Our research reveals the critical role of the suprachiasmatic nucleus (SCN) vasoactive intestinal peptide (VIP) neurons in mediating light-induced transient forgetting. Acute exposure to bright light selectively impairs trace fear memory by activating VIP neurons in the SCN, as demonstrated by increased c-Fos expression and Ca²⁺ recording. This effect can be replicated and reversed through optogenetic and chemogenetic manipulations of SCN VIP neurons. Furthermore, we identify the SCN → PVT (paraventricular nucleus of the thalamus) VIP neuronal circuitry as essential in this process. These findings establish a novel role for SCN VIP neurons in modulating memory accessibility in response to environmental light cues, extending their known function beyond circadian regulation and revealing a mechanism for transient forgetting.
Animals ; Vasoactive Intestinal Peptide/metabolism* ; Male ; Mice ; Neurons/metabolism* ; Suprachiasmatic Nucleus/physiology* ; Light ; Mice, Inbred C57BL ; Memory/physiology* ; Fear/physiology* ; Suprachiasmatic Nucleus Neurons/metabolism* ; Optogenetics ; Proto-Oncogene Proteins c-fos/metabolism*

Renal ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI), leading to substantial morbidity and mortality. Spexin (SPX), a 14-amino acid endogenous peptide involved in metabolic regulation and immune modulation, has not yet been studied in the context of chronic treatment and renal IRI. This study evaluated the effects of exogenous SPX on renal function, histopathological changes, and molecular pathways in both IRI-induced injured and healthy kidneys. Twenty-eight male BALB/c mice were divided into four groups: control, SPX, IRI, and SPX+IRI. IRI was induced by 30 minutes of bilateral renal ischemia followed by 6 hours of reperfusion. Renal injury markers, histopathological changes, inflammatory mediators, apoptotic markers, and fibrosis-related proteins were analyzed. SPX significantly exacerbated IRI-induced kidney injury by activating the Wnt/β-catenin signaling pathway and promoting the upregulation of pro-inflammatory, pro-apoptotic, and pro-fibrotic mediators. It is noteworthy that SPX exerted more severe deleterious nephrotoxic effects in the healthy kidney compared to those observed in the IRI-induced injured kidney. These findings indicate that chronic treatment with SPX administration may have intrinsic pro-inflammatory, pro-apoptotic and fibrotic properties, raising concerns about its therapeutic potential. Further research is needed to clarify its physiological role and therapeutic implications in kidney diseases.
Animals ; Reperfusion Injury/chemically induced* ; Male ; Mice, Inbred BALB C ; Mice ; Acute Kidney Injury/metabolism* ; Kidney/blood supply* ; Peptide Hormones/adverse effects* ; Apoptosis/drug effects* ; Wnt Signaling Pathway/drug effects* ; Disease Models, Animal

OBJECTIVE: To investigate the effects of calcitonin gene-related peptide (CGRP) on autophagy in hypoxic/reoxygenated (H/R) cardiomyocytes and its relationship with the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. METHODS: The rat cardiomyocyte cell line H9c2 was routinely cultured in vitro and passaged for experiments when the cells grew to 80% fusion. (1) CGRP dosage screening experiment: the cells were divided into blank control group, H/R group and different dosages of CGRP pretreatment groups. H9c2 cells were placed in a closed hypoxia chamber for 2 hours and then reoxygenated in a conventional incubator for 12 hours to prepare the H/R model. The CGRP pretreatment groups were pretreated with 0.01, 0.1, 0.5, 1, 5, and 10 μmol/L CGRP before the modeling process. The blank control group was not given any treatment. Cell counting kit-8 (CCK-8) was used to detect the cell survival rate, and the most suitable drug dosage was screened out. (2) Intervention experiment: H9c2 cells were divided into blank control group, H/R group, CGRP+H/R group, and CGRP+PI3K target inhibitor ly294002 (LY)+H/R group. H/R group was prepared as cellular H/R model. CGRP (1 μmol/L) alone or in combination with LY (10 μmol/L) was administered to CGRP+H/R group and CGRP+LY+H/R group, respectively, prior to the preparation of cellular H/R model. The blank control group was cultured routinely without treatment. The cell survival rate was detected by CCK-8. The level of lactate dehydrogenase (LDH) release was detected by colorimetric assay. The expressions of autophagy-related proteins [autophagy effector protein Beclin-1, microtubule-associated protein 1 light chain 3-II (LC3-II), autophagy protein p62] and PI3K/Akt/mTOR signaling pathway proteins [phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR)] were detected by Western blotting. RESULTS: (1) Results of CGRP dosage screening experiment: compared with the blank control group, the cell survival rate of the H/R group decreased significantly; and after giving 0.1, 0.5, 1, 5 μmol/L CGRP for pretreatment, the cell survival rate increased significantly, and intervention effect of 1 μmol/L CGRP was the best, and the difference was statistically significant when compared with that of the H/R group [(74.23±6.18)% vs. (23.43±4.09)%, P < 0.01], so it was used as the intervention dosage for the subsequent experiment. (2) Intervention experiment results: compared with the blank control group, the cell survival rate in the H/R group was significantly reduced, the level of LDH release was significantly increased, the protein expressions of Beclin-1 and LC3-II were significantly increased, and the protein expressions of p62, p-Akt and p-mTOR were significantly reduced, indicating that the death of cardiomyocytes occurred after the treatment of H/R and was accompanied by the elevation of autophagy level, and this process was associated with the activation of PI3K/Akt/mTOR signaling pathway. Compared with the H/R group, CGRP pretreatment increased cell survival rate [(76.02±2.43)% vs. (46.15±3.29)%, P < 0.01], decreased the level of LDH release (U/L: 169.83±11.65 vs. 590.17±34.50, P < 0.01), and down-regulated the protein expressions of Beclin-1 and LC3-II [Beclin-1 protein (Beclin-1/β-actin): 1.27±0.15 vs. 1.93±0.19, LC3-II protein (LC3-II/LC3-I): 1.27±0.13 vs. 1.98±0.18, both P < 0.01], up-regulated the protein expressions of p62, p-Akt, p-mTOR [p62 protein (p62/β-actin): 0.96±0.02 vs. 0.63±0.05, p-Akt protein (p-Akt/Akt): 0.76±0.04 vs. 0.48±0.02, p-mTOR protein (p-mTOR/mTOR): 1.13±0.09 vs. 0.68±0.15, all P < 0.05], suggesting that CGRP was able to reduce the H/R-induced cardiomyocyte injury, and this process was accompanied by a decrease in the level of cellular autophagy and activation of the PI3K/Akt/mTOR signaling pathway. Compared with the CGRP+H/R group, the cell survival rate was significantly lower than that in the CGRP+LY+H/R group [(56.95±6.63)% vs. (76.02±2.43)%, P < 0.01], LDH release level was significantly higher (U/L: 436.00±27.44 vs. 169.83±11.65, P < 0.01), and the protein expressions of Beclin-1 and LC3-II were significantly up-regulated [Beclin-1 protein (Beclin-1/β-actin): 1.63±0.12 vs. 1.27±0.15, LC3-II protein (LC3-II/LC3-I): 1.61±0.13 vs. 1.27±0.13, both P < 0.01], and significantly down-regulated p62, p-Akt, and p-mTOR protein expressions [p62 protein (p62/β-actin): 0.57±0.09 vs. 0.96±0.02, p-Akt protein (p-Akt/Akt): 0.45±0.01 vs. 0.76±0.04, p-mTOR protein (p-mTOR/mTOR): 0.66±0.06 vs. 1.13±0.09, all P < 0.05], suggesting that PI3K-targeted inhibitor was able to reverse the protective effect of CGRP on H/R cells. CONCLUSIONS CGRP pretreatment attenuated H/R-induced cardiomyocyte injury, increased cell survival rate, and reduced cellular LDH release. This effect may be achieved through inhibiting the activation of PI3K/Akt/mTOR signaling pathway.
Animals ; Myocytes, Cardiac/drug effects* ; Signal Transduction/drug effects* ; Rats ; TOR Serine-Threonine Kinases/metabolism* ; Calcitonin Gene-Related Peptide/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Cell Line ; Cell Hypoxia ; Phosphatidylinositol 3-Kinases/metabolism*

Objective To investigate the role and mechanism of eukaryotic translation elongation factor 1(EEF1) family members (EEF1D,EEF1A1,and EEF1A2) in lung adenocarcinoma (LUAD) based on public databases.Methods We examined EEF1 member expression levels in human LUAD samples via The Cancer Genome Atlas in the UCSC Xena browser and the Clinical Proteomic Tumor Analysis Consortium.We analyzed the mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 and their correlations with pathological variables via the Mann-Whitney U test.The Kaplan-Meier curves were established to assess the prognostic values of EEF1D,EEF1A1,and EEF1A2.The single-sample gene set enrichment analysis algorithm was employed to explore the relationship between the expression levels of EEF1 members and tumor immune cell infiltration.Spearman and Pearson correlation analyses were performed to examine the relationship between the expression levels of EEF1 members and those of the genes in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.The immunohistochemical assay was employed to determine the expression levels of EEF1D,EEF1A1,and EEF1A2 in the LUAD tissue (n=75) and paracancer tissue (n=75) samples.Results The mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 showed significant differences between tumor and paracancer tissues (all P<0.001).The patients with high protein levels of EEF1A1 showed bad prognosis in terms of overall survival (P=0.039),and those with high protein levels of EEF1A2 showed good prognosis in terms of overall survival (P=0.012).The influence of the mRNA level of EEF1D on prognosis was associated with pathological characteristics.The expression levels of EEF1 members were significantly associated with the infiltration of various immune cells and the expression of key molecules in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.Conclusion EEF1D,EEF1A1,and EEF1A2 are associated with the progression of LUAD,serving as the candidate prognostic markers for LUAD.
Humans ; Peptide Elongation Factor 1/metabolism* ; Proteomics ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinogenesis ; Adenocarcinoma of Lung ; Lung Neoplasms ; RNA, Messenger/genetics* ; Phosphatidylinositol 3-Kinases ; Prognosis

Our previous studies have shown that calcitonin gene-related peptide (CGRP) exerts protective effects on the acute lung injury induced by oxidative stress. This study was aimed to investigate whether autophagy was involved in the protection of CGRP against oxidative stress-induced lung injury in neonatal rats. Newborn Sprague-Dawley (SD) rats were randomly divided into five groups: Control group, oxidative stress model group (Model group), Model + CGRP group, Model + CGRP + Rapamycin (an autophagy agonist) group, and Model + CGRP + LY294002 (an autophagy inhibitor) group. The model of hyperoxia-induced lung injury was established by continuous inhalation of oxygen (FiO₂ = 90%-95%) for 14 days in neonatal SD rats. Pathological changes of lung tissue were observed by hematoxylin and eosin (HE) staining, and mean linear intercept (MLI) was measured. The quantitative changes of autophagic vesicles (AV) in type II alveolar epithelial cells (AECII) were measured under the transmission electron microscope. The protein expressions of Caspase-3, Bcl-2, mTOR, and Beclin-1 in lung tissue lysates were detected by Western blot. The results showed that, compared to the Model group at the same time point, the number of AV in AECII and the expression level of Beclin-1 protein of the lung tissue were increased, while the expression level of mTOR protein was decreased, with alleviated pathological changes, reduced MLI value and Caspase-3 protein expression level, increased Bcl-2 protein expression level in the lung tissue of Model + CGRP group. In addition, we found that the protective effect of CGRP on hyperoxia-induced lung injury could be enhanced by autophagy activator Rapamycin and abolished by autophagy inhibitor LY294002. Together, these findings indicate that CGRP could attenuate hyperoxia-induced lung injury in neonatal rats by enhancing autophagy.
Acute Lung Injury/pathology* ; Animals ; Animals, Newborn ; Autophagy ; Calcitonin/metabolism* ; Calcitonin Gene-Related Peptide/metabolism* ; Caspase 3/metabolism* ; Hyperoxia/pathology* ; Lung/pathology* ; Lung Injury/prevention & control* ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; Sirolimus/pharmacology*

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is recommended by current ST-elevation myocardial infarction (STEMI) guidelines. But it has inherent defects. The present study aimed to investigate the more compatible risk stratification for Chinese patients with STEMI and to determine whether the addition of biomarkers to the Korea Acute Myocardial Infarction Registry (KAMIR) score could enhance its predictive value for long-term outcomes. METHODS: A total of 1093 consecutive STEMI patients were included and followed up 48.2 months. Homocysteine, hypersensitive C-reactive protein (hs-CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected. The KAMIR score and the GRACE score were calculated. The performance between the KAMIR and the GRACE was compared. The predictive power of the KAMIR alone and combined with biomarkers were assessed by the receiver-operating characteristic (ROC) curve. RESULTS: The KAMIR demonstrated a better risk stratification and predictive ability than the GRACE (death: AUC = 0.802 vs. 0.721, P < 0.001; major adverse cardiovascular events (MACE): AUC = 0.683 vs. 0.656, P < 0.001). It showed that the biomarkers could independently predict death [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.052 (1.000-1.104), P = 0.018; NT-pro BNP: HR = 1.142 (1.004-1.280), P = 0.021] and MACE [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.012 (1.003-1.021), P = 0.020; NT-pro BNP: HR = 1.136 (1.104-1.168), P = 0.006]. When they were used in combination with the KAMIR, the area under the ROC curve (AUC) significantly increased for death [homocysteine: AUC = 0.802 vs. 0.890, Z = 5.982, P < 0.001; hs-CRP: AUC = 0.802 vs. 0.873, Z = 3.721, P < 0.001; NT-pro BNP: AUC = 0.802 vs. 0.871, Z = 2.187, P = 0.047; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.802 vs. 0.940, Z = 6.177, P < 0.001] and MACE [homocysteine: AUC = 0.683 vs. 0.771, Z = 6.818, P < 0.001; hs-CRP: AUC = 0.683 vs. 0.712, Z = 2.022, P = 0.031; NT-pro BNP: AUC = 0.683 vs. 0.720, Z = 2.974, P = 0.003; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.683 vs. 0.789, Z = 6.900, P < 0.001]. CONCLUSION The KAMIR is better than the GRACE in risk stratification and prognosis prediction in Chinese STEMI patients. A combination of above-mentioned biomarkers can develop a more predominant prediction for long-term outcomes.
Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Humans ; Myocardial Infarction ; blood ; metabolism ; Natriuretic Peptide, Brain ; blood ; metabolism ; Peptide Fragments ; blood ; metabolism ; ROC Curve ; Registries ; Risk Factors ; ST Elevation Myocardial Infarction ; blood ; metabolism

BACKGROUND: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.METHODS: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15+6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.RESULTS: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).CONCLUSION: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.
Blood Glucose ; C-Peptide ; Diabetes, Gestational ; Drug Therapy ; Fasting ; Female ; Glucose Metabolism Disorders ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Insulin Resistance ; Metabolic Diseases ; Metabolism ; Pregnancy ; ROC Curve

OBJECTIVE: To discuss the clinical significance of antibacterial peptide LL-37 in the early diagnosis of patients with sepsis in emergency department. METHODS: Forty patients diagnosed with sepsis in the emergency department of the Affiliated Hospital of Zunyi Medical College from December 2017 to March 2018 were enrolled as sepsis group. Twenty healthy volunteers were enrolled contemporaneously in our hospital at medical center as healthy control group. Peripheral blood was collected immediately after diagnosis in sepsis group or during physical examination in healthy control group. The expression of antibacterial peptide LL-37 was determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, serum procalcitonin (PCT) and C-reactive protein (CRP) levels were determined. The differences in antibacterial peptide LL-37, PCT and CRP levels between the two groups were compared. Pearson correlation method was used to analyze the correlation between antibacterial peptide LL-37, PCT and CRP. Receiver operating characteristic (ROC) curve was drawn, and the early individually or jointly diagnostic value of each detected index for sepsis was analyzed. RESULTS: The levels of antimicrobial peptide LL-37, PCT and CRP in peripheral blood of sepsis group were significantly higher than those of healthy control group [LL-37 (μg/L): 1.34±0.69 vs. 0.10±0.06, PCT (μg/L): 46.67±39.51 vs. 0.03±0.02, CRP (mg/L): 129.68±49.83 vs. 3.16±2.85], with statistically significant differences (all P < 0.05). Pearson correlation analysis showed that the expression of antimicrobial peptide LL-37 was positively correlated with PCT and CRP levels (r₁ = 0.835, r₂ = 0.932, both P < 0.01). ROC curve analysis showed that the area under ROC curve (AUC) of LL-37, PCT and CRP for early diagnosis of sepsis was 0.885, 0.963 and 0.983, respectively, and the AUC of combined diagnosis of the three parameters was as high as 0.994, indicating that the value of combined diagnosis of sepsis was greater than that of single diagnosis; when the combined prediction probability of the three parameters was 0.92, the sensitivity was 97.5%, and the specificity was 95.0%. CONCLUSIONS Antibacterial peptide LL-37 has certain clinical value in early diagnosis of patients with sepsis, which can be used as early routine monitoring indicators for patients with early sepsis when combined with PCT and CRP.
Antimicrobial Cationic Peptides/metabolism* ; C-Reactive Protein ; Calcitonin ; Calcitonin Gene-Related Peptide ; Early Diagnosis ; Emergency Service, Hospital ; Humans ; Protein Precursors ; ROC Curve ; Sepsis/metabolism* ; Cathelicidins

OBJECTIVETo analyze the effects of acupuncture on the level of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) in adrenal gland and the content of corticosterone (CORT) in plasma in rats withchronic emotional stress anxiety, and to explore the partial action mechanism of acupuncture on anxiety disorder.

METHODSThirty-two healthy Sprague-Dawley (SD) rats, after 7 days of feeding and domestication, were randomly divided into a blank group (10 rats), a model group (11 rats) and an acupuncture group (11 rats). The rats inthe model group and acupuncture group were treated with unpredictable chronic emotional stress (CES) method toestablish the model of anxiety. Rats in the acupuncture group were treated with acupuncture at "Neiguan" (PC 6)and "Shenmen" (HT 7), once every other day, 30 minutes each time. The model establishment and treatment lasted 15 days. Rats in the blank group were treated with identical immobilization but no treatment was given. Theelevated plus maze was used to test the behavioral changes of rats with anxiety; the level of CORT in plasma wasdetected by ELISA, and the expression level of CNP and ANP in adrenal cortex and medulla was detected by immunohistochemical method.

RESULTS(1) The percentage of open-arms time in total time (OT%) in elevated plus maze in the model group was significantly lower than that in the blank group (P<0. 05); the OT% in the acupuncture group was significantly higher than that in the model group (P<0.01). (2) The content of CORT in plasma in the model group was higher than that in the blank group (P<0. 05), while that in the acupuncture group was significantly lower than that in the model group (P<0. 05). (3) The expression of ANP in adrenal medulla and cortex in the model group was lower than that in the blank group (P<0. 01), while the expression of CNP in adrenal medulla and cortex in the model group was higher than that in the blank group (P<0. 01).

CONCLUSIONThe effects of acupuncture against anxiety are likely to be related to the regulation on the expression of ANP and CNP in adrenal medulla, affecting the release of CORT and inhibition on the activity !f hypothalamic-pituitary-adrenal axis (HPA axis).

Acupuncture Therapy ; Adrenal Glands ; metabolism ; Animals ; Anxiety ; blood ; psychology ; therapy ; Atrial Natriuretic Factor ; blood ; metabolism ; Behavior, Animal ; Corticosterone ; blood ; Humans ; Male ; Natriuretic Peptide, C-Type ; blood ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological

PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
Blotting, Western ; Caffeic Acids ; Cell Line, Tumor ; Cell Proliferation ; DNA, Bacterial/analysis/genetics ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/*metabolism ; Gastric Mucosa/*metabolism/pathology ; Gastritis/pathology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/metabolism/pathology/physiopathology ; Helicobacter pylori/pathogenicity/physiology ; Humans ; NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism ; Peptide Fragments ; Phenylethyl Alcohol/analogs & derivatives ; Proto-Oncogene Proteins c-jun ; Repressor Proteins ; Transcription Factor AP-1/*biosynthesis ; Transcription Factors/*metabolism ; beta Catenin/*metabolism