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Background: The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. Methods: This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. Results: Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36–2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82–0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32–2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51–5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. Conclusion: We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population. [ABSTRACT FROM AUTHOR]

Background: Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB. Methods: Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry. Results: RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis. Conclusions: These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy. [ABSTRACT FROM AUTHOR]

Background: Polyunsaturated fatty acid (PUFA) intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, the relationship between the PUFA and inflammatory factors in the healthy vegetarians were not clear. We aimed to investigate the plasma fatty acids status, and its association with plasma inflammatory factors in Chinese vegetarians and omnivores. Methods: A total of 89 male vegetarians and 106 male omnivores were participated the study. Plasma concentrations of inflammatory factors were detected by ELISA, and as standard methods fatty acids were extracted and determined by chromatography. Results: Compared with omnivores, vegetarians have significant higher interleukin-6 (IL-6), plasma n-6 PUFA, n-6/n-3, and 18:3n-3; while they have significant lower leukotriene B4 (LTB4), cyclo-oxygenase-2 (COX2) and prostaglandin E2 (PGE2), 20:5n-3, 22:5n-3, 22:6n-3, and n-3 PUFA. In vegetarians, plasma 20:4n-6 was significant positively related to TNF-α. LTB4 was significantly positively related to plasma 22:6n-3, and negatively associated with n-6 PUFA. Conclusion: Vegetarians have higher plasma n-6 PUFA and IL-6, but lower LTB4, n-3 PUFA, 22:6n-3, COX2 and PGE2 levels. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA, while reduce dietary n-6 PUFA and thus reduce the risk of chronic inflammatory-related diseases.

Background: We tested the hypothesis that elevated homocysteine (Hcy) level is causally associated with increased risk of type 2 diabetes mellitus (T2DM). Results: The meta-analysis and Mendelian randomization analysis were performed among 4011 cases and 4303 controls. The absolute pooled mean Hcy concentration in subjects with MTHFR 677TT was 5.55 μmol/L (95% CI, 1.33 to 9.77) greater than that in subjects with MTHFR 677CC in T2DM. Overall, the T allele of the MTHFR 677 C > T conferred a greater risk for T2DM [Random effect (RE) OR = 1.31(1.17-1.64), I2 = 41.0%, p = 0.055]. The random effect (RE) pooled OR associated with T2DM for MTHFR 677TT relative to the 677CC was [RE OR = 1.38(1.18-1.62)]. The fixed-effect pooled OR of the association for the MTHFR 677 TT vs CT was 1.29 (95% CI, 1.09-1.51). MTHFR 677 TT showed a significantly higher risk for T2DM compared with MTHFR 677 CC + CT [Fixed effect (FE) OR = 1.32(1.14-1.54), I2 = 0.0%, p = 0.686]. The absolute pooled mean Hcy concentration in individuals with T2DM was 0.94 μmol/L (95% CI, 0.40-1.48) greater than that in control subjects. The estimated causal OR associated with T2DM was 1.29 for 5 μmol/L increment in Hcy. Conclusions: Our findings provided strong evidence on the causal association of Hcy level with the development of T2DM.

