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1.
Artigo em Inglês | MEDLINE | ID: mdl-38558103

RESUMO

PURPOSE: To evaluate the clinical outcomes following arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) in patients over 60 years and to investigate the potential impact of preoperative osteoarthritis (OA) on these outcomes. METHODS: A retrospective study included ACL-injured patients over 60 years who underwent primary arthroscopic ACLR between 2010 and 2020. The Lysholm score and the International Knee Documentation Committee (IKDC) score were assessed preoperatively and at the final follow-up. The Tegner activity scale was performed to evaluate patients' activity levels. Data on return to sports, patient satisfaction, subsequent injuries and complications were collected. Preoperative radiographs were used to grade OA according to the Kellgrene-Lawrence classification. Correlation analysis between OA and clinical outcomes was performed. The rates of achieving the minimal clinically significant difference and patient-acceptable symptoms state were documented. RESULTS: A total of 37 patients were included in this study. The mean age at surgery was 62.3 ± 2.3 years, with a mean follow-up of 6.3 ± 3.2 years (range: 2.1-12.4). Patients showed statistically significant (all p < 0.001) improvements in the mean IKDC (38.9 ± 9.4-66.8 ± 12.5), Lysholm (48.8 ± 15.4-83.0 ± 12.8) and Tegner (1-3) scores. Fourteen patients (37.8%) returned to sports. No correlation was observed between the degree of preoperative OA and clinical outcomes (n.s.). CONCLUSION: Patients over 60 years with symptomatic ACL-deficient knees could benefit from ACLR, even when mild to moderate OA is present preoperatively. LEVEL OF EVIDENCE: Level IV.

2.
World J Gastroenterol ; 30(9): 1108-1120, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577179

RESUMO

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Gastrite/epidemiologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Úlcera Gástrica/patologia , Gastroscopia , Dor , Estilo de Vida , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38634120

RESUMO

UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we explore the role of UBE2C in regulating temozolomide (TMZ) resistance in glioma and investigate the underlying mechanisms involved. Twenty normal brain tissues and 100 glioma tissues from 50 TMZ-resistant patients and 50 TMZ-sensitive patients are included in this study. TMZ-resistant cell lines are constructed to explore the role of UBE2C in regulating glioma cell viability and TMZ resistance. Our results show that both the mRNA and protein levels of UBE2C are significantly elevated in the brain tissues of glioma patients, especially in those of TMZ-resistant patients. Consistently, UBE2C expression is markedly upregulated in TMZ-resistant cell lines. Overexpression of UBE2C rescues glioma cells from TMZ-mediated apoptosis and enhances cell viability. In contrast, downregulation of UBE2C expression further enhances TMZ function, increases cell apoptosis and decreases cell viability. Mechanistically, UBE2C overexpression decreases p53 expression and enhances aerobic glycolysis level by increasing ATP level, lactate production, and glucose uptake. Downregulation of p53 level abolishes the role of UBE2C downregulation in inhibiting TMZ resistance and aerobic glycolysis in glioma cells. Moreover, an animal assay confirms that downregulation of UBE2C expression further suppresses tumor growth in the context of TMZ treatment. Collectively, this study reveals that downregulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.

4.
ACS Appl Mater Interfaces ; 16(15): 18959-18970, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38569111

RESUMO

Fe-based Prussian blue (Fe-PB) analogues have emerged as promising cathode materials for sodium-ion batteries, owing to their cost-effectiveness, high theoretical capacity, and environmental friendliness. However, their practical application is hindered by [Fe(CN)6] defects, negatively impacting capacity and cycle stability. This work reports a hollow layered Fe-PB composite material using 1,3,5-benzenetricarboxylic acid (BTA) as a chelating and etching agent by the hydrothermal method. Compared to benzoic acid, our approach significantly reduces defects and enhances the yield of Fe-PB. Notably, the hollow layered structure shortens the diffusion path of sodium ions, enhances the activity of low-spin Fe in the Fe-PB lattice, and mitigates volume changes during Na-ion insertion/extraction into/from Fe-PB. As a sodium-ion battery cathode, this hollow layered Fe-PB exhibits an impressive initial capacity of 95.9 mAh g-1 at a high current density of 1 A g-1. Even after 500 cycles, it still maintains a considerable discharge capacity of 73.1 mAh g-1, showing a significantly lower capacity decay rate (0.048%) compared to the control sample (0.089%). Moreover, the full cell with BTA-PB-1.6 as the cathode and HC as the anode provides a considerable energy density of 312.2 Wh kg-1 at a power density of 291.0 W kg-1. This research not only enhances the Na storage performance of Fe-PB but also increases the yield of products obtained by hydrothermal methods, providing some technical reference for the production of PB materials using the low-yield hydrothermal method.

5.
J Immunother Cancer ; 12(4)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580333

RESUMO

BACKGROUND: The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells' immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors' immunotherapy landscape. METHODS: By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC). RESULTS: While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies. CONCLUSIONS: We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments. TRIAL REGISTRATION NUMBER: NCT06165874.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Compostos Heterocíclicos com 1 Anel , Neoplasias Pulmonares , Anticorpos de Domínio Único , Humanos , Antígeno B7-H1/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Radioisótopos de Gálio , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Receptor de Morte Celular Programada 1 , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/uso terapêutico
6.
Heliyon ; 10(7): e29098, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601662

RESUMO

Objectives: Our previous studies revealed the significant roles of FK506-binding protein 4 (FKBP4) in tumorigenesis, however, there has been no pan-cancer analysis of FKBP4. Using bioinformatics, the current study reported the expression and prognostic role of FKBP4, and the correlation between FKBP4 and clinicopathological parameters, methylation, molecular network, immunological traits and drug sensitivity. Methods: RNA sequencing data, somatic mutation, and related clinical information were obtained from TCGA using UCSC Xena. The association between FKBP4 expression and clinical features was assessed using TISIDB. The relationships between FKBP4 expression and tumour stage, OS, DSS, DFS, and PFS were analysed using univariate cox regression analysis. The radar plots for TMB and MSI were obtained using "Fmsb" R package. UALCAN was used to explore the effect of FKBP4 methylation on tumour and normal samples. CBioportal was used to analyse copy number mutations in FKBP4 Gene expression and drug sensitivity data were downloaded from the CellMiner database. GO analysis was performed for the high and the low expression of FKBP4 compared with the median level of FKBP4 using clusterProfiler4.0. Results: FKBP4 expression is significantly upregulated in various types of cancers. Cox regression analysis showed that high FKBP4 levels were correlated with poor OS, DSS, DFS, and PFS in most patients with cancer. Methylation of FKBP4 DNA was upregulated in most cancers, and FKBP4 expression is positively associated with transmethylase expression. FKBP4 and its copy were significantly associated with the expression of immune-infiltrating cells, immune checkpoint genes, immune modulators, TMB, MMR, and MSI. FKBP4 expression levels significantly correlated with 16 different drug sensitivities (all p < 0.05). Conclusions: Our pan-cancer bioinformatic analysis revealed a potential mechanism underlying the effects of FKBP4 on the prognosis and progression of various cancers.

8.
APL Bioeng ; 8(2): 021501, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38572313

RESUMO

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail.

9.
Nat Commun ; 15(1): 3008, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589420

RESUMO

The construction of functional three-dimensional covalent organic frameworks (3D COFs) for gas separation, specifically for the efficient removal of ethane (C2H6) from ethylene (C2H4), is significant but challenging due to their similar physicochemical properties. In this study, we demonstrate fine-tuning the pore environment of ultramicroporous 3D COFs to achieve efficient one-step C2H4 purification. By choosing our previously reported 3D-TPB-COF-H as a reference material, we rationally design and synthesize an isostructural 3D COF (3D-TPP-COF) containing pyridine units. Impressively, compared with 3D-TPB-COF-H, 3D-TPP-COF exhibits both high C2H6 adsorption capacity (110.4 cm3 g-1 at 293 K and 1 bar) and good C2H6/C2H4 selectivity (1.8), due to the formation of additional C-H···N interactions between pyridine groups and C2H6. To our knowledge, this performance surpasses all other reported COFs and is even comparable to some benchmark porous materials. In addition, dynamic breakthrough experiments reveal that 3D-TPP-COF can be used as a robust absorbent to produce high-purity C2H4 directly from a C2H6/C2H4 mixture. This study provides important guidance for the rational design of 3D COFs for efficient gas separation.

10.
J Am Chem Soc ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615324

RESUMO

The development of novel soft porous crystals (SPCs) that can be transformed from nonporous to porous crystals is significant because of their promising applications in gas storage and separation. Herein, we systematically investigated for the first time the gas-triggered gate-opening behavior of three-dimensional covalent organic frameworks (3D COFs) with flexible building blocks. FCOF-5, a 3D COF containing C-O single bonds in the backbone, exhibits a unique "S-shaped" isotherm for various gases, such as CO2, C2, and C3 hydrocarbons. According to in situ characterization, FCOF-5 undergoes a pressure-induced closed-to-open structural transition due to the rotation of flexible C-O single bonds in the framework. Furthermore, the gated hysteretic sorption property of FCOF-5 can enable its use as an absorbent for the efficient removal of C3H4 from C3H4/C3H6 mixtures. Therefore, 3D COFs synthesized from flexible building blocks represent a new type of SPC with gate-opening characteristics. This study will strongly inspire us to design other 3D COF-based SPCs for interesting applications in the future.

11.
Perfusion ; : 2676591241242018, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557237

RESUMO

Background: In lung transplantation surgery, extracorporeal life support (ECLS) is essential for safety. Various support methods, including cardiopulmonary bypass (CPB) and off-pump techniques, are used, with extracorporeal membrane oxygenation (ECMO) gaining prominence. However, consensus on the best support strategy is lacking.Purpose: This article reviews risks, benefits, and outcomes of different support strategies in lung transplantation. By consolidating knowledge, it aims to clarify selecting the most appropriate ECLS modality.Research Design: A comprehensive literature review examined CPB, off-pump techniques, and ECMO outcomes in lung transplantation, including surgical results and complications.Study Sample: Studies, including clinical trials and observational research, focused on ECLS in lung transplantation, both retrospective and prospective, providing a broad evidence base.Data Collection and/or Analysis: Selected studies were analyzed for surgical outcomes, complications, and survival rates associated with CPB, off-pump techniques, and ECMO to assess safety and effectiveness.Results: Off-pump techniques are preferred, with ECMO increasingly vital as a bridge to transplant, overshadowing CPB. However, ECMO entails hidden risks and higher costs. While safer than CPB, optimizing ECMO postoperative use and monitoring is crucial for success.Conclusions: Off-pump techniques are standard, but ECMO's role is expanding. Despite advantages, careful ECMO management is crucial due to hidden risks and costs. Future research should focus on refining ECMO use and monitoring to improve outcomes, emphasizing individualized approaches for LT recipients.

12.
Mol Pharm ; 21(5): 2394-2405, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38647653

RESUMO

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.


Assuntos
Cálcio , Doxorrubicina , Liberação Controlada de Fármacos , Glutationa , Lipossomos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Animais , Camundongos , Lipossomos/química , Humanos , Cálcio/química , Cálcio/metabolismo , Glutationa/química , Feminino , Géis/química , Gelatina/química , Camundongos Nus , Nanopartículas/química , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Reagentes de Ligações Cruzadas/química , Sistemas de Liberação de Medicamentos/métodos
13.
Research (Wash D C) ; 7: 0340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665846

RESUMO

The methylation of adenosine base at the nitrogen-6 position is referred to as "N6-methyladenosine (m6A)" and is one of the most prevalent epigenetic modifications in eukaryotic mRNA and noncoding RNA (ncRNA). Various m6A complex components known as "writers," "erasers," and "readers" are involved in the function of m6A. Numerous studies have demonstrated that m6A plays a crucial role in facilitating communication between different cell types, hence influencing the progression of diverse physiological and pathological phenomena. In recent years, a multitude of functions and molecular pathways linked to m6A have been identified in the osteogenic, adipogenic, and chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Nevertheless, a comprehensive summary of these findings has yet to be provided. In this review, we primarily examined the m6A alteration of transcripts associated with transcription factors (TFs), as well as other crucial genes and pathways that are involved in the differentiation of BMSCs. Meanwhile, the mutual interactive network between m6A modification, miRNAs, and lncRNAs was intensively elucidated. In the last section, given the beneficial effect of m6A modification in osteogenesis and chondrogenesis of BMSCs, we expounded upon the potential utility of m6A-related therapeutic interventions in the identification and management of human musculoskeletal disorders manifesting bone and cartilage destruction, such as osteoporosis, osteomyelitis, osteoarthritis, and bone defect.

