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The development and maintenance of chronic pain involves the reorganization of spinal nociceptive circuits. The mechanistic target of rapamycin complex 2 (mTORC2), a central signaling hub that modulates both actin-dependent structural changes and mTORC1-dependent mRNA translation, plays key roles in hippocampal synaptic plasticity and memory formation. However, its function in spinal plasticity and chronic pain is poorly understood. Here we show that pharmacological activation of spinal mTORC2 induces pain hypersensitivity, whereas its inhibition, using downregulation of the mTORC2-defining component Rictor, alleviates both inflammatory and neuropathic pain. Cell-type-specific deletion of Rictor showed that the selective inhibition of mTORC2 in a subset of excitatory neurons impairs spinal synaptic potentiation and alleviates inflammation-induced mechanical and thermal hypersensitivity, and nerve injury-induced heat hyperalgesia. The ablation of mTORC2 in inhibitory interneurons strongly alleviated nerve injury-induced mechanical hypersensitivity. Our findings reveal the role of mTORC2 in chronic pain and highlight its cell-type-specific functions in mediating pain hypersensitivity in response to peripheral inflammation and nerve injury.
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Alpha-lipoic acid (ALA) is a naturally occurring compound synthesized by mitochondria and widely distributed in both animal and plant tissues. It primarily influences cellular metabolism and oxidative stress networks through its antioxidant properties and is an important drug for treating metabolic diseases associated with oxidative damage. Nevertheless, research indicates that the mechanism by which ALA affects cancer cells is distinct from that observed in normal cells, exhibiting pro-oxidative properties. Therefore, this review aims to describe the main chemical and biological functions of ALA in the cancer environment, including its mechanisms and effects in tumor prevention and anticancer activity, as well as its role as an adjunctive drug in cancer therapy. We specifically focus on the interactions between ALA and various carcinogenic and anti-carcinogenic pathways and discuss ALA's pro-oxidative capabilities in the unique redox environment of cancer cells. Additionally, we elaborate on ALA's roles in nanomedicine, hypoxia-inducible factors, and cancer stem cell research, proposing hypotheses and potential explanations for currently unresolved issues.
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RATIONALE AND OBJECTIVES: Secondary vertebral compression fractures (SVCF) are very common in patients after vertebral augmentation (VA). The aim of this study was to establish a radiomic-based model to predict SVCF and specify appropriate treatment strategies. MATERIALS AND METHODS: Patients diagnosed with osteoporotic vertebral compression fracture (OVCF) and undergoing VA surgery at our center between 2017 and 2021 were subject to a retrospective analysis. Radiological features of the T6-L5 vertebrae were derived from CT images. Clustering analysis, t-test, and LASSO (least absolute shrinkage and selection operator) regression were used to identify the optimization characteristics. A radiological signature model was constructed through the best combination of 13 machine learning algorithms. Radiomics signature was integrated with clinical characteristics into a nomogram for clinical applications. The model reliability was assessed by receiver operating characteristic (ROC) curve, calibration curve, clinical decision analysis (DCA), log-rank test, and confusion matrix. RESULTS: A total of 470 eligible patients (81 with SVCF and 389 without) were identified in the clinical cohort. Eight radiomics features were identified and incorporated into machine learning, and "XGBoost" model showed the best performance. Final logistic nomogram included radiomics signature (P < 0.001), bone cement volume (P = 0.034), and T-scores of L1-L4 (P = 0.001), and showed satisfactory prediction capability in training set (0.986, 95%CI 0.969-1.000) and verification set (0.884, 95%CI 0.823-0.946). CONCLUSION: Our radiomics-clinical model based on machine learning showed potential to prospectively predict SVCF after VA and provide precise treatment strategies.
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Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell-type-specific profiling revealed that spinal inhibitory neurons exhibited greater changes in translation after peripheral nerve injury compared to excitatory neurons. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV+) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV+ neurons decreased their intrinsic excitability and spiking activity, whereas reducing translation in spinal PV+ neurons prevented the nerve injury-induced decrease in excitability. Thus, translational control mechanisms in the spinal cord, particularly in inhibitory neurons, play a role in mediating neuropathic pain hypersensitivity.
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Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1-EVs substantially improved motor function in spinal cord-injured mice. Rg1-EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1-EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1-EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1-EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2-phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1-EVs in neuronal protection and functional recovery following SCI through MYCBP2-mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1-EVs.
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Modelos Animais de Doenças , Vesículas Extracelulares , Ginsenosídeos , Neurônios , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Ginsenosídeos/farmacologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/efeitos dos fármacos , Camundongos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/imunologia , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
OBJECTIVES: To compare magnetic resonance (MR) short T1 inversion recovery (STIR) sequence with MR T2-weighted (T2W) sequence for detecting increased signal intensity (ISI) and assessing outcomes of ISI in cervical spondylotic myelopathy (CSM). METHODS: Data of patients with CSM who showed ISI on MR imaging and had undergone cervical spine surgery were retrospectively reviewed. STIR and T2W images were examined to assess signal intensity ratio (SIR), length and grading of the ISI, maximal spinal cord compression, canal narrowing ratio, and ligamentum flavum hypertrophy. The patients were divided into good and poor groups based on their outcomes. χ2 tests and variance analysis were used to assess intergroup differences. Univariate and multivariate logistic regression analyses were performed to identify risk factors for poor outcomes, and receiver operating characteristic curves were plotted to detect prognostic effects. RESULTS: SIR and ISI lengths were significantly different between the STIR and T2 images. In the univariate logistic regression analysis, age, diabetes, SIRT2, SIRSTIR, and ISISTIR grading were significant factors. Accordingly, in the multivariate logistic regression analysis, age, diabetes, SIRT2, and SIRSTIR were included in the model. Among patients with diabetes, we observed a significant difference between SIRT2 and SIRSTIR. CONCLUSIONS: The STIR sequence demonstrated superior capability to the T2W sequence in detecting ISI; however, there was no obvious difference in predicted outcomes. STIR sequence has a better prognostic value than T2W sequence in patients with diabetes who have CSM. ISI grading based on the STIR sequence may be a clinically valuable indicator.
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Vértebras Cervicais , Imageamento por Ressonância Magnética , Espondilose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Espondilose/cirurgia , Espondilose/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Adulto , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico por imagemRESUMO
A novel H-shaped miniplate (HSM) was specifically designed for restorative laminoplasties to restore patients' posterior elements after laminectomies. A validated finite element (FE) model of L2/4 was utilized to create a laminectomy model, as well as three restorative laminoplasty models based on the fixation of different miniplates after a laminectomy (the RL-HSM model, the RL-LSM model, and the RL-THM model). The biomechanical effects of motion and displacement on a laminectomy and restorative laminoplasty with three different shapes for the fixation of miniplates were compared under the same mechanical conditions. This study aimed to validate the biomechanical stability, efficacy, and feasibility of a restorative laminoplasty with the fixation of miniplates post laminectomy. The laminectomy model demonstrated the greatest increase in motion and displacement, especially in axial rotation, followed by extension, flexion, and lateral bending. The restorative laminoplasty was exceptional in preserving the motion and displacement of surgical segments when compared to the intact state. This preservation was particularly evident in lateral bending and flexion/extension, with a slight maintenance efficacy observed in axial rotation. Compared to the laminectomy model, the restorative laminoplasties with the investigated miniplates demonstrated a motion-limiting effect for all directions and resulted in excellent stability levels under axial rotation and flexion/extension. The greatest reduction in motion and displacement was observed in the RL-HSM model, followed by the RL-LSM model and then the RL-THM model. When comparing the fixation of different miniplates in restorative laminoplasties, the HSMs were found to be superior to the LSMs and THMs in maintaining postoperative stability, particularly in axial rotation. The evidence suggests that a restorative laminoplasty with the fixation of miniplates is more effective than a conventional laminectomy due to the biomechanical effects of restoring posterior elements, which helps patients regain motion and limit load displacement responses in the spine after surgery, especially in axial rotation and flexion/extension. Additionally, our evaluation in this research study could benefit from further research and provide a methodological and modeling basis for the design and optimization of restorative laminoplasties.
