Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine.

O-linked ß-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.

Medical expenses of urban Chinese patients with stomach cancer during 2002-2011: a hospital-based multicenter retrospective study.

BACKGROUND: In China, stomach cancer is the third most common cancer and the third leading cause of cancer death. Few studies have examined Chinese stomach cancer patients' medical expenses and their associated trends. The Cancer Screening Program in Urban China (CanSPUC) is a Major Public Health Project funded by the central government. Through this project, we have extracted patients' medical expenses from hospital billing data to examine the costs of the first course treatments (which refers to 2 months before and 10 months after the date of cancer diagnosis) in Chinese patients with stomach cancer and the associated trends. METHODS: The expense data of 14,692 urban Chinese patients with stomach cancer were collected from 40 hospitals in 13 provinces. We estimated the inflation-adjusted medical expenses per patient during 2002-2011. We described the time trends of medical expenses at the country-level, and those trends by subgroup, and analyzed the compositions of medical expenses. We constructed the Generalized Linear Mixed (GLM) regression model with Poisson distribution to examine the factors that were associated with medical expenses per patient. RESULTS: The average medical expenses of the first course treatments were about 43,249 CNY (6851 USD) in 2011, more than twice of that in 2002. The expenses increased by an average annual rate of 7.4%. Longer stay during hospitalization and an increased number of episodes of care are the two main contributors to the expense increase. The upward trend of medical expenses was observed in almost all patient subgroups. Drug expenses accounted for over half of the medical expenses. CONCLUSIONS: The average medical expenses of the first course (2 months before and 10 months after the date of cancer diagnosis) treatments per stomach cancer patient in urban China in 2011 were doubled during the previous 10 years, and about twice as high as the per capita disposable income of urban households in the same year. Such high expenses indicate that it makes economic sense to invest in cancer prevention and control in China.

Rheinheimera marina sp. nov., isolated from a deep-sea seamount.

A bacterial strain designated TP462T, isolated from a seamount near the Yap Trench in the tropical western Pacific, was characterized using a polyphasic taxonomic approach. Strain TP462T was found to be Gram-stain-negative, aerobic, rod-shaped and motile by means of a single polar flagellum. Growth occurred at 4-37 °C (optimum, 25-30 °C) and with 0-4.0 % NaCl (optimum, 2-3 %). Phylogenetic analysis based on 16S rRNA gene sequence showed that strain TP462T was related to the genus Rheinheimera and had the highest 16S rRNA gene sequence similarity with the type strain Rheinheimera tangshanensis JA3-B52T (96.8 %). The predominant cellular fatty acids were C17 : 1ω8c, summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1ω7c) and C16 : 0. The polar lipid profile contained phosphatidylglycerol, phosphatidylethanolamine and two unidentified lipids. The genomic DNA G+C content of strain TP462T was 48.7 mol%. On the basis of the evidence presented in this study, strain TP462T represents a novel species of the genus Rheinheimera, for which we propose the name Rheinheimera marina sp. nov. (type strain TP462T=KACC 18560T=CGMCC 1.15399T).

Ponticaulis profundi sp. nov. isolated from a deep-sea seamount.

A Gram-stain negative, rod-shaped, strictly aerobic, motile bacterial strain, designated YC239T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain YC239T is related to the genus Ponticaulis and has high 16S rRNA gene sequence similarity with the type strain of Ponticaulis koreensis GSW-23T (97.9%). The predominant cellular fatty acids were C18:1ω7c, C16:0, C17:0 and C17:1ω6c. Strain YC239T had Q-10 as the predominant ubiquinone. The polar lipid profile contained phosphatidylglycerol, two unidentified aminolipids and six unidentified polar lipids. The genomic DNA G+C content of strain YC239T was 52.8 mol%. Strain YC239T shared DNA relatedness of 38% with Ponticaulis koreensis KCTC 22146T. On the basis of the evidence presented in this study, strain YC239T represents a novel species of the genus Ponticaulis, for which we propose the name Ponticaulis profundi sp. nov. (type strain YC239T = KACC 19027T = CGMCC 1.15741T).

Maribacter marinus sp. nov. isolated from a deep-sea seamount.