15.
J Hepatocell Carcinoma ; 11: 747-766, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680213

RESUMO

Purpose: Nonsense-mediated RNA decay (NMD), a surveillance pathway for selective degradation of aberrant mRNAs, is associated with cancer progression. Its potential as a predictor for aggressive hepatocellular carcinoma (HCC) is unclear. Here, we present an innovative NMD risk model for predicting HCC prognosis. Methods: The Cancer Genome Atlas (TCGA) data of 374 liver HCC (LIHC) and 50 normal liver samples were extracted. A risk model based on NMD-related genes was developed through least absolute shrinkage and selection operator Cox (LASSO-Cox) regression of the LIHC-TCGA data. Prognostic validation was done using GSE54236, GSE116174, and GSE76427 data. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the model. We also constructed nomograms for survival prediction. Tumor immune infiltration was evaluated using the CIBERSORT algorithm, and the tumor cell phenotype was assessed. Finally, mouse experiments verified UPF3B knockdown effects on HCC tumor characteristics. Results: We developed a risk model based on four NMD-related genes (PABPC1, RPL8, SMG5, and UPF3B) and validated it using GSE54236, GSE116174, and GSE76427 data. The model effectively distinguished high- and low-risk groups corresponding to unfavorable and favorable HCC outcomes. Its prognostic prediction accuracy was confirmed through time-dependent ROC analysis, and clinical-use nomograms with calibration curves were developed. Single-cell RNA sequencing results indicated significantly higher expression of SMG5 and UPF3B in tumor cells. Knockdown of SMG5 and UPF3B inhibited HCC cell proliferation, invasion, and migration, while affecting cell-cycle progression and apoptosis. In vivo, UPF3B knockdown delayed tumor growth and increased immune cell infiltration. Conclusion: Our NMD-related gene-based risk model can help identify therapeutic targets and biomarkers for HCC. Additionally, it assists clinicians in predicting the prognosis of HCC patients.

16.
Int Immunopharmacol ; 132: 112054, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608477

RESUMO

γδT cells are unconventional T cells only accounting for 1-5 % of circulating T lymphocytes. Their potent anti-tumor capability has been evidenced by accumulating studies. However, the prognostic value of γδT cells remains not well documented in head and neck squamous cell carcinoma (HNSCC). In this study, we utilized the TCGA HNSCC database to evaluate the infiltration of γδT cells and the association between γδT cells and clinicopathological factors by related gene signature, which were then validated by a total of 100 collected tumor samples from HNSCC patient cohort. Heterogeneity and functional characteristics of distinct infiltrating γδT cell profiles in HNSCC were then investigated based on the scRNA-seq data from the GEO database. We found higher γδT cell gene signature score was significantly associated with longer survival. Cox regression models showed that γδT cell gene signature could serve as an independent prognostic indicator for HNSCC patients. A high level of γδT cell-related gene signature was positively correlated with the infiltration of tumor-infiltrating lymphocytes and immune score. Through scRNA-seq analysis, we identified that γδ+ Trm cells and γδ+ CTL cells possessed anti-tumor and immunoregulatory properties. Notably, we found a significant association between the presence of these cells and improved survival outcomes. In our cell-cell communication analyses, we identified that γδT cells have the potential to eliminate tumor cells through the secretion of interferon-gamma and granzyme. Collectively, the infiltration of γδT cells may serve as a promising prognostic tool, prompting the consideration of treatment options for patients with HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Linfócitos do Interstício Tumoral , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Prognóstico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Transcriptoma , Linfócitos Intraepiteliais/imunologia , Regulação Neoplásica da Expressão Gênica , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Idoso
17.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674123

RESUMO

Cleft palate only (CPO) is one of the most common craniofacial birth defects. Environmental factors can induce cleft palate by affecting epigenetic modifications such as DNA methylation, histone acetylation, and non-coding RNA. However, there are few reports focusing on the RNA modifications. In this study, all-trans retinoic acid (atRA) was used to simulate environmental factors to induce a C57BL/6J fetal mouse cleft palate model. Techniques such as dot blotting and immunofluorescence were used to find the changes in m6A modification when cleft palate occurs. RNA-seq and KEGG analysis were used to screen for significantly differentially expressed pathways downstream. Primary mouse embryonic palate mesenchymal (MEPM) cells were successfully isolated and used for in vitro experimental verification. We found that an increased m6A methylation level was correlated with suppressed cell proliferation in the palatine process mesenchyme of cleft palate mice. This change is due to the abnormally high expression of m6A methyltransferase METTL14. When using siRNAs and the m6A methyltransferase complex inhibitor SAH to interfere with the expression or function of METTL14, the teratogenic effect of atRA on primary cells was partially alleviated. In conclusion, METTL14 regulates palatal mesenchymal cell proliferation and cycle-related protein expression relies on m6A methylation modification, affecting the occurrence of cleft palate.


