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This prospective clinical investigation focused on the addition of venetoclax and decitabine to myeloablative conditioning regimens, targeting high-risk and elderly individuals undergoing allogeneic hematopoietic stem cell transplantation. In total, 19 patients were enrolled in the trial between December 2021 and February 2023, and their progress was monitored for a median follow-up period of 258 days, ranging from 35 to 544 days. In the initial regimen (n=11), venetoclax was administered at a dosage of 400 mg per day from day -14 to day -1, while in the modified regimen (n=8), it was administered from day -14 to day -5. Decitabine was orally administered at a dosage of 20mg/m2/day from day -7 to day -3. Grade 3/4 adverse events observed included hematological events, hypertension, infections, allergy, and increased amylase. In the entire cohort, the overall survival (OS) and relapse-free survival (RFS) rates at 6 months were 63% (95% CI, 45-89) and 63% (95% CI, 45-89), respectively. The non-relapse mortality (NRM) rate at 6 months was 37% (95% CI, 16-58), while the cumulative incidence of relapse (CIR) was 0. However, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD within 100 days was found to be 31% (95% CI, 12-53) and 26% (95% CI, 9-47), respectively. These rates indicate a relatively high occurrence, making it less suitable to administer the regimen to elderly patients. Therefore, further high-quality studies are required to enhance the conditioning regimen specifically for high-risk and elderly patients diagnosed with myeloid neoplasms. Clinical trial registration: ChiCTR2100050272.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Neoplasias , Humanos , Idoso , Decitabina , Estudos Prospectivos , Neoplasias/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transtornos Mieloproliferativos/complicações , Recidiva , Condicionamento Pré-Transplante/efeitos adversos , Leucemia Mieloide Aguda/complicações , BussulfanoRESUMO
Due to the unique and excellent biological, physical, and chemical properties of peptide hydrogels, their application in the biomedical field is extremely wide. The applications of peptide hydrogels are closely related to their unique responsiveness and excellent properties. However, its defects in mechanical properties, stability, and toxicity limit its application in the food field. In this review, we focus on the fabrication methods of peptide hydrogels through the physical, chemical, and biological stimulations. In addition, the functional design of peptide hydrogels by the incorporation with materials is discussed. Meanwhile, the excellent properties of peptide hydrogels such as the stimulus responsiveness, biocompatibility, antimicrobial properties, rheology, and stability are reviewed. Finally, the application of peptide hydrogel in the food field is summarized and prospected.
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Hidrogéis , Peptídeos , Hidrogéis/química , Peptídeos/química , Reologia , Tecnologia de AlimentosRESUMO
Resveratrol has several functions, including protection of the heart and nervous system and exerts antidiabetic, anti-inflammatory, anti-aging, and antitumor effects. It is reported to impede the occurrence and development of tumors in cancer cell lines, animal models, and clinical studies. In vitro and in vivo experiments show that it exerts preventive or adjuvant therapeutic effects in pancreatic, colorectal, prostate, liver, and lung cancers. Mechanistic research reports show that resveratrol can induce tumor cell apoptosis and autophagy, inhibit cell cycle and angiogenesis, regulate nuclear factors and cyclooxygenase signal transduction pathways, and inhibit carcinogens' metabolic activation and alter tumor-related expression patterns; anti-oxidation affects tumor cell proliferation, metastasis, and apoptosis. However, the exact mechanism underlying its action remains unclear. This review highlights multiple aspects of the biological impacts and mechanisms underlying resveratrol action on the occurrence and development of lung cancer.
