Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation.

Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.

Immune prognostic risk score model in acute myeloid leukemia with normal karyotype.

Acute myeloid leukemia with normal karyotype (NK-AML) is a group of diseases with high heterogeneity and immunological processes are significantly associated with its initiation and development. The implication of the immunogenomic landscape in the prognosis of patients with NK-AML has remained largely elusive. In the present study, the expression profiles of immune-related genes (IRGs) were examined and their association with overall survival (OS) was determined in 60 patients with NK-AML from The Cancer Genome Atlas dataset and 104 patients from the Gene Expression Omnibus (GEO) dataset no. GSE71014. Univariate Cox regression analysis was used to identify 42 and 203 IRGs in the two respective cohorts, which were significantly associated with OS in NK-AML. A risk model was constructed based on the regression coefficient and expression values of nine survival-associated IRGs shared between the two datasets [zinc finger CCCH-type containing, antiviral 1 like; transferrin receptor; suppressor of cytokine signaling 1; ELAV like RNA binding protein 1; roundabout guidance receptor 3; unc-93 homolog B1, Toll-like receptor signaling regulator; protein tyrosine phosphatase non-receptor type 6; interleukin 2 receptor subunit alpha (IL2RA) and IL3RA]. Using this risk model, patients with NK-AML may be divided into high- and low-risk groups in prognostic predictions. The area under the receiver operating characteristic curve for predicting OS was 0.793. The prognostic role of this risk model was successfully verified in another independent cohort (GEO dataset no. GSE71014). The prognostic risk score was positively associated with age and fms related receptor tyrosine kinase 3 mutation and correlated with infiltration by T regulatory cells. In conclusion, the results of the present study provided an IRG score model for prognostic stratification of adult patients with NK-AML, as well as further insight into the implication of IRGs in NK-AML that may lead to the development of novel immunotherapy approaches for this disease.

Antiproliferative effects of L-asparaginase in acute myeloid leukemia.

The antitumor enzyme L-asparaginase (L-Asp) has commonly been used for the treatment of acute lymphoblastic leukemia. However, the effects of L-Asp on acute myeloid leukemia (AML) and their underlying mechanisms have not been fully elucidated. In the present study, the effects of L-Asp on cell proliferation and apoptosis were investigated using the AML cell lines U937, HL-60 and KG-1a. The effects of combining L-Asp with mitoxantrone (MIT) and cytarabine (Ara-c) were also analyzed. The combination of MIT and Ara-C is known as MA therapy, and is a widely used therapeutic regimen for the treatment of elderly patients with refractory AML. When applied alone, L-Asp inhibited cell proliferation and induced apoptosis in each of the cell lines tested. Furthermore, the combined use of L-Asp with MA therapy further potentiated the inhibition of cell proliferation while increasing the induction of apoptosis. These findings provide evidence for the potential antitumor effect of L-Asp in AML, and indicate that improved efficacy maybe achieved by combining L-Asp with MIT and Ara-c. This combination may provide a promising new therapeutic strategy for the treatment of AML.

A 3-O-methylated heterogalactan from Pleurotus eryngii activates macrophages.

Mushroom-derived polysaccharides exhibit various biological activities owing to their diverse structural features. Here, we purified a 3-O-methylated heterogalactan (WPEP-N-b, Mw 21.4 kDa) from the fruiting bodies of Pleurotus eryngii. WPEP-N-b is composed primarily of galactose (43.8%), mannose (39.3%), methyl-galactose (11.7%) and glucose (9.2%) residues, with the main chain being composed of α-1,6-linked D-Galp and 3-O-Me-D-Galp, branched at O-2 with single t-ß-D-Manp as major the side chain. ß-1,6-D-Glcp residues are present as minor components either in side-chains or backbone. WPEP-N-b increases macrophage phagocytosis and secretion of NO, TNF-α, IL-6 and IL-1ß. Mechanistic studies demonstrate that WPEP-N-b promotes the degradation of IκB-α, and enhances phosphorylation of MAPKs and the NF-κB p65 subunit. Our results also indicate that this polysaccharide activates RAW264.7 cells via MAPK and NF-κB signaling pathways and the Toll-like receptor 2(TLR2). These results increase our understanding as to how mushroom-derived polysaccharides modulate the immunologic process.

The impact of inflammation and cytokine expression of PM2.5 in AML.

Environmental and health issues have become a major focus of research worldwide in recent years. Particulate matter with diameter ≤2.5 µm (PM2.5) is a common air pollutant that has been demonstrated to be associated with various diseases, including acute myeloid leukemia (AML). In the present study, the effects of PM2.5 on the proliferation and inflammation were assessed using three human acute myeloid cell lines (U937, HL-60 and KG-1a) in vitro. Additionally, the levels of several cytokines [interleukin (IL)-2, IL-10, IL-17A and tumor necrosis factor (TNF)α] in AML cells and Sprague Dawley rats were evaluated to investigate the effects of PM2.5 on cytokine expression in AML. The results revealed that PM2.5 was capable of enhancing inflammatory responses in AML cells, and increasing IL-2, IL-10, IL-17A and TNFα mRNA expression in AML cells to different degrees. Furthermore, PM2.5 increased IL-2 and IL-10 contents in rats following 12 weeks of exposure. These results suggested that PM2.5 may serve a role in promoting the occurrence and progression of leukemia by affecting cytokine expression, and that there may be various mechanisms active in different AML subtypes.

