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BACKGROUND: Pulmonary hypertension (PH) is a long-term disease that impacts approximately 1% of the world's population. Currently, levosimendan (Lev) is proposed for PH treatment. However, the mechanism of Lev in the treatment of PH is unknown. METHODS: We used hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) to establish a PH cell model. A number of cell biology methods were performed to assay alterations in cell proliferation, migration and apoptosis after Lev treatment. qRT-PCR and WB were performed to test the levels of circUSP34 and miR-1298, and BMP/Smad protein respectively. In addition, the regulatory relationship between circUSP34 or BMPR2 with miR-1298 was verified through the use of double luciferase as well as RIP assay. In addition, we explored the regulatory effect of Lev on the circUSP34/miR-1298/BMP/Smad axis using a rat PH model. RESULTS: Our results demonstrate that Lev inhibited PASMCs cell proliferation, migration and promoted apoptosis exposed to hypoxia. In hypoxia-treated PASMCs, circUSP34 expression got downregulated while miR-1298 upregulated, whereas the addition with Lev resulted in upregulation of circUSP34 expression and downregulation of miR-1298 expression, indicating that circUSP34 can target and regulate miR-1298. In addition, miR-1298 targets and regulates the expression of BMPR2. In a rat PH model induced by hypoxia combined with SU5416, Lev upregulated circUSP34 targeting miR-1298-mediated BMP/Smad axis to alleviate the PH phenotype. CONCLUSION: We have shown that Lev can be used as a therapeutic drug for PH patients, which works through the circUSP34/miR-1298/BMP/Smad axis to alleviate PH symptoms.
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Hipertensão Pulmonar , MicroRNAs , Ratos Sprague-Dawley , Simendana , Regulação para Cima , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Ratos , Regulação para Cima/efeitos dos fármacos , Simendana/farmacologia , Masculino , Células Cultivadas , Proteínas Smad/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Proliferação de Células/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Apoptose/efeitos dos fármacosRESUMO
BACKGROUND: Sublobar resection for ground-glass opacity became a recommend surgery choice supported by the JCOG0804/JCOG0802/JCOG1211 results. Sublobar resection includes segmentectomy and wedge resection, wedge resection is suitable for non-invasive lesions, but in clinical practice, when pathologists are uncertain about the intraoperative frozen diagnosis of invasive lesions, difficulty in choosing the appropriate operation occurs. The purpose of this study was to analyze how to select invasive lesions with clinic-pathological characters. METHODS: A retrospective study was conducted on 134 cases of pulmonary nodules diagnosed with minimally invasive adenocarcinoma by intraoperative freezing examination. The patients were divided into two groups according to intraoperative frozen results: the minimally invasive adenocarcinoma group and the at least minimally invasive adenocarcinoma group. A variety of clinical features were collected. Chi-square tests and multiple regression logistic analysis were used to screen out independent risk factors related to pathological upstage, and then ROC curves were established. In addition, an independent validation set included 1164 cases was collected. RESULTS: Independent risk factors related to pathological upstage were CT value, maximum tumor diameter, and frozen result of AL-MIA. The AUC of diagnostic mode was 71.1% [95%CI: 60.8-81.3%]. The independent validation included 1164 patients, 417 (35.8%) patients had paraffin-based pathology of invasive adenocarcinoma. The AUC of diagnostic mode was 75.7% [95%CI: 72.9-78.4%]. CONCLUSIONS: The intraoperative frozen diagnosis was AL-MIA, maximum tumor diameter larger than 15 mm and CT value is more than - 450Hu, highly suggesting that the lung GGO was invasive adenocarcinoma which represent a higher risk to recurrence. For these patients, sublobectomy would be insufficient, lobectomy or complementary treatment is encouraged.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Estadiamento de Neoplasias , Pneumonectomia , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Idoso , Pneumonectomia/métodos , Prognóstico , Seguimentos , Invasividade Neoplásica , China/epidemiologia , Fatores de Risco , Adulto , Tomografia Computadorizada por Raios X/métodos , Curva ROC , População do Leste AsiáticoRESUMO
