PCK2 maintains intestinal homeostasis and prevents colitis by protecting antibody-secreting cells from oxidative stress.

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.

ITGAM-mediated macrophages contribute to basement membrane damage in diabetic nephropathy and atherosclerosis.

BACKGROUND: Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive. METHODS: Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues. RESULTS: Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM. CONCLUSION: Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications.

Novel flavonoid 1,3,4-oxadiazole derivatives ameliorate MPTP-induced Parkinson's disease via Nrf2/NF-κB signaling pathway.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a complex etiology. Neuroinflammation and oxidative stress are important factors driving the progression of PD. It has been reported that 1,3,4-oxadiazole and flavone derivatives have numerous biological functions, especially in the aspect of anti-inflammatory and antioxidant. Based on the strategy of pharmacodynamic combination, we introduced 1,3,4-oxadiazole moiety into the flavonoid backbone, designed and synthesized a series of novel flavonoid 1,3,4-oxadiazole derivatives. Further, we evaluated their toxicity, anti-inflammatory and antioxidant activities using BV2 microglia. Following a comprehensive analysis, compound F12 showed the best pharmacological activity. In vivo, we induced the classical PD animal model by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57/BL6J mice. Our results showed that compound F12 ameliorated MPTP-induced dysfunction in mice. Further, compound F12 reduced oxidative stress by promoting the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inflammatory response by inhibiting the nuclear translocation of nuclear factor-κB (NF-κB) in vivo and in vitro. Meanwhile, compound F12 inhibited the mitochondrial apoptotic pathway to rescue microglia inflammation-mediated loss of dopaminergic neurons. In conclusion, compound F12 reduced oxidative stress and inflammation and could be as a potential agent for PD treatment.

Fisetin treatment alleviates kidney injury in mice with diabetes-exacerbated atherosclerosis through inhibiting CD36/fibrosis pathway.

Diabetes-related vascular complications include diabetic cardiovascular diseases (CVD), diabetic nephropathy (DN) and diabetic retinopathy, etc. DN can promote the process of end-stage renal disease. On the other hand, atherosclerosis accelerates kidney damage. It is really an urge to explore the mechanisms of diabetes-exacerbated atherosclerosis as well as new agents for treatment of diabetes-exacerbated atherosclerosis and the complications. In this study we investigated the therapeutic effects of fisetin, a natural flavonoid from fruits and vegetables, on kidney injury caused by streptozotocin (STZ)-induced diabetic atherosclerosis in low density lipoprotein receptor deficient (LDLR-/-) mice. Diabetes was induced in LDLR-/- mice by injecting STZ, and the mice were fed high-fat diet (HFD) containing fisetin for 12 weeks. We found that fisetin treatment effectively attenuated diabetes-exacerbated atherosclerosis. Furthermore, we showed that fisetin treatment significantly ameliorated atherosclerosis-enhanced diabetic kidney injury, evidenced by regulating uric acid, urea and creatinine levels in urine and serum, and ameliorating morphological damages and fibrosis in the kidney. In addition, we found that the improvement of glomerular function by fisetin was mediated by reducing the production of reactive oxygen species (ROS), advanced glycosylation end products (AGEs) and inflammatory cytokines. Furthermore, fisetin treatment reduced accumulation of extracellular matrix (ECM) in the kidney by inhibiting the expression of vascular endothelial growth factor A (VEGFA), fibronectin and collagens, while enhancing matrix metalloproteinases 2 (MMP2) and MMP9, which was mainly mediated by inactivating transforming growth factor ß (TGFß)/SMAD family member 2/3 (Smad2/3) pathways. In both in vivo and in vitro experiments, we demonstrated that the therapeutic effects of fisetin on kidney fibrosis resulted from inhibiting CD36 expression. In conclusion, our results suggest that fisetin is a promising natural agent for the treatment of renal injury caused by diabetes and atherosclerosis. We reveal that fisetin is an inhibitor of CD36 for reducing the progression of kidney fibrosis, and fisetin-regulated CD36 may be a therapeutic target for the treatment of renal fibrosis.

Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity.

BACKGROUND: NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non-apoptotic form of cell death induced by iron-dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression. METHOD: Mice were fed on MCD-diet to mimic NASH progression and gene expression in liver was analysed by RNA-seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture. RESULTS: RNA-seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD-diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD-fed mice. Scavenging of ferroptosis-linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD-diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation. CONCLUSION: Our results demonstrate an important role of ferroptosis in the progression of MCD-diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.

