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145537

RESUMO

Recently, the Deep Neural Networks (DNNs) have had a large impact on imaging process including medical image segmentation, and the real-valued convolution of DNN has been extensively utilized in multi-modal medical image segmentation to accurately segment lesions via learning data information. However, the weighted summation operation in such convolution limits the ability to maintain spatial dependence that is crucial for identifying different lesion distributions. In this paper, we propose a novel Quaternion Cross-modality Spatial Learning (Q-CSL) which explores the spatial information while considering the linkage between multi-modal images. Specifically, we introduce to quaternion to represent data and coordinates that contain spatial information. Additionally, we propose Quaternion Spatial-association Convolution to learn the spatial information. Subsequently, the proposed De-level Quaternion Cross-modality Fusion (De-QCF) module excavates inner space features and fuses cross-modality spatial dependency. Our experimental results demonstrate that our approach compared to the competitive methods perform well with only 0.01061 M parameters and 9.95G FLOPs.


Assuntos
Redes Neurais de Computação , Aprendizagem Espacial , Humanos , Processamento de Imagem Assistida por Computador
9.
PeerJ ; 11: e16424, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077439

RESUMO

Purpose: Optimal serological biomarkers have been absent for the early diagnosis of endometrial cancer, to date. In this study, we aimed to define the diagnostic performances of individual and combined detection of serum cysteine protease inhibitor 1 (CST1) with traditional tumor markers, including glycated antigen 125 (CA125) and human epididymis protein 4 (HE4), in patients with early-stage endometrial cancer (EC). Methods: The performances of individual and combined detection of serum CST1, HE4, and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay, respectively. A training data set of 67 patients with early EC, 67 patients with endometrial benign lesion (EBL), and 67 healthy controls (HC) was used to develop a predictive model for early EC diagnosis, which was validated by an independent validation data set. Results: In the training data set, serum CST1 and HE4 levels in the early EC group were significantly higher than in EBL/HC groups (P < 0.05), while there was no significant difference of serum CA125 level between the early EC and EBL/HC groups (P > 0.05). Serum CST1 and HE4 exhibited areas under the curve (AUC) of 0.715 with 31.3% sensitivity at 90.3% specificity, and 0.706 with 23.9% sensitivity at 95.5% specificity, respectively. Combined detection of serum CST1 and HE4 exhibited an AUC of 0.788 with 49.3% sensitivity at 92.5% specificity. The combination of serum CST1 and HE4 showed promise in diagnosis. Conclusion: CST1 is a prospective serological biomarker for early EC diagnosis, and the combination of CST1 and HE4 contributes to the further improvement in the diagnosis of patients with early-stage EC.


Assuntos
Neoplasias do Endométrio , Proteínas , Feminino , Humanos , Antígeno Ca-125 , Detecção Precoce de Câncer , Neoplasias do Endométrio/diagnóstico , Estudos Prospectivos , Proteínas/análise
10.
Phys Med Biol ; 69(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38061066

RESUMO

Objective.Due to non-invasive imaging and the multimodality of magnetic resonance imaging (MRI) images, MRI-based multi-modal brain tumor segmentation (MBTS) studies have attracted more and more attention in recent years. With the great success of convolutional neural networks in various computer vision tasks, lots of MBTS models have been proposed to address the technical challenges of MBTS. However, the problem of limited data collection usually exists in MBTS tasks, making existing studies typically have difficulty in fully exploring the multi-modal MRI images to mine complementary information among different modalities.Approach.We propose a novel quaternion mutual learning strategy (QMLS), which consists of a voxel-wise lesion knowledge mutual learning mechanism (VLKML mechanism) and a quaternion multi-modal feature learning module (QMFL module). Specifically, the VLKML mechanism allows the networks to converge to a robust minimum so that aggressive data augmentation techniques can be applied to expand the limited data fully. In particular, the quaternion-valued QMFL module treats different modalities as components of quaternions to sufficiently learn complementary information among different modalities on the hypercomplex domain while significantly reducing the number of parameters by about 75%.Main results.Extensive experiments on the dataset BraTS 2020 and BraTS 2019 indicate that QMLS achieves superior results to current popular methods with less computational cost.Significance.We propose a novel algorithm for brain tumor segmentation task that achieves better performance with fewer parameters, which helps the clinical application of automatic brain tumor segmentation.


Assuntos
Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Redes Neurais de Computação , Imageamento por Ressonância Magnética/métodos , Algoritmos
11.
BMC Pulm Med ; 23(1): 417, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907906

RESUMO

BACKGROUND: We aimed to investigate the factors influencing the cure, recurrence, and metastasis rates of stage IA lung adenocarcinoma, using a mixed cure model. METHODS: A total of 1,064 patients who underwent video-assisted thoracoscopic pulmonectomy were included. Variable screening was performed using the random forest algorithm and least absolute shrinkage and selection operator approaches. The mixed cure model was used to identify factors affecting patient cure and survival, and a sequential analysis was performed on 5%, 10%, and 20% of the presentational subtype concurrently. A receiver operating characteristics curve was used to determine the best model and construct a nomogram to predict the cure rate. RESULTS: The median follow-up time was 58 (range: 3-115) months. Results from the cure part of the mixed model indicated that the predominant subtype, presentational subtype, and tumor diameter were the main prognostic factors affecting cure rate. Therefore, the nomogram to predict the cure rate was constructed based on these factors. The survival part indicated that the predominant subtype was the only factor that influenced recurrence and metastasis. A sequential analysis of the presentational subtype showed it had no significant effect on survival (P > 0.05). Regardless of the recording mode, no significant improvement was observed in the model's discriminative ability. Only a few postoperative pathological specimens showed lymphovascular invasion (LVI); however, the survival curve suggested a significant effect on patient survival. CONCLUSIONS: After excluding the existence of long-term survivors, the predominant tumor subtype was determined to be the only factor influencing recurrence and metastasis. Although LVI is rare in stage IA lung adenocarcinoma, its significance cannot be discounted in terms of determining patient prognosis.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Prognóstico
12.
Cancer Cell Int ; 23(1): 293, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007439

RESUMO

The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5's function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5's demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer.

13.
iScience ; 26(11): 108072, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37867952

RESUMO

The recycling of spent batteries is an important concern in resource conservation and environmental protection, while it is facing challenges such as insufficient recycling channels, high costs, and technical difficulties. To address these issues, a review of the recycling of spent batteries, emphasizing the importance and potential value of recycling is conducted. Besides, the recycling policies and strategies implemented in representative countries are summarized, providing legal and policy support for the recycling industry. Moreover, a comprehensive classification and comparison of recycling technologies identify the characteristics and current status of different approaches. The integrated recycling technology provides a better recycling performance with zero-pollution recycling of spent battery. Biorecycling technology is expected to gain a broad development prospect in the future owing to the superiority of energy-saving and environmental protection, high recycling efficiency, via microbial degradation, enzymatic degradation, etc. Consequently, as for the existing recycling challenges of waste batteries, developing new recycling technology and perfecting its recycling system is an indispensable guarantee for the sustainable development of waste battery. Meanwhile, theoretical support is offered for the recycling of spent batteries.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(10): 1034-1039, 2023 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-37905760

RESUMO

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS: For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.


Assuntos
Miastenia Gravis , Tacrolimo , Humanos , Criança , Prednisona/efeitos adversos , Tacrolimo/efeitos adversos , Estudos Retrospectivos , Atividades Cotidianas , Imunossupressores/efeitos adversos , Miastenia Gravis/tratamento farmacológico , Glucocorticoides/uso terapêutico , Ácido Micofenólico/efeitos adversos
15.
Int J Med Sci ; 20(12): 1631-1643, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859694

RESUMO

Background: Urethral stricture is a common disorder of the lower urinary tract in men. A complex network of pathways and interactions are involved in the pathogenesis of urethral fibrosis. However, the mechanisms underlying urethral fibrosis remain poorly understood. Objectives: To investigate the critical role of the canonical Wnt pathway in development of urethral fibrosis and explore DKK1, the endogenous inhibitor of Wnt pathway, as a potential target to prevent urethral fibrosis in vitro and in vivo. Methods: Urethral fibrosis tissue derived from patients and rat models were harvested to assess the activation of the canonical Wnt pathway by using western blot, qRT-PCR and immunohistochemistryWe performed histological staining, western blot, qRT-PCR and immunohistochemistry to examine the effects of DKK1 treatment on in vivo rat urethral fibrosis models. In vitro, human urethral fibroblasts (HUFs) were cultured to examine the effects of DKK1 in TGFß1-induced HUFs by CCK-8 assay, hydroxyproline assay, flow cytometry, cell migration assay, western blot, qRT-PCR and immunofluorescence. Results: The key components of Wnt signaling were upregulated in urethral fibrosis tissue derived from patients and rat models while DKK 1 was downregulated. DKK1 ameliorated TGFß1-induced urethral fibrosis in rats. TGFß1 induced myofibroblast differentiation by upregulating collagen I, collagen III, α-SMA, ß-catenin and p-GSK-3ß, while DKK1 was decreased. DKK1 significantly inhibited cell proliferation, collagen content, cell migration and promoted cell apoptosis in TGFß1-induced HUFs. DKK1 significantly suppressed myofibroblast differentiation of TGFß1-induced HUFs by downregulating collagen I, collagen III, α-SMA, ß-catenin and p-GSK-3ß with a mechanism independent of Smad2/3. Conclusions: Our study demonstrated that canonical Wnt pathway may be an essential mechanism underlying the pathogenesis of urethral fibrosis and explored the potential role of DKK1 participation in the development of urethral fibrosis.


