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1.
ACS Omega ; 9(28): 30654-30664, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39035926

RESUMO

Currently, research on enhancing imbibition oil recovery in tight oil reservoirs through the ion-tuning technique remains limited. Two critical parameters for capillary imbibition are the wettability and interfacial tension between oil and water. In this investigation, we manipulate the properties of two types of formation water for both aged and unaged samples by diluting brine and altering ion composition. Subsequently, we employ captive and pendant-drop methods to assess rock wettability and interfacial tension under varied brine conditions. Additionally, we elucidate the primary mechanisms underlying changes in rock wettability and interfacial tension. Meanwhile, we analyze capillarity characteristics and assess the relative significance of wettability and interfacial tension. Results indicate that there is a critical interfacial tension with progressive dilution of two types of formation water. However, modifying ion composition leads to a complex trend in interfacial tension, which can be explained qualitatively through the Gibbs adsorption isotherm. For unaged samples, the contact angle demonstrates a pronounced water-wet characteristic, showing a nonmonotonic trend with respect to dilution times. Remarkably, the rock surface exhibits the strongest water-wet, particularly evident in the case of FW-10, largely influenced by variations in interfacial tension. Conversely, aged samples demonstrate strong oil-wet, with a critical salinity resulting in the lowest contact angle, while altering brine ion types can alter rock wettability from strongly oil-wet to intermediate-wet, which is not sufficient to result in the wettability alteration. The removal of multivalent cations is proposed as the most effective method for wettability modification. Furthermore, capillarity variations among different brine cases are primarily contingent upon contact angle changes, and interfacial tension does not have a significant change when regulating the brine properties. Consequently, we emphasize the significance of wettability in the adoption of ion-tuned brine techniques for tight oil reservoirs. Overall, our study underscores the potential of reasonably regulating brine properties to enhance capillarity and, thereby, improve imbibition oil recovery.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39042094

RESUMO

The development of an artificial ligament with a multifunction of promoting bone formation, inhibiting bone resorption, and preventing infection to obtain ligament-bone healing for anterior cruciate ligament (ACL) reconstruction still faces enormous challenges. Herein, a novel artificial ligament based on a PI fiber woven fabric (PIF) was fabricated, which was coated with a phytic acid-gallium (PA-Ga) network via a layer-by-layer assembly method (PFPG). Compared with PIF, PFPG with PA-Ga coating significantly suppressed osteoclastic differentiation, while it boosted osteoblastic differentiation in vitro. Moreover, PFPG obviously inhibited fibrous encapsulation and bone absorption while accelerating new bone regeneration for ligament-bone healing in vivo. PFPG remarkably killed bacteria and destroyed biofilm, exhibiting excellent antibacterial properties in vitro as well as anti-infection ability in vivo, which were ascribed to the release of Ga ions from the PA-Ga coating. The cooperative effect of the surface characteristics (e.g., hydrophilicity/surface energy and protein absorption) and sustained release of Ga ions for PFPG significantly enhanced osteogenesis while inhibiting osteoclastogenesis, thereby achieving ligament-bone integration as well as resistance to infection. In summary, PFPG remarkably facilitated osteoblastic differentiation, while it suppressed osteoclastic differentiation, thereby inhibiting osteoclastogenesis for bone absorption while accelerating osteogenesis for ligament-bone healing. As a novel artificial ligament, PFPG represented an appealing option for graft selection in ACL reconstruction and displayed considerable promise for application in clinics.

3.
Anal Chem ; 96(27): 11009-11017, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38934578

RESUMO

Zero-depth interfacial nanopores, which are formed by two crossed nanoscale channels at their intersection interface, have been proposed to increase the spatial resolution of solid-state nanopores. However, research on zero-depth interfacial nanopores is still in its early stages. Although it has been shown that the current passing through an interfacial nanopore is largely independent of the membrane thickness, existing studies have not fully considered the impact of membrane thickness on other ion transport characteristics within these nanopores. In this paper, we investigate the electrokinetic ion transport phenomenon in the zero-depth interfacial nanopores, especially focusing on the influence of membrane thickness on the ion transport phenomenon. Our model incorporates the Poisson-Nernst-Planck equations and the Navier-Stokes equations, featuring a pH-regulated surface charge density. We find that when the thickness of the nanochannels is close to the interface size of the formed interfacial nanopore, the phenomenon of ion transport in the interfacial nanopore is similar to that in a conventional cylindrical nanopore. However, when the thickness of the nanochannels is much greater than the interface size of the formed interfacial nanopore, several distinct phenomena occur. The surface charge density on the inner walls of the interfacial nanopores has a small peak at the interface of the two crossing nanochannels, and the anion concentration changes greatly between the two nanochannels; that is, a much greater anion concentration forms in the nanochannel near the anode side than in the nanochannel near the cathode side. When the surface charge is nonzero, the electric field within the interfacial nanopore creates three extreme points, and the directions of the local electric fields are opposite at the ends of the membrane.

