Liyang Liang

Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor.

Invasiveness is a major clinical feature of glioma, an aggressive brain tumor with poor prognosis. Although there is emerging evidence that some microRNAs are involved in the glioma cell invasion process, it remains necessary to find functional microRNAs and elucidate the underlying molecular mechanisms. Here, we reported that a microRNA, miR-383, was downregulated in gliomas and inversely correlated with glioma pathological grades. Downregulation of miR-383 enhanced, whereas upregulation of miR-383 inhibited, the glioma cell invasive ability. Furthermore, we found that downregulation of miR-383 activated the AKT signaling following upregulation of MMP2 expression by directly targeting insulin-like growth factor 1 receptor (IGF1R). Importantly, we demonstrated that IGF1R expression is critical for miR-383 downregulation-induced cell invasion. Taken together, these findings uncover a novel regulatory mechanism for constitutive IGF1R signaling activation in glioma cancer and may provide miR-383 as a useful diagnostic marker or therapeutic target.

Effect of intravenous immunoglobulin treatment on brain interferon-gamma and interleukin-6 levels in a rat kindling model.

Many studies indicate that intravenous immunoglobulin (IgG) therapy may decrease symptoms of epilepsy. In this study, we assessed the effects of intravenous IgG in an experimental rat kindling model and attempted to elucidate the underlying mechanism of the IgG effect. For induction of kindling, Wistar rats received repeated intraperitoneal injections of picrotoxin. The serum level of neuron-specific enolase (NSE) was measured to determine seizure severity. Interferon (IFN)-gamma and interleukin (IL)-6 levels were measured in rat hippocampus homogenates. The serum NSE level and hippocampal IFN-gamma level were significantly higher in fully kindled, untreated rats compared to unkindled control rats, whereas IL-6 levels were similar in all groups. Intravenous IgG-treated kindled rats showed NSE and IFN-gamma levels similar to those of control rats, along with lower seizure severity and longer seizure latent period than fully kindled, untreated rats. These results indicate that intravenous immunoglobulin exerts a protective effect on the neurons of kindled rats, potentially by downregulating cytokines in the brain. These results shed light on the mechanism by which intravenous immunoglobulin decreases the severity of epileptic seizures.

Human intravenous immunoglobulins suppress seizure activities and inhibit the activation of GFAP-positive astrocytes in the hippocampus of picrotoxin-kindled rats.

ABSTRACT We previously showed that human intravenous immunoglobulin (IVIG) can lower seizure severity and prolong seizure latency in picrotoxin-kindled rats. The aim of this study was to further characterize the effects of IVIG on seizure activity and investigate its influence on astrocytes in the hippocampus of picrotoxin-kindled rats. A rat kindling model was established by peritoneal injections of picrotoxin for 21 days in Wistar rats. Seventy-five rats were equally divided into five groups: picrotoxin, IVIG pretreatment, IVIG post-treatment, normal saline control, and IVIG control. Seizure severity was evaluated according to a six-stage classification. The number and morphology of glial fibrillary acidic protein (GFAP)-positive astrocytes were studied by immunohistochemistry using the anti-GFAP antibody. The cross-sectional area and grayscale of GFAP-positive astrocytes were also determined. In picrotoxin-kindled rats, pretreatment with IVIG appeared to inhibit full kindling rates, and it significantly reduced the number of GFAP-positive cells in the hippocampus (p < .001). IVIG also significantly (p < .001) attenuated the increase in the cross-sectional area and grayscale of GFAP-positive astrocytes in the hippocampus. Our results suggest that by suppressing the expression of GFAP, IVIGs may reduce seizure activity and inhibit the activation of GFAP-positive astrocytes in picrotoxin-kindled rats.

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability

BackgroundInterstitial duplications distal to 15q13 are very rare.Case PresentationHere, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient’s clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well.ConclusionThe results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Merosin-deficient congenital muscular dystrophy type 1A: A case report

The aim of this study was to characterize the clinical and genetic features of a 4-year-old female with merosin-deficient congenital muscular dystrophy type 1A (MDC1A). MDC1A is the most common form of congenital muscular dystrophy. MDC1A is caused by mutation of the laminin α-2 gene (LAMA2), localized to chromosome 6q22–23. Clinical presentation, as well as the results of neuro-imaging, electrophysiology and molecular genetic tests were used to evaluate a patient with MDC1A. The patient exhibited severe hypotonia and marked proximal weakness at 6 months of age, as well as delayed developmental milestones. The serum creatine kinase levels of the patient were elevated at 1,556 IU/l. Magnetic resonance imaging (MRI) showed that the white matter in the frontal, parietal, temporal and occipital lobes was abnormal with low signal intensities on T1-weighted images and high signal intensities on T2-weighted images; however, the cortex was normal. Sequencing of the 65 exons of the LAMA2 revealed a homozygous nonsense mutation in exon 50: a C>T exchange in nucleotide 7147 that resulted in a stop codon (Arg2383X stop). Molecular genetic testing is a reliable method for confirming a diagnosis of MDC1A. When a patient presents with severe congenital hypotonia, muscle weakness, high serum creatine kinase (CK) levels and white matter abnormalities, the evaluation may directly proceed to molecular genetic testing of the LAMA2 gene without performing a muscle biopsy.

Endocrine complications in patients with thalassaemia major

Thalassemia major is an inherited hemoglobin disorder characterized by chronic anemia and iron overload due to transfusion therapy and gastrointestinal absorption. Iron overload causes severe endocrine complications in patients with multi-transfused thalassaemia major. Endocrine complications includes short stature, acquired hypothyroidism and hypoparathyroidism, hypogonadism, glucose intolerance and diabetes mellitus.