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OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.
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Antígeno B7-H1 , Fibroblastos Associados a Câncer , Quimiocina CXCL1 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Antígeno B7-H1/metabolismo , Masculino , Feminino , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/mortalidade , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Quimiocina CXCL1/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Adulto , Estudos Retrospectivos , Metástase Neoplásica , Prognóstico , Fenótipo , Biomarcadores Tumorais/metabolismo , Idoso , Serina Endopeptidases/metabolismo , Endopeptidases/metabolismo , Proteínas de Membrana/metabolismoRESUMO
Introduction: Cytomegalovirus (CMV) can cause various end-organ diseases in immunocompromised hosts, including allogeneic hematopoietic cell transplant (allo-HSCT) recipients. Interestingly, CMV viremia has been associated with various complications and poor prognosis in allo-HSCT recipients. Complications involving the central nervous system (CNS) occur in 9-14% of patients following allo-HSCT. However, autoimmune encephalitis (AE) secondary to CMV infection after allo-HSCT has rarely been reported. Here we report a case of possible AE following CMV viremia after allo-HSCT, which was successfully treated with high-dose pulsed methylprednisolone and intravenous immunoglobulins (IVIg). Case description: A 53-year-old female underwent allo-HSCT for T-lymphoblastic lymphoma/leukemia. The patient developed CMV viremia on day 36 after transplantation, and serum CMV-DNA remained positive after initiating ganciclovir antiviral therapy, turning negative one month later. Four months later, she started experiencing memory impairment, weakness in the left limbs, cognitive dysfunction, and hallucinations. A magnetic resonance imaging brain scan showed scattered ischemic lesions under the bilateral frontal cortex. Viral detection in cerebral spinal fluid (CSF) by next-generation gene sequencing technology showed no obvious abnormality. Antibodies specific to AE and paraneoplastic diseases in serum and CSF were absent. The oligoclonal bands in the CSF were detected using isoelectric focusing and immunofixation, and the results were negative. However, after extensive investigation regarding infections, autoimmune disorders, and recurrence of the malignancy, possible AE could not be excluded. The patient was treated with high-dose steroids combined with IVIg therapy; the patient's symptoms were significantly improved. Conclusion: The mechanisms of AE after allo-HSCT and the relationship with CMV infection should be further studied. Therefore, reporting this and similar cases will improve our awareness and understanding of the underlying disease mechanisms.
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Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.
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Compostos Bicíclicos Heterocíclicos com Pontes , Imunoterapia Adotiva , Células Matadoras Naturais , Leucemia Mieloide Aguda , Sulfonamidas , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Humanos , Sulfonamidas/farmacologia , Animais , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Camundongos , Imunoterapia Adotiva/métodos , Linhagem Celular Tumoral , NF-kappa B/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos Endogâmicos NODRESUMO
Esophageal cancer (EC) is a common and serious form of cancer, and while DNA methyltransferase-1 (DNMT1) promotes DNA methylation and carcinogenesis, the role of F-box protein 32 (FBXO32) in EC and its regulation by DNMT1-mediated methylation is still unclear. FBXO32 expression was examined in EC cells with high DNMT1 expression using GSE163735 dataset. RT-qPCR assessed FBXO32 expression in normal and EC cells, and impact of higher FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with EMT-related proteins. The xenograft model established by injecting EC cells transfected with FBXO32 was used to evaluate tumor growth, apoptosis, and tumor cells proliferation and metastasis. Chromatin immunoprecipitation (ChIP) assay was employed to study the interaction between DNMT1 and FBXO32. HitPredict, co-immunoprecipitation (Co-IP), and Glutathione-S-transferase (GST) pulldown assay analyzed the interaction between FBXO32 and cyclin dependent kinase 9 (CDK9). Finally, the ubiquitination assay identified CDK9 ubiquitination, and its half-life was measured using cycloheximide and confirmed through western blotting. DNMT1 negatively correlated with FBXO32 expression in esophageal cells. High FBXO32 expression was associated with better overall survival in patients. Knockdown of DNMT1 in EC cells increased FBXO32 expression and suppressed malignant phenotypes. FBXO32 repressed EC tumor growth and metastasis in mice. Enrichment of DNMT1 in FBXO32 promoter region led to increased DNA methylation and reduced transcription. Mechanistically, FBXO32 degraded CDK9 through promoting its ubiquitination.