A Gram-stain negative, rod-shaped, aerobic strain, designated YC973T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on its 16S rRNA gene sequence showed that strain YC973T is related to the genus Maribacter and has high 16S rRNA gene sequence similarity to Maribacter orientalis KMM 3947T (97.6%). The predominant cellular fatty acids were iso-C15:0, iso-C15:1 G and an unidentified fatty acid of equivalent chain-length 13.565. The polar lipid profile contained phosphatidylethanolamine and five unidentified lipids. The genomic DNA G+C content of strain YC973T was 36.1 mol%. On the basis of the evidence presented in this study, strain YC973T represents a novel species of the genus Maribacter, for which we propose the name Maribacter marinus sp. nov. (type strain YC973T = KACC 19025T = CGMCC 1.16328T).

Serum level of fetuin B is associated with osteoporosis: a 4-year prospective study in China.

PURPOSE: As a novel hepatokine, fetuin B involves in various functions of energy metabolism. Recent advance reveals a complex interaction between bone and liver via the secretion of hepatokines. The association between serum fetuin B and osteoporosis was evaluated in a 4-year hospital-based prospective study of 1,370 Chinese postmenopausal women. METHODS: Bone mineral densities (BMDs) were obtained on femoral neck and lumbar spines by dual energy X-ray absorptiometry. Serum fetuin B level was tested by enzyme-linked immunosorbent assay. RESULTS: Of the 1,370 participants in the baseline study (2012), 650 subjects were included in the 4-year follow-up study (2016). Serum fetuin B level presented higher in subjects with osteoporosis (106.7 ± 17.6 µg/ml) than it in controls (86.3 ± 17.5 µg/ml) (P < 0.001). Meanwhile, fetuin B positively correlated with triglycerides (r = 0.227, P = 0.001), femoral BMD (r = -0.426, P < 0.001) and lumbar BMD (r = -0.332, P < 0.001). At the 4-year follow-up, 116 subjects had developed osteoporosis. Serum fetuin B concentration was significantly higher in subjects who developed (P < 0.001). The osteoporosis incidence increased from Q1 9.9%, Q2 14.7%, and Q3 17.8% to Q4 30.2% (P for trend < 0.001), among the quartiles of baseline fetuin B. A higher fetuin B baseline level was linked to the incidence of osteoporosis (adjusted OR = 1.179, 95% CI [1.119 - 1.243], P = 0.009). CONCLUSION: Serum fetuin B levels increased with the development of osteoporosis.

Thalassotaleaprofundi sp. nov. isolated from a deep-sea seamount.

The Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain, designated YM155T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain YM155T was related to the genus Thalassotalea and had highest 16S rRNA gene sequence similarities with the type strains of Thalassotalea piscium T202T (97.2 %) and Thalassotalea agariperforans M-M1T (97.2 %). The predominant cellular fatty acids were C17 : 1ω8c, summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1ω7c) and iso-C16 : 0. Ubiquinone 8 (Q-8) was the respiratory quinone. The polar lipid profile contained phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and one unidentified lipid. The genomic DNA G+C content of strain YM155T was 36.1 mol%. On the basis of the evidence presented in this study, strain YM155T represents a novel species of the genus Thalassotalea, for which we propose the name Thalassotalea profundi sp. nov. (type strain YM155T=KACC 18563T=CGMCC 1.15922T).

Oceanisphaera marina sp. nov., isolated from a deep-sea seamount.

A Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain, designated YM319T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain YM319T was related to the genus Oceanisphaera and had highest 16S rRNA gene sequence similarities with the type strains Oceanisphaera profunda SM1222T (97.4 %), Oceanisphaera sediminis TW92T (97.3 %) and Oceanisphaera ostreae T-w6T (97.1 %). The predominant cellular fatty acids were summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1 ω7c), C16 : 0 and C18 : 1ω7c. Strain YM319T had Q-8 as the predominant ubiquinone. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and four unidentified lipids. The genomic DNA G+C content of strain YM319T was 54.8 mol%. On the basis of the evidence presented in this study, strain YM319T represents a novel species of the genus Oceanisphaera, for which we propose the name Oceanisphaera marina sp. nov. (type strain YM319T=KACC 18564T=CGMCC 1.15923T).

