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BACKGROUND: Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. METHODS: We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. RESULTS: The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. CONCLUSION: The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.
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In the present study, the anti-inflammation effect of Phellinus igniarius extract was detected on an in vitro model of RAW 264.7 cells stimulated using sodium urate. In this cell model, the content changes of inflammatory cytokines, intercellular adhesion molecule-1, and interleukin-1 beta, in cell culture supernatants were detected using an enzyme-linked immunosorbent assay. The xanthine oxidase inhibitory activity of P. igniarius extracts was determined using a microplate reader. Furthermore, in order to identify the active compounds of P. igniarius, ultrafiltration liquid chromatography mass spectrometry was utilized to screen xanthine oxidase inhibitors from the extract. Our results showed that in the presence of P. igniarius extract, the expressions of interleukin-1 beta and intercellular adhesion molecule-1 decreased (p < 0.01 and p < 0.05, respectively) compared to that in the control group. The extract effective inhibited the xanthine oxidase activity. Finally, seven compounds were screened and identified as potential xanthine oxidase inhibitors from P. igniarius. Taken together, these results demonstrate a potential anti-inflammation bioactivity of P. igniarius in vitro, providing a basis for further in vivo research for the prevention and treatment of gout.
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Cromatografia Líquida/métodos , Supressores da Gota/análise , Espectrometria de Massas/métodos , Phellinus/química , Ultrafiltração/métodos , Animais , Técnicas In Vitro , Camundongos , Extratos Vegetais/farmacologia , Células RAW 264.7 , Xantina Oxidase/antagonistas & inibidoresRESUMO
BACKGROUND: The inflammatory phenotypes of asthma predict the treatment response and prognosis. The phenotype distributions differ depending on the geographical region. This study aimed to assess the distribution of different inflammatory phenotypes among asthma patients in Jilin Province, China. METHODS: A total of 255 patients with asthma were recruited from Jilin Province, China for this cross-sectional study. Each patient underwent sputum induction following clinical assessment and peripheral blood collection. Inflammatory phenotypes were classified according to the inflammatory cell counts in the sputum. RESULTS: Paucigranulocytic asthma (PGA) was the most common inflammatory phenotype (52.2%), followed by eosinophilic asthma (EA, 38.3%), mixed granulocytic asthma (MGA, 5.2%), and neutrophilic asthma (NA, 4.3%). NA was more common among patients over 45 years old and those who were treated with higher doses of inhaled corticosteroids (ICS), but was less common following antibiotics treatment (p < 0.05). The proportion of patients with EA decreased as the ICS treatment dose and time increased (p = 0.038). Patients with uncontrolled asthma had higher numbers of sputum eosinophils and neutrophils (p < 0.05). Patients with severe asthma had a higher percentage of sputum neutrophils (p < 0.05). A greater proportion of patients with NA had severe asthma (60%) compared to those with EA (18.2%) (p = 0.016). CONCLUSIONS: The most common asthma inflammatory cell phenotype in Jilin Province, China is PGA, followed by EA, MGA, and NA. The low prevalence of NA in Jilin Province compared to other countries and also other regions in China might be due to excessive antibiotic use and irregular ICS treatment in this region.