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Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1 , Epigênese Genética , Neoplasias Esofágicas , Proteínas F-Box , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/metabolismo , Humanos , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Animais , Proliferação de Células/genética , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Linhagem Celular Tumoral , Epigênese Genética/genética , Camundongos , Metilação de DNA/genética , Ubiquitinação , Movimento Celular/genética , Apoptose/genética , Camundongos Endogâmicos BALB C , Sobrevivência Celular/genética , Feminino , MasculinoRESUMO
Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis. To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase ß (IKKß) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKß siRNA-loaded liposome (siIKKß-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKß-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.
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Neovascularização de Coroide , Quinase I-kappa B , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Quinase I-kappa B/genética , Quinase I-kappa B/farmacologia , Lipossomos/farmacologia , Manose , Neovascularização de Coroide/genética , Macrófagos , Terapia GenéticaRESUMO
PURPOSE: To evaluate the changes in macular structures following subthreshold micropulse laser (SHML) treatment for chronic central serous chorioretinopathy (cCSC). METHODS: Data of 33 eyes from 31 cCSC patients treated with SHML and followed up for at least 6 months has been included in this retrospective study. Main outcome measurements include resolution of subretinal fluid (SRF) and pigment epithelial detachment (PED), the recovery of ellipsoid zone (EZ) continuity, and the foveal outer nuclear layer (ONL) thickness along with its ratio. RESULTS: Mean observation period is 7.355 months (ranging from 6 to 24 months) and mean number of treatments administered is 1.839 (ranging from 1 to 5). 6 months after SHML treatment, there is a significant decrease in the area of SRF and PED (P < 0.001, P = 0.010, respectively). Additionally, the frequency of continuous EZ and the foveal ONL thickness reveal a significant increase (P<0.001, P = 0.005, respectively). The ratio of foveal ONL thickness is significantly higher after laser treatment, particularly in patients with a disease duration of ≤12 months (p = 0.022, P=0.036, respectively). CONCLUSION: SHML treatment proves to be effective in cCSC eyes, leading to satisfactory recovery of macular structures, especially the photoreceptor layer.
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Coriorretinopatia Serosa Central , Terapia a Laser , Humanos , Coriorretinopatia Serosa Central/radioterapia , Coriorretinopatia Serosa Central/cirurgia , Estudos Retrospectivos , Angiofluoresceinografia , Acuidade Visual , Retina , Tomografia de Coerência Óptica , Doença CrônicaAssuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Anemia Aplástica/diagnóstico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , China/epidemiologia , População do Leste AsiáticoRESUMO
BACKGROUND: Immune-related scores are currently used for prognostic evaluation and as an immunotherapy reference in various cancers. However, the relationship between immune-related score and hepatocellular carcinoma (HCC) prognosis has not yet been investigated. This study aimed to explore the clinical application value of immune-related score for predicting HCC prognosis-related indicators including disease-free survival (DFS) and overall survival (OS), and to construct a clinical nomogram prediction model related to verification. METHODS: This study included 284 HCC patients who were selected from the Cancer Genome Atlas (TCGA) database and linked to the immune-related score downloaded from the public platform. A Cox proportional hazards regression model was used to estimate the adjusted risk ratio, and a nomogram was constructed based on multivariate analysis results and clinical significance. The model was internally verified by bootstrap. The performance of the prediction model was evaluated using the C-index and calibration curves. RESULTS: Patients were divided into three subgroups according to the immune-related score level. Compared with patients in the low immune-related score group, the DFS of patients in the medium and high immune-related score groups was significantly prolonged (HR: 0.53, 95% CI: 0.32-0.87; HR: 0.37, 95% CI: 0.21-0.63, respectively). The OS of patients in the medium and high immune-related score groups was also significantly prolonged (HR: 0.43, 95% CI: 0.20-0.95, p = 0.038; HR: 0.29, 95% CI: 0.14-0.58, p < 0.001, respectively). The C-indexes for predicting DFS and OS were 0.687 (95% CI: 0.665-0.700) and 0.743 (95% CI: 0.709-0.776), respectively. The calibration curves of 3-year and 5-year DFS and OS showed that the results predicted by the nomogram were in good agreement with the actual observations. CONCLUSIONS: Moderate/high-grade immune-related score was significantly associated with better DFS and OS in HCC patients. In addition, a nomogram for prognosis estimation can help clinicians predict the survival status of patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Nomogramas , Intervalo Livre de DoençaRESUMO
In this study, carotenoids and polyphenols were demonstrated to be the major active substances in the crude pigment extracts (CPE) of mango peels, accounting for 0.26 mg/g and 0.15 mg/g, respectively. The interactions between carotenoids and polyphenols in CPE was observed, as evidenced by that polyphenols significantly improved the antioxidant activity and storage stability of carotenoids in the CPE. Meanwhile, scanning electron microscopy showed that polyphenols are tightly bound to carotenoids. To further elucidate the interaction mechanism, the monomers of carotenoids and polyphenols were identified by HPLC and LC-MS analysis. Lutein (203.85 µg/g), ß-carotene (41.40 µg/g), zeaxanthin (4.20 µg/g) and α-carotene (1.50 µg/g) were authenticated as the primary monomers of carotenoids. Polyphenols were mainly consisted of gallic acid (95.10 µg/g), quercetin-3-ß-glucoside (29.10 µg/g), catechin (11.85 µg/g) and quercetin (11.55 µg/g). The interaction indexes between carotenoid and polyphenol monomer of CPE were calculated. The result indicated that lutein and gallic acid showed the greatest synergistic effect on the scavenging of DPPH and ABTS radical, suggesting the interaction between carotenoids and polyphenols in CPE was mainly caused by lutein and gallic acid. Molecular dynamics simulations and thermodynamic parameters analysis demonstrated that hydrogen bonding, electrostatic interactions, and van der Waals forces played dominant roles in the interaction between lutein and gallic acid, which was confirmed by Raman and X-ray diffraction. These results provided a new perspective on the interaction mechanism between carotenoids and polyphenols, which offered a novel strategy for the enhancement of the activities and stability of bioactive substances.
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Mangifera , Polifenóis , Luteína , Mangifera/química , Quercetina , Carotenoides/análise , Ácido GálicoRESUMO
The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high priority for global health. Increasing awareness of the "back to nature" approach for improving human health has prompted renewed interest in natural products, especially dietary polyphenols, as an additional therapeutic strategy to treat SARS-CoV-2 patients, owing to its good safety profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, and availability. Herein, we describe the biological properties and pleiotropic molecular mechanisms of dietary polyphenols curcumin, resveratrol, and gossypol as inhibitors against SARS-CoV-2 and its variants as observed in in vitro and in vivo studies. Based on the advantages and disadvantages of dietary polyphenols and to obtain maximal benefits, several strategies such as nanotechnology (e.g., curcumin-incorporated nanofibrous membranes with antibacterial-antiviral ability), lead optimization (e.g., a methylated analog of curcumin), combination therapies (e.g., a specific combination of plant extracts and micronutrients), and broad-spectrum activities (e.g., gossypol broadly inhibits coronaviruses) have also been emphasized as positive factors in the facilitation of anti-SARS-CoV-2 drug development to support effective long-term pandemic management and control.
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COVID-19 , Curcumina , Gossipol , Humanos , Resveratrol , Curcumina/farmacologia , Pandemias , SARS-CoV-2 , Polifenóis/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
Cisplatin (CPT) is one of the standard treatments for hepatocellular carcinoma (HCC). However, its use is limits as a monotherapy due to drug resistance, and the underlying mechanism remains unclear. To solve this problem, we tried using canagliflozin (CANA), a clinical drug for diabetes, to reduce chemoresistance to CPT, and the result showed that CANA could vigorously inhibit cell proliferation and migration independent of the original target SGLT2. Mechanistically, CANA reduced aerobic glycolysis in HCC by targeting PKM2. The downregulated PKM2 directly bound to the transcription factor c-Myc in the cytoplasm to form a complex, which upregulated the level of phosphorylated c-Myc Thr58 and promoted the ubiquitination and degradation of c-Myc. Decreased c-Myc reduced the expression of GLS1, a key enzyme in glutamine metabolism, leading to impaired glutamine utilization. Finally, intracellular glutamine starvation induced ferroptosis and sensitized HCC to CPT. In conclusion, our study showed that CANA re-sensitized HCC to CPT by inducing ferroptosis through dual effects on glycolysis and glutamine metabolism. This is a novel mechanism to increase chemosensitivity, which may provide compatible chemotherapy drugs for HCC.