4.
J Immunol Res ; 2024: 3604935, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774604

RESUMO

Objective: Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. Materials and Methods: The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-α, IL-1ß, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results: When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1ß, IL-2R, IL-10, IL-17, and TNF-α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. Conclusion: Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy.


Assuntos
Biomarcadores Tumorais , Inibidores de Checkpoint Imunológico , Interleucina-6 , Interleucina-8 , Receptor de Morte Celular Programada 1 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Neoplasias Gástricas/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/sangue , Inibidores de Checkpoint Imunológico/uso terapêutico , Interleucina-6/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Interleucina-8/sangue , Estudos Retrospectivos , Resultado do Tratamento , Adulto , Prognóstico , Imunoterapia/métodos , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
Cell Rep Med ; 5(5): 101550, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38723624

RESUMO

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor ß to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.


Assuntos
Linfócitos T CD8-Positivos , Senescência Celular , Quimiorradioterapia , Recidiva Local de Neoplasia , Neoplasias do Colo do Útero , Humanos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/tratamento farmacológico , Quimiorradioterapia/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/genética , Animais , Camundongos , Linhagem Celular Tumoral , Prognóstico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Fator de Crescimento Transformador beta/metabolismo , Senescência de Células T
7.
Stem Cell Rev Rep ; 20(5): 1285-1298, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38598065

RESUMO

Our previous studies have highlighted the pivotal role of gastric cancer mesenchymal stem cells (GCMSCs) in tumor initiation, progression, and metastasis. In parallel, it is well-documented that endothelial cells (ECs) undergo functional alterations in response to challenging tumor microenvironment. This study aims to elucidate whether functional changes in ECs might be induced by GCMSCs and thus influence cancer progression. Cell proliferation was assessed through CCK-8 and colony formation assays, while cell migration and invasion capabilities were evaluated by wound-healing and Transwell assays. Immunohistochemistry was employed to examine protein distribution and expression levels. Additionally, quantitative analysis of protein and mRNA expression was carried out through Western blotting and qRT-PCR respectively, with gene knockdown achieved using siRNA. Our findings revealed that GCMSCs effectively stimulate cell proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs), both in vitro and in vivo. GCMSCs promote the migration and invasion of gastric cancer cells by inducing the expression of Slit2 in HUVECs. Notably, the inhibition of phosphorylated AKT partially mitigates the aforementioned effects. In conclusion, GCMSCs may exert regulatory control over Slit2 expression in ECs via the AKT signaling pathway, thereby inducing functional changes in ECs that promote tumor progression.


Assuntos
Movimento Celular , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana , Células-Tronco Mesenquimais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proliferação de Células/genética , Animais , Progressão da Doença , Linhagem Celular Tumoral , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Microambiente Tumoral , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas do Tecido Nervoso
8.
J Clin Neurosci ; 123: 209-215, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38626528

RESUMO

BACKGROUND: Endoscopic surgery has shown promise in treating Spontaneous Intracerebral Hemorrhage (sICH), but its adoption in county-level hospitals has been hindered by the high level of surgical expertise required. METHODS: In this retrospective study at a county hospital, we utilized a Cumulative Sum (CUSUM) control chart to visualize the learning curve for two neurosurgeons. We compared patient outcomes in the learning and proficient phases, and compared them with expected outcomes based on ICH score and ICH functional outcome score, respectively. RESULTS: The learning curve peaked at the 12th case for NS1 and the 8th case for NS2, signifying the transition to the proficient stage. This stage saw reductions in operation time, blood loss, rates of evacuation < 90 %, rebleeding rates, intensive care unit stay, hospital stay, and overall costs for both neurosurgeons. In the learning stage, 6 deaths occurred within 30 days, less than the 10.66 predicted by the ICH score. In the proficient stage, 3 deaths occurred, less than the 15.88 predicted. In intermediate and high-risk patients by the ICH functional outcome score, the proficient stage had fewer patients with an mRS ≥ 3 at three months than the learning stage (23.8 % vs. 69.2 %, P = 0.024; 40 % vs. 80 %, P = 0.360). Micromanipulating bipolar precision hemostasis and aspiration devices in the endoport's channels sped up the transition from learning to proficient. CONCLUSION: The data shows a learning curve, with better surgical outcomes as surgeons gain proficiency. This suggests cost benefits of surgical proficiency and the need for ongoing surgical education and training in county hospitals.


