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BACKGROUND: Cancer-therapy-induced mucosal injury (CMI) is a common and deleterious complication that affects patients undergoing cancer therapies. This study was aimed at elucidating knowledge bases and predicting research trends of this field, by analyzing the bibliographic data of CMI. METHODS: The bibliographic data of CMI from 2001 to 2021 were extracted from the Web of Science Core Collection database in March 2022. After screening, a total of 8181 articles and reviews were included in the study. CiteSpace and VOSviewer were applied to analyze and visualize cooperation, cooccurrence, cocitation, and coupling networks. RESULTS: A steady increase in publications and a burst of citation since 2019 were seen in the subject. Supportive Care in Cancer, International Journal of Radiation Oncology Biology Physics, Annals of Oncology, Cancer, and Radiotherapy and Oncology were the most influential journals of this field. The University of Adelaide, University of Texas MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center were the top three most productive institutions. ST Sonis, RV Lalla, JB Epstein, and DMK Keefe were the authors with impressive publications and citations. The intellectual base was the publication network of improved treatments based on updating knowledge of CMI. The future trends would be the pathogenesis of CMI, mechanism-based interventions, microbiota of oral and gastrointestinal mucosa, and photobiomodulation. CONCLUSION: This study introduced the evolving publication network and predicted the research trends of CMI, which helped researchers to obtain detailed and reliable knowledge of the discipline, and focus on the most urgent unsolved problems in this field.
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Membrana Mucosa , Neoplasias , Humanos , Bibliometría , Bases de Datos Factuales , Neoplasias/radioterapiaRESUMEN
OBJECTIVES: Circular RNAs (circRNAs), with their multilevel and versatile regulation, have emerged as promising targets for treating complex and heterogeneous malignancies such as oral squamous cell carcinoma (OSCC). It is crucial to explore the function of key circRNAs and elucidate the underlying mechanisms to establish an effective in vivo delivery system to better utilize circRNAs as cancer treatment strategies. MATERIALS AND METHODS: circRNA (circ-OCAC) was identified as significantly downregulated in tumor samples compared to paracancerous tissues by RNA-seq analysis of eight pairs of OSCC tissues. Functional experiments of circ-OCAC were performed both in vitro and in vivo. The interactions between circ-OCAC and miR-411-5p were clarified by RNA pull down and RNA immunoprecipitation (RIP) assays. RESULTS: We observed that circ-OCAC inhibits OSCC growth and metastasis by blocking the PI3K/Akt signaling pathway. To translate this observation in vivo, a pH-responsive nanoparticle (pNP) was developed to target circ-OCAC. Our results confirmed the advantages of the pNP-circ-OCAC system: high tumor enrichment capacity and good biosafety, which resulted in a significantly enhanced antitumor effect. CONCLUSIONS: This study demonstrated that targeting circ-OCAC serves as a promising potential therapeutic strategy for OSCC.
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OBJECTIVES: Accumulating studies have proved that the circular RNAs (circRNAs) play vital roles in human cancers. However, few circRNAs have been elucidated with lymph node metastasis. This study demonstrated that circ-oral cancer metastasis-associated circRNA (circ-OMAC) is required to regulate the oral squamous cell carcinoma (OSCC) metastasis. MATERIALS AND METHODS: The circ-OMAC were detected by circRNA-sequencing and further verified by in situ hybridization (ISH). The role of circ-OMAC was assessed by transwell assay and wound healing assay. Mechanistically, circ-OMAC regulated OSCC metastasis by initiating the epithelial-to-mesenchymal transition (EMT) signaling pathway. RESULTS: Our findings suggested that circ-OMAC was aberrantly elevated in the metastatic lymph nodes as compared to primary OSCC tissues. OSCC patients with high levels of circ-OMAC were prone to a poor prognosis. By developing functional assays, we confirmed that circ-OMAC promotes metastasis of OSCC cells via initiation of EMT pathways. CONCLUSIONS: We provide new insights whereby Circ-OMAC as an oncogene is a potential therapeutic target and prognostic marker in oral cancer.
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OBJCTIVE: To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. RESULTS: The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. CONCLUSIONS: Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.
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Tumores Neuroectodérmicos Primitivos , Protocolos de Quimioterapia Combinada Antineoplásica , Niño , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Two-dimensional speckle-tracking echocardiography (2D-STE) enables objective assessment of left atrial (LA) deformation through the analysis of myocardial strain, which can be measured by different speckle-tracking software. The aim of this study was to compare the consistency of 3 different commercially available software, which include vendor-specific software for measuring left ventricle (VSSLV), vendor-independent software packages for measuring LV strain (VISLV) and vendor-independent software packages for measuring LA strain (VISLA). METHODS: Sixty-four subjects (mean age: 44 ± 16 years, 50% males) underwent conventional echocardiograms using a GE Vivid 9 (GE Ultrasound, Horten, Norway) cardiac ultrasound system. Standard apical 4 and 2 chamber views of the left atrium were obtained in each subject with a frame-rate range of 40-71 frames/s. LA strain during the contraction phase (Sct), conduit phase (Scd), reservoir phase (Sr = Sct + Scd) were analyzed by 2 independent observers and 3 different software. RESULTS: Sct, Scd, Sr were, respectively, - 11.26 ± 2.45%, - 16.77 ± 7.06%, and 28.03 ± 7.58% with VSSLV, - 14.77 ± 3.59%, - 23.17 ± 10.33%, and 38.23 ± 10.99% with VISLV, and - 14.80 ± 3.88%, - 23.94 ± 10.48%, and 38.73 ± 11.56% when VISLA was used. A comparison of strain measurements between VSSLV and VIS (VISLV and VISLA) showed VIS had significantly smaller mean differences and narrower limits of agreement. Similar results were observed in the coefficient of variation (CV) for measurements between VSSLV and VIS (VISLV and VISLA). Comparison of the intra-class correlation coefficients (ICCs) indicated that measurement reliability was weaker with VSSLV (ICC < 0.6) than with VIS (VISLV and VISLA) (ICC > 0.9). For intra-observer ICCs, VISLA > VSSLV = VISLV. For inter-observer ICCs, VSSLV > VISLA > VISLV. CONCLUSIONS: Software measurement results of LA strain vary considerably. We recommended not measuring LA strain across vendor platforms.
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Fibrilación Atrial/diagnóstico , Función del Atrio Izquierdo/fisiología , Comercio , Ecocardiografía/métodos , Atrios Cardíacos/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Programas Informáticos , Adulto , Fibrilación Atrial/fisiopatología , Femenino , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG). METHODS: A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy. RESULTS: The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P<0.05), while there were no significant differences between the two groups in the proportion of children with improved visual acuity or adverse reactions (P>0.05). No chemotherapy-related death was observed in either group. CONCLUSIONS: Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.
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Glioma del Nervio Óptico , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carboplatino , Niño , Humanos , Estudios Retrospectivos , VincristinaRESUMEN
OBJECTIVES: The aim of the study was to examine the association of CHADS2/CHA2DS2-VASc scores with left atrial thrombus (LAT) and spontaneous echocardiographic contrast (SEC) in non-anticoagulated nonvalvular atrial fibrillation (NVAF) spontaneous patients, and to develop a new scoring system for LAT/SEC prediction. METHODS: Consecutive non-anticoagulated NVAF patients with or without LAT/SEC by transesophageal echocardiography were identified in the Guangdong General Hospital. RESULTS: Among 2,173 patients, the prevalence of LAT/SEC was 4.9%. Both predictive values of CHADS2 and CHA2DS2-VASc scores for the presence of LAT/SEC were low-to-moderate (receiver operating characteristic [ROC] = 0.591 and 0.608, respectively, p = 0.90). By multivariate analysis, non-paroxysmal AF, decreased left ventricular ejection fraction, and left atrial enlargement were positively associated with LAT/SEC, while CHADS2/CHA2DS2VASc scores were not. A new scoring system based on these 3 factors above significantly improved the discrimination for LAT/SEC (ROC = 0.792). CONCLUSIONS: CHADS2/CHA2DS2-VASc scores had limited value in predicting LAT/SEC; a new scoring system that combines AF type and echocardiographic parameters may better predict LAT/SEC as a surrogate for cardioembolic risk in NVAF patients.
