Genetic analysis of the LRP10 gene in Chinese patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by resting tremor, bradykinesia, muscle rigidity, and abnormal gait. The low-density lipoprotein receptor-related protein 10 (LRP10) was recently shown to be a causal gene for PD, and different ethnic cohorts have distinct frequencies and spectrum of LRP10 variants. METHODS: We sequenced the full coding regions and exon-intron boundaries of LRP10 in 129 patients with sporadic Chinese PD to further investigate the connection of LRP10 with PD in a sample of Chinese patients. RESULTS: In this study, we identified four potentially pathogenic mutations, including one novel mutation of p.Gly328Asp and three known mutations of p.Cys165Tyr, p.Arg230Trp, and p.Arg661His in four of the 129 Chinese patients with PD. CONCLUSION: According to our study, the LRP10 gene may attribute to PD pathogenesis.

Anticancer effects and mechanisms of astragaloside­IV (Review).

Astragalus membranaceus Bunge is widely used in Traditional Chinese Medicine to treat various cancers. Astragaloside­IV (AS­IV) is one of the major compounds isolated from A. membranaceus Bunge and has been demonstrated to have antitumor effects by inhibiting cell proliferation, invasion and metastasis in various cancer types. Numerous studies have used in vitro cell culture and in vivo animal models of cancer to explore the antitumor activities of AS­IV. In the present study, the antitumor effects and mechanisms of AS­IV reported in studies recorded in the PubMed database were reviewed. First, the antitumor effects of AS­IV on proliferation, cell cycle, apoptosis, autophagy, invasion, migration, metastasis and epithelial­mesenchymal transition processes in cancer cells and the tumor microenvironment, including angiogenesis, tumor immunity and macrophage­related immune responses to cancer cells, were comprehensively discussed. Subsequently, the molecular mechanisms and related signaling pathways associated with antitumor effects of AS­IV as indicated by in vitro and in vivo studies were summarized, including the Wnt/AKT/GSK-3ß (glycogen synthase kinase­3ß)/ß­catenin, TGF­ß/PI3K/AKT/mTOR, PI3K/MAPK/mTOR, PI3K/AKT/NF­κB, Rac family small GTPase 1/RAS/MAPK/ERK, TNF­α/protein kinase C/ERK1/2­NF­κB and Tregs (T­regulatory cells)/IL­11/STAT3 signaling pathways. Of note, several novel mechanisms of Toll­like receptor 4 (TLR4)/NF­κB/STAT3, pSmad3C/3L, nuclear factor erythroid 2­related factor (NrF2)/heme oxygenase 1, circDLST/microRNA­489­3p/eukaryotic translation initiation factor 4A1 and macrophage­related high­mobility group box 1­TLR4 signaling pathways associated with the anticancer activity of AS­IV were also included. Finally, the limitations of current studies that must be addressed in future studies were pointed out to facilitate the establishment of AS­IV as a potent therapeutic drug in cancer treatment.

Establishment and characterization of human induced pluripotent stem cell line from a Parkinson's disease patient harboring VPS13A gene mutation.

Mutations in VPS13 gene have been recently reported as a genetic cause of Parkinson's disease (PD). In this study, we isolated the skin fibroblasts from a PD patient harboring VPS13A gene mutation (c. 4282_4289delinsA) and reprogrammed the fibroblasts to a novel patient-specific induced pluripotent stem cell (iPSC) line LCPHi002-A using transgene-free episomal plasmids to express OCT3/4, SOX2, KLF4, L-MYC, and LIN28. The LCPHi002-A line showed the normal karyotype, expression of pluripotency markers, and had multi-lineage differentiation capacity in vivo. This iPSC line of LCPHi002-A could be used for studying pathogenic mechanisms of PD.

miRNAs as potential therapeutic targets and diagnostic biomarkers for cardiovascular disease with a particular focus on WO2010091204.

INTRODUCTION: A number of miRNAs have been reported to be critically involved in the regulation of cardiovascular disease (CVDs). Therefore, the development of potent analogues/inhibitors for miRNAs have thus become a key focus in the present drug discovery. In this review, we discuss the basic research and clinical use of miRNAs as the early diagnosis and therapeutic targets for CVD. We have also focused on the efficiency of therapeutically targeting miR-499, which is considered as one of the most promising molecules for treating CVDs. Areas covered: In this review, we have discussed the patents and patent applications related to miRNAs detected in CVD patients published in recent years. This review also covers the expression pattern of miR-499, as well as it highlights functions of its inhibitors in CVD. We used Google and Pubmed search engines to find relevant patents. Expert opinion: Although a massive number of miRNAs are patented as CVD biomarkers, further work is absolutely required to evaluate the reliable diagnostic values and therapeutic potential of these candidates. Overall, targeting miRNAs is definitely a promising strategy to be investigated for diagnosis and treatment of CVDs in future, however, the delivery system and off-targets effects are still a difficult challenge need to be elucidated.

A FGFR1 inhibitor patent review: progress since 2010.

INTRODUCTION: FGFR1 is a well known molecular target for anticancer therapy. Many studies have proved that the regulation of FGFR1 activity is a promising therapeutic approach to treat a series of cancers. Therefore, the development of potent inhibitors has consequently become a key focus in the present drug discovery, and it is encouraging that several highly selective FGFR1 inhibitors have been identified from various sources in recent years. Areas covered: This article reviews patents and patent applications related to selective FGFR1 inhibitors published from 2010 to 2016. This summary highlights about 15 patents from different pharmaceutical companies and academic research groups. We used Baidu and NCBI search engines to find relevant patents as a search term. Expert opinion: In the past few years, considerable progress has been made in the identification and development of selective FGFR1 inhibitors in use. At present, at least 10 inhibitors of FGFR1 are in clinical trials, and several agents have shown encouraging results under experimental conditions. Given the fact that FGFR1 plays a crucial role in the regulation of cancer and other diseases, we hope that it will gain further attraction from pharmaceutical companies and encourage development of more novel, safe and efficient FGFR1 inhibitors in the future.

The Role of MicroRNA and LncRNA-MicroRNA Interactions in Regulating Ischemic Heart Disease.

Approximately 2% of the human genome consists of protein-coding regions. Therefore, the majority of transcripts are noncoding RNAs, such as microRNA (miRNA) and long noncoding RNAs (lncRNAs). In ischemic heart disease, the majority of miRNAs are repressors or destabilizers of target messenger RNAs. The lncRNAs are a second class of noncoding RNAs that have recently gained attention for their roles in heart disease and in regulating the functions of miRNA. In this review, we summarize the role of miRNA in pathological cardiac hypertrophy and myocardial infarction. In addition, we discuss the functional interactions of miRNA and lncRNA and its impact on these ischemic heart diseases.