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1.
J Chromatogr A ; 1730: 465095, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897108

RESUMO

Low carbon aldehydes and ketones are typical substances harmful to human body produced during cigarette smoking. Their contents in cigarette smoke are important indicators for evaluating its toxicity and the filtration effect of cigarette filter tips, which provides important guidance for its rational design. In this work, MXene membrane with unique lamellar structure was synthesized and loaded onto glass fiber filters to achieve effective enrichment of low carbon aldehydes and ketones. Compared to commercial Cambridge filters, the MXene-loaded filters exhibited higher extraction efficiency towards low-carbon aldehydes and ketones, making viable the detection of butyraldehyde, which was not detected by that enriched with Cambridge filters. Therefore, a MXene-based membrane enrichment-HPLC method was developed for the determination of low-carbon aldehydes and ketones in cigarette smoke with detection limits ranging from 0.133 µg/mL to 0.285 µg/mL. The applicability of the method was verified by analyzing three different types of filter cigarettes with the concentration in the range of 0.5-140 µg/branch for all the analytes, which were in good agreement with the manufacturer's results. The method is accurate and sensitive, and can be used for the quantitative determination of low carbon aldehydes and ketones in cigarette smoke.

2.
Mol Biotechnol ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902578

RESUMO

SIRT2 play important roles in cell cycle and cellular metabolism in the development of non-small cell lung cancer (NSCLC), and SIRT2 exhibits its therapeutic effect on NSCLC tumors with high expression of SIRT2. Nevertheless, the clinical relevance of SIRT2 in lung adenocarcinoma (LUAD), particularly its impact on tumor growth and prognostic implications, remains obscure. This investigation entailed a comprehensive analysis of SIRT2 mRNA and protein expression levels in diverse tumor and corresponding healthy tissues, utilizing databases such as TIMER 2.0, UALCAN, and HPA. Prognostic correlations of SIRT2 expression in LUAD patients, stratified by distinct clinicopathological characteristics, were evaluated using the KM Plotter database. Additionally, the TCGA and TIMER 2.0 databases were employed to assess the relationship between SIRT2 and immune infiltration, as well as to calculate immunity, stromal, and estimation scores, thus elucidating the role of SIRT2 in modulating tumor immunotherapy responses. Furthermore, Gene Set Enrichment Analysis (GSEA) was utilized to elucidate SIRT2's biological functions in pan-cancer cells. Our findings revealed a marked reduction in both mRNA and protein levels of SIRT2 in LUAD tumors relative to healthy tissue. Survival analysis indicated that diminished SIRT2 expression correlates with adverse prognostic outcomes in LUAD. Furthermore, SIRT2 expression demonstrated a significant association with various clinicopathologic attributes of LUAD patients, influencing survival outcomes across different clinicopathologic states. Functional enrichment analyses highlighted SIRT2's involvement in cell cycle regulation and immune response. Notably, SIRT2 exhibited a positive correlation with immune cell infiltration, including natural killer (NK) cells, macrophages, and dendritic cells (DCs). In summary, SIRT2 was a potential prognostic biomarker for LUAD and and a new immunotherapy target.

3.
J Transl Med ; 22(1): 507, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802851

RESUMO

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.


Assuntos
Fibronectinas , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas c-myc , RNA Circular , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Proteólise , Camundongos Nus , Sequência de Bases , Movimento Celular/genética , Feminino , Camundongos
4.
Food Chem ; 454: 139753, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795625

RESUMO

The utilization of cold plasma (CP) treatment to promote covalent conjugation of ovalbumin (OVA) and gallic acid (GA), as well as its functionality, were investigated. Results demonstrated that CP significantly enhanced the covalent grafting of OVA and GA. The maximum conjugation of GA, 24.33 ± 2.24 mg/g, was achieved following 45 s of CP treatment. Covalent conjugation between GA and OVA were confirmed through analyses of total sulfhydryl (-SH) group, Fourier transform infrared (FTIR) spectroscopy, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Unfolding of the OVA molecule occurred upon conjugation with GA, as evidenced by multiple spectroscopy analyses. Additionally, conjugation with GA resulted in significant improvements in the antioxidant activity and emulsifying properties of OVA. This study demonstrated that CP is a robust and sustainable technique for promoting the covalent conjugate of polyphenols and proteins, offering a novel approach to enhance the functional properties of proteins.


