Jul 2018, Volume 32 Issue 4

    
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  • Original Article
    Fei Chang, Na Li, Kang Yan, Yumin Huang, Hongfei Xu, Yongjian Liu
    Journal of Biomedical Research. 2018, 32 (4) : 245-256. https://doi.org/10.7555/JBR.32.20180044

    The membrane trafficking of cation-independent mannose 6-phosphate receptor (CI-M6PR) between the trans-Golgi network (TGN) and endosomal compartments is not only critical for maintaining lysosomal function but also a well-known event for understanding molecular and cellular mechanisms in retrograde endosome-to-TGN trafficking. Although it has been well established in literature that the C-terminus of bovine CI-M6PR determines its retrograde trafficking, it remains unclear whether the luminal domain of the protein plays a role on these sorting events. In this study, we found that partial deletion of luminal domain of human CI-M6PR mistargeted the mutant protein to non-TGN compartments. Moreover, replacing the luminal domain of both bovine and human CI-M6PR with that from irrelevant membrane proteins such as CD8 or Tac also altered the TGN targeting of the chimeric proteins. On the other hand, only short sequence from HA fused with the transmembrane domain and C-terminus of the receptor, HA-hCI-M6PR-tail, resulted in its preferential targeting to TGN as for the full length receptor, strongly suggesting that sorting of the receptor may be influenced by luminal sequence. Furthermore, using this luminal truncated form of HA-hCI-M6PR as a model cargo, we found that the trafficking of the chimeric protein was regulated by the retromer complex through interacting with SNX5. In conclusion, our study strongly suggested that the disrupted luminal domain from hCI-M6PR or other irrelevant membrane proteins interfere with the process of membrane trafficking and TGN targeting of CI-M6PR.

  • Original Article
    Sang-Yong Eom, Dong-Hyuk Yim, Dae-Hoon Kim, Hyo-Yung Yun, Young-Jin Song, Sei-Jin Youn, Taisun Hyun, Joo-Seung Park, Byung Sik Kim, Yong-Dae Kim, Heon Kim
    Journal of Biomedical Research. 2018, 32 (4) : 257-263. https://doi.org/10.7555/JBR.32.20170089

    There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations, but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway. The effects of vitamin D intake, vitamin D related genetic polymorphisms, and their association with the incidence of gastric cancer were investigated in a hospital case-control study, including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex. Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects. No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls, nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses. Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels, but not with the active form of the vitamin, 1,25-dihydroxyvitamin D. There were no statistically significant interactions between vitamin D intake, and VDR or TXNIP polymorphisms. This study suggests that dietary vitamin D intake is not associated with gastric cancer risk, and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.

  • Original Article
    Xiaoyan Qu, Lijuan Chen, Tian Tian, Limin Duan, Ruinan Lu, Hua Lu, Hanxin Wu, Jianyong Li
    Journal of Biomedical Research. 2018, 32 (4) : 264-269. https://doi.org/10.7555/JBR.31.20140090

    This study sought to analyze the clinical features and prognosis of multiple myeloma with isolated extramedullary relapse and with the absence of systemic progression. The clinical features and outcome were retrospectively analyzed in six multiple myeloma patients. These patients had secretory multiple myeloma at diagnosis. When relapsed, the dissociation between medullary and extramedullary response was detected. The serum or urine monoclonal component was extremely low or absent. The plasma cells in bone marrow were <5%. All patients received new targeted therapies (thalidomide or bortezomib) before extramedullary relapse. It is difficult to achieve second remission for them. Even in those showing response, the duration of response was extremely short. The median of overall survival from diagnosis and from extramedullary relapse was 19 months and 6 months, respectively. The overall survival was significantly shorter compared to the patients without extramedullary involvement (84 months, P= 0.001). These patients exhibited a special and rare relapse pattern. Patients with this relapse pattern were resistant to current therapies, including novel targeted agents and associated with poor prognosis.

  • Original Article
    Huanyu Ni, Yixuan Song, Haiyin Wu, Lei Chang, Chunxia Luo, Dongya Zhu
    Journal of Biomedical Research. 2018, 32 (4) : 270-280. https://doi.org/10.7555/JBR.32.20180014

    Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia. Inhibiting oxidative stress has been considered as an effective approach for stroke treatment. Edaravone, a free radical scavenger, has been shown to prevent cerebral ischemic injury. However, the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions (O2·). Here, we report that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine, a novel small-molecule compound structurally related to edaravone, showed a stronger inhibitory effect on oxidative stress in vitro. In vivo, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde, two proteins crucial for oxidative stress, suggesting a strengthened antioxidant system. Moreover, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability. Then, we found that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone. More importantly, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period, indicating enhanced neuroprotection, sensorimotor function and spatial memory. Together, these findings suggest that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.

  • Original Article
    Zhimin Zha, Junhong Wang, Shiling Li, Yan Guo
    Journal of Biomedical Research. 2018, 32 (4) : 281-287. https://doi.org/10.7555/JBR.31.20160116

    This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products (AGEs) in neonatal rat cardiomyocytes, and to examine the underlying mechanisms. Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs (100 mg/mL), receptor for advanced glycation end products (RAGE), antibody (1 mg/mL) and pitavastatin (600 ng/mL). The levels of p62 and beclin1 were determined by Western blotting. Mitochondrial membrane potential (DYm) and the generation of reactive oxygen species (ROS) were measured through the JC-1 and DCFH-DA. In the AGEs group, the expression of beclin1 was remarkably increased compared to the control group, while the expression of p62 was significantly decreased. AGEs also markedly decreased DYm and significantly increased ROS compared with the control group. After treatment with RAGE antibody or pitavastatin, the level of beclin1 was markedly decreased compared with the AGEs group, but the level of p62 was remarkably increased. In the AGEs+ RAGE antibody group and AGEs+ pitavastatin group, DYm was significantly increased and ROS was remarkably decreased compared with the AGEs group. In conclusion, AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.

  • Original Article
    Muyi Yang, Zhenyu Diao, Zhiyin Wang, Guijun Yan, Guangfeng Zhao, Mingming Zheng, Anyi Dai, Yimin Dai, Yali Hu
    Journal of Biomedical Research. 2018, 32 (4) : 288-297. https://doi.org/10.7555/JBR.32.20180039

    Preeclampsia is associated with over-activation of the innate immune system in the placenta, in which toll-like receptor 4 (TLR4) plays an essential part. With their potent anti-inflammatory effects, statins have been suggested as potential prevention or treatment of preeclampsia, although evidence remains inadequate. Herewith, we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide (LPS)-induced rat preeclampsia model, through targeting the TLR4/NF-kB pathway. The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day (GD) 12, (101.33±2.49) mmHg vs. (118.3±1.37) mmHg, P<0.05] and urine protein level [maximum decline on GD9, (3,726.23±1,572.86) mg vs. (1,991.03±609.37) mg, P<0.05], which were elevated following LPS administration. Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats (34.10% vs. 8.99%, P<0.05). Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment. These effects of pravastatin were associated with decreased TLR4/NF-kB protein levels in the placenta and IL-6/MCP-1 levels in serum. Additionally, no obvious abnormalities in fetal liver, brain, and kidney were found after administration of pravastatin. These results provide supportive evidence for use of pravastatin in preventing preeclampsia.

  • Original Article
    Kaixiang Yang, Shaohua Zhang, Dawei Ge, Tao Sui, Hongtao Chen, Xiaojian Cao
    Journal of Biomedical Research. 2018, 32 (4) : 298-304. https://doi.org/10.7555/JBR.32.20180012

    The study aimed to demonstrate the feasibility of an extradural nerve anastomosis technique for the restoration of a C5 and C6 avulsion of the brachial plexus. Nine fresh frozen human cadavers were used. The diameters, sizes, and locations of the extradural spinal nerve roots were observed. The lengths of the extradural spinal nerve roots and the distance between the neighboring nerve root outlets were measured and compared in the cervical segments. In the spinal canal, the ventral and dorsal roots were separated by the dura and arachnoid. The ventral and dorsal roots of C7 had sufficient lengths to anastomose those of C6. The ventral and dorsal of C4 had enough length to be transferred to those of C5, respectively. The feasibility of this extradural nerve anastomosis technique for restoring C5 and C6 avulsion of the brachial plexus in human cadavers was demonstrated in our anatomical study.

  • Original Article
    Chen Liang, Ling Yang, Shiwen Guo
    Journal of Biomedical Research. 2018, 32 (4) : 305-310. https://doi.org/10.7555/JBR.32.20170028

    The present study aimed to compare the complications and clinical outcomes of serial lumbar puncture (LP) and lumbar cerebrospinal fluid (CSF) drainage (LD) of patients with aneurysmal subarachnoid hemorrhage and provide more evidence to guide clinical management. In this retrospective study, 41 and 39 aneurysmal subarachnoid hemorrhage patients were enrolled in the LP and LD group, respectively. Clinical outcomes, including CSF infection, intracerebral hemorrhage, vasospasm, hydrocephalus, death, length of stay, duration of drainage and the Glasgow Outcome Scale score were compared between the two groups. By comparing with the LP group, the LD group showed a significantly higher rate of CSF infection (P=0.029) and shorter duration of drainage (P<0.001). Both groups displayed similar rates of vasospasm, hydrocephalus, intracerebral hemorrhage, the Glasgow Outcome Scale score one month after endovascular coiling and length of stay (P>0.05, respectively). In conclusion, both LD and serial LP are effective methods in the treatment of aneurysmal subarachnoid hemorrhage; besides, serial LP can reduce the incidence of CSF infection in draining hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling.

  • Case Report
    Nina Schloemerkemper
    Journal of Biomedical Research. 2018, 32 (4) : 311-313. https://doi.org/10.7555/JBR.32.20180023

    The use of “bath salts” or other new psychoactive substances, otherwise known as “legal highs”, is increasing. Illicit drug use during pregnancy is not uncommon. Nevertheless, literature reporting bath salts and their effect on pregnancy is scant. Besides, there seems to be no literature about bath salts and conduct of general anesthesia. This case report describes a general anesthetic for the surgical delivery of an infant to a woman under the acute influence of bath salts and methamphetamines.

  • Letter to the Editor
    Liang Chen, Zhongyin Zhou, Huihe Lu, Ye Xie, Gang Li, Jianfei Huang, Dongsheng Zhao
    Journal of Biomedical Research. 2018, 32 (4) : 314-316. https://doi.org/10.7555/JBR.32.20180003