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1.
Materials (Basel) ; 17(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38730776

RESUMO

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented.

2.
BMC Gastroenterol ; 24(1): 178, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773451

RESUMO

BACKGROUND: A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection. METHODS: Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined. RESULTS: A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69-0.85) compared to 0.73 (95% CI: 0.65-0.80); specificity of 0.89 (95% CI: 0.81-0.95) compared to 0.86 (95% CI: 0.77-0.91); PLR of 7.4 (95% CI: 3.7-14.9) compared to 5.1 (95% CI: 3.3-8.1); NLR of 0.24 (95% CI: 0.16-0.37) compared to 0.31 (95% CI: 0.24-0.41); DOR of 30.19 (95% CI: 10.68-85.37) compared to 16.34 (95% CI: 9.69-27.56); and AUC of 0.90 (95% CI: 0.87-0.92) compared to 0.85 (95% CI: 0.82-0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82-0.95), 0.94 (95% CI: 0.82-0.98), 14.5 (95% CI: 4.6-45.4), 0.11 (95% CI: 0.06-0.20), 133.34 (95% CI: 29.65-599.61), and 0.96 (95% CI: 0.94-0.98) for the combination of HSPs and AFP. CONCLUSION: Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Proteínas de Choque Térmico , Neoplasias Hepáticas , Sensibilidade e Especificidade , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/sangue , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/sangue , Biomarcadores Tumorais/sangue , Proteínas de Choque Térmico/sangue , Curva ROC , Área Sob a Curva
3.
Int J Biol Sci ; 20(7): 2422-2439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725842

RESUMO

Background & Aims: Reactive oxygen species (ROS) act as modulators triggering cellular dysfunctions and organ damage including liver fibrosis in which hepatic stellate cell (HSC) activation plays a key role. Previous studies suggest that microRNA-144 (miR-144) acts as a pro-oxidant molecule; however, whether and how miR-144 affects HSC activation and liver fibrosis remain unknown. Methods: Carbon tetrachloride (CCl4) and bile duct ligation (BDL)-induced experimental liver fibrosis models were used. Hepatic miR-144 expression was analyzed by miRNA in situ hybridization with RNAscope probe. The in vivo effects of silencing or overexpressing miR-144 were examined with an adeno-associated virus 6 (AAV6) carrying miR-144 inhibitor or mimics in fibrotic mouse experimental models. Results: In this study, we demonstrated that ROS treatment significantly upregulated miR-144 in HSCs, which further promoted HSC activation in vitro. Interestingly, miR-144 was preferentially elevated in HSCs of experimental liver fibrosis in mice and in human liver fibrotic tissues. Furthermore, in vivo loss or gain-of-function experiments via AAV6 carrying miR-144 antagomir or agomir revealed that blockade of miR-144 in HSCs mitigated, while overexpression of miR-144 in HSCs accelerated the development of experimental liver fibrosis. Mechanistically, SIN3 transcription regulator family member A (SIN3A), a transcriptional repressor, was identified to be the target of miR-144 in HSCs. MiR-144 downregulated Sin3A, and in line with this result, specific knockdown of Sin3a in HSCs remarkedly activated p38 MAPK signaling pathway to promote HSC activation, eventually exacerbating liver fibrosis. Conclusions: Oxidative stress-driven miR-144 fuels HSC activation and liver fibrogenesis by limiting the SIN3A-p38 axis. Thus, a specific inhibition of miR-144 in HSCs could be a novel therapeutic strategy for the treatment of liver fibrosis.


Assuntos
Células Estreladas do Fígado , Cirrose Hepática , MicroRNAs , Estresse Oxidativo , Espécies Reativas de Oxigênio , Complexo Correpressor Histona Desacetilase e Sin3 , Proteínas Quinases p38 Ativadas por Mitógeno , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos , Humanos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Complexo Correpressor Histona Desacetilase e Sin3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Tetracloreto de Carbono
4.
Front Public Health ; 12: 1375533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756891

RESUMO

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.