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Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , Humanos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Glutamina/metabolismo , Glicólise , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-myc/efeitos dos fármacos , Proteínas de Ligação a Hormônio da TireoideRESUMO
Organ growth is controlled by both intrinsic genetic factors and external environmental signals. However, the molecular mechanisms that coordinate plant organ growth and nutrient supply remain largely unknown. We have previously reported that the B3 domain transcriptional repressor SOD7 (NGAL2) and its closest homologue DPA4 (NGAL3) act redundantly to limit organ and seed growth in Arabidopsis. Here we report that SOD7 represses the interaction between the transcriptional coactivator GRF-INTERACTING FACTOR 1 (GIF1) and growth-regulating factors (GRFs) by competitively interacting with GIF1, thereby limiting organ and seed growth. We further reveal that GIF1 physically interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT), which acts as a central regulator of iron uptake and homeostasis. SOD7 can competitively repress the interaction of GIF1 with FIT to influence iron uptake and responses. The sod7-2 dpa4-3 mutant enhances the expression of genes involved in iron uptake and displays high iron accumulation. Genetic analyses support that GIF1 functions downstream of SOD7 to regulate organ and seed growth as well as iron uptake and responses. Thus, our findings define a previously unrecognized mechanism that the SOD7/DPA4-GIF1 module coordinates organ growth and iron uptake by targeting key regulators of growth and iron uptake.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Transporte Biológico , Desenvolvimento Vegetal , Regulação da Expressão Gênica de Plantas , Transativadores/metabolismoRESUMO
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica , Humanos , Prognóstico , Transplante Homólogo/efeitos adversos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologiaRESUMO
Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.
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Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Resistencia a Medicamentos Antineoplásicos , Taxoides , Transdução de SinaisRESUMO
BACKGROUND: Hepatocellular Carcinoma (HCC) is a common malignant neoplasm with limited treatment options and poor outcomes. Thus, there is an urgent need to find sensitive biomarkers for HCC. METHODS: Gene expression and clinicopathological information were obtained from public databases, based on which a pyroptosis-related gene signature was constructed by the least absolute shrinkage and selection operator Cox regression. The applicability of the signature was evaluated via Kaplan-Meier curve and time-dependent ROC curve. TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT, ssGSEA, and ESTIMATE were employed to assess the immune status. Comparisons between groups were analyzed with Wilcoxon test. Pearson and Spearman correlation analyses were adopted for linear correlation analysis. Genetic knockdown was conducted using siRNA transfection and the mRNA expression levels of interest genes were measured using quantitative reverse transcription PCR. Finally, protein levels in 10 paired tumor tissues and adjacent non-tumor tissues from HCC patients were measured using immunohistochemistry. RESULTS: A pyroptosis-related gene signature was established successfully to calculate independent prognostic risk scores. It was found that survival outcomes varied significantly between different risk groups. In addition, an attenuated antitumor immune response was found in the high-risk group. Meanwhile, multiple immune checkpoints were up-regulated in high-risk score patients. Cell cycle-related genes, angiogenesis-related genes and tumor drug resistance genes were also markedly elevated. Knockdown of prognostic genes in the signature significantly inhibited the expression of immune checkpoint genes and angiogenesis-related genes. Besides, each prognostic gene was expressed at a higher level in HCC tissues than in adjacent normal tissues. CONCLUSIONS: We successfully established a novel pyroptosis-related gene signature which could help predict the overall survival and assess the immune status of HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Piroptose/genética , Neoplasias Hepáticas/genética , Prognóstico , Bases de Dados Factuais , Biomarcadores Tumorais/genéticaRESUMO
Supramolecular host-guest ferroelectrics based on solution processing are highly desirable because they are generally created with intrinsic piezoelectricity/ferroelectricity and do not need further poling. Poly(vinylidene fluoride) (PVDF) in the electric-active beta phase after stretching/annealing still shows no piezoelectric response unless poled. Although many supramolecular host-guest ferroelectrics have been discovered, their piezoelectricity is relatively small. Based on H/F substitution, we reported a supramolecular host-guest compound [(CF3-C6H4-NH3)(18-crown-6)][TFSA] (CF3-C6H4-NH3 = 4-trifluoromethylanilinium, TFSA = bis(trifluoromethanesulfonyl)ammonium) with a remarkable piezoelectric response of 42 pC/N under no poling condition. The introduction of F atoms increases phase transition temperature, polar axes, second harmonic generation (SHG) intensity, and piezoelectric coefficient d33. To our knowledge, such a large piezoelectric performance of [(CF3-C6H4-NH3)(18-crown-6)][TFSA] makes its d33, piezoelectric voltage coefficient g33, and mechanical quality factor Qm the highest among the reported supramolecular host-guest ferroelectric compounds and even larger than the values of PVDF. This work provides inspiration for optimizing piezoelectricity on molecular materials.