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1.
Biochem Biophys Res Commun ; 727: 150270, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38917617

RESUMO

Neuroinflammation has been implicated in cognitive deficits of neurological and neurodegenerative diseases. There is abundant evidence that the application of ghrelin, an orexigenic hormone regulating appetite and energy balance, abrogates neuroinflammation and rescues associated memory impairment. However, the underlying mechanism is uncertain. In this study, we find that both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) impairs spatial memory in mice. LPS treatment causes neuroinflammation and microglial activation in the hippocampus. Ghsr1a deletion suppresses LPS-induced microglial activation and neuroinflammation, and rescued LPS-induced memory impairment. Our findings thus suggest that GHS-R1a signaling may promote microglial immunoactivation and contribute to LPS-induced neuroinflammation. GHS-R1a may be a new therapeutic target for cognitive dysfunction associated with inflammatory conditions.

2.
Discov Oncol ; 15(1): 184, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795254

RESUMO

Tumor dormancy is a stage in the growth and development of malignant cells and is one of the biological characteristics of malignant cells. Complex transitions involving dormant tumor cells between quiescent and proliferative states pose challenges for tumor eradication. This paper explores the biological features and molecular mechanisms of tumor dormancy and highlights emerging therapies. The strategies discussed promise innovative clinical potential against malignant tumors. Understanding the mechanisms of dormancy can help provide valuable insights into the diagnosis and treatment of malignant tumors to advance the fight against this world problem.

3.
PLoS One ; 19(5): e0301358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771804

RESUMO

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 µg/mL and 16 µg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Platina , Rutênio , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Platina/química , Platina/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Rutênio/química , Rutênio/farmacologia , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Peroxidase/metabolismo , Peróxido de Hidrogênio/química , Catálise , Humanos
4.
ACS Nano ; 18(19): 12049-12095, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38693611

RESUMO

Cancer, as one of the leading causes of death worldwide, drives the advancement of cutting-edge technologies for cancer treatment. Transition-metal-based nanozymes emerge as promising therapeutic nanodrugs that provide a reference for cancer therapy. In this review, we present recent breakthrough nanozymes for cancer treatment. First, we comprehensively outline the preparation strategies involved in creating transition-metal-based nanozymes, including hydrothermal method, solvothermal method, chemical reduction method, biomimetic mineralization method, and sol-gel method. Subsequently, we elucidate the catalytic mechanisms (catalase (CAT)-like activities), peroxidase (POD)-like activities), oxidase (OXD)-like activities) and superoxide dismutase (SOD)-like activities) of transition-metal-based nanozymes along with their activity regulation strategies such as morphology control, size manipulation, modulation, composition adjustment and surface modification under environmental stimulation. Furthermore, we elaborate on the diverse applications of transition-metal-based nanozymes in anticancer therapies encompassing radiotherapy (RT), chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), immunotherapy, and synergistic therapy. Finally, the challenges faced by transition-metal-based nanozymes are discussed alongside future research directions. The purpose of this review is to offer scientific guidance that will enhance the clinical applications of nanozymes based on transition metals.


Assuntos
Antineoplásicos , Neoplasias , Elementos de Transição , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Elementos de Transição/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Fotoquimioterapia , Nanoestruturas/química , Animais
5.
Medicine (Baltimore) ; 103(19): e37999, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728502

