Primary cerebral epithelioid angiosarcoma: a case report.

BACKGROUND: Primary cerebral epithelioid angiosarcoma (PCEA) is a rare malignant tumor of the central nervous system. To the best of our knowledge, only three cases have been reported in the English language literature thus far. CASE PRESENTATION: Here, we report a fourth case in a 73-year-old man admitted for headache. Radiological examination revealed a mass in the right occipital lobe, which was removed by right occipital craniotomy. Histopathological examination revealed epithelioid angiosarcoma. The patient received radiotherapy after resection but survived for only nine months due to recurrence of the tumor and his declining further surgery. CONCLUSIONS: In this report, we add to the knowledge base on this exceedingly rare tumor, review the small number of relevant cases published previously, and analyze and summarize the clinical and pathological characteristics, treatment options and prognosis of this cancer.

A Reconfigurable Differential-to-Single-Ended Autonomous Current Adaptation Buffer Amplifier Suitable for Biomedical Applications.

A reconfigurable differential-to-single-ended autonomous current adaptation buffer amplifier (ACABA) is proposed. The ACABA, based on floating-gate technologies, is a capacitive circuit, of which output DC level and bandwidth can be adjusted by programming charges on floating nodes. The gain is variable by switching different amounts of capacitors without altering the output DC level. Without extra sensing and control circuitries, the current consumption of the proposed ACABA increases spontaneously when the input signal is fast or large, achieving a high slew rate. The supply current dwindles back to the low quiescent level autonomously when the output voltage reaches equilibrium. Therefore, the proposed ACABA is power-efficient and suitable for processing physiological signals. A prototype ACABA has been designed and fabricated in a [Formula: see text] CMOS process occupying an area of [Formula: see text]. When loaded by a [Formula: see text] capacitor, it consumes [Formula: see text] to achieve a unity-gain bandwidth of [Formula: see text] with a measured IIP2 value of [Formula: see text] and a slew rate of [Formula: see text].

Medulloblastoma malignant biological behaviors are associated with HOTAIR/miR-483-3p/CDK4 axis.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Although the 5-year survival rate is high, patients with relapsed medulloblastoma have a guarded prognosis. HOX transcript antisense RNA (HOTAIR) has been proved to be related to the metastasis of various tumors. Therefore, the molecular mechanism of HOTAIR in medulloblastoma cells was investigated in this study. METHODS: HOTAIR was stably silenced in medulloblastoma cells (Daoy and D341). Cell proliferation and apoptosis were detected by 5'-Bromo-2'-deoxyuridine (BrdU) staining, Hoechst 33342 staining, immunohistochemical (IHC), Terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, respectively. The targeted relationship between HOTAIR/Cyclin-dependent kinase 4 (CDK4) and miR-483-3p were predicted by bioinformatics and confirmed by luciferase reporter assay. Balb/C nude mice were inoculated with shRNA-HOTAIR transfected Daoy cells. RESULTS: We found that the down-regulation of HOTAIR inhibited proliferation and induced apoptosis. Sh-RNA-HOTAIR also inhibited the expression of CKD4. The CDK4 dependent increase of cell proliferation and decrease of cell apoptosis were reversed by shRNA-HOTAIR. Finally, a xenograft model of medulloblastoma in nude mice was built, and the effect of shRNA-HOTAIR on the growth of tumors was analyzed by RT-PCR, immunofluorescence staining, and TUNEL staining. The data suggested interference of HOTAIR inhibited the growth, tumor weight, cell proliferation, and promoted cell apoptosis. CONCLUSIONS: Our study altogether demonstrated HOTAIR influence cell proliferation and apoptosis by regulation of miR-483-3p and CDK4 in medulloblastoma cells. HOTAIR can be used as a candidate for potential applications in the treatment of medulloblastoma.

MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells and Tissue Through Cell Cycle Arrest.

BACKGROUND: Glioma is a type of tumor that starts in the glial cells of brain and spine. However, the underlying molecular mechanisms of miRNAs dysregulation in glioma initiation and progression is largely unclear. OBJECTIVE: To further understand the molecular mechanism of miR-490-5P functions and how miR-490 regulated CCND1 function. METHODS: The expression of miR-490-5P in glioma tissues and cells was measured by qRT-PCR and ISH. Cell transfection is responsible for miR-490-5P overexpression and knockdown. CCK-8 and clone formation assay are applicable to examine the capacity of glioma cells proliferation. Cell cycle analysis is used to test glioma cells cycle distribution with miR-490-5P overexpression or downregulation. Further, in vivo tumor exnograft studies are used to examine the effects of miR- 490-5P on glioma malignancy in vivo. RESULTS: We found overexpression of miR-490 lead to glioma cells cycle arrest at G1 phase and decreased proliferation. Next-step functional assays showed miR-490 regulated CCND1 expression and manipulated giloma cells proliferation. Finally, negative regulation of miR-490 in CCND1 function was validated through in vivo nude mice tumorigenesis assay and IHC examination in glioma tissue. CONCLUSION: Overall, these results showed that epigenetic regulation of CCND1 via miR-490 was essential to glioma and provide a new insight into glioma diagnosis, treatment, prognosis and further translational investigations.

Histone deacetylase 1 promotes glioblastoma cell proliferation and invasion via activation of PI3K/AKT and MEK/ERK signaling pathways.

Histone deacetylase 1 (HDAC1) plays a crucial role in cancer progression and development. This enzyme has been confirmed to be a key regulator of tumor biology functions, such as tumor cell proliferation, migration and invasion. However, HDAC1 expression in glioma remains controversial, and its specific function and molecular mechanism in glioblastoma is poorly understood. In this study, our findings demonstrated that protein and mRNA levels of HDAC1 were increased in glioma cell lines and glioma tissues compared to normal glial cell lines and non-neoplastic brain tissues, respectively. Furthermore, HDAC1 knockdown cells displayed decreased proliferation and invasion capabilities, whereas HDAC1 overexpressing glioblastoma cells displayed more proliferation and invasion capabilities in vitro. These novel outcomes suggested that knockdown of HDAC1 possibly suppressed the expression of phosphorylated AKT (p-AKT) and phosphorylated ERK (p-ERK) proteins, while overexpression of HDAC1 significantly increased p-AKT and p-ERK protein in glioblastoma cells. In addition, knockdown of HDAC1 repressed subcutaneous tumor growth in vivo, and led to down-regulation of p-AKT and p-ERK protein in U87 MG xenograft tumors. For the first time, we have demonstrated that HDAC1 promotes proliferation and invasion in glioblastoma cells by activating PI3K/AKT and MEK/ERK signaling pathways in vitro and in vivo. These results suggest that HDAC1 may be a novel biomarker and potential therapeutic target in glioblastoma.

Maternal and embryonic exposure to the water soluble fraction of crude oil or lead induces behavioral abnormalities in zebrafish (Danio rerio), and the mechanisms involved.

The water-soluble fraction (WSF) of crude oil plays an important role in the toxicity of crude oil in aquatic environments. Heavy metals, such as lead (Pb) are also important environmental contaminants, which can reach aquatic systems via the effluents of industrial, urban and mining sources. In the present study, we investigated whether maternal and embryonic exposure to the WSF (5, 50 µg/L) or Pb (10, 100 µg/L) could induce behavioral abnormalities in zebrafish. Our results showed that maternal and embryonic exposure to the WSF (5, 50 µg/L) and Pb (10, 100 µg/L) induced swimming activity alterations in larval and juvenile zebrafish. In 15 days post-fertilization (dpf) larval zebrafish, the distance moved was significantly increased in the groups treated with the WSF (5, 50 µg/L), but the angular velocity and turn angle were decreased after treatment with the WSF (5, 50 µg/L) or Pb (10, 100 µg/L). In 30 dpf juvenile zebrafish, the distance moved was markedly decreased in both groups treated with the WSF (5, 50 µg/L) and the Pb (10 µg/L) group, but the percentage of zebrafish moving up and the inter-fish distance of two juvenile fish were increased after treatment with the WSF (5, 50 µg/L) or Pb (10, 100 µg/L). Maternal and embryonic exposure to the WSF (5, 50 µg/L) or Pb (10, 100 µg/L) likely impaired the brain neurons growth and induced behavioral abnormalities in the larval and juvenile zebrafish. Furthermore, the expressions of some key genes, which were associated with calcium channels, behavioral development or the metabolism of environmental contaminants, were changed.

MicroRNA-200b inhibits pituitary tumor cell proliferation and invasion by targeting PKCα.

The present study aimed to investigate the expression of miR-200b and protein kinase Cα (PKCα) in pituitary tumors and to determine whether miR-200b may inhibit proliferation and invasion of pituitary tumor cells. The regulation of PKCα expression was targeted in order to find novel targets for the treatment of pituitary tumors. In total, 53 pituitary tumor tissue samples were collected; these included 28 cases of invasive pituitary tumors and 25 cases of non-invasive tumors, in addition to 5 normal pituitaries. The expression level of miR-200b in the pituitary tumor tissue was detected by quantitative polymerase chain reaction (qPCR) and the expression of PKCα protein was detected by immunohistochemistry. A PKCα 3'untranslated region (UTR) luciferase vector was constructed and a dual luciferase reporter gene assay was employed in order to examine the effect of miR-200b on the PKCα 3'UTR luciferase activity. AtT-20 cells were transfected with miR-200b mimics, PKCα siRNA and miR-200b mimics + PKCα, and the changes in cellular proliferation, invasion and apoptosis were observed via MTT, Transwell assay and flow cytometric analysis. Furthermore, PKCα mRNA expression was determined by qPCR, and Western blotting was performed to detect the expression of PKCα protein. miR-200b revealed downregulation in invasive pituitary tumor tissue, and the expression level was significantly down-regulated compared with normal and non-invasive pituitary tumor tissue (P<0.01). In addition, the positive rate of PKCα protein expression in invasive pituitary tumor tissues was significantly higher than in normal and non-invasive tissues (P<0.01). PKCα protein levels are inversely correlated with miR-200b levels in invasive pituitary tumor tissues (r=-0.436, P=0.021). The dual luciferase reporter gene assay revealed that miR-200b could specifically bind to the 3'UTR of PKCα and significantly inhibit the luciferase activity by 39% (P<0.01). Upregulation of miR-200b or downregulation of PKCα could suppress cell proliferation and invasion, and increase apoptosis of AtT-20 cells. It was revealed that PKCα siRNA could suppress both proliferation and invasion of AtT-20 cells and partially simulate the function of miR-200b. Expression of PKCα mRNA and protein decreased significantly in AtT-20 cells overexpressing miR-200b. Additionally, miR-200b was significantly down-regulated in invasive pituitary tumor tissue and inversely correlated with PKCα protein levels. In conclusion, miR-200b inhibited proliferation and invasiveness and promoted the apoptosis of pituitary tumor cells by targeting PKCα. The observations of the present study indicate that miR-200b and PKCα may serve as promising therapeutic targets for invasive pituitary tumors.

Early-Life Benzo[a]Pyrene Exposure Causes Neurodegenerative Syndromes in Adult Zebrafish (Danio rerio) and the Mechanism Involved.

There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration. Additionally, BaP increased amyloid ß protein and cell apoptosis in the adult zebrafish brain. Further, DNA methyltransferase 1 (DNMT1) and DNMT3a were up-regulated in 96 hpf larvae and the adult brain. MeDIP-sequencing data of the 96 hpf larvae identified 235 differentially methylated genes in promoter, with the fold change > 1.5. Guanylate cyclase 2F (gucy2f) and dopamine receptor D4 related sequence (drd4-rs) were hypermethylation promoters, whereas zinc finger C4H2 domain (zc4h2) was a hypomethylation promoter in 96 hpf larvae and the adult brain. The mRNA levels of gucy2f and drd4-rs were down-regulated, and zc4h2 was up-regulated. Our findings suggested that the lasting modifications of DNA methylation were associated with neurodegenerative syndromes in adult zebrafish as a result of early-life BaP exposure.