BACKGROUND: This article summarizes the treatment experience for congenital complete atrioventricular block (CCAVB) in newborns and infants, and discusses the necessity and feasibility of treating CCAVB with permanent pacemaker implantation in this population. METHODS: In this study, the clinical data and follow-up results of nine children admitted at our center with CCAVB from January 2005 to March 2023 were retrospectively analyzed. Among them, two children received early implantation of permanent pacemakers (within 1 year of age), two children received non-early implantation (1 year or older), and the remaining five children received no pacemaker implantation. CCAVB diagnosis was confirmed by clinical symptoms and clinical examinations, including electrocardiography and echocardiography before surgery. After surgery, the pacing and sensing functions of the pacemaker were observed using electrocardiography, echocardiography, and pacing threshold monitoring. A comprehensive assessment of the treatment efficacy was conducted, encompassing improvements in clinical symptoms, growth and development, as well as the absence of any additional potential complications. The children who did not receive pacemaker implantation were followed up. RESULTS: Among the four children who successfully received pacemaker implantation, one child who received non-early implantation died. For the remaining three children, the threshold level, amplitude, impedance, and minute ventilation sensor function of the pacemaker were good during the follow-up period, with a heart rate at the pacing rate. The growth and development of the aforementioned patients who received pacemaker implantation demonstrated adherence to the percentile curve, and their motor and cognitive development remained unaffected. However, among the children who did not undergo pacemaker implantation, two experienced death, while three were lost to follow-up, thereby limiting the evaluation of their long-term outcomes. CONCLUSIONS: Early implantation of an epicardial pacemaker at an early stage in newborns and infants diagnosed with CCAVB can significantly improve clinical symptoms without affecting their growth and development. These data are in line with current literature and suggest that early implantation of an epicardial pacemaker in newborns and infants diagnosed with CCAVB but further studies are needed.
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Bloqueio Atrioventricular , Marca-Passo Artificial , Criança , Humanos , Lactente , Recém-Nascido , Pré-Escolar , Estudos Retrospectivos , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/terapia , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/métodos , SeguimentosRESUMO
BACKGROUND: Microcystic adnexal carcinoma (MAC) is a skin cancer with challenges in diagnosis and management. This study was aimed to detect molecular alterations of MAC and guide its pathologic diagnosis and treatment. METHODS: We performed transcriptome analysis on 5 MAC and 5 normal skin tissues, identified the differentially expressed genes, and verified them by immunohistochemistry. RESULTS: Three hundred four differentially expressed genes (DEGs) in MAC were identified by next-generation transcriptome sequencing, among which 225 genes were upregulated and 79 genes were downregulated. Four genes of the calcium signaling pathway, including calcium voltage-gated channel subunit alpha 1 S (CACNA1S), ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 (ATP2A1), ryanodine receptor 1 (RYR1), and myosin light chain kinase 3 (MYLK3), were upregulated and then been verified by immunohistochemistry. The expression of CACNA1S, ATP2A1, RYR1, and MYLK3 was upregulated in MAC compared with normal sweat glands and syringoma tumor cells and was generally negative in trichoepithelioma and infundibulocystic type basal cell carcinoma. CONCLUSIONS: The four genes of the calcium signaling pathway were upregulated in MAC at both RNA and protein levels. CACNA1S, ATP2A1, RYR1, and MYLK3 may be new diagnostic molecular markers and therapeutic targets for MAC.
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Canal de Liberação de Cálcio do Receptor de Rianodina , Neoplasias Cutâneas , Sinalização do Cálcio , Carcinoma Basocelular , Perfilação da Expressão Gênica , Humanos , Neoplasias de Anexos e de Apêndices Cutâneos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Protein secondary structure provides rich structural information, hence the description and understanding of protein structure relies heavily on it. Identification or prediction of secondary structures therefore plays an important role in protein research. In protein NMR studies, it is more convenient to predict secondary structures from chemical shifts as compared to the traditional determination methods based on inter-nuclear distances provided by NOESY experiment. In recent years, there was a significant improvement observed in deep neural networks, which had been applied in many research fields. Here we proposed a deep neural network based on bidirectional long short term memory (biLSTM) to predict protein 3-state secondary structure using NMR chemical shifts of backbone nuclei. While comparing with the existing methods the proposed method showed better prediction accuracy. Based on the proposed method, a web server has been built to provide protein secondary structure prediction service.
