Caveolin-1 and glucose transporter 4 involved in the regulation of glucose-deprivation stress in PC12 cells.

Recent evidence suggests that caveolin-1 (Cav-1), the major protein constituent of caveolae, plays a prominent role in neuronal nutritional availability with cellular fate regulation besides in several cellular processes such as cholesterol homeostasis, regulation of signal transduction, integrin signaling and cell growth. Here, we aimed to investigate the function of Cav-1 and glucose transporter 4 (GLUT4) upon glucose deprivation (GD) in PC12 cells. The results demonstrated firstly that both Cav-1 and GLUT4 were up-regulated by glucose withdrawal in PC12 cells by using Western blot and laser confocal technology. Also, we found that the cell death rate, mitochondrial membrane potential (MMP) and intracellular free Ca(2+) concentration ([Ca(2+)]i) were also respectively changed followed the GD stress tested by CCK8 and flow cytometry. After knocking down of Cav-1 in the cells by siRNA, the level of [Ca(2+)]i was increased, and MMP was reduced further in GD-treated PC12 cells. Knockdown of Cav-1 or methylated-ß-Cyclodextrin (M-ß-CD) treatment inhibited the expression of GLUT4 protein upon GD. Additionally, we found that GLUT4 could translocate from cytoplasm to cell membrane upon GD. These findings might suggest a neuroprotective role for Cav-1, through coordination of GLUT4 in GD.

Angioimmunoblastic T-cell lymphoma induced hemophagocytic lymphohistiocytosis and disseminated intravascular coagulopathy: A case report.

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma, with heterogenous clinical manifestations and poor prognosis. Here, we report a case of AITL induced hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulopathy (DIC). CASE SUMMARY: An 83-year-old man presented with fever and purpura of both lower limbs for one month. Groin lymph node puncture and flow cytometry indicated a diagnosis of AITL. Bone marrow examination and other laboratory related indexes indicated DIC and HLH. The patient rapidly succumbed to gastrointestinal bleeding and septic shock. CONCLUSION: This is the first reported case of AITL induced HLH and DIC. AITL is more aggressive in older adults. In addition to male gender, mediastinal lymphadenopathy, anaemia, and sustained high level of neutrophil-to-lymphocyte ratio may indicate a greater risk of death. Early diagnosis, early detection of severe complications, and prompt and effective treatment are vital.

Clinical significance of long noncoding RNA maternally expressed gene 3 in acute promyelocytic leukemia.

INTRODUCTION: Long noncoding RNA maternally expressed gene 3 (MEG3) expression was significantly decreased in acute myeloid leukemia (AML). However, its expression and clinical significance in acute promyelocytic leukemia (APL) remain unclear. Thus, the present study aimed to investigate the expression of MEG3 in APL and explore its clinical value. METHODS: A total of 287 AML patients derived from The Cancer Genome Atlas (TCGA) and Vizome database were enrolled. A development and validation cohort, including APL, AML with AML1/ETO, and other types of AML patients and disease controls, from the First Affiliated Hospital of Nanchang University, were also enrolled in this study. The correlation between MEG3 expression and the clinicopathological features in APL was investigated. The diagnostic values of MEG3 expression in APL were analyzed by receiver operating characteristic (ROC) curves. RESULT: In the development set, MEG3 expression was significantly increased in APL than AML with AML1/ETO, other types of AML, and disease controls, which was consistent with the results from the database analysis. MEG3 expression in APL was associated with age (P = .0053) but did not correlate with other clinicopathological features (P > .05). ROC curve analysis in the development set and diagnostic test analysis in the validation set suggested that MEG3 expression has a significant value in the diagnosis of APL. Furthermore, the expression of MEG3 decreased during the follow-up of patients with negative PML/RARα fusion gene. CONCLUSION: MEG3 serves as a novel marker for the diagnosis of APL, evaluates the curative effect, and provides a novel direction for further research.

Overexpression of IFIT2 inhibits the proliferation of chronic myeloid leukemia cells by regulating the BCR­ABL/AKT/mTOR pathway.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for ~10% of all newly diagnosed leukemia cases. Early diagnosis is essential for long­term beneficial outcomes. The present study observed that interferon­induced protein with tetratricopeptde repeats 2 (IFIT2) expression levels were reduced in bone marrow samples from CML patients compared with control samples using RNA sequencing and reverse transcription­PCR. IFIT2 expression levels were restored in patients treated with tyrosine kinase inhibitors. To investigate the effect of IFIT2 on CML patients, a stable IFIT2 expressing K562 cell line was established. It was demonstrated that IFIT2 overexpression in K562 cells inhibits cell proliferation and arrests the cell cycle at the G1 phase. In addition, it was demonstrated by western blotting that IFIT2 inhibits the BCR­ABL oncoprotein and regulates its downstream AKT/mTOR signaling pathway. IFIT2 could induce cell cycle arrest­associated gene p27kip1 by degrading cullin1­mediated E3 ligases. In summary, the present study demonstrated that IFIT2 was efficacious in inhibiting CML and is a potential therapeutic target.