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1.
J Cancer Res Clin Oncol ; 150(8): 386, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110225

RESUMEN

Colorectal cancer (CRC) remains a highly prevalent gastrointestinal neoplasm, presenting significant prevalence and lethality rate. DEAD/H box RNA helicase 10 (DDX10) has been proposed as a potential oncogene in CRC, the specific action mechanism by which DDX10 modulates the aggressive biological cellular events in CRC remains implicitly elucidated, however. During this study, DDX10 expression was detected via RT-qPCR and Western blotting. Cell proliferation was estimated via EDU staining. TUNEL staining and Western blotting appraised cell apoptosis. Cell stemness was evaluated by sphere formation assay, RT-qPCR, Western blotting as well as immunofluorescence staining. Relevant assay kit examined aldehyde dehydrogenase (ALDH) activity. Western blotting and immunofluorescence staining also detected autophagy. DDX10 was hyper-expressed in CRC cells. Down-regulation of DDX10 hampered cell proliferation, aggravated the apoptosis while eliminated the ability to form spheroid cells in CRC. In addition, DDX10 deletion improved ATG10 expression and therefore activated autophagy in CRC cells. Consequently, ATG10 depletion or treatment with autophagy inhibitor 3-Methyladenine (3-MA) partially compensated the influences of DDX10 silencing on the proliferation, apoptosis and stemness of CRC cells. Accordingly, DDX10 deficiency may aggravate autophagy mediated by ATG10 to impede cell proliferation, stemness and facilitate cell apoptosis, hence blocking the progression of CRC.


Asunto(s)
Apoptosis , Proteínas Relacionadas con la Autofagia , Autofagia , Proliferación Celular , Neoplasias Colorrectales , ARN Helicasas DEAD-box , Células Madre Neoplásicas , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Autofagia/fisiología , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Línea Celular Tumoral , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Ratones , Animales , Proteínas de Transporte Vesicular
2.
Cancers (Basel) ; 16(14)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39061140

RESUMEN

Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma.

3.
Int J Surg ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935124

RESUMEN

BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

4.
BMC Infect Dis ; 24(1): 642, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926657

RESUMEN

OBJECTIVE: Given the high prevalence of hypertension among Chinese adults, this population is at a significantly increased risk of severe COVID-19 complications. The purpose of this study is to assess the willingness of Chinese hypertensive adults to receive the COVID-19 vaccine and to identify the diverse factors that shape their vaccination decisions. METHODS: Sampling was conducted utilizing multistage stratified random sampling, and ultimately, a total of 886 adult hypertensive patients from Luzhou City in Southwest China were included in this study. The questionnaire design was based on the Theory of Planned Behaviour and was used to investigate their willingness to be vaccinated with COVID-19. Structural equation modeling was employed for data analysis. RESULTS: The results showed that 75.6% of hypertensive individuals were willing to receive COVID-19 vaccination. The structural equation modeling revealed that Subjective Norms (path coefficient = 0.361, CR = 8.049, P < 0.001) and Attitudes (path coefficient = 0.253, CR = 4.447, P < 0.001) had positive effects on vaccination willingness, while Perceived Behavioral Control (path coefficient=-0.004, CR=-0.127, P = 0.899) had no significant impact on Behavioral Attitudes. Mediation analysis indicated that Knowledge (indirect path coefficient = 0.032, LLCI = 0.014, ULCI = 0.058), Risk Perception (indirect path coefficient = 0.077, LLCI = 0.038, ULCI = 0.124), and Subjective Norms (indirect path coefficient = 0.044, LLCI = 0.019, ULCI = 0.087) significantly influenced vaccination willingness through Attitudes as a mediating factor. CONCLUSION: The willingness of hypertensive individuals to receive the COVID-19 vaccination is not satisfactory. The Theory of Planned Behavior provides valuable insights into understanding their vaccination intentions. Efforts should be concentrated on enhancing the subjective norms, attitudes, and knowledge about vaccination of hypertensive patients.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Hipertensión , Intención , SARS-CoV-2 , Vacunación , Humanos , Hipertensión/epidemiología , Hipertensión/psicología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/psicología , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Vacunas contra la COVID-19/administración & dosificación , Vacunación/psicología , Vacunación/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios , Análisis de Clases Latentes , Anciano , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios Transversales , Pueblos del Este de Asia
5.
Int J Oncol ; 65(1)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38818827

RESUMEN

Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit­8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylin­eosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcription­quantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786­O and ACHN) than the effect on normal renal tubular epithelial cell (HK­2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dose­dependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.


Asunto(s)
Proteínas Relacionadas con la Autofagia , Autofagia , Carcinoma de Células Renales , Movimiento Celular , Proliferación Celular , Ácido Gálico , Neoplasias Renales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Humanos , Ácido Gálico/farmacología , Autofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular/efectos de los fármacos , Animales , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Progresión de la Enfermedad , Masculino , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas Portadoras/metabolismo
6.
Clin Oral Investig ; 28(5): 269, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656417

RESUMEN

OBJECTIVE: Radial Forearm Free flap (RFFF) is widely used in head and neck reconstruction, yet its donor site defect remains a significant drawback. The Medial Sural Artery Perforator Free Flap (MSAPFF) is considered an alternative flap to RFFF. This study aims to comprehensively analyze their characteristics, outcomes, and their impact on patient quality of life. METHODS: All patients who underwent oral cavity reconstruction using RFFF and MSAPFF between February 2017 and April 2023 were included in this study. Flap characteristics, outcomes and post-operative complications were recorded and compared. Subjective donor site morbidity, aesthetic and functional results, and quality of life were also analyzed. RESULTS: The study included 76 patients: 37 underwent reconstruction with RFFF, and 39 with MSAPFF. There was no significance difference between the RFFF and MSAPFF regarding the success rate (97.2% vs 97.4%), flap size (4.8 × 8.8 cm2 vs 5 × 9.8 cm2), hospital of stay (15.5 days vs 13.5 days) and recipient site complications (P > 0.05). However, MSAPFF showed larger flap thickness (P = 0.001), smaller arterial caliber (P = 0.008), shorter pedicle length (P = 0.001), and longer harvesting time (P < 0.001). No significant difference was observed between the pre-and postoperative ranges of wrist and ankle movements or in recipient site complications. MSAPFF showed a significant difference in donor site morbidity (P < 0.05). CONCLUSION: The MSAPFF is an excellent alternative to the RFFF for repairing oral cavity defects, with additional advantage of a well-hidden scar on the posterior calf, a larger flap thickness, accepted pedicle length and arterial caliber. However, one should consider the harvesting time and surgical skills required in comparison to the RFFF. CLINICAL RELEVANCE: The study highlights the importance of the MSAPFF as an alternative option for RFFF with less donor site morbidity and high success rate in oral cavity reconstruction and improved patient Quality of life after ablative surgery.


Asunto(s)
Antebrazo , Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Calidad de Vida , Humanos , Femenino , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Colgajo Perforante/irrigación sanguínea , Antebrazo/cirugía , Sitio Donante de Trasplante/cirugía , Adulto , Anciano , Estudios Retrospectivos , Neoplasias de la Boca/cirugía , Boca/cirugía
7.
Biomed Chromatogr ; 38(5): e5835, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38304995

RESUMEN

The saponin-enriched extract from Celosiae Semen is a promising resource owing to its lipid-lowering activity. However, triterpenoid saponins are difficult to extract owing to their high molecular weight and strong water solubility. The aim of this paper was to explore an eco-friendly and effective technology of extraction and enrichment of total triterpenoid saponins to obtain high lipid-lowering fractions. Initially, Box-Behnken design experiments were employed to optimize the heat reflux extraction process on the basic of mono-factor experiments. Afterwards, the crude extract was further purified using D-101 resin, and the purification parameters were investigated based on adsorption/desorption experiments and biological activity assay. Under optimal conditions, the purity of the finally obtained total triterpenoid saponins was increased by 7.28-fold. The lipid-lowering activities of the six main triterpenoid saponins were evaluated in HepG2 cells induced by palmitic acid. The results of Oil Red O staining showed that the compounds all exhibited potential lipid-lowering activity. The structure-activity relationship analysis suggested that the oligosaccharide chain at C-28 played an essential role in their lipid-lowering activity and the substituent group at C-23 site also showed important effects. The optimal extraction and purification methods may facilitate the utilization of Celosiae Semen for the industrial production as a functional food and drug.


Asunto(s)
Amaranthaceae , Metabolismo de los Lípidos , Saponinas/química , Saponinas/farmacología , Triterpenos/química , Amaranthaceae/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Humanos , Células Hep G2 , Etanol/química
8.
ACS Mater Au ; 4(1): 14-29, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38221923

RESUMEN

Radical prostatectomy is a primary treatment option for localized prostate cancer (PCa), although high rates of recurrence are commonly observed postsurgery. Photodynamic therapy (PDT) has demonstrated efficacy in treating nonmetastatic localized PCa with a low incidence of adverse events. However, its limited efficacy remains a concern. To address these issues, various organic polymeric nanoparticles (OPNPs) loaded with photosensitizers (PSs) that target prostate cancer have been developed. However, further optimization of the OPNP design is necessary to maximize the effectiveness of PDT and improve its clinical applicability. This Review provides an overview of the design, preparation, methodology, and oncological aspects of OPNP-based PDT for the treatment of PCa.

9.
Head Neck ; 46(3): 528-540, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38111234

RESUMEN

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/genética , Epigénesis Genética , China , Neoplasias de Cabeza y Cuello/genética , Mutación
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