Assuntos
Hemorragia Cerebral , Curva de Aprendizado , Neuroendoscopia , Humanos , Estudos Retrospectivos , Hemorragia Cerebral/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neuroendoscopia/métodos , Neuroendoscopia/educação , Hospitais de Condado , Resultado do Tratamento , Neurocirurgiões/educação , Competência Clínica
9.
Sensors (Basel) ; 24(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38610321

RESUMO

The sensitivity and accuracy of nanopore sensors are severely hindered by the high noise associated with solid-state nanopores. To mitigate this issue, the deposition of organic polymer materials onto silicon nitride (SiNx) membranes has been effective in obtaining low-noise measurements. Nonetheless, the fabrication of nanopores sub-10 nm on thin polymer membranes remains a significant challenge. This work proposes a method for fabricating nanopores on polymethyl methacrylate (PMMA) membrane by the local high electrical field controlled breakdown, exploring the impact of voltage and current on the breakdown of PMMA membranes and discussing the mechanism underlying the breakdown voltage and current during the formation of nanopores. By improving the electric field application method, transient high electric fields that are one-seven times higher than the breakdown electric field can be utilized to fabricate nanopores. A comparative analysis was performed on the current noise levels of nanopores in PMMA-SiNx composite membranes and SiNx nanopores with a 5 nm diameter. The results demonstrated that the fast fabrication of nanopores on PMMA-SiNx membranes exhibited reduced current noise compared to SiNx nanopores. This finding provides evidence supporting the feasibility of utilizing this technology for efficiently fabricating low-noise nanopores on polymer composite membranes.

10.
BMC Med Genomics ; 17(1): 69, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443946

RESUMO

Recent evidence has shed light on the significant role of FANCD2 in cancer initiation, development, and progression. However, a comprehensive pan-cancer analysis of FANCD2 has been lacking. In this study, we have conducted a thorough investigation into the expression profiles and prognostic significance of FANCD2, as well as its correlation with clinicopathological parameters and immune cell infiltration, using advanced bioinformatic techniques. The results demonstrate that FANCD2 is significantly upregulated in various common cancers and is associated with prognosis. Notably, higher expression levels of FANCD2 are linked to poor overall survival, as indicated by Cox regression and Kaplan-Meier analyses. Additionally, we have observed a decrease in the methylation of FANCD2 DNA in some cancers, and this decrease is inversely correlated with FANCD2 expression. Genetic alterations in FANCD2 predominantly manifest as mutations, which are associated with overall survival, disease-specific survival, disease-free survival, and progression-free survival in certain tumor types. Moreover, FANCD2 exhibits a strong correlation with infiltrating cell levels, immune checkpoint genes, tumor mutation burden (TMB), and microsatellite instability (MSI). Enrichment analysis further highlights the potential impact of FANCD2 on Fanconi anemia (FA) pathway and cell cycle regulation. Through this comprehensive pan-cancer analysis, we have gained a deeper understanding of the functions of FANCD2 in oncogenesis and metastasis across different types of cancer.


Assuntos
Anemia de Fanconi , Humanos , Prognóstico , Carcinogênese/genética , Transformação Celular Neoplásica , Cognição , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética
11.
Signal Transduct Target Ther ; 9(1): 73, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528050

RESUMO

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).


Assuntos
Anticorpos Monoclonais Humanizados , Piridinas , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Oxaliplatina , Piridinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Quimioterapia Combinada/métodos
12.
Eur J Clin Microbiol Infect Dis ; 43(5): 829-840, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38388738