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Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 in vivo. Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis in vitro and in vivo. Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.
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Apoptose , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Hepáticas , Camundongos Nus , RNA Circular , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Animais , Proliferação de Células/genética , Movimento Celular/genética , Apoptose/genética , Masculino , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Camundongos , Pessoa de Meia-Idade , Camundongos Endogâmicos BALB C , Invasividade Neoplásica/genética , RNA/metabolismo , RNA/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Endógeno CompetitivoRESUMO
Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.
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Neoplasias Hepáticas , Neoplasias de Células Epitelioides Perivasculares , Humanos , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico , Hepatectomia , Cuidados Pré-Operatórios/métodos , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Fígado/patologia , Fígado/cirurgia , Fígado/diagnóstico por imagemRESUMO
Snoring is common in children and is associated with many adverse consequences. One must study the relationships between pharyngeal morphology and snoring physics to understand snoring progression. Although some model studies have provided fluid-structure interaction dynamic descriptions for the correlation between airway size and snoring physics, the descriptions still need to be further investigated in patient-specific airway models. Fluid-structure interaction studies using patient-specific airway structures complement the above model studies. Based on reported cephalometric measurement methods, this study quantified and preset the size of the palatopharynx airway in a patient-specific airway and investigated how the palatopharynx size affects the pharyngeal airflow fluctuation, soft palate vibration, and glossopharynx vibration with the help of a verified FSI method. The results showed that the stenosis anterior airway of the soft palate increased airway resistance and airway resistance fluctuations, which can lead to increased sleep effort and frequent snoring. Widening of the anterior airway can reduce airflow resistance and avoid obstructing the anterior airway by the soft palate vibration. The pharyngeal airflow resistance, mouth inflow proportion, and soft palate apex displacement have components at the same frequencies in all airway models, and the glossopharynx vibration and instantaneous inflow rate have components at the same frequencies, too. The mechanism of this same frequency fluctuation phenomenon can be explained by the fluid-structure interaction dynamics of an ideal coupled model consisting of a flexible plate model and a collapsible tube model. The results of this study demonstrate the potential of FSI in studying snoring physics and clarify to some degree the mechanism of airway morphology affecting airway vibration physics.
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Palato Mole , Faringe , Ronco , Vibração , Humanos , Faringe/fisiologia , Ronco/fisiopatologia , Criança , Palato Mole/fisiologia , Palato Mole/fisiopatologia , Masculino , Resistência das Vias Respiratórias/fisiologia , Modelos BiológicosRESUMO
Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.
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Células Endoteliais , Traumatismos da Medula Espinal , Animais , Camundongos , Ratos , Angiogênese , Barreira Hematoencefálica/metabolismo , Enzimas Desubiquitinantes/metabolismo , Células Endoteliais/metabolismo , Proteínas HMGB/metabolismo , Proteínas HMGB/farmacologia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Fatores de Transcrição SOXF/genética , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismoRESUMO
STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to assess the potential of utilizing the MRI-based vertebral bone quality (VBQ) score as a predictive tool for pedicle screw loosening (PSL) in patients who have undergone pedicle screw fixation and to identify risk factors associated with VBQ scores. METHODS: One hundred and sixteen patients who had undergone pedicle screw fixation between December 2019 and January 2021 and had more than a year of follow-up were divided into two groups of PSL and non-PSL. The radiological and clinical parameters investigated were age, gender, body mass index, the VBQ score, length of fusion and the DXA T-score. RESULTS: Of the 116 patients included in the study, 22 patients developed pedicle screw loosening after surgery (18.97%). VBQ score of PSL group was higher than the non-PSL group (3.61 ± 0.63 vs. 2. 86 ± 0.43, p < 0.001). According to logistic regression, PSL was independently linked with a higher VBQ score (OR = 3.555, 95% confidence interval [1.620-7.802], p < 0.005). The AUC of predicting screw loosening was 0.774 (p < 0.001) for VBQ score, and the best threshold was 3.055 (sensitivity, 81.8%; specificity, 71.3%). High VBQ score was associated with age (r (114) = 0.29, p = 0.002), while it was not negatively correlated with T-scores of each part. CONCLUSION: VBQ score is an independent predictor of pedicle screw loosening, with higher scores indicating a greater risk. Our results showed that older patients and women had higher VBQ scores.