Assuntos
Proliferação de Células , Fissura Palatina , Células-Tronco Mesenquimais , Metiltransferases , Palato , Tretinoína , Animais , Fissura Palatina/genética , Fissura Palatina/metabolismo , Fissura Palatina/patologia , Tretinoína/farmacologia , Camundongos , Metiltransferases/metabolismo , Metiltransferases/genética , Proliferação de Células/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Palato/embriologia , Palato/metabolismo , Palato/patologia , Palato/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Feminino , Regulação para Cima/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Adenosina/análogos & derivados , Adenosina/metabolismo
18.
Support Care Cancer ; 32(4): 237, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509239

RESUMO

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/complicações , Qualidade de Vida , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Exame Físico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
19.
Inorg Chem ; 63(11): 5167-5174, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38442484

RESUMO

Exploring highly effective bifunctional electrocatalysts with surface structural advantages and synergistic optimization effects among multimetals is greatly important for overall water splitting. Herein, we successfully synthesized Pt-loaded NiFe-metal-organic framework nanosheet arrays grown on nickel foam (Pt-NiFe-MOF/NF) via a facile hydrothermal-electrodeposition process. Benefiting from large exposed specific surface, optimal electrical conductivity and efficient metal-support interaction endow Pt-NiFe-MOF/NF with highly catalytic performance, exhibiting small overpotential of 261 mV toward oxygen evolution reaction and 125 mV toward hydrogen evolution reaction at a current density of 100 mA cm-2 in alkaline medium. More significantly, the assembled water electrolyzer comprising the Pt-NiFe-MOF/NF//Pt-NiFe-MOF/NF couple demands a low cell voltage of 1.45 V to reach 10 mA cm-2. This work renders a viable approach to design dual-functional electrocatalysts with exceptional electrocatalytic activity and stability at high current density, showing the great prospect of water electrolysis for commercial application.

20.
Mol Cell Endocrinol ; 587: 112200, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38518841

RESUMO

OBJECTIVE: Myocardial injuries resulting from hypoxia are a significant concern, and this study aimed to explore potential protective strategies against such damage. Specifically, we sought to investigate the cardioprotective effects of 16α-hydroxyestrone (16α-OHE1). METHODS: Male Sprague‒Dawley (SD) rats were subjected to hypoxic conditions simulating high-altitude exposure at 6000 m in a low-pressure chamber for 7 days. Before and during hypoxic exposure, estradiol (E2) and various doses of 16α-OHE1 were administered for 14 days. Heart weight/body weight (HW/BW), myocardial structure, Myocardial injury indicators and inflammatory infiltration in rats were measured. H9C2 cells cultured under 5% O2 conditions received E2 and varying doses of 16α-OHE1; Cell viability, apoptosis, inflammatory infiltration, and Myocardial injury indicators were determined. Expression levels of ß2AR were determined in rat hearts and H9C2 cells. The ß2AR inhibitor, ICI 118,551, was employed to investigate ß2AR's role in 16α-OHE1's cardioprotective effects. RESULTS: Hypoxia led to substantial myocardial damage, evident in increased heart HW, CK-MB, cTnT, ANP, BNP, structural myocardial changes, inflammatory infiltration, and apoptosis. Pre-treatment with E2 and 16α-OHE1 significantly mitigated these adverse changes. Importantly, the protective effects of E2 and 16α-OHE1 were associated with the upregulation of ß2AR expression in both rat hearts and H9C2 cells. However, inhibition of ß2AR by ICI 118,551 in H9C2 cells nullified the protective effect of 16α-OHE1 on myocardium. CONCLUSION: Our findings suggest that 16α-OHE1 can effectively reduce hypoxia-induced myocardial injury in rats through ß2ARs, indicating a promising avenue for cardioprotection.


Assuntos
Hidroxiestronas , Inflamação , Propanolaminas , Masculino , Animais , Ratos , Hidroxiestronas/farmacologia , Ratos Sprague-Dawley , Miocárdio , Receptores Adrenérgicos
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