RESUMO
OBJECTIVES: The project intended to analyze the impact of burden and related risk factors of late-onset colorectal cancer (LOCRC) and early-onset colorectal cancer (EOCRC) in China, thus offering essential references for optimizing prevention and control strategies. METHOD: Global Burden of Disease Study was employed to describe burden changes of EOCRC and LOCRC in China during 1990-2019, containing the numbers of incidence, deaths, prevalence, and disability-adjusted life years (DALYs), and to compare attributable deaths and DALYs risk factors in varying age and sex segments. RESULTS: The numbers and corresponding crude rates of incidence, deaths, prevalence, and DALYs of EOCRC and LOCRC in China during 1990-2019 demonstrated an upward trend across all age categories, with males being dramatically predominant. Overall, over time, the impact of a low-calcium diet and a low-fiber diet on mortality and DALY rates decreased, while the impact of other risk factors increased. In terms of gender, the risk factors affecting males changed greatly, with smoking, inadequate milk intake, and the low whole-grain diet being the main factors in 2019, while in 1990, the main factors were the low-calcium diet, smoking, and inadequate milk intake. CONCLUSION: The burden of colorectal cancer in China is concerning. Patients grouped by diagnostic age exhibit different characteristics, indicating the need for high-quality research in the future to achieve personalized medicine tailored to different population characteristics.
RESUMO
BACKGROUND: Arsenic is a toxic metalloid that can cause acute and chronic adverse health problems. Unfortunately, rice, the primary staple food for more than half of the world's population, is generally regarded as a typical arsenic-accumulating crop plant. Evidence indicates that arsenic stress can influence the growth and development of the rice plant, and lead to high concentrations of arsenic in rice grain. But the underlying mechanisms remain unclear. METHODS: In the present research, the possible molecules and pathways involved in rice roots in response to arsenic stress were explored using bioinformatics methods. Datasets that involving arsenic-treated rice root and the "study type" that was restricted to "Expression profiling by array" were selected and downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the arsenic-treated group and the control group were obtained using the online web tool GEO2R. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to investigate the functions of DEGs. The protein-protein interactions (PPI) network and the molecular complex detection algorithm (MCODE) of DEGs were analyzed using STRING and Cystoscope, respectively. Important nodes and hub genes in the PPI network were predicted and explored using the Cytoscape-cytoHubba plug-in. RESULTS: Two datasets, GSE25206 and GSE71492, were downloaded from Gene Expression Omnibus (GEO) database. Eighty common DEGs from the two datasets, including sixty-three up-regulated and seventeen down-regulated genes, were then selected. After functional enrichment analysis, these common DEGs were enriched mainly in 10 GO items, including glutathione transferase activity, glutathione metabolic process, toxin catabolic process, and 7 KEGG pathways related to metabolism. After PPI network and MCODE analysis, 49 nodes from the DEGs PPI network were identified, filtering two significant modules. Next, the Cytoscape-cytoHubba plug-in was used to predict important nodes and hub genes. Finally, five genes [Os01g0644000, PRDX6 (Os07g0638400), PRX112 (Os07g0677300), ENO1(Os06g0136600), LOGL9 (Os09g0547500)] were verified and could serve as the best candidates associated with rice root in response to arsenic stress. CONCLUSIONS: In summary, we elucidated the potential pathways and genes in rice root in response to arsenic stress through a comprehensive bioinformatics analysis.
Assuntos
Arsênio , Oryza , Mapas de Interação de Proteínas , Oryza/genética , Arsênio/toxicidade , Biologia Computacional , Perfilação da Expressão Gênica , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Redes Reguladoras de Genes/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ontologia GenéticaRESUMO
RATIONALE: The intrauterine device is one of the effective, safe, convenient, economical, and reversible contraceptive methods. Although its contraceptive effect is definite, some female patients may experience complications such as expulsion, bleeding, and pregnancy with the device in place. Rectal perforation is one of the rare and serious complications, which can lead to complications such as abdominal infection and intestinal adhesions, severely affecting the quality of life of patients. PATIENT CONCERNS: A 34-year-old female was sent to the Department of Gastroenterology with noticeable left lower quadrant abdominal pain. She had presented with abdominal discomfort and anal tenesmus 1 year earlier. Two months ago, her abdominal pain had gradually worsened and she was presented to our hospital. DIAGNOSES: Investigations, including colonoscopy and computed tomography scan, had revealed an intrauterine device migrated and perforated into the rectum. INTERVENTIONS AND OUTCOMES: The patient underwent successful colonoscopic removal of the intrauterine device. She recovered well after the treatment. LESSONS: This case proves that endoscopic therapy can be considered the preferred method for removing intrauterine devices displaced into the digestive tract lumen.
Assuntos
Colonoscopia , Perfuração Intestinal , Migração de Dispositivo Intrauterino , Reto , Humanos , Feminino , Adulto , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Perfuração Intestinal/cirurgia , Perfuração Intestinal/etiologia , Reto/lesões , Migração de Dispositivo Intrauterino/efeitos adversos , Remoção de Dispositivo/métodos , Dispositivos Intrauterinos/efeitos adversosRESUMO
Leukemia is a life-threatening malignant tumor of the hematopoietic system. Currently, the main treatment modalities are chemotherapy and hematopoietic stem cell transplantation. However, increased drug resistance due to decreased sensitivity of leukemia cells to chemotherapeutic drugs presents a major challenge in current treatments. Autophagy-associated proteins involved in autophagy initiation have now been shown to be involved in the development of various types of leukemia cells and are associated with drug resistance. Therefore, this review will explore the roles of autophagy-related proteins involved in four key autophagic processes: induction of autophagy and phagophore formation, phagophore extension, and autophagosome formation, on the development of various types of leukemias as well as drug resistance. Autophagy may become a promising therapeutic target for treating leukemia.
RESUMO
Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.
RESUMO
Conventional type 1 dendritic cells (cDC1) are the essential antigen-presenting DC subset in antitumor immunity. Suppressing B-cell lymphoma 9 and B-cell lymphoma 9-like (BCL9/BCL9L) inhibits tumor growth and boosts immune responses against cancer. However, whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely understood. Here, we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into tumor. Pharmacological inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8+ T cell responses. Mechanistically, targeting BCL9/BCL9L promoted antigen presentation in tumors. This is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 axis. Importantly, using single-cell transcriptomics analysis, we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type (WT) cDC1 at activation and antigen presentation via NF-κB/IRF1 signaling. Together, we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens, as well as CD8+ T cell activation and tumor infiltration. Targeting BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.
Assuntos
Apresentação de Antígeno , Células Dendríticas , Animais , Humanos , Camundongos , Apresentação de Antígeno/imunologia , Apresentação de Antígeno/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Camundongos Knockout , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/patologia , Receptores de Quimiocinas , Fatores de Transcrição/genética , Fatores de Transcrição/imunologiaRESUMO
Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.
Assuntos
Nanopartículas , Radioimunoterapia , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/terapia , Animais , Camundongos , Feminino , Radioimunoterapia/métodos , Nanopartículas/química , Humanos , Modelos Animais de Doenças , Metais Terras Raras/química , Linhagem Celular TumoralRESUMO
BACKGROUND: Dietary rationality and health concept have certain influence on individual health level. This study aims to explore the characteristics and existing problems of Chinese residents' health behaviors from both macro and micro perspectives, and explore the feasibility and realization path of Healthy China strategy. METHODS: We utilized regression models to evaluate the correlation between diet and the risk of disease causes of death. By use of the linear regression analysis model, we distinguished the impact of each dimension on health literacy index at the individual level. Then, we explored the influential factors of the diet health index using the binary logit regression model. RESULTS: Increased consumption of animal-derived foods in China has contributed to the burden of non-communicable diseases. The individuals' health awareness is still weak, and the health literacy index is greatly affected by the diet, while the individual gender and age are positively correlated with the diet health index, and the individual body mass index (BMI) level is negatively correlated with the diet health index. CONCLUSIONS: This study provided a comprehensive understanding of existing problems of Chinese residents' health behaviors. We have proposed a path model for the implementation of the Healthy China strategy from the perspectives of "diet health, physical health, conceptual health and environmental health," which is also a great contribution to the world.
Assuntos
Comportamentos Relacionados com a Saúde , Humanos , China , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dieta , Letramento em Saúde , Idoso , Dieta Saudável , Adulto JovemRESUMO
Ulcerative colitis (UC) is characterized by chronic inflammatory processes of the intestinal tract of unknown origin. Current treatments lack understanding on how to effectively alleviate oxidative stress, relieve inflammation, as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously. In this study, a novel drug delivery system based on a metal polyphenol network (MPN) was constructed via metal coordination between epigallocatechin gallate (EGCG) and Fe3+. Curcumin (Cur), an active polyphenolic compound, with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN. The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical (O2â¢-) as well as hydroxyl radical (·OH). By hitchhiking yeast microcapsule (YM), Cur-MPN was then encapsulated into YM to obtain CM@YM. Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon. When administered orally, CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS, reducing pro-inflammatory cytokines, and regulating the polarization of macrophages to M1, thus restoring barrier function and maintaining intestinal homeostasis. Importantly, CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids (SCFA) (such as acetic acid, propionic acid, and butyric acid). Collectively, with excellent biocompatibility, our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.
RESUMO
Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are time-consuming and not highly sensitive. Thus, we are aiming to develop feasible and efficient models to optimize the differential diagnosis in clinical practice. This study included 191 febrile patients from our center, including 85 with CRS-related fever and 106 with infectious fever. By leveraging the serum cytokine profile at the peak of fever, we generated differential models using a classification tree algorithm and a stepwise logistic regression analysis, respectively. The first model utilized three cytokines (IFN-ß, CXCL1, and CXCL10) and demonstrated high sensitivity (90% training, 100% validation) and specificity (98.44% training, 90.48% validation) levels. The five-cytokine model (CXCL10, CCL19, IL-4, VEGF, and CCL20) also showed high sensitivity (91.67% training, 95.65% validation) and specificity (98.44% training, 100% validation). These feasible and accurate differentiation models may prompt early diagnosis of infections during immune therapy, allowing for early and appropriate intervention.
RESUMO
A growing number of studies have revealed an association between proteasome activator complex subunit 2 (PSME2) and the progression of various forms of cancer. However, the effect of PSME2 on osteosarcoma progression is unknown. Pan-cancer analyses focused on the immunological activity and prognostic relevance of PSME2 have yet to be conducted. The Cancer Genome Atlas and Genome-Tissue Expression databases were leveraged to evaluate PSME2 expression and activity across 33 cancer types. Significant PSME2 dysregulation was noted in a wide range of cancer types and this gene was found to offer significant diagnostic and prognostic utility in most analyzed cancers. From a mechanistic perspective, PSME2 expression levels were correlated with DNA methylation, DNA repair, genomic instability, and TME scores in multiple cancer types. PSME2 was subsequently established as a pan-cancer biomarker of M1 macrophage infiltration based on a combination of bulk, single-cell, and spatial transcriptomic data and confirmatory fluorescent staining results. In osteosarcoma cells, overexpressing PSME2 significantly suppressed tumor proliferative, migratory, and invasive activity. Screening efforts also successfully identified the PSME2-activating drug irinotecan, which can synergistically promote the death of osteosarcoma cells when combined with the chemotherapeutic drug paclitaxel. As a biomarker of M1 macrophage infiltration, PSME2 expression levels may offer insight into tumor development and progression for a wide range of cancers including osteosarcoma, emphasizing its potential utility as a prognostic and therapeutic target worthy of further study.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Osteossarcoma/genética , Fenótipo , Biomarcadores Tumorais/genética , Macrófagos , Neoplasias Ósseas/genética , Complexo de Endopeptidases do ProteassomaRESUMO
Background: Patients with hematologic malignancies usually have severe immunodeficiency and are much more likely to be severe after COVID-19 infection. Tocilizumab is a monoclonal antibody of interleukin-6 (IL-6) and is recommended for treating severe conditions in the latest COVID-19 treatment guidelines. However, the efficacy and safety of tocilizumab in hematologic malignancy patients have yet to be clarified. We report five hematologic malignancy patients with severe COVID-19 infection who were all successfully recovered with tocilizumab treatment. Methods: We reported five hematologic malignant patients who developed severe COVID-19 infection and received tocilizumab at the First Affiliated Hospital of Zhejiang University School of Medicine during the COVID-19 pandemic in China from Dec 2022 to Mar 2023. We observed the effect of tocilizumab on COVID-19 infection and evaluated its safety. Results: Five hematologic malignancy patients with severe COVID-19 infection were retrospectively enrolled. The dosage of tocilizumab was 400-480mg once; one patient used a second dose of tocilizumab on the third day of medication. After receiving tocilizumab treatment, all five patients experienced a rapid decrease in body temperature and C-reactive protein (CRP) within 24 hours and improved oxygen requirement within one to three days (one patient did not experience hypoxia). Chest CT scans after one week showed absorption of lung infection. The serum IL-6 levels of three patients showed an initial increase followed by a decrease. None of the patients experienced grade 3-4 hematologic or non-hematologic toxicity. Conclusion: Tocilizumab can improve the outcome of severe COVID-19 infection in hematologic malignancy patients with severe immunodeficiency without severe adverse reactions.
RESUMO
Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography-time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound-target-disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.
Assuntos
Ansiolíticos , Sesquiterpenos , Humanos , Ansiolíticos/farmacologia , Farmacologia em Rede , Microextração em Fase Sólida , Transtornos de Ansiedade , Cromatografia Gasosa-Espectrometria de Massas , Sesquiterpenos/farmacologiaRESUMO
Preeclampsia (PE) is a life-threatening disease that severely harms pregnant women and infants' health but has a poorly understood etiology. Peptidomics can supply important information about the occurrence of diseases. However, application of peptidomics in preeclamptic placentas has never been reported. We conducted a comparative peptidomics analysis of PE placentas and performed bio-informatics analysis on differentially expressed peptides. Effects of differential peptide 405SPLFMGKVVNPTQK418 on the behaviors of trophoblasts and angiogenesis were assessed by CCK8, transwell assays, and tube network formation assays. And we also confirmed the role of peptide in the zebrafish xenograft model. A total of 3582 peptide were identified. 48 peptides were differentially expressed. Bioinformatics analysis indicated that precursor proteins of these differentially expressed peptides correlate with "complement and coagulation cascades," and "platelet activation" pathways. Of the 48 differential peptides, we found that peptide 405SPLFMGKVVNPTQK418 can significantly increase proliferation, migration of trophoblasts and stimulate angiogenesis of HUVECs in vitro and zebrafish model. These findings suggest peptidomes can aid in understanding the pathogenesis of PE more comprehensively. Peptide 405SPLFMGKVVNPTQK418 can be novel target and strategy to alleviate the condition of preeclampsia.
Assuntos
Pré-Eclâmpsia , Peixe-Zebra , Animais , Humanos , Gravidez , Feminino , Pré-Eclâmpsia/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Peptídeos/metabolismo , Peptídeos/farmacologia , Proteômica , alfa 1-Antitripsina/metabolismo , alfa 1-Antitripsina/farmacologiaRESUMO
BACKGROUND AND AIMS: The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. MATERIALS AND METHODS: uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. RESULTS: Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729-0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage â ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727-0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. CONCLUSION: Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC.
Assuntos
Carcinoma de Células Renais , Vesículas Extracelulares , Neoplasias Renais , MicroRNAs , Humanos , MicroRNAs/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Estudos de Casos e Controles , Biomarcadores Tumorais/genética , Biomarcadores , Vesículas Extracelulares/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genéticaRESUMO
Glucosinolates (GLS) in cruciferous vegetables are anti-nutritional factors. Excessive or long-term intake of GLS-containing feed is harmful to animal health and may cause kidney damage. Phenethyl isothiocyanate (PEITC) is a GLS. In this study, we investigated the inhibitory effect of PEITC on a porcine kidney (PK-15) cell line and explored the mechanism of PEITC-induced apoptosis. We found that PEITC could affect cell viability and induce cell apoptosis after incubating cells for 24 h. High concentrations of PEITC can induce intracellular ROS accumulation, resulting in impaired mitochondrial function (decreased MMP, decreased ATP) and DNA damage (increased 8-OHdG), cytochrome c in mitochondria is released into the cytoplasm and activates mitochondrial pathway apoptosis-related proteins (Bcl-2 family and caspase-9, -3). Meanwhile, PEITC could induce intracellular Ca2+ accumulation, disrupt ER homeostasis, and activate the expression levels of three ER-resident transmembrane proteins orchestrating the UPR (PERK, IRE-1α and ATF6) and ER-related proteins (GRP78 and CHOP), thereby activating ERS-pathway apoptosis-related proteins (caspase-12, -7). Our results showed that low concentration (2.5 µM) of PEITC had no damaging effect on cells. In comparison, a high concentration (10 µM) of PEITC could induce cell damage in porcine kidney cells and induce apoptosis in PK-15 cells via the Mitochondrial ROS-associated ERS pathway.
Assuntos
Proteínas Reguladoras de Apoptose , Apoptose , Animais , Suínos , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial , Proteínas Reguladoras de Apoptose/metabolismo , Mitocôndrias , Rim/metabolismo , Linhagem Celular TumoralRESUMO
Serum is a common biomaterial in cell culture that provides nutrients and essential growth factors for cell growth. Serum heat inactivation is a common treatment method whose main purpose is to remove complement factors and viruses. As serum contains many heat-labile factors, heat inactivation may affect cell proliferation, migration, differentiation, and other functions. However, the specific mechanism of its effect on cell function has not been studied. Thus, we investigate the exact effects of heat-inactivated FBS on the viability of various cells and explore the possible molecular mechanisms. We treated HCT116, HT-29, and HepG2 cell lines with heat-inactivated (56 °C for 30 min) medium, DMEM, or fetal bovine serum (FBS) for different times (0, 10, 15, 30, 60, or 90 min); we found that heat-inactivated FBS significantly promoted the viability of these cells, whereas DMEM did not have this effect. Moreover, heat-inactivated FBS stimulated cells to produce a small amount of ROS and activated intracellular signaling pathways, mainly the p38/AKT signaling pathway. These results indicate that heat-inactivated FBS may regulate the p38/AKT signaling pathway by promoting the production of appropriate amounts of ROS, thereby regulating cell viability.
Assuntos
Temperatura Alta , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Proliferação de Células , Transdução de SinaisRESUMO
Glioma is the most common malignancy in the central nervous system. This study aims to disclose the impacts of Xihuang pill (XHP), a traditional Chinese formula, on glioma cell pyroptosis and relevant molecular mechanism. U251 and SHG-44 cells were treated with XHP alone or together with oe-POU4F1 and sh-STAT3. CCK8 assay detected the viability, flow cytometry evaluated pyroptosis, and microscopy observed cell morphology. LDH release was determined by the LDH kit and the levels of IL-1ß and IL-18 were detected by ELISA. Immunofluorescence showed NLRP3 expression in glioma cells and western blotting measured the levels of POU4F1, STAT3, NLRP3, ASC, cleaved caspase-1, and IL-1ß. The binding of POU4F1 to STAT3 was verified. Primary glioma model was established to observe tumor change by in vivo imaging, determine the levels of Ki67 and NLRP3 by immunochemistry, and detect relevant protein levels by western blotting. XHP treatment alone downregulated POU4F1 and STAT3 levels, aroused pyroptotic appearance in glioma cells such as ballooning swelling, reduced cell viability and number of pyroptotic cells, increased LDH release and IL-1ß and IL-18 levels, formed NLRP3 sports in cells, and elevated the levels of pyroptosis-related proteins. However, POU4F1 overexpression or STAT3 silencing suppressed XHP-promoted pyroptosis. Mechanistically, POU4F1 acted as a transcription factor of STAT3 and regulated its transcription. In primary glioma models, XHP enhanced glioma cell pyroptosis and blocked glioma growth. XHP facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.
Assuntos
Glioma , Interleucina-18 , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Glioma/tratamento farmacológico , Glioma/genética , Fator de Transcrição Brn-3A , Fator de Transcrição STAT3/genéticaRESUMO
Background: Death education has been confirmed to be an effective method to enhance nursing students' attitudes and coping abilities toward death. However, integrated Narrative Pedagogy into the death education to explore educational effectiveness is still limited. The study aimed to evaluate the effects of a death education based on Narrative Pedagogy in a palliative care course on the attitude toward death, coping with death, and attitude toward caring for the dying among undergraduate nursing students in China. Methods: The study was designed as a pre-post intervention study with a quasi-experimental design. All the participants received 6 class hours of death education which was designed in a palliative care course. The death education includes preparation, presentation, discussion, reflection, and practice of the narrative materials. Death Attitude Profile-Revised (DAP-R), Coping with Death Scale (CDS), and Frommelt Attitude Toward Care of the Dying-Form B (FATCOD-Form B) were used to measure outcomes. Results: Sixty undergraduate nursing students who consented. There were statistically significant increases in the mean score of neutral acceptance and approach acceptance in the DAP-R, CDS, and FATCOD-Form B before and after the intervention. Conclusion: This death education integrated Narrative Pedagogy which indicated to improve attitude toward death, competence to cope with death, and attitude toward the care of dying patients. The findings assist teachers in understanding the importance and urgency of death education, as well as providing a favorable approach to death education. However, the long-term effectiveness still needs to study in further.