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Memória de Curto Prazo , Proteínas , Redes Neurais de Computação , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de ProteínaRESUMO
OBJECTIVE: The role of mismatch repair (MMR) deficiency in ovarian cancer (OC) pathogenesis and its association with other clinicopathologic features, such as microsatellite instability (MSI) and expression of checkpoint proteins, remain largely elusive. METHODS: We performed Immunohistochemistry (IHC) for MLH1, MSH2, MSH6 and PMS2 on full-section slides from 419 OCs to assess the MMR status. The clinical relevance of MMR deficiency was analyzed in combination with clinical data. The MSI status (by MSI assay) and expression of CD3, CD8, PD-1 and PD-L1 (by IHC) were compared in OCs with different MMR status. RESULTS: We found that 2.6% OCs were MMR-negative, 4.3% OCs were MMR-low, and 63.6% of MMR-negative OCs were of endometrioid subtype. A significantly higher proportion of MMR-negative OCs were diagnosed at stage I or II compared to MMR-proficient OCs (p=0.0041). MSI was observed in all tested MMR-negative OCs, 14.3% of tested MMR-low OCs and 3.2% of tested MMR-proficient OCs. In addition, MMR-negative OCs had better progression free survival compared to MMR-proficient and MMR-low OCs (p=0.0046). Furthermore, the majority of OCs were PD-1-positive in intratumoral lymphocytes regardless of MMR status; while MMR-negative OCs exhibited significantly increased CD3+ and CD8+ tumor-infiltrating lymphocytes, and PD-L1+ intratumoral immune cells compared to MMR-proficient OCs. CONCLUSION: Our data suggests that MMR deficient OC is a unique molecular subgroup, characterized by early stage of diagnosis, MSI phenotype, and increased tumor-infiltrating lymphocytes. These patients may be good candidates for anti-PD-1/PD-L1 therapy.
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Antígeno B7-H1/biossíntese , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Instabilidade de Microssatélites , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/imunologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/imunologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Adulto , Idoso , Antígeno B7-H1/imunologia , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologiaRESUMO
Background and Aims: Neonatal diseases are a significant threat to global public health, affecting the homeostasis and well-being of patients and reflecting the status of, and challenges to, regional, national, and global healthcare systems. This study sought to investigate how the disease spectrum observed among neonatal inpatients changed after the onset of the coronavirus disease 2019 (COVID-19) pandemic. Methods: The present hospital-based retrospective study analyzed the demographic and clinical characteristics of 19,943 hospitalized newborns from January 2018 to December 2022 using data derived from pediatric department registers. Results: According to the International Classification of Diseases 11th Revision (ICD-11) classification criteria, the two most common neonatal disorders during this study period were "Certain conditions originating in the perinatal period" and "Disease of the respiratory system." Following the start of the COVID-19 pandemic (2020 onwards), the number of neonatal patients declined markedly (5742 per year vs. 2820 per year), and the incidence of "Disease of the respiratory system" was significantly lower than in 2018-2019 (25.72% vs. 17.46%). Conclusion: The study offers detailed insights into the shifts in neonatal disease patterns at the Seventh Medical Center of the PLA General Hospital following the onset of the COVID-19 pandemic, providing a foundation for future research and policymaking efforts.
