Alzheimer's disease (AD) is a devastating neurodegenerative disease with progressive loss of memory and cognitive function, pathologically hallmarked by aggregates of the amyloid-beta (Aβ) peptide and hyperphosphorylated tau in the brain. Aggregation of Aβunder the form of amyloid fibrils has long been considered central to the pathogenesis of AD. However, recent evidence has indicated that soluble Aβ oligomers, rather than insoluble fibrils, are the main neurotoxic species in AD. The cellular prion protein (PrP^C) has newly been identified as a cell surface receptor for Aβ oligomers. PrP^C is a cell surface glycoprotein that plays a key role in the propagation of prions, proteinaceous infectious agents that replicate by imposing their abnormal conformation to PrP^C molecules. In AD, PrP^C acts to transduce the neurotoxic signals arising from Aβ oligomers, leading to synaptic failure and cognitive impairment. Interestingly, accumulating evidence has also shown that aggregated Aβ or tau possesses prion-like activity, a property that would allow them to spread throughout the brain. In this article, we review recent findings regarding the function of PrP^C and its role in AD, and discuss potential therapeutic implications of PrP^C-based approaches in the treatment of AD.

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Achondroplasia is a rare autosomal dominant genetic disease. Research on achondroplasia in China, however, has received little emphasis. Around 80-90% of cases of neonatal achondroplasia result from mutations in fibroblast growth factor receptor 3 (FGFR3) according to polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Recently, genetic research on achondroplasia in China made a major breakthrough by revealing two novel mutations located on the FGFR3 gene, thus helping to complete the pathological molecular map of achondroplasia. There are still, however, unknown aspects of the diagnosis and treatment of achondroplasia. This review will summarize advances in research on and the clinical diagnosis and treatment of achondroplasia in China.

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Melorheostosis is an uncommon, non-genetic, non-developmental, sclerosing dysplasia of bone and adjacent soft tissues, with deformity of the extremity, pain, limb stiffness and limitation of motion. The characteristic radiographic appearance consists of irregular hyperostotic changes of the cortex resembling melted wax dripping down the side of a candle. In this review, clinical characteristics of Melorheostosis are discussed and reports in the Chinese literature are summarized.

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Microvascular damage is one of the primary pathologic components of systemic sclerosis (SSc). Serological abnormalities of angiogenic and angiostatic factors in SSc have previously been described. Like these factors, the plasma levels of leptin were significantly elevated in patients with SSc in comparison to normal controls. However, leptin receptor has not been examined in patients with SSc. The current study used sandwich ELISA to evaluate the serum levels of leptin receptor in patients with SSc. Serum samples were obtained from 36 patients with SSc. Samples were also obtained from 12 healthy control subjects and 10 patients with scleroderma spectrum disorder (SSD) who did not fulfill the criteria for SSc but who had the potential to develop SSc. Mean serum leptin receptor levels were significantly higher in patients with SSD than in patients with SSc (255.7 ng/mL vs. 184.6 ng/mL, p < 0.05 according to a Mann-Whitney test). There were no statistically significant differences between healthy control subjects and patients with SSc. Clinical parameters were evaluated, and the frequency of esophageal reflux was significantly lower in patients with elevated serum leptin receptor levels than in those with reduced levels (6.3% vs. 35.3%, p < 0.05). In summary, these results suggest that the serum levels of leptin receptor are a clinically useful marker of SSD, and measurement of serum leptin receptor over time in patients with SSD may lead to early detection of SSc.

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Matrix vesicles (MVs) play an important role in the initial stage of the process of bone mineralization, and are involved in multiple rare skeletal diseases with pathological mineralization or calcification. The aim of the study was to compare the proteomic profiling of osteoblast-like cells with and without mineralization ability (Saos-2 and U2-OS), and to identify novel mineralization-associated MV proteins. MVs were extracted using ExoQuick solution from mineralization-induced Saos-2 and U2-OS cells, and then were validated by transmission electron microscopy. A label-free quantitative proteomic method was used to compare the protein profiling of MVs from Saos-2 and U2-OS cells. Western-blots were used to confirm the expression of MVs proteins identified in proteomic studies. In our proteomic studies, we identified that 89 mineralization-related proteins were significantly up-regulated in Saos-2 MVs compared with U2-OS MVs. We further validated that two MVs proteins, protein kinase C α and ras-related protein Ral-A, were up-regulated in MVs of Saos-2 cells compared to those of U2-OS cells under mineralization-induction. Our findings suggest that protein kinase C α and ras-related protein Ral-A might be involved in bone mineralization as MVs components.

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Biliary cystic tumors are rare hepatic neoplasms, and knowledge regarding the origin and pathology of these tumors remains vague. They should be analyzed in more detail. In our institution, 4 biliary cystic tumor surgeries were performed between December 1999 and March 2010. Pathological evaluation of resected specimens was performed to evaluate the characteristics of the intracystic epithelium and to determine the presence or absence of interstitial infiltrate, ovarian mesenchymal stroma (OMS), luminal communication between the cystic tumor and the bile duct, and mucin (MUC) protein expression. We evaluated the following 4 cases: case 1, a 21-year-old woman with a biliary cystadenoma who underwent extended right hepatectomy; case 2, a 39-year-old woman with a biliary cystadenoma who underwent left hepatectomy; case 3, an 80-year-old man with a biliary cystadenoma who underwent left hepatectomy; and case 4, a 61-year-old man with a biliary cystadenocarcinoma revealing papillary proliferation of atypical epithelium and interstitial infiltrates who underwent left hepatectomy. Case 3 had papillary proliferation of the intracystic atypical epithelium but showed interstitial infiltrates. Luminal communication with the bile duct, centrally or peripherally, was found in all 4 cases. Only case 2 showed OMS. Immunohistochemical staining revealed the following findings: cases 1 and 2, MUC1-/MUC2-; case 3, MUC1+/MUC2-; and case 4, MUC1+/MUC2+. It is important to gather information on more cases of biliary cystic tumors because atypical cases were observed, where both OMS and luminal communication with the bile duct were present or absent.

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The features of intractable diseases make it an important public health issue and a challenge to medical care worldwide. Investigation of intractable diseases with the support of government is urgently expected to activate clinical and pharmaceutical research to promote diagnosis and treatment for patients with intractable diseases. Moreover, linkage to the international database for research achievement is also necessary so that both researchers and other general citizens can assess research trends in the field of intractable diseases. In Japan, supportive activities for patients and researchers of intractable diseases have been well developed with the support of the Ministry of Health, Labor and Welfare (MHLW). Furthermore, in April 2013, a specific academic communication platform on intractable diseases – the Intractable and Rare Diseases Research (IRDR) Journal – was approved to join a governmental project and receive support from the Japan Society for the Promotion of Science (JSPS) under the auspices of Ministry of Education, Culture, Sports, Science and Technology (MEXT). Cooperation with the Japanese government starting this year is hoped to promote information-sharing based on an academic communication platform and further activate research on intractable diseases.

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