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1.
Eur J Radiol ; 176: 111516, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38772162

RESUMO

OBJECTIVES: This study aimed to compare the safety and effectiveness of percutaneous endobiliary radiofrequency ablation with stent placement (RFA group) versus stent placement alone (stent group) in patients with type IV hilar cholangiocarcinoma. METHODS: This prospective nonrandomized study was conducted between October 2021 and April 2023. The study included 56 participants (33 men and 23 women, median age 73 years) who underwent percutaneous endobiliary RFA with stent placement (n = 25) or stent placement alone (n = 31) for type IV hilar cholangiocarcinoma. The primary end point was stent patency, while the secondary end points were procedure-related adverse events (AE) and overall survival. RESULTS: The percutaneous endobiliary RFA and/or stent placement were successfully completed in all patients in both groups. The median stent patency rate was higher in the RFA group than the stent group (188 days vs. 155 days, p = 0.048). There were no differences in AEs (grade 1 [5 in RFA group vs. 5 in stent group, p = 0.74] and grade 2 AEs [2 vs. 4, p = 0.68]) and patients' survival (median 222 days vs. 214 days, p = 0.49) between the two groups. CONCLUSIONS: In patients with type IV hilar cholangiocarcinoma, percutaneous endobiliary RFA with stent placement may improve stent patency without increasing the risk of AEs compared to stent placement alone.

2.
Chin Clin Oncol ; 13(2): 25, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38711178

RESUMO

BACKGROUND AND OBJECTIVE: Well-differentiated pancreatic neuroendocrine tumors (pNETs) are a group of rare, heterogeneous tumors that originate in the endocrine tissue of the pancreas and account for 1-2% of all pancreatic neoplasms. The majority of pNETs are non-functional and typically follow a more indolent course. Especially at early stages, the primary management of pNETs is surgical resection which is associated with relatively low rates of recurrence and excellent long-term prognosis. On the other hand, some patients will present with locally advanced primary tumors or low volume metastatic disease in which complete surgical resection may be more difficult to achieve and recurrence rates are significant. Unlike treatment of borderline resectable (BR) pancreatic adenocarcinoma, in which neoadjuvant treatment strategies are becoming standardized, borderline resectability is not a currently established terminology for pNETs and the optimal multidisciplinary treatment approach is poorly understood. METHODS: We performed a literature search on PubMed, Google Scholar, and ClinicalTrials.gov using keywords, including 'pancreatic neuroendocrine tumor' and 'borderline resectable'. All studies and review articles in English with full text were considered. Each publication was independently reviewed. KEY CONTENT AND FINDINGS: We introduce the concept of BR-pNETs, focusing on important criteria that should be included in their definition by balancing the feasibility of resection and the clinical utility of surgery. We suggest that extended resection, involving vascular reconstruction, adjacent organ resection, and/or liver metastasis, should be considered at experienced, high volume centers. Furthermore, we outline multidisciplinary treatment strategies, including systemic and locoregional treatment options, for optimizing outcomes for this growing patient population. CONCLUSIONS: Formalizing the definition of resectability in pNETs through multidisciplinary collaborative research will be important for standardizing the indications for multimodality treatment and aggressive surgical approaches for patients.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/cirurgia
3.
J Liver Cancer ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741422

RESUMO

Background/Aim: To evaluate the safety and effectiveness of superselective ablative chemoethanol embolization (SACE) for the treatment of patients with recurrent single hepatocellular carcinoma (rHCC). Materials and Methods: This retrospective study included 22 patients (19 men, median age 63 [range 38-86 y]) with Child-Pugh class of A/B/C (16/3/3) that underwent SACE between January and June 2023 for recurrent single HCCs measuring ≤ 5 cm in diameter using a mixture of 99% Ethanol and ethiodized oil/doxorubicin emulsion. The primary endpoint was the 6-month tumor response, and the secondary endpoints were the 1-month tumor response and treatment-related safety. This study was approved by our institutional review board, and the requirement for informed consent was waived. Results: SACE was successfully performed in 22 (95.2%) patients. The complete response rates at 1-month and 6-month after treatment were 100% and 83.3%, respectively. At 6-month, local tumor progression occurred in one patient and intrahepatic distant metastasis was found in 6 (30%) patients. No 6-month mortalities were reported. No adverse events greater than grade 2 or laboratory deteriorations were observed. Biliary complications or liver abscesses were not observed. Conclusion: SACE for a single rHCC was highly effective in achieving a favorable 6-month tumor response and showed acceptable adverse events. However, further prospective studies are required to verify these findings.

4.
Plant J ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507319

RESUMO

Rapid alkalinization factors (RALFs), belonging to a family of small secreted peptides, have been considered as important signaling molecules in diverse biological processes, including immunity. Current studies on RALF-modulated immunity mainly focus on Arabidopsis, but little is reported in crop plants. The rice immune receptor XA21 confers immunity to the bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo). Here, we pursued functional characterization of rice RALF26 (OsRALF26) up-regulated by Xoo during XA21-mediated immune response. When applied exogenously as a recombinant peptide, OsRALF26 induced a series of immune responses, including pathogenesis-related genes (PRs) induction, reactive oxygen species (ROS) production, and callose deposition in rice and/or Arabidopsis. Transgenic rice and Arabidopsis overexpressing OsRALF26 exhibited significantly enhanced resistance to Xoo and Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), respectively. In yeast two-hybrid, pull-down assays, and co-immunoprecipitation analyses, rice FER-like receptor 1 (OsFLR1) was identified as a receptor of OsRALF26. Transient expression of OsFLR1 in Nicotiana benthamiana leaves displayed significantly increased ROS production and callose deposition after OsRALF26 treatment. Together, we propose that OsRALF26 induced by Xoo in an XA21-dependent manner is perceived by OsFLR1 and may play a novel role in the enforcement of XA21-mediated immunity.

5.
J Nat Prod ; 87(4): 966-975, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38441877

RESUMO

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.


Assuntos
Aspergillus , Imunossupressores , Aspergillus/química , Humanos , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Estrutura Molecular , Cristalografia por Raios X , Interleucina-6/metabolismo , Antraquinonas/farmacologia , Antraquinonas/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Linfócitos T/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos
6.
Biosens Bioelectron ; 254: 116195, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38479341

RESUMO

The fluorescence-quenching method is crucial in vitro analysis, particularly for immunochromatographic test strips (ICTs) using noble metal nanoparticles as probes. However, ICTs still fall short in meeting the requirements for the detection of traces biomarkers due to the noble metal nanoparticles can only quench fluorescence of the dyes within a confined distance. Interestingly, noble metal nanoparticles, such as Pt NPs cannot only perform fluorescence-quenching ability based on the Förster resonance energy transfer (FRET), but also show perfect oxidase-like catalytic performance on many kinds of substrates, such as 3,3',5,5' -tetramethylbenzidine (TMB). We observed that the oxTMB (the oxidation products of TMB) exhibited notable effectiveness in quenching Cy5 fluorescence by the strong inner filter effect (IFE), which obviously improved the fluorescence-quenching efficiency with extremely low background signal. Through the dual-enhanced fluorescence quenching mechanism, the fluorescence quenching constant (Kn) was 661.24-fold that of only Pt NPs on the NC membrane. To validate the feasibility of this technique, we employed two types of biomarkers, namely microRNA (miR-15a-5p) and the signature protein (PSA). The sensitivity of miR-15a-5p was 9.286 × 10-18 mol/L and 17.5-fold more than that based on Pt NPs. As for the PSA, the LOD (0.6265 pg/mL) was 15.5-fold enhancement more sensitive after catalysis. Overall, the dual-enhanced fluorescence quenching rFICTs could act as a practical detection for biomarker in real samples.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Nanopartículas Metálicas/química , Transferência Ressonante de Energia de Fluorescência , Biomarcadores
7.
Cornea ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377438

