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1.
Chin J Integr Med ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39172302

RESUMO

OBJECTIVES: To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill (QSYQ) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: This multicentre prospective cohort study was conducted at 40 centers in China. Patients with ACS after PCI entered either the QSYQ or Western medicine (WM) groups naturally based on whether they had received QSYQ before enrollment. QSYQ group received QSYQ (0.52 g, 3 times a day for 12 months) in addition to WM. The primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, and other thrombotic events. Quality of life was assessed by the Seattle Angina Questionnaire (SAQ). RESULTS: A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December 2018. Overall, 487 patients received QSYQ and WM. During a median follow-up of 566 days (inter quartile range, IQR, 517-602), the primary endpoint occurred in 46 (9.45%) and 65 (14.48%) patients in QSYQ and WM groups respectively [adjusted hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.41-0.90; P=0.013]. The secondary endpoint occurred in 61 (12.53%) and 74 (16.48%) patients in QSYQ and WM groups, respectively (adjusted HR 0.76, 95% CI 0.53-1.09; P=0.136). In sensitivity analysis, the results still demonstrated that WM combined with QSYQ reduced the risk of the primary endpoint (HR 0.67, 95% CI 0.46-0.98; P=0.039). Moreover, QSYQ improved the disease perception domain of the SAQ (P<0.05). CONCLUSION: In patients with ACS after PCI, QSYQ combined with WM reduced the incidence of the primary endpoint. These findings provide a promising option for managing ACS after PCI and suggest the potential treatment for reducing the risk of primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization through intermittent administration of QSYQ (Registration No. ChiCTR-OOC-14005552).

2.
Heliyon ; 10(13): e33738, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39050439

RESUMO

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.

3.
Angew Chem Int Ed Engl ; : e202408551, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858167

RESUMO

Heat-activated second harmonic generation (SHG) switching materials are gaining interest for their ability to switch between SHG on and off states, offering potential in optoelectronic applications. The novel nonlinear optical (NLO) switch, (C5H6NO)+(CH3SO3)- (4-hydroxypyridinium methylsulfonate, 4HPMS), is a near-room-temperature thermal driven material with a strong SHG response (3.3 × KDP), making it one of the most potent heat-stimulated NLO switches. It offers excellent contrast of 13 and a high laser-induced damage threshold (2.5 × KDP), with reversibility > 5 cycles. At 73 °C, 4HPMS transitions from the noncentrosymmetric Pna21 room temperature phase (RTP) to the centrosymmetric P21/c phase, caused by the rotation of the (C5H6NO)+ and (CH3SO3)- due to partially thermal breaking of intermolecular hydrogen bonds. The reverse phase change exhibits a large 50 °C thermal hysteresis. Density functional theory (DFT) calculations show that (C5H6NO)+ primarily dictates both the SHG coefficient (dij) and birefringence (▵n(Zeiss) = 0.216 vs ▵n(cal.) = 0.202 at 546 nm; Δn(Immersion) = 0.210 vs ▵n(cal.) = 0.198 at 589.3 nm), while the band gap (Eg) is influenced synergistically by (C5H6NO)+ and (CH3SO3)-. Additionally, 4HPMS-RTP also exhibits mechanochromism upon grinding as well as an aggregation-enhanced emission in a mixture of acetone and water.

