LncRNA SNHG1 protects SH-SY5Y cells from hypoxic injury through miR-140-5p/Bcl-XL axis.

Background: Hypoxic brain injury is one of the major causes of neurodevelopmental impairment and cardiovascular disability. LncRNA SNHG1 works as a critical factor in hypoxic induced injury, however, the potential mechanism is still not known well.Methods: The expression level of small nucleolar RNA host gene 1 (SNHG1) and miR-140-5p was detected by qRT-PCR. The western blot assay was performed to measure the level of Bcl-XL and apoptosis-related proteins. The target relationship between lncRNA SNHG1 and miR-140-5p, as well as miR-140-5p and Bcl-XL was detected by dual luciferase reporter gene assay. Cell apoptosis was assessed using Annexin V/PI staining by flow cytometry. Cell viability was analyzed by MTT assay.Results: Oxygen glucose deprivation (OGD) treatment inhibited SNHG1 and Bcl-XL expression and enhanced miR-140-5p expression. OGD treatment-induced cell viability inhibition, cell apoptosis promotion were partially abrogated when SH-SY5Y cells were transfected with pcDNA3.1-SNHG1 or miR-140-5p inhibitor. Moreover, luciferase reporter assay revealed that lncRNA SNHG1 bound directly to miR-140-5p, and miR-140-5p directly targeted Bcl-XL. The protective effect of SNHG1 overexpressing on cell apoptosis induced by OGD was attenuated after transfected with miR-140-5p mimic or sh-Bcl-XL in SH-SY5Y cells.Conclusion: LncRNA SNHG1-modulated miR-140-5p inhibition regulates Bcl-XL expression, thereby reducing cell apoptosis and recovering cell viability of SH-SY5Y cells. The results in this study provide novel insight into the mechanism of SNHG1 mediated signaling pathway during hypoxic brain injury.

Systematic analysis of long non-coding RNA and mRNA expression changes in ApoE-deficient mice during atherosclerosis.

Atherosclerosis plays an important role in the pathology of coronary heart disease, cerebrovascular disease, and systemic vascular disease. Long non-coding RNAs (lncRNAs) are involved in most biological processes and are deregulated in many human diseases. However, the expression alteration and precise role of lncRNAs during atherosclerosis are unknown. We report here the systematic profiling of lncRNAs and mRNAs in an ApoE-deficient (ApoE-/-) mouse model of atherosclerosis. Clariom D solutions for the mouse Affymetrix Gene Chip were employed to analyze the RNAs from control and ApoE-/- mice. The functions of the differentially expressed mRNAs and lncRNAs and the relationships of their expression with atherosclerosis were analyzed by gene ontology, co-expression network, pathway enrichment, and lncRNA target pathway network analyses. Quantitative real-time PCR (QRT-PCR) was used to determine the expression of mRNAs and lncRNAs. A total of 2212 differentially expressed lncRNAs were identified in ApoE-/- mice, including 1186 up-regulated and 1026 down-regulated lncRNAs (|FC| ≥ 1.1, p < 0.05). A total of 1190 differentially expressed mRNAs were found in the ApoE-/- mice with 384 up-regulated and 806 down-regulated (|FC| ≥ 1.1, p < 0.05). Bioinformatics analyses demonstrated extensive co-expression of lncRNAs and mRNAs and concomitant deregulation of multiple signaling pathways associated with the initiation and progression of atherosclerosis. The identified differentially expressed mRNAs and lncRNAs as well as the related signaling pathways may provide systematic information for understanding the pathogenesis and identifying biomarkers for the diagnosis, treatment, and prognosis of atherosclerosis.

Decreased percentage of NKG2D+NK cells in patients with incident onset of Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency owing to autoimmune destruction of the pancreatic ß cells. A significant decrease in natural killer (NK) cells in peripheral blood has been observed in patients with untreated T1DM. In the present study, we aimed to explore the role of NK cells and their subsets in young T1DM patients. A total of 30 children and adolescents with untreated T1DM and 27 healthy controls (HC) were recruited in this study. Flow cytometry analysis indicated that the percentage of peripheral blood CD3-CD56+ NK cells and NK cells subsets (CD56bright, CD56dim and CD56neg), were significantly decreased in the T1DM patients compared to healthy controls. In addition, the percentage of inducible CD107a+ and IFN-γ-secreting NK cells was significantly decreased compared to HC. Interestingly, the percentage of NKG2D+ NK cells negatively correlated with the level of serum TCHOL and TG in T1DM patients. Our data indicate that decreased number and impaired function of NK cells may have a role in the pathogenesis of T1DM.

A successfully treated case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis.

INTRODUCTION: This study aimed to report a rare case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis. CASE PRESENTATION: Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. It often leads to hypoglycaemia, but in this case the patient was complicated with hyperosmolar hyperglycaemic state. The patient received prompt medical treatment, which effectively prevented the occurrence of possible acute kidney failure and other complications. CONCLUSION: This is a complicated and rare case. Our report provides some indications for the timely diagnosis and the standardised treatments for a patient who has hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis.

Mechanism of microRNA regulating the progress of atherosclerosis in apoE-deficient mice.

