ストレス セイギョ イガク ノ カクリツ オ メザシテ : DNA チップ オ モチイタ ストレス ヒョウカ

Stress is an essential response for all organisms to adapt new, hazardous environments and is mediated by mutation, reconstitution, and transcription of distinct genes. In mammals, stress response is regulated by complex neuro-endocrine-immune systems. Recently, RNA splicing and cap-independent translation are suggested to be involved in stress responses by facilitating the synthesis of novel stress-related gene products. The human genome project and micoarray techniques make it possible to correctly evaluate complex stress response. We have developed a DNA chip specifically designed to examine the expression profile of stress-related genes in human peripheral leukocytes. This novel biomental technique is a powerful tool to simply, objectively assess stress responses in healthy individuals and patients with psychiatric disorders. The diagnostic system consisting of the DNA chip and stress bioinfomatics may provide a new insight into the pathogenesis of stress-related disorders

Studies on proliferation and differentiation of gastric epithelial cells using primary culture systems

Gastric fundic glands have a complex organization of several types of epithelial cells, including pit cells, parietal cells, neck cells, chief cells, and a variety of enteroendocrine cells. These functionally active cells come from multipotent stem cells that are found in the isthmus, and filiation and kinetics of these cells have been intensively studied in experimental animals. Transgenic mice have been introduced to study the mechanisms of cell lineage-specific and differentiation-dependent patterns of gene expression in the gastric units. Primary cultures of gastric epithelial cells from rat, dog, rabbit, and guinea pig have been used to study interactions between distinct growth factors and gastric epithelial cells, and several growth factors, including epidermal growth factor (EGF). transforming growth factor-α, hepatocyte growth factor, insulin, and insulin-like growth factor 1, have been shown to stimulate proliferation of gastric epithelial cells. These primary cultures usually requires the presence of a high concentration of fetal calf serum, and cultured cells rapidly formed a monolayer within 2-3 days. A majority of the cells (90%) was identified as pit cells. We developed a complete serum-free culture of guinea pig gastric epithelial cells. The cells maintained in our culture conditions did not exhibit mitotic activity, and a great majority of the cells was in a pre-pit cell stage. EGF stimulated cell growth and then maturation into pit cells, suggesting that this culture system may be a excellent model to study the processes of maturation of a pit cell lineage. Recently, gastric surface mucous cell lines (GSMO cells) from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene were established. A normal gastric epithelial cell line from rat gastric mucosa (RGM 1 cells) was also established. These cell lines may be useful for studying the proliferation and differentiation of a pit cell lineage

The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2

Acquisition of cell migration capacity is an early and essential process in cancer development. The aim of this study was to identify microRNA gene expression networks that induced high migration capacity. Using colon cancer HCT116 cells subcloned by transwell-based migrated cell selection, microRNA array analysis was performed to examine the microRNA expression profile. Promoter activity and microRNA targets were assessed with luciferase reporters. Cell migration capacity was assessed by either the transwell or scratch assay. In isolated subpopulations with high migration capacity, the expression levels of the miR-23b/27b/24 cluster increased in accordance with the increased expression of the short C9orf3 transcript, a host gene of the miR-23b/27b/24 cluster. E2F1-binding sequences were involved in the basic transcription activity of the short C9orf3 expression, and E2F1-small-interfering (si)RNA treatment reduced the expression of both the C9orf3 and miR-23b/27b/24 clusters. Overexpression experiments showed that miR-23b and miR-27b promoted cell migration, but the opposite effect was observed with miR-24. Forkhead box P2 (FOXP2) mRNA and protein levels were reduced by both/either miR-23b and miR-27b. Furthermore, FOXP2 siRNA treatment significantly promoted cell migration. Our findings demonstrated a novel role of the miR-23b/27b/24 cluster in cell migration through targeting FOXP2, with potential implications for the development of microRNA-based therapy targeted at inhibiting cancer migration

Daily intake of Lactobacillus gasseri CP2305 ameliorates psychological premenstrual symptoms in young women : A randomized, double-blinded, placebo-controlled study

Lactobacillus gasseri CP2305 (CP2305) ameliorates stress-induced symptoms in young adults. In this study, we evaluated the effects of CP2305 on the premenstrual symptoms of healthy young women. Fifty-six women ingested CP2305 or placebo tablets over the course of six menstrual cycles. The CP2305 group reported fewer premenstrual symptoms than the placebo group, particularly psychological symptoms, such as depressed mood and anxiety. Whereas water retention-related physical symptom scores, such as those for breast tenderness and swelling, were reduced in the placebo group, they remained unchanged in the CP2305 group. In addition, significant differences were observed in the changes from baseline levels of salivary estradiol and progesterone in the luteal phase between the two groups, resulting in sustained elevated levels of reproductive hormones in the CP2305 group. Therefore, daily intake of CP2305 tablets might improve the premenstrual psychological symptoms of healthy young women in association with changes in reproductive hormone levels

HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells

The human TRA2B gene consists of 10 exons and 9 introns and produces 5 splice isoforms (TRA2β1 to TRA2β5). TRA2B exon 2 encodes multiple premature termination codons. TRA2β1 lacks exon 2 and is translated into a functional transformer 2β (Tra2β) protein, whereas TRA2β4 contains 10 exons and works as a functional RNA. Overexpressed Tra2β and ectopic expression of TRA2β4 may be oncogenic. We found that heterogeneous nuclear ribonucleoprotein (hnRNP)A1 and hnRNPU interacted with TRA2β4 exon 2. Minigene assays revealed that hnRNPA1 facilitated inclusion of exon 2, whereas hnRNPU promoted its skipping. However, knockdown of hnRNPA1 or hnRNPU reduced both TRA2β1 and TRA2β4 levels, and overexpression of these hnRNPs increased levels of both isoforms, suggesting that hnRNPA1 and hnRNPU mainly regulate the transcription of TRA2B. In fact, hnRNPA1 and hnRNPU positively regulated the promoter activity of TRA2B. Circular dichroism analyses, electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated the presence of G-quadruplex (G4) formation in the promoter of TRA2B. Formation of G4 suppressed TRA2B transcription, whereas hnRNPA1, but not hnRNPU, interacted with the G4 to facilitate transcription. Our results suggest that hnRNPA1 may modulate TRA2B transcription through its regulation of G4 formation in its promoter in colon cancer cells

Health Benefits of Lactobacillus gasseri CP2305 Tablets in Young Adults Exposed to Chronic Stress: A Randomized, Double-Blind, Placebo-Controlled Study

Short-term administration of Lactobacillus gasseri CP2305 improves stress-associated symptoms and clinical symptoms in healthy young adults and in patients with irritable bowel syndrome, respectively. We evaluated the efficacy and health benefits of the long-term use of a tablet containing heat-inactivated, washed Lactobacillus gasseri CP2305 (CP2305) in healthy young adults. Sixty Japanese medical students (41 men and 19 women) preparing for the national examination for medical practitioners ingested CP2305-containing or placebo tablets once daily for 24 weeks. Intake of the CP2305 tablet significantly reduced anxiety and sleep disturbance relative to placebo, as quantitated by the Spielberger State-Trait Anxiety Inventory and the Pittsburgh Sleep Quality Index. Single-channel sleep electroencephalograms show that CP2305 significantly shortened sleep latency and wake time after sleep onset and increased the delta power ratio in the first sleep cycle. CP2305 also significantly lowered salivary chromogranin A levels compared with placebo. Furthermore, 16S rRNA gene sequencing of participant feces demonstrated that CP2305 administration attenuated the stress-induced decline of Bifidobacterium spp. and the stress-induced elevation of Streptococcus spp. We conclude that the long-term use of CP2305-containing tablets may improve the mental state, sleep quality, and gut microbiota of healthy adults under stressful conditions

ショクヨク ノ チョウセツ キコウ

Human disorders of food intake and body weight control are very complicated and aredifficult to treat. One cause is the disruption of physiology of controlling feeding behaviorand the other is the psychological origin.Hunger center in the lateral hypothalamus initiates feeding and satiety center in theventromedial hypothalamus stops eating. There are a number of amines, peptides,hormones and drugs which modify feeding behavior. Metabolites of macronutrients suchas glucose, fatty acids and amino acids are the signals to the hypothalamus. The liver playsa key role in controlling appetite, sending signals to the brain via vagus nerve.Recently, there has been important progress in the molecular genetics of animal obesityand leptin was discovered in 1994. More recently orexin and ghrelin have been found. Themechanism of food intake and body weight regulation has been investigated throughly butthe prboblem of obesity is not solved yet

メンタル ヘルス オ ササエル アラタナ ストレス バイオ マーカー

Stress plays an important role in both mental and physical problems. Stressful life events initiate a coordinated physiological process that is produced by interactions between the hypothalamuspituitary- adrenal axis, sympathetic nervous system, and immune system. The response to psychological stress varies considerably and depends on a wide range of environmental and genetic factors. Establishment of a new biomental tool for objectively assessing stress response is required. We focus on high-throughput analysis of gene expression using microarray system to study the complex stress responses. Alternative splicing（AS）regulates the gene expression program in response to surrounding environment. However, acute psychological stress-initiated AS events have not been documented yet. Academic examinations are one of the brief naturalistic stressors and have been shown to change gene expression in peripheral leukocytes, which is postulated to be involved in the psychological response. Using the GeneChip human exon１．０ST array, AS events of ２７ genes with splicing indices ＞１．０could be detected immediately after the examination among healthy university students. Real-time reverse transcription PCR validated the stress-initiated skipping of exon ６３ of SMG -１ that encodes a phosphatidylinositol ３-kinase-related protein kinase crucial for activations of p ５３-dependent pathways and mRNA decay system. These results indicate that AS mediated regulation of gene expression in response to brief naturalistic stressors in peripheral leukocytes, and suggest the SMG -１ splice variant as a potential biomarker for acute psychological stress

RNA Binding Proteins and Genome Integrity

Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system. Furthermore, RNA modification such as m6A methylation might also contribute to the ultraviolet-responsive DNA damage response. Accumulating evidence suggests that RNA metabolism is more deeply involved in diverse cellular functions than previously expected, and is also intricately associated with the maintenance of genome integrity. In this review, we highlight the roles of RBPs in the maintenance of genome integrity