条条大路通罗马？

一定转阴

dfyy8989

大家一起来追逐梦想吧

特深沉

原帖由 齐欢畅2 于 2010-4-7 17:31 发表

同疑问，好像是大公司，但又好像很缺钱，药效那么好，应该不会缺投资者？？疑问中。

未上市的公司，募集投资有严格规定。不能随便到市面上圈钱。投资者必须要有100万以上的资产或年收入20的收入证明。穷人想投钱都不允许。

lemonades

Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus
Marjoleine L Op den Brouw,1 Rekha S Binda,1 Mark H van Roosmalen,2 Ulrike Protzer,3 Harry L A Janssen,1 Renate G van der Molen,1*† and Andrea M Woltman1*
Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Myeloid dendritic cells (mDC) of patients with chronic HBV are impaired in their maturation and function, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. The mechanism responsible for altered mDC function remains unclear. The HBV-infected patients display large amounts of HBV particles and viral proteins in their circulation, especially the surface antigen HBsAg, which allows multiple interactions between the virus, its viral proteins and DC. To assess whether HBV directly influences mDC function, the effects of HBV and HBsAg on human mDC maturation and function were investigated in vitro. As already described for internalization of HBV by DC, the present study shows that peripheral blood-derived mDC of healthy controls also actively take up HBsAg in a time-dependent manner. Cytokine-induced maturation in the presence of HBV or HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated by a diminished up-regulation of costimulatory molecules and a decreased T-cell stimulatory capacity, as assessed by T-cell proliferation and interferon-γ production. In addition, the presence of HBV significantly reduced interleukin-12 production by mDC. These results show that both HBV particles and purified HBsAg have an immune modulatory capacity and may directly contribute to the dysfunction of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity.

lemonades

Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by interfering with the NFkappaB pathway in a human monocytic cell line, THP-1.
Cheng J, Imanishi H, Morisaki H, Liu W, Nakamura H, Morisaki T, Hada T.

Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663, Japan. [email protected]

Abstract
BACKGROUND/AIMS: Hepatitis B virus suppresses the human immune-system and HBsAg inhibits the induction of cytokines by LPS in human macrophages, but the mechanisms involved remain unclear. COX-2 and its product, PGE2, play a role in hepatitis B and IL-18 has also been shown to inhibit HBV infection in vivo. We investigated whether rHBsAg affects induction of COX-2 and IL-18 by LPS and, if so, which signal pathways are involved in a human monocytic cell line, THP-1. METHODS: Cell culture, Western blotting for COX-2, ERK and IKB-alpha, immunofluorescence for HBsAg and NFkappaB protein and ELISA for PGE2, IL-18 and IL-12 were performed. RESULTS: rHBsAg inhibits LPS-induced COX-2 expression in a time- and dose-dependent manner by blocking the ERK and NFkappaB pathways. LPS-induced IL-18 production was also down-regulated by rHBsAg by interfering mainly with the NFkappaB pathway. PGE2 reversed the inhibition of LPS-induced IL-18 production by rHBsAg. rHBsAg was also found to inhibit the induction of IL-12 by LPS in THP-1 cells. CONCLUSIONS: These results showed a novel anti-inflammatory property of rHBsAg which involves inhibition of COX-2 and suggested that hepatitis B virus may regulate IFN-gamma production by inhibiting IL-18 and IL-12 production.

lemonades

Hepatitis B virus surface antigen suppresses the activation of monocytes through interaction with a serum protein and a monocyte-specific receptor.
Vanlandschoot P, Van Houtte F, Roobrouck A, Farhoudi A, Leroux-Roels G.

Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. [email protected]

Abstract
During hepatitis B virus (HBV) infection, high numbers of non-infectious HBV surface antigen (HBsAg) particles are present in circulation. It is shown here that recombinant HBsAg (rHBsAg) particles, which contain the S protein only, bind almost exclusively to monocytes. Attachment of rHBsAg to the THP-1 pre-monocytic cell line occurs upon 1,25-dihydroxyvitamin D3-induced differentiation. Binding to monocytes is enhanced by a heat-labile serum protein and is inhibited by Ca(2+)/Mg(2+), low pH and an HBsAg-specific monoclonal antibody. Furthermore, it is shown that rHBsAg suppresses lipopolysaccharide- and IL-2-induced production of cytokines. These results suggest the existence of a monocyte-specific receptor, the engagement of which by HBsAg suppresses the activity of these cells.

lemonades

Hepatitis B virus suppresses toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells.
Wu J, Meng Z, Jiang M, Pei R, Trippler M, Broering R, Bucchi A, Sowa JP, Dittmer U, Yang D, Roggendorf M, Gerken G, Lu M, Schlaak JF.

Department of Gastroenterology and Hepatology, University Hospital of Essen, Essen, Germany.

Abstract
We have previously shown that Toll-like receptor (TLR)-activated murine nonparenchymal liver cells [(NPC); Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC)] can suppress hepatitis B virus (HBV) replication. Therefore, the aim of this study was to investigate whether HBV has the ability to counteract the TLR-mediated control of its replication. Freshly purified murine hepatocytes and NPCs obtained from C57BL6 mice were stimulated by TLR 1-9 ligands in the presence or absence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), HBV virions, or supernatants from HBV-producing HBV-Met cells, and HBV replication was suppressed by anti- hepatitis B virus X protein (HBx) small interfering RNA (siRNA) in HBV-Met cells. Supernatants were collected and tested for antiviral cytokines by viral protection assay. HBV gene expression and replication was analyzed by southern blot. RNA and proteins were analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) or western blot and enzyme-linked immunosorbent assay, respectively. Pretreatment of hepatocytes and NPCs with HBV-Met cells supernatants, HBsAg, HBeAg, or HBV virions almost completely abrogated TLR-induced antiviral activity, which correlated with suppression of interferon beta (IFN-beta) production and subsequent interferon-stimulated gene induction as well as suppressed activation of interferon regulatory factor 3 (IRF-3), nuclear factor kappa B (NF-kappaB), and extracellular signal-regulated kinase (ERK) 1/2. In HBV-infected HBV-Met cells, TLR stimulation did not induce antiviral cytokines in contrast to primary hepatocytes. TLR-stimulated expression of proinflammatory cytokines [tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6)], and activation of IRF-3 was suppressed after up-regulation of HBV replication in HBV-Met cells. Accordingly, suppression of HBV replication by siRNA led to activation or expression of proinflammatory transcription factors and cytokines. CONCLUSION: Our data indicate that HBV can suppress the TLR-induced antiviral activity of liver cells. This has major implications for the interaction between HBV and the immune system.

lemonades

J Viral Hepat. 2004 May;11(3):217-24.

Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection.
Zheng BJ, Zhou J, Qu D, Siu KL, Lam TW, Lo HY, Lee SS, Wen YM.

Department of Microbiology, The University of Hong Kong, Hong Kong.

Abstract
A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti-HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-alpha improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.

PMID: 15117323 [PubMed - indexed for MEDLINE]

肝胆相照009

楼上的资料大概意思就是乙肝病毒和乙肝抗原抑制人体免疫，但具体机制还不太明朗。 。 那有个疑问就是多少的病毒含量会压制人体免疫呢？

Interferon

我觉得这种药就算不能清除cccDNA，但至少能发展成为一种应付体检的zb药。
因为它能清除表面抗原，把表面抗原降到极低的水平，到时候战友们就再也不用怕体检了。
它清除血液内表面抗原的机理可能类似于联苯双酯对血清丙氨酸氨基转移酶的降解中和作用。