Quantum Phase Transition between a Topological and a Trivial Semimetal from Holography.

We present a holographic model of a topological Weyl semimetal. A key ingredient is a time-reversal breaking parameter and a mass deformation. Upon varying the ratio of mass to time-reversal breaking parameter the model undergoes a quantum phase transition from a topologically nontrivial semimetal to a trivial one. The topological nontrivial semimetal is characterized by the presence of an anomalous Hall effect. The results can be interpreted in terms of the holographic renormalization group (RG) flow leading to restoration of time reversal at the end point of the RG flow in the trivial phase.

Odd Viscosity in the Quantum Critical Region of a Holographic Weyl Semimetal.

We study odd viscosity in a holographic model of a Weyl semimetal. The model is characterized by a quantum phase transition from a topological semimetal to a trivial semimetal state. Since the model is axisymmetric in three spatial dimensions there are two independent odd viscosities. Both odd viscosity coefficients are nonvanishing in the quantum critical region and nonzero only due to the mixed axial gravitational anomaly. It is therefore a novel example in which the mixed axial gravitational anomaly gives rise to a transport coefficient at first order in derivatives at finite temperature. In the quantum critical region, the physics of viscosities as well as conductivities is governed by the quantum critical point.

[Expression of Cocktail DNA Vaccine Comprising Toxoplasma gondii SAGI, MIC3 and ROP2 Using Fluorescent Protein-Reporting Vectors and Evaluation of Its Immunogenicity].

OBJECTIVE: To construct a cocktail DNA vaccine that expresses multiple genes of Toxoplasma gondii and investigate its immunogenicity in mice. METHODS: Genes for surface antigens (SAG), microneme(MIC), and rhoptry protein(ROP) were amplified from genomic DNA of T. gondii and then cloned separately into eukaryotic fluorescent protein expression vectors pShuttle-CMV-MCS-EFlα-AmCyan, pLVX-IRES-Zsgreen and pLVX-IRES-rfp, to construct expression plasmids pShuttle-SAG1, pLVX-Zsgreen-MIC3 and pLVX-rfp-ROP2. 293F cells were transfected with a combination of the three plasmids using the polyethylenimine (PEI) method. Forty-eight hours later, the expression of the three genes was observed under a fluorescence microscope. In addition, 30 C57BL/6 mice were randomized to receive intramuscular injection of saline (50 pA, group A), pShuttle+pLVX-Zsgreen+pLVX-rfp empty plasmids(2 µg/µL, 17 µL of each, group B) and pShuttle-SAG1+pLVX-Zsgreen-MIC3+ pLVX-rfp-ROP2 recombinant plasmid (2 µg/µL, 17 µL of each, group C). After 28 days, anti-T. gondii antibody in mouse serum was detected by ELISA, to evaluate the immunogenicity of the vaccine. RESULTS: The SAG1, MIC3 and ROP2 genes were amplified from the genomic DNA, with product sizes of 1, 1.1 and 1.7 kb. The eukaryotic expression plasmids pShuttle-SAG1, pLVX-Zsgreen-MIC3 and pLVX-rfp-ROP2 were constructed, and the corresponding fluorescences (blue, green and red) were observed after transfection. On day 28 after mouse vaccination, ELISA showed that the mean A(450) values for serum IgG in groups A, B and C were (0.620±0.029), (0.741±0.040) and (1.561±0.131), respectively, with the group C value being significantly higher than the others (P<0.01). CONCLUSION: The cocktail DNA vaccine comprising T. gondii SAG1, MIC3 and ROP2 shows promising immunogenicity in mice, and the fluorescent protein expression vectors are reliable tools for expression of the target genes.

Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.

BACKGROUND: Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. METHODS: Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. RESULTS: There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. CONCLUSIONS: Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process.

Protein succinylation, hepatic metabolism, and liver diseases.

Succinylation is a highly conserved post-translational modification that is processed via enzymatic and non-enzymatic mechanisms. Succinylation exhibits strong effects on protein stability, enzyme activity, and transcriptional regulation. Protein succinylation is extensively present in the liver, and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism. For instance, histone acetyltransferase 1 promotes liver glycolysis, and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism. Therefore, the effects of succinylation on hepatic glucose, amino acid, and lipid metabolism under the action of various enzymes will be discussed in this work. In addition, how succinylases regulate the progression of different liver diseases will be reviewed, including the desuccinylation activity of sirtuin 7, which is closely associated with fatty liver disease and hepatitis, and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma. In view of the diversity and significance of protein succinylation, targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.