RESUMO

PURPOSE: Surgery for pseudopterygia in Fuchs superficial marginal keratitis (FSMK) bears the risk of corneal perforation, as described in a few case reports. The aim of this case series was to understand the clinical course and surgical outcomes of pseudopterygia in FSMK. METHODS: A retrospective case series included patients meeting FSMK criteria with pseudopterygia in at least 1 eye. The severity grading of pseudopterygia and peripheral infiltration events at follow-up were analyzed. Pseudopterygia involving corneal central 3 mm diameter (grade III) received surgery. Peripheral corneal infiltrate events within 1 week after surgery were recorded. RESULTS: Thirty-three eyes of 19 patients (8 men, 11 women; age 40-85 years; mean, 65 years) were included, with an average 48.1-month follow-up (range 0-188.8 months). At presentation, 7 eyes (21%) had grade III pseudopterygia. One patient showed corneal perforation 3 days after "pterygium" surgery elsewhere. The contralateral eye met the diagnosis of FSMK. During follow-up, 16 eyes (49%) exhibited peripheral corneal infiltrates, and 7 eyes (21%) showed progression of pseudopterygia to higher grades before or without any surgery. Ten eyes with grade III pseudopterygia underwent surgery. The best-corrected visual acuity in Logarithm of the Minimum Angle of Resolution improved from 0.34 ± 0.18 (range 0.05-0.52) to 0.13 ± 0.11 (range 0.05-0.4) (P = 0.0023). Six eyes (60%) developed peripheral corneal infiltrates within 1 week after surgery, which responded well to topical corticosteroids. CONCLUSIONS: Pseudopterygia in FSMK may progress to threaten visual acuity. Surgical excision can be safe and can effectively improve vision on the condition that the patients are closely followed in the early postoperative period to notice the corneal infiltrates.

8.
Clin Orthop Surg ; 16(1): 141-148, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38304214

RESUMO

Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the three-dimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computer-aided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions: We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.


Assuntos
Tornozelo , Osteoartrite , Humanos , Radiografia , Articulação do Tornozelo/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Suporte de Carga , Computadores , Reprodutibilidade dos Testes
9.
Nanomedicine (Lond) ; 19(2): 145-161, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38270976

RESUMO

Aim: This study aimed to develop a sonodynamic-chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper-cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4+ and CD8+ T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.


Assuntos
Nanopartículas Multifuncionais , Nanopartículas , Neoplasias , Feminino , Animais , Camundongos , Linfócitos T CD8-Positivos , Cobre , Cisteína , Glutationa , Imunoterapia , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de Hidrogênio
10.
Exp Ther Med ; 27(2): 80, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38274341

RESUMO

MicroRNAs (miRs) have been found to play a fundamental role in the pathology and progression of hemangioma. Of note, miR-203a-3p prevents hemangioma progression via inactivation of the PI3K/AKT pathway. Bleomycin and pingyangmycin are drugs used in sclerotherapy, but certain hemangioma patients experience drug resistance, leading to poor clinical outcomes. The present study aimed to explore the impact of miR-203a-3p on bleomycin and pingyangmycin sensitivity in hemangioma, as well as the involvement of the PI3K/AKT pathway. miR-203a-3p or negative control mimics were transfected into human hemangioma endothelial cells, which were treated with 0-20 µM bleomycin or pingyangmycin. Subsequently, 740 Y-P, a PI3K/AKT pathway agonist, was added. Cell viability, rate of apoptosis and the expression levels of proteins involved in the PI3K/AKT pathway, including phosphorylated (p)-PI3K, PI3K, p-AKT and AKT, were detected. miR-203a-3p overexpression significantly decreased the half-maximal inhibitory concentration (IC50) values of bleomycin (5.84±0.87 vs. 14.23±2.17 µM; P<0.01) and pingyangmycin (5.13±0.55 vs. 12.04±1.86 µM; P<0.01), compared with untreated cells. In addition, under bleomycin or pingyangmycin treatment, miR-203a-3p overexpression significantly reduced the proportion of EdU positive cells (both P<0.05) and B-cell leukemia/lymphoma-2 (BCL2) protein expression levels (both P<0.05), whilst increasing cell apoptosis rate (both P<0.05) and cleaved caspase 3 protein expression levels (both P<0.05) compared with untreated controls. Furthermore, miR-203a-3p overexpression significantly inhibited the phosphorylation of PI3K and AKT (both P<0.05), an effect that was significantly diminished by 740 Y-P treatment (both P<0.01). In addition, 740 Y-P significantly increased IC50 values of bleomycin (P<0.01) and pingyangmycin (P<0.001) and also significantly increased the proportion of EdU-positive cells and BCL2 protein expression levels, while decreasing the apoptosis rate and cleaved caspase 3 protein expression levels in cells treated with bleomycin or pingyangmycin (all P<0.05). Of note, 740 Y-P weakened the effect of miR-203a-3p overexpression on the aforementioned cellular characteristics. The present study demonstrated that miR-203a-3p improved the sensitivity of cells to bleomycin and pingyangmycin treatment by inhibiting PI3K/AKT signaling in hemangioma.