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Parafusos Pediculares , Fusão Vertebral , Humanos , Feminino , Parafusos Pediculares/efeitos adversos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Radiografia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodosRESUMO
The fluorescent non-canonical amino acid tagging (FUNCAT) technique has been used to visualize newly synthesized proteins in cell lines and tissues. Here, we present a protocol for measuring protein synthesis in specific cell types in the mouse brain using in vivo FUNCAT. We describe steps for metabolically labeling newly synthesized proteins with azidohomoalanine, which introduces an azide group into the polypeptide. We then detail procedures for binding a fluorophore-conjugated alkyne to the azide group to allow its visualization. For complete details on the use and execution of this protocol, please refer to tom Dieck et al. (2012)1 and Hooshmandi et al. (2023).2.
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Aminoácidos , Neoplasias Cutâneas , Animais , Camundongos , Azidas , Alcinos , Corantes Fluorescentes , EncéfaloRESUMO
Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA-miRNA-mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Endógeno Competitivo , RNA Circular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Circular RNAs (circRNAs) are noncoding RNAs with a circular colsed structure that play an important role in the occurrence and development of cancers. The functional mechanism of circRNAs as ceRNAs in hepatocellular carcinoma (HCC) and its effect on the invasion and metastasis of HCC need to be further studied. Five pairs of HCC tissues were selected for high-throughput sequencing, and 19 circRNAs with differential expression were obtained. The expression of circSLCO1B7 was obviously downregulated in 50 pairs of tumor tissues and plasma of HCC patients, which was closely related to the TNM stage, lymph node metastasis and tumor size. Cell functional experiments showed that circSLCO1B7 could inhibit cell growth, migration, invasion and promote cell apoptosis. In the regulatory mechanism, circSLCO1B7 sponged miR-556-3p to regulate the expression of the downstream target gene DAB2IP and induced the Epithelial-mesenchymal transition (EMT) progression. Our results indicated that circSLCO1B7 significantly inhibits the metastasis of HCC via the miR-556-3p/DAB2IP axis. Thus, circSLCO1B7 is a good candidate as a therapeutic target.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , RNA Circular/genéticaRESUMO
Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.
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Carcinoma Hepatocelular , Di-Hidrolipoil-Lisina-Resíduo Acetiltransferase , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Prognóstico , Sorafenibe/uso terapêuticoRESUMO
BACKGROUND: Semaphorin4F (Sema4F) is a member of the semaphorin family and exhibits important regulatory functions in cancer biology. We aimed to explore the prognostic value and biologic function of Sema4F in gastric cancer (GC) through clinical data, laboratory studies, and bioinformatic methods. METHODS: We investigated Sema4F-related data and the prognostic values of patients with GC based on several databases, including Tumor Immune Estimation Resource (TIMER), the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), The University Of Alabama At Birmingham Cancer Data Analysis Portal (UALCAN) and Kaplan-Meier Plotter. We detected the expression of Sema4F in cell lines and tumor tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The prognostic value of Sema4F expression on patient overall survival was analyzed retrospectively using Kaplan-Meier survival and Cox regression analyses. Moreover, we used Kyoto encyclopedia of genes and genomes (KEGG), Gene Ontology (GO) and Gene-set enrichment analysis (GSEA) analyses to explore the relevant pathways of Sema4F in GC. RESULTS: The expression of Sema4F was markedly increased in cancer tissues and cancer cell lines. Furthermore, high Sema4F expression was positively associated with various clinicopathologic data and independently predicted poor prognosis for overall survival in GC. Our functional enrichment analysis revealed that Sema4F was mainly involved in oxidative phosphorylation and tumor-related signaling pathways. CONCLUSIONS: Sema4F may be a valuable prognostic biomarker and a novel target for gastric cancer.
