Glucose induced-AKT/mTOR activation accelerates glycolysis and promotes cell survival in acute myeloid leukemia.

Multiple studies have demonstrated that excessive glucose utilization is a common feature of cancer cells to support malignant phenotype. Acute myeloid leukemia (AML) is recognized as a heterogeneous disorder of hematopoietic stem cells characterized by altered glucose metabolism. However, the role of glucose metabolic dysfunction in AML development remains obscure. In this study, glucose and 2-Deoxy-D-glucose (2-DG) treatment were applied to analyze the relationship between glucose metabolism and cell survival. Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) assays were used to examine the cell viability and apoptosis rate. Glucose consumption and lactate production were measured to assess the glucose metabolism pathway. The results demonstrated that abnormally increased glucose effectively promoted proliferation of leukemic cells and inhibited cell apoptosis, while 2-DG ameliorated leukemic phenotypes. Importantly, glucose exposure induced active glycolysis by increasing glucose consumption and lactate production. Furthermore, the levels of key glycolysis-related genes glucose transporter 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) were upregulated. Mechanistic investigations revealed that AKT/mTOR signaling pathway was activated in glucose condition. In conclusion, our findings indicate that glucose induced-AKT/mTOR activation plays a growth-promoting role in AML, highlighting that inhibition of glycolysis would be a vital adjuvant therapy strategy for AML.

Whole Genome Sequencing of Brucella melitensis Isolated from Patients in Hohhot, China.

Brucellosis is a class B infectious disease that is spreading rapidly in Inner Mongolia, China. Investigating the genetics of this disease might provide insights into the mechanism by which the bacteria adapt to their hosts. Here, we report the genome sequence of Brucella melitensis strain BM6144, which was isolated from a human patient.

Persistent Facial Flushing in a Patient with Telangiectasia Macularis Eruptiva Perstans: An Unusual but Should Emphasized Clinical Finding.

Facial flushing is one of the common conditions in dermatology, which affects the aesthetic of patients to a great extent, and even leads to psychological and economic burdens. The most common causes of facial flushing are often inflammatory skin diseases such as rosacea, contact dermatitis, and others, but the facial flushing as a sign can also be the cutaneous manifestation of systemic disease. Telangiectasia macularis eruptiva perstans (TMEP) is a rare disease associated with mast cells. Here, we describe an unusual clinical finding with persistent facial flushing in a patient with TMEP.

Oral Delivery of SARS-CoV-2 DNA Vaccines Using Attenuated Salmonella typhimurium as a Carrier in Rat.

The 2019 novel coronavirus disease (COVID-19) is the disease that has been identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the prophylactic treatment of SARS-CoV-2 is still under investigation. The effective delivery of eukaryotic expression plasmids to the immune system's inductive cells constitutes an essential requirement for generating effective DNA vaccines. Here, we have explored the use of Salmonella typhimurium as vehicles to deliver expression plasmids orally. The attenuated Salmonella phoP was constructed by the one-step gene inactivation method, and plasmid-encoded the spike protein of SARS-CoV-2 was transform into the Salmonella phoP by electroporation. Western blot experiment was used for the detection of SARS-CoV-2 expression on 293T cells. Wistar rats were immunized orally with Salmonella that carried a eukaryotic expression plasmid once a week for three consecutive weeks. The ELISA was performed to measure the SARS-CoV-2 specific IgG at rat's serum samples. pSARS-CoV-2 can be successfully expression on 293T cells, and all immunized animals generated immunity against the SARS-CoV-2 spike protein, indicating that a Salmonella-based vaccine carrying the Spike gene can elicit SARS-CoV-2-specific secondary immune responses in rats. Oral delivery of SARS-CoV-2 DNA vaccines using attenuated Salmonella typhimurium may help develop a protective vaccine against SARS-CoV-2 infection.

Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway.

The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells. High expression of Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was observed in the U937 cell line. We transduced K562 cells with two independent adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell cycle arrest by increasing the expression of p21 and decreasing the expression of cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore, Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK pathways, but no remarkable change in p-AKT was observed. These data provide evidence that Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment.