Induction of apoptosis in Lewis lung carcinoma cells by an intestinal bacterial metabolite produced from orally administered ginseng protopanaxadiol saponins

The present study demonstrated that oral administration of an intestinal bacterial metabolite (M1) of protopanaxadiol-type saponin significantly inhibited the tumor growth at the implantation site after intrapulmonary implantation of Lewis lung carcinoma (LLC) cells, and suppressed the metastasis to mediastinal lymph nodes. We also investigated the inhibitory mechanism of M1 on the growth of LLC cells. M1 inhibited the proliferation of LLC cells in a concentration-dependent manner, with characteristic morphological changes at the concentration of 30 μM. Treatment of LLC cells with M1 resulted in marked elevation of the caspase-3 activity, peaking at 2 h, and a subsequent time-dependent induction of apoptosis during the period from 3 to 24 h, as evidenced by DNA fragmentation analysis. Since M1-induced growth inhibition of LLC cells was completely abrogated by the pretreatment with a specific inhibitor of caspase-3, Z-DEVD-FMK, M1 functions via the activation of caspase-3 in the process of apoptosis in LLC cells. Thus, the anti-proliferative activity of M1 against LLC cells is primarily due to the induction of apoptosis via promotion of caspase-3 activity, and this induction may lead to the anti-tumor activity in vivo

An intestinal bacterial metabolite (M1) of ginseng protopanaxadiol saponins inhibits tumor-induced neovascularization

The present study demonstrated that an intestinal bacterial metabolite (M1) of protopanaxadiol-type ginsenosides significantly inhibited the growth of implanted tumor and the intrahepatic metastasis by the implantation of a small fragment of colon 26-L5 tumor into the liver when it was administered orally. These findings indicates that M1 was effective for the inhibition of the growth and metastasis of colon26-L5 cells in addition to lung metastasis of B16-BL6 melanoma cells as have been reported previously. The conditioned medium of colon 26-L5 cellS (CM-L5) induced in vitro tube formation of hepatic sinusoidal endothelial (HSE) cells on Matrigel-coated substrates, which is considered to be an important step in the processes of tumor angiogenesis. \u27This activity of CML5 was abrogated by noncytotoxic concentrations of M1 in a concentration-dependent manner. Similarly, M1 eliminated the ability of CM-L5 to promote the migration of HSE cells concentration-dependently. These findings indicate that M1-induced inhibition of tumor growth and intrahepatic metastasis may be partly related to the suppression of tumor angiogenic responses including capillary tube formation and migration of HSE cells. 本研究では,薬用人参(Panax ginseng C.A.MEYER)のprotopanaxadiol-type ginsenosidesの主要な腸内細菌代謝物M1の経口投与は,マウス結腸癌colon 26-L5細胞の腫瘍小片を肝へ直接移植した後の移植部位での増殖と肝内移転に対して有意に抑制効果を示すことを明らかにした。この結果は,B16-BL6メラノーマ細胞による肺転移を抑制した以前の報告と同様に,co1on 26-L5細胞に対しても有効であることが示された。肝類洞内度細胞(HSE細胞)をマトリゲルをコートした基質上で,colon 26-L5細胞の培養上清(CM-L5)とともに培養すると,腫瘍血管新生の週程における重要なステップのひとつである,内度細胞の菅腔形成を誘導した。CM-L5による菅形成能は,細胞傷害性を示さない濃度範囲のM1により,濃度依存的に抑制された。同様に,CM-L5によるHSE細胞の移動能の亢進を,M1は濃度に依存して抑制した。以上,M1による結腸癌の肝における増殖及び肝内転移の抑制は,内度細胞の骨腔形成及ぴ移動能を含む血管新生反応の抑制と部分的に関係していることが示唆された

Transannular patch repair of double-outlet right ventricle, {s,d,l}, and single right coronary artery

AbstractJ Thorac Cardiovasc Surg 1999;117:622-

University Students’ Knowledge about Developmental and Intellectual Disabilities: A Questionnaire Analysis of Faculty of Education Students

This study explores the results of a questionnaire concerning faculty of education university students’ understanding of intellectual and developmental disabilities and considered how a class may change the students’ image and consciousness of disabilities. Thirty-six firstyear Faculty of Education students majoring in a special education program completed a questionnaire before and after a class to identify their image and understanding of disabilities. The results showed no change before and after the class focusing on the students’ image and understanding of disabilities. Concerning the students’ image of disabilities, the responses rated the ideas “we can live together” and “should live together” highly, which was a similar result to the preliminary research. Concerning the students’ understanding, they showed a understanding of disabilities similar to their image, and scored highly in their response to their “will to understand and interact with people with disabilities.” Therefore, the respondent’s specialty was inferred to affect their image and understanding of disabilities

A Study of the Efficacy of Lectures Incorporating the Handicap Simulation Activities in the Department of Education

本稿では，教育学部において実施した障害シミュレーションを中心とした授業の有効性について検討を行った。視覚障害，聴覚障害，肢体不自由の各領域でシミュレーションを中心とした授業を実施し，障害に対する受講前後の考えおよび自分にできると思う取り組みについて受講生にアンケートを実施した。その結果，障害に対する考えについては，自分自身の態度や行動に関する4項目および障害者に対する肯定的，積極的意見に関する4項目においてシミュレーション後の得点が有意に増加した。自分にできると思う取り組みについては，［持続的な学びと関わり］［具体的支援］［障害への配慮］のカテゴリーグループが抽出された。シミュレーションを通じて自身の意見をまとめたり，他者の意見を聞いたりすることによって知識の幅を広げたことが，自身の態度や行動に関する項目および障害者に対する肯定的，積極的な意見に関する項目の得点増加につながったと考えられるなど，一定の効果が見られた。しかし，より障害理解を促すための授業内容について引き続き検討することなどが課題として挙げられた。In the present study, the effectiveness of the class that centered on the handicap simulation executed to the students of Department of Education was examined. The class that centered on the simulation in each area of visual impairment, hearing impairment, and physical disability was executed. Afterwards, the questionnaire of the idea before and after the class to handicaps and of the approach that they would be able to do for handicaps was executed to the participant. As a result, for the idea to handicaps, the score after the simulation has increased significantly about four items concerning their attitudes and action, and four items concerning an affirmative, positive opinion to people with handicaps. On the other hand, for the approach that they would be able to do, the category group of “Continued learning and participation”, “Concrete support”, and “Consideration to handicaps” has been extracted. It was thought that having expanded the width of knowledge by integrating their own opinions through the simulation, and hearing others’ opinions led to a score increase about items concerning their attitudes and action, and an affirmative, positive opinion to people with handicaps. However, it is necessary to continue to examine the course content that can urge understanding about handicaps more

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study

Introduction Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment. Methods In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR  Results In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (− 11.6/− 5.2 mmHg, both p  Conclusion Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction