M2 macrophage subset decrement is an indicator of bleeding tendency in pediatric dengue disease

Background/purpose

Dengue disease is widespread in tropical and sub-tropical regions. Severe dengue infection is characterized by plasma leakage, fluid accumulation, severe bleeding, or vital organ impairment. Bleeding is a critical complication of dengue disease. However, the biomarkers of dengue disease are still unknown. Macrophages have a distinct polarization phenotype related to M1/M2 classification. Macrophage polarization toward the pro-inflammatory M1 phenotype is considered critical for efficient antiviral immune responses, whereas the anti-inflammatory M2 phenotype is considered essential for tissue remodeling. We investigated macrophage polarization patterns in the peripheral blood of pediatric patients with dengue disease.

The Catalytic Subunit of DNA-Dependent Protein Kinase Coordinates with Polo-Like Kinase 1 to Facilitate Mitotic Entry

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is the key regulator of the non-homologous end joining pathway of DNA double-strand break repair. We have previously reported that DNA-PKcs is required for maintaining chromosomal stability and mitosis progression. Our further investigations reveal that deficiency in DNA-PKcs activity caused a delay in mitotic entry due to dysregulation of cyclin-dependent kinase 1 (Cdk1), the key driving force for cell cycle progression through G₂/M transition. Timely activation of Cdk1 requires polo-like kinase 1 (Plk1), which affects modulators of Cdk1. We found that DNA-PKcs physically interacts with Plk1 and could facilitate Plk1 activation both in vitro and in vivo. Further, DNA-PKcs–deficient cells are highly sensitive to Plk1 inhibitor BI2536, suggesting that the coordination between DNA-PKcs and Plk1 is not only crucial to ensure normal cell cycle progression through G₂/M phases but also required for cellular resistance to mitotic stress. On the basis of the current study, it is predictable that combined inhibition of DNA-PKcs and Plk1 can be employed in cancer therapy strategy for synthetic lethality.Abbreviations: DNA-PKcs, DNA-dependent protein kinase catalytic subunit; Plk1, polo-like kinase 1; PBD, polo box domain     

NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor

The current standard of care for lung cancer consists of concurrent chemotherapy and radiation. Several studies have shown that the DNA-PKcs inhibitor NU7441 is a highly potent radiosensitizer, however, the mechanism of NU7441''s anti-proliferation effect has not been fully elucidated. In this study, the combined effect of NU7441 and ionizing radiation (IR) in a panel of non-small cell lung cancer cell lines (A549, H460 and H1299) has been investigated. We found that NU7441 significantly enhances the effect of IR in all cell lines. The notable findings in response to this combined treatment are (i) prolonged delay in IR-induced DNA DSB repair, (ii) induced robust G2/M checkpoint, (iii) increased aberrant mitosis followed by mitotic catastrophe specifically in H1299, (iv) dramatically induced autophagy in A549 and (v) IR-induced senescence specifically in H460. H1299 cells show greater G2 checkpoint adaptation after combined treatment, which can be attributed to higher expression level of Plk1 compared to A549 and H460. The enhanced autophagy after NU7441 treatment in A549 is possibly due to the higher endogenous expression of pS6K compared to H1299 and H460 cells. In conclusion, choice of cell death pathway is dependent on the mutation status and other genetic factors of the cells treated.     

Antioxidant Activity in Extracts of 27 Indigenous Taiwanese Vegetables

The objectives of this study were to identify the antioxidants and antioxidant axtivity in 27 of Taiwan’s indigenous vegetables. Lycium chinense (Lc), Lactuca indica (Li), and Perilla ocymoides (Po) contained abundant quercetin (Que), while Artemisia lactiflora (Al) and Gynura bicolor (Gb) were rich in morin and kaempferol, respectively. Additionally, Nymphoides cristata (Nc) and Sechium edule (Se)-yellow had significantly higher levels of myricetin (Myr) than other tested samples. Cyanidin (Cyan) and malvidin (Mal) were abundant in Gb, Abelmoschus esculentus Moench (Abe), Po, Anisogonium esculentum (Retz.) Presl (Ane), Ipomoea batatas (Ib)-purple, and Hemerocallis fulva (Hf)-bright orange. Relatively high levels of Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorption capacity (ORAC), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenger were generated from extracts of Toona sinensis (Ts) and Po. Significant and positive correlations between antioxidant activity and polyphenols, anthocyanidins, Que, Myr, and morin were observed, indicating that these phytochemicals were some of the main components responsible for the antioxidant activity of tested plants. The much higher antioxidant activity of Po, Ts, and Ib (purple leaf) may be related to their higher Cyan, Que, and polyphenol content.     

Trajectories of fasting plasma glucose variability and mortality in type 2 diabetes

Aim

To investigate the effect of changes in fasting plasma glucose (FPG) variability, as assessed by 2-year trajectories of FPG variability, on mortality risk in patients with type 2 diabetes (T2D).

In vitro hepatic differentiation of human mesenchymal stem cells

This study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from embryonic mesoderm, are able to differentiate into functional hepatocyte-like cells in vitro. MSCs were isolated from human bone marrow and umbilical cord blood, and the surface phenotype and the mesodermal multilineage differentiation potentials of these cells were characterized and tested. To effectively induce hepatic differentiation, we designed a novel 2-step protocol with the use of hepatocyte growth factor and oncostatin M. After 4 weeks of induction, cuboidal morphology, which is characteristic of hepatocytes, was observed, and cells also expressed marker genes specific of liver cells in a time-dependent manner. Differentiated cells further demonstrated in vitro functions characteristic of liver cells, including albumin production, glycogen storage, urea secretion, uptake of low-density lipoprotein, and phenobarbital-inducible cytochrome P450 activity. In conclusion, human MSCs from different sources are able to differentiate into functional hepatocyte-like cells and, hence, may serve as a cell source for tissue engineering and cell therapy of hepatic tissues. Furthermore, the broad differentiation potential of MSCs indicates that a revision of the definition may be required.     

脾虚证胃粘膜形态DNA cAMP微量元素改变的临床与实验研究

目的研究脾虚证实质、脾虚证与胃癌发生的关系。方法采用 IBAS2000型图象分析系统、501B 型扫描电镜附有9100/60型能量色散 X 分析仪,以及组织化学与放射免疫方法,检测脾虚证患者胃粘膜超微结构、肠化生亚型、DNA、cAMP、微量元素及其氧化物。结果脾虚色滞证患者中胃癌发生率、不完全性结肠型肠化生发生率和"背景病变"发生率均显著高于脾气虚证患者;胃粘膜 cAMP、Zn、Cu、ZnO 和 Cuo 含量,随着肠化生完全性至不完全性、小肠型至结肠型的顺序递减;而 DNA 含量则随以上顺序递增,P<0.05～0.001。胃粘膜不完全性结肠型肠化生组织内 DNA、cAMP、Zn、Cu、ZnO 和 CuO 含量则与胃癌组织同元显著性差异。结论脾虚气滞证胃病有癌变倾向;不完全性结肠型肠化生与胃癌的发生有密切关系。@何雪芬$目的!研究脾虚证实质、脾虚证与胃癌发生的关系。方法采用 IBAS2000型图象分析系统、501B 型扫描电镜附有9100/60型能量色散 X 分析仪,以及组织化学与放射免疫方法,检测脾虚证患者胃粘膜超微结构、肠化生亚型、DNA、cAMP、微量元素及其氧化物。结果脾虚色滞证患者中胃癌发生率、不完全性结肠型肠化生发生率和"背景病变"发生率均显著高于脾气虚证患者;胃粘膜 cAMP、Zn、Cu、ZnO 和 Cuo 含量,随着肠化生完全性至不完全性、小肠型至结肠型的顺序递减;而 DNA 含量则随以上顺序递增,P<0.05～0.001。胃粘膜不完全性结肠型肠化生组织内 DNA、cAMP、Zn、Cu、ZnO 和 CuO 含量则与胃癌组织同元显著性差异。结论脾虚气滞证胃病有癌变倾向;不完全性结肠型肠化生与胃癌的发生有密切关系。@尹玉芬$目的!研究脾虚证实质、脾虚证与胃癌发生的关系。方法采用 IBAS2000型图象分析系统、501B 型扫描电镜附有9100/60型能量色散 X 分析仪,以及组织化学与放射免疫方法,检测脾虚证患者胃粘膜超微结构、肠化生亚型、DNA、cAMP、微量元素及其氧化物。结果脾虚色滞证患者中胃癌发生率、不完全性结肠型肠化生发生率和"背景病变"发生率均显著高于脾气虚证患者;胃粘膜 cAMP、Zn、Cu、ZnO 和 Cuo 含量,随着肠化生完全性至不完全性、小肠型至结肠型的顺序递减;而 DNA 含量则随以上顺序递增,P<0.05～0.001。胃粘膜不完全性结肠型肠化生组织内 DNA、cAMP、Zn、Cu、ZnO 和 CuO 含量则与胃癌组织同元显著性差异。结论脾虚气滞证胃病有癌变倾向;不完全性结肠型肠化生与胃癌的发生有密切关系。