Identification of a crucial amino acid responsible for the loss of specifying FGFR1-KLB affinity of the iodinated FGF21.

Previous studies suggest that specific binding to the complex consisting of fibroblast growth factor receptor-1 (FGFR1) and the coreceptor beta-Klotho (KLB) is the premise for human FGF19 and FGF21 activating the downstream signaling cascades, and regulating the metabolic homeostasis. However, it was found that human FGF21 loses its ability to bind to FGFR1-KLB after iodination with Na125 I and chloramine T, whereas human FGF19 retained its affinity for FGFR1-KLB even after iodination. The molecular mechanisms underlying these differences remained elusive. In this study, we first demonstrated that an intramolecular disulfide bond was formed between cysteine-102 and cysteine-121 in FGF21, implying that the oxidation of the cysteine to cysteic acid, which may interfere with the active conformation of FGF21, did not occur during the iodination procedures, and thus ruled out the possibility of the two conserved cysteine residues mediating the loss of FGF21 binding affinity to FGFR1-KLB upon iodination. Site-directed mutagenesis and molecular modeling were further applied to determine the residue(s) responsible for the loss of FGFR1-KLB affinity. The results showed that mutation of a single tyrosine-207, but not the other five tyrosine residues in FGF21, to a phenylalanine retained the FGFR1-KLB affinity of FGF21 even after iodination, whereas replacing the corresponding phenylalanine residue with tyrosine in FGF19 did not alter its binding affinity to FGFR1-KLB, but decreased the receptor binding ability of the iodinated protein, suggesting that tyrosine-207 is the crucial amino acid responsible for the loss of specifying FGFR1-KLB affinity of the iodinated FGF21.

Antitumor effect of a short peptide on p53-null SKOV3 ovarian cancer cells.

Fibroblast growth factor-2 (FGF2) is a protein ligand, which exerts essential roles in development, angiogenesis, and tumor progression via activation of the downstream signaling cascades. Accumulating evidence has demonstrated that FGF2 is involved in the progression of ovarian cancer, providing a novel potential target for ovarian cancer therapy. In this study, we showed that FGF2 is significantly increased in ovarian tumors, and is negatively associated with the overall survival of ovarian cancer by database analysis. A short peptide obtained from a heptapeptide phage display library suppressed FGF2-induced proliferation, migration, and invasion of the p53-null epithelial ovarian cancer (EOC) cells. Further investigations revealed that the short peptide antagonized the effects of FGF2 on G0/G1 to S cell phase promotion, cyclin D1 expression, and MAPK and Akt signaling activation, which might contribute to the mechanism underlying the inhibitory effects of the short peptide on the aggressive phenotype of the ovarian cancer cells triggered by FGF2. Moreover, the short peptide might have the potentials of reversing FGF2-induced resistance to the doxorubicin via downregulation of the antiapoptotic proteins and counteracting of the antiapoptotic effects of FGF2 on p53-null EOC cells. Taken together, the short peptide targeting FGF2 may provide a novel strategy for improving the therapeutic efficiency in a subset of EOC.

Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis.

Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone from Salvia miltiorrhiza (Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition.

A Class of Disulfide Compounds Suppresses Ferroptosis by Stabilizing GPX4.

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation and has been implicated in multiple pathological conditions. Glutathione peroxidase 4 (GPX4) plays an essential role in inhibiting ferroptosis by eliminating lipid peroxide using glutathione (GSH) as a reductant. In this study, we found Ellman's reagent DTNB and a series of disulfide compounds, including disulfiram (DSF), an FDA-approved drug, which protect cells from erastin-induced ferroptosis. Mechanistically, DTNB or DSF is conjugated to multiple cysteine residues in GPX4 and disrupts GPX4 interaction with HSC70, an adaptor protein for chaperone mediated autophagy, thus preventing GPX4 degradation induced by erastin. In addition, DSF ameliorates concanavalin A induced acute liver injury by suppressing ferroptosis in a mouse model. Our work reveals a novel regulatory mechanism for GPX4 protein stability control. We also discover disulfide compounds as a new class of ferroptosis inhibitors and suggest therapeutic repurposing of DSF in treating ferroptosis-related diseases.