Assuntos
Análise Custo-Benefício , Cadeias de Markov , Carcinoma Nasofaríngeo , Humanos , China/epidemiologia , Pessoa de Meia-Idade , Masculino , Adulto , Feminino , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Idoso , Neoplasias Nasofaríngeas/diagnóstico , Detecção Precoce de Câncer/economia , Programas de Rastreamento/economia , Herança Multifatorial , Fatores de Risco , Medição de Risco
6.
J Stomatol Oral Maxillofac Surg ; : 101868, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588856

RESUMO

BACKGROUND AND PURPOSE: Hirudin, a potent anticoagulant, is used in traditional Chinese medicine (TCM) to treat thrombotic conditions and prevent postoperative thrombosis. Coagulation-related vascular complications are a common cause of perforator flaps failure. This study explores hirudin's potential to enhance flap growth by mitigating coagulation-related issues. MATERIALS AND METHODS: Patients were divided into GroupⅠ(hirudin group) and GroupⅡ(control). Laboratory tests covered red blood cell count (RBC), hematocrit (HCT), platelet count (PLT), monocyte count (MONO), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-Dimer. Clinical parameters, including capillary refill time (CRT), flap swelling, and survival status, were evaluated. Animal experiments used Sprague-Dawley (SD) rats to establish random skin flaps. The experimental side received hirudin injection, while the control side received saline. Flaps were photographed to calculate survival rate, and CD31 immunohistochemical (IHC) analysis was performed to calculate microvessel density (MVD). RESULTS: The study, with 29 patients, found significant CRT differences between groups on postoperative days 2 and 6 (p = 0.027; p = 0.019), favoring GroupⅠ. Swelling severity varied significantly over time; GroupⅡhad more pronounced swelling. GroupⅠshowed superior flap growth with fewer complications, statistically significant (p = 0.033). Specific lab indicators (MONO, PT, and FIB) were significant at certain times. In animal experiments, the experimental side consistently had higher flap survival and slightly increased CD31 expression at various times, with higher MVD on days 2 and 6. CONCLUSIONS: Hirudin enhances flap survival through diverse mechanisms, supporting its role as a complementary approach in perforator flap surgeries.

7.
Quant Imaging Med Surg ; 14(4): 2857-2869, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617154

RESUMO

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

8.
BMC Cancer ; 24(1): 507, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654231

RESUMO

BACKGROUND: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. METHODS: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. RESULTS: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. CONCLUSIONS: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.


Assuntos
Neoplasias da Mama , Técnicas de Cultura de Células , Células Neoplásicas Circulantes , Células Neoplásicas Circulantes/patologia , Animais , Neoplasias da Mama/patologia , Humanos , Camundongos , Feminino , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Metástase Neoplásica
9.
Kidney Med ; 6(4): 100801, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38562969

RESUMO

The low 1-year patency rate of mature arteriovenous fistulas (AVFs) remains a significant clinical problem. Although vessel properties and biomechanics have been suggested to affect AVF function, understanding their roles in AVF patency failure is challenging owing to the heterogeneity within the patient population, including demographics and comorbid conditions. In this study, we present a case of a patient with 2 upper-arm AVFs with different 1-year patency outcomes and investigate whether they had different histologic features before the AVF creation surgery and biomechanics at 1 day and 6 weeks after the AVF creation surgery using magnetic resonance imaging-based fluid structure interaction simulations. Despite both AVFs being in the upper arm, created <1 year apart by the same surgeon, and having similar preoperative vessel diameters, the 1-year patent AVF had less preoperative intimal collagen and higher wall shear stress 1 day after AVF creation, when compared with the AVF that failed by 1 year. Thus, a low intimal collagen content before the AVF surgery and higher wall shear stress immediately after the AVF creation surgery may be important for long-term AVF patency and should be investigated with larger cohorts.