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Neoplasias Pulmonares , Estilbenos , Masculino , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Transdução de Sinais , Anti-Inflamatórios/farmacologia , Proliferação de Células , Apoptose , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral , Estilbenos/farmacologia , Estilbenos/uso terapêuticoRESUMO
Lung adenocarcinoma (LUAD) is a malignant tumor that occurs in the lungs. Numerous reports have substantiated the participation of long non-coding RNAs (lncRNAs) in the tumorigenesis of LUAD. Previously, lncRNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) was confirmed to be an important regulator in the biological processes of LUAD and dysregulation of A2M-AS1 was associated with non-small cell lung cancer (NSCLC) progression. However, the precise mechanism of A2M-AS1 in LUAD has not been elucidated. Therefore, our study was designed to investigate the detailed molecular mechanism of A2M-AS1 in LUAD. Herein, the expression of lncRNA A2M-AS1, microRNA (miRNA) miR-587, and bone morphogenetic protein 3 (BMP3) in LUAD cell lines and tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. The viability, proliferation, migration and invasion of LUAD cells were tested by cell counting kit-8 (CCK-8), colony formation and Transwell assays. In vivo tumor growth was investigated by xenograft animal experiment. Interactions among A2M-AS1, miR-587 and BMP3 were measured by RNA pulldown and luciferase reporter assays. In this study, A2M-AS1 was downregulated in LUAD tissues and cells and related to poor prognosis in LUAD patients. A2M-AS1 overexpression suppressed LUAD cell proliferation, migration and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, A2M-AS1 directly bound with miR-587 to promote BMP3 expression in LUAD cells. Low expression of BMP3 was found in LUAD tissues and cells and was closely correlated with poor prognosis in LUAD patients. BMP3 deficiency reserved the inhibitory influence of A2M-AS1 overexpression on LUAD cell behaviors. Overall, A2M-AS1 inhibits cell growth and aggressiveness via regulating the miR-587/BMP3 axis in LUAD.
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Adenocarcinoma de Pulmão , Proteína Morfogenética Óssea 3 , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , alfa-Macroglobulinas , Animais , Humanos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , alfa-Macroglobulinas/genética , alfa-Macroglobulinas/metabolismo , Proteína Morfogenética Óssea 3/genética , Proteína Morfogenética Óssea 3/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/fisiopatologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/fisiopatologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Progressão da DoençaRESUMO
Background: Esophageal cancer is the most prevalent digestive system tumor. Due to a lack of characteristic symptoms and early diagnosis, a confirmed esophageal cancer is typically detected at a progressively harmful stage. Therefore, it is critical to investigate the molecular mechanisms governing the formation and progression of esophageal cancer in order to identify new treatment targets for esophageal cancer early detection. Methods: We first screened the differentially expressed gene LINC00240 in the TCGA database. Multivariate analysis and Cox regression were performed, and a nomogram was constructed for internal validation. The correlation between LINC00240 and immune cells was analyzed using the TIMER database. The possible mechanism of action was explored through GSEA enrichment analysis. Then, in 43 esophageal cancer tissues, paracancour tissues, and cell lines, the LINC00240 expression was found. Transwell assays, CCK-8, and clone formation assays were utilized to assess the impact of LINC00240 on the metastasis of esophageal cancer cells. The binding activity of LINC00240 to downstream miRNAs was assessed using the luciferase reporter gene. Results: TCGA database showed that LINC00240 expression was increased in cancer tissues compared to adjacent tissues. The C-index of the nomogram is 0.712 (0.666-0.758), and the prediction model has good accuracy. According to the TIMER database, the LINC00240 expression is linked to immune infiltration and may be crucial in encouraging the immune escape of tumor cells. Gene enrichment analysis depicts that LINC00240 could influence the biological events of esophageal cancer by taking part in pathways such as affecting the cell cycle. LINC00240 expression was substantially greater in the plasma of esophageal cancer patients (3.94 ± 1.55) than in the normal control group (2.13 ± 0.89). Plasma expression of LINC00240 was linked to the degree of differentiation (P=0.0345) and TNM stage (P=0.0409). Knocked down LINC00240 inhibited esophageal cancer cells proliferation, lone formation, and invasion. LINC00240 might bind itself to miR-26a-5p and influence its expression. MiR-26a-5p inhibitor can dramatically limit the ability of LINC00240 knockdown on plate colony formation and relocation of esophageal cancerous cells was demonstrated in colony formation and migration experiments. Conclusion: LINC00240 expression is elevated in esophageal cancerous tissues, and knocking down LINC00240 decreases esophageal cancer cell proliferation, clone formation, invasion, and migration via miR-26a-5p. As a result, LINC00240 could be a novel target for esophageal cancer patients' early diagnosis and treatment.
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Neoplasias Esofágicas , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sincalida/genética , Sincalida/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.
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Hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). The incidence is about 7% to 68%, and some patients have to suffer a long period of frequent, urgent, and painful urination, which brings great pain. This study aimed to analyze risk factors of HC and its effect on patient survival. We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020. Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex, age, and diagnosis, and logistic regression analyses were used to identify factors associated with HC. We used Kaplan-Meier curves to analyze the survival rates of patients in the HC and non-HC groups. We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve (ROC) analysis. After propensity score matching, there were 131 patients each in the HC and non-HC groups. In the HC group, 89 patients (67.9%) had mild HC (stage II°) and 43 (32.1%) had severe HC (stage III-IV). The median interval between stem cell transplantation and HC development was 31 (3-244) days. Univariate analysis indicated that donor age, hematopoietic stem cell source, HLA, acute graft-versus-host disease, busulfan, anti-thymocyte globulin (ATG), total body irradiation, cytomegalovirus (CMV) (urine), and BK polyomavirus (BKV) (urine) were significantly associated with HC. ATG, CMV (urine), and BKV (urine) were independent risk factors for HC based on the multivariate analysis. The Kaplan-Meier survival analysis showed no significant difference between the HC and non-HC groups (Pâ=â.14). The 1- and 2-year survival rates in the HC group were 78.4% and 69.6%, respectively, and the corresponding rates in the non-HC group were 84.4% and 80.7%, respectively. ROC analysis indicated that a urine BKV load of 1â×â107âcopies/mL was able to stratify the risk of HC. In conclusion, when the BKV load is >1â×â107, we need to be aware of the potential for the development of HC.
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Objective: To assess whether providing nasal continuous positive airway pressure (nCPAP) during delayed cord clamping is beneficial for preterm infants <32 weeks. Study Design: A randomized controlled trial was performed from March 2020 to May 2021. Premature infants (<32 weeks of gestational age; n = 160) were allocated to receive at least 60 s of delayed cord clamping with nCPAP (DCC+nCPAP; n = 80) or without nCPAP (DCC only; n = 80). For both groups, after the umbilical cord was clamped, the infants were carried immediately to the resuscitation room to continue receiving standard transition. The primary outcome was the mechanical ventilation (MV) rate within 24 h of life. The measurements related to early respiratory support effect before cord clamping including positive end-expiratory pressure (PEEP) and FiO2 during transition/leaving the delivery room, intubation rate during transition, pulmonary surfactant (PS) administration ≥2 times after birth, extubation failure, and incidence of bronchopulmonary dysplasia (BPD) were collected as the secondary outcomes. Furthermore, other neonatal short-term outcomes and safety assessment were also included. Results: The measurements were calculated using intention-to-treat analysis. The median time for cord clamping were 60 s with interquartile range (IQR) (60.00-60.00 vs. 60.00-70.00) in both groups. There were no difference in the primary outcome of MV rate within 24 h of life (p = 0.184). The arterial blood gas pH at 1 h after birth in the DCC+nCPAP group was 7.28 ± 0.08 vs. 7.25 ± 0.07 in the control group (mean difference = 0.01, 95% CI: -0.01-0.05, p = 0.052), which approached statistical significance. There was no significant statistical difference in the other short-term neonatal outcomes and the safety indicators between the two groups. Conclusions: Our study showed that delayed cord clamping with nCPAP was feasible and safe in preterm infants with gestational age <32 weeks. Although there was a trend toward a higher arterial blood gas pH at 1 h after birth in the DCC+nCPAP group, DCC+nCPAP neither resulted in a corresponding measurable clinical improvement nor did it reduce subsequent neonatal morbidity. A larger multi-center study including more infants with gestational age <28 weeks is needed to evaluate the full effects of DCC in combination with nCPAP in preterm infants.
