MiR-181d acts as a tumor suppressor in glioma by targeting K-ras and Bcl-2

Purpose

Recently, several microRNAs (miRNAs) were reported to be involved in the modulation of glioma development. The aim of our study was to determine the effect of miR-181d on the growth of glioma and to investigate whether this growth is modulated by targeting K-ras and Bcl-2.

Methods

Real-time PCR was used to analyze the expression of miR-181d in human glioma samples and glioma cell lines. Apoptosis, cell cycle, and proliferation (MTT) assays were performed to assess the phenotypic changes in glioma cells. Immunohistochemistry was used to determine the expression of K-ras and Bcl-2 in glioma tissues, and a luciferase reporter assay was carried out to confirm whether K-ras and Bcl-2 are direct targets of miR-181d. Western blotting was used to identify the potential signaling pathways affected glioma cell growth by miR-181d. In vivo, xenograft tumors were examined for an anti-glioma effect of miR-181d.

Results

MiR-181d was down-regulated in human glioma samples and up-regulated in transfected glioma cells. Ectopic expression of miR-181d suppressed proliferation and triggered cell cycle arrest and apoptosis in glioma cell lines. K-ras and Bcl-2 were identified as direct targets of miR-181d and were up-regulated in glioma samples. The results showed evidence linking the tumor suppressor activity of miR-181d in glioma cells with the K-ras-related PI3K/AKT and MAPK/ERK pathways. Furthermore, xenograft tumors from miR-181d-treated U251 cells were suppressed in vivo.

Conclusion

MiR-181d may act as a glioma suppressor by targeting K-ras and Bcl-2.     

S-1 combined with oxaliplatin as first line chemotherapy for chinese advanced gastric cancer patients

Background/Aims: To evaluate the efficacy and safety profile of S-1 combined with oxaliplatin (SOX) against unresectable advanced or metastatic gastric cancer. Methodology: Oxaliplatin was administered intravenously at 100mg/m2 for two hours on day 1 and S-1 was administered b.i.d. at 80mg/m2/day on days 1-14 followed by a 7-day rest during the 3-week schedule. Results: All 51 patients were assessed for efficacy and adverse events. The response and disease control rates were 41% and 90%, respectively. The response rate was significantly improved in patients with ECOG performance status of no more than 1, elevated CEA levels or unresected primary cancers. The median follow-up time was 11.8 months, the median time to progression was 6.8 months, the median overall survival was 11.8 months and the 1-year survival rate was 47.4%. Patients with diffused type exhibited significantly decreased time to progression and overall survival. The grade 3/4 adverse events were hematological toxicities, including neutropenia (13.7%), thrombocytopenia (13.7%) and anemia (11.8%). The incidence of grade 3/4 non-hematological events was low (≤2%). Conclusions: The SOX regimen (oxaliplatin, 100mg/m2 d1; S-1, 80mg/m2/day, b.i.d. d1-14, q3w) provided a favorable efficacy and safety profile in Chinese patients with advanced gastric cancer.     

Fak depletion in both hematopoietic and nonhematopoietic niche cells leads to hematopoietic stem cell expansion

Hematopoietic stem cells (HSCs) reside in complex bone marrow microenvironments, where niche-induced signals regulate hematopoiesis. Focal adhesion kinase (Fak) is a nonreceptor protein tyrosine kinase that plays an essential role in many cell types, where its activation controls adhesion, motility, and survival. Fak expression is relatively increased in HSCs compared to progenitors and mature blood cells. Therefore, we explored its role in HSC homeostasis. We have used the Mx1-Cre-inducible conditional knockout mouse model to investigate the effects of Fak deletion in bone marrow compartments. The total number as well as the fraction of cycling Lin(-)Sca-1(+)c-kit(+) (LSK) cells is increased in Fak(-/-) mice compared to controls, while hematopoietic progenitors and mature blood cells are unaffected. Bone marrow cells from Fak(-/-) mice exhibit enhanced, long-term (i.e., 20-week duration) engraftment in competitive transplantation assays. Intrinsic Fak function was assessed in serial transplantation assays, which showed that HSCs (Lin(-)Sca-1(+)c-kit(+)CD34(-)Flk-2(-) cells) sorted from Fak(-/-) mice have similar self-renewal and engraftment ability on a per-cell basis as wild-type HSCs. When Fak deletion is induced after engraftment of Fak(fl/fl)Mx1-Cre(+) bone marrow cells into wild-type recipient mice, the number of LSKs is unchanged. In conclusion, Fak inactivation does not intrinsically regulate HSC behavior and is not essential for steady-state hematopoiesis. However, widespread Fak inactivation in the hematopoietic system induces an increased and activated HSC pool size, potentially as a result of altered reciprocal interactions between HSCs and their microenvironment.     