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Aim: To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the arachidonic acid metabolic pathway and nuclear factor kappa-B(NF-κB) signal path in the hippocampi of postpartum depression rats. Methods: The rats were subcutaneous injected estradiol benzoate and progesterone to build PPD rat model. SJF, paroxetine hydrochloride and sEH inhibitor (AUDA) were used to treat PPD rats for 3 weeks. Then the morphological changes of hippocampi and various proteins were observed after that behavioral test were conducted in all 36 SD rats in six group: SJF, paroxetine, AUDA, PPD, sham and normal group. Results: Weight, results of sucrose preference, upright times, total and center squares crossing decreased significantly (P < 0.01), whereas immobility time increased (P < 0.01). Results above were reversed in animals that in the SJF, paroxetine and AUDA groups. Hippocampal neurons in PPD rats partially degenerated with narrowed nuclei, increased autophagy and mitochondria bound to lysosomes were visible while the autophagy of hippocampal neurons in the paroxetine and AUDA group decreased, with a small amount of lysosomes. sEH, COX-2, 5-LOX, TNF-α, IL-1, IL-6, NF-κB p65, and Cor increased in hippocampi of PPD rats while EETs and 5-HT decreased. Protein expressions of Ibal, GFAP, p-IκBα, p65, and p-p65(S536)increased in PPD animals. Those changes were reversed by SJF, paroxetine and AUDA. Gene expressions of TNF-α, IL-1ß, IL-6, 5-LOX, COX-2 and p65 increased in PPD rats and the changes of expression in these genes were reversed by paroxetine and AUDA. SJF reversed the gene expression changes of COX-2, TNF-α, and IL-1ß. Conclusion: SJF may have an analogous effect as sEH inhibitor to relieve depressive symptoms by suppressing inflammatory signaling pathways in hippocampi of PPD rats, which involves AA metabolic pathway and NF-κB signal pathway.
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Right aortic arch with isolation of left brachiocephalic artery is a rare congenital aortic arch anomaly. Herein, we reported a case of this rare anomaly with ventricular septal defect in a 9-month-old infant. We successfully reconstructed the islolated left brachiocephalic artery and repaired the ventricular septal defect in one stage.
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Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Fusobacterium nucleatum/fisiologia , Neoplasias Colorretais/microbiologia , Via de Sinalização Hippo , Resistencia a Medicamentos Antineoplásicos , Piroptose , Recidiva Local de NeoplasiaRESUMO
The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.
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G-protein-coupled receptor 48 (GPR48) is an orphan receptor belonging to the G-protein-coupled receptors family, which plays an important role in the development of various organs and cancer development and progression such as gastric cancer and colorectal cancer (CRC). However, the prognostic value of GPR48 expression in patients with CRC has not been reported. In this study, we observed that GPR48 was overexpressed in primary CRC and metastatic lymph nodes and closely correlated with tumor invasion and metastasis. Multivariate analysis indicated that high GPR48 expression was a poor prognostic factor for overall survival in CRC patients. In vitro and in vivo assays demonstrated that enforced expression of GPR48 contributed to enhance migration and invasion of cancer cells and tumor metastasis. In addition, we found that GPR48 increased nuclear ß-catenin accumulation, T-cell factor 4 (TCF4) transcription activity, and expression of its target genes including Cyclin D1 and c-Myc in CRC cells. Correlation analysis showed that GPR48 expression in CRC tissues was positively associated with ß-catenin expression. Upregulation of GPR48 resulted in increased phosphorylation of glycogen synthase kinase 3ß, Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) in CRC cells, while inhibition of PI3K/Akt and mitogen-activated protein kinase /ERK1/2 pathways was sufficient to abolish the effect of GPR48 on ß-catenin/TCF signaling. Taken together, GPR48 could serve as both a prognostic biomarker and a therapeutic target for resectable CRC patients.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Metástase Linfática/patologia , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética , beta Catenina/genética , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Células HCT116 , Células HEK293 , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/genética , Sistema de Sinalização das MAP Quinases/genética , Masculino , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Fator de Transcrição 4 , Fatores de Transcrição/metabolismo , Transcrição Gênica/genética , Regulação para Cima/genética , beta Catenina/metabolismoRESUMO
In this research, a repetitive bending and straightening process was carried out on the Ti-3Al-4Cr-Mo alloy for 20 passes. The changes in mechanical properties of the titanium alloy before and after repetitive bending and annealing were studied. The microstructure evolution and deformation mechanism were analyzed. The results show that after the repetitive bending and straightening process, the microstructure of the Ti-3Al-4Cr-Mo alloy is obviously refined, and, simultaneously, the yield strength is significantly improved. After annealing at 850 °C, the plastic ductility of the material was improved. The combined effects of grain refinement and dislocation behavior were the main reasons for the improvement in mechanical properties of the Ti-3Al-4Cr-Mo alloy. Twinning rarely occurred during plastic deformation of the Ti-3Al-4Cr-Mo alloy. The fine grains strongly inhibited the formation of twins. In addition, a small amount of α to ß phase transformation was observed during the repetitive bending and straightening process of the material, which may have been induced by strain accumulation.