Background: Increased ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) in diet or serum may have a protective effect on the risk of breast cancer (BC); however, the conclusions from prospective studies are still controversial. The purpose of this study is to ascertain the relationship between intake ratio of n-3/n-6 PUFAs and the risk of BC, and estimate the potential summarized dose-response trend.Methods: Relevant English-language studies were identified through Cochrane Library, PubMed and EMBASE database till April 2013. Eligible prospective studies reporting the multivariate adjusted risk ratios (RRs) for association of n-3/n-6 PUFAs ratio in diet or serum with BC risk. Data extraction was conducted independently by 2 investigators; disagreements were reconciled by consensus. Study quality was assessed using the Newcastle-Ottawa scale. Study-specific RRs were combined via a random-effects model.Results: Six prospective nested case-control and 5 cohort studies, involving 8,331 BC events from 274,135 adult females across different countries, were included in present study. Subjects with higher dietary intake ratio of n-3/n-6 PUFAs have a significantly lower risk of BC among study populations (pooled RR = 0.90; 95% CI: 0.82, 0.99), and per 1/10 increment of ratio in diet was associated with a 6% reduction of BC risk (pooled RR = 0.94; 95% CI: 0.90, 0.99; P for linear trend = 0.012). USA subjects with higher ratio of n-3/n-6 in serum phospholipids (PL) have a significantly lower risk of BC (pooled RR = 0.62; 95% CI: 0.39, 0.97; I2 = 0.00%; P for metaregression = 0.103; P for a permutation test = 0.100), and per 1/10 increment of ratio in serum PL was associated with 27% reduction of BC risk (pooled RR = 0.73; 95% CI: 0.59, 0.91; P for linear trend = 0.004; P for metaregression = 0.082; P for a permutation test = 0.116).Conclusions: Higher intake ratio of n-3/n-6 PUFAs is associated with lower risk of BC among females, which implies an important evidence for BC prevention and treatment is by increasing dietary intake ratio of n-3/n-6 PUFA. No firm conclusions from USA populations could be obtained, due to the limited numbers of USA studies. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that plasma n-3 polyunsaturated fatty acid (PUFA) was negatively associated with plasma homocysteine (Hcy).Objective: We investigated the regulatory effect of n-3 PUFA on mRNA expression of the critical genes encoding the enzymes involved in Hcy metabolism.Methods: HepG2 cells were treated with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA) respectively for 48 h. The cells were collected and total RNA was isolated. The mRNA expression levels of the genes were determined by using Real Time-PCR.Results: Compared with controls, the mRNA expression levels of 5-methyltetrahydrofolate reductase (MTHFR) were significantly increased in the DHA group (p < 0.05) and ALA group (p < 0.05); Significantly down-regulated mRNA expression of methionine adenosyltransferase (MAT) was observed with the treatments compared with the controls; the level of MAT expression was significant lower in the DHA group than the ALA group (p < 0.05); Cystathionine-γ-lyase (CSE) expression was significantly increased in the DHA (p < 0.05) and EPA groups (p < 0.05) compared with control. No significant changes were shown in mRNA expression levels of S-adenosylhomocysteine hydrolases (SAHH), cystathionine β-synthase (CBS), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR).Conclusions: Our results suggest that DHA up-regulates CSE and MTHFR mRNA expression and down-regulates MAT mRNA expression involved in Hcy metabolism. [ABSTRACT FROM AUTHOR]

Background: Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points., Results: Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time., Conclusions: Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice.

Background: Cancer stem cells (CSCs) are considered as the origin of tumor relapse. Here, we investigated the effects of Fructus Viticis total flavonoids (FVTF) on the characteristics of lung cancer stem-like cells (LCSLCs) derived from human small cell lung cancer NCI-H446 cell line and its potential mechanism., Methods: Human small cell lung cancer NCI-H446 cell line was cultured in vitro. The CD133(+) cells were sorted from NCI-H446 cell line by magnetic separation. The suspended culture with stem cell-conditioned medium was used to amplify CD133(+) sphere-forming cells (SFCs). The stem cell characteristics of CD133(+) SFCs were evaluated using cell self-renewal capacity by tumor sphere formation assay, migration and invasion capacity by Transwell assay, tumorigenicity by xenograft model in nude mouse and cancer stem cell markers expression levels by western blot. The effects of FVTF on the properties of LCSLCs were examined by tumorsphere formation assay and transwell chamber assay. The expression level of p-Akt was determined by western blot analysis., Result: CD133(+) SFCs derived from human small cell lung cancer NCI-H446 cells exhibited stemness properties of tumorsphere formation and tumorigenesis capacity comparing to the parental cells. FVTF relative selectively inhibited the proliferation of LCSLCs, suppressed tumor sphere forming capacity and migration and invasion of LCSLCs, and down-regulated the protein expression of stem cell markers (CD133, CD44 and ALDH1), self-renewal associated transcription factors (Bmi1, Nanog and OCT4) and invasion associated transcription factors (Twist1 and Snail1) in a dose-dependent manner. Moreover, we found that FVTF treatment could significantly decrease the phosphorylation level of Akt in LCSLCs. Meanwhile, LY294002 and FVTF synergistically inhibited the characteristics of LCSLCs., Conclusion: FVTF inhibits the characteristics of LCSLCs through down-regulating expression of p-Akt.

