Osteopontin-enriched formula feeding improves the T-cell-dependent humoral immune responses in infant rats.

Previous studies have shown that osteopontin (OPN) can enhance infant resistance to infection. However, the underlying mechanisms remain to be explored. Here, we studied the effects of OPN on the development and functions of immune cells in infant rats fed with OPN-enriched formula (OF) compared with regular formula (RF). After 21 days feeding, the proportion of infant rats' CD3+ T cells of lymph nodes in the OF group is significantly increased compared with the RF group. The proportion of CD4+ and CD8+ T cells of lymph nodes in the OF group is closer to the breast feeding (BF) group than to the RF group. Upon immunisation with the thymus-dependent antigen ovalbumin (OVA), the concentration of OVA-specific IgG in the OF group was significantly higher than that in the RF group. Altogether OPN-enriched infant formula feeding can promote the differentiation of CD3+ T cells and improve the T-cell-dependent humoral immune responses in infant rats.

Protein tyrosine phosphatase receptor U (PTPRU) is required for glioma growth and motility.

The membrane protein tyrosine phosphatase receptor U (PTPRU) has been shown to function as a negative regulator of adhesion and proliferation in certain cancer cell types, primarily through its dephosphorylation of ß-catenin and inhibition of subsequent downstream signaling. In the present study, we set out to characterize the role of PTPRU in glioma and found that, while the expression of full-length PTPRU protein is low in these tumors, a number of non-full-length PTPRU isoforms are highly expressed. Among these isoforms, one in particular is localized to the nucleus, and its expression is increased in glioma tissues in a manner that positively correlates with malignancy grade. Short hairpin RNA knockdown of endogenous PTPRU in human and rat glioma cell lines suppressed proliferation, survival, invasion, migration, adhesion and vasculogenic tube formation in vitro, as well as intracranial tumor progression in vivo. In addition, knocking down PTPRU reduced tyrosine phosphorylation (pY) and transcriptional activity of ß-catenin, and we were able to specifically rescue the cell migration defect by expressing a LEF1-ß-catenin fusion protein in PTPRU-depleted cells. PTPRU knockdown also led to increased tyrosine pY of the E3 ubiquitin ligase c-Cbl and to the destabilization of several focal adhesion proteins. Taken together, our findings demonstrate that endogenous PTPRU promote glioma progression through their effect on ß-catenin and focal adhesion signaling.

Notch-Rbpj signaling is required for the development of noradrenergic neurons in the mouse locus coeruleus.

The locus coeruleus (LC) is the main source of noradrenaline in the brain and is implicated in a broad spectrum of physiological and behavioral processes. However, genetic pathways controlling the development of noradrenergic neurons in the mammalian brain are largely unknown. We report here that Rbpj, a key nuclear effector in the Notch signaling pathway, plays an essential role in LC neuron development in the mouse. Conditional inactivation of Rbpj in the dorsal rhombomere (r) 1, where LC neurons are born, resulted in a dramatic increase in the number of Phox2a- and Phox2b-expressing early-differentiating LC neurons, and dopamine-ß-hydroxylase- and tyrosine-hydroxylase-expressing late-differentiating LC neurons. In contrast, other neuronal populations derived from the dorsal r1 were either reduced or unchanged. In addition, a drastic upregulation of Ascl1, an essential factor for noradrenergic neurogenesis, was observed in dorsal r1 of conditional knockout mice. Through genomic sequence analysis and EMSA and ChIP assays, a conserved Rbpj-binding motif was identified within the Ascl1 promoter. A luciferase reporter assay revealed that Rbpj per se could induce Ascl1 transactivation but this effect was counteracted by its downstream-targeted gene Hes1. Moreover, our in vitro gene transfection and in ovo electroporation assays showed that Rbpj upregulated Ascl1 expression when Hes1 expression was knocked down, although it also exerted a repressive effect on Ascl1 expression in the presence of Hes1. Thus, our results provide the first evidence that Rbpj functions as a key modulator of LC neuron development by regulating Ascl1 expression directly, and indirectly through its target gene Hes1.

ZFX regulates glioma cell proliferation and survival in vitro and in vivo.