Development of miRNA-Based Approaches to Explore the Interruption of Mosquito-Borne Disease Transmission.

MicroRNA (miRNA or miR)-based approaches to interrupt the transmission of mosquito-borne diseases have been explored since 2005. A review of these studies and areas in which to proceed is needed. In this review, significant progress is reviewed at the level of individual miRNAs, and miRNA diversification and relevant confounders are described in detail. Current miRNA studies in mosquitoes include four steps, namely, identifying miRNAs, validating miRNA-pathogen interactions, exploring action mechanisms, and performing preapplication investigations. Notably, regarding the Plasmodium parasite, mosquito miRNAs generally bind to mosquito immunity- or development-related mRNAs, indirectly regulating Plasmodium infection; However, regarding arboviruses, mosquito miRNAs can bind to the viral genome, directly modifying viral replication. Thus, during explorations of miRNA-based approaches, researchers need select an ideal miRNA for investigation based on the mosquito species, tissue, and mosquito-borne pathogen of interest. Additionally, strategies for miRNA-based approaches differ for arboviruses and protozoan parasites.

MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells.

The dysregulated microRNAs (miRNAs) are involved in diabetic retinopathy progression. Epithelial mesenchymal transition (EMT) and cell permeability are important events in diabetic retinopathy. However, the function and mechanism of miR-195 in EMT and cell permeability in diabetic retinopathy remain largely unclear. Diabetic retinopathy models were established using streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated ARPE-19 cells. Retina injury was investigated by hematoxylin-eosin (HE) staining. EMT and cell permeability were analyzed by western blotting, immunofluorescence, wound healing, and FITC-dextran assays. MiR-195 expression was detected via qRT-PCR. YY1, VEGFA, Snail1, and Smurf2 levels were detected via western blotting. The interaction relationship was analyzed via ChIP, Co-IP, or dual-luciferase reporter assay. The retina injury, EMT, and cell permeability were induced in STZ-induced diabetic mice. HG induced EMT and cell permeability in ARPE-19 cells. MiR-195, YY1, VEGFA, and Snail1 levels were enhanced, but Smurf2 abundance was reduced in STZ-induced diabetic mice and HG-stimulated ARPE-19 cells. VEGFA knockdown decreased Snail1 expression and attenuated HG-induced EMT and cell permeability. YY1 silence reduced VEGFA and Snail1 expression, and mitigated HG-induced EMT and cell permeability. YY1 could bind with VEGFA and Snail1, and it was degraded via Smurf2-mediated ubiquitination. MiR-195 knockdown upregulated Smurf2 to decrease YY1 expression and inhibited HG-induced EMT and cell permeability. MiR-195 targeted Smurf2, increased expression of YY1, VEGFA, and Snail1, and promoted HG-induced EMT and cell permeability. MiR-195 promotes EMT and cell permeability of HG-stimulated ARPE-19 cells by increasing VEGFA/Snail1 via inhibiting the Smurf2-mediated ubiquitination of YY1.

Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated. AIM: To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC. METHODS: In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated. RESULTS: Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components. CONCLUSION: Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.

Targeted drugs for systemic therapy of lung cancer with brain metastases.

Brain metastases are very common in lung cancer patients. The condition of these patients is complicated and difficult to treat, and adverse reactions following treatment can affect the nervous system, which severely reduces quality of life. Lung cancers are categorized as small cell lung cancers and non-small cell lung cancers. Patients with brain metastasis of small cell lung cancers are generally treated with brain radiotherapy and systemic chemotherapy, but stage III/IV patients with brain metastasis of non-small cell lung cancers are generally not responsive to radiotherapy or chemotherapy. With the recent development of targeted drugs, tumor molecular profile detection allows the selection of appropriate targeted drugs for adjuvant pharmacological treatment of brain metastasis in lung cancer patients. In recent years, immune checkpoint inhibitors have emerged and have been approved by the Food and Drug Administration (FDA) for the treatment of certain cancers, but their efficacy in lung cancer patients with brain metastases still needs to be confirmed. This paper focuses on highlighting drugs for targeted therapy of brain metastasis in lung cancer patients and their molecular targets and mechanisms of drug resistance.