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OBJECTIVE: To investigate whether sEH inhibitor AUDA can mitigate postpartum depression (PPD)-like symptoms in the rat model and regulate the AA/NF-κB pathway to suppress the inflammatory response in the prefrontal lobes of PPD rats. METHODS: Five groups of Sprague Dawley rats were used: normal, sham operated, PPD model, AUDA, and paroxetine hydrochloride. During the 21-day treatment period, animals in all groups underwent assessments (open field test, forced swimming test, and sucrose consumption) for depression-like behavior. At the conclusion of the treatment period, animals in all study groups were euthanized and various proteins in the prefrontal lobes were measured. RESULTS: Depression-like behavior in rats was attenuated by AUDA. In the prefrontal lobes of PPD rats, levels of 5-LOX, COX-2, sEH, IL-1ß, IL- 6, p65, p-p65, P-IκBα, NF-κB p65, and GFAP were increased while levels of epoxyeicosatrienoic acids and 5-HT were decreased. AUDA reversed these changes, thus having a similar effect as the classic antidepressant paroxetine hydrochloride. CONCLUSION: AUDA may constrain AA/NF-κB in the prefrontal cortex of PPD rats, thus inhibiting the inflammatory response and ultimately attenuating postpartum depression-like behavior.
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Depressão Pós-Parto , NF-kappa B , Animais , Feminino , Ratos , Ácidos Araquidônicos , Depressão Pós-Parto/tratamento farmacológico , Paroxetina/farmacologia , Paroxetina/uso terapêutico , Ratos Sprague-DawleyRESUMO
MicroRNAs (miRNA) are a class of endogenous, non-coding, small RNAs with about 22 nucleotides (nt), that are widespread in plants and are involved in various biological processes, such as development, flowering phase transition, hormone signal transduction, and stress response. The transcriptional regulation of miRNAs is an important process of miRNA gene regulation, and it is essential for miRNA biosynthesis and function. Like mRNAs, miRNAs are transcribed by RNA polymerase II, and these transcription processes are regulated by various transcription factors and other proteins. Consequently, the upstream genes regulating miRNA transcription, their specific expression, and the regulating mechanism were reviewed to provide more information for further research on the miRNA regulatory mechanism and help to further understand the regulatory networks of plant miRNAs.
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Deciphering the genomic profiles and tumor microenvironment (TME) in large cell carcinomas of the lung (LCC), large cell neuroendocrine of the lung (LCNEC), and small cell lung cancer (SCLC) might contribute to a better understanding of lung cancer and then improve outcomes. Ten LCC patients, 12 LCNEC patients, and 18 SCLC patients were enrolled. Targeted next-generation sequencing was used to investigate the genomic profiles of LCC, LCNEC, and SCLC. Tumor-infiltrating lymphocytes (TILs) within cancer cell nests and in cancer stroma were counted separately. Precise 60% of LCNEC patients harbored classical non-small cell lung cancer driver alterations, occurring in BRAF, KRAS, ROS1, and RET. More than 70% of SCLC patients harbored TP53-RB1 co-alterations. Moreover, 88.9%, 40%, and 77.8% of LCC, LCNEC, and SCLC cases had a high tumor mutation burden level with more than 7 mutations/Mb. Furthermore, high index of CD68+ CD163+ (TILs within cancer cell nests/ TILs within cancer cell nests and in cancer stroma, P = .041, 548 days vs not reached) and CD163+ TILs (P = .041, 548 days vs not reached) predicted a shorter OS in SCLC. Our findings revealed the distinct genomic profiles and TME contexture among LCC, LCNEC, and SCLC. Our findings suggest that stratifying LCNEC/SCLC patients based on TME contexture might help clinical disease management.
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Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Proteínas Tirosina Quinases , Microambiente Tumoral/genética , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Proteínas Proto-Oncogênicas , Carcinoma de Pequenas Células do Pulmão/genética , Genômica , Pulmão/patologiaRESUMO
Background: Congenital heart diseases (CHDs) are conditions that involve structural problems to the heart's structure existing at birth, with an incidence of approximately 8 per 1,000 live births globally. CHD is one of the leading causes of maternal, fetal, and neonatal morbidity and mortality worldwide. The present study sought to examine the clinical profiles of CHD patients and provide important implications for therapeutic interventions. Methods: This was a retrospective, observational, cohort study. The medical records of all CHDs patients aged between 0 and 18 years were collected from July 1, 2021 to June 30, 2022. Clinical profiles and demographic data were collected from cardiology and pediatric department registers for analysis. Results: Of the 265 children with CHDs, 201 were diagnosed with acyanotic CHD (ACHD), while 64 children had cyanotic CHD (CCHD). Based on the eleventh revision of the International Classification of Diseases (ICD-11), "congenital anomaly of a ventricle or the ventricular septum" was the most common CHD. The most common symptom was failure to thrive, accounting for 18.5% of all CHD cases. The most frequent symptom in ACHD was murmur (93.53%) and sweating (80.60%), whereas the most common symptom in CCHD was sweating (95.31%) and cyanosis (84.38%). Conclusions: This study retrospectively analyzed CHD clinical characteristics from children receiving care at the seventh center, which forms a proper basis for appropriate clinical treatments and further studies.
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Maladaptation of host-microbiota metabolic interplay plays a critical role in colorectal cancer initiation. Here, through a combination of single-cell transcriptomics, microbiome profiling, metabonomics, and clinical analysis on colorectal adenoma and carcinoma tissues, we demonstrate that host's urea cycle metabolism is significantly activated during colorectal tumorigenesis, accompanied by the absence of beneficial bacteria with ureolytic capacity, such as Bifidobacterium, and the overabundance of pathogenic bacteria lacking ureolytic function. Urea could enter into macrophages, inhibit the binding efficiency of p-STAT1 to SAT1 promotor region, and further skew macrophages toward a pro-tumoral phenotype characterized by the accumulation of polyamines. Treating a murine model using urea cycle inhibitors or Bifidobacterium-based supplements could mitigate urea-mediated tumorigenesis. Collectively, this study highlights the utility of urea cycle inhibitors or therapeutically manipulating microbial composition using probiotics to prevent colorectal cancer.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Carcinogênese , Neoplasias Colorretais/patologia , Transformação Celular NeoplásicaRESUMO
Intestinal cancer is one of the most frequent and lethal types of cancer. Modeling intestinal cancer using organoids has emerged in the last decade. Human intestinal cancer organoids are physiologically relevant in vitro models, which provides an unprecedented opportunity for fundamental and applied research in colorectal cancer. "Human intestinal cancer organoids" is the first set of guidelines on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods for human intestinal cancer organoids, which apply to the production and quality control during the process of manufacturing and testing of human intestinal cancer organoids. It was released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practocal protocols, and accelerate the international standardization of human intestinal cancer organoids for clinical development and therapeutic applications.
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Organoids have attracted great interest for disease modelling, drug discovery and development, and tissue growth and homeostasis investigations. However, lack of standards for quality control has become a prominent obstacle to limit their translation into clinic and other applications. "Human intestinal organoids" is the first guideline on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods, inspection rules for human intestinal organoids, which is applicable to quality control during the process of manufacturing and testing of human intestinal organoids. It was originally released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of human intestinal organoids for applications.