10.
Front Microbiol ; 15: 1376819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525077

RESUMO

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

11.
J Nucl Med ; 65(4): 527-532, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453362

RESUMO

Fibroblast activation protein (FAP) is a promising diagnostic and therapeutic target in various solid tumors. This study aimed to assess the diagnostic efficiency of 68Ga-labeled FAP inhibitor (FAPI)-04 PET/CT for detecting lymph node metastasis in non-small cell lung cancer (NSCLC) and to investigate the correlation between tumor 68Ga-FAPI-04 uptake and FAP expression. Methods: We retrospectively enrolled 136 participants with suspected or biopsy-confirmed NSCLC who underwent 68Ga-FAPI-04 PET/CT for initial staging. The diagnostic performance of 68Ga-FAPI-04 for the detection of NSCLC was evaluated. The final histopathology or typical imaging features were used as the reference standard. The SUVmax and SUVmean, 68Ga-FAPI-avid tumor volume (FTV), and total lesion FAP expression (TLF) were measured and calculated. FAP immunostaining of tissue specimens was performed. The correlation between 68Ga-FAPI-04 uptake and FAP expression was assessed using the Spearman correlation coefficient. Results: Ninety-one participants (median age, 65 y [interquartile range, 58-70 y]; 69 men) with NSCLC were finally analyzed. In lesion-based analysis, the diagnostic sensitivity and positive predictive value of 68Ga-FAPI-04 PET/CT for detection of the primary tumor were 96.70% (88/91) and 100% (88/88), respectively. In station-based analysis, the diagnostic sensitivity, specificity, and accuracy for the detection of lymph node metastasis were 72.00% (18/25), 93.10% (108/116), and 89.36% (126/141), respectively. Tumor 68Ga-FAPI-04 uptake (SUVmax, SUVmean, FTV, and TLF) correlated positively with FAP expression (r = 0.470, 0.477, 0.582, and 0.608, respectively; all P ≤ 0.001). The volume parameters FTV and TLF correlated strongly with FAP expression in 31 surgical specimens (r = 0.700 and 0.770, respectively; both P < 0.001). Conclusion: 68Ga-FAPI-04 PET/CT had excellent diagnostic efficiency for detecting lymph node metastasis, and 68Ga-FAPI-04 uptake showed a close association with FAP expression in participants with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ivermectina , Neoplasias Pulmonares , Quinolinas , Idoso , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fibroblastos , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Ivermectina/análogos & derivados , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Endopeptidases/genética , Endopeptidases/metabolismo
12.
Am J Case Rep ; 25: e943020, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446721

RESUMO

BACKGROUND Endoscopic biliary stent implantation is a recognized and effective method for the treatment of benign and malignant diseases of the bile duct and pancreas, ensuring smooth bile drainage. Currently, stent migration is considered a long-term and complex process, and in most cases, stents are removed through endoscopy or expelled from the body through the intestinal cavity. In rare cases, stents lead to formation of duodenocolic fistulas. CASE REPORT We report a case of duodenal colon fistula caused by a biliary stent penetrating the duodenum and entering the ascending colon. We removed the stent through endoscopy and clamped the fistulas of the colon and duodenum separately with titanium clips. Due to the presence of large common bile duct stones, nasobiliary drainage was performed again. Later, laparoscopic choledocholithotomy was performed, and the patient was discharged after rehabilitation. CONCLUSIONS ERCP endoscopy must consider the possibility of stent displacement in patients with biliary stents. In the case of CBD biliary stent dislocation in the patient, continuous abdominal plain films and physical examinations are required until spontaneous discharge is confirmed. In addition, for patients with benign bile duct stenosis undergoing biliary drainage, doctors should urge them to return to the hospital on time to remove the stent. For patients with postoperative abdominal pain or peritonitis symptoms, abdominal CT scan confirmation is required and early intervention should be considered.


Assuntos
Fístula Intestinal , Laparoscopia , Humanos , Fístula Intestinal/etiologia , Fístula Intestinal/cirurgia , Drenagem , Ductos Biliares , Stents
13.
Acta Pharmacol Sin ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438582

RESUMO

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.