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Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that primarily occurs in the liver and spleen. The etiology of IPT-like FDCS is unknown, and it has nonspecific clinical manifestations, imaging performance and laboratory test results. Recently, a patient with IPT-like FDCS was admitted to our hospital because of abdominal distension and anemia. Over the past 3 years, the patient has been followed up after a liver mass was found in a physical examination. The lesion gradually enlarged and caused compression symptoms. In November 2022, a tumor with a diameter of approximately 20 cm was found in the right posterior lobe of the liver after abdominal enhanced Magnetic resonance imaging (MRI) in our hospital. Liver tumor biopsy before the operation revealed a large number of hyperplastic plasma cells and a small number of spindle cells, and the spindle cells were atypical. After a complete examination, the patient underwent liver resection. Pathology after surgery confirmed liver IPT-like FDCS.
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Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants, they are prone to excessive degradation and accidental scratching in practice. Bone implant-related infection and limited osteointegration are other factors that adversely impact clinical application of Mg-based biomedical implants. Herein, a self-healing polymeric coating is constructed on the Mg alloy together with incorporation of a stimuli-responsive drug delivery nanoplatform by a spin-spray layer-by-layer (SSLbL) assembly technique. The nanocontainers are based on simvastatin (SIM)-encapsulated hollow mesoporous silica nanoparticles (S@HMSs) modified with polydopamine (PDA) and polycaprolactone diacrylate (PCL-DA) bilayer. Owing to the dynamic reversible reactions, the hybrid coating shows a fast, stable, and cyclical water-enabled self-healing capacity. The antibacterial assay indicates good bacteria-killing properties under near infrared (NIR) irradiation due to synergistic effects of hyperthermia, reactive oxygens species (ROS), and SIM leaching. In vitro results demonstrate that NIR laser irradiation promotes the cytocompatibility, osteogenesis, and angiogenesis. The coating facilitates alkaline phosphatase activity and expedites extracellular matrix mineralization as well as expression of osteogenesis-related genes. This study reveals a useful strategy to develop multifunctional coatings on bioabsorbable Mg alloys for orthopedic implants.
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Ligas , Osteogênese , Ligas/farmacologia , Magnésio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Bactérias , Concentração de Íons de Hidrogênio , CorrosãoRESUMO
Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Worldwide, liver cancer is the fourth most common cause of cancer-related death. Recent studies have found that PIWI-interacting RNAs (piRNAs) participate in the occurrence and development of various tumors and are closely related to the growth, invasion, metastasis and prognosis of malignant tumors. Studies on the role and functional mechanism of piRNAs in HCC development and progression are limited. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of piR-017724 in both HCC tissues and cells. Based on the clinical data of HCC patients, the clinical and prognostic value of piR-017724 was further analyzed. Then, targeted silencing and overexpressing of piR-017724 in HCC cells was further used to examine the biological functions of piR-017724. In addition, the downstream target protein of piR-017724 was predicted and validated through high-throughput sequencing and public databases. Results: The piR-017724 was significantly downregulated in HCC tissues and cells, and the downregulation of piR-017724 was associated with tumor stage and poor prognosis in HCC. The piR-017724 inhibitor promoted the proliferation, migration and invasion of HCC cells, while the piR-017724 mimic had the opposite effect. However, the piR-017724 did not affect apoptosis of HCC cells. High-throughput sequencing and qRT-PCR confirmed a reciprocal relationship between piR-017724 and PLIN3. Therefore, we speculate that piR-017724 may inhibit the development and progression of HCC by affecting the downstream protein PLIN3. Conclusions: Our study shows that piR-017724, which is lowly expressed in HCC, inhibits the proliferation, migration and invasion of HCC cells and may affect the development of hepatocellular liver cancer through PLIN3, which provides new insights into the clinical application of piR-017724 in the treatment of hepatocellular carcinoma.