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Asma/classificação , Asma/epidemiologia , Inflamação/complicações , Inflamação/epidemiologia , Fenótipo , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Idoso , Asma/sangue , Asma/tratamento farmacológico , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
Resveratrol, a natural compound extracted from the skins of grapes, berries, or other fruits, has been shown to have anti-tumor effects against multiple myeloma (MM) via promoting apoptosis and inhibiting cell viability. In addition to apoptosis, autophagy also plays a significant role in anti-tumor effects. However, whether autophagy is involved in anti-MM activity of resveratrol remains unclear. In this study, human MM cell lines U266, RPMI-8226, and NCI-H929 were treated with resveratrol. Cell Counting Kit-8 assay and colony formation assay were used to measure cell viability. Western blot analysis was used to detect apoptosis- and autophagy-associated proteins. 3-Methyladenine (3-MA) was applied to inhibit autophagy. Results showed that resveratrol inhibited cell viability and colony formation via promoting apoptosis and autophagy in MM cell lines U266, RPMI-8226, and NCI-H929. Resveratrol promoted apoptosis-related proteins, Caspase-3 activating poly-ADP-ribose polymerase and Caspase-3 cleavage, and decreased the protein level of Survivin in a dose-dependent manner. Additionally, resveratrol upregulated the levels of LC3 and Beclin1 in a dose-dependent way, indicating that autophagy might be implicated in anti-MM effect of resveratrol. Furthermore, 3-MA relieved the cytotoxicity of resveratrol by blocking the autophagic flux. Resveratrol increased the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream substrates p70S6K and 4EBP1 in a dose-dependent manner, leading to autophagy. Therefore, our results suggest that resveratrol exerts anti-MM effects through apoptosis and autophagy, which can be used as a new therapeutic strategy for MM in clinic.
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Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Mieloma Múltiplo/metabolismo , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Monofosfato de Adenosina/metabolismo , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Mieloma Múltiplo/patologia , Fosforilação/efeitos dos fármacosRESUMO
Unlike other members of the tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) family that play a carcinogenic role and regulate apoptosis, TNFAIP8-like 2 (TIPE2) can not only maintain immune homeostasis but also regulate inflammation. TIPE2 mainly restrains the activation of T cell receptor (TCR) and Toll-like receptors (TLR), regulating its downstream signaling pathways, thereby regulating inflammation. Interestingly, TIPE2 is abnormally expressed in many inflammatory diseases and may promote or inhibit inflammation in different diseases. This review summarizes the molecular target and cellular function of TIPE2 in immune cells and inflammatory diseases and the underlying mechanism by which TIPE2 regulates inflammation. The function and mechanism of TIPE2 in asthma is also explained in detail. TIPE2 is abnormally expressed in asthma and participates in the pathogenesis of different phenotypes of asthma through regulating multiple inflammatory cells' activity and function. Considering the indispensable role of TIPE2 in asthma, TIPE2 may be an effective therapeutic target in asthma. However, the available data are insufficient to provide a full understanding of the complex role of TIPE2 in human asthma. Further study is still necessary to explore the possible mechanism and functions of TIPE2 in different asthma phenotypes.
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Asma/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Animais , Asma/patologia , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Inflamação/patologia , Modelos BiológicosRESUMO
In situ monitoring of Sb speciation improves the understanding of Sb biogeochemistry and toxicity in ecosystems. Precise measurement of Sb is a challenge due to its instability of oxidation and ultratrace concentration. The development of simple and reliable methods specific to SbIII measurement is not only appealing but essential for implementing regulations. Here, we present an in situ speciation analysis method for SbIII, using the diffusive gradients in thin films (DGT) technique, combined with mercapto-functionalized SBA-15 mesoporous silica nanoparticles (MSBA). Laboratory performance tests confirmed MSBA-DGT uptake was independent of pH (4-9) and ionic strength (0.1-200 mmol L-1). DGT devices equipped with MSBA-based binding gels showed a theoretically linear accumulation of SbIII and exhibited a high capacity for SbIII at 65 µg/gel disc, with negligible accumulation of SbV over a 72 h deployment. Compared with commercial 3-mercaptopropyl-functionalized silica (MFS), the nanosized MSBA facilitate its even distribution in the binding gels. Furthermore, the good selectivity and high homogeneity of the MSBA gel enabled it to be applied in a rice rhizosphere in conjunction with AgI gel to investigate the effects of sulfur application on the SbIII solubility. In summary, the newly developed MSBA-DGT provides a selective measurement of SbIII, showing potential for environmental monitoring and further application in understanding the biogeochemical process of Sb.
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Antimônio/análise , Dióxido de Silício/química , Solo/química , Difusão , PorosidadeRESUMO
BACKGROUND: In December 2019, the outbreak of a disease subsequently termed COVID-19 occurred in Wuhan, China. The number of cases increased rapidly and spread to six continents. However, there is limited information on the chest computed tomography (CT) results of affected patients. Chest CT can assess the severity of COVID-19 and has sufficient sensitivity to assess changes in response to glucocorticoid therapy. OBJECTIVE: Analyze COVID-19 patients to determine the relationships of clinical characteristics, chest CT score, and levels of inflammatory mediators. METHODS: This retrospective, single-center case series of 108 consecutive hospitalized patients with confirmed COVID-19 at Tongji Hospital, Tongji Medical College of HUST (Wuhan, China) examined patients admitted from January 28 to February 20, 2020. Patient demographics, comorbidities, clinical findings, chest CT results, and CT scores of affected lung parenchyma were recorded. The relationships between chest CT score with levels of systemic inflammatory mediators were determined. RESULTS: All patients exhibited signs of significant systemic inflammation, including increased levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, chest CT score, and a decreased lymphocyte (LY) count. Chest CT score had positive associations with white blood cell (WBC) count, CRP, ESR, procalcitonin, and abnormal coagulation function, and a negative association with LY count. Treatment with a glucocorticoid increased the LY count, reduced the CT score and CRP level, and improved coagulation function. CONCLUSIONS: COVID-19 infection is characterized by a systemic inflammatory response that affects the lungs, blood, digestive system, and circulatory systems. The chest CT score is a good indicator of the extent of systemic inflammation. Glucocorticoid treatment appears to reduce systemic inflammation in these patients.
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Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Centros Médicos Acadêmicos , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19 , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pró-Calcitonina/metabolismo , Radiografia Torácica/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Análise de SobrevidaRESUMO
OBJECTIVES: This study proposes a chairside digital design and manufacturing method for band and loop space maintainers and preliminarily validates its clinical feasibility. METHODS: Clinical cases of 10 children requiring space maintenance caused by premature loss of primary teeth were collected. Intraoral scan data of the affected children were also collected to establish digital models of the missing teeth. Using a pediatric band and loop space maintainer design software developed by our research team, a rapid personalized design of band and loop structures was achieved, and a digital model of an integrated band and loop space maintainer was ultimately generated. A chairside space maintainer was manufactured through metal computer numerical control machining for the experimental group, whereas metal 3D printing in the dental laboratory was used for the control group. A model fitting assessment was conducted for the space maintainers of both groups, and senior pediatric dental experts were invited to evaluate the clinical feasibility of the space maintainers with regard to fit and stability using the visual analogue scale scoring system. Statistical analysis was also performed. RESULTS: The time spent in designing and manufacturing the 10 space maintainers of the experimental group was all less than 1 h. Statistical analysis of expert ratings showed that the experimental group outperformed the control group with regard to fit and stability. Both types of space maintainers met clinical requirements. CONCLUSIONS: The chairside digital design and manufacturing method for pediatric band and loop space maintainers proposed in this study can achieve same-day fitting of space maintainers at the first appointment, demonstrating good clinical feasibility and significant potential for clinical application.
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Perda de Dente , Humanos , Criança , Impressão Tridimensional , Mantenedor de Espaço em Ortodontia , Desenho Assistido por ComputadorRESUMO
Objective: With the improvement in health awareness, humanistic care ability of nurses has become a focus of public attention. The aim of the study was to confirm the relationship between psychological capital and humanistic care ability of nurses, and to provide suggestions on improving the humanistic care ability of nurses. Methods: A cross-section survey was conducted. Three hundred thirty-nine nurses were recruited from a tertiary general hospital in Taizhou, China. Psychological capital and humanistic care ability were measured using a self-reported questionnaire. Correlation analysis and stepwise multiple regression analysis were performed to analyze the correlation between psychological capital and humanistic care ability. Results: The psychological capital and humanistic care ability scores were 91.57 ± 13.96 and 189.08 ± 20.37, respectively. Differences in psychological capital scores across professional titles (F = 4.88, p = 0.01), departments (F = 3.69, p < 0.001), years of work (F = 4.68, p < 0.001), and marital status (t = 3.25, p < 0.001) were statistically significant. There were statistical differences for the humanistic care ability scores among nurses based on marital status (p = 0.01). The total psychological capital scores and the four sub-dimensions scores were positively correlated with the humanistic care ability scores among nurses. Self-efficacy was the main predictor of nurses' humanistic care ability. Conclusion: Psychological capital positively affected the humanistic care ability of nurses. Self-efficacy was the main predictor of humanistic care ability. Nursing managers can formulate strategies from the perspective of positive psychology to improve humanistic care ability of nurses.
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Objective: Lung cancer is the leading cause of cancer-related deaths worldwide. The aim of this study was to investigate the effects of hypoxic microenvironment on PTEN-L secretion and the effects of PTEN-L on the metastasis of non-small cell lung cancer (NSCLC) and the potential mechanisms. Methods: The expression levels of PTEN-L in NSCLC tissues, cells, and cell culture media were detected. The transfection of PTEN-L overexpression construct or HIF-1α-siRNAs was conducted to manipulate the expression of PTEN-L or HIF-1α. NSCLC cells were introduced into 200 µM CoCl2 medium for 72 hours under 37°C to simulate hypoxia. The proliferation and apoptosis of the A549 cells were determined by the Cell Counting Kit-8 assay and Annexin V-FITC/PI-stained flow cytometry assay, respectively. Wound healing assay and transwell invasion assay were used to measure the migration and invasion of A549 cells. The protein expression of PTEN, PTEN-L, PI3K/AKT pathway-related proteins, and HIF-1α was detected by Western blot. Results: PTEN and PTEN-L are downregulated in lung cancer tissues and cells. The protein expression of PTEN-L in the culture medium of lung cancer cell lines is decreased. The hypoxic microenvironment inhibits PTEN-L secretion. The low level of PTEN-L promotes cell proliferation, migration, and invasion, as well as inhibits apoptosis of A549 cells. The overexpression of PTEN-L attenuated the activation of the PI3K/AKT pathway by the hypoxic microenvironment. The knockdown of HIF-1α upregulates PTEN-L secretion under hypoxia. Conclusions: The hypoxic microenvironment inhibits PTEN-L secretion and thus activates PI3K/AKT pathway to induce proliferation, migration, and invasion promotion, and apoptosis inhibition in NSCLC cells.
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Objective: Using metagenomic next-generation sequencing (mNGS) to profile the bacterial pathogen of pleural infection in aspiration pneumonia for therapeutic decision-making. Methods: Collection and analysis of the clinical and laboratory data of aspiration pneumonia patients who underwent mNGS detection of pleural effusion at the Second Hospital of Jilin University from November 2020 and March 2022. Results: Nine males and one female were included, aged 33 to 69 years. All patients had chest pain, fever, cough, and hypoxemia symptoms; 90% had expectoration. The laboratory tests revealed that all patients had elevated white blood cell, neutrophil, and C-reactive protein (CRP) levels. Furthermore, erythrocyte sedimentation rate (ESR) increased in 8 patients, and procalcitonin increased in only one patient. Chest CT indicated different degrees of lobar pneumonia and pleural effusion in all patients, and biochemical results implied exudative effusion according to Light criteria. Most routine culture results were negative. Among bacteria identified by mNGS, Fusobacterium nucleatum (n=9) was the most common, followed by Parvimonas micra (n=7) and Filifactor alocis (n=6). Three patients underwent surgical treatment after applying targeted antibiotics, thoracic puncture and drainage, and fibrinolytic septum treatment. After the adjusted treatment, the number of white blood cells, neutrophils, and lymphocytes decreased significantly, indicating the eradication of the infection. Conclusions: Improving the vigilance of atypical people suffering from aspiration pneumonia is essential. The mNGS detection of pleural effusion clarified the microbial spectrum of aspiration pneumonia, allowing targeted antibiotic administration.
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Derrame Pleural , Pneumonia Aspirativa , Pneumonia Pneumocócica , Feminino , Humanos , Masculino , Antibacterianos/uso terapêutico , Bactérias , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Pneumonia Aspirativa/diagnóstico , Pneumonia Aspirativa/tratamento farmacológico , Pneumonia Pneumocócica/tratamento farmacológico , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Purpose: Although recent studies have highlighted the link of TIPE2 and asthma airway inflammation, its roles and molecular mechanisms in different asthma inflammatory phenotypes remain largely unknown. We evaluated sputum TIPE2 expression level and its correlation with different asthma phenotypes. Additionally, we explored the roles and mechanism of TIPE2 in M1 polarization of macrophages. Methods: A total of 102 asthma patients who underwent sputum induction were enrolled to evaluate the expression level of TIPE2 and its association with different asthma phenotypes. To explore the roles and mechanism of TIPE2 in M1 polarization of macrophages, THP-1 monocytes stimulated with phorbol-12-myristate-13-acetate, were used as a model of undifferentiated (M0) macrophages, and M0 macrophages were treated with lipopolysaccharide to induce M1 macrophages. Results: The sputum TIPE2 level was significantly lower in patients with neutrophilic asthma (NA) and higher in patients with eosinophilic asthma (EA) compared with patients with paucigranulocytic asthma. The levels of IL-1ß, TNF-α and IL-6 were highest in NA compared with other groups. TIPE2 levels in sputum negatively correlated with IL-1ß and TNF-α levels but positively correlated with IL-4, IL-5, IL-13, and IL-10 levels (P < 0.05). In vitro, TIPE2 enhanced Nrf2/HO-1 pathway activation in macrophages and inhibited LPS-induced M1 macrophage differentiation and related cytokine release. Further analysis showed that the Nrf2 inhibitor ML385 weakened TIPE2-induced activation of the Nrf2/HO-1 pathway, as well as TIPE2-induced suppression in M1 polarization of macrophage and inflammatory cytokines secretion. Conclusions: TIPE2 expression level was highly down-regulated in NA and was negatively correlated with inflammatory factors (IL-1ß and TNF-α). Aberrant expression of TIPE2 may target the Nrf2/HO-1 pathway to inhibit M1 macrophage-related neutrophilic inflammation in asthma.
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Asma , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fator 2 Relacionado a NF-E2 , Asma/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Acetato de Tetradecanoilforbol , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a common cause of cancer-related death. Better understanding of the molecular mechanisms, pathogenesis, and treatment of NSCLC can help improve patient outcomes. Significant progress has been made in the treatment of NSCLC, and immunotherapy can prolong patient survival. However, the overall cure and survival rates are low, especially in patients with advanced metastases. Interleukin-35 (IL-35), an immunosuppressive factor, is associated with the onset and prognosis of various cancers. Studies have shown that IL-35 expression is elevated in NSCLC, and it is closely related to the progression and prognosis of NSCLC. However, there are few studies on the mechanism of IL-35 in NSCLC. This study discusses the role of IL-35 and its downstream signaling pathways in the pathogenesis of NSCLC and provides new insights into its therapeutic potential.