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Secondary failure of platelet recovery (SFPR) is a life-threatening complication that may affect up to 20% of patients after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, to evaluate the efficacy of recombinant human thrombopoietin (rhTPO), we retrospectively analyzed 29 patients who received continuous rhTPO for the treatment of SFPR. Overall response and complete response were observed in 24 (82.8%) patients and 10 (34.5%) patients, at a median time of 21.5 days (range, 3-41 days) and 39.5 days (range, 7-53 days) after initiation of rhTPO treatment, respectively. Among the responders, the probability of keeping overall response and complete response at 1 year after response was 77.3% and 80.0%, respectively. In multivariate analysis, higher CD34+ cells (≥3 × 106/kg) infused during HSCT (HR: 7.22, 95% CI: 1.53-34.04, P = 0.01) and decreased ferritin after rhTPO treatment (HR: 6.16, 95% CI: 1.18-32.15, P = 0.03) were indicated to associate with complete response to rhTPO. Importantly, rhTPO was well tolerated in all patients without side effects urging withdrawal and clinical intervention. The results of this study suggest that rhTPO may be a safe and effective treatment for SFPR.
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Plaquetas/fisiologia , Rejeição de Enxerto/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Recuperação de Função Fisiológica , Trombocitopenia/terapia , Trombopoetina/administração & dosagem , Adolescente , Adulto , Criança , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Trombocitopenia/sangue , Fatores de Tempo , Transplante Homólogo , Adulto JovemRESUMO
Autologous hematopoietic stem cell transplantation (ASCT) remains an important postremission treatment for acute leukemia (AL). It is known that some prognostic factors, such as age, cytogenetic and molecular risk stratification, and minimal residual disease (MRD) status, are closely related to clinical outcomes following ASCT. Moreover, there are multiple measurements, including pretransplant treatment, stem cell mobilization and collection, conditioning regimens, and maintenance treatment after transplantation, that can affect prognosis after ASCT. Our clinical practice of ASCT should be better standardized to further improve patient outcomes. This review outlines optimization and quality control measures for ASCT developed at the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences, the first established and largest autologous stem cell transplant center in China. These measures will enhance the development of best practices and strategies for AL ASCT therapies, thereby improving patient outcomes.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Humanos , Neoplasia Residual , Transplante Autólogo , Resultado do TratamentoRESUMO
Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.
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Antibody-drug conjugates (ADCs) are biopharmaceuticals for the targeted delivery of antitumor agents. ADCs can be highly heterogeneous with various drug-to-antibody ratio (DAR) species, conjugation sites, and occupancy levels. The conjugation site can modulate the ADC stability and efficacy and therefore can be considered to be a critical quality attribute (CQA) during development. Traditional mass spectrometry (MS)-based peptide mapping methods cannot accurately quantify site-specific conjugations due to a significant ionization discrepancy between unconjugated native peptides and conjugated peptides. Here, we developed a novel protease-assisted drug deconjugation and linker-like labeling (PADDLL) method to quantify the levels of linker payload at specific conjugation sites. We utilized optimized papain digestion to deconjugate the drug payload and labeled unoccupied conjugation sites with a linker-like structure to provide comparable ionization efficiency for MS-based quantitation. This method was successfully applied on two cysteine-linked, protease-cleavable ADCs, and the method demonstrated good linearity and reliability, reaching a limit of quantitation of below 1%. The calculated DARs were comparable with the results from intact mass analysis. The lot-to-lot variation in conjugation distribution and inferior conjugation stability at HC Cys225 to other interchain cysteines were observed. This method provides a valuable tool for ADC design and product development. To the best of our knowledge, this is the first analytical method developed to accurately quantify site-specific linker-drug payload conjugations for ADCs.