MicroRNAs play important roles in atherosclerogenesis and are important novel pharmaceutic targets in atherosclerosis management. The whole spectrum of miRNAs dysregulation is still under intense investigation. This study intends to identify more novel dysregulated microRNAs in atherosclerotic mice. Half of eight-week-old male ApoE-/- mice were fed with high-fat-diet for 12 weeks as a model mice, and the remaining half of ApoE-/- mice were fed with a normal-diet as a control. A serum lipid profile was performed with ELISA kits, and atherosclerotic lesions were assessed. Aortic tissues were dissected for gene expression profiling using a Multispecies miRNA 4.0 Array, and significant differentially expressed miRNAs were identified with fold change ≥ 2 and p < 0.05. Real-time quantitative PCR was used to validate microarray gene expression data on selected genes. Predicted target genes were extracted and subjected to bioinformatic analysis for molecular function and pathway enrichment analysis. Model mice showed a 15.32% atherosclerotic lesion compared to 1.52% in the control group. A total of 25 significant differentially expressed microRNAs were identified, with most of them (24/25) downregulated. Real-time quantitative PCR confirmed the GeneChip data. Bioinformatic analysis of predicted target genes identified high involvement of the PI3K/Akt/mTOR signaling pathway. Microarray profiling of miRNAs in high-fat-fed Model mice identified 25 differentially expressed miRNAs, including some novel miRNAs, and the PI3K/Akt/mTOR signaling pathway is highly enriched in the predicted target genes. The novel identified dysregulated miRNAs suggest a broader spectrum of miRNA dysregulation in the progression of atherosclerosis and provide more research and therapeutic targets for atherosclerosis.

New thoughts on the diagnosis and treatment of patients with diabetes mellitus in relation to coronavirus disease.

The coronavirus disease 2019 (COVID-19) outbreak that occurred in late 2019 has posed a huge threat to the health of all humans, especially for individuals who already have diabetes mellitus (DM). DM is one of the most serious diseases that affect human health, with high morbidity and rates of complications. Medical scientists worldwide have been working to control blood sugar levels and the complications associated with sugar level alterations, with an aim to reduce the adverse consequences of acute and chronic complications caused by DM. Patients with DM face great challenges during the pandemic owing to not only changes in the allocation of medical resources but also their abnormal autoimmune status, which reduces their resistance to infections. This increases the difficulty in treatment and the risk of mortality. This review presents, from an epidemiological viewpoint, information on the susceptibility of patients with DM to COVID-19 and the related treatment plans and strategies used in this population.

Male asymptomatic hyperuricemia patients display a lower number of NKG2D+ NK cells before and after a low-purine diet.

BACKGROUND: Aberrant activation of the immune system has been reported in asymptomatic hyperuricemia (HUA) patients. However, very few studies have elucidated the role of natural killer (NK) cells in this disease. METHODS: In this study, we evaluated the relationship between NK cells and HUA in 16 control subjects and 20 patients, who were all on a low-purine diet. We analyzed the number of circulating NK cells, its subsets, interferon-γ, and CD107 NK cells, by flow cytometry, before and after 4 and 24 weeks of diet control. We also assessed the potential association of the NK cells with clinical measures. RESULTS: The patients consistently had a lower number of NKG2D NK cells before and after low-purine diet, even the serum uric acid (SUA) levels <7 mg/dL after diet control. Moreover, a lower number of NK cells and a higher number of CD107a NK cells were observed on recruitment. Low-purine diet was benefit on the improvement of the SUA levels, body mass index (BMI), and the number and functions of NK cells. Furthermore, the number of CD3CD56 NK cells and NKG2D NK cells negatively correlated with the BMI before and after diet control. CONCLUSION: The consistent lower number of NKG2D NK cells and correlated with BMI before and after low-purine diet may be involved in the occurrence and development of HUA.

Quercetin protects against inflammation, MMP­2 activation and apoptosis induction in rat model of cardiopulmonary resuscitation through modulating Bmi­1 expression.

With extensive pharmacological actions, quercetin has anti­oxidant, free radical scavenging, anti­tumor, anti­inflammatory, anti­bacterial and anti­viral activity. Quercetin also reduces blood glucose and reduces high blood pressure, and has immunoregulation and cardiovascular protection functions. Additionally, it has been reported that it can reduce depression. The current study evaluated whether quercetin protects against inflammation, matrix metalloproteinase­2 (MMP­2) activation and apoptosis induction in a rat model of cardiopulmonary resuscitation (CPR), and whether Bmi­1 expression was involved in the effects. In CPR model rats, treatment with quercetin significantly recovered left ventricular ejection fraction, left ventricular fractional shortening, ejection fraction (%), and left ventricle weight/body weight. Treatment with quercetin significantly inhibited ROS generation, inflammation and MMP­2 protein expression in the rat model CPR. Finally, quercetin significantly suppressed caspase­3 activity and activated Bmi­1 protein expression in the rat model of CPR. The results demonstrated that quercetin protects against inflammation, MMP­2 activation and apoptosis induction in a rat model of CPR, and that this may be mediated by modulating Bmi­1 expression.

NKG2A expression and impaired function of NK cells in patients with new onset of Graves' disease.

BACKGROUND: Graves' disease (GD) is an organ-specific autoimmune disease. A significant decrease of the distribution of NK cells in the peripheral blood in children and adolescents with untreated GD has been observed. However, the role of NK and its subsets in adults with GD remains unclear. METHODS: A total of 28 adult patients with new onset of GD and 23 healthy controls (HC) were recruited. The number of activated inhibitory NK cells in peripheral blood of individual subjects was determined by flow cytometry. RESULTS: The number of CD3(-)CD56(+) and CD3(-)CD16(+)NK cells in peripheral blood was significantly decreased in the GD patients than the HC. Compared to the HCs, decreased number of NKG2D(+), NKG2C(+), NKp30(+) and NKG2A(+) NK cells and increased number of KIR3DL1(+) NK cells were detected in the GD patients. Moreover, the number of inducible CD107a(+) and IFN-γ-secreting NK cells in GD patients significantly decreased than those in HC. Interestingly, the number of NKG2A(+)NK cells was negatively correlated with the level of serum TRAb in GD patients. CONCLUSION: Our data indicate that decreased number and impaired function of NK cells may contribute to the pathogenesis of GD.