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The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled "host-modulation therapy," has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugated tetracycline with odanacatib (a selective inhibitor of cathepsin K) to construct a multifunctional drug (TC-ODN). We discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. In vivo, TC-ODN could be absorbed and distributed specifically to the bone after systemic administration, and accumulation of TC-ODN increased bone mineral density in ovariectomized rats. Importantly, periodontal administration of TC-ODN could successfully promote bone healing in periodontitis rats with alveolar bone loss. The findings in our study uncovered the excellent biocompatibility and multifunction of TC-ODN, including bone-targeted accumulation, immunoregulation, anti-inflammatory activity and promotion of bone healing, which might contribute to the clinical treatment of periodontitis.
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BACKGROUND: There is a need to identify the asthma inflammatory phenotypes of patients to facilitate personalized asthma treatment. Sputum induction is time-consuming and requires expert clinical technique. This study aimed to assess the distribution and characteristics of asthma inflammatory phenotypes in Jilin Province, China; it also aimed to identify an easier method for characterization of an asthma phenotype, rather than sputum cellular analysis. METHODS: In this study, 232 asthma patients underwent sputum induction following clinical assessment and blood collection. Inflammatory cell counts in sputum were used to classify asthma inflammatory phenotypes. Receiver operating characteristic curve and Spearman correlation coefficient analyses were used to identify correlations between clinical parameters. RESULTS: Among the included patients, there had 52.1% paucigranulocytic, 38.4% eosinophilic, 4.3% neutrophilic, and 5.2% mixed granulocytic asthma phenotypes, respectively. In total, 129 (55.6%) patients had asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO); these patients had higher proportion of smokers, higher sputum neutrophil count, worse lung function, and worse asthma control, compared with patients who had asthma alone (p < 0.05). Sputum eosinophil/neutrophil counts were positively correlated with blood eosinophil/neutrophil counts (p < 0.01). To identify the presence of sputum eosinophil proportion ≥ 3%, optimal cut-off values for blood eosinophil count and fractional exhaled nitric oxide (FeNO) were 0.2 × 109/L and 30.25 ppd (area under the curve (AUC) = 0.744; AUC = 0.653, p < 0.001). AUCs did not significantly differ between FeNO and blood eosinophil count (p = 0.162), but both exhibited poor specificity (57% and 49%, respectively). To identify the presence of sputum neutrophil proportion ≥ 61%, the optimal cut-off value for blood neutrophil proportion was 69.3% (AUC = 0.691, p = 0.0003); however, this exhibited poor sensitivity (50%). CONCLUSIONS: Paucigranulocytic asthma was the most common phenotype, followed by eosinophilic asthma. Higher proportion of smokers, poor patient compliance, insufficient treatment, and poor asthma control may have been the main causes of high ACO proportion among patients in this study. Blood eosinophil/neutrophil counts exhibited poor specificity and sensitivity for prediction of airway eosinophilic/neutrophilic inflammation.
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The aim of this study was to evaluate the effect of mineral trioxide aggregate (MTA) and Brazilian propolis on the cell viability, mineralization, anti-inflammatory ability, and migration of human dental pulp cells (hDPCs). The cell viability was evaluated with CCK-8 kit after 1, 5, 7, and 9 days. The deposition of calcified matrix and the expression of osteogenesis-related genes were evaluated by Alizarin Red staining and real-time PCR after incubation in osteogenic medium for 21 days. The expression of inflammation-related genes in cells was determined after exposure to 1 µg/mL LPS for 3 h. Finally, the numbers of cells that migrated through the permeable membranes were compared during 15 h. Propolis and MTA significantly increased the viability of hDPCscompared to the control group on days 7 and 9. In the propolis group, significant enhancement of osteogenic potential and suppressed expression of IL-1ß and IL-6 was observed after LPS exposure compared to the MTA and control groups. The number of migration cells in the propolis group was similar to that of the control group, while MTA significantly promoted cell migration. Propolis showed comparable cell viability to that of MTA and exhibited significantly higher anti-inflammatory and mineralization promotion effects on hDPCs.