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Medición de Riesgo/métodos , Tromboembolia/diagnóstico por imagen , Tromboembolia/epidemiología , Trombosis/epidemiología , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Función del Atrio Izquierdo , China/epidemiología , Medios de Contraste , Ecocardiografía Transesofágica , Cardiopatías , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Accidente Cerebrovascular/etiología , Trombosis/complicaciones , Trombosis/diagnóstico por imagenRESUMEN
Relapsed medulloblastoma (MB) has a dire prognosis, and chemotherapy remains the main therapeutic option. We retrospectively analyzed the clinical characteristics and survival rates of 60 Chinese children with relapsed MB. The patients received 11 cycles of chemotherapy in sequence, followed by 12 cycles of oral temozolomide and etoposide. Thirty patients were simultaneously administered intrathecal methotrexate (IT-MTX). The Kaplan-Meier method was used to determine survival rates; the patients' median survival time after relapse was 2.8 years, 5-year progression-free survival (PFS) and overall survival (OS) rates were 26.7%±5.7% and 31.6%±6.9%, respectively. There was no significant difference between these rates according to histology or molecular subgroup. Tumor cells were detected in the cerebrospinal fluid of over 40% of patients; such patients had significantly shorter OS and PFS rates. Patients who received IT-MTX showed significantly longer survival than those who did not (3.73 vs. 2.06 y, respectively, P=0.000); the corresponding 5-year PFS and OS rates were 43.3%±9.0% versus 10.0%±5.5% and 49.5%±11.1% versus 14.6%±6.9%, respectively (P=0.000). In addition, tumor cell-positive cerebrospinal fluid and IT-MTX use significantly influenced PFS and OS in relapsed patients. Taken together, our data show that IT-MTX improves the survival of patients with relapsed MB.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Cerebelosas , Meduloblastoma , Recurrencia Local de Neoplasia , Adolescente , Neoplasias Cerebelosas/líquido cefalorraquídeo , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/mortalidad , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Meduloblastoma/líquido cefalorraquídeo , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/mortalidad , Recurrencia Local de Neoplasia/líquido cefalorraquídeo , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Bovine viral diarrhoea virus (BVDV) can infect cows on days 30-110 of gestation and crossing the placental barrier, resulting in persistently infected (PI) and causing significant economic losses to dairy farming. Bovine placental trophoblast cells (BTCs) are the major cells in the early chorionic tissue of the placenta and play important roles in placental resistance to viral transmission. In this study, we have confirmed that BTCs is among a groups of cell types those could be infected by BVDV in vivo, and BVDV infection stimulates the autophagic responses in BTCs and promotes the release of exosomes. Meanwhile, the exosomes derived from BTCs can be used by BVDV to spread between placental trophoblast cells, and this mode of transmission cannot be blocked by antibodies against the BVDV E2 protein, whereas the replication and spread of BVDV in BTCs can be blocked by inhibiting autophagy and exosomogenesis. Our study provides a theoretical and practical basis for scientific prediction and intervention of reproductive disorders caused by BVDV infection in cows of different gestation periods from a novel perspective.
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Autofagia , Diarrea Mucosa Bovina Viral , Virus de la Diarrea Viral Bovina , Exosomas , Trofoblastos , Animales , Bovinos , Femenino , Trofoblastos/virología , Trofoblastos/inmunología , Exosomas/metabolismo , Exosomas/virología , Diarrea Mucosa Bovina Viral/transmisión , Diarrea Mucosa Bovina Viral/virología , Diarrea Mucosa Bovina Viral/inmunología , Embarazo , Virus de la Diarrea Viral Bovina/fisiología , Virus de la Diarrea Viral Bovina/inmunología , Placenta/virología , Placenta/inmunología , Células Cultivadas , Replicación ViralRESUMEN
Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin, and hepatic cell necrosis. Moreover, LcS alleviated acetaminophen-induced intestinal mucosal permeability, decreased serum IL-1α and lipopolysaccharide levels, and elevated serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol, and sugars in the gut. Additionally, the transcriptomic and proteomic results showed that LcS mitigated the decrease in metabolic and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.IMPORTANCEAcetaminophen is the most frequently used antipyretic analgesic worldwide. As a result, overdoses easily occur and lead to drug-induced acute liver injury, which quickly progresses to liver failure with a mortality of 60%-80% if not corrected in time. The current emergency treatment for overused acetaminophen needs to be administered within 8 hours to avoid liver injury or even liver failure. Therefore, developing preventive strategies for liver injury during planned acetaminophen medication is particularly important, preferably nonpharmacological methods. Lacticaseibacillus casei Shirota (LcS) is a famous probiotic that has been used for many years. Our study found that LcS significantly alleviated acetaminophen-induced acute liver injury, especially acetaminophen-induced liver injury toward fulminant hepatic failure. Here, we elucidated the function and potential mechanisms of LcS in alleviating acetaminophen-induced acute liver injury, hoping it will provide preventive strategies to people during acetaminophen treatment.
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Antipiréticos , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Lacticaseibacillus casei , Fallo Hepático , Humanos , Ratones , Animales , Acetaminofén/efectos adversos , Proteómica , Ratones Endogámicos C57BL , Administración Oral , Analgésicos , Glutatión , BilirrubinaRESUMEN
BACKGROUND: Cancer stem cells (CSCs) are a sub-population of cancer cells present in many kinds of malignant tumors that have the potential for self-proliferation and differentiation. These cells have been demonstrated as the main cause of tumor recurrence and metastasis. Strong evidence indicates that CSCs prefer reprogrammed fatty acid ß-oxidation over oxidative phosphorylation for sustaining energy supply. Although mitochondrial dynamics participate in the regulation of cancer stemness, the correlation between the inhibition of mitochondrial fission and the regulation of lipid metabolism in CSCs remains poorly understood. METHODS: The human tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SAS were used to obtain the CSCs by 3D Spheroid Culture. Then,western blot methods, RT-PCR and flow cytometry analysis were used to identify the TSCC CSCs. Next, Immunofluorescence method, transmission electron microscopy detection and western blot methods were used to evaluate the mitochondrial morphology and the quantity of lipid droplets (LDs). Lastly, lipidomic analysis was applied to explored the lipidomic alterations of TSCC CSCs with different mitochondrial morphology. RESULTS: Here, we show that the quantity of lipid droplets containing intracellular triglyceride (TG) can be decreased by regulating mitochondrial morphology. Lipidomic analysis using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) also compared alterations in lipid metabolites in tongue squamous cell carcinoma (TSCC) CSCs, TSCC cells (non-CSCs), and CSCs with different mitochondrial morphology. Discriminant lipids of statistical significance were successfully annotated, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), sphingomyelins (SMs), triacylglycerols (TGs), phosphatidylglycerols (PGs), phosphatidylserines (PSs), lysophosphatidylcholines (LPCs), and lysophosphatidylethanolamines (LPEs). CONCLUSION: This study provides a deeper insight into the alterations of lipid metabolism associated with TSCC CSCs, non-CSCs and CSCs regulated by mitochondrial dynamics and thus serves as a guide toward novel targeted therapies.
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Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in tumor therapy. The engineering approaches discussed include enhancing in vivo immune response, improving replication efficiency within the tumor cells, enhancing safety profiles, and improving targeting capabilities. In addition, this review describes the potential mechanisms of OVs combined with radiotherapy, chemotherapy, cell therapy and immune checkpoint inhibitors (ICIs), and summarizes the data of ongoing clinical trials. By continuously optimizing engineering strategies and combination therapy programs, we can achieve improved treatment outcomes and quality of life for cancer patients.
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BACKGROUND: Placental exosomes are a kind of intercellular communication media secreted by placental cells during pregnancy, exosomogenesis and release are regulated by many secretory glycoproteins. CREG1 is a kind of secreted glycoprotein widely expressed in various organs and tissues of the body, which inhibits cell proliferation and enhances cell differentiation. The aim of this study was to explore the role of CREG1 in regulating exosomogenesis during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R and participating in regulating organoid differentiation via exosomes transport. METHODS: Molecular biological methods were firstly used to investigate the expression patterns of CREG1, IGF2R and exosomal marker proteins in early placental development of pregnant dairy cows. Subsequently, the effects of CREG1 on the formation and release of bovine placental trophoblast (BTCs) derived exosomes by targeting IGF2R were investigated. Further, the effects of CREG1 on the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the differentiation of organoids were explored. RESULTS: The expression of CREG1, IGF2R and exosomal marker proteins increased with the increase of pregnancy months during the early evolution of placental trophoblast cells in dairy cows. Overexpression of Creg1 enhanced the genesis and release of exosomes derived from BTCs, while knocking down the expression of Igf2r gene not only inhibited the genesis of exosomes, but also inhibited the genesis and release of exosomes induced by overexpression of CREG1 protein. Interestingly, IGF2R can regulate the expression of CREG1 through reverse secretion. What's more, the occurrence and release of trophoblast-derived exosomes are regulated by CREG1 binding to IGF2R, which subsequently binds to Rab11. CREG1 can not only promote the formation and release of exosomes in donor cells, but also regulate the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the early development of placenta. CONCLUSIONS: Our study confirmed that CREG1 is involved in the exosomogenesis and release of exosomes during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R, and is involved in the regulation of organoid differentiation through exosome transport.