4.
BMC Cancer ; 24(1): 772, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937681

RESUMO

BACKGROUND: Wilms tumor is the most prevalent embryonal kidney malignancy in children worldwide. Previous genome-wide association study (GWAS) identified that LIM domain only 1 (LMO1) gene polymorphisms affected the susceptibility to develop certain tumor types. Apart from LMO1, the LMO gene family members also include LMO2-4, each of which has oncogenic potential. METHODS: We conducted this five-center case‒control study to assess the correlations between single nucleotide polymorphisms in LMO family genes and Wilms tumor susceptibility. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association. RESULTS: We found LMO1 rs2168101 G > T and rs11603024 C > T as well as LMO2 rs7933499 G > A were significantly associated with Wilms tumor risk. Stratified analysis demonstrated a protective role of rs2168101 GT/TT genotypes against Wilms tumor in the subgroups of age ≤ 18 months, males and clinical stages I/II compared to the rs2168101 GG genotype. Nevertheless, carriers with the rs11603024 TT genotype were more likely to have an increased risk of Wilms tumor than those with rs11603024 CC/CT genotypes in age > 18 months. And the rs11603024 was identified as a protective polymorphism for reducing the risk of Wilms tumor in the sex- and gender- subgroup. Likewise, carriers with the rs7933499 GA/AA genotypes were at significantly elevated risk of Wilms tumor in age ≤ 18 months and clinical stages I/II. CONCLUSION: Overall, our study identified the importance of LMO family gene polymorphisms on Wilms tumor susceptibility in Chinese children. Further investigations are needed to validate our conclusions.


Assuntos
Predisposição Genética para Doença , Neoplasias Renais , Proteínas com Domínio LIM , Polimorfismo de Nucleotídeo Único , Tumor de Wilms , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Proteínas Adaptadoras de Transdução de Sinal/genética , Estudos de Casos e Controles , China/epidemiologia , Proteínas de Ligação a DNA/genética , População do Leste Asiático/genética , Genótipo , Neoplasias Renais/genética , Proteínas com Domínio LIM/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Tumor de Wilms/genética , Família Multigênica
5.
Clin Transl Oncol ; 26(8): 2020-2024, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38478261

RESUMO

OBJECTIVE: The primary goal of this study was to investigate the expressions of TUFT1 (Tuftelin) and Rac1-GTP in the cancerous tissues of individuals with triple-negative breast cancer (TNBC). Additionally, we aimed to explore the correlation between TUFT1 and Rac1-GTP expressions and examine the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. METHODS: Ninety-six patients diagnosed with TNBC, scheduled for surgery between May 2022 and November 2022, were enrolled in this study. Cancerous tissue specimens were collected from these patients, and immunohistochemistry was employed to evaluate the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues. Subsequent to data collection, a comprehensive analysis was conducted to examine the correlation between TUFT1 and Rac1-GTP expressions. Furthermore, we sought to assess the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. RESULTS: The TUFT1 protein was expressed in both the membrane and cytoplasm of TNBC cancer cells, with notably higher expression observed in the cytoplasm. Rac1-GTP was primarily expressed in the cytoplasm. There was a positive correlation between the levels of TUFT1 and Rac1-GTP expressions (χ2 = 9.816, P < 0.05). The levels of TUFT1 and Rac1-GTP protein expressions showed no correlation with patient age (χ2 = 2.590, 2.565, P > 0.05); however, they demonstrated a positive correlation with tumor size (χ2 = 5.592,5.118), histological grading (χ2 = 6.730, 5.443), and lymph node metastasis (χ2 = 8.221, 5.180) (all with a significance level of P < 0.05). CONCLUSION: A significant correlation was identified between the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues of patients with TNBC, suggesting a close association with the progression of TNBC. The two molecules play significant roles in facilitating an early diagnosis and treatment of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas rac1 de Ligação ao GTP , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Metástase Linfática , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Citoplasma/metabolismo
6.
Huan Jing Ke Xue ; 45(3): 1428-1438, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471858

RESUMO

To understand the water pollution status and environmental risks of Changshou Lake, the concentrations of heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the water were collected and analyzed during different seasons. The study investigated temporal and spatial variations, distribution characteristics, pollution levels, and health risks associated with heavy metals in Changshou Lake. The results showed that all six heavy metals were below than the Class Ⅰ standard of the Surface Water Environmental Quality Standard (GB 3838-2002), but recent years have witnessed an increasing trend, with Cu, As, and Pb showing a significant increase (P<0.05). The temporal and spatial distributions of these heavy metals were different. Temporally, Cr and Cd concentrations in surface water were higher in summer, As and Zn were higher in spring, and Pb and Cu were higher in autumn and winter. Spatially, the concentrations of Cr, As, Cu, Zn, and Pb showed higher concentrations in the southern outlet of the reservoir, the northwestern Longxi River inlet, and the central part of the reservoir, whereas Cd was higher in the northern stagnant area. The overall levels of heavy metals in the water body of Changshou Lake were low, with Cr and Cu slightly polluted, while other heavy metals were identified as having an insignificant pollution level. Drinking water was the primary exposure pathway to carcinogenic and non-carcinogenic heavy metals in surface water bodies. The health risk values of Cr and As in water bodies were high, ranging from 6.2×10-10 to 3.0×10-4 and 5.1×10-8 to 3.9×10-5, respectively. The corresponding contribution rates for children and adults to the total health risk were high, with Cr accounting for 87.18% and 87.20%, respectively, while As accounted for 12.73% and 12.71%, respectively. Therefore, it is crucial to prioritize environmental risks associated with Cr and Cu, as well as the health risks associated with Cr and As in Changshou Lake These findings provide a scientific foundation for water pollution control and environmental quality improvement in Changshou Lake, and rational development and utilization of water resources.


Assuntos
Água Potável , Metais Pesados , Poluentes Químicos da Água , Cádmio , China , Monitoramento Ambiental , Sedimentos Geológicos , Lagos/análise , Chumbo , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análise , Humanos , Criança , Adulto
7.
J Intensive Med ; 4(1): 101-107, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38263967

RESUMO

Background: Abdominal organs are important organs that sense and respond to ischemia and hypoxia, but there are few evaluation methods.We use ultrasonography to evaluate abdominal organ function and blood flow in patients with mechanical ventilation (MV) after cardiopulmonary bypass and to obtain a semiquantitative score for abdominal organ function and blood flow. Methods: Patients with cardiopulmonary bypass in the Critical Care Department of Peking Union Medical College Hospital in China from March to July 2021 were enrolled in this prospective observational study. The correlation of the abdominal-visceral-blood-flow-and-function score (AVBFS) with the duration of MV, number of days spent in the intensive care unit (ICU), acute physiology and chronic health evaluation II (APACHE-II), sequential organ failure assessment (SOFA), lactate, epinephrine, and norepinephrine use was analyzed, and the results were used to assess the predictive value of the receiver operating characteristic curve (ROC) regression analysis score for the duration of MV. Results: Of the 92 patients who underwent cardiopulmonary bypass, 41 were finally included. The AVBFS were significantly correlated with the duration of MV, number of days spent in the ICU, APACHE-II score, SOFA score, and norepinephrine use time. The AVBFS in a group of patients using ventilators ≥36 h were significantly higher than those obtained for a group of patients using ventilators <36 h (P <0.05). The evaluation results for the AVBFS at 0-12 h after ICU admission were as follows: area under the ROC curve (AUC)=0.876 (95% confidence interval [CI]: 0.767 to 0.984), cut-off value=2.5, specificity=0.842, and sensitivity=0.773. Conclusions: Abdominal visceral organ function and blood perfusion can be used to evaluate gastrointestinal function. It is related to early and late extubation after cardiac surgery.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1027924

RESUMO

In recent years, artificial intelligence (AI) technology represented by deep learning (DL) has developed rapidly, and smart medical care has become one of the most important application areas of AI. As the most accurate noninvasive test to assess myocardial blood flow, myocardial perfusion imaging (MPI) has important clinical values. At present, the use of DL algorithms to establish learning models for MPI images is still in the research stage, and more external verification and iterative updates are needed before it can be widely used in real time clinical practice. In this article, the application of DL algorithms in MPI is comprehensively elaborated to provide a basis and direction for further research.

9.
Regen Ther ; 24: 507-514, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37841661

RESUMO

The facial nerve, also known as the seventh cranial nerve, is critical in controlling the movement of the facial muscles. It is responsible for all facial expressions, such as smiling, frowning, and moving the eyebrows. However, damage to this nerve can occur for a variety of reasons, including maxillofacial surgery, trauma, tumors, and infections. Facial nerve injuries can cause severe functional impairment and can lead to different degrees of facial paralysis, significantly affecting the quality of life of patients. Over the past ten years, significant progress has been made in the field of facial nerve repair. Different approaches, including direct suture, autologous nerve grafts, and tissue engineering, have been utilized for the repair of facial nerve injury. This article mainly summarizes the clinical methods and basic research progress of facial nerve repair in the past ten years.

10.
World J Oncol ; 14(4): 277-284, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560336

RESUMO

Background: Several traditional observational studies and Mendelian randomization (MR) studies have indicated an association between leukocyte telomere length (LTL) and the risk of lung cancer in the European population. However, the results in the Asian population are still unclear. The objective was to reveal the genetic causal association between LTL and the risk of lung cancer in the Asian population. Methods: We conducted a two-sample MR analysis using summary statistics. Instrumental variables (IVs) were obtained from the genome-wide association studies (GWAS) of LTL (n = 23,096) and lung cancer (n = 212,453) of Asian ancestry. We applied the random-effects inverse-variance weighted (IVW) model as the main method. As well, several other models were performed as complementary methods to assess the impact of potential MR assumption violations, including MR-Egger regression, weighted median, and weighted mode models. Results: We included eight single-nucleotide polymorphisms (SNPs) as IVs for LTL and found that LTL was significantly associated with the risk of lung cancer in the IVW model (odds ratio (OR): 1.60; 95% confidence interval (CI): 1.31 - 1.97; P = 5.96 × 10-6), which was in line with the results in the weighted median and weighted mode models. However, the relationship was not statistically significant in the MR-Egger regression model (OR: 1.44; 95% CI: 0.92 - 2.26; P = 0.160). Sensitivity analyses indicated the robustness of the results. Conclusions: This two-sample MR study confirmed that longer telomere length significantly increased the risk of lung cancer in the Asian population, which was in accord with findings in the Western population.

11.
Gene ; 882: 147646, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37473973

RESUMO

tRNA methyltransferase 6 (TRMT6)is an enzyme catalyzing N1-methyladenosine, a reversible modification in RNA, including tRNA, mRNA, rRNA, and lncRNA. Increasing evidence has shown the implications of this post-transcriptional modification and its regulators in carcinogenesis. However, its roles in Wilms tumor haven't been reported. In this study, four TRMT6 gene polymorphisms (rs236170 A > G, rs451571 T > C, rs236188 G > A, and rs236110 C > A) were tested for association with susceptibility to Wilms tumor, the most frequently diagnosed pediatric renal tumor. TaqMan method was adopted to analyze the genotypes of these polymorphisms in 414 cases and 1199 controls. Among the four TRMT6 gene polymorphisms, only the rs236110 C > A displayed a significant association with the risk of Wilms tumor [AA vs. CC, adjusted odds ratio (OR) = 1.93, 95 % confidence interval (CI) = 1.14-3.27, P = 0.015]. This association was confirmed under the recessive models (AA vs. CC/CA, OR = 1.92, 95 % CI = 1.14-3.23, P = 0.015). Furthermore, after stratifying by age, gender, and clinical stage, we mainly detected significant associations for the rs236110 C > A in children older than 18 months, boys, and those with stage IV or III + IV diseases. The rs236110 A allele was significantly associated with decreased expression of MCM8. In conclusion, we identified the rs236110 C > A in the TRMT6 gene as a Wilms tumor susceptibility locus, and this polymorphism warrants more validation studies to be translated into individualized risk prediction strategies for children.


Assuntos
Neoplasias Renais , Tumor de Wilms , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Estudos de Casos e Controles , Predisposição Genética para Doença , Neoplasias Renais/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Tumor de Wilms/genética , Tumor de Wilms/patologia
12.
Expert Rev Anti Infect Ther ; 21(8): 891-900, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450490

RESUMO

BACKGROUND: We compared Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), Quick Sepsis-related Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) for sepsis diagnosis and adverse outcomes prediction. METHODS: Clinical studies that used SIRS, SOFA, qSOFA, and NEWS for sepsis diagnosis and prognosis assessment were included. Data were extracted, and meta-analysis was performed for outcome measures, including sepsis diagnosis, in-hospital mortality, 7/10/14-day mortality, 28/30-day mortality, and ICU admission. RESULTS: Fifty-seven included studies showed good overall quality. Regarding sepsis prediction, SIRS demonstrated high sensitivity (0.85) but low specificity (0.41), qSOFA showed low sensitivity (0.42) but high specificity (0.98), and NEWS exhibited high sensitivity (0.71) and specificity (0.85). For predicting in-hospital mortality, SOFA demonstrated the highest sensitivity (0.89) and specificity (0.69). In terms of predicting 7/10/14-day mortality, SIRS exhibited high sensitivity (0.87), while qSOFA had high specificity (0.75). For predicting 28/30-day mortality, SOFA showed high sensitivity (0.97) but low specificity (0.14), whereas qSOFA displayed low sensitivity (0.41) but high specificity (0.88). CONCLUSIONS: NEWS independently demonstrates good diagnostic capability for sepsis, especially in high-income countries. SOFA emerges as the optimal choice for predicting in-hospital mortality and can be employed as a screening tool for 28/30-day mortality in low-income countries.


Assuntos
Escore de Alerta Precoce , Sepse , Humanos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Escores de Disfunção Orgânica , Sepse/diagnóstico , Hospitalização , Prognóstico , Estudos Retrospectivos
13.
J Cancer ; 14(8): 1293-1300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283791

RESUMO

Wilms tumor is the most common embryonal renal malignancy in children. WDR4 is an indispensable noncatalytic subunit of the RNA N7-methylguanosine (m7G) methyltransferase complex and plays an essential role in tumorigenesis. However, the relationship between polymorphisms in the WDR4 gene and susceptibility to Wilms tumor remains to be fully investigated. We performed a large case-control study involving 414 patients and 1199 cancer-free controls to investigate whether single nucleotide polymorphisms (SNPs) in the WDR4 gene are associated with Wilms tumor susceptibility. WDR4 gene polymorphisms (rs2156315 C > T, rs2156316 C > G, rs6586250 C > T, rs15736 G > A, and rs2248490 C > G) were genotyped using the TaqMan assay. In addition, unconditioned logistic regression analysis was performed, odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between WDR4 gene SNPs and Wilms tumor susceptibility as well as the strength of the associations. We found that only the rs6586250 C>T polymorphism was significantly associated with an increased risk of Wilms tumor (adjusted OR=2.99, 95% CI = 1.28-6.97, P = 0.011 for the rs6586250 TT genotype; adjusted OR=3.08, 95% CI = 1.33-7.17, P = 0.009 for the rs6586250 CC/CT genotype). Furthermore, the stratification analysis revealed that patients with the rs6586250 TT genotype and carriers with 1-5 risk genotypes exhibited statistically significant associations with increased Wilms tumor risk in specific subgroups. However, the rs2156315 CT/TT genotype was identified as having a protective effect against Wilms tumor in the age >18 months subgroup compared with the rs2156315 CC genotype. In brief, our study demonstrated that the rs6586250 C > T polymorphism of the WDR4 gene was significantly associated with Wilms tumor. This finding may contribute to the understanding of the genetic mechanism of Wilms tumor.

14.
World J Clin Cases ; 11(10): 2315-2320, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37122516

RESUMO

BACKGROUND: Chronic subdural effusion is very common in the cranial imaging of middle-aged and older people. Herein, we report a patient misdiagnosed with subdural effusion, who was eventually diagnosed with chronic subdural empyema (SDE) caused by Streptococcus pneumoniae. CASE SUMMARY: A 63-year-old man was brought to our emergency room with a headache, vomiting, and disturbed consciousness. Computed tomography (CT) revealed a bilateral subdural effusion at the top left side of the frontal lobe. Cerebrospinal fluid examination after lumbar puncture indicated suppurative meningitis, which improved after anti-infective therapy. However, the patient then presented with acute cognitive dysfunction and right limb paralysis. Repeat CT showed an increase in left frontoparietal subdural effusion, disappearance of the left lateral ventricle, and a shift of the midline to the right. Urgent burr hole drainage showed SDE that was culture-positive for Streptococcus pneumoniae. His condition improved after adequate drainage and antibiotic treatment. CONCLUSION: Patients with unexplained subdural effusion, especially asymmetric subdural effusion with intracranial infection, should be assessed for chronic SDE. Early surgical treatment may be beneficial.

16.
J Exp Clin Cancer Res ; 42(1): 60, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36899380

RESUMO

BACKGROUND: EGFR is an important signal involved in tumor growth that can induce tumor metastasis and drug resistance. Exploring targets for effective EGFR regulation is an important topic in current research and drug development. Inhibiting EGFR can effectively inhibit the progression and lymph node metastasis of oral squamous cell carcinoma (OSCC) because OSCC is a type of cancer with high EGFR expression. However, the problem of EGFR drug resistance is particularly prominent, and identifying a new target for EGFR regulation could reveal an effective strategy. METHODS: We sequenced wild type or EGFR-resistant OSCC cells and samples from OSCC patients with or without lymph node metastasis to find new targets for EGFR regulation to effectively replace the strategy of directly inhibiting EGFR and exert an antitumor effect. We then investigated the effect of LCN2 on OSCC biological abilities in vitro and in vivo through protein expression regulation. Subsequently, we elucidated the regulatory mechanism of LCN2 through mass spectrometry, protein interaction, immunoblotting, and immunofluorescence analyses. As a proof of concept, a reduction-responsive nanoparticle (NP) platform was engineered for effective LCN2 siRNA (siLCN2) delivery, and a tongue orthotopic xenograft model as well as an EGFR-positive patient-derived xenograft (PDX) model were applied to investigate the curative effect of siLCN2. RESULTS: We identified lipocalin-2 (LCN2), which is upregulated in OSCC metastasis and EGFR resistance. Inhibition of LCN2 expression can effectively inhibit the proliferation and metastasis of OSCC in vitro and in vivo by inhibiting EGFR phosphorylation and downstream signal activation. Mechanistically, LCN2 binds EGFR and enhances the recycling of EGFR, thereby activating the EGFR-MEK-ERK cascade. Inhibition of LCN2 effectively inhibited the activation of EGFR. We translated this finding by systemic delivery of siLCN2 by NPs, which effectively downregulated LCN2 in the tumor tissues, thereby leading to a significant inhibition of the growth and metastasis of xenografts. CONCLUSIONS: This research indicated that targeting LCN2 could be a promising strategy for the treatment of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Lipocalina-2/genética , Lipocalina-2/farmacologia , Neoplasias Bucais/patologia , Metástase Linfática , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Proliferação de Células , Movimento Celular/fisiologia
17.
Phytother Res ; 37(5): 1883-1899, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36723382

RESUMO

Neuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.


Assuntos
Emodina , Neuralgia , Ratos , Animais , NF-kappa B/metabolismo , Emodina/farmacologia , Emodina/uso terapêutico , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Proteômica , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Ácido gama-Aminobutírico
18.
Acta Pharmaceutica Sinica ; (12): 339-350, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965704

RESUMO

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1025634

RESUMO

Objective To explore the optimal falling height parameters for single-leg drop jump,so as toaddress the bilateral imbalance in the lower limbs of athletes and provide a reference for coaches to design training plans accurately and effectively.Methods Twelve first-grade male athletes were re-cruited for the study,including five track and field sprinters and seven basketball players(age:20.41±1.11 years,height:189.19±9.15 cm,weight:83.50±12.08 kg).The vertical jump platform was used to test the optimal counter-movement jump(CMJ)height for the dominant and non-dominant sides of the subject's lower extremities,and to determine the three falling heights of the low height(medium height minus 5 cm),medium height(50%of the optimal unilateral lower-limb CMJ height)and high height(medium height plus 5 cm).Six parameters of the drop jump performance,including buffer time,leg stiffness,peak vertical ground reaction force(vGRFpeak),the rate of force development(RFD),power,root mean square(RMS)of surface electromyogram signals were collected synchronous-ly using the Vicon Motion Capture System(200 Hz),Delsys portable wireless telemetry EMG test sys-tem and Kistler three-dimensional force platform(1000 Hz).Results(1)At the medium height,the av-erage buffer time,leg stiffness,vGRFpeak,RFD,RMS and power of either leg were significantly bet-ter than at the other two heights(P<0.05),and the leg stiffness of the non-dominant leg was signifi-cantly inferior to the dominant leg(P<0.05).(2)At the high height,the average buffer time,vGRFpeak and RMS of the dominant leg were significantly better than at low height(P<0.05),while the average buffer time,leg stiffness,vGRFpeak,RFD,power and RMS of the non-dominant legs were significant-ly worse than the dominant legs(P<0.05).Conclusion Coaches or athletes can choose the medium height(50%optimal unilateral lower-limb CMJ height)designed in this study and schedule unilateral lower limb drop jump training to optimize the athletic performance of the dominant or non-dominant legs to the greatest extent.However,as the falling height increases,the gap in athletic performance between the bilateral lower limbs tends to become more pronounced(especially at high height),thus the training should focus on strengthening the eccentric contraction ability and stability of the non-dom-inant side to avoid bilateral imbalance.

20.
Curr Mol Med ; 23(6): 550-558, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35619282

RESUMO

BACKGROUND: Hemorrhagic shock (HS) is the most common cause of potentially preventable death after traumatic injury. Acute liver injury is an important manifestation of HS. Apoptosis plays an important role in liver injury. Farnesoid X receptor (FXR) can alleviate liver injury. This study aimed to examine the effects of ursodeoxycholic acid (UDCA) on hepatocyte apoptosis in HS and its relationship with the FXR pathway. METHODS: Mice were randomly divided into 4 groups: sham group, HS group, HS + UDCA group, and FXR (-) + HS + UDCA group. There were 6 mice in each group. As to the model of HS, MAP of 40 ± 5 mmHg was maintained for 1 hour. As to UDCA intervention, UDCA (300mg/kg) was given nasally. Real-time RT-PCR and Western blotting were used to detect changes in the expression level of Caspase-3, Bax, LC3Ⅰ, LC3Ⅱ, Bcl-2, and Beclin-1 in the liver. TUNEL assay was used to detect changes in hepatocyte apoptosis. RESULTS: The expression level of Caspase-3 and Bax in the liver decreased significantly after treatment with UDCA under HS conditions. The expression level of LC3Ⅰ, LC3Ⅱ, Bcl-2, and Beclin-1 in the liver increased significantly after treatment with UDCA under HS conditions. TUNEL positive percentage of liver decreased significantly after treatment with UDCA under HS conditions. In the case of FXR (-), the influence of UDCA was inhibited. CONCLUSION: These results indicated that UDCA could reduce hepatocyte apoptosis during HS through the FXR pathway.


Assuntos
Choque Hemorrágico , Ácido Ursodesoxicólico , Camundongos , Animais , Ácido Ursodesoxicólico/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Fígado/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Hepatócitos
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