Background: Epidemiological studies have assessed relationships between circulating levels of fatty acid (FA) and blood pressure (BP), and their results remain controversial. Nevertheless, data are sparse on serum FA as biomarker and BP in China. The aim of the study was to investigate the association between serum FA and BP in Chinese populations., Methods: We conducted a cross-sectional study nested within a community-based cohort of 2447 Chinese participants aged 35-79 years who completed a baseline assessment between October 2012 and April 2013. Baseline assessment included the collection of fasting blood samples, anthropometric measurements and a personal interview using a validated questionnaire. Serum FA was determined by gas-liquid chromatography. Exploratory factor analyses were employed to identify FA-factor as a reflection of serum FA pattern. A multiple regression model was conducted to estimate adjusted mean of BP with 95% confidence interval (CI) by tertile groups of the generated FA-factor scores., Results: Hypertensive patients have significantly higher serum 14:0, 16:0, 16:1n-7, 18:3n-6, 20:3n-6 and Δ(6)-desaturase index (18:3n-6/18:2n-6) as well as lower 18:2n-6, 22:6n-3 and Δ(5)-desaturase index (20:4n-6/20:3n-6) compared with normotensive participants. Factor 1 (low linoleic acid/high saturated FA pattern: 14:0, 16:0, 16:1n-7, 18:2n-6, 18:3n-6, 20:3n-6) and Factor 2 (n-3 PUFA pattern: 20:5n-3, 22:5n-3, 22:6n-3, 18:1n-9) were identified as indicators of the serum FA pattern. After adjustment for age, gender, body mass index, hypertension treatment, smoking, alcohol intake, education, profession, exercise habit, salt intake, family history of hypertension, heart rate, blood lipids and fasting blood-glucose levels, per a standard deviation (SD) increment of Factor 1 scores was associated with an increment of 2.44 (95% CI: 1.73, 3.15) mm Hg for systolic BP, whereas per a SD increment of Factor 2 scores was associated with a reduction of 1.40 (95% CI: 0.80, 2.04) mm Hg for diastolic BP., Conclusions: The serum FA pattern characterized by low proportions of 14:0, 16:0, 16:1n-7 and 18:3n-6 as well as high 18:2n-6 and 22:6n-3 was beneficially associated with BP levels in this Chinese population. This evidence well supports the current dietary recommendations in the communities to replace saturated fat with polyunsaturated fat.

Background: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716)., Results: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033)., Conclusion: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.

Background: Cardiovascular disease (CVD) and colon cancer incidence are known to be closely related to dietary factors. This article evaluated effects of krill oil (KO) on serum lipids of hyperlipidemia rats and human colon cancer cells (SW480). Serum lipids of rats fed with high fat diet (HFD) and different doses of KO were measured by automatic analyzer. Effect of KO on viability of cells was determined by methyl thiazolyl tetrazolium (MTT) assay., Results: Except for higher dose group, body weights decreased significantly. Total cholesterol (TC), LDL-cholesterol (LDL-C) of all dose groups, Triglycerides (TG) of low and mid dose groups descended significantly, while there were no significant differences of HDL-cholesterol (HDL-C), compared with control group. Treatment of colon cancer cells with KO also resulted in time-dependent inhibition of cell growth., Conclusion: Our findings indicated that the consumption of KO may provide benefits to control serum lipid levels in certain diseases and inhibit growth of colon cancer cells. Therefore, KO may be a good candidate for development as a functional food and nutraceutical.