The zinc finger transcription factor ZFX functions as an important regulator of self-renewal in multiple stem cell types, as well as a sex determinant of mammals. Moreover, ZFX expression is abnormally elevated in several cancers, and correlates with malignancy grade. To investigate its role in the pathogenesis of gliomas, we used lentivirus-mediated RNA interference (RNAi) to knockdown ZFX expression in human glioma cell lines. Our results demonstrate that ZFX plays a crucial role in glioma proliferation and survival, confirming recent reports. We also show for the first time that ZFX knockdown decreases the in vivo growth potential of U87 glioma xenografts in both subcutaneous and intracranial models in nude mice. We conclude that lentivirus-mediated RNAi targeting of ZFX may serve as a promising strategy for glioma therapy.

Inducible Prrxl1-CreER(T2) recombination activity in the somatosensory afferent pathway.

Prrxl1-CreER(T2) transgenic mice expressing tamoxifen-inducible Cre recombinase were generated by modifying a Prrxl1-containing BAC clone. Cre recombination activity was examined in Prrxl1-CreER(T2); Rosa26 reporter mice at various embryonic and postnatal stages. Pregnant mice were treated with a single dose of tamoxifen at embryonic day (E) 9.5 or E12.5, and X-gal staining was performed 2 days later. Strong X-gal staining was observed in the somatosensory ganglia (e.g., dorsal root and trigeminal ganglia) and the first central sites for processing somatosensory information (e.g., spinal dorsal horn and trigeminal nerve-associated nuclei). When tamoxifen was administered at postnatal day (P) 20 or in adulthood (P120), strong Cre recombination activity was present in the primary somatosensory ganglia, while weak Cre recombination activity was found in the spinal dorsal horn, mesencephalic trigeminal nucleus, principal sensory trigeminal nucleus, and spinal trigeminal nucleus. This mouse line provides a useful tool for exploring genes' functions in the somatosensory system in a time-controlled way.

Conditional ablation of protein tyrosine phosphatase receptor U in midbrain dopaminergic neurons results in reduced neuronal size.

Protein tyrosine phosphatase receptor U (PTPRU) is involved in midbrain patterning during early stages of development and is continuously expressed in the adult midbrain areas where dopaminergic neurons reside in. However, whether PTPRU is also involved in the maintenance and survival of midbrain dopaminergic (mDA) neurons during the late stages of development or in the adult midbrain remains largely unknown. In the present study, Ptpru was ablated by crossing a floxed Ptpru mouse strain with tyrosine hydroxylase (TH)-Cre mice that express Cre recombinase in postmitotic mDA neurons. Conditional ablation of Ptpru in postmitotic mDA neurons resulted in a reduction of somatic and nuclear size in adulthood. However, TH-immunoreactivity of Ptpru-ablated mDA neurons and their projections to the striatum appeared undisturbed. We also investigated the maintenance of several mDA neuronal markers following Ptpru ablation and found no significant changes. Taken together, these findings suggest that PTPRU is involved in regulating the neuronal size of mDA neurons and provided mechanistic insights into the development and maintenance of mDA neurons.

Characterization of cellular senescence in doxorubicin-induced aging mice.

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice. We found that the 5 mg/kg doxorubicin dose is optimal to induce cellular senescence in mice. Subsequently, using this dose, we found that doxorubicin-induced an increase in senescence-associated ß-galactosidase (SA-ß-gal) positive cells in the kidney and lipofuscin accumulation in the liver. Some markers of senescent cells (p21WAF1/CIP1, p16INK4A, and γH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment. These preliminary findings support the application of doxorubicin-induced aging mice as an animal model to evaluate the efficacy of anti-aging drug candidates.

Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9.

While screening our in-house 1072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic, and anti-aging effects, and could further lead to promising application prospects.

Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

Nicandra physalodes Extract Exerts Antiaging Effects in Multiple Models and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1.

The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese herbal medicine extracts, Nicandra physalodes extract (HL0285) was found to exhibit lifespan extension activity in Caenorhabditis elegans (C. elegans). In further experiments, HL0285 improved healthspan, enhanced stress resistance, and delayed the progression of neurodegenerative diseases in C. elegans. Additionally, it ameliorated senescence in human lung fibroblasts (MRC-5 cells) and reversed liver function damage and reduced senescence marker levels in doxorubicin- (Dox-) induced aging mice. In addition, the longevity effect of HL0285 in C. elegans was dependent on the DAF-16 and HSF-1 signaling pathways, as demonstrated by the results of the mutant lifespan, gene level, and GFP level assays. In summary, we discovered that HL0285 had an antiaging effect in C. elegans, MRC-5 cells, and Dox-induced aging mice and deserves to be explored in the future studies on antiaging agents.

DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina.

Netrin-1 and DCC are well known for their roles in neurite growth, axonal guidance, and neuronal migration. Recently, a number of studies showed that DCC is involved in the induction of apoptosis, and this proapoptotic activity can be blocked in the presence of Netrin-1. However, here, we found that DCC is required for the survival of two types of neurons selectively in the developing mouse retina where DCC is abundantly expressed. Our results showed that the DCC(-/-) retina displayed a reduced ganglion cell layer with relatively normal neuroblastic layer. Immunostaining assays revealed that in DCC(-/-) mice, initial neurogenesis within retina was unchanged while the numbers of differentiated retinal ganglion cells and displaced amacrine cells in ganglion cell layer were greatly reduced due to increased apoptosis. By contrast, other neuronal types including horizontal cells, bipolar cells, amacrine cells, photoreceptors, and Müller cells appeared normal in DCC mutant retinas. Moreover, DCC(kanga) mice that lack the intracellular P3 domain of DCC receptor displayed the same defects as DCC(-/-) mice. Thus, our findings suggest that DCC is a key regulator for the survival of specific types of neurons during retinal development and that DCC-P3 domain is essential for this developing event.

Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice.

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy.

Previous evidence has revealed that increase in intracellular levels of calcium promotes cellular senescence. However, whether calcium channel blockers (CCBs) can slow aging and extend lifespan is still unknown. In this study, we showed that verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. We also found that verapamil acted on the α1 subunit of an L-type calcium channel in C. elegans. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity. Furthermore, verapamil significantly promoted autophagy as reflected by the expression levels of LGG-1/LC3 and the mRNA levels of autophagy-related genes. In addition, verapamil could not further induce autophagy when tax-6, calcineurin gene, was knocked down, indicating that verapamil-induced lifespan extension is mediated via promoting autophagy processes downstream of calcineurin. In summary, our study provided mechanistic insights into the anti-aging effect of verapamil in C. elegans.

First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated ß-galactosidase.

Human senescence-associated ß-galactosidase (SA-ß-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell 'healthy aging' and potentially predicting the health life span of an individual. Human SA-ß-gal is an endogenous lysosomal enzyme expressed from GLB1, the catalytic domain of which is very different from that of E. coli ß-gal, a bacterial enzyme encoded by lacZ. However, existing chemical probes for this marker still lack the ability to distinguish human SA-ß-gal from ß-gal of other species, such as bacterial ß-gal, which can yield false positive signals. Here, we show a molecular design strategy to construct fluorescent probes with the above ability with the aid of structure-based steric hindrance adjustment catering to different enzyme pockets. The resulting probes normally work as traditional SA-ß-gal probes, but they are unique in their powerful ability to distinguish human SA-ß-gal from E. coli ß-gal, thus achieving species-selective visualization of human SA-ß-gal for the first time. NIR-emitting fluorescent probe KSL11 as their representative further displays excellent species-selective recognition performance in biological systems, which has been herein verified by testing in senescent cells, in lacZ-transfected cells and in E. coli-ß-gal-contaminated tissue sections of mice. Because of our probes, it was also discovered that SA-ß-gal content in mice increased gradually with age and SA-ß-gal accumulated most in the kidneys among the main organs of naturally aging mice, suggesting that the kidneys are the organs with the most severe aging during natural aging.

Erythropoietin inhibits the increase of intestinal labile zinc and the expression of inflammatory mediators after traumatic brain injury in rats.

