Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
1.
Crit Rev Eukaryot Gene Expr ; 34(3): 1-15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305284

RESUMO

Breast cancer is one of the malignant tumors with a high incidence and mortality rate among women worldwide, and its prevalence is increasing year by year, posing a serious health risk to women. UTP23 (UTP23 Small Subunit Processome Component) is a nucleolar protein that is essential for ribosome production. As we all know, disruption of ribosome structure and function results in improper protein function, affecting the body's normal physiological processes and promoting cancer growth. However, little research has shown a connection between UTP23 and cancer. We analyzed the mRNA expression of UTP23 in normal tissue and breast cancer using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, and the protein expression of UTP23 using The Human Protein Atlas (HPA) database. Next, we examined the relationship between UTP23 high expression and Overall Survival (OS) using Kaplan-Meier Plotters and enriched 980 differentially expressed genes in UTP23 high and low expression samples using GO/KEGG and GSEA to identify potential biological functions of UTP23 and signaling pathways that it might influence. Finally, we also investigated the relationship between UTP23 and immune infiltration and examined the effect of UTP23 on the proliferation of human breast cancer cell lines by knocking down UTP23. We found that UTP23 levels in breast cancer patient samples were noticeably greater than those in healthy individuals and that high UTP23 levels were strongly linked with poor prognoses (P = 0.008). Functional enrichment analysis revealed that UTP23 expression was connected to the humoral immune response. Besides, UTP23 expression was found to be positively correlated with immune cell infiltration. Furthermore, UTP23 knockdown has been shown to inhibit the proliferation of human breast cancer cells MDA-MB-231 and HCC-1806. Taken together, our study demonstrated that UTP23 is a promising target in detecting and treating breast cancer and is intimately linked to immune infiltration.


Assuntos
Neoplasias da Mama , Proteínas Nucleares , Feminino , Humanos , Biomarcadores , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Prognóstico , Proteínas Nucleares/genética
2.
Biochem Biophys Res Commun ; 675: 146-154, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37473529

RESUMO

Metformin (MET) is a well-documented drug used in the treatment of type II diabetes. Recent studies have revealed its potential anti-tumor effects in various types of cancer. However, the dosage of MET required to exhibit anti-tumor activity is considerably higher than the clinically recommended dosage. In this study, we investigated the synergistical anti-tumor effect of glucose deprivation and MET in MDA-MB-231 cells, which represents a triple-negative breast cancer subtype (TNBC). Our findings demonstrate that glucose deprivation significantly enhances the anti-tumor activity of MET by reducing cell proliferation and increasing cell apoptosis. RNA-seq was performed to identify the key molecules involved in this process. Our results indicate that unfolded protein response of endoplasmic reticulum (UPRER) was significantly activated upon glucose starvation combining with MET compared to glucose starvation alone. Notably, the combined treatment significantly activated UPRER signaling pathway through ATF4/ATF3/CHOP axis, due to enhanced UPRER stress. In conclusion, our study suggests that the synergistic effects of MET and glucose deprivation suppress cell proliferation in TNBC by activating pro-apoptotic molecules through UPRER stress. These findings have potential implications for the anti-tumor application of MET in TNBC.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Neoplasias de Mama Triplo Negativas , Humanos , Glucose/farmacologia , Metformina/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático , Apoptose
3.
Langmuir ; 39(40): 14384-14395, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37770467

RESUMO

The high content of nitrogen and sulfur-doped carbon dots (N, S-CDs) was designed to prevent the corrosion of X65 steel in an acidic medium. The corrosion-inhibiting abilities of related nanomaterials for X65 steel were acquired by electrochemical experiments, and the corroded products were investigated by FT-IR, XPS, and Raman analysis. The conclusions confirm that the N, S-CDs are a high-efficiency inhibitor. When the concentration is 200 mg/L, the inhibitive efficiency of X65 steel can reach up to 99.1% and it interacts with X65 steel through chemical and physical adsorption. Additionally, results from the spectroscopic studies show that the S-group is the main contributor to the chemical adsorption process.