Compound heterozygosity for Hb S [β6(A3)Glu→Val] and Hb Kenya (Aγ81Leu-β86Ala) in a Ugandan woman

Hb Kenya is a hemoglobin (Hb) tetramer composed of two normal α- and two non α-globin chains. The latter are the product of a fusion gene in which the 5' end is (A)γ and the 3' end is β. The crossover point is between codon 81 of the (A)γ gene and codon 86 of the β gene. Like the other non α genes, the hybrid protein product ((A)γ81Leu-β86Ala) has 146 amino acids. The purpose of this report is to highlight the laboratory findings of Hb Kenya and to emphasize the pitfalls in misdiagnosis, particularly when associated with another variant such as Hb S [β6(A3)Glu→Val].     

Prevalence and risk factors of depression in the elderly nursing home residents in Singapore

Objectives: Depression is a common health problem in elderly nursing home (NH) residents and is often under-recognized and under-treated. This study aimed to determine the prevalence rates of depression and identify the risk factors associated with depression in the elderly NH population in Singapore.

Methods: A sample of 375 residents in six NHs in Singapore, aged 55 years and above, was assessed with the Structural Clinical Interview (SCID), based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The association of demographic, functional and health-related characteristics with depression was examined using multivariate logistic regression analyses.

Results: Overall point prevalence for depression in the elderly NH residents was found to be 21.1% (95% confidence intervals (CI): 17.1%–25.6%). The prevalence rate for minor depression in the elderly NH residents was 14.4% (95% CI: 11.1%–18.5%) and 6.7% (95% CI: 4.5%–9.8%) for major depression. Significant risk factors that were found to be associated with depression were length of stay for more than 2 years, known history of depression, pain, and no or lack of social contact.

Conclusion: The prevalence rates for depression were high among NH residents in Singapore. More attention is needed to care for the psychosocial needs of elderly NH residents in Singapore.     

Receptor Trafficking and the Regulation of Synaptic Plasticity by SUMO

Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.     

瑞舒伐他汀与辛伐他汀治疗缺血性脑卒中的疗效比较

目的探讨瑞舒伐他汀与辛伐他汀治疗缺血性脑卒中的疗效。方法选取我院缺血性脑卒中患者90例,随机分为2组,观察组45例在基础治疗基础上加用瑞舒伐他汀,对照组45例在基础治疗基础上加用辛伐他汀,比较治疗前与治疗3个月后患者空腹静脉血中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及超敏C反应蛋白(hs-CRP)的变化。观察2组不良反应。结果治疗后2组TC、TG、LDL-C、hs-CRP水平均显著低于治疗前,HDL-C水平显著高于治疗前,且瑞舒伐他汀组变化幅度更大,差异均有统计学意义(P<0.05)。瑞舒伐他汀组与辛伐他汀组的缺血性脑卒中复发率分别为11.11%(5/45)和24.44%(11/45),2组比较差异有统计学意义(P<0.05)。观察组不良反应较轻微,与对照组相比,差异有统计学意义(P<0.05)。结论瑞舒伐他汀与辛伐他汀对于缺血性脑卒中患者均有很好的降脂及抗炎作用,且不良反应情况类似,但瑞舒伐他汀效果更为显著且复发率更低。     

多烯磷脂酰胆碱对癫患者认知功能的影响

目的观察多烯磷脂酰胆碱治疗癫患者认知功能的临床疗效。方法选取2011-02—2013-02我院收治的50例癫患者,按数字法随机分为观察组和对照组各25例。对照组给予卡马西平,观察组给予多烯磷脂酰胆碱,比较2组患者认知功能情况。结果观察组蒙特利尔认知评分及MMSE评分均显著优于对照组,差异有统计学意义(P<0.05)。结论应用多烯磷脂酰胆碱治疗癫,可促进患者认知功能的恢复。