Assuntos
Ácido Gálico , Ovalbumina , Gases em Plasma , Ácido Gálico/química , Ovalbumina/química , Gases em Plasma/química , Antioxidantes/química , Animais
5.
PLoS One ; 19(3): e0300067, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527072

RESUMO

INTRODUCTION: There is currently no gold standard or specific nutritional assessment tool to assess malnutrition in patients with nasopharyngeal carcinoma (NPC). Our study aims to develop a new nutritional assessment tool for NPC patients. METHODS AND ANALYSIS: NPC patients will be required to complete a risk factor questionnaire after obtaining their informed consent. The risk factor questionnaire will be used to collect potential risk factors for malnutrition. Univariate and multivariate logistic regression analyses will be used to identify risk factors for malnutrition. A new nutritional assessment tool will be developed based on risk factors. The new tool's performance will be assessed by calibration and discrimination. The bootstrapping will be used for internal validation of the new tool. In addition, external validation will be performed by recruiting NPC patients from another hospital. DISCUSSION: If the new tool is validated to be effective, it will potentially save medical staff time in assessing malnutrition and improve their work efficiency. Additionally, it may reduce the incidence of malnutrition and its adverse consequences. STRENGTHS AND LIMITATIONS OF THIS STUDY: The study will comprehensively analyze demographic data, disease status, physical examination, and blood sampling to identify risk factors for malnutrition. Furthermore, the new tool will be systematically evaluated, and validated to determine their effectiveness. However, the restricted geographical range may limit the generalizability of the results to other ethnicities. Additionally, the study does not analyze subjective indicators such as psychology. ETHICS AND DISSEMINATION: The ethical approval was granted by the Ethical Committee of the First Affiliated Hospital of Guangxi Medical University (NO. 2022-KT-GUI WEI-005) and the Second Affiliated Hospital of Guangxi Medical University (NO. 2022-KY-0752). CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2300071550.


Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Humanos , China/epidemiologia , Desnutrição/epidemiologia , Carcinoma Nasofaríngeo/complicações , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/diagnóstico , Avaliação Nutricional , Estado Nutricional
6.
Front Cell Infect Microbiol ; 14: 1366472, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500502

RESUMO

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.


Assuntos
Obstrução das Vias Respiratórias , Mucormicose , Masculino , Humanos , Pessoa de Meia-Idade , Anfotericina B/uso terapêutico , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/patologia , Rhizopus oryzae , Necrose/patologia , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/patologia , Tecido de Granulação/patologia , Tosse/patologia
7.
Cell Signal ; 117: 111074, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38309549

RESUMO

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein, which participates in many important physiological processes. Recently, the roles of TCTP in cell proliferation and apoptosis, especially its close relationship with various tumors, have attracted widespread attention. In this study, we found that the protein level of TCTP was significantly reduced in acute promyelocytic leukemia cell line NB4 transfected with retinoic acid-induced gene G (RIG-G). The RIG-G was found in our previous work as a key mediator of anti-proliferative activity in retinoid/interferon-related pathways. Here, we tried to further explore the function of TCTP in the development of acute myeloid leukemia (AML) from different levels. Our results showed that inhibiting TCTP expression could attenuate AML cells proliferation and induce apoptosis both in AML cell lines and in xenograft of NOD-SCID mice. In addition, either compared with patients in complete remission or non-leukemia patients, we detected that the expression of TCTP was generally high in the fresh bone marrow of AML patients, suggesting that there was a certain correlation between TCTP and AML disease progression. Taken together, our study revealed the role of TCTP in AML development, and provided a potential target for AML treatment.


Assuntos
Apoptose , Leucemia Mieloide Aguda , Proteína Tumoral 1 Controlada por Tradução , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Leucemia Mieloide Aguda/patologia , Camundongos Endogâmicos NOD , Camundongos SCID , Tretinoína , Proteína Tumoral 1 Controlada por Tradução/genética , Proteína Tumoral 1 Controlada por Tradução/metabolismo
8.
Medicine (Baltimore) ; 102(48): e36297, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050208

RESUMO

BACKGROUND: Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION: We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION: To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Progressão , Fluoruracila/uso terapêutico
9.
Support Care Cancer ; 31(12): 723, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38008866

RESUMO

BACKGROUND: Malnutrition is a common complication in patients with nasopharyngeal carcinoma (NPC). However, there are few studies on risk factors for malnutrition in NPC patients. Our aims were to identify the risk factors for malnutrition in NPC patients. METHODS: NPC patients were recruited in this cross-sectional study, and they were divided into well-nourished and malnourished groups according to the Global Leadership Initiative on Malnutrition (GLIM). Potential risk factors were initially screened using univariate analysis (p < 0.1), and the selected ones were analyzed by logistic regression analysis (p < 0.05) to identify the risk factors for malnutrition in NPC patients. RESULTS: In total, 305 NPC patients meeting eligibility criteria were enrolled. Multivariate logistic regression analysis revealed that low body mass index (BMI) (OR = 0.596, 95% CI 0.520-0.683, p < 0.001), the high total radiation dose received (OR = 1.046, 95% CI 1.023-1.069, p < 0.001), appetite loss (OR = 2.839, 95% CI 1.269-6.353, p = 0.011), and low PA (OR = 0.993, 95% CI 0.988-0.998, p = 0.008) were risk factors for malnutrition in NPC patients. CONCLUSIONS: The low BMI, the high total radiation dose received, appetite loss, and low prealbumin were risk factors for malnutrition in NPC patients.


Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Estudos Transversais , Desnutrição/epidemiologia , Desnutrição/etiologia , Redução de Peso , Fatores de Risco , Avaliação Nutricional , Estado Nutricional
10.
Open Life Sci ; 18(1): 20220747, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854319

RESUMO

Osteoarthritis (OA) is a painful joint disease that is common among the middle-aged and elderly populations, with an increasing prevalence. Therapeutic options for OA are limited, and the pathogenic mechanism of OA remains unclear. The roles of cytokines and signaling pathways in the development of OA is a current research hot spot. Interleukin (IL)-17 is a pleiotropic inflammatory cytokine produced mainly by T helper 17 cells that has established roles in host defense, tissue repair, lymphoid tissue metabolism, tumor progression, and pathological processes of immune diseases, and studies in recent years have identified an important role for IL-17 in the progression of OA. This narrative review focuses on the mechanisms by which IL-17 contributes to articular cartilage degeneration and synovial inflammation in OA and discusses how IL-17 and the IL-17 signaling pathway affect the pathological process of OA. Additionally, therapeutic targets that have been proposed in recent years based on IL-17 and its pathway in OA are summarized as well as recent advances in the study of IL-17 pathway inhibitors and the potential challenges of their use for OA treatment.

11.
Foods ; 12(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37685231

RESUMO

This study described the distribution of As, Cd, Cr, Hg, and Pb in 692 bean samples from Zhejiang province, southeast China, and estimated the health risk using Monte Carlo simulation. The average levels of As, Cd, Cr, Hg, and Pb were 0.0349, 0.0379, 0.246, 0.0019, and 0.0246 mg kg-1. Correlation analyses showed very strong positive correlations for Cd-Pb in kidney beans and mung beans, Cd-As in black beans, and Pb-As in red beans. The target hazard quotients (THQs) were adopted for non-carcinogenic risk assessment, and THQs at the 50th percentile were all less than 1, indicating that there are no deleterious effects from rice exposure to these elements. When evaluating THQ for multiple elements, the certainty with a hazard index (HI) greater than 1 for children was 12.64%, for teens 11.54%, and for adults 1.01%. The sensitivity analysis reveals that the concentration of Cd in beans and ED (exposure duration) are the main principal factors that contributed to the total risk. The mean carcinogenic risks for children, teens, and adults were all less than 1 × 10-4, indicating no potential carcinogenic risk. Despite that, the routine monitoring of these elements, especially for Cd should be continued.

12.
Front Oncol ; 13: 1215717, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37746280

RESUMO

Background: Esophageal carcinoma accompanied by a right aortic arch (RAA) is very rare. When combined with Kommerell diverticulum (KD), a right aortic arch forms a vascular ring encircling both the esophagus and trachea. Due to abnormal anatomy of the upper mediastinum, it is very difficult to dissociate the esophagus and its surrounding tissues, especially the left recurrent laryngeal nerve. Herein, we report a case of successful thoracoscopic esophagectomy in an esophageal cancer patient concurrent with a RAA and KD. Case presentation: A 62-year-old male patient was diagnosed with esophageal squamous carcinoma in the middle esophagus at clinical stage I (cT1N0M0) according to UICC-TNM classification 8th edition. Further examinations revealed RAA and KD. Based on the three-dimensional CT (3D-CT) reconstruction, a Mckeown esophagectomy via a left thoracoscopic approach in semi-prone position was performed. During the operation, the left recurrent laryngeal nerve was accurately exposed and well protected. Postoperatively, severe complications, including anastomotic leakage and recurrent laryngeal nerve palsy, were not observed. The patient was discharged 12 days after the surgery. Conclusion: Preoperative 3D-CT reconstruction is useful to clarify the vascular malformation in esophageal cancer patients with RAA, and helpful to formulate a reasonable surgical approach.

13.
World J Gastrointest Oncol ; 15(8): 1400-1411, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37663938

RESUMO

BACKGROUND: Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma (HCC). Physcion is a common bioactive anthraquinone that has potential as an anticancer agent. AIM: To study the effect of physcion on sensitizing HCC cells to sorafenib. METHODS: Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion. The cell viability, proliferation and apoptosis were measured by cell counting kit-8, colony formation, flow cytometry, and in vivo xenograft model. Glucose uptake, lactate acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) were measured to analyze glycolysis. Expression of glycolysis-related regulators was assessed by western blotting. RESULTS: The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells, manifested by enhanced apoptosis and suppressed cell growth. The glucose uptake, lactate acid production, and ECAR were elevated, and OCR was suppressed by physcion treatment. The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells, which was suppressed by physcion treatment. Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells. CONCLUSION: Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.

14.
Hum Vaccin Immunother ; 19(2): 2240689, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37529904

RESUMO

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Derrame Pleural , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Derrame Pleural/induzido quimicamente , Derrame Pleural/tratamento farmacológico , Imunoterapia/efeitos adversos
15.
Front Public Health ; 11: 1149964, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497023

RESUMO

Objective: Regular check-up with ultrasound in underserved rural and/or remote areas is hampered due to the limited availability of sonologists and ultrasound devices. This study aimed to assess the feasibility and satisfaction of health check-ups with a 5G-based robotic teleultrasound diagnostic system. Methods: In this prospective study, sonologists from two hospitals manipulated the telerobotic ultrasound system to perform teleultrasound check-ups of the liver, gallbladder, pancreas, spleen, kidneys, bladder, prostate (male), uterus and ovaries (female) for the subjects. The feasibility and satisfaction of health check-ups with a 5G-based robotic teleultrasound diagnostic system were evaluated in terms of examination results, examination duration, and satisfaction questionnaire survey. Results: A total of 546 subjects were included with the most frequently diagnosed being abdominal disorders (n = 343) and male reproductive illnesses (n = 97), of which fatty liver (n = 204) and prostatic calcification (n = 54) were the most. The median teleultrasound examination duration (interquartile range) for men and women was 9 (9-11) min and 9 (7-11) min (p = 0.236), respectively. All the subjects were satisfied with this new type of telerobotic ultrasound check-ups and 96% reported no fear of the robotic arm during the examination. Conclusion: The 5G-based teleultrasound robotic diagnostic system in health check-ups is feasible and satisfactory, indicating that this teleultrasound robot system may have significant application value in underserved rural and/or remote areas to mitigate disparity in achieving health equity.


Assuntos
Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Feminino , Estudos Prospectivos , Estudos de Viabilidade , Ultrassonografia/métodos , Fígado
16.
Biochem Biophys Res Commun ; 674: 27-35, 2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37393641

RESUMO

Intrinsic or acquired chemoresistance represents a major obstacle in cancer treatment. Multiple mechanisms can contribute to cancer cells' resistance to chemotherapy. Among them, an aberrantly strengthened DNA repair mechanism is responsible for a large proportion of drug resistance to alkylating agents and radiation therapy. In cancer cells, damping overactivated DNA repair system can overcome survival advantages conferred by chromosomal translocations or mutations and lead to cytostatic effects or cytotoxic. Therefore, selectively targeting DNA repair system in cancer cells holds promise for overcoming chemoresistance. In this study, we revealed that the endonuclease Flap Endonuclease 1 (FEN1), essential for DNA replication and repair, directly interacts with phosphatidylinositol 3-phosphate [PI(3)P], and FEN1-R378 is the primary PI(3)P-binding site. PI(3)P-binding deficient FEN1 mutant (FEN1-R378A) cells exhibited abnormal chromosomal structures and were hypersensitized to DNA damage. The PI(3)P-mediated FEN1 functionality was essential for repairing DNA damages caused by multiple mechanisms. Furthermore, VPS34, the major PI(3)P synthesizing enzyme, was negatively associated with patients' survival in various cancer types, and VPS34 inhibitors significantly sensitized chemoresistant cancer cells to genotoxic agents. These findings open up an avenue for counteracting chemoresistance by targeting VPS34-PI(3)P-mediated DNA repair pathway, and call for assessing the efficacy of this strategy in patients suffering from chemoresistance-mediated cancer recurrence in clinical trials.

17.
Neuroscience ; 527: 37-51, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37468029

RESUMO

To investigate intermittent theta-burst stimulation (iTBS) effect on ischemic stroke and the underlying mechanism of neurorehabilitation, we developed an ischemia/reperfusion (I/R) injury model in Sprague-Dawley (SD) rats using the middle cerebral artery occlusion/reperfusion (MCAO/r) method. Next, using different behavioral studies, we compared the improvement of the whole organism with and without iTBS administration for 28 days. We further explored the morphological and molecular biological alterations associated with neuronal apoptosis and neuroinflammation by TTC staining, HE staining, Nissl staining, immunofluorescence staining, ELISA, small RNA sequencing, RT-PCR, and western blot assays. The results showed that iTBS significantly protected against neurological deficits and neurological damage induced by cerebral I/R injury. iTBS also significantly decreased brain infarct volume and increased the number of surviving neurons after 28 days. Additionally, it was observed that iTBS decreased synaptic loss, suppressed activation of astrocytes and M1-polarized microglia, and simultaneously promoted M2-polarized microglial activation. Furthermore, iTBS intervention inhibited neuronal apoptosis and exerted a positive impact on the neuronal microenvironment by reducing neuroinflammation in cerebral I/R injured rats. To further investigate the iTBS mechanism, this study was conducted using small RNA transcriptome sequencing of various groups of peri-infarcted tissues. Bioinformatics analysis and RT-PCR discovered the possible involvement of miR-34c-5p in the mechanism of action. The target genes prediction and detection of dual-luciferase reporter genes confirmed that miR-34c-5p could inhibit neuronal apoptosis in cerebral I/R injured rats by regulating the p53/Bax signaling pathway. We also confirmed by RT-PCR and western blotting that miR-34c-5p inhibited Bax expression. In conclusion, our study supports that iTBS is vital in inhibiting neuronal apoptosis in cerebral I/R injured rats by mediating the miR-34c-5p involvement in regulating the p53/Bax signaling pathway.


