The Lipid-Bound Apolipoprotein A-I Cysteine Mutant (N74C) Inhibits the Activation of NF-κB,JNK and p38 in Endotoxemic Mice and RAW264.7 Cells

Our previous studies showed that recombinant high-density lipoprotein (rHDL) rHDL74 exhibited higher anti-inflammatory capabilities compared to wild-type rHDL (rHDLwt), while rHDL228 showed hyper-proinflammation. In this paper, we further investigated the potential mechanisms involved in their different inflammatory functions using two models: endotoxemic mice and the RAW264.7 inflammation model. Our results showed that 24 h after the injection of lipopolysaccharide (LPS), mice treated with rHDL74 had a significant decrease in plasma CRP (P<0.01 vs. rHDLwt; P<0.01 vs. LPS), MCP-1 (P<0.05 vs. rHDLwt; P<0.01 vs. LPS) and CD14 (P<0.01 vs. LPS) compared with the mice treated with rHDLwt or the controls that received LPS only. Similar to our previous study, rHDL228 increased the plasma level of CRP (P<0.05 vs. LPS) and MCP-1 (P<0.01 vs. LPS). Our immunohistochemistry and western blot analysis showed that rHDL74 inhibited the activation of NF-κB in endotoxemic mice and JNK and p38 in the RAW264.7 inflammation model, while rHDL228 exacerbated the activation of NF-κB and ERK. In summary, our data suggest that rHDL74 exhibits higher anti-inflammatory activity by decreasing inflammatory factors and inhibiting the activation of NF-κB, JNK and p38, while rHDL228 appears to be hyper-proinflammation by increasing these inflammatory factors and aggravating the activation of NF-κB and ERK.     

Androgen deficiency and aging in men.

Androgen levels decrease with age in men. Androgen deficiency in men older than 65 years leads to asthenia, a decrease in muscle mass, osteoporosis, and a decrease in sexual activity. Androgen deficiency has been reported to cause changes in mood and cognitive function. The combination of these factors results in impaired quality of life in older men. Androgen replacement therapy in hypogonadal men increases bone and muscle mass, enhances muscle and cardiovascular function, and improves sexual function and general well-being; whether elderly men experience benefits of androgen replacement is not known. These benefits have to be weighed against the possible adverse effects of prostate and cardiovascular diseases. Careful long-term studies are needed to assess the risk-to-reward ratios of androgen or other hormone replacement therapy before treatment strategies similar to estrogen therapy for postmenopausal women are implemented.     

Hydrogel design for supporting neurite outgrowth and promoting gene delivery to maximize neurite extension

Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration.     

Polymorphism attribution of cSNPs in cancer-related genes located in loss regions with a high frequency of HCC between HBV and health groups

Cancer-related genes harbored in the loss regions containing a high frequency of hepatocellular carcinoma (HCC) were selected.Related information was gathered and the coding single nucleotide polymorphism (cSNP) sequences were obtained from the single nucleotide polymorphism (SNP) database.The appropriate primers and oligonucleotide probes were then designed in accordance with the SNP sites,and subsequently,the gene chips for detecting SNPs were constructed.Genomic DNA was extracted from blood samples of healthy controls and from patients with HBV infection.The sequences,including the SNPs,were amplified via polymerase chain reaction (PCR) and labeled using digoxigenin deoxyuridine tri-phosphate (Dig-dUTP).The labeled products were then hybridized with the SNP chips.Results confirmed that the differences in allele frequencies of three SNPs EGFL3 (rs947345),Caspase9 (rs2308950),and E2F2 (rs3218171) were distinct between HBV-infected patients and controls,suggesting that these SNPs ocuring in high frequency in HBV-infected individuals may be associated with susceptibility to HCC.     

MicroRNA 155 Control of p53 Activity Is Context Dependent and Mediated by Aicda and Socs1

In biological processes, the balance between positive and negative inputs is critical for an effective physiological response and to prevent disease. A case in point is the germinal center (GC) reaction, wherein high mutational and proliferation rates are accompanied by an obligatory suppression of the DNA repair machinery. Understandably, when the GC reaction goes awry, loss of immune cells or lymphoid cancer ensues. Here, we detail the functional interactions that make microRNA 155 (miR-155) a key part of this process. Upon antigen exposure, miR-155^−/− mature B cells displayed significantly higher double-strand DNA break (DSB) accumulation and p53 activation than their miR-155^+/+ counterparts. Using B cell-specific knockdown strategies, we confirmed the role of the miR-155 target Aicda (activation-induced cytidine deaminase) in this process and, in combination with a gain-of-function model, unveiled a previously unappreciated role for Socs1 in directly modulating p53 activity and the DNA damage response in B lymphocytes. Thus, miR-155 controls the outcome of the GC reaction by modulating its initiation (Aicda) and termination (Socs1/p53 response), suggesting a mechanism to explain the quantitative defect in germinal center B cells found in mice lacking or overexpressing this miRNA.     

中药博落回的药理实验研究

博落回对四氯化碳、半乳糖胺所致急性肝损伤模型,均有显著改善肝脏功能作用;对四氯化碳所致慢性肝损伤大鼠模型,博落回可显著降低血清LDH水平。降低动物死亡率。提高血清A/G比值,有效保护肝细胞胰。抑制肝脏纤维化;博落回还可显著增强T和B淋巴细胞功能。