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Imunoconjugados , Preparações Farmacêuticas , Anticorpos Monoclonais , Peptídeo Hidrolases , Reprodutibilidade dos TestesRESUMO
Megakaryocytes (MKs) and their progeny platelets function in a variety of biological processes including coagulation, hemostasis, inflammation, angiogenesis, and innate immunity. However, the divergent developmental and cellular landscape of adult MKs remains mysterious. Here, by deriving the single-cell transcriptomic profiling of MKs from human adult bone marrow (BM), cellular heterogeneity within MKs is unveiled and an MK subpopulation with high enrichment of immune-associated genes is identified. By performing the dynamic single-cell transcriptomic landscape of human megakaryopoiesis in vitro, it is found that the immune signatures of MKs can be traced back to the progenitor stage. Furthermore, two surface markers, CD148 and CD48, are identified for mature MKs with immune characteristics. At the functional level, these CD148+ CD48+ MKs can respond rapidly to immune stimuli both in vitro and in vivo, exhibit high-level expression of immune receptors and mediators, and may function as immune-surveillance cells. The findings uncover the cellular heterogeneity and a novel immune subset of human adult MKs and should greatly facilitate the understanding of the divergent functions of MKs under physiological and pathological conditions.
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Perfilação da Expressão Gênica/métodos , Megacariócitos/imunologia , Animais , Medula Óssea/imunologia , Diferenciação Celular , Humanos , Imunidade Inata/imunologia , Camundongos , Modelos AnimaisRESUMO
BACKGROUND: To examine the clinical significance of miR-125b in esophageal squamous cell carcinoma (ESCC) and to research the effect of miR-125b on the biological function of ESCC cells and the relevant underlying mechanism. METHODS: The expression of miR-125b in ESCC tissues and cell lines were discovered by RT-PCR assay. The interrelation between miR-125b expression and clinicopathological parameters and the forecasting of ESCC patients were analyzed. CCK-8 method and Transwell methods were used to detect the increased growth, shifting, and irruption of ESCC cells. Bioinformatics analysis was applied to forecast the possible target genes of miR-125b and verified through dual-luciferase reporter gene assay. After that, the expression of p38-MAPK mRNA and protein were found out by RT-PCR and Western blot. RESULTS: The expression of miR-125b was down-regulated in ESCC tissues and cell lines (P<0.05). And the expression of miR-125b was closely about tumor differentiation, TNM level, and lymph node metastasis in ESCC patients. The low miR-125b formulation was closely related to rough forecasting in ESCC patients. Large scale expression of miR-125b can effectively decrease the acceleration, shifting, and irrupting strengths of ESCC cells. Bioinformatics analysis showed p38-MAPK was forecasted to be a potential mark of miR-125b, which was confirmed by dual luciferase assay, and extreme expression of miR-125b can stop the expression of p38-MAPK mRNA and protein. CONCLUSIONS: miR-125b is down-regulated in ESCC. Moreover, its expression level is significant concerning tumor progression and prognosis in patients with ESCC. MiR-125b can stop the high growth and shifting of ESCC cells having p38-MAPK at target.
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A dual-sensitive drug delivery system (DDS) based on graphene oxide (GO) which is simultaneously loaded with proapoptotic peptides and anticancer drugs was rationally designed and fabricated for cancer synergetic therapy. Specifically, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on the surface of GO via a disulfide bond to obtain GO-SS-KLA. Then, the aromatic anticancer drug doxorubicin (DOX) was loaded on GO through π-π conjugation and hydrogen bonding interactions. Finally, bovine serum albumin (BSA) was used to coat the GO carrier to obtain a biological medium-stable GO-based DDS, DOX@GO-SS-KLA/BSA. The results show that KLA and DOX can be released responding to the reductive and pH stimulus inside the cells, respectively, and achieve a synergetic therapy for cancer. Moreover, the results of stability studies show that DOX@GO-SS-KLA/BSA could be stably dispersed in water for more than 8 days and in 10% fetal bovine serum for at least 6 days. The constructed DOX@GO-SS-KLA/BSA exhibits great potential as a drug carrier for co-delivery of various therapeutic agents.
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Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Grafite , Neoplasias , Peptídeos , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Grafite/química , Grafite/farmacocinética , Grafite/farmacologia , Células HeLa , Humanos , Células MCF-7 , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologiaRESUMO
A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.