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Diferenciación Celular , Exosomas , Placenta , Receptor IGF Tipo 2 , Trofoblastos , Animales , Exosomas/metabolismo , Bovinos , Trofoblastos/metabolismo , Trofoblastos/citología , Femenino , Embarazo , Receptor IGF Tipo 2/metabolismo , Receptor IGF Tipo 2/genética , Placenta/metabolismo , Placenta/citología , Organoides/metabolismo , Organoides/citología , Proliferación CelularRESUMEN
Objectives: Chondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post-translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development. Methods: Human and mouse cartilage tissues were used to measure SIRT5 and MaK levels. Both systemic and cartilage-specific conditional knockout mouse models were subject to high-fat diet (HFD) treatment to induce obesity and OA. Proteomics analysis was performed in Sirt5 -/- and WT chondrocytes. SIRT5 mutation was identified in the Utah Population Database (UPDB). Results: We found that SIRT5 decreases while MAK increases in the cartilage during aging. A combination of Sirt5 deficiency and obesity exacerbates joint degeneration in a sex dependent manner in mice. We further delineate the malonylome in chondrocytes, pinpointing MaK's predominant impact on various metabolic pathways such as carbon metabolism and glycolysis. Lastly, we identified a rare coding mutation in SIRT5 that dominantly segregates in a family with OA. The mutation results in substitution of an evolutionally invariant phenylalanine (Phe-F) to leucine (Leu-L) (F101L) in the catalytic domain. The mutant protein results in higher MaK level and decreased expression of cartilage ECM genes and upregulation of inflammation associated genes. Conclusions: We found that Sirt5 mediated MaK is an important regulator of chondrocyte cellular metabolism and dysregulation of Sirt5-MaK could be an important mechanism underlying aging and obesity associated OA development.
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BACKGROUND: Ferroptosis is a new type of programmed apoptosis and plays an important role in tumour inhibition and immunotherapy. OBJECTIVE: In this study, we aimed to explore the potential role of ferroptosis-related genes (FRGs) and the potential therapeutic targets in oral cavity squamous cell carcinoma (OCSCC). METHODS: The transcription data of OCSCC samples were obtained from the Cancer Genome Atlas (TCGA) database as a training dataset. The prognostic FRGs were extracted by univariate Cox regression analysis. Then, we constructed a prognostic model using the least absolute shrinkage and selection operator (LASSO) and Cox analysis to determine the independent prognosis FRGs. Based on this model, risk scores were calculated for the OCSCC samples. The model's capability was further evaluated by the receiver operating characteristic curve (ROC). Then, we used the GSE41613 dataset as an external validation cohort to confirm the model's predictive capability. Next, the immune infiltration and somatic mutation analysis were applied. Lastly, single-cell transcriptomic analysis was used to identify the key cells. RESULTS: A total of 12 prognostic FRGs were identified. Eventually, 6 FRGs were screened as independent predictors and a prognostic model was constructed in the training dataset, which significantly stratified OCSCC samples into high-risk and low-risk groups based on overall survival. The external validation of the model using the GSE41613 dataset demonstrated a satisfactory predictive capability for the prognosis of OCSCC. Further analysis revealed that patients in the highrisk group had distinct immune infiltration and somatic mutation patterns from low-risk patients. Mast cell infiltrations were identified as prognostic immune cells and played a role in OCSCC partly through ferroptosis. CONCLUSION: We successfully constructed a novel 6 FRGs model and identified a prognostic immune cell, which can serve to predict clinical prognoses for OCSCC. Ferroptosis may be a new direction for immunotherapy of OCSCC.