BACKGROUND: The objective of this study was to determine the effect of erythropoietin (Epo) on the intestinal labile zinc and the inflammatory factor in rats after traumatic brain injury (TBI). METHODS: Male Sprague-Dawley rats were randomly divided into nine groups: (a) normal group; (b) sham-operation group; (c, d, e, f, and g) TBI group, killed at 1 hour, 6 hour, 24 hour, and 72 hour and 7 days postinjury, respectively; (h and i) TBI + saline and TBI + Epo, killed at 24 hour or 72 hour postinjury. Parietal brain contusion was produced by a free-falling weight on the exposed dura of the right parietal lobe. Intestinal labile zinc, the tumor necrosis factor-alpha, interleukin (IL)-8, and wet/dry weight ratio were investigated in different groups. RESULTS: The gut contains a certain amount of labile zinc in normal animals and TBI caused obviously gradual increment of intestinal liabled zinc. The levels of inflammatory mediators and the gut wet/dry weight ratio were also found to increase in the trauma group (p < 0.05). There was a highly positive correlation between the abundance of zinc fluorescence and these proinflammation factors. Epo significantly reduced the intestinal labile zinc, the inflammatory mediators, and the gut wet/dry weight ratio compared with TBI group (p < 0.05). CONCLUSIONS: Epo can protect intestine from TBI-induced injury by attenuating intestinal inflammation and labile zinc accumulation in vivo.

Lactose induced redox-dependent senescence and activated Nrf2 pathway.

Lactose is a disaccharide found in milk and thus a part of our daily food intake. Upon ingestion, it is hydrolyzed to glucose and galactose by the enzyme lactase and absorbed in the small intestine. People who suffer from lactose intolerance are unable to completely digest it due to deficiency of lactase, leading to intestinal problems such as diarrhoea, and bloating. Various studies have focused on treating these symptoms. However, the effects of lactose that diffuses passively into cells, on cellular senescence have largely remained unknown. Thus, the present study investigated the effects and mechanisms of lactose on senescence both in vitro and in vivo. The study was conducted in MRC-5 cells. The cellular senescence was estimated by determining the expression of SA-ß-gal and p16ink4a. The cell viability of MRC-5 cells was determined by the CCK-8 Assay. Activity of intracellular reactive oxygen species was estimated by measuring the levels of superoxide dismutase (SOD), glutathione (GHS), and reactive oxygen species (ROS). The mechanism of lactose on cellular senescence was explored by western blotting. We also studied the effect of lactose on the lifespan of Caenorhabditis elegans. Increased activities of SA-ß-gal and p16ink4a revealed the ability of lactose to induce senescence in MRC-5 cells. The elevated intracellular ROS level and decreased GSH and SOD levels in these cells were indicative of cellular oxidative stress induced by lactose. Furthermore, western blotting analysis of Nrf2 and mRNA expression of its downstream genes suggested the Nrf2/ARE pathway was involved in the oxidative stress induced by lactose. These results were further validated by the shortened lifespan of C. elegans after lactose supplement. Moreover, the lactose-induced senescence could be alleviated by an antioxidant, N-Acetyl-L-cysteine (NAC), both in vitro and in vivo. The present study observed a positive correlation between lactose and cellular oxidative stress, suggesting the latter to be an underlying mechanism of lactose-induced senescence.

Expression of the transcription factor GATA3 in the postnatal mouse central nervous system.

GATA binding protein 3 (GATA3) is an important regulator of central nervous system (CNS) development, but its expression pattern in the postnatal CNS has not been studied. In the present study, we examined the distribution of GATA3 mRNA in the mouse CNS at different postnatal stages by in situ hybridization. During the first 2 weeks of postnatal development, numerous GATA3-expressing cells were found in the intergeniculate leaf, ventral lateral geniculate nucleus, pretectal nucleus, nucleus of the posterior commissure, superior colliculus, inferior colliculus, periaqueductal grey, substantia nigra and raphe nuclei. Few notable changes in the profile of GATA3 expression occurred over this time period. As postnatal development progressed, however, GATA3 expression weakened, and was maintained in only a few regions of the adult CNS. Throughout the brain, we found that GATA3-expressing cells were NeuN-positive, and no colocalization with glial fibrillary acidic protein (GFAP) was observed. In the substantia nigra, GATA3 was exclusively expressed in cells of the reticulate part and some of which were found to be GABAergic. This study presents a comprehensive overview of GATA3 expression in the CNS throughout postnatal life, and the dynamics that we observed provide insights for further investigations of the roles of GATA3 in postnatal development and the maintenance of the mature CNS.