Nomograms for predicting the overall and cancer-specific survival of patients with classical Hodgkin lymphoma: a SEER-based study.

The aim of this study was to establish nomograms, based on significant clinicopathologic parameters, for predicting the overall survival (OS) and the cancer-specific survival (CSS) of patients with classical Hodgkin lymphoma (CHL). The data of 43,330 CHL patients, diagnosed between 1983 and 2014, were obtainedfrom the database of the Surveillance, Epidemiology, and End Results (SEER) program. These patients were randomly divided into training (n = 30,339) and validation (n = 12,991) cohorts. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic effects of multiple clinicopathologic parameters on survival. Significant prognostic factors were combined to build nomograms. The predictive performance of nomograms was evaluated using the index of concordance (C-index) and calibration curves. In the training cohort, on univariate and multivariate analyses, age at diagnosis, gender, race, Ann Arbor stage, and histological type significantly correlated with the survival outcomes. These characteristics were used to establish nomograms. The nomograms showed good accuracy in predicting 1-, 5-, and 10-year OS and CSS, with a C-index of 0.794 (95% confidence interval [CI], 0.789-0.799) for OS and 0.760 (95% CI, 0.753-0.767) for CSS. In the validation cohort, the C-index for nomogram-based predictions was 0.787 (95% CI, 0.779-0.795) for OS and 0.769 (95% CI, 0.758-0.780) for CSS. All calibration curves revealed excellent consistency between predicted and actual survival. In summary, novel nomograms were established and validated to predict OS and CSS for patients with CHL. These new prognostic models could aid in improved prediction of survival outcomes leading to reasonable treatment recommendations.

Spontaneous splenic rupture in an acute leukemia patient with splenic tuberculosis: A case report.

Spontaneous splenic rupture, also referred to as atraumatic splenic rupture, is a rare but life-threatening emergency condition. Without timely diagnosis and treatment, the mortality rate of splenic rupture approaches 100%. The etiology of atraumatic splenic rupture varies; it is reportedly associated with neoplasms or splenic infection, but is rarely encountered in patients with both conditions. We herein report the case of a 58-year-old male patient with acute myeloid leukemia (AML) complicated by splenic tuberculosis (TB), who presented with spontaneous rupture of the spleen. Pathological examination of the resected spleen revealed multifocal granulomatosis with caseous necrosis. However, with timely diagnosis and surgical intervention, the patient recovered successfully and is currently on consolidation therapy. To the best of our knowledge, this is the first case of spontaneous splenic rupture in AML with splenic TB. The relevant literature on spontaneous splenic rupture was also reviewed and the potential etiology and treatment were discussed.

[Establishment and analysis of chronic periodontitis and atherosclerosis model in Wistar rat].

OBJECTIVE: To investigate the possible correlation between atherosclerosis and chronic periodontitis by establishing an animal model of chronic periodontitis and atherosclerosis in Wistar rat. METHODS: Sixty male Wistar rats were divided into four groups: A (control group), B (chronic periodontitis group), C (atherosclerosis group), D (chronic periodontitis accompany with atherosclerosis group). Every group was accepted the corresponding treatment. Animals were sacrificed after 12 weeks. The periodontal index, levels of serum total cholesterol (TC) and low-density lipoprotein (LDL), the concentration of TNF-alpha and matrix metalloproteinase (MMP-3) were examined. The severity of chronic periodontitis and atherosclerosis was quantified by histopathology. The date were statistically analyzed. RESULTS: Through detection of periodontal tissue of experimental teeth, serum and histopathology, animal models were successful. Histopathologic observation revealed:obvious inflammation of periodontal tissue was observed in group B and D. Attachment loss level in group B [(137.86 +/- 28.39) microm] and D [(162.36 +/- 22.69) microm] was higher than that in group A [(4.26 +/- 1.07) microm] and C [(68.07 +/- 18.25) microm] (P < 0.05), and that in group C was higher than group A (P < 0.05). Atherosclerotic lesions of abdominal aorta were formed in group C and D. The level of TC, LDL in group C and D was higher than that in group A and B (P < 0.05), and that in group D was higher than group C (P < 0.05). Animals in group B and D showed higher level of TNF-alpha, MMP-3 in serum than that in group A and C (P < 0.05). There was no correlation between the level of MMP-3 and TC (P = 0.971) or LDL (P = 0.604). CONCLUSIONS: Chronic periodontitis may be a risk factor and contribute to the pathogenesis of atherosclerosis. MMP-3 may be an independent risk factor of atherosclerosis exclude TC and LDL.