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Ferroptosis , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Ferroptosis/genética , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Pronóstico , Análisis de Secuencia de ARNRESUMEN
The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the potential of immune checkpoint blockade, innate immune cell therapy (including T cells, iNKT cells, macrophages, and NK cells), as well as CAR-T cell therapy for inducing and augmenting immune responses aimed at eliminating senescent cells. In addition to CAR-T cells, we also explore the possibility of engineered immune cells such as CAR-NK and CAR-M cells to eliminate senescent cells. In summary, immunotherapy, as an emerging strategy for the treatment of aging, offers new prospects for age-related research.
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Privacy-preserving federated learning, as one of the privacy-preserving computation techniques, is a promising distributed and privacy-preserving machine learning (ML) approach for Internet of Medical Things (IoMT), due to its ability to train a regression model without collecting raw data of data owners (DOs). However, traditional interactive federated regression training (IFRT) schemes rely on multiple rounds of communication to train a global model and are still under various privacy and security threats. To overcome these problems, several noninteractive federated regression training (NFRT) schemes have been proposed and applied in a variety of scenarios. However, there are still several challenges: 1) how to protect the privacy of DOs' local dataset; 2) how to realize highly scalable regression training without linear dependence on sample dimension; 3) how to tolerate DOs' dropout; and 4) how to enable DOs to verify the correctness of aggregated results returned from the cloud service provider (CSP). In this article, we propose two practical noninteractive federated learning schemes with privacy-preserving for IoMT, named homomorphic encryption based NFRT (HE-NFRT) and double-masking protocol based NFRT (Mask-NFRT), respectively, which are based on a comprehensive consideration of NFRT, privacy concerns, high-efficiency, robustness, and verification mechanism. The security analyses display that our proposed schemes are able to protect the privacy of DOs' local training data, resist collusion attack, and support strong verification to each DO. The performance evaluation results demonstrate that our proposed HE-NFRT scheme is desirable for a high-dimensional and high-security IoMT application while Mask-NFRT scheme is desirable for a high-dimensional and large-scale IoMT application.
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Cancer-associated fibroblasts (CAFs) are widely involved in the development and progression of tumours. As a direct junction between tumour and normal host tissue, the invasive tumour front can remodel host tissue to generate a microenvironment more suitable for tumour invasion. However, whether CAFs derived from the invasive front (CAFs-F) have a greater ability to promote tumour invasion than CAFs derived from the superficial tumour (CAFs-S) is unclear. In this study, we characterized primary CAFs from different spatial locations of tumours. We demonstrated that CAFs-F had an increased ability to promote oral squamous cell carcinoma (OSCC) proliferation and invasion in vitro and significantly enhanced tumour growth in vivo compared to CAFs-S. Mechanistically, transcriptome profiling analysis revealed that the expression of MFAP5, encoding microfibril associated protein 5, was dramatically increased in CAFs-F compared to CAFs-S, which further confirmed that the MFAP5 protein level was elevated in head and neck squamous cell carcinoma (HNSCC) and that this increase was correlated with poor survival. Genetic ablation of MFAP5 impaired the preinvasive capabilities of CAFs-F. Together, our findings demonstrated that CAFs-F had a greater ability to promote tumour invasion than CAFs-S and that MFAP5 might be involved in this process.
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Fibroblastos Asociados al Cáncer , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/genética , Neoplasias de la Boca/genética , Fibroblastos Asociados al Cáncer/metabolismo , Regulación hacia Arriba , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/patología , Fibroblastos/metabolismo , Microambiente Tumoral/fisiologíaRESUMEN
BACKGROUND: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. METHODS: We performed combined single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell (TIL) subtype, CD103+ CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+ CD8+ TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images. RESULTS: We established intratumoral CD103+ CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA-seq results indicated that the population of CD103+ CD8+ TILs was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+ CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+ CD8+ TILs were tumor-reactive T cells, while programmed cell death protein-1 (PD-1) blockade enhanced CD103+ CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2-positive (TREM2+ ) macrophages might enhance the population of CD103+ CD8+ TILs and facilitate antitumor immunity during NACI treatment. CONCLUSIONS: Our study highlights the impact of intratumoral CD103+ CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.
Asunto(s)
Linfocitos T CD8-positivos , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Linfocitos T CD8-positivos/metabolismo , Terapia Neoadyuvante , Neoplasias de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
Background: Chimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field. Methods: Literature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software. Results: A total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing. Conclusion: CAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.