4.
J Enzyme Inhib Med Chem ; 38(1): 2241118, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37528657

RESUMO

Prostate cancer (PCa) is a clinically heterogeneous disease with a progressively increasing incidence. Concurrent inhibition of coactivator-associated arginine methyltransferase 1 (CARM1) and histone deacetylase 2 (HDAC2) could potentially be a novel strategy against PCa. Herein, we identified seven compounds simultaneously targeting CARM1 and HDAC2 through structure-based virtual screening. These compounds possessed potent inhibitory activities at the nanomolar level in vitro. Among them, CH-1 was the most active inhibitor which exhibited excellent and balanced inhibitory effects against both CARM1 (IC50 = 3.71 ± 0.11 nM) and HDAC2 (IC50 = 4.07 ± 0.25 nM). MD simulations presented that CH-1 could stably bind the active pockets of CARM1 and HDAC2. Notably, CH-1 exhibited strong anti-proliferative activity against multiple prostate-related tumour cells (IC50 < 1 µM). In vivo, assessment indicated that CH-1 significantly inhibited tumour growth in a DU145 xenograft model. Collectively, CH-1 could be a promising drug candidate for PCa treatment.


Assuntos
Antineoplásicos , Neoplasias da Próstata , Masculino , Humanos , Histona Desacetilase 2/metabolismo , Antineoplásicos/farmacologia , Proteína-Arginina N-Metiltransferases/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Inibidores de Histona Desacetilases/farmacologia
5.
Zhongguo Zhong Yao Za Zhi ; 48(1): 220-225, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725274

RESUMO

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/ß-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/ß-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and ß-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and ß-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/ß-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.


Assuntos
Fagopyrum , PPAR gama , Ratos , Animais , PPAR gama/metabolismo , Fagopyrum/genética , Ratos Sprague-Dawley , Proteína X Associada a bcl-2 , beta Catenina/genética , beta Catenina/metabolismo , Interleucina-6 , Flavonoides/farmacologia , Propranolol/farmacologia , Fibrilação Ventricular , Dinoprostona , Via de Sinalização Wnt , Folhas de Planta/metabolismo , Flores/metabolismo , Apoptose , Complexos Cardíacos Prematuros
6.
Hepatobiliary Pancreat Dis Int ; 20(3): 240-250, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33454220

RESUMO

BACKGROUND: Both natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. METHODS: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. RESULTS: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. CONCLUSIONS: SBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células T Matadoras Naturais , Radiocirurgia , Complexo CD3 , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Citometria de Fluxo , Humanos , Células Matadoras Naturais , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Radiocirurgia/efeitos adversos
7.
BMC Med ; 18(1): 383, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33287816

RESUMO

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe condition with high mortality due to lack of efficient therapy. Until now, the use of methylprednisolone (MP) in HBV-ACLF is still controversial. We aimed to evaluate the efficacy and safety of MP in HBV-ACLF. METHODS: Totally 171 HBV-ACLF patients from three medical centers were randomly allocated into MP group (83 patients treated with MP intravenously guttae for 7 days plus standard treatment: 1.5 mg/kg/day [day 1-3], 1 mg/kg/day [day 4-5], and 0.5 mg/kg/day [day 6-7]) and control group (88 patients treated with standard treatment). The primary endpoints were 6-month mortality and prognostic factors for 6-month survival. The survival time, cause of death, adverse events, liver function, and HBV DNA replication were analyzed. RESULTS: The 6-month mortality was significantly lower in MP group than control group [32.4% vs. 42.5%, P = 0.0037]. MP treatment was an independent prognostic factor for 6-month survival [HR (95% CI) 0.547(0.308-0.973); P = 0.040]. Factors associated with reduced 6-month mortality in MP group included HBV DNA and lymphocyte/monocyte ratio (LMR) (P < 0.05). Based on ROC curve, LMR+MELD had a better predictive value for prognosis of HBV-ACLF under MP treatment. No significant difference in HBV DNA replication was observed between groups (P > 0.05). CONCLUSIONS: MP therapy is an effective and safe clinical strategy in HBV-ACLF, increasing the 6-month survival rate. Clinical trials registered at http://www.chictr.org.cn as ChiCTR-TRC-13003113 registered on 16 March 2013.