Identification of LmUAP1 as a 20-hydroxyecdysone response gene in the chitin biosynthesis pathway from the migratory locust, Locusta migratoria.

In Locusta migratoria, we found that two chitin biosynthesis genes, UDP N-acetylglucosamine pyrophosphorylase gene LmUAP1 and chitin synthase gene LmCHS1, are expressed mainly in the integument and are responsible for cuticle formation. However, whether these genes are regulated by 20-hydroxyecdysone (20E) is still largely unclear. Here, we showed the developmental expression pattern of LmUAP1, LmCHS1 and the corresponding 20E titer during the last instar nymph stage of locust. RNA interference (RNAi) directed toward a common region of the two isoforms of LmEcR (LmEcRcom) reduced the expression level of LmUAP1, while there was no difference in the expression of LmCHS1. Meantime, injection of 20E in vivo induced the expression of LmUAP1 but not LmCHS1. Further, we found injection-based RNAi of LmEcRcom resulted in 100% mortality. The locusts failed to molt with no apolysis, and maintained in the nymph stage until death. In conclusion, our preliminary results indicated that LmUAP1 in the chitin biosynthesis pathway is a 20E late-response gene and LmEcR plays an essential role in locust growth and development, which could be a good potential target for RNAi-based pest control.

ING5 is a Potential Target for Osteosarcoma Therapy.

Osteosarcoma is one of the most common primary malignant bone tumors. The inhibitor of growth family of protein 5 has been identified as a tumor suppressor in many cancers. In this study, we confirmed the downregulation of the both inhibitor of growth family of protein 5 and messenger RNA levels in cancer tissues using Western blot and real-time polymerase chain reaction. In order to find the antitumor roles of inhibitor of growth family of protein 5, osteosarcoma cells, HOS, and MG63 were transfected with the plasmid pCDNA-3.1-inhibitor of growth family of protein 5. Overexpression of Inhibitor of growth family of protein 5 could induce apoptosis and inhibit cell proliferation in osteosarcoma cells. Furthermore, Western blot analysis showed that p-Smad2, p-Smad3, and Smad4 were increased in inhibitor of growth family of protein 5-expressing osteosarcoma cells. Our results indicated that overexpression of inhibitor of growth family of protein 5 in osteosarcoma cells induces apoptosis by activating the Smad pathway, thus proposing a promising role for inhibitor of growth family of protein 5 in treatment of patients with osteosarcoma.

Maternal exposure to TCDD during gestation advanced sensory-motor development, but induced impairments of spatial learning and memory in adult male rat offspring.

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) is an endocrine disrupting chemical (EDC) with high persistency. Even a low amount can pass the placental barrier during gestational exposure. Exposure to TCDD exposure can impair the development of the nervous system in children, leading to impaired learning ability in later-life. But the changes in neurobehavioral developments in infancy and childhood caused by TCDD are unknown. Pregnant Sprague-Dawley rats were given a consecutive daily dose of TCDD (200 or 800 ng/day/kg) or an equivalent volume of vehicle by gavage on gestational days 8-14 (GD 8-14) as the prenatal TCDD exposure model. In the offspring, early neurobehavioral development was assessed at postnatal day 5 (PND5) and eye-opening was monitored from PND10 onwards. Adult male offspring was tested by Morris Water Maze for spatial memory and learning ability evaluation. Hippocampus Nissl's staining and astrocyte GFAP immunohistochemistry were used to evaluate the activity of astrocytes. The results of the behavioral tests showed that gestational TCDD exposure induced premature motor activity and earlier eyes-opening, but lead to serious deficits of spatial memory and learning ability in the adult male offspring. Morphology and number of neurons in the hippocampus CA1 region was not affected, while the activity of astrocytes in the same region was significantly reduced. These data indicate that perinatal TCDD exposure induced premature neurobehavioral development but impaired the spatial learning and memory in adult male rat offspring. The decreased activity of astrocytes in the hippocampus may play a role in these adverse effects.