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Compostos de Alumínio/farmacologia , Anti-Inflamatórios/farmacologia , Compostos de Cálcio/farmacologia , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Óxidos/farmacologia , Própole/farmacologia , Silicatos/farmacologia , Antraquinonas , Brasil , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Combinação de Medicamentos , Humanos , Interleucina-1beta/análise , Interleucina-6/análise , Odontoblastos/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/análiseRESUMO
Background: The exacerbation of chronic obstructive pulmonary disease (COPD) seriously affects the patient's quality of life and prognosis. This multicenter cross-sectional study investigated the characteristics of stable COPD and risk factors for acute exacerbation of COPD (AECOPD) in patients in Changchun, Jilin Province, China. Methods: The study included 400 outpatients admitted to four secondary hospitals and four tertiary hospitals in Jilin Province from March 2018 to March 2019. Data on the general condition of stable COPD patients, patient self-management, COPD Assessment Test (CAT) scores, number of acute exacerbations in the past 12 months, and medications received during the study period were collected using a questionnaire. Results: Sociodemographic characteristics and clinical data were obtained from 306 patients, and drug prescription data were obtained from 329 patients. Pearson correlation analysis revealed that CAT scores were positively correlated with the number of acute exacerbations. Age, education level, smoking history, disease duration, number of comorbidities, and the presence of ischemic heart disease (IHD) were associated with AECOPD. Moreover, the level of education, disease duration, and the presence of IHD were independent risk factors for AECOPD. Poor compliance due to the lack of understanding of the disease and the high cost of treatment is a risk factor for AECOPD. In addition, increased air pollution in industrial cities and vitamin D deficiency are closely related to AECOPD. Conclusion: Low education level, long disease duration, and the presence of IHD may promote the exacerbation and poor control of COPD in patients in Jilin Province.
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Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Fatores de RiscoRESUMO
Multiple myeloma (MM) is a highly invasive and incurable plasma cell malignant disease with frequent recurrence. DCZ0801 is a natural compound synthesized from osalmide and pterostilbene and has few adverse effects. Here, we aimed to observe the therapeutic effects of DCZ0801 on myeloma cells and clarify the specific molecular mechanism underlying its anti-tumor activity. The Cell Counting Kit-8 assay, apoptosis detection, cell cycle analysis, western blot analysis, and tumor xenograft models were used to determine the effect of DCZ0801 treatment both in vivo and in vitro. We revealed that DCZ0801 treatment suppressed MM cell survival by inducing apoptosis and blocking the cell cycle at S phase. Deranged glycolysis and downregulated Akt/mTOR pathway may also be responsible for cell proliferation inhibition. Moreover, DCZ0801 treatment could remarkably reduce the tumor size in the xenograft mouse model. Therefore these findings indicate that DCZ0801 can be used as a novel therapeutic drug for patients suffering from multiple myeloma.
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Abstract: The aim of this study was to evaluate the effect of mineral trioxide aggregate (MTA) and Brazilian propolis on the cell viability, mineralization, anti-inflammatory ability, and migration of human dental pulp cells (hDPCs). The cell viability was evaluated with CCK-8 kit after 1, 5, 7, and 9 days. The deposition of calcified matrix and the expression of osteogenesis-related genes were evaluated by Alizarin Red staining and real-time PCR after incubation in osteogenic medium for 21 days. The expression of inflammation-related genes in cells was determined after exposure to 1 μg/mL LPS for 3 h. Finally, the numbers of cells that migrated through the permeable membranes were compared during 15 h. Propolis and MTA significantly increased the viability of hDPCscompared to the control group on days 7 and 9. In the propolis group, significant enhancement of osteogenic potential and suppressed expression of IL-1β and IL-6 was observed after LPS exposure compared to the MTA and control groups. The number of migration cells in the propolis group was similar to that of the control group, while MTA significantly promoted cell migration. Propolis showed comparable cell viability to that of MTA and exhibited significantly higher anti-inflammatory and mineralization promotion effects on hDPCs.