Assuntos
Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Metilprednisolona/uso terapêutico , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Feminino , Humanos , Masculino , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
8.
BMC Cardiovasc Disord ; 20(1): 79, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054458

RESUMO

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications. CASE PRESENTATION: Here, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient's EEG was normal. No antiepileptic drugs were administered throughout this process. CONCLUSIONS: CIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.


Assuntos
Angina Instável/diagnóstico por imagem , Angina Instável/terapia , Ondas Encefálicas/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cateterismo Cardíaco/efeitos adversos , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Convulsões/induzido quimicamente , Ácidos Tri-Iodobenzoicos/efeitos adversos , Idoso , Aterectomia Coronária , Encéfalo/fisiopatologia , Stents Farmacológicos , Eletroencefalografia , Humanos , Masculino , Intervenção Coronária Percutânea/instrumentação , Recidiva , Convulsões/diagnóstico , Convulsões/fisiopatologia , Fatores de Tempo
9.
BMC Cancer ; 19(1): 846, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455251

RESUMO

BACKGROUND: To explore the association between biologically effective dose (BED) and survival rates in Child-Pugh A classification (CP-A) small hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT). METHODS: This retrospective study included 108 small HCC patients who were treated with SBRT between 2011 and 2014. The prescribed dose delivered to the tumor were 48Gy/8f, 49Gy/7f, 50Gy/5f and 54Gy/6f. The median biologically effective dose (BED10) of the total prescribed dose was 100Gy (76.8-102.6Gy). Factors associated with the survival rate were examined using the Cox proportion hazards model, and the factors associated with radiation-induced liver injury (RILD) were examined by logistic regression analysis. RESULTS: For these patients, the median follow-up time was 42 months (6-77 months), and the 1-, 2- and 3-year overall survival (OS) rates were 96.3, 89.8 and 80.6%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 85.2, 70.1 and 60.6%, respectively. The 1-, 2- and 3-year local control (LC) rates were 98.1, 96.2 and 95.1%, respectively. The 1-, 2- and 3-year distant metastasis- free survival (DMFS) rates were 86.1, 72.8 and 61.2%. The OS, PFS and DMFS were significantly higher in the BED10 ≥ 100Gy group than in the BED10 < 100Gy group (OS: p = 0.020; PFS: p = 0.017; DMFS: p = 0.012). The PLT count was a predictive factor of RILD. CONCLUSIONS: SBRT is a safe and effective option for CP-A HCC patients. A BED10 value greater than 100Gy and lower CP score are associated with improved OS and PFS. Additionally, the peripheral PLT count are predictive factors of RILD.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Radiocirurgia , Dosagem Radioterapêutica , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Recidiva , Retratamento , Resultado do Tratamento , Carga Tumoral
10.
BMC Cancer ; 18(1): 451, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29678159

RESUMO

BACKGROUND: To evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in patients with small hepatocellular carcinoma(sHCC) who were ineligible for surgery or ablation therapies. METHODS: From March 2011 to December 2012, 28 cases with sHCC which were ineligible or refused surgical resection, transplantation or local ablation were treated with CyberKnife SBRT. Median size of tumors was 2.1 cm (range:1.1-3.0 cm), a dose of 10-15Gy per faction was given over 3-6 consecutive days, resulting in a total dose of 35-60Gy. RESULTS: The median follow-up period was 36 months, with the response rate of complete response (CR) in 17 cases, partial response (PR) in 8 cases, stable disease (SD) in 2 cases and progressive disease (PD) in one case. Overall response rate was 89.28%. Overall survival rates in 1, 2 and 3 years were 92.86, 85.71 and 78.57%, respectively. Local control rates in 1, 2 and 3 years were 96.43, 92.86 and 89.28%, respectively. No grade ≥ 3 hepatic toxicity was observed. CONCLUSION: CyberKnife treatment was a safe and effective option for sHCC, which had shown good local control, high overall survival rates and low toxicity. CyberKnife SBRT could be served as an alternative treatment for patients with sHCC which is unsuitable for surgical treatment or local ablation.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Radiocirurgia , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiocirurgia/métodos , Dosagem Radioterapêutica , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
11.
Molecules ; 21(6)2016 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-27338322

