Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-α and PPAR expression

AbstractGlucose concentration may be an important factor in breast cancer cell proliferation, and the prevalence of breast cancer is high in diabetic patients. Leptin may also be an important factor since plasma levels of leptin correlated with TNM staging for breast cancer patients. The effects of glucose and leptin on breast cancer cell proliferation were evaluated by examining cell doubling time, DNA synthesis, levels of cell cycle related proteins, protein kinase C (PKC) isozyme expression, and peroxisome proliferator-activated receptor (PPAR) subtypes were determined following glucose exposure at normal (5.5 mM) and high (25 mM) concentrations with/without leptin in MCF-7 human breast cancer cells. In MCF-7 cells, leptin and high glucose stimulated cell proliferation as demonstrated by the increases in DNA synthesis and expression of cdk2 and cyclin D1. PKC-α, PPARγ, and PPARα protein levels were up-regulated following leptin and high glucose treatment in drug-sensitive MCF-7 cells. However, there was no significant effect of leptin and high glucose on cell proliferation, DNA synthesis, levels of cell cycle proteins, PKC isozymes, or PPAR subtypes in multidrug-resistant human breast cancer NCI/ADR-RES cells. These results suggested that hyperglycemia and hyperleptinemia increase breast cancer cell proliferation through accelerated cell cycle progression with up-regulation of cdk2 and cyclin D1 levels. This suggests the involvement of PKC-α, PPARα, and PPARγ

Cooperation in Repeated Prisoner’s Dilemma with Outside Options

経済学 / EconomicsIn many repeated interactions, repetition is not guaranteed but instead must be agreed upon. We formulate a model of voluntary repetition by introducing outside　options to a repeated Prisoner’s Dilemma and investigate how the structure of outside options affects the sustainability of mutual cooperation. When the outside　option is deterministic and greater than the value of mutual defection, the lower bound of the discount factors that sustain repeated cooperation is greater than the　one for ordinary repeated Prisoner’s Dilemma, making cooperation more difficult. However,stochastic outside options with the same mean may reduce the lower　bound of discount factors as compared to the deterministic case. This is possible when the stochasticity of the options increases the value of the cooperation phase　more than the value of the punishment phase. Necessary and sufficient conditions for this positive effect are given under various option structures.JEL Classification Codes: C73http://www.grips.ac.jp/list/jp/facultyinfo/yasuda_yosuke

iPSC screening for drug repurposing identifies anti‐RNA virus agents modulating host cell susceptibility

RNAウイルスの感染を阻害する既存薬の同定 --複数の異なるRNAウイルスに対して宿主細胞の感受性を下げることにより感染を抑制する薬剤--. 京都大学プレスリリース. 2021-04-07.iPS cells in drug screenings for COVID-19. 京都大学プレスリリース. 2021-04-07.Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re‐emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad‐spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human‐induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti‐RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS‐CoV‐2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS‐CoV‐2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS‐CoV‐2 into host cells. These findings suggest that the identified FDA‐approved drugs can modulate host cell susceptibility against RNA viruses

フィジカルイグザミネーション ヲ モチイタ ロウネン リンショウ カンゴロン ジッシュウ 2 ノ ガクシュウ コウカ

目的 本研究では老年看護学実習IIにおいて,学生がフィジカルイグザミネーションでどのような学びを習得しているのかを明らかにするとともに,実習までの他領域実習経験数に応じた学びの特徴を明らかにすることを目的とした.方法 A大学の老年臨床看護論実習IIでは実習初日の患者の状態・状況把握において,カルテを見ることなく学生自身の五感を駆使して情報を得る方法を導入している.A大学における老年臨床看護論実習IIを受講した学生59名を対象に,この手法を用いての実習の学びのレポートに対しテキスト分析を行った.結果 回収されたレポートは39名分(回収率66.1%)であった.テキスト分析の結果,対象の約1/4の使用にあたる9個以上の頻度で出現した単語は31個であった.単語同士の関係の深さより学びの内容を集約した結果,【実際−考える】,【カルテ−自分−五感−大切】,【患者−知る−必要】,【情報−できる−ない】の4つのグループが抽出された.これにより,学生は対象のアセスメントに必要な情報の構成を考え,情報収集の手段を考え,手順を考えていく過程の中で,対象の現状を理解するために必要な知識の大切さを学び,対象のもてる力を実際に関わって把握していく難しさと大切さを学んだことが明らかとなった.また,老年臨床看護論実習IIまでに経験した他領域の臨床看護学実習数を「初期:0回～ 1回」「中期:2回～ 6回」「後期:7回～ 8回」とした場合,後期群は「先入観」「情報収集する」「接する」の記述が多いことが示され,実習後期の学生においては先入観なく高齢者本来の姿を見ることができたという学びが明らかとなった.Objectives The purpose of this study was to clarify what to learn by a physical examination in gerontological nursing practice,we determine whether their learning is characteristic by the number of past training experience. Methods University A makes the five senses of student oneself act without watching a clinical record on the training first day and obtains information.In 59 students who attended clinical training of gerontorogical nursing practice in University A,we performed a text assay in nalyzed a text of the learning that we obtained using this technique. Results/Discussion The collected report was for 39 peoples(66.1% of recover rate).As a result of text analysis,the word that appeared at frequency nine or more was 31.We found what four groups of [Actually- Think],[Clinical record- Oneself─The five senses-Important],[Patients-Know- Need],[Information-Possibility- Impossibility] were done when we compiled a relevant word.Students learned importance of necessary knowledge through experience,it is about what kind of information is necessary,about how you gather information,about what do you gather information from.And the student learned importance and difficulty to understand what they can do.The latter term group of gerontorogical nursing practice was able to watch the true figure of elderly people without a preconception

Neurocytotoxic effects of iron-ions on the developing brain measured in vivo using medaka (Oryzias latipes), a vertebrate model

Purpose: Exposure to heavy-ion radiation is considered a critical health risk on long-term space missions. The developing central nervous system (CNS) is a highly radiosensitive tissue; however, the biological effects of heavy-ion radiation, which are greater than those of low-linear energy transfer (LET) radiation, are not well studied, especially in vivo in intact organisms. Here, we examined the effects of iron-ions on the developing CNS using vertebrate organism, fish embryos of medaka (Oryzias latipes)

Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5

Sox9 is a transcription factor of the SRY family required for several steps of chondrogenesis. It activates the expression of various chondrocyte-specific genes, but the mechanisms and role of cofactors involved in Sox9-regulated gene transcription are not fully understood. Here, we report on the characterization of a Tat interactive protein-60 (Tip60) as Sox9-associated protein identified in a yeast two-hybrid screen. Both in vitro and in vivo assays confirmed the specificity of interactions between Sox9 and Tip60 including the existence of an endogenous complex containing both polypeptides in chondrocytes. Gel shift assays showed the presence of a complex containing Sox9, Tip60 and the DNA of an enhancer region of the Col2a1 promoter. Reporter assays using a Col2a1 promoter with multimerized Col2a1 Sox9-binding sites indicated that Tip60 enhanced the transcriptional activity of Sox9. A larger Col2a1 promoter showed that Tip60 increased the activity of this promoter in the presence of both Sox9 and Sox5. Ectopic expression of Sox9 and transient-cotransfection with Tip60 in COS7 cells showed a more diffuse subnuclear colocalization, suggesting changes in the chromatin structure. Chromatin immunoprecipitation assays showed that Tip60, Sox9 and Sox5 associated with the same Col2a1 enhancer region. Consistent with a role of Tip60 in chondrogenesis, addition of Tip60 siRNA to limb-bud micromass cultures delayed chondrocyte differention. Tip60 enhances acetylation of Sox9 mainly through K61, 253, 398 residues; however, the K61/253/398A mutant of Sox9 still exhibited enhanced transcriptional activity by Tip60. Our results support the hypothesis that Tip60 is a coactivator of Sox9 in chondrocytes

Real-world evidence of the impact of obesity on residual teeth in the Japanese population : A cross-sectional study

Background:Tooth loss is associated with nutritional status and significantly affects quality of life, particularly in older individuals. To date, several studies reveal that a high BMI is associated with tooth loss. However, there is a lack of large-scale studies that examined the impact of obesity on residual teeth with respect to age and tooth positions.Objective:We assessed the impact of obesity on the number and position of residual teeth by age groups using large scale of Japanese database.Methods:This was a cross-sectional study of 706150 subjects that were included in the database that combined the data from health insurance claims and health check-up, those lacking information about BMI, HbA1c level, smoking status, and the number of residual teeth were excluded. Thus, a total of 233517 aged 20-74 years were included. Subjects were classified into 4 categories based on BMI, and the number of teeth was compared between age-groups. The percentage of subjects with residual teeth in each position was compared between groups with obesity (BMI ≥25.0 kg/m2) and non-obesity. Logistic regression analysis was performed to clarify whether obesity predicts having <24 teeth.Results:Higher BMI was associated with fewer teeth over 40s (P for trend <0.0001 when <70s). Obesity was associated with the reduction of residual teeth in the maxillary; specifically, the molars were affected over the age 30. Smoking status further affected tooth loss at positions that were not affected by obesity alone. After adjusting for age, sex, smoking status, and HbA1c ≥6.5%, obesity remained an independent predictive factor for having <24 teeth (ORs: 1.35, 95% CIs: 1.30-1.40).Conclusions:We found that an increase in BMI was associated with a decrease in the number of residual teeth from younger ages independently of smoking status and diabetes in the large scale of Japanese database

GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination

RAD51 is a key factor in homologous recombination (HR) and plays an essential role in cellular proliferation by repairing DNA damage during replication. The assembly of RAD51 at DNA damage is strictly controlled by RAD51 mediators, including BRCA1 and BRCA2. We found that human RAD51 directly binds GEMIN2/SIP1, a protein involved in spliceosome biogenesis. Biochemical analyses indicated that GEMIN2 enhances the RAD51–DNA complex formation by inhibiting RAD51 dissociation from DNA, and thereby stimulates RAD51-mediated homologous pairing. GEMIN2 also enhanced the RAD51-mediated strand exchange, when RPA was pre-bound to ssDNA before the addition of RAD51. To analyze the function of GEMIN2, we depleted GEMIN2 in the chicken DT40 line and in human cells. The loss of GEMIN2 reduced HR efficiency and resulted in a significant decrease in the number of RAD51 subnuclear foci, as observed in cells deficient in BRCA1 and BRCA2. These observations and our biochemical analyses reveal that GEMIN2 regulates HR as a novel RAD51 mediator