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Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Peptídeos/administração & dosagem , Dióxido de Silício/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Peptídeos/farmacocinética , PorosidadeRESUMO
For phase-change cooling schemes for electronics, quick activation of nucleate boiling helps safeguard the electronics components from thermal shocks associated with undesired surface superheating at boiling incipience, which is of great importance to the long-term system stability and reliability. Previous experimental studies show that bubble nucleation can occur surprisingly early on mixed-wettability surfaces. In this paper, we report unambiguous evidence that such unusual bubble generation at extremely low temperatures-even below the boiling point-is induced by a significant presence of incondensable gas retained by the hydrophobic surface, which exhibits exceptional stability even surviving extensive boiling deaeration. By means of high-speed imaging, it is revealed that the consequently gassy boiling leads to unique bubble behaviour that stands in sharp contrast with that of pure vapour bubbles. Such findings agree qualitatively well with numerical simulations based on a diffuse-interface method. Moreover, the simulations further demonstrate strong thermocapillary flows accompanying growing bubbles with considerable gas contents, which is associated with heat transfer enhancement on the biphilic surface in the low-superheat region.
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The application of Bacillus sp. in the biological control of plant soilborne diseases has been shown to be an environmentally friendly alternative to the use of chemical fungicides. In this study, the effects of bioorganic fertilizer (BOF) fortified with Bacillus amyloliquefaciens SQY 162 on the suppression of tomato bacterial wilt were investigated in pot experiments. The disease incidence of tomato wilt after the application of BOF was 65.18% and 41.62% lower at 10 and 20 days after transplantation, respectively, than in the control condition. BOF also promoted the plant growth. The SQY 162 populations efficiently colonized the tomato rhizosphere, which directly suppressed the number of Ralstonia solanacearum in the tomato rhizosphere soil. In the presence of BOF, the activities of defense-related enzymes in tomato were lower than in the presence of the control treatment, but the expression levels of the defense-related genes of the plants in the salicylic acid and jasmonic acid pathways were enhanced. It was also found that strain SQY 162 could secrete antibiotic surfactin, but not volatile organic compounds, to suppress Ralstonia. The strain could also produce plant growth promotion compounds such as siderophores and indole-3-acetic acid. Thus, owing to its innate multiple-functional traits and its broad biocontrol activities, we found that this antagonistic strain isolated from the tobacco rhizosphere could establish itself successfully in the tomato rhizosphere to control soilborne diseases.
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Bacillus/metabolismo , Fertilizantes , Controle Biológico de Vetores/métodos , Ralstonia solanacearum/efeitos dos fármacos , Solanum lycopersicum/microbiologia , Bacillus/química , Bacillus/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Rizosfera , Microbiologia do SoloRESUMO
BACKGROUND: Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. METHODS: Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. RESULTS: Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). CONCLUSIONS: This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.
Assuntos
Cafeína , Café , Comportamento de Ingestão de Líquido , Melanoma/etiologia , Neoplasias Cutâneas/etiologia , Humanos , Fatores de Risco , Comportamento de Redução do RiscoRESUMO
Bacillus amyloliquefaciens is a plant-beneficial Gram-positive bacterium involved in suppressing soil-borne pathogens through the secretion of secondary metabolites and high rhizosphere competence. Biofilm formation is regarded as a prerequisite for high rhizosphere competence. In this work, we show that plant extracts affect the chemotaxis and biofilm formation of B. amyloliquefaciens SQY 162 (SQY 162). All carbohydrates tested induced the chemotaxis and biofilm formation of the SQY 162 strain; however, the bacterial growth rate was not influenced by the addition of carbohydrates. A strong chemotactic response and biofilm formation of SQY 162 were both induced by pectin through stimulation of surfactin synthesis and transcriptional expression of biofilm formation related matrix genes. These results suggested that pectin might serve as an environmental factor in the stimulation of the biofilm formation of SQY 162. Furthermore, in pot experiments the surfactin production and the population of SQY 162 in the rhizosphere significantly increased with the addition of sucrose or pectin, whereas the abundance of the bacterial pathogen Ralstonia decreased. With increased production of secondary metabolites in the rhizosphere of tobacco by SQY 162 and improved colonization density of SQY 162 in the pectin treatment, the disease incidences of bacterial wilt were efficiently suppressed. The present study revealed that certain plant extracts might serve as energy sources or environmental cues for SQY 162 to enhance the population density on tobacco root and bio-control efficacy of tobacco bacterial wilt.