11.
Small ; : e2310248, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38234145

RESUMO

Interfering with intratumoral metabolic processes is proven to effectively sensitize different antitumor treatments. Here, a tumor-targeting catalytic nanoplatform (CQ@MIL-GOX@PB) loading with autophagy inhibitor (chloroquine, CQ) and glucose oxidase (GOX) is fabricated to interfere with the metabolisms of tumor cells and tumor-associated macrophages (TAMs), then realizing effective antitumor chemodynamic therapy (CDT). Once accumulating in the tumor site with the navigation of external biotin, CQ@MIL-GOX@PB will release Fe ions and CQ in the acid lysosomes of tumor cells, the latter can sensitize Fe ions-involved antitumor CDT by blocking the autophagy-dependent cell repair. Meanwhile, the GOX component will consume glucose, which not only generates many H2 O2 for CDT but also once again decelerates the tumor repair process by reducing energy metabolism. What is more, the release of CQ can also drive the NO anabolism of TAMs to further sensitize CDT. This strategy of multiple metabolic regulations is evidenced to significantly improve the antitumor effect of traditional CDT nanoagents and might provide a new sight to overcome the bottlenecks of different antitumor treatments.

12.
World J Clin Cases ; 11(34): 8153-8157, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38130782

RESUMO

BACKGROUND: Hepatic artery obstruction is a critical consideration in graft outcomes after living donor liver transplantation. We report a case of diffuse arterial vasospasm that developed immediately after anastomosis and was managed with an intra-arterial infusion of lipo-prostaglandin E1 (PGE1). CASE SUMMARY: A 57-year-old male with hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma underwent ABO-incompatible living donor liver transplant. The grafted hepatic artery was first anastomosed to the recipient's right hepatic artery stump. However, the arterial pulse immediately weakened. Although a new anastomosis was performed using the right gastroepiploic artery, the patient's arterial pulse rate remained poor. We attempted angiographic intervention immediately after the operation; it showed diffuse arterial vasospasms like 'beads on a string'. We attempted continuous infusion of lipo-PGE1 overnight via an intra-arterial catheter. The next day, arterial flow improved without any spasms or strictures. The patient had no additional arterial complications or related sequelae at the time of writing, 1-year post-liver transplantation. CONCLUSION: Angiographic evaluation is helpful in cases of repetitive arterial obstruction, and intra-arterial infusion of lipo-PGE1 may be effective in treating diffuse arterial spasms.

13.
Sci Rep ; 13(1): 22288, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38097801

RESUMO

The aim of this study is to determine whether contrast-enhanced computed tomography (CECT)-based texture parameters can predict high (> 30 Gy) expected lung dose (ELD) calculated using 99mTc macroaggregated albumin single-photon emission computed tomography/computed tomography (SPECT/CT) for pre-trans-arterial radioembolization (TARE) dosimetry. 35 patients were analyzed, with a treatable planned dose of ≥ 200 Gy for unresectable hepatocellular carcinoma (HCC). Lung shunt fraction (LSF) was obtained from planar and SPECT/CT scans. Texture features of the tumor lesion on CECT before TARE were analyzed. Univariate and multivariate linear regression analyses were performed to determine potential ELD > 30 Gy predictors. Among the 35 patients, nine (25.7%) had ELD > 30 Gy, and had a higher LSF than the ELD ≤ 30 Gy group using the planar (20.7 ± 8.0% vs. 6.3 ± 3.3%; P < 0.001) and SPECT/CT (12.4 ± 5.1% vs. 3.5 ± 2.0%; P < 0.001) scans. The tumor integral total (HU × L) value was a predictor for high LSF using SPECT/CT, with an area under the curve, sensitivity, and specificity of 0.983 (95% confidence interval: 0.869-1.000, P < 0.001), 100%, and 88.5%, respectively. The tumor integral total value is an imaging marker for predicting ELD > 30 Gy. Applying CECT texture analysis may assist in reducing time and cost in patient selection and modifying TARE treatment plans.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Radioisótopos de Ítrio/uso terapêutico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Embolização Terapêutica/métodos , Pulmão , Albuminas , Tomografia Computadorizada de Emissão de Fóton Único , Estudos Retrospectivos
14.
J Cancer Res Ther ; 19(6): 1646-1653, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38156933