14.
Cancer Lett ; 588: 216762, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38408602

RESUMO

The third-generation EGFR-TKI osimertinib is widely used in EGFR-mutated positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. The currently known mechanisms only explain resistance in a small proportion of patients. For most patients, the mechanism of osimertinib resistance is still unclear, especially for EGFR-independent resistance. Herein, we thoroughly investigated the novel mechanism of osimertinib resistance and treatment strategies. We identified that ST3GAL4, a sialyltransferase, catalyzes terminal glycan sialylation of receptor protein tyrosine kinases, which induces acquired resistance to osimertinib in vitro and in vivo. In addition, ST3GAL4 is generally overexpressed in osimertinib-resistant patients with unknown resistance mechanisms. ST3GAL4 modifies MET glycosylation on N785 with sialylation, which antagonizes K48-related ubiquitin-dependent MET degradation and subsequently activates MET and its downstream proliferation signaling pathways. Meanwhile, ST3GAL4 knockdown or inhibition by brigatinib resensitizes resistant non-small cell lung cancer cells to osimertinib in vitro and in vivo This study suggests that ST3GAL4 can induce acquired resistance to osimertinib, which may be an important EGFR-independent resistance mechanism Furthermore, targeting ST3GAL4 with brigatinib provides new strategies to overcome osimertinib resistance.


Assuntos
Acrilamidas , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Compostos Organofosforados , Pirimidinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Compostos de Anilina/farmacologia , Sialiltransferases/genética
15.
Environ Res ; 249: 118402, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309560

RESUMO

Microcystins (MC)-RR is a significant analogue of MC-LR, which has been identified as a hepatotoxin capable of influencing lipid metabolism and promoting the progression of liver-related metabolic diseases. However, the toxicity and biological function of MC-RR are still not well understood. In this study, the toxic effects and its role in lipid metabolism of MC-RR were investigated in hepatoblastoma cells (HepG2cells). The results demonstrated that MC-RR dose-dependently reduced cell viability and induced apoptosis. Additionally, even at low concentrations, MC-RR promoted lipid accumulation through up-regulating levels of triglyceride, total cholesterol, phosphatidylcholines and phosphatidylethaolamine in HepG2 cells, with no impact on cell viability. Proteomics and transcriptomics analysis further revealed significant alterations in the protein and gene expression profiles in HepG2 cells treated with MC-RR. Bioinformatic analysis, along with subsequent validation, indicated the upregulation of CD36 and activation of the AMPK and PI3K/AKT/mTOR in response to MC-RR exposure. Finally, knockdown of CD36 markedly ameliorated MC-RR-induced lipid accumulation in HepG2 cells. These findings collectively suggest that MC-RR promotes lipid accumulation in HepG2 cells through CD36-mediated signal pathway and fatty acid uptake. Our findings provide new insights into the hepatotoxic mechanism of MC-RR.


Assuntos
Antígenos CD36 , Ácidos Graxos , Metabolismo dos Lipídeos , Microcistinas , Transdução de Sinais , Humanos , Células Hep G2 , Antígenos CD36/metabolismo , Antígenos CD36/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Microcistinas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Ácidos Graxos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos
16.
Radiol Med ; 129(3): 439-456, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38349417

RESUMO

PURPOSE: We aimed to systematically assess the methodological quality and clinical potential application of published magnetic resonance imaging (MRI)-based radiomics studies about endometrial cancer (EC). METHODS: Studies of EC radiomics analyses published between 1 January 2000 and 19 March 2023 were extracted, and their methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses and separate meta-analyses of studies exploring differential diagnoses and risk prediction were also performed. RESULTS: Forty-five studies involving 3 aims were included. The mean RQS was 13.77 (range: 9-22.5); publication bias was observed in the areas of 'index test' and 'flow and timing'. A high RQS was significantly associated with therapy selection-aimed studies, low QUADAS-2 risk, recent publication year, and high-performance metrics. Raw data from 6 differential diagnosis and 34 risk prediction models were subjected to meta-analysis, revealing diagnostic odds ratios of 23.81 (95% confidence interval [CI] 8.48-66.83) and 18.23 (95% CI 13.68-24.29), respectively. CONCLUSION: The methodological quality of radiomics studies involving patients with EC is unsatisfactory. However, MRI-based radiomics analyses showed promising utility in terms of differential diagnosis and risk prediction.


Assuntos
Neoplasias do Endométrio , Radiômica , Humanos , Feminino , Imageamento por Ressonância Magnética , Neoplasias do Endométrio/diagnóstico por imagem , Diagnóstico Diferencial
17.
J Environ Manage ; 354: 120337, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38417357

RESUMO

China, being a major agricultural nation, employs aerobic composting as an efficient approach to handle agricultural solid waste. Nevertheless, the composting process is often accompanied by greenhouse gas emissions, which are known contributors to global warming. Therefore, it is urgent to control the formation and emission of greenhouse gases from composting. This study provides a comprehensive analysis of the mechanisms underlying the production of nitrous oxide, methane, and carbon dioxide during the composting process of agricultural wastes. Additionally, it proposes an overview of the variables that affect greenhouse gas emissions, including the types of agricultural wastes (straw, livestock manure), the specifications for compost (pile size, aeration). The key factors of greenhouse gas emissions during composting process like physicochemical parameters, additives, and specific composting techniques (reuse of mature compost products, ultra-high-temperature composting, and electric-field-assisted composting) are summarized. Finally, it suggests directions and perspectives for future research. This study establishes a theoretical foundation for achieving carbon neutrality and promoting environmentally-friendly composting practices.


Assuntos
Compostagem , Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Agricultura , Dióxido de Carbono/análise , Aquecimento Global , Metano/análise , Óxido Nitroso/análise , Esterco/análise , Solo
18.
Quant Imaging Med Surg ; 14(2): 1860-1872, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415146

RESUMO

Background: For patients with suspected simultaneous coronary and cerebrovascular atherosclerosis, conventional single-site computed tomography angiography (CTA) for both sites can result in nonnegligible radiation and contrast agent dose. The purpose of this study was to validate the feasibility of one-stop coronary and carotid-cerebrovascular CTA (C&CC-CTA) with a "double-low" (low radiation and contrast) dose protocol reconstructed with deep learning image reconstruction with high setting (DLIR-H) algorithm. Methods: From February 2018 to January 2019, 60 patients referred to C&CC-CTA simultaneously in West China Hospital were recruited in this prospective cohort study. By random assignment, patients were divided into two groups: double-low dose group (n=30) used 80 kVp and 24 mgI/kg/s contrast dose with images reconstructed using DLIR-H; and routine-dose group (n=30) used 100 kVp and 32 mgI/kg/s contrast dose with images reconstructed using 50% adaptive statistical iterative reconstruction-V (ASIR-V50%). Radiation and contrast doses, subjective image quality score, CT attenuation values, noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured and compared between the groups. Results: The DLIR-H group used 30% less contrast dose (35.80±4.85 vs. 51.13±6.91 mL) and 48% less overall radiation dose (1.00±0.09 vs. 1.91±0.42 mSv) than the ASIR-V50% group (both P<0.001). There was no statistically significant difference on subjective quality score between the two groups (C-CTA: 4.38±0.67 vs. 4.17±0.81, P=0.337 and CC-CTA: 4.18±0.87 vs. 4.08±0.79, P=0.604). For coronary CTA, lower background noise (18.93±1.43 vs. 22.86±3.75 HU) was reached in DLIR-H group, and SNR and CNR at all assessed branches were significantly increased compared to ASIR-V50% group (all P<0.05), except SNR of left anterior descending (P>0.05). For carotid-cerebrovascular CTA, DLIR-H group was comparable in background noise (19.25±1.42 vs. 20.23±2.40 HU), SNR and CNR at all assessed branches with ASIR-V50% group (all P>0.05). Conclusions: The "double-low" dose one-stop C&CC-CTA with DLIR-H obtained higher image quality compared with the routine-dose protocol with ASIR-V50% while achieving 48% and 30% reduction in radiation and contrast dose, respectively.

19.
Chin Med J (Engl) ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403898

RESUMO

BACKGROUND: Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors. METHODS: The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020. RESULTS: The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy. CONCLUSIONS: We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

20.
Nat Commun ; 15(1): 1645, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388556

RESUMO

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/complicações , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/patologia , Translocação Genética , Boca , Microambiente Tumoral
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