Impacts of Artificial Underground Reservoir on Groundwater Environment in the Reservoir and Downstream Area.

Artificial underground reservoirs have changed the hydrological cycle from its natural condition. This modification may trigger a series of negative environmental effects both at the local and regional levels. This study investigated the impact of the Wanghe artificial underground reservoir on groundwater flow and quality in the reservoir and its downstream area. Wanghe is a typical artificial underground reservoir scheme in China, which assumes the dual function of fresh-water preservation and control of seawater intrusion. The groundwater flow pattern has changed after the reservoir construction, and the water level in the reservoir rose rapidly. Evaluation of long-term groundwater level fluctuation suggested that the reservoir deprived the downstream aquifer of the runoff, which it received under the natural flow regime. A preliminary isotopic evaluation using 3H was developed to understand the groundwater flow and renewal rates in the study area. The uniform distribution of tritium levels in the reservoir indicated that the stored water was well-mixed in both horizontal and vertical directions. The intervention on groundwater circulation also made differences in groundwater renewal rates between stored and downstream water. Field investigations on groundwater nitrogen pollution showed that the construction of the artificial underground reservoir resulted in nitrate accumulation in the stored water. Agriculturally derived nitrate was the largest contributor, and NO 3 - concentration varied considerably over time due to fertilization and irrigation activities, rainfall, and denitrification. NO 3 - -N distributed homogeneously in the reservoir, which was attributed to the construction of the subsurface dam, land use pattern and artificial groundwater flow.

The oncometabolite 2-hydroxyglutarate produced by mutant IDH1 sensitizes cells to ferroptosis.

Ferroptosis is a non-apoptotic form of cell death characterized by the iron-dependent lipid peroxidation and is implicated in several human pathologies, such as tissue ischemia, neurodegeneration, and cancer. Ferroptosis appears to be high cell-context dependent and the regulation of ferroptosis by physiological or pathological conditions are unclear. Here, we report that tumor-derived IDH1 mutation sensitizes cells to ferroptosis. Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. Conversely, ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-HG promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4), a key enzyme in removing lipid ROS and ferroptosis, and promotes depletion of glutathione. Our results uncover a new role of mutant IDH1 and 2-HG in ferroptosis.

Cisplatin induces chemoresistance through the PTGS2-mediated anti-apoptosis in gastric cancer.

It has been proposed that the aberrant expressions of the classical apoptosis-related genes and the subsequent decrease of apoptosis contribute to the development of cisplatin resistance in gastric cancer. However, little is known about the correlation and the molecular regulation mechanisms of cisplatin and the apoptosis-related gene expressions. Herein, we first identified the expressions of the anti-apoptotic BCL2 and the prostaglandin-endoperoxide synthase-2 (PTGS2) genes, which were abundant in the gastric carcinoma and associated with poor patient survival, were closely related with the resistance against cisplatin. Further investigations revealed that PTGS2 served as an essential mediator involved in the developing process of the resistance against cisplatin via mediating the inhibition effects of cisplatin on BCL2 expression. Mechanistically, cisplatin induced PTGS2 expression through ROS/NF-κB pathway. In addition, PTGS2 mediated cisplatin-induced BCL2 expression and subsequent resistance to apoptosis via PGE2/EP4/MAPKs (ERK1/2, P38) axis. Analysis of the clinical specimens demonstrated that PTGS2 and BCL2 were positively correlated in human gastric cancer. Moreover, in the xenograft models, inhibition of PTGS2 by celecoxib significantly augmented the cytotoxic efficacy of cisplatin in the resistant gastric cancer via suppression of PTGS2 and BCL2 expressions regulated by ERK1/2 and P38 signal axis, suggesting PTGS2 might be employed as an adjunctive therapeutic target for reversal of the chemoresistance in a subset of cisplatin resistant gastric cancer.

Palladium-catalyzed cross-coupling of enamides with sterically hindered α-bromocarbonyls.

Palladium-catalyzed intermolecular alkylation of enamides with α-bromo carbonyls was developed. Under mild reaction conditions, various cyclic and acyclic enamides reacted well with α-bromo carbonyls to afford the corresponding multi-substituted alkene products in good yields. The coupling products could be converted into very useful γ-amino acid, δ-amino alcohol, 1,4-dicarbonyl and γ-lactam derivatives.

Equilibrium and Kinetics of Bromine Hydrolysis.

Equilibrium constants for bromine hydrolysis, K(1) = [HOBr][H(+)][Br(-)]/[Br(2)(aq)], are determined as a function of ionic strength (&mgr;) at 25.0 degrees C and as a function of temperature at &mgr; approximately 0 M. At &mgr; approximately 0 M and 25.0 degrees C, K(1) = (3.5 +/- 0.1) x 10(-)(9) M(2) and DeltaH degrees = 62 +/- 1 kJ mol(-)(1). At &mgr; = 0.50 M and 25.0 degrees C, K(1) = (6.1 +/- 0.1) x 10(-)(9) M(2) and the rate constant (k(-)(1)) for the reverse reaction of HOBr + H(+) + Br(-) equals (1.6 +/- 0.2) x 10(10) M(-)(2) s(-)(1). This reaction is general-acid-assisted with a Brønsted alpha value of 0.2. The corresponding Br(2)(aq) hydrolysis rate constant, k(1), equals 97 s(-)(1), and the reaction is general-base-assisted (beta = 0.8).

[Expression and significance of pericytes and TGF-ß in infantile parotid hemangioma].

PURPOSE: To study the expression and significance of pericytes and TGF-ß in infantile parotid hemangioma. METHODS: The expressions of pericytes and TGF-ß at protein level were examined in 76 cases of infant parotid hemangioma by strep avidin-biotin complex (SABC) immunohistochemical technique. All statistical analysis were performed using SPSS 13.0 statistical package. The relationship between the expression of pericytes and TGF-ß and clinical phase of hemangioma was analyzed by using Chi-square test. Kappa test was used to determine the relationship between pericytes and TGF-ß expression. RESULTS: The rates of positive expression of pericytes were 86.7%(13/15), 45.5%(10/22) and 51.3%(20/39) in early, middle and advanced stage of hemangioma, respectively. The rates of positive expression of TGF-ß were 33.3%(5/15), 40.9%(9/22) and 76.9%(30/39) in early, middle and advanced stage of hemangioma, respectively. There was significantly close correlation between the level of pericytes and clinical phase of hemangioma, as well as between TGF-ß expression and clinical phase of hemangioma(P<0.05). CONCLUSION: Pericytes and TGF-ß may significantly contribute to the proliferation of infantile parotid hemangioma.

[Expression of ERK and nm23-H1 in tongue squamous cell carcinoma and its relation with invasion and metastasis].

PURPOSE: To reveal the relations between expression of extracellular signal-regulated kinase (ERK) and nm23-H1 and tumor invasion and metastasis in tongue squamous cell carcinoma (TSCC). METHODS: The expression of ERK and nm23-H1 at protein level was examined in 74 cases of TSCC by strep avidin-biotin complex (SABC) immunohistochemical technique. SPSS10.0 software package was used for data analysis. RESULTS: The expression of ERK was positively related to TNM clinical stage and cervical lymph node metastasis. The expression of nm23-H1 was negatively related to TNM clinical stage and cervical lymph node metastasis. The expression of ERK had a negative correlation with the expression of nm23-H1. TSCC cases with ERK(+)/nm23-H1(-) revealed significant higher tendency to cervical lymph node metastasis than those with ERK(-)/nm23-H1(+). CONCLUSION: The expression of ERK and nm23-H1 is correlated with invasion and cervical lymph node metastasis in TSCC.

Rapid construction of a plant RNA interference expression vector for hairpin RNA-mediated targeting using a PCR-based method.

Here we describe a rapid and efficient PCR-mediated ligation protocol for constructing a plant RNA interference vector to express long hairpin RNA (hpRNA). In the protocol, four oligonucleotide primers were used and three rounds of PCRs performed. The product of the first PCR was used as a megaprimer for the second PCR to generate a chimeric molecule with a gene-specific sequence and a spacer spliced together. The chimeric product could be used as another megaprimer for the third PCR to ligate another gene-specific sequence to the other end of the spacer, but in the reverse orientation. Thus, within a few days, two gene-specific sequences could be ligated to a spacer in the antisense and sense orientations using the PCR-mediated ligation method, without reliance on restriction cleavage and DNA ligation. The ligated product could be inserted into the plant expression vector for plant transformation. The transcribed RNA formed hpRNA constructs containing sense/antisense arms for specific gene targeting. Overexpression of hpRNA constructed by a Medicago truncatula xyloglucan endotransglycosylase gene retarded the growth of transgenic M. truncatula roots.

BRAFV600E mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma.

BACKGROUND: The BRAF mutation V600E (BRAF(V600E)) is the most common genetic alteration in papillary thyroid carcinoma (PTC), while overexpression of X-linked inhibitor of apoptosis (XIAP) has been found in various tumors. Both of these events are implicated in carcinogenesis, tumor progression, recurrence, etc. There are few reports, however, of the BRAF(V600E) mutation and XIAP overexpression in PTC patients. The aim of this study was to investigate the frequency of the BRAF(V600E) mutation in PTC and its relationship to clinicopathological parameters and the expression of XIAP. METHODS: Genomic DNA was extracted from 123 paraffin-embedded PTC tumor tissue samples and amplified for analysis of the V600E mutation in exon 15 of the BRAF gene by polymerase chain reaction. XIAP expression was examined by immunohistochemical methods in 46 PTCs, 18 benign nodular goiters, and 10 Hashimoto's thyroiditis samples. RESULTS: The BRAF(V600E) mutation was found in 34.1% of PTC, and was especially prevalent in the classic type. BRAF(V600E) was significantly correlated with younger age at diagnosis (p = 0.026), tumor size (p = 0.009), and histological variants (p = 0.024). There was a trend towards association with extrathyroidal invasion (p = 0.067). By logistic regression analysis, a significant relationship was found between tumor size and the BRAF(V600E) mutation (p = 0.03). XIAP was expressed in 82.6% of PTCs, which was a higher percentage than observed in the group of benign thyroid disorders (35.7%, p < 0.001). Neither the intensity (p = 0.611) nor the extent (p = 0.723) of XIAP staining was correlated with the presence of BRAF(V600E) in PTC patients. CONCLUSIONS: These data indicate that BRAF(V600E) is associated some of the aggressive clinicopathological features of PTC including younger age at diagnosis, larger tumor size, and classic histological type, as well as also extrathyroidal invasion. XIAP-positive staining was more prevalent in PTCs than in the benign thyroid disorders. Although BRAF(V600E) and XIAP expression are commonly seen in PTC, their presence together seems unrelated.

[The expression and significance of ERK1, ERK2 gene in tongue squamous cell carcinoma].

PURPOSE: The aim of this study is to investigate the relationship between ERK1, ERK2 gene expression and tumor behavior such as invasion, metastasis in tongue squamous cell carcinoma (TSCC). METHODS: The expressions of ERK1, ERK2 at gene level were examined in 45 cases of TSCC by reverse transcriptase polymerase chain reaction(RT-PCR). Student's t test was used for data analysis using SPSS 12.0 software package. RESULTS: No correlation between the expression intensity of ERK gene and tumor pathological degree of TSCC.A significant relationship was observed between the expression intensity of ERK gene and T stage of TSCC. A significant relationship was observed between the expression intensity of ERK gene and lymphnode metastasis of TSCC. CONCLUSIONS: Activation of ERK gene may play a strong role in cervical lymph node metastasis of TSCC. Intensive expression of ERK may be an important presage marker in TSCC patient. Supported by Key Science and Technology Research Project of Liaoning Province (Grant No.2005225013-2).

[Effect of implantation and implant connection on craniofacial bone growth in Beagle dogs].

PURPOSE: To study the effects of implantation and implant connection on Beagle craniofacial bone growth. METHODS: Eight Beagle dogs were randomly divided into two groups: unconnection group (4 dogs) and connection group (4 dogs). Two implant were implanted respectively in the lateral maxilla and zygomatic bone in each dog, the contra lateral side was used as normal control. Two implant was connected in the connection group 1 month later. Student's t test was used to analyze the data using SPSS11.5 software package. RESULTS: In the unconnection group, the distance increased between implants along with craniofacial bone growth; In the connection group, the distance fixed between implants along with craniofacial bone growth. The craniofacial values revealed no significant differences in the two groups (P > 0.05). CONCLUSION: The effect of implantation is localized and no inhibition in development of craniofacial bone is noted.