The potential therapeutic application of oligonucleotides (ONs) that selectively suppress target genes through antisense and RNA interference mechanisms has attracted great attention. The clinical applications of ONs have overcome multiple obstacles and become one of the most active areas for the development of novel therapeutics. To achieve efficient and specific cellular internalization, conjugation of a variety of functional groups to ONs has been the subject of intensive investigations over the past decade. Among them, a promising liver-targeted N -acetylgalactosamine (GalNAc) ligand has been evaluated in multiple preclinical and clinical trials for improving the cellular uptake and tissue specific delivery of ONs. GalNAc-based delivery relies on the fact that liver hepatocytes abundantly and specifically express the asialoglycoprotein receptor that binds and uptakes circulating glycoproteins via receptor-mediated endocytosis. In recent years, encouraging progress has been made in the field of GalNAc conjugates. This review aims to provide an overview of GalNAc-mediated liver-targeted delivery of small interfering RNA and antisense oligonucleotides, and the immense effort as well as recent advances in the development of GalNAc-conjugated agents are described.

Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has been shown to play a role in cancer development and progression. However, the detailed role of HPIP in cancer cell growth and the exact mechanism by which HPIP regulates cancer cell proliferation remains unclear. Here, we report that HPIP is overexpressed in most of 328 liver cancer patients and regulates hepatoma cell proliferation through G2=M checkpoint activation. HPIP increased anchorage-dependent and -independent growth of human liver cancer cell lines. The amino acid region 531-631 of HPIP was important for its modulation of liver cancer cell growth. The increased effects of HPIP on liver cancer cell proliferation were associated with activation of the G2=M cell-cycle concomitant with a marked increase of cyclin B1 and the inhibition of the negative G2=M phase regulator GADD45a. HPIP knockdown dramatically suppressed the growth of HepG2 liver cancer cells in nude mice. These data highlight the important role of HPIP in liver cancer cell growth and suggest that HPIP may be a good target for liver cancer therapy. V C 2013 IUBMB Life, 65(10): [873][874][875][876][877][878][879][880][881][882] 2013

Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAHinduced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca 2? overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.

Purpose The present study examined the risk factors of psychological disorders after COVID-19 outbreak and tested the possible mediating role of social support and emotional intelligence on the relationship between COVID-19 pandemic exposure and psychological disorders. Methods We conducted an online survey from May 25, 2020 until June 10, 2020 among Chinese university students who had been quarantined at home due to the COVID-19 pandemic. Social support was assessed using the Social Support Rating Scale. Self-perceived emotional competency was measured using a Chinese version of the self-report Wong Law Emotional Intelligence Scale. The 10-item Kessler Psychological Distress Scale was used to assess nonspecific symptoms of psychological disorders. Results A total of 6,027 college students participated in the survey, of whom 2,732 (45.3%) reported mental health issues. Men and people in a relationship showed higher frequencies of psychological disorders. Social support and emotional intelligence were both negatively associated with psychological disorders. Stepwise linear regression revealed that the most important predictors of psychological disorders were self-emotion appraisal, family relationships, and showing panic about COVID-19 on the social media. Path analysis suggested that the association between pandemic exposure and psychological disorders was partially mediated by emotional intelligence, but not by social support. Conclusions Emotional intelligence may mediate the relationship between COVID-19 pandemic exposure and psychological disorders. Psychological interventions fostering emotional intelligence and social support should be implemented among university students to reduce the psychological harm caused by the COVID-19 pandemic