Maternal exposure to the water soluble fraction of crude oil, lead and their mixture induces autism-like behavioral deficits in zebrafish (Danio rerio) larvae.

Autism spectrum disorder (ASD) is a serious debilitating mental illness with complex symptoms and multi-factorial pathogenesis. Although the pathogenesis of ASD remains unclear, etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In the present study, we used zebrafish (Danio rerio) as a model to investigate whether maternal exposure to the water soluble fraction of crude oil (WSF, 5µg/L), lead (Pb, 20µg/L) and their mixture (5 µg/L WSF+20 µg/L Pb) could induce autism-like behavior in larvae. Our results showed that isolated and combined WSF/Pb exposure altered the behavioral pattern of fish swimming. WSF significantly increased anxiety and locomotor activity, decreased repetitive behavior in the open field test, and reduced the level of serotonin. However, co-exposure to WSF/Pb decreased behavioral activity and shoaling behavior, and increased cycle swimming and edge preference. Significant changes in the expression level of the multiple genes potentially critical for regulating environmental factor induced autism-like behavior were found. A gene network regulating ASD disturbed by WSF/Pb exposure was established using computational analysis. The information from the network could provide a clue for further mechanistic studies explaining molecular events regulating WSF/Pb mediated ASD.

Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans.

Chronic exposure to tributyltin chloride induces pancreatic islet cell apoptosis and disrupts glucose homeostasis in male mice.

It has been reported that organotin compounds such as triphenyltin or tributyltin (TBT) induce diabetes and insulin resistance. However, histopathological effects of organotin compounds on the Islets of Langerhans and exocrine pancreas are still unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 µg/kg) once every 3 days. The fasting plasma glucose levels significantly elevated, and the levels of serum insulin or glucagon decreased in the animals treated with TBT for 60 days. In animals treated for 45 days, the number of apoptotic cells in the islets and exocrine pancreas was elevated in a dose-dependent manner. The percentage of proliferating (PCNA-positive) cells was decreased in the islets, while it was increased in exocrine acinar cells. Immunohistochemistry analysis showed that estrogen receptor (ER) and androgen receptor (AR) were present in vascular endothelium, ductal cells, and islet cells, but absent from pancreatic exocrine cells. TBT exposure decreased the production of estradiol and triiodothyronine and elevated the concentration of testosterone, and resulted in a decrease of ERα expression and an elevation of AR in the pancreas measured by Western boltting. The results suggested that TBT inhibited the proliferation and induced the apoptosis of islet cells via multipathways, causing a decrease of relative islet area in the animals treated for 60 days, which could result in a disruption of glucose homeostasis. The different presence of ERs and AR between the islets and exocrine pancreas might be one of reasons causing different effects on cell proliferation.

Molecular characterization of drug-resistant Mycobacterium tuberculosis isolates in Guangdong, China.

The aim of this study was to characterize 160 clinical Mycobacterium tuberculosis isolates from Guangdong with respect to their drug susceptibility phenotypes to three common anti-tuberculosis drugs, isoniazid (INH), rifampin (RIF) and streptomycin (SM), and with respect to genetic mutations in the most commonly corresponding resistance genes (katG, rpoB and rpsL). The drug susceptibility profiles were evaluated by the absolute concentration method, and genetic mutations in the corresponding resistance genes were identified by DNA sequencing. Among these isolates, 33.1% (53/160) were drug-resistant. The percentages of isolates resistant to INH, RIF and SM were 21.9% (35/160), 16.9% (27/160) and 15.6% (25/160), respectively. Twenty-five of 35 (71%) INH-resistant isolates, 22 of 27 (81.5%) RIF-resistant isolates and 19 of 25 (76%) SM-resistant isolates were found to have mutations in the analyzed katG, rpoB and rpsL gene fragments. The most frequent mutation patterns for the three drugs were as follows: INH, Ser315Thr (68.6%) in katG; RIF, Ser531Leu (55.6%) in rpoB; and SM, Lys43Arg (72%) in rpsL. These findings provide useful data on the mutation types of drug-resistant genes in M. tuberculosis isolates from Guangdong province in China.