Assuntos
Isquemia Encefálica , MicroRNAs , Traumatismo por Reperfusão , Ratos , Animais , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo , Proteína Supressora de Tumor p53 , Doenças Neuroinflamatórias , MicroRNAs/metabolismo , Isquemia Encefálica/metabolismo , Apoptose , Infarto da Artéria Cerebral Média/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
18.
World J Clin Cases ; 11(15): 3631-3636, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37383917

RESUMO

BACKGROUND: Hysteromyoma is not a rare tumor among pregnant women. During pregnancy, the symptoms caused by hysteromyoma can be improved through conservative treatment in most cases. However, in order to ensure the safety of mothers and children, surgeries are necessary in some special cases. CASE SUMMARY: We report a case of pregnancy complicated with hysteromyoma red degeneration. The patient had peritonitis after sudden abdominal pain during the 20th week of pregnancy. Laparoscopic exploration suggested rupture and bleeding of hysteromyoma, which were improved after drainage and an anti-inflammatory treatment. A cesarean section was performed after full term. This case shows the complications of rupture after red degeneration of hysteromyoma during pregnancy. CONCLUSION: We should be alert to rupture of hysteromyoma during pregnancy, and active laparoscopic exploration is essential to improve the prognosis of such patients.

19.
Front Oncol ; 13: 1197447, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333814

RESUMO

Ultrasound elastography (USE) provides complementary information of tissue stiffness and elasticity to conventional ultrasound imaging. It is noninvasive and free of radiation, and has become a valuable tool to improve diagnostic performance with conventional ultrasound imaging. However, the diagnostic accuracy will be reduced due to high operator-dependence and intra- and inter-observer variability in visual observations of radiologists. Artificial intelligence (AI) has great potential to perform automatic medical image analysis tasks to provide a more objective, accurate and intelligent diagnosis. More recently, the enhanced diagnostic performance of AI applied to USE have been demonstrated for various disease evaluations. This review provides an overview of the basic concepts of USE and AI techniques for clinical radiologists and then introduces the applications of AI in USE imaging that focus on the following anatomical sites: liver, breast, thyroid and other organs for lesion detection and segmentation, machine learning (ML) - assisted classification and prognosis prediction. In addition, the existing challenges and future trends of AI in USE are also discussed.

20.
Arch Biochem Biophys ; 744: 109678, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37356609

RESUMO

Malignant melanoma is an invasive and highly aggressive skin cancer that-if diagnosed-poses a serious threat to the patient's health and life. In this work, a novel purified cell-wall polysaccharide (termed Abwp) was obtained from the discarded stipe of Agaricus bisporus (A. bisporus) and characterized to be a novel homogeneous polysaccharide consisted of a ß-(1 â†’ 4)- glucosyl backbone with ß-(1 â†’ 2) and (1 â†’ 6)-d-glucosyl side-chains. The anti-melanoma effects of Abwp and its associated mechanisms in mice were then explored using in vitro and in vivo approaches. In vitro results showed that Abwp inhibited B16 melanoma cell proliferation and promoted their apoptosis in both time- and dose-dependent manners. In B16 cells induced with tumor necrosis factor (TNF-α), Abwp significantly decreased the protein expression of inflammatory-related signaling pathway (e.g., p38 MAPK and NF-κB) in time-, concentration-, and dose-dependent manners. Moreover, Abwp blocked nuclear entry of NF-κB-p65. In an in vivo mouse model featuring neoplasm transplantation with B16 melanoma cells, Abwp significantly inhibited the growth and proliferation of mouse melanoma. Hematoxylin staining showed that the invasion of melanoma cells into the lung tissue of the Abwp-treated group was significantly reduced. Immunohistochemical analysis showed that the expression of proliferation cell nuclear antigen (PCNA), N-cadherin, MMP-9, and Snail in the lung of mouse was significantly inhibited. Immunofluorescence showed that Abwp significantly interfered with the nuclear transcription of NF-κB-p65 in a dose-dependent manner. Collectively, these results showed that Abwp mediated p38 MAPK and NF-κB signaling pathways to inhibit the inflammatory response and malignant proliferation and metastasis of melanoma in mice.


Assuntos
Melanoma Experimental , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Melanoma Experimental/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Proliferação de Células , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral
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