RESUMO

BACKGROUND: Ferroptosis is a novel subtype of programmed cell death caused by iron-dependent lipid peroxidation and excessive reactive oxygen species (ROS) production. Small-molecule ferroptotic drugs have the probability of selectively targeting the specific features of aggressive tumor cells. In particular, pseudolaric acid B (PAB) triggered ferroptosisin breast cancer cells. The aim of this study is to explore the antitumor effect of PAB on A549 cells and provide a theoretical basis for the further development and clinical application of PAB. METHODS: First, relevant databases were used to predict of target genes related to PAB, Then, EdU proliferation assay, colony formation and wound-healing assays were applied to calculate A549 cells proliferative abilities. Measurement of ferrous iron, lipid peroxidation, ROS, malondialdehyde (MDA) and glutathione (GSH) were utilized to explore the relevant mechanism. RESULTS: We showed that PAB decreased the viability of lung adenocarcinoma cells in vitro, which was accompanied by abnormally elevated levels of intracellular ferrous iron and overproduction of lipid reactive oxidate species (L-ROS). In turn, deferoxamine (DFO) significantly rescued PAB-induced lipid peroxidation. PAB also improved the intracellular labile iron pool by promoting ferritin autophagy via the upregulation of the nuclear receptor coactivator 4 (NCOA4). Moreover, silencing of NCOA4 alleviated PAB-inducedferroptotic death and reduced the levels of intracellular ferrous iron. CONCLUSIONS: In summary, PAB-triggered ferroptosis in lung adenocarcinoma cells by enhancing ferritinophagy. thus, PAB is a potential therapeutic agent for lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Ferroptose , Humanos , Espécies Reativas de Oxigênio/metabolismo , Ferro/metabolismo , Autofagia , Fatores de Transcrição/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Coativadores de Receptor Nuclear/metabolismo
15.
Int J Mol Sci ; 24(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37958901

RESUMO

Activation of mammalian target of rapamycin (mTOR) has been known as one of the contributing factors in nociceptive sensitization after peripheral injury. Its activation followed by the phosphorylation of downstream effectors causes hyperexcitability of primary sensory neurons in the dorsal root ganglion. We investigated whether a single injection of rAAV-shmTOR would effectively downregulate both complexes of mTOR in the long-term and glial activation as well. Male SD rats were categorized into shmTOR (n = 29), shCON (n = 23), SNI (n = 13), and Normal (n = 8) groups. Treatment groups were injected with rAAV-shmTOR or rAAV-shCON, respectively. DRG tissues and sciatic nerve were harvested for Western blot and immunohistochemical analyses. Peripheral sensitization was gradually attenuated in the shmTOR group, and it reached a peak on PID 21. Western blot analysis showed that both p-mTORC1 and p-mTORC2 were downregulated in the DRG compared to shCON and SNI groups. We also found decreased expression of phosphorylated p38 and microglial activation in the DRG. We first attempted a therapeutic strategy for neuropathic pain with a low dose of AAV injection by interfering with the mTOR signaling pathway, suggesting its potential application in pain treatment.


Assuntos
Neuralgia , Traumatismos do Sistema Nervoso , Ratos , Masculino , Animais , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Ratos Sprague-Dawley , Neuralgia/etiologia , Neuralgia/terapia , Neuralgia/metabolismo , Nervo Isquiático/metabolismo , Traumatismos do Sistema Nervoso/metabolismo , Sirolimo , Serina-Treonina Quinases TOR/metabolismo , Gânglios Espinais/metabolismo , Mamíferos
16.
Cancer Cell Int ; 23(1): 267, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946181

