中药抗乙肝病毒活性及作用机制的研究进展

乙肝病毒是一种能导致机体产生急性或慢性乙型肝炎（乙肝）的嗜肝性DNA病毒。乙肝现已成为全球性公共卫生疾病，易恶化发展为肝硬化、肝衰竭，甚至肝癌，严重威胁着人类的健康。中药及其活性成分发挥着重要的抗乙肝病毒活性，对中药抗乙肝病毒活性及其作用机制进行综述，以期为今后抗乙肝病毒研究提供一定的参考。     

Imaging biomarkers for Alzheimer’s disease and glaucoma: Current and future practices

Glaucoma is a leading cause of blindness worldwide. Although intraocular pressure is the main risk factor for glaucoma, several intraocular pressure independent factors have been associated with the risk of developing the disease and its progression. The diagnosis of glaucoma relies on clinical features of the optic nerve, visual field test, and optical coherence tomography. However, the multidisciplinary aspect of the disease suggests that other biomarkers may be useful for the diagnosis, thus underling the importance of novel imaging techniques supporting clinicians.This review analyzes the common pathogenic mechanisms between glaucoma and Alzheimer’s disease and the possible novel approaches for diagnosis and follow up.     

The Mechanisms of Pei‑yuan‑Tong‑nao Capsule as a Therapeutic Agent against Cerebrovascular Disease

Objective: Pei?Yuan?Tong?Nao (PYTN) capsule has been widely used for the treatment of cerebrovascular disease (CVD), including cerebral ischemia. However, due to the complexity of traditional Chinese Medicine (TCM) and the lack of proper inspection methods, the pharmacological mechanisms of the actions of PYTN capsule on CVD remain ambiguous. In this investigation, a network pharmacology method was used to investigate the mechanism of action of PYTN capsule in the treatment of CVD. Methods: In this method, a chemical similarity ensemble approach was employed to predict putative targets for chemicals derived from PYTN capsule. Results: Thus, a total of 351 compounds and 650 proteins were identified as potential active ingredients and putative CVD?related targets. In addition, two interaction networks were constructed, including a network between putative targets of PYTN capsule and known CVD?related targets, and a network between candidate active compounds and putative CVD?related targets. Conclusion: The mechanism of PYTN capsule in the treatment of CVD was found to be based on three functional modules, namely, antioxidation, anti?inflammation, and antiapoptosis modules through multiple signaling pathways, such as PI3K?Akt, mitogen?activated protein kinase, and TNF signaling pathways. We hope that this work can provide insight into the pharmacological mechanisms of TCMs in the treatment of CVD and provide a basis for further development and the discovery of more effective clinical strategies for the treatment of complicated diseases.     

Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region

The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population’s currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry of individuals from Oceanian populations. The sensitivity of Pacifiplex enabled successful genotyping of population samples from 50-year-old serum samples obtained from several Oceanian regions that would otherwise be unlikely to produce useful population data. This indicates tests primarily developed for forensic ancestry analysis also provide an important contribution to studies of populations where useful samples are in limited supply.     

(−)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis,oxidative stress and inflammatory response in human gastric epithelial cells

(−)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0 μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0 U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions.     

Discovering novel lung cancer associated antigens and the utilization of their autoantibodies in detection of lung cancer

ObjectiveThe identification of tumor-associated antigens (TAAs) and their corresponding autoantibodies in lung cancer (LC) may expand our vision of cancer immunity. This study aims to screen novel TAAs to distinguish LC from the healthy population.MethodsIn our previous study, 35 genes encoding LC-associated TAAs were identified from the serological analysis of recombinant cDNA expression libraries (SEREX), and Oncomine database was further used to identify potential genes in cancer progression. Autoantibody to TAAs were tested by enzyme-linked immunosorbent assay (ELISA) in sera from 1379 participants in validation set and verification set.FindingsBased on analysis of three independent microarrays in Oncomine, ten genes were consistently dysregulated in LC. The sera level and positive frequency of the anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 from LC patients were higher than normal control in validation set. The area under curve (AUC) of anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 was respectively 0.758, 0.787, 0.707, 0.668. The sensitivity of these four autoantibodies for LC detection ranged from 26.63 % to 32.07 % with the specificity over 90 %. Data from the verification set confirmed the results. Except that, the frequency of serum autoantibody against TOP2A (43.3 %) and ACTR3 (50.0 %) was significantly higher in early stage LC than late stage (23.6 % and 22.3 %, respectively).ConclusionTOP2A, ACTR3, RPS6KA5 and PSIP1 can elicit humoral immune response in LC and their autoantibodies have relationship with the tumorigenesis of LC. Anti-TOP2A and anti-ACTR3 have the potential to serve as a serological biomarkers in early stage LC.     

Schwann cell-derived CXCL1 contributes to human immunodeficiency virus type 1 gp120-induced neuropathic pain by modulating macrophage infiltration in mice

The neuroinflammatory responses to human immunodeficiency virus type 1 (HIV-1) coat proteins, such as glycoprotein 120 (gp120), are considered to be responsible for the HIV-associated distal sensory neuropathy. Accumulating evidences suggest that T-cell line tropic X4 gp120 increases macrophage infiltration into the peripheral nerves, and thereby induces neuroinflammation leading to pain. However, the mechanisms underlying X4 gp120-induced macrophage recruitment to the peripheral nervous systems remain unclear. Here, we demonstrated that perineural application of X4 gp120 from HIV-1 strains IIIB and MN elicited mechanical hypersensitivity and spontaneous pain-like behaviors in mice. Furthermore, flow cytometry and immunohistochemical studies revealed increased infiltration of bone marrow-derived macrophages into the parenchyma of sciatic nerves and dorsal root ganglia (DRG) 7 days after gp120 IIIB or MN application. Chemical deletion of circulating macrophages using clodronate liposomes markedly suppressed gp120 IIIB-induced pain-like behaviors. In in vitro cell infiltration analysis, RAW 264.7 cell (a murine macrophage cell line) was chemoattracted to conditioned medium from gp120 IIIB- or MN-treated cultured Schwann cells, but not to conditioned medium from these gp120-treated DRG neurons, suggesting possible involvement of Schwann cell-derived soluble factors in macrophage infiltration. We identified using a gene expression array that CXCL1, a chemoattractant of macrophages and neutrophils, was increased in gp120 IIIB-treated cultured Schwann cells. Similar to gp120 IIIB or MN, perineural application of recombinant CXCL1 elicited pain-like behaviors accompanied by macrophage infiltration to the peripheral nerves. Furthermore, the repeated injection of CXCR2 (receptor for CXCL1) antagonist or CXCL1 neutralizing antibody prevented both pain-like behaviors and macrophage infiltration in gp120 IIIB-treated mice. Thus, the present study newly defines that Schwann cell-derived CXCL1, secreted in response to X4 gp120 exposure, is responsible for macrophage infiltration into peripheral nerves, and is thereby associated with pain-like behaviors in mice. We propose herein that communication between Schwann cells and macrophages may play a prominent role in the induction of X4 HIV-1-associated pain.     

闽台两地“药缘”历史探析

闽台两地独特的地缘优势使得闽台中药文化交流频繁,在历史的演化、变迁过程中不断交融、发展,形成了闽台两地密切的“药缘”关系。本研究从闽台两地中药材贸易交流、“药签”的传播、人口迁徙带动中药交流与发展、具有药用价值作物的引种栽培,以及中药知识本土化融合发展几个方面,浅析闽台两地深厚的“药缘”历史,探究闽台中药文化渊源及其发展的推动力,为拓展与延伸闽台中药的交流合作提供借鉴与启示。