RESUMO

PURPOSE: The detection rate of Salmonella enterica serovar 1,4,[5], 12: i: - (S. 1,4,[5], 12: i: -) has increased as the most common serotype globally. A S. 1,4,[5], 12: i: - strain named ST3606 (sequence type 34), isolated from a fecal specimen of a child with acute diarrhea hospitalized in a tertiary hospital in China, was firstly reported to be resistant to carbapenem and ceftazidime-avibactam. The aim of this study was to characterize the whole-genome sequence of S. 1,4,[5], 12: i: - isolate, ST3606, and explore its antibiotic resistance genes and their genetic environments. METHODS: The genomic DNA of S. 1,4,[5], 12: i: - ST3606 was extracted and performed with single-molecule real-time sequencing. Resistance genes, plasmid replicon type, mobile elements, and multilocus sequence types (STs) of ST3606 were identified by ResFinder 3.2, PlasmidFinder, OriTfinder database, ISfinder database, and MLST 2.0, respectively. The conjugation experiment was utilized to evaluate the conjugation frequency of pST3606-2. Protein expression and enzyme kinetics experiments of CTX-M were performed to analyze hydrolytic activity of a novel CTX-M-261 enzyme toward several antibiotics. RESULTS: Single-molecule real-time sequencing revealed the coexistence of a 109-kb IncI1-Iα plasmid pST3606-1 and a 70.5-kb IncFII plasmid pST3606-2. The isolate carried resistance genes, including blaNDM-5, sul1, qacE, aadA2, and dfrA12 in pST3606-1, blaTEM-1B, aac(3)-lld, and blaCTX-M-261, a novel blaCTX-M-1 family member, in pST3606-2, and aac(6')-Iaa in chromosome. The blaCTX-M-261 was derived from blaCTX-M-55 by a single-nucleotide mutation 751G>A leading to amino acid substitution of Val for Met at position 251 (Val251Met), which conferred CTX-M increasing resistance to ceftazidime verified by antibiotics susceptibility testing of transconjugants carrying pST3606-2 and steady-state kinetic parameters of CTX-M-261. pST3606-1 is an IncI1-α incompatibility type that shares homology with plasmids of pC-F-164_A-OXA140, pE-T654-NDM-5, p_dm760b_NDM-5, and p_dmcr749c_NDM-5. The conjugation experiment demonstrated that pST3606-2 was successfully transferred to the Escherichia coli recipient C600 with four modules of OriTfinder. CONCLUSION: Plasmid-mediated horizontal transfer plays an important role in blaNDM-5 and blaCTX-M-261 dissemination, which increases the threat to public health due to the resistance to most ß-lactam antibiotics. This is the first report of blaCTX-M-261 and blaNDM-5 in S. 1,4,[5], 12: i: -. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of CTX-M enzymes and confirms urgency to control resistance of S. 1,4,[5], 12: i: -.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , Testes de Sensibilidade Microbiana , Infecções por Salmonella , Salmonella enterica , beta-Lactamases , Ceftazidima/farmacologia , Humanos , China , beta-Lactamases/genética , beta-Lactamases/metabolismo , Compostos Azabicíclicos/farmacologia , Antibacterianos/farmacologia , Salmonella enterica/genética , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/enzimologia , Infecções por Salmonella/microbiologia , Sequenciamento Completo do Genoma , Farmacorresistência Bacteriana Múltipla/genética , Sorogrupo , Plasmídeos/genética , Fezes/microbiologia , Genoma Bacteriano
13.
J Transl Med ; 22(1): 90, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254099

RESUMO

BACKGROUND: Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. METHODS: Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. RESULTS: CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. CONCLUSIONS: CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Herpesvirus Humano 4/genética , Biomarcadores , Imunoterapia , Instabilidade de Microssatélites , Microambiente Tumoral
14.
Oncoimmunology ; 13(1): 2303195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38235318

RESUMO

Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-ß signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias Gástricas , Humanos , Antígeno B7-H1/genética , Cromatina , Imunoterapia , Neoplasias Gástricas/patologia , Oncogenes/genética
15.
ACS Appl Mater Interfaces ; 16(3): 3187-3201, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38206677

RESUMO

Cancer pain seriously reduces the quality of life of cancer patients. However, most research about cancer focuses solely on inhibiting tumor growth, neglecting the issue of cancer pain. Therefore, the development of therapeutic agents with both tumor suppression and cancer pain relief is crucial to achieve human-centered treatment. Here, the work reports curcumin (CUR) and ropivacaine (Ropi) coincorporating CaCO3/PDA nanoparticles (CaPNMCUR+Ropi) that realized efficient tumor immunotherapy and cancer pain suppression. The therapeutic efficiency and mechanism are revealed in vitro and in vivo. The results indicate that CaPNMCUR+Ropi underwent tumor microenvironment-responsive degradation and realized rapid release of calcium ions, Ropi, and CUR. The excessive intracellular calcium triggered the apoptosis of tumor cells, and the transient pain caused by the tumor injection was relieved by Ropi. Simultaneously, CUR reduced the levels of immunosuppressive factor (TGF-ß) and inflammatory factor (IL-6, IL-1ß, and TNF-α) in the tumor microenvironment, thereby continuously augmenting the immune response and alleviating inflammatory pain of cancer animals. Meanwhile, the decrease of TGF-ß leads to the reduction of transient receptor potential vanilloid 1 (TRPV1) expression, thereby alleviating hyperalgesia and achieving long-lasting analgesic effects. The design of the nanosystem provides a novel idea for human-centered tumor treatment in the future.