RESUMO

BACKGROUND: Disulfidptosis and Ferroptosis are two novel forms of cell death. Although their mechanisms differ, research has shown that there is a relationship between the two. Investigating the connection between these two forms of cell death can further deepen our understanding of the development and progression of cancer, and provide better prediction models for accurate prognosis. METHODS: In this study, RNA sequencing (RNA-seq) data, clinical data, single nucleotide polymorphism (SNP) data, and single-cell sequencing data were obtained from public databases. We used weighted gene co-expression network analysis (WGCNA) and unsupervised clustering to identify new Disulfidptosis/Ferroptosis-Related Genes (DFRG), and constructed a LASSO COX prognosis model that was externally validated. To further explore this novel signature, pathway and function analysis was performed, and differences in gene mutation frequency between high- and low-risk groups were studied. Importantly, we also conducted research on immune checkpoint, immune cell infiltration levels and immune resistance indicators, in addition to analyzing real clinical immunotherapy data. RESULTS: We have identified four optimal disulfidptosis/ferroptosis-related genes (ODFRGs) that are differentially expressed and associated with the prognosis of Lung Adenocarcinoma (LUAD). These genes include GMPR, MCFD2, MRPL13, and SALL2. Based on these ODFRGs, we constructed a robust prognostic model in this study, and the high-risk group showed significantly lower overall survival (OS) compared to the low-risk group. Furthermore, this model can also predict the immunotherapy outcomes of LUAD patients to some extent.

17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(5): 809-813, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37927022

RESUMO

Objective To assess the effects of different application sequences of neodymium-doped yttrium aluminum garnet(Nd∶YAG)laser and the desensitizing toothpaste containing stannous fluoride on dentinal tubule occlusion.Methods Twelve intact third molars freshly extracted from human were selected and prepared into dentin slices with a thickness of 0.8 mm.Each dentin slice was subdivided into four small slices,three of which were etched with 6% citric acid and randomly assigned to the following three groups(n=12):(1)control group:no treatment;(2)Nd∶YAG+toothbrushing(TB)group:first irradiated with Nd∶YAG laser and then brushed with desensitizing toothpaste;(3)TB+Nd∶YAG group:first brushed with desensitizing toothpaste and then irradiated with Nd∶YAG laser.The Nd∶YAG laser irradiation were carried out at 1 W,15 pulses/s,and the pulse width of 150 µs for 10 s(for a total of 6 cycles).After the above treatment,the 12 dentin slices from the Nd∶YAG+TB and TB+Nd∶YAG groups were randomly assigned to four subgroups(n=3)and subjected to acid etching in the Coca-Cola solution for 0,5,10,and 15 min.A scanning electron microscope was used to observe and photograph the dentin slices in each group,and eight single-blinded examiners scored the slices according to uniform criteria.The analysis of variance was carried out to compared the scores between groups.Results Before acid etching,the dentin tubule occlusion scores of the Nd∶YAG+TB and TB+Nd∶YAG groups were(4.83±0.09) scores and(3.85±0.66) scores,respectively,which had no significant difference between each other(P=0.0590)and were higher than that[(0.10±0.07)scores]of the control group(both P<0.0001).The dentin tubule occlusion scores of the Nd∶YAG+TB group after acid etching for 5,10,and 15 min were(4.33±0.60)scores,(4.27±0.24)scores,and(3.63±0.07)scores,respectively,which were not significantly different from those[(4.04±0.10)scores,(3.76±0.59)scores,and(3.17±0.29)scores,respectively]of the TB+Nd∶YAG group(all P>0.05).In the Nd∶YAG+TB subgroup,the dentin tubule occlusion score after acid etching for 15 min was significantly lower than that before acid etching(P=0.0011).In the TB+Nd∶YAG group,there was no statistically significant difference in the score between before and after acid etching(P>0.05).Conclusions Nd∶YAG laser irradiation with appropriate parameters combined with the use of desensitizing toothpaste could produce an excellent occluding effect on dentinal tubules regardless of the sequence.However,brushing with desensitizing toothpaste followed by Nd∶YAG laser irradiation produced more consistent dentin sealing after acid etching.


