Changes and significance of Treg and Th17 in adult patients with primary membranous nephropathy.

OBJECTIVE: To investigate the changes in Treg and Th17 cells and explore the significance of Treg/Th17 balance in adult primary membranous nephropathy (PMN) patients. MATERIALS AND METHODS: A total of 60 PMN patients and 50 healthy adults from June 2013 to October 2016 were enrolled in this study. The levels of Treg, Th17, and related cytokines were assessed. Pearson correlation was used for conducting correlation analysis. RESULTS: There was a significant increase in Th17 frequencies and IL-17 (Th17-related cytokines) in the peripheral blood mononuclear cells (PBMCs), as well as a significant decrease in Treg frequencies and IL-10 (Treg-related cytokines). The IL-17 concentrations in the peripheral blood of PMN patients were positively correlated with urinary protein, while IL-10 levels were negatively correlated with urinary protein. Protein expression of Treg transcription factor (Foxp3) was significantly low in the renal tissues of PMN patients, while the expression of IL-17 was much higher. Th17/Treg imbalance was reversed to normal after effective treatment with tacrolimus in 15 PMN patients. CONCLUSION: These results suggested the existence of Treg/Th17 imbalance in PMN patients, showing the importance of Treg/Th17 imbalance in PMN pathogenesis.

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model.

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.

[LncRNA MALAT1 Modulates the Immunoreaction of Rats with Lipopolysaccharide-induced Sepsis by Targeting the miR-146a/NF-κB P65 Pathway].

OBJECTIVE: To determine the regulatory and molecular mechanism of lncRNA MALAT1 in response to sepsis induced by lipopolysaccharide (LPS) in rats. METHODS: The expressions of lncRNA MALAT1 and miR-146a in U937 cells and peripheral blood samples of the rats with and without LPS-induced sepsis were detected using quantitative real-time reverse transcription PCR (qRT-PCR). The relationship between lncRNA MALAT1 and miR-146a was affirmed through luciferase assay. The expressions of p-P65, P65, TNF-α and iNOS were tested by Western blot. The expressions of TNF-α and iNOS in the lung tissues of the rats were measured by immunohistochemistry. RESULTS: The rats with LPS-induced sepsis had higher expressions of lncRNA MALAT1 in U937 cells than those without sepsis (P<0.001). In comparison with scramble, si-MALAT1 attenuated the expression of lncRNA MALAT1 and increased the expression of miR-146a (P<0.001). MiR-146a was the target of lncRNA MALAT1. si-MALAT1 decreased the p-P65/P65 ratio and and the expressions of TNF-α and iNOS in the rats with LPS-induced sepsis. In contrast, miR-146a inhibitor increased p-P65/P65 ratio and the expressions of TNF-α and iNOS in the rats with LPS-induced septis (P<0.001). Co-transfection with si-MALAT1 attenuated the elevated level of p-P65/P65 ratio and expressions of TNF-α and iNOS resulting from miR-146a inhibitor (P<0.001). LPS and scramble decreased the expression of miR-146a and increased the p-P65/P65 ratio compared with the healthy controls (P<0.01). Compared with scramble, si-MALAT1 increased the expression of miR-146a and attenuated the p-P65/P65 ratio (P<0.01). Higher numbers of TNF-α and iNOS positive cells were found in those with LPS-induced sepsis and those with scramble interventions (P<0.001). Compared with scramble, si-MALAT1 reduced the number of TNF-α and iNOS positive cells (P<0.01). CONCLUSIONS: LncRNA MALAT1 modulates the immunoreaction of rats with LPS -induced sepsis by targeting miR-146a/NF-κB P65.

Surface Energy and Surface Stability of Ag Nanocrystals at Elevated Temperatures and Their Dominance in Sublimation-Induced Shape Evolution.

The surface energy and surface stability of Ag nanocrystals (NCs) are under debate because the measurable values of the surface energy are very inconsistent, and the indices of the observed thermally stable surfaces are apparently in conflict. To clarify this issue, a transmission electron microscope is used to investigate these problems in situ with elaborately designed carbon-shell-capsulated Ag NCs. It is demonstrated that the {111} surfaces are still thermally stable at elevated temperatures, and the victory of the formation of {110} surfaces over {111} surfaces on the Ag NCs during sublimation is due to the special crystal geometry. It is found that the Ag NCs behave as quasiliquids during sublimation, and the cubic NCs represent a featured shape evolution, which is codetermined by both the wetting equilibrium at the Ag-C interface and the relaxation of the system surface energy. Small Ag NCs (≈10 nm) no longer maintain the wetting equilibrium observed in larger Ag NCs, and the crystal orientations of ultrafine Ag NCs (≈6 nm) can rotate to achieve further shape relaxation. Using sublimation kinetics, the mean surface energy of Ag NCs at 1073 K is calculated to be 1.1-1.3 J m-2 .

Porphyromonas gingivalis infected macrophages upregulate CD36 expression via ERK/NF-κB pathway.

CD36, a scavenger receptor, plays an important role in the progression of atherosclerosis through its interaction with oxidized low-density lipoprotein (ox-LDL). Porphyromonas gingivalis (P. gingivalis, Pg) has been shown to promote macrophage-derived foam cell formation by affecting the expression of CD36. However, the regulatory role of CD36 in macrophages infected with Pg remains largely unknown. Therefore, the aim of the present study was to explore the molecular mechanism of Pg induced CD36 expression in macrophages. Our results showed that Pg promoted ox-LDL uptake by macrophages and the formation of foam cells. Pg infection increased CD36 mRNA and protein levels in ox-LDL-untreated macrophages. Moreover, small interferon RNA (siRNA) targeting CD36 significantly reduced foam cell formation induced by Pg. Additionally, Pg stimulated nuclear translocation of p65, which directly bound to the promoters of CD36 to facilitate its transcription. Inhibition of p65, NF-κB or ERK1/2 blocked Pg-induced CD36 production; whereas, overexpression of NF-κB subunits p65 and p50 upregulated CD36. Furthermore, Ras inhibitors significantly attenuated ERK1/2 activation and CD36 expression. Taken together, the data indicated that stimulation of the ERK/NF-κB pathway by Pg led to transactivation of the CD36 promoters, thereby upregulating CD36 expression in the infected macrophages. These findings may help design new treatment strategies in atherosclerosis.

Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and malignant development of human hepatocellular carcinoma (HCC).

Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. LAP3 is one important member of this family. However, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3 expression was significantly up-regulated in HCC tissues as well as cells and was closely correlated with lower differentiation, positive lymph node metastasis and high Ki-67 expression, indicating a poor prognosis. Then cell viability assays, flow cytometry assays, wound-healing assays and matrigel invasion assays were performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to cisplatin, thus promoting the cell death of HCC cells. Collectively, our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of HCC. Our data gains greater insight into the cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing potential therapeutic strategies for clinical trials.

[A comparative study of efficacy for treating conjunctivochalasis with positioning and quantified patch].

OBJECTIVE: To investigate the efficacy for treating conjunctivochalasis with conjunctival positioning and quantified patch. METHODS: It was a case-control study. A case-control study of 30 patients from the First Hospital of Jiaxing from 2007 to 2008 with binocular conjunctivochalasis. Every patient was treated one eye with simple logadectomy while the other eye with positioning and quantified logadectomy randomly. Subjective and objective evaluations were taken on the 1st, 3rd and 6th months post-operation. Subjective evaluations include effective rate and cure rate. Objective evaluations include slit-lamp biomicroscope morphological variety, tear meniscus height, break-up time (BUT), Schirmer I test (SIT), fluorescein stain test (Fl), the first fluorescein stain. Cure rate and efficacy rate were compared in two groups with chi-square test. RESULTS: Subjective evaluations were on the 1st month post-operation. There were 5 eyes (16.7%) curing, 13 eyes (43.3%) improved, 12 eyes (40.0%) ineffective in simply logadectomy group; While there were 12 eyes (40.0%) curing, 16 eyes (53.3%) improved, 2 eyes (6.7%) ineffective in the positioning and quantified logadectomy group. The effective rate (chi2=9.317, P<0.01) and cure rate(chi2=4.022, P<0.05)had statistic significance. Effective rate in simply logadectomy group was increasing gradually on the 3rd and 6th month post-operation while effective rate in positioning and quantified logadectomy group was stable. But the effective rate in this group was still higher than the simple logadectomy group. To objectively evaluate the cure rate on the 1st month post-operation: slit-lamp biomicroscope morphological variety: there were 10 eyes turn to normal in simply logadectomy group while 29 eyes (chi2=26.447, P<0.01) in the positioning and quantified logadectomy group. Tear meniscus height: there were 18 eyes turn to normal in simply logadectomy group while 30 eyes (chi2=15.000, P<0.01) in the positioning and quantified logadectomy group. BUT: There were 12 eyes turn to normal in simply logadectomy group while 28 eyes (chi2=19.200, P<0.01) in the positioning and quantified logadectomy group. SIT: there were 18 eyes turn to normal in simply logadectomy group while 25 eyes (chi2=4.022, P<0.05) in the positioning and quantified logadectomy group. Fl: there were 20 eyes turn to normal in simply logadectomy group while 28 eyes (chi2=6.667, P<0.05) in the positioning and quantified logadectomy group. The first fluorescein stain: there were 12 eyes turn to normal in simply logadectomy group while 24 eyes (chi2=10.000, P<0.01) in the positioning and quantified logadectomy group. The difference had statistic significance. On the 3rd month post-operation: SIT: there were 18 eyes turn to normal in simply logadectomy group while 19 eyes (chi2=0.071, P>0.05) in the positioning and quantified logadectomy group, without statistic significance. All the other objective evaluations indicatrix had statistic significance. On the 6th month post-operation: SIT: there were 20 eyes turn to normal in simply logadectomy group while 21 eyes (chi2=0.077, P>0.05) in the positioning and quantified logadectomy group, without statistic significance. Fl: there were 23 eyes turn to normal in simply logadectomy group while 28 eyes (chi2=3.268, P>0.05) in the positioning and quantified logadectomy group, without statistic significance. All the other objective evaluations indicatrix had statistic significance. CONCLUSIONS: Positioning and quantified patch resection method not only makes it easier and safer for treating the conjunctivochalasis, but also reduces the complications and creates good result for patients in early period.

[A new C-glycosylflavone from Peperomia dindygulensis].

OBJECTIVE: To study the chemical constituents of Peperomia dindygulensis. METHOD: Several column chromatographic methods were used to isolated compounds from P. dindygulensis and spectroscopic methods (1H-NMR, 13C-NMR, HMQC, HMBC, 1D- HOHAHA, NOE) were used to identify the structures of isolated compounds. RESULT: Compound 1 was isolated and identified as 2"-O-beta-D-galactosylisoswertisin. CONCLUSION: Compound 1 was a new compound.