Assuntos
Dor do Câncer , Curcumina , Indóis , Neoplasias , Polímeros , Animais , Humanos , Fator de Crescimento Transformador beta , Carbonato de Cálcio , Dor do Câncer/tratamento farmacológico , Cálcio , Qualidade de Vida , Ropivacaina/uso terapêutico , Neoplasias/tratamento farmacológico , Curcumina/uso terapêutico , Imunoterapia , Microambiente Tumoral
16.
Bioelectrochemistry ; 157: 108651, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38281367

RESUMO

Due to the wide range of electrochemical devices available, DNA nanostructures and material-based technologies have been greatly broadened. They have been actively used to create a variety of beautiful nanostructures owing to their unmatched programmability. Currently, a variety of electrochemical devices have been used for rapid sensing of biomolecules and other diagnostic applications. Here, we provide a brief overview of recent advances in DNA-based biomolecular assays. Biosensing platform such as electrochemical biosensor, nanopore biosensor, and field-effect transistor biosensors (FET), which are equipped with aptamer, DNA walker, DNAzyme, DNA origami, and nanomaterials, has been developed for amplification detection. Under the optimal conditions, the proposed biosensor has good amplification detection performance. Further, we discussed the challenges of detection strategies in clinical applications and offered the prospect of this field.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Nanoporos , Nanoestruturas , Técnicas Eletroquímicas/métodos , DNA/química , Nanoestruturas/química , DNA Catalítico/química , Técnicas Biossensoriais/métodos
17.
Ann Biomed Eng ; 52(3): 462-466, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37500980

RESUMO

Artificial intelligence (AI) has been driving the continuous development of the Physical Medicine and Rehabilitation (PM&R) fields. The latest release of ChatGPT/GPT-4 has shown us that AI can potentially transform the healthcare industry. In this study, we propose various ways in which ChatGPT/GPT-4 can display its talents in the field of PM&R in future. ChatGPT/GPT-4 is an essential tool for Physiatrists in the new era.


Assuntos
Inteligência Artificial , Medicina Física e Reabilitação , Exame Físico
19.
Neurosurg Rev ; 47(1): 2, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057420

RESUMO

Supratentorial spontaneous intracerebral hemorrhage (SICH) can be treated with endoscopic surgery, but the optimal timing remains uncertain. We retrospectively analyzed data from 46 patients who underwent endoscopic surgery for supratentorial SICH. We examined the relationship between time to evacuation and functional outcome at 3 months, adjusting for prognostic factors. Surgical outcomes and complications were compared between patients with early (≤ 12 h) or late (> 12 h) evacuation. Median time to evacuation was 12 h, and the rate of unfavorable outcome (modified Rankin Scale > 3 at 3 months) was 32.6%. Longer time to evacuation was independently associated with unfavorable outcome (odds ratio per hour delay: 1.26). Late evacuation carried a 7.25-fold higher risk of unfavorable outcome compared to early evacuation. This association held across subgroups based on hematoma volume, location, and intraventricular extension (P for interaction > 0.05). Patients with late evacuation had fewer spot signs (24% vs. 4.8%, P = 0.035) and markers of hemorrhagic expansion (36% vs. 9.5%, P = 0.018), longer neurosurgical intensive care unit (NSICU) stay (3.2 vs. 1.9 days, P = 0.011) and hospital stay (15.7 vs. 11.9 days, P = 0.014), and higher 30-day mortality (28.6 vs. 4%, P = 0.036) and complication rates (57.1% vs. 28.0%, P = 0.023). This study suggests a potential association between early endoscopic evacuation of supratentorial SICH and improved functional outcomes, lower 30-day mortality and reduced complications. The need for timely intervention in managing supratentorial SICH is highlighted, yet further validation through multi-center prospective studies is essential to substantiate these findings and provide a higher level of evidence.


Assuntos
Hemorragia Cerebral , Endoscopia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Estudos Prospectivos , Hemorragia Cerebral/complicações , Hematoma/cirurgia , Hematoma/diagnóstico
20.
Trends Analyt Chem ; 1622023 May.
Artigo em Inglês | MEDLINE | ID: mdl-38106545

RESUMO

Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic Covid-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.

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