Assuntos
Sensibilidade da Dentina , Lasers de Estado Sólido , Humanos , Dentina , Sensibilidade da Dentina/terapia , Lasers de Estado Sólido/uso terapêutico , Microscopia Eletrônica de Varredura , Cremes Dentais/farmacologia
18.
J Clin Med ; 12(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37834870

RESUMO

Several methods have been introduced to measure the host bone coverage of the acetabular component after total hip arthroplasty (THA). The aims of this study were (1) to validate two-dimensional- and three-dimensional-based host bone coverage measurements by comparing intra-operative measurements, and (2) to determine the minimum host bone coverage for achieving stable cup fixation after THA in hip dysplasia. The clinical outcomes of each patient were evaluated during their final follow-up period using the Harris Hip score (HHS). The coverage of the host bone was analyzed by comparing 2D-based, 3D-based, and intraoperative assessments. The mean HHS was increased significantly from 60.84 ± 14.21 pre-operatively to 93.13 ± 4.59 (p < 0.0001). The host bone coverage ratio measured intraoperatively was 83.67 ± 3.40%, while the ratio measured by 3D CT reconstruction was 82.72 ± 3.59%. There was a strong positive correlation between the intra-operative host bone coverage and the 3D-based one (r = 0.826, p < 0.0001). It is recommended that 3D-based measurements are used to evaluate the host bone coverage after THA in patients with hip dysplasia. In addition, achieving a minimum host bone coverage of 75% is recommended for the attainment of stable cup fixation.

19.
Cancers (Basel) ; 15(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37835438

RESUMO

BACKGROUND AND OBJECTIVES: Although radiofrequency ablation (RFA) is a well-established locoregional treatment modality for hepatocellular carcinoma (HCC), the optimal strategy to handle local recurrence after ablation is still debated. This study aims to investigate the role of salvage hepatectomy (SH) as a rescue therapy for recurrent HCC after RFA. MATERIALS AND METHODS: Between January 2004 and December 2020, 1161 patients were subject to surgical resection for HCC. Among them, 47 patients who underwent SH for local recurrence after ablation were retrospectively analyzed and compared to a propensity score-matched group of controls (n = 47) who received primary hepatectomy (PH). Short-term and long-term outcomes were analyzed between the two groups. RESULTS: After matching, operation time, intraoperative blood loss, postoperative hospital stay, and postoperative morbidity rates showed no statistically significant difference. Tumors in the SH group were associated with poor differentiation (SH 9 (19.1%) vs. PH 1 (2.1%), p < 0.001). The 5-year disease-free survival rates (31.6% vs. 73.4%, p < 0.001) and overall survival rates (80.3% vs. 94.2%, p = 0.047) were significantly lower in the SH group. In multivariable analysis, less extensive resection compared to the initial plan (hazard ratio (HR) 4.68, p = 0.024), higher grade (HR 5.38, P < 0.001), negative but close (<0.1 cm) resection margin (HR 22.14, p = 0.007), and R1 resection (HR 3.13, p = 0.006) were significant predictors for recurrence. CONCLUSIONS: SH for recurrent tumors after ablation showed safety and effectiveness equivalent to primary resection. As recurrent tumors show a higher grade and more aggressive behavior, more extensive resections with wide surgical margins are necessary to prevent recurrence.

20.
Materials (Basel) ; 16(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687653

RESUMO

In order to study the flexural performance of the combined structure of steel-pipe and steel slag powder ultra-high-performance concrete (UHPC), nine round steel-pipe beams filled with steel slag powder UHPC of different types were fabricated according to the orthogonal test method with the steel pipe type, coarse aggregate content, steel fiber admixture, and curing system as parameters. The broken ring morphology, deformation characteristics, deflection distribution, and flexural bearing capacity of the steel-pipe-UHPC beams were analyzed via a pure bending test and a finite element simulation. The results show that the damage morphology of the round steel-tube-UHPC beams prepared by using steel slag powder UHPC as the inner filling material was "bow damage" under the pure bending load, and the load capacity was higher. When the cross-sectional deflection reached L/30, the external load was still not reduced, and the steel-tube-steel-slag powder-UHPC beam had a better plastic deformation capacity and a later flexural bearing capacity. The type of steel tube had a significant influence on the flexural bearing capacity of the steel-tube-UHPC beam, and the larger the diameter of the steel tube section and the thicker the tube wall, the higher its flexural bearing capacity. The calculated ultimate flexural bearing capacity by the finite element software and the test results had a stable error between 5.6% and 11.2%, which indicates that the model was reasonably established. The research results can provide a reference for the application of steel pipe UHPC engineering.

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