RESUMO

A series of C2-symmetric chiral benzimidazolium salts, the precursor of N-heterocyclic carbene ligands, were designed and synthesized from 1,2-dibromobenzene. In situ prepared corresponding carbenes were tested in the asymmetric palladium-catalyzed intramolecular α-arylation of amides, affording chiral diarylmethanols with high yields and moderate enantioselectivities.


Assuntos
Amidas/química , Anestésicos Locais/química , Bromobenzenos/química , Indóis/química , Amidas/síntese química , Anestésicos Locais/síntese química , Bromobenzenos/síntese química , Catálise , Indóis/síntese química , Metano/análogos & derivados , Metano/química , Paládio/química , Sais/química , Estereoisomerismo
12.
Eur J Med Res ; 29(1): 474, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39343893

RESUMO

BACKGROUND: Staphylococcus aureus is one of the most important bacteria in human colonization and infection. Clonal complex1 (CC1) is one of the largest and most important S. aureus CCs, and it is a predominant clone in S. aureus colonization and can cause a series of S. aureus infections including bloodstream infections. No studies on the relationship of CC1 S. aureus between colonization and infection have been published. METHODS: To figure out if there are some significant factors in CC1 S. aureus help its colonization or infection, 15 CC1 S. aureus isolates including ten from colonization and five from bloodstream infections were enrolled in this study. Whole-genome sequencing and bioinformatics analysis were performed. RESULTS: Virulence factor regulators XdrA, YSIRK signal peptide, CPBP family and OmpR family specifically found in infection isolates can promote virulence factors and enhance the pathogenicity of S. aureus. In addition, some significant differences in metabolism and human diseases were discovered between colonization and infection. Fst family of type I toxin-antitoxin system that mainly maintains stable inheritance was specifically found in CC1 S. aureus colonization isolates and might help S. aureus survive for colonization. No significant differences in genomic evolutionary relationship were found among CC1 S. aureus isolates between colonization and infection. CONCLUSIONS: Virulence factor regulators and metabolic state can promote CC1 S. aureus pathogenic process compared with colonization, and it seems that the strains of colonization origin cannot have pathogenic potential. Experimental confirmation and a bigger number of CC1 S. aureus strains are necessary for further study about the details and mechanism between colonization and infection.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Fatores de Virulência , Humanos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Fatores de Virulência/genética , Genoma Bacteriano , Sequenciamento Completo do Genoma/métodos
13.
J Ethnopharmacol ; 321: 117490, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38030025

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. AIM OF THE STUDY: NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. MATERIALS AND METHODS: BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. RESULTS: XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1ß and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. CONCLUSIONS: The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Rinite Alérgica , Camundongos , Animais , Inflamassomos/metabolismo , Interleucina-13 , Camundongos Endogâmicos BALB C , Piroptose , Interleucina-4 , Interleucina-5 , Simulação de Acoplamento Molecular , Rinite Alérgica/tratamento farmacológico , Modelos Animais de Doenças , Ovalbumina
14.
Chin Med ; 19(1): 40, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433216

RESUMO

BACKGROUND: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis. METHODS: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB. RESULTS: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1ß in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSIONS: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.

15.
Cell Chem Biol ; 31(3): 577-592.e23, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38042151

RESUMO

Hyperpolarization-activated and cyclic-nucleotide-gated 1 (HCN1) ion channels are proposed to be critical for cognitive function through regulation of synaptic integration. However, resolving the precise role of HCN1 in neurophysiology and exploiting its therapeutic potential has been hampered by minimally selective antagonists with poor potency and limited in vivo efficiency. Using automated electrophysiology in a small-molecule library screen and chemical optimization, we identified a primary carboxamide series of potent and selective HCN1 inhibitors with a distinct mode of action. In cognition-relevant brain circuits, selective inhibition of native HCN1 produced on-target effects, including enhanced excitatory postsynaptic potential summation, while administration of a selective HCN1 inhibitor to rats recovered decrement working memory. Unlike prior non-selective HCN antagonists, selective HCN1 inhibition did not alter cardiac physiology in human atrial cardiomyocytes or in rats. Collectively, selective HCN1 inhibitors described herein unmask HCN1 as a potential target for the treatment of cognitive dysfunction in brain disorders.


Assuntos
Memória de Curto Prazo , Canais de Potássio , Ratos , Animais , Humanos , Canais de Potássio/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Encéfalo/metabolismo
16.
Front Microbiol ; 14: 1301744, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107851

RESUMO

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most commonly encountered pathogens among burn patients incurring substantial morbidity and mortality. To investigate the epidemiology and features of MRSA in burn wound infections, we conducted a 10-year retrospective study on MRSA isolated from burn patients with burn wound infections from southeast China from 2013 to 2022. Methods: One hundred MRSA isolates (10 isolates each year) from burn wound infection among burn patients from 2013 to 2022 were randomly selected and enrolled. In addition to the clinical data of the 100 burn patients, MRSA isolates were characterized by antimicrobial susceptibility testing, detection of toxin genes, and molecular typing. Results: The median time from the onset of burns and admission to MRSA detected was 13 and 5 days, respectively. No MRSA isolate was found resistant to quinupristin/dalfopristin, linezolid, and vancomycin. Toxin gene seg was found most frequently (90%) followed by sea (70%) and eta (64%). CC8 (74%), ST239 (70%), and SCCmec III (72%) were the most common CC, ST, and SCCmec types, respectively. Conclusion: ST239-III (70%) was the predominant clone found in MRSA from burn wound infection among burn patients in southeast China. ST239-III was less found from 2018 to 2022. A higher diversity of MRSA clones was observed in these recent 5 years than that from 2013 to 2017.

17.
Sci Rep ; 13(1): 8181, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210562

RESUMO

To compare the clinicopathologic characteristics of second primary squamous cell carcinoma (SPSCC) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT) with that after radiotherapy (RT). From 49,021 patients with NPC who treated by definitive RT, we were able to identify 15 male patients with SPSCC after IMRT, and 23 male patients with SPSCC after RT. We examined the difference between groups. In IMRT group, 50.33% developed SPSCC within 3 years, whereas 56.52% developed SPSCC after more than 10 years in RT group. Receiving IMRT was related positively to an increased risk of SPSCC (HR = 4.25; P < 0.001). There was no significant correlation between receiving IMRT and the survival of SPSCC (P = 0.051). Receiving IMRT was related positively to an increased risk of SPSCC, and the latency was much shorter. A follow-up protocol, especially in the first three years, should be designed for NPC patients with IMRT.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Masculino , Carcinoma Nasofaríngeo , Radioterapia de Intensidade Modulada/métodos , Neoplasias Nasofaríngeas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/etiologia , Estudos Retrospectivos
18.
Int J Adv Manuf Technol ; : 1-23, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37360661

RESUMO

In mixed reality (MR) remote collaborative assembly, remote experts can guide local users to complete the assembly of physical tasks by sharing user cues (eye gazes, gestures, etc.) and spatial visual cues (such as AR annotations, virtual replicas). At present, remote experts need to carry out complex operations to transfer information to local users, but the fusion of virtual and real information makes the display of information in the MR collaborative interaction interface appear messy and redundant, and local users sometimes find it difficult to pay attention to the focus of information transferred by experts. Our research aims to simplify the operation of remote experts in MR remote collaborative assembly and to enhance the expression of visual cues that reflect experts' attention, so as to promote the expression and communication of collaborative intention that user has and improve assembly efficiency. We developed a system (EaVAS) through a method that is based on the assembly semantic association model and the expert operation visual enhancement mechanism that integrates gesture, eye gaze, and spatial visual cues. EaVAS can give experts great freedom of operation in MR remote collaborative assembly, so that experts can strengthen the visual expression of the information they want to convey to local users. EaVAS was tested for the first time in an engine physical assembly task. The experimental results show that the EaVAS has better time performance, cognitive performance, and user experience than that of the traditional MR remote collaborative assembly method (3DGAM). Our research results have certain guiding significance for the research of user cognition in MR remote collaborative assembly, which expands the application of MR technology in collaborative assembly tasks.