Assuntos
Via de Sinalização Wnt , beta Catenina , Animais , Humanos , Masculino , Ratos , beta Catenina/metabolismo , Diferenciação Celular/genética , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fibrose , Glicogênio Sintase Quinase 3 beta/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologia
16.
Cell Death Discov ; 9(1): 391, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872157

RESUMO

As a highly enriched endosomal protein within neuronal cells, NSG1 has been discovered to facilitate the process of epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC). However, the precise mechanisms behind this phenomenon have yet to be elucidated. The pivotal role of transforming growth factor-ß (TGF-ß) in triggering the EMT and its significant contribution towards tumor metabolic reprogramming-responsible for EMT activation-has been robustly established. Nevertheless, the extent of TGF-ß involvement in the NSG1-mediated EMT within ESCC and the processes through which metabolic reprogramming participates remain ambiguous. We accessed an array of extensive public genome databases to analyze NSG1 expression in ESCC. Regulation of TGF-ß by NSG1 was analyzed by transcriptome sequencing, quantitative Real-Time PCR (qRT-PCR), co-immunoprecipitation (CO-IP), and immunofluorescence (IF). Additionally, cellular functional assays and western blot analyses were conducted to elucidate the effect of NSG1 on TGF-ß/Smad signaling pathway, as well as its role in ESCC cell metastasis and proliferation. We validated the influence of the NSG1/TGF-ß axis on metabolic reprogramming in ESCC by measuring extracellular acidification, glucose uptake, and lactate production. Our findings identify an oncogenic role for NSG1 in ESCC and show a correlation between high NSG1 expression and poor prognosis in ESCC patients. Additional research indicated TGF-ß's involvement in the NSG1-induced EMT process. From a mechanistic perspective, NSG1 upregulates TGF-ß, activating the TGF-ß/Smad signaling pathway and subsequently fostering the EMT process by inducing cell metabolic reprogramming-evident from elevated glycolysis levels. In conclusion, our study highlights the NSG1/TGF-ß axis as a promising therapeutic target for ESCC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37831079

RESUMO

Early identification of high-risk patients with Major depressive disorder (MDD) having suicide attempts (SAs) is essential for timely targeted and tailored psychological interventions and medications. This study aimed to develop and validate a web-based dynamic nomogram as a personalized predictor of SA in MDD patients. A dynamic nomogram was developed using data collected from 1718 patients in China. The dynamic model was established based on a machine learning-based regression technique in the training cohort. We validated the nomogram internally using 1000 bootstrap replications. The nomogram performance was assessed using estimates of discrimination (via the concordance index) and calibration (calibration plots). The nomogram incorporated five predictors, including Hamilton anxiety rating scale (odds ratio [OR]: 1.255), marital status (OR: 0.618), clinical global impressions (OR: 2.242), anti-thyroid peroxidase antibodies (OR: 1.002), and systolic pressure levels (OR: 1.037). The model demonstrated good overall discrimination (Harrell's C-index = 0.823). Using decision curve analysis, this model also demonstrated good clinical applicability. An online web server was constructed ( https://odywong.shinyapps.io/PRSM/ ) to facilitate the use of the nomogram. Based on these results, our study developed a nomogram to predict SA in MDD patients. The application of this nomogram may help for patients and clinicians to make decisions.

18.
Transl Stroke Res ; 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37442918

RESUMO

Endovascular treatment (EVT) has been proven to be the standard treatment for acute vertebrobasilar artery occlusion (VBAO). This study aimed to analyze the effects of international normalized ratio (INR) indicators on outcomes in patients with acute VBAO treated with EVT. Dynamic data on INR in patients with VBAO who received endovascular treatment (EVT) at 65 stroke centers in China were retrospectively enrolled. Outcome measures included the modified Rankin Scale (mRS) score at 90 days and 1 year and symptomatic intracranial hemorrhage (sICH). The associations between elevated INR (INR > 1.1), INR variability (time-weighted variance of INR changes), and various clinical outcomes were analyzed in all patients and subgroups stratified by oral anticoagulation (OAC) by mixed logistic regression analysis. A total of 1825 patients met the study criteria, of which 1384 had normal INR and 441 had elevated INR. Multivariate analysis showed that elevated INR was significantly associated with poor functional outcomes (mRS 4-6) at 90 days (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.08-1.72) and 1 year (OR 1.32, 95% CI 1.05-1.66), but was not associated with an increased risk of sICH (OR 1.00, 95% CI 0.83-1.20). Similar associations exist between INR variability and poor functional outcomes at 90 days (OR 2.17, 95% CI 1.09-4.30), 1 year (OR 2.28, 95% CI 1.16-4.46), and sICH (OR 1.11, 95% CI 0.93-1.33). Subgroup analyses further revealed that elevated INR and INR variability remained associated with poor functional outcomes in patients not receiving oral anticoagulation (OAC) therapy, while no significant associations were observed in OAC-treated patients, regardless of whether they were on warfarin or direct oral anticoagulants. Elevated INR and INR variability in VBAO patients treated with EVT were associated with poor functional outcomes. The mechanism underlying the association between elevated INR and poor functional outcomes might be attributed to the fact that elevated INR indirectly reflects the burden of comorbidities, which could independently worsen outcomes. These findings underscore the importance of a comprehensive and dynamic evaluation of INR levels in the management of VBAO patients receiving EVT, providing valuable insights for optimizing patient outcomes.

19.
Inorg Chem ; 62(32): 12920-12930, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37523448

RESUMO

Hierarchical porosity of carbonates can facilitate their performance in massive applications as compared to their corresponding bulk samples. Traditional solution-based precipitation is typically utilized to fabricate porous carbonates. However, this tactic is generally employed under humid conditions, which demand soluble metal precursors, solvents, and extended dry periods. A salt-assisted mechanochemistry is exploited in contemporary work to settle the shortcomings. Enlighted by solid-state technology, this approach eliminates the utilization of solvents, and the process of ball milling can create pores in 5 min. A range of highly porous carbonates and their derivatives are acquired, with several materials surpassing recording surface areas (e.g., H-CaCO3: 108 m2/g, SrCO3: 125 m2/g, BaCO3: 172 m2/g, Pd/H-CaCO3 catalyst: 101 m2/g). The results display that Pd/H-CaCO3 shows superior catalytic efficiency in the synthesis of aniline (turnover frequency [TON] = 1.33 × 104/h-1, yield ≥ 99%, and recycle stability: 11 cycles) and dye degradation. Combining mechanochemistry and salt-assisted tactic provides a facile and efficient pathway for processing porous materials.

20.
Cerebrovasc Dis ; 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37524066

RESUMO

BACKGROUND AND PURPOSE: The purpose of the present study was to evaluate the agreement on pc-ASPECTS (posterior circulation Acute Stroke Prognosis Early Computed Tomography Scores) based on non-contrast CT (NCCT) and CT angiography (CTA) source images in patients with acute basilar artery occlusion (BAO). METHODS: We prospectively enrolled consecutive patients with acute BAO from January 2022 to August 2022 at The First Affiliated Hospital of University of Science and Technology of China. The NCCT and CTA were scored independently by 15 raters during 2 different reading sessions at least 3 weeks apart. The pc-ASPECTS based on NCCT and CTA were analyzed on the full scale or were dichotomized (0-6 versus 7-10, 0-7 versus 8-10 and 0-8 versus 9-10). The level of agreement was measured using Fleiss κ Statistics. RESULTS: The median (IQR) CT-based pc-ASPECTS was 8 (6.75-9). The interrater agreement for CT-based pc-ASPECTS (κ=0.133 [0.132-0.133]) and CTA-based pc-ASPECTS (κ=0.204 [0.203-0.204]) was slight for all raters. Dichotomizations obtaining the highest concordance for the CT-based pc-ASPECTS (0-6 versus 7-10) and the CTA-based pc-ASPECTS (0-8 versus 9-10) failed to increase the interrater agreement to a substantial level (κ=0.350 [0.348-0.351] and 0.396 [0.395-0.398], respectively). Intrarater agreement for global CT-based pc-ASPECTS was less than substantial for the 14/15 raters and reached the level of substantial for the 3/15 raters with dichotomization. CONCLUSIONS: Agreement between clinicians assessing CT-based and CTA-based pc-ASPECTS cannot be sufficient to make reproducible clinical decisions and assessments. The dichotomization failed to improve interrater and intrarater agreement to the level of substantial.

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