RESUMO

Glioma is a typical malignant tumor of the nervous system. It is of great significance to identify new biomarkers for accurate diagnosis of glioma. In this context, THOC6 has been studied as a highly diagnostic prognostic biomarker, which contributes to improve the dilemma in diagnosing gliomas. We used online databases and a variety of statistical methods, such as Wilcoxon rank sum test, Dunn test and t test. We analyzed the mutation, location and expression profile of THOC6, revealing the network of THOC6 interaction with disease. Wilcoxon rank sum test showed that THOC6 is highly expressed in gliomas (P < 0.001). Dunn test, Wilcoxon rank sum test and t test showed that THOC6 expression was correlated with multiple clinical features. Logistic regression analysis further confirmed that THOC6 gene expression was a categorical dependent variable related to clinical features of poor prognosis. Kaplan-Meier survival analysis showed that the overall survival (OS) of glioma patients with high expression of THOC6 was poor (P < 0.001). Both univariate (P < 0.001) and multivariate (P = 0.04) Cox analysis confirmed that THOC6 gene expression was an independent risk factor for OS in patients with glioma. ROC curve analysis showed that THOC6 had a high diagnostic value in glioma (AUC = 0.915). Based on this, we constructed a nomogram to predict patient survival. Enrichment analysis showed that THOC6 expression was associated with multiple signal pathways. Immuno-infiltration analysis showed that the expression of THOC6 in glioma was closely related to the infiltration level of multiple immune cells. Molecular docking results showed that THOC6 might be the target of anti-glioma drugs. THOC6 is a novel diagnostic factor and prognostic biomarker of glioma.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Biologia Computacional , Glioma , Simulação de Acoplamento Molecular , Proteínas de Ligação a RNA , Feminino , Humanos , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Biologia Computacional/métodos , Glioma/genética , Glioma/patologia , Estimativa de Kaplan-Meier , Prognóstico , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
6.
Dev Cell ; 59(13): 1737-1749.e7, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38677285

RESUMO

Photomorphogenesis is a light-dependent plant growth and development program. As the core regulator of photomorphogenesis, ELONGATED HYPOCOTYL 5 (HY5) is affected by dynamic changes in its transcriptional activity and protein stability; however, little is known about the mediators of these processes. Here, we identified PHOTOREGULATORY PROTEIN KINASE 1 (PPK1), which interacts with and phosphorylates HY5 in Arabidopsis, as one such mediator. The phosphorylation of HY5 by PPK1 is essential to establish high-affinity binding with B-BOX PROTEIN 24 (BBX24) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), which inhibit the transcriptional activity and promote the degradation of HY5, respectively. As such, PPKs regulate not only the binding of HY5 to its target genes under light conditions but also HY5 degradation when plants are transferred from light to dark. Our data identify a PPK-mediated phospho-code on HY5 that integrates the molecular mechanisms underlying the regulation of HY5 to precisely control plant photomorphogenesis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição de Zíper de Leucina Básica , Regulação da Expressão Gênica de Plantas , Luz , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fosforilação , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Morfogênese/efeitos da radiação , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Proteínas Repressoras
7.
Chem Biol Drug Des ; 103(1): e14440, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230784

RESUMO

Naoxintong capsule (NXT) is a clinical drug for the treatment of cardiovascular diseases, but its pharmacological mechanism against hypertension remains unclear. Data concerning the compounds and targets of NXT were obtained from the TCMSP and DrugBank, whereas data concerning hypertension-related genes were obtained from DisGeNET. The network was analyzed and established by STRING and Cytoscape, and function enrichment was analyzed by GO and KEGG analysis. Molecular docking was performed to analyze the interaction between ingredients and targets, cellular activity was evaluated by MTT assay, and RT-qPCR and western blot were used to evaluate the expressions of related genes. The results showed that 146 active therapeutic components can target hypertension-related genes, and we found that core genes were mainly involved in the metabolism of lipids, lipopolysaccharides, the inflammatory signaling pathway, and the oxidative stress pathway. In addition, there was high affinity between the components of NXT and targets of hypertension, where the former can increase cell viability and reduce the expressions of NOX4, MCP-1, BAX, TNF-α and IL-1ß. Moreover, NXT inhibited the expressions of IL-6 and Fis1, as well as increased the expression of MCL-1. These results revealed the active compounds, hypertension targets, signaling pathways, and molecular mechanisms of NXT for treating hypertension, offering references for the clinical application of NXT and the treatment of hypertension.


Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Simulação de Acoplamento Molecular , Hipertensão/tratamento farmacológico , Fator de Necrose Tumoral alfa , Medicamentos de Ervas Chinesas/farmacologia
9.
Sex Med ; 11(5): qfad055, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38028734

RESUMO

Background: Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with multiple psychological disorders, such as depression and anxiety. However, the correlation between PE and TDP remains unknown. Aim: The study sought to investigate the relationships between depressive symptoms, TDP, and PE. Methods: Adult males in Taiwan who were 20 to 40 years of age and who had sexual intercourse in the past 6 months were recruited to complete online questionnaires composed of general demographics, the Premature Ejaculation Diagnostic Tool (PEDT), 5-item International Index of Erectile Function (IIEF-5), Type D Scale-14, and Depression and Somatic Symptom Scale (DSSS). Chi-square test and independent Student's t test were used to compare the parameters between the TDP and non-TDP groups. Univariate and multivariate logistic regression analyses were conducted to evaluate factors related to PE. Outcomes: Outcomes were the prevalence of PE and TDP in young Taiwanese men, the associations between depressive symptoms and PE and TDP, and the predictive factors of PE. Results: In total, 2558 men with a mean age of 31.3 ± 5.3 years were included in the present study. Among them, 315 (12.3%) and 767 (30.1%) participants were classified as having PE and moderate-to-severe erectile dysfunction (ED), respectively. In total, 1249 (48.8%) participants met the criteria for TDP. The PEDT, IIEF-5, and DSSS, including the total scores and depression and somatic subscales, were significantly higher in men with TDP (all P < .001). PE prevalence was significantly greater in men with TDP than in those without TDP (16.2% vs 8.6%; P < .001). Most parameters, including age, moderate-to-severe ED, the Type D Scale-14 subscales, and the DSSS somatic and depressive subscales, were significantly associated with PE in the univariate analysis. Only the depressive subscale of the DSSS and moderate-to-severe ED (IIEF-5 ≤16) were the independent predictors of PE in the multivariate analysis. Clinical Implications: The results suggest that it is important to consider the psychological effects of PE in young men, and the study has provided a biopsychosocial aspect to manage patients with PE. Strengths and Limitations: This is the first study to evaluate the association between PE, TDP, and depression in a large population of young adult males. However, the cross-sectional design may have limited the investigation of causality, and selection bias may be present. Conclusion: Men with TDP tended to have higher PEDT scores and a prevalence of PE and ED. Moderate-to-severe ED and depressive symptoms are the independent predictive factors of PE.

10.
J Nanobiotechnology ; 21(1): 388, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875896

RESUMO

Multi-drug resistant (MDR) bacterial infections are gradually increasing in the global scope, causing a serious burden to patients and society. The formation of bacterial biofilms, which is one of the key reasons for antibiotic resistance, blocks antibiotic penetration by forming a physical barrier. Nano/micro motors (MNMs) are micro-/nanoscale devices capable of performing complex tasks in the bacterial microenvironment by transforming various energy sources (including chemical fuels or external physical fields) into mechanical motion or actuation. This autonomous movement provides significant advantages in breaking through biological barriers and accelerating drug diffusion. In recent years, MNMs with high penetrating power have been used as carriers of antibiotics to overcome bacterial biofilms, enabling efficient drug delivery and improving the therapeutic effectiveness of MDR bacterial infections. Additionally, non-antibiotic antibacterial strategies based on nanomaterials, such as photothermal therapy and photodynamic therapy, are continuously being developed due to their non-invasive nature, high effectiveness, and non-induction of resistance. Therefore, multifunctional MNMs have broad prospects in the treatment of MDR bacterial infections. This review discusses the performance of MNMs in the breakthrough and elimination of bacterial biofilms, as well as their application in the field of anti-infection. Finally, the challenges and future development directions of antibacterial MNMs are introduced.


Assuntos
Infecções Bacterianas , Nanoestruturas , Humanos , Nanotecnologia , Antibacterianos/farmacologia , Bactérias , Biofilmes
11.
Front Mol Biosci ; 10: 1107651, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36714260

RESUMO

Gastric cancer (GC) is a malignant cancer that reduces life expectancy worldwide. Although treatment strategies have improved, patients with GC still have poor prognoses. Hence, it is necessary to understand the molecular mechanisms of GC and to find new therapeutic targets. Mitochondrial dynamics and mitochondrial dysfunction are associated with cancer cell growth and progression. Numerous studies have reported that non-coding RNAs (ncRNAs) can participate in the occurrence and development of GC by regulating mitochondrial dynamics. Elucidating the crosstalk between ncRNAs and mitochondria would be helpful in preventing and treating GC. Herein, we review and summarize the functions of oncogenes and tumor suppressors in suppressing ncRNAs and regulating mitochondrial dynamics in GC tumor growth, proliferation, invasion and metastasis. This review provides new insights into the pathogenesis of and intervention for GC.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 51-59, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36655664

RESUMO

OBJECTIVES: To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis. METHODS: The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24). CONCLUSIONS: The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.


Assuntos
Linfoma de Células B , Criança , Adolescente , Humanos , Rituximab/efeitos adversos , Linfoma de Células B/tratamento farmacológico , Intervalo Livre de Progressão , Indução de Remissão , China , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
13.
J Microbiol Biotechnol ; 32(10): 1226-1233, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36196014

RESUMO

Probiotics are live microorganisms that can be consumed by humans in amounts sufficient to offer health-promoting effects. Owing to their various biological functions, probiotics are widely used in biological engineering, industry and agriculture, food safety, and the life and health fields. Lactobacillus acidophilus (L. acidophilus), an important human intestinal probiotic, was originally isolated from the human gastrointestinal tract and its functions have been widely studied ever since it was named in 1900. L. acidophilus has been found to play important roles in many aspects of human health. Due to its good resistance against acid and bile salts, it has broad application prospects in functional, edible probiotic preparations. In this review, we explore the basic characteristics and biological functions of L. acidophilus based on the research progress made thus far worldwide. Various problems to be solved regarding the applications of probiotic products and their future development are also discussed.


Assuntos
Lactobacillus acidophilus , Probióticos , Humanos , Lactobacillus acidophilus/fisiologia , Intestinos , Trato Gastrointestinal , Ácidos e Sais Biliares/farmacologia
14.
J Microbiol Biotechnol ; 32(10): 1-8, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36192851

RESUMO

Probiotics are live microorganisms that can be consumed by humans in amounts sufficient to offer health-promoting effects. Owing to their various biological functions, probiotics are widely used in biological engineering, industry and agriculture, food safety, and the life and health fields. Lactobacillus acidophilus (L. acidophilus), an important human intestinal probiotic, was originally isolated from the human gastrointestinal tract and its functions have been widely studied ever since it was named in 1900. L. acidophilus has been found to play important roles in many aspects of human health. Due to its good resistance against acid and bile salts, it has broad application prospects in functional, edible probiotic preparations. In this review, we explore the basic characteristics and biological functions of L. acidophilus based on the research progress made thus far worldwide. Various problems to be solved regarding the applications of probiotic products and their future development are also discussed.

15.
Biomed Res Int ; 2022: 7281120, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924262

RESUMO

MRG-binding protein (MRGBP) is a transcription factor widely involved in physiological and pathological processes. Many studies have discussed the relationship between the expression level of MRGBP and the prognosis of various malignant tumours. However, the role and clinicopathological significance of MRGBP in head and neck squamous cell carcinoma (HNSC) are unclear. In this study, the Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinical characteristics and MRGBP expression in HNSC. The Kaplan-Meier plotter analysis and Cox regression analysis were established to evaluate the effect of MRGBP on prognosis, and the receiver operating characteristic (ROC) curve and nomogram was constructed. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were used to analyze the correlation between MRGBP and immune infiltration. The results showed that the expression of MRGBP in HNSC tissues was significantly higher than that in normal tissues. The KM plotter analysis showed that the OS of HNSC patients was shorter. The multivariate Cox analysis further confirmed that increased expression of MRGBP was an independent risk factor for OS in HNSC patients. In addition, ROC analysis confirmed its diagnostic value and constructed prognostic nomograms, including age, T, M, N classification, pathological stage, and MRGBP. GSEA showed that MRGBP was associated with high expression of GPCR ligand binding, interleukin receptor binding, and neutrophil degranulation, and ssGSEA showed that MRGBP was associated with T cells and mast cells. In conclusion, MRGBP can serve as an independent prognostic biomarker related to immune invasion of head and neck squamous cell carcinoma.


Assuntos
Proteínas de Transporte , Neoplasias de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Humanos , Ligantes , Prognóstico , Receptores Acoplados a Proteínas G , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(5): 561-565, 2022 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-35644197

RESUMO

OBJECTIVES: To study the clinical features and chemotherapy response of Burkitt's lymphoma (BL) in children and the influence of rituximab on the prognosis of children with BL. METHODS: A retrospective analysis was performed for the medical data of 62 children with BL, including clinical features, therapeutic efficacy, and prognostic factors. The Cox regression model was used to identify the factors associated with poor prognosis in children with BL. According to whether rituximab was used, the children with advanced (stage III/IV) BL were divided into two groups: chemotherapy plus rituximab and chemotherapy alone. The prognosis was compared between the two groups. RESULTS: For these 62 children, the median age of onset was 5 years (range 1-14 years), and there were 58 boys (94%) and 4 girls (6%). The primary site was abdominal cavity in 41 children (66%), and head and neck in 16 children (26%). There were 1 child with stage I BL (2%), 8 with stage II BL (13%), 33 with stage III BL (53%), and 20 with stage IV BL (32%). The median follow-up time was 29 months, with progression/recurrence observed in 15 children (24%), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±5.2% and 77.3%±5.8%, respectively. For the children with stage III/IV BL, there was a significant difference in the 3-year the OS rate between the chemotherapy plus rituximab group (16 children) and the chemotherapy alone group (30 children) (93.3%±6.4% vs 65.6%±9.9%, P=0.042), while there was no significant difference in the 3-year EFS rate between the two groups (86.2%±9.1% vs 61.8%±10.1%, P>0.05). The Cox regression analysis showed that central nervous system involvement, lactate dehydrogenase >1 000 U/L, and early incomplete remission were the factors associated with poor prognosis (P<0.05). CONCLUSIONS: Chemotherapy combined with rituximab can improve the prognosis of children with stage III/IV BL. Central nervous system involvement, elevated lactate dehydrogenase level, and early incomplete remission may indicate a poor prognosis in children with BL.


Assuntos
Linfoma de Burkitt , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Lactato Desidrogenases , Masculino , Prognóstico , Estudos Retrospectivos , Rituximab
17.
Sci Rep ; 12(1): 5798, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388113

RESUMO

Acute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and 3-day rebleeding rate (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in EE than non-EE group. The mortality, minor and major complication rates were not different between two groups. Male patients were at higher risk of minor and major complications after EE with OR (95% CI) of 3.50 (1.15-10.63) and 4.25 (1.43-12.63), respectively. In multivariate analysis, EE was associated with lower needs for blood transfusion (HR 0.13, 95% CI 0.02-0.98). Among patients who discontinued DAPT during acute UGIB, a higher risk (OR 5.25, 95% CI 1.21-22.74) of coronary artery stent re-thrombosis within 6 months was noticed. EE for acute UGIB in recent ACS patients has higher rate of bleeding control, lower 3-day rebleeding rate and lower needs for blood transfusion, but more complications in male patients. Further enrollment is mandatory to avoid bias from small sample size (ClinicalTrial.gov Number NCT02618980, registration date 02/12/2015).


Assuntos
Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Endoscopia Gastrointestinal/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Fatores de Risco , Resultado do Tratamento
18.
Anticancer Drugs ; 33(1): e491-e499, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261923

RESUMO

The most common pathological subtype of renal carcinoma is RCC, and its development is closely related to immune infiltration. In our study, we investigated the relationship between zinc finger protein 668 and the prognostic risk, clinical characteristics, overall survival and related pathways. We analyzed the association between ZNF668 and immune cell infiltration through the TIMER database. The results showed that the expression of ZNF668 in RCC was higher than that in normal tissues (P < 0.001). The high expression of ZNF668 is clinically relevant, such as tumor stage (P = 0.001) and TNM classification (T: P = 7.37 e-04; N: P = 0.008; M: P < 0.001). Survival analysis showed that patients with high ZNF668 expression had a significantly poor prognosis (P = 0.023). Univariate analysis showed a significant decrease in overall survival in RCC patients with high ZNF668 expression (P = 0.023). Immuno-cell infiltration showed a significant decrease in CD4+ T cell and dendritic cell infiltration in RCC patients with high expression of ZNF668. GO/KEGG analysis showed that multiple pathways were differentially enriched in the high expression pathway of ZNF668, such as complement activation, and estrogen signaling pathway. In conclusion, high ZNF668 expression is a predictor in RCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Proteínas Supressoras de Tumor/genética , Idoso , Biomarcadores Tumorais , Linfócitos T CD4-Positivos/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Proteínas do Sistema Complemento/agonistas , Células Dendríticas/metabolismo , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Transdução de Sinais/fisiologia , Análise de Sobrevida
19.
J Integr Plant Biol ; 63(9): 1595-1599, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33751803

RESUMO

A new deaminase, TadA8e, was recently evolved in the laboratory. TadA8e catalyzes DNA deamination over 1,000 times faster than ABE7.10. We developed a high-efficiency adenine base editor, rABE8e (rice ABE8e), combining monomeric TadA8e, bis-bpNLS and codon optimization. rABE8e had substantially increased editing efficiencies at NG-protospacer adjacent motif (PAM) and NGG-PAM target sequences compared with ABEmax. For most targets, rABE8e exhibited nearly 100% editing efficiency and high homozygous substitution rates in the specific editing window, especially at Positions A5 and A6. The ability to rapidly generate plant materials with homozygous base substitutions will benefit gene function research and precision molecular breeding.


Assuntos
Aminoidrolases/metabolismo , Edição de Genes/métodos , Oryza/genética , Proteína 9 Associada à CRISPR
20.
Transl Cancer Res ; 10(12): 5065-5075, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35116358

RESUMO

BACKGROUND: Breast invasive carcinoma (BRCA) has a poor prognosis. Numerous studies have shown that SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is involved in the initiation and progression of many cancers. This study aims to reveal the potential mechanism of SETDB1 in the development and progression of BRCA. METHODS: The ONCOMINE database, TIMER database, UALCAN database and GEPIA database were used to analyze the expression of SETDB1 in human cancers. We evaluated the expression level of SETDB1 in cell lines by quantitative real-time polymerase chain reaction (qPCR), and the survival analysis of SETDB1 was performed on PrognoScan and Kaplan-Meier plotter websites. The upstream regulator was obtained from starBase database. RESULTS: We confirmed that SETDB1 messenger RNA (mRNA) level showed high expression in breast cell lines, and we also found that SETDB1 showed high expression in many types of cancers. Moreover, SETDB1 overexpression was positively correlated with poor prognosis in BRCA. Furthermore, we first predicted miR-29a-3p was a potential upstream regulator of SETDB1 in BRCA. Our findings indicated that SETDB1 might play a carcinogenic role by increasing the infiltration of immune cell and influencing immune checkpoint expression. CONCLUSIONS: This study suggested that miR-29a-3p can mediate the expression of SETDB1 with poor prognosis and tumor immune infiltration in BRCA.

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