Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin-α3γ2, integrin-α6β4, CD151, collagen α-1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642-phosphorylation at the basement membrane, and deposits of laminin-α3 and laminin-γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease.     

甲胎蛋白和GGT-Ⅱ联合检测在肝癌患者诊断中的意义

目的：探讨两种肝癌标志物甲胎蛋白（α-fetoprotein,AFP）和γ-谷氨酰转移酶同工酶Ⅱ（γ-glutamyltransferase isoenzymeII,GGT-Ⅱ）单独检测和联合检测原发性肝癌（primaryhepatocellularcar cinoma,PHC）的早期诊断价值。方法：GGT-Ⅱ检测采用聚丙烯酰胺凝胶电泳法,AFP检测采用电化学发光免疫分析法。分别对33例乙型肝炎患者,30例肝炎后肝硬化患者,44例原发性肝癌患者以及35名健康体检者进行GGT-Ⅱ和AFP检测,综合分析2项指标对PHC的诊断价值。结果：PHC组的GGT-Ⅱ和AFP的阳性率均明显高于肝硬化组、肝炎组和健康对照,差异有统计学意义（P〈O．01）,联合检测敏感性高于单一检测指标。结论：血清GGT-Ⅱ及AFP联合检测可提高PHC的诊断灵敏度,提高肝癌的早期检出率。     

Recent advances in the etiology and treatment of inflammatory bowel disease

Crohn’s disease and ulcerative colitis, together comprising the inflammatory bowel diseases, currently affect up to 2 million people in the western developed countries. The pathogenesis of the disease is a complex one in which genetic, immunogenic, microbial and environmental factors contribute to the etiology of the disease. Recent advances in understanding the molecular mechanisms that determine this complex entity have provided insight for promising new therapies.     

Interleukin-15 in the treatment of cancer

IL-15 is a 14–15 kDa member of the four α-helix bundle of cytokines that acts through a heterotrimeric receptor involving IL-2/IL-15R β, γc and the IL-15 specific receptor subunit IL-15R α. IL-15 stimulates the proliferation of T, B and NK cells, and induces stem, central and effector memory CD8 T cells. In rhesus macaques, continuous infusion of recombinant human IL-15 at 20 μg/kg/day was associated with approximately a 10-fold increase in the numbers of circulating NK, γ/δ cells and monocytes, and an 80- to 100-fold increase in the numbers of effector memory CD8 T cells. IL-15 has shown efficacy in murine models of malignancy. Clinical trials involving recombinant human IL-15 given by bolus infusions have been completed and by subcutaneous and continuous intravenous infusions are underway in patients with metastatic malignancy. Furthermore, clinical trials are being initiated that employ the combination of IL-15 with IL-15R α^+/- IgFc.     

Type 1 reaction in leprosy: a model for a better understanding of tissue immunity under an immunopathological condition

Type 1 reaction (T1R) or reversal reaction is the leading cause of physical disabilities and deformities in leprosy. Leprosy patients, even after being considered cured and released from treatment, may suffer from reactional episodes for long periods of time. Early diagnosis is a great challenge for effectively treating and managing T1R. There is an urgent need to identify the most significant biomarkers to prevent recurrent T1R and to differentiate late T1R from relapse. T1R continues to be treated with corticosteroids and complications due to iatrogenic treatment remain frequent. This review aims to provide a framework from which to approach the great challenges that still persist in T1R management and debate key issues in order to reduce the distance between basic research and the clinic.     

Bacteriomimetic poly-γ-glutamic acid surface coating for hemocompatibility and safety of nanomaterials

Poly-γ-glutamic acid (PGA), a major component of the bacterial capsule, is known to confer hydrophilicity to bacterial surfaces and protect bacteria from interactions with blood cells. We tested whether applying a bacteriomimetic surface coating of PGA modulates interactions of nanomaterials with blood cells or affects their safety and photothermal antitumor efficacy. Amphiphilic PGA (APGA), prepared by grafting phenylalanine residues to PGA, was used to anchor PGA to reduced graphene oxide (rGO) nanosheets, a model of hydrophobic nanomaterials. Surface coating of rGO with bacterial capsule-like APGA yielded APGA-tethered rGO nanosheets (ArGO). ArGO nanosheets remained stable in serum over 4?weeks, whereas rGO in plain form precipitated in serum within 5?minutes. Moreover, ArGO did not interact with blood cells, whereas rGO in plain form or as a physical mixture with PGA formed aggregates with blood cells. Mice administered ArGO at a dose of 50?mg/kg showed 100% survival and no hepatic or renal toxicity. No mice survived exposure at the same dose of rGO or a PGA/rGO mixture. Following intravenous administration, ArGO showed a greater distribution to tumors and prolonged tumor retention compared with other nanosheet formulations. Irradiation with near-infrared light completely ablated tumors in mice treated with ArGO. Our results indicate that a bacteriomimetic surface modification of nanomaterials with bacterial capsule-like APGA improves the stability in blood, biocompatibility, tumor distribution, and photothermal antitumor efficacy of rGO. Although APGA was used here to coat the surfaces of rGO, it could be applicable to coat surfaces of other hydrophobic nanomaterials.