Effects of sleeve gastrectomy on lipid and energy metabolism in ZDF rats via PI3K/AKT pathway.

Sleeve Gastrectomy (SG), as the most effective bariatric surgery, has been using to chronically lose weight and control glucose metabolism in Type 2 diabetes mellitus patients. However, the underlining mechanism is still unclear. In this study, we performed SG on Zucker diabetes fatty (ZDF) rat and investigated visceral lipid metabolism and energy metabolism. After performance of SG, weight, food intake, fasting plasma glucose (FPG) and oral glucose tolerance teat (OGTT) of rats were measured. Furthermore, whole-body metabolic parameters were obtained through TSE LabMaster. Blood lipid and renal function were analyzed by serum from rats' tail vein. Furthermore, the renal genes expression was either detected by real-time PCR, while western blotting was employed to detect the AKT/PI3K proteins level in rats' kidney. Compared to control groups, body weight of ZDF rats treated with SG were significantly reduced, simultaneously with glucose homeostasis and energy metabolism improved including RER (P<0.05), energy expenditure (P<0.05) at night and activity of animal. Meanwhile, serum lipid of ZDF rats after SG was decreased, and renal function recovered. Histology analysis confirmed that the size of perirenal adipose from SD treated ZDF rats obviously decreased (P<0.001), effectively stimulating up-regulation of lipogenesis genes (P<0.05), while adipogenesis genes (P<0.05) in kidney was down-regulated. In addition, phosphorylation of PI3K (p-PI3K) and AKT (p-AKT) in rats kidney were significantly decreased in SG group (P<0.05). Weight loss, food intake, fasting plasma glucose and glucose tolerance in SG surgery rats were improved, which were coincident with energy metabolism changes. In conclusion, SG improves lipid and energy metabolism in ZDF rats model due to activating PI3K/Akt signaling pathway, which was contributed to the mechanism of bariatric surgery toward kidney.

Knockdown of protein tyrosine phosphatase receptor U inhibits growth and motility of gastric cancer cells.

Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating ß-catenin and reducing the activation of ß-catenin signaling. Here, we investigate the expression of PTPRU protein in gastric cancer cell lines, gastric cancer tissues and respective adjacent non-cancer tissues and find that the 130 kDa nuclear-localized PTPRU fragment is the main PTPRU isoform in gastric cancer cells, whereas the full-length PTPRU is relatively lowly expressed. The level of the 130 kDa PTPRU is higher in gastric cancer tissues than in adjacent non-cancer tissues. Knockdown of endogenous PTPRU in gastric cancer cells using lentivirus-delivered specific shRNA results in the attenuation of cell growth, migration, invasion and adhesion. Knockdown of PTPRU also inhibits tyrosine phosphorylation and transcriptional activity of ß-catenin as well as levels of focal adhesion proteins and lysine methylation of histone H3. These results indicate that PTPRU is required for gastric cancer progression and may serve as a potential therapeutic target.

Androglobin knockdown inhibits growth of glioma cell lines.

Globin family was famous for oxygen supply function of its members such as hemoglobin and myoglobin. With the progress of research, several members of this protein family have been proven to play roles in tumors including glioma. Androglobin (ADGB) is a recently identified member of globin family with very few studies about its function. In the present study, we show that ADGB plays an oncogene role in glioma. Lentiviral vector mediated ADGB knockdown inhibited the proliferation of glioma cell lines determined by MTT assay and colony formation assay. ADGB knockdown also increased the apoptosis of glioma cell line U251 assessed by flow cytometry. In addition, western blot showed that ADGB knockdown altered levels of several proteins related to proliferation, survival or apoptosis in U251 cells. These findings suggest ADGB is involved in the progression of glioma in vitro.