19.
Front Endocrinol (Lausanne) ; 14: 1182062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361530

RESUMO

Background: To investigate the risk factors for hypoparathyroidism, discuss the prevention of postoperative hypoparathyroidism, and explore permanent postoperative hypoparathyroidism evaluation (PPHE). Methods: A total of 2,903 patients with thyroid nodules were treated between October 2012 and August 2015. Serum calcium and intact parathyroid hormone (iPTH) levels were measured at 1 day, 1 month, and 6 months postoperatively. The incidence and management of hypoparathyroidism were analyzed. The PPHE was established based on the risk factors and clinical practice. Results: A total of 637 (21.94%) patients developed hypoparathyroidism, and 92.15% of them had malignant nodules. The incidence rates of transient and permanent hypoparathyroidism were 11.47% and 10.47%, respectively. The iPTH level was lower in patients with malignant nodules who underwent total thyroidectomy (TT) and central-compartment neck dissection (CND). These factors were independently associated with the recovery rate of parathyroid function. The formula for PPHE is as follows: {iPTH} + {sCa} + {surgical procedure} + {reoperation} + {pathologic type}. A scoring system was developed, and we scored low, middle, and high risk of permanent postoperative hypoparathyroidism as 4-6, 7-9, and 10-13, respectively. The differences in the recovery rates of parathyroid function in several risk groups were statistically significant (p < 0.001). Conclusion: Simultaneous TT and CND is a risk factor for hypoparathyroidism. The reoperation is not associated with hypoparathyroidism. Identification of parathyroid glands in situ and preservation of their vascular pedicles are key factors in managing hypoparathyroidism. PPHE can forecast the risk of permanent postoperative hypoparathyroidism well.


Assuntos
Hipoparatireoidismo , Glândula Tireoide , Humanos , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Hormônio Paratireóideo , Glândulas Paratireoides/cirurgia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos
20.
Cell Transplant ; 32: 9636897231196493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37688441

RESUMO

Adipose-derived stem cells (ADSCs) are employed as a promising alternative in treating cartilage injury. Regulating the inflammatory "fingerprint" of ADSCs to improve their anti-inflammatory properties could enhance therapy efficiency. Herein, a novel injectable decorin/gellan gum hydrogel combined with ADSCs encapsulation for arthritis cartilage treatment is proposed. Decorin/gellan gum hydrogel was prepared according to the previous manufacturing protocol. The liquid-solid form transition of gellan gum hydrogel is perfectly suitable for intra-articular injection. Decorin-enriched matrix showing an immunomodulatory ability to enhance ADSCs anti-inflammatory phenotype under inflammation microenvironment by regulating autophagy signaling. This decorin/gellan gum/ADSCs hydrogel efficiently reverses interleukin-1ß-induced cellular injury in chondrocytes. Through a mono-iodoacetate-induced arthritis mice model, the synergistic therapeutic effect of this ADSCs-loaded hydrogel, including inflammation attenuation and cartilage protection, is demonstrated. These results make the decorin/gellan gum hydrogel laden with ADSCs an ideal candidate for treating inflammatory joint disorders.


Assuntos
Artrite , Hidrogéis , Camundongos , Animais , Hidrogéis/farmacologia , Decorina/farmacologia , Cartilagem , Injeções Intra-Articulares , Células-Tronco , Inflamação/terapia , Autofagia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA