Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.
{"title":"Yishen Huatan Huoxue decoction and quercetin ameliorate decidualization dysfunction in polycystic ovary syndrome: A comprehensive investigation combining clinical trial and experimental studies.","authors":"Jing Wang, Lisha Li, Jing Zhou, Xinyao Pan, Qing Qi, Hongmei Sun, Ling Wang","doi":"10.5582/ddt.2024.01003","DOIUrl":"10.5582/ddt.2024.01003","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We have established several models of infectious diseases in silkworms to explore disease-causing mechanisms and identify new antimicrobial substances. These models involve injecting laboratory-cultured pathogens into silkworms and monitoring their survival over a period of days. The use of silkworms is advantageous because they are cost-effective and raise fewer ethical concerns than mammalian subjects, allowing for larger experimental group sizes. To capitalize on these benefits, there is a growing importance in mechanizing and automating the experimental processes that currently require manual labor. This paper discusses the future of laboratory automation, specifically through the mechanization and automation of silkworm-based experimental procedures.
{"title":"The prospects of automation in drug discovery research using silkworms.","authors":"Atsushi Miyashita, Masanobu Miyauchi, Fumiaki Tabuchi","doi":"10.5582/ddt.2024.01013","DOIUrl":"10.5582/ddt.2024.01013","url":null,"abstract":"<p><p>We have established several models of infectious diseases in silkworms to explore disease-causing mechanisms and identify new antimicrobial substances. These models involve injecting laboratory-cultured pathogens into silkworms and monitoring their survival over a period of days. The use of silkworms is advantageous because they are cost-effective and raise fewer ethical concerns than mammalian subjects, allowing for larger experimental group sizes. To capitalize on these benefits, there is a growing importance in mechanizing and automating the experimental processes that currently require manual labor. This paper discusses the future of laboratory automation, specifically through the mechanization and automation of silkworm-based experimental procedures.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06Epub Date: 2024-04-24DOI: 10.5582/ddt.2024.01023
Yiwen Jiang, Hong Liu, Lingrui Yang, Chen Wu, Feng Jiang, Yaosheng Wang
Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VS-DTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management.
高血压患者和非高血压患者都会发生与高血压相关的疾病。然而,迄今为止很少有研究探讨非高血压患者的血压控制问题。这项前后对比研究旨在探讨基于视觉刺激的数字疗法(VS-DTx)对血压和心率(HR)的影响。本研究共纳入了 83 名符合条件的非高血压患者。采用 McNemar 检验和配对样本 Wilcoxon Signed Rank 检验来评估对照阶段与干预阶段(使用 VS-DTx)之间血压和心率的下降率和差异。配对相关分析用于分析两个阶段之间的相关性。研究发现,VS-DTx 阶段的收缩压(SBP)和平均动脉压(MAP)呈下降趋势(66.2% vs 49.3%;68.7% vs 55.4%)。在 VS-DTx 阶段,平均 SBP 从 114.73 mm Hg 降至 111.18 mm Hg,平均 MAP 从 87.96 mm Hg 降至 84.88 mm Hg。成对样本 Wilcoxon 检验显示,ΔSBP(Z = -3.296;P < 0.01)和ΔMAP(Z = -2.386;P < 0.05)均存在差异(Δ定义为基线与刺激后的差异)。成对相关分析显示,VS-DTx 影响了浏览数字设备阶段和 VS-DTx 阶段的 MAP 降低(r = 0.33;P < 0.01)。结果表明,VS-DTx 可能对血压(包括 SBP 和 MAP)有一定的影响。本研究初步探讨了 VS-DTx 对血压可能产生的影响,为今后的数字血压管理研究提供了一些有益的启示。
{"title":"Beneficial impact of visual stimulation-based digital therapeutics on blood pressure control in non-hypertensive individuals.","authors":"Yiwen Jiang, Hong Liu, Lingrui Yang, Chen Wu, Feng Jiang, Yaosheng Wang","doi":"10.5582/ddt.2024.01023","DOIUrl":"10.5582/ddt.2024.01023","url":null,"abstract":"<p><p>Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VS-DTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06Epub Date: 2024-04-24DOI: 10.5582/ddt.2024.01012
Li Jin, Huan Fang, Jie Shen, Zhigao He, Yi Li, Liang Dong, Jiali Feng, Tetsuya Asakawa
This study was designed to investigate the state quo of the appropriateness of alerts overrides of the medication-related clinical decision support system (MRCDSS) in China. The medication-related alerts in one hospital from Jan 2022 to Dec 2022 were acquired and sampled. Rates of alert overrides, appropriateness of alert generation and physicians' responses were observed. Total 14,612 medication-related alerts (≤ level 3) were recorded, of those, 12,659 (86.6%) alerts were overridden. The top 3 alert types were: drug and diagnosis contraindications (23.8%), drug and test value contraindications (23.3%), and compatibility issues (17.7%). Of all sampled 1,501 alerts, 80.2% of them were appropriately overridden by the physicians. The appropriate rate of alert generation was 57.9% and the inappropriate rate was 42.1%. The inappropriate rate of physicians' responses was 17.8%, and 2.0% physicians' responses were undetermined. A few medications accounted for over 10% of overrides, 88.3% of "overridden reasons" inputted by the physicians were meaningless characters or values, indicating an obvious "alert fatigue" in these physicians. Our results indicated that the overridden rate of MRCDSS in China was still high, and appropriateness of generation of alert was quite low. These data indicated that the MRCDSS currently using in China still needs constantly optimization and timely maintenance. Proper sensitivity to reduce triggering of useless alerts and generation of alert fatigue might play a vital role. We believed that these findings are helpful for better understanding the state quo of MRCDSS in China and providing useful insights for future developing and improving MRCDSS.
{"title":"Evaluation of appropriateness of alerts overrides and physicians' responses of the medication-related clinical decision support system in China, a hospital-based study.","authors":"Li Jin, Huan Fang, Jie Shen, Zhigao He, Yi Li, Liang Dong, Jiali Feng, Tetsuya Asakawa","doi":"10.5582/ddt.2024.01012","DOIUrl":"10.5582/ddt.2024.01012","url":null,"abstract":"<p><p>This study was designed to investigate the state quo of the appropriateness of alerts overrides of the medication-related clinical decision support system (MRCDSS) in China. The medication-related alerts in one hospital from Jan 2022 to Dec 2022 were acquired and sampled. Rates of alert overrides, appropriateness of alert generation and physicians' responses were observed. Total 14,612 medication-related alerts (≤ level 3) were recorded, of those, 12,659 (86.6%) alerts were overridden. The top 3 alert types were: drug and diagnosis contraindications (23.8%), drug and test value contraindications (23.3%), and compatibility issues (17.7%). Of all sampled 1,501 alerts, 80.2% of them were appropriately overridden by the physicians. The appropriate rate of alert generation was 57.9% and the inappropriate rate was 42.1%. The inappropriate rate of physicians' responses was 17.8%, and 2.0% physicians' responses were undetermined. A few medications accounted for over 10% of overrides, 88.3% of \"overridden reasons\" inputted by the physicians were meaningless characters or values, indicating an obvious \"alert fatigue\" in these physicians. Our results indicated that the overridden rate of MRCDSS in China was still high, and appropriateness of generation of alert was quite low. These data indicated that the MRCDSS currently using in China still needs constantly optimization and timely maintenance. Proper sensitivity to reduce triggering of useless alerts and generation of alert fatigue might play a vital role. We believed that these findings are helpful for better understanding the state quo of MRCDSS in China and providing useful insights for future developing and improving MRCDSS.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06Epub Date: 2024-04-04DOI: 10.5582/ddt.2023.01097
Hiroshi Maruta, Hong He
Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on "PAK1", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity. Interestingly, rapamycin, the first TOR-inhibitor, promotes melanogenesis, clearly indicating that TOR suppresses melanogenesis. However, a new TOR-inhibitor called TORin-1 no longer suppresses immune system, and blocks melanogenesis in cell culture. These observations strongly indicate that TORin-1 acts as PAK1-blockers, instead of TOR-blockers, in vivo. Thus, it is most likely that melanogenesis in cell culture could enable us to discriminate PAK1-blockers from TORblockers.
PAK1(RAC/CDC42 激活激酶 1)和 TOR(雷帕霉素靶蛋白)都是主要的致癌/老化激酶。然而,它们在我们的免疫系统中却扮演着相反的角色,即免疫系统受到 PAK1 的抑制,而需要 TOR。因此,PAK1 受体阻断剂比 TOR 受体阻断剂更能有效治疗癌症。自2015年我们从基因上发现PDGF诱导的黑色素生成依赖于 "PAK1 "以来,我们能够筛选出一系列PAK1受体阻断剂,作为黑色素生成抑制剂,最终促进长寿。有趣的是,雷帕霉素作为第一种TOR抑制剂能促进黑色素生成,这清楚地表明TOR抑制了黑色素生成。然而,一种名为 TORin-1 的新型 TOR 抑制剂不再抑制免疫系统,而且还能阻止细胞培养中的黑色素生成。这些观察结果有力地表明,TORin-1 在体内的作用是 PAK1 受体阻断剂,而不是 TOR 受体阻断剂。因此,细胞培养中的黑色素生成极有可能使我们能够区分 PAK1 受体阻断剂和 TOR 受体阻断剂。
{"title":"Rapamycin vs TORin-1 or Gleevec vs Nilotinib: Simple chemical evolution that converts PAK1-blockers to TOR-blockers or vice versa?","authors":"Hiroshi Maruta, Hong He","doi":"10.5582/ddt.2023.01097","DOIUrl":"10.5582/ddt.2023.01097","url":null,"abstract":"<p><p>Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on \"PAK1\", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity. Interestingly, rapamycin, the first TOR-inhibitor, promotes melanogenesis, clearly indicating that TOR suppresses melanogenesis. However, a new TOR-inhibitor called TORin-1 no longer suppresses immune system, and blocks melanogenesis in cell culture. These observations strongly indicate that TORin-1 acts as PAK1-blockers, instead of TOR-blockers, in vivo. Thus, it is most likely that melanogenesis in cell culture could enable us to discriminate PAK1-blockers from TORblockers.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous reports proposed the concept and criteria of epidermotropic metastatic malignant melanoma (EMMM): (a) dermal involvement equal to or broader than the epidermal involvement, (b) atypical melanocytes within the dermis, (c) thinning of the epidermis, (d) widening of the papillary dermis with an epithelial collarette, and (e) vascular invasion of atypical melanocytes. However, it remains unclear whether EMMM also involves the mucosal epithelium. In this case, the patient was diagnosed with EMMM based on the histopathological findings of the patient's multiple skin lesions and clinical course. The patient also developed metastasis to the hypopharynx. Although histopathological findings of the lesion suggested the possibility of melanoma in situ, as the lesion included atypical melanocytes in the mucosal epithelium, the clinical course supported the diagnosis of hypopharyngeal metastasis from EMMM. This case suggests that EMMM may have epitheliotropic features not only in the skin but also in the mucosa.
{"title":"Metastasis to hypopharynx from epidermotropic metastatic malignant melanoma.","authors":"Satoru Mizuhashi, Azusa Miyashita, Haruka Kuriyama, Toshihiro Kimura, Hisashi Kanemaru, Satoru Miyamaru, Sho Saeki, Satoshi Fukushima","doi":"10.5582/ddt.2024.01017","DOIUrl":"10.5582/ddt.2024.01017","url":null,"abstract":"<p><p>Previous reports proposed the concept and criteria of epidermotropic metastatic malignant melanoma (EMMM): (a) dermal involvement equal to or broader than the epidermal involvement, (b) atypical melanocytes within the dermis, (c) thinning of the epidermis, (d) widening of the papillary dermis with an epithelial collarette, and (e) vascular invasion of atypical melanocytes. However, it remains unclear whether EMMM also involves the mucosal epithelium. In this case, the patient was diagnosed with EMMM based on the histopathological findings of the patient's multiple skin lesions and clinical course. The patient also developed metastasis to the hypopharynx. Although histopathological findings of the lesion suggested the possibility of melanoma in situ, as the lesion included atypical melanocytes in the mucosal epithelium, the clinical course supported the diagnosis of hypopharyngeal metastasis from EMMM. This case suggests that EMMM may have epitheliotropic features not only in the skin but also in the mucosa.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20Epub Date: 2024-02-15DOI: 10.5582/ddt.2023.01094
Yoko Iio, Mamoru Tanaka, Hana Kozai, Yuka Aoyama, Yukihiro Mori, Manato Seguchi, Morihiro Ito
Exertional heatstroke (EHS), a severe form of exertional heat illness (EHI), is the third leading cause of death in athletes; thus, early detection and prevention of EHI can help prevent EHS, which is a life-threatening condition. This study aimed to clarify the association between the cognizance of experiencing EHI and living conditions and specific EHI symptoms among collegiate athletes. This study was conducted in October 2022 by administering a questionnaire to 237 male collegiate athletes. Of the 215 (90.7%) respondents, 197 (91.6%) provided valid responses; among them, 88 (44.7%) responded they had experienced EHI, while 109 (55.3%) had not. A history of medical examinations due to EHI, having experienced headaches during summer activities, and having read the EHI manual were factors indicating cognizance of EHI. The number of times meals containing a staple food, main dish, and side dish were eaten in a day was a factor in preventing EHI. Early detection of EHI is important for its prevention, and it is important that athletes themselves have knowledge of symptoms and can correctly self-diagnose EHI. Emphasizing the potential of a well-balanced dietary intake has the potential to prevent EHI is crucial.
{"title":"Association between the experience of exertional heat illness (EHI) and living conditions of collegiate student athletes.","authors":"Yoko Iio, Mamoru Tanaka, Hana Kozai, Yuka Aoyama, Yukihiro Mori, Manato Seguchi, Morihiro Ito","doi":"10.5582/ddt.2023.01094","DOIUrl":"10.5582/ddt.2023.01094","url":null,"abstract":"<p><p>Exertional heatstroke (EHS), a severe form of exertional heat illness (EHI), is the third leading cause of death in athletes; thus, early detection and prevention of EHI can help prevent EHS, which is a life-threatening condition. This study aimed to clarify the association between the cognizance of experiencing EHI and living conditions and specific EHI symptoms among collegiate athletes. This study was conducted in October 2022 by administering a questionnaire to 237 male collegiate athletes. Of the 215 (90.7%) respondents, 197 (91.6%) provided valid responses; among them, 88 (44.7%) responded they had experienced EHI, while 109 (55.3%) had not. A history of medical examinations due to EHI, having experienced headaches during summer activities, and having read the EHI manual were factors indicating cognizance of EHI. The number of times meals containing a staple food, main dish, and side dish were eaten in a day was a factor in preventing EHI. Early detection of EHI is important for its prevention, and it is important that athletes themselves have knowledge of symptoms and can correctly self-diagnose EHI. Emphasizing the potential of a well-balanced dietary intake has the potential to prevent EHI is crucial.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A fluorescence immunochromatography (FIC) kit was developed recently using fluorescent silica nanoparticles coated with a recombinant C-terminal fragment of the surface lectin intermediate subunit (C-Igl) of Entamoeba histolytica to establish rapid serodiagnosis of amebiasis. We further evaluated the system using serum samples from 52 Thai patients with amebiasis. Of the patients, 50 (96%) tested positive using FIC. The samples were also tested using enzyme-linked immunosorbent assay (ELISA) with C-Igl as the antigen. Two samples were negative on ELISA but positive on FIC. The correlation coefficient between the fluorescence intensity using FIC and the optical density value using ELISA was 0.5390, indicating a moderate correlation between the two tests. Serum samples from 20 patients with malaria and 22 patients with Clostridioides difficile infection were also tested using FIC. The false-positive rates were 4/20 (20%) and 1/22 (4%) in patients with malaria and C. difficile infection, respectively. Combining the data from the present study with our previous study, the sensitivity and specificity of FIC were determined to be 98.5% and 95.2%, respectively. The results of the 50 samples were studied using a fluorescence scope and a fluorescence intensity reader, and the findings were compared. Disagreements were found in only two samples showing near-borderline fluorescence intensity, indicating that the use of scope was adequate for judging the results. These results demonstrate that FIC is a simple and rapid test for the serodiagnosis of amebiasis.
{"title":"Usefulness of a new immunochromatographic assay using fluorescent silica nanoparticles for serodiagnosis of Thai patients with amebiasis.","authors":"Azumi Kakino, Urassaya Pattanawong, Napaporn Kuamsab, Tatsuya Imai, Chaturong Putaporntip, Satomi Asai, Xunjia Cheng, Somchai Jongwutiwes, Hiroshi Tachibana","doi":"10.5582/ddt.2023.01102","DOIUrl":"10.5582/ddt.2023.01102","url":null,"abstract":"<p><p>A fluorescence immunochromatography (FIC) kit was developed recently using fluorescent silica nanoparticles coated with a recombinant C-terminal fragment of the surface lectin intermediate subunit (C-Igl) of Entamoeba histolytica to establish rapid serodiagnosis of amebiasis. We further evaluated the system using serum samples from 52 Thai patients with amebiasis. Of the patients, 50 (96%) tested positive using FIC. The samples were also tested using enzyme-linked immunosorbent assay (ELISA) with C-Igl as the antigen. Two samples were negative on ELISA but positive on FIC. The correlation coefficient between the fluorescence intensity using FIC and the optical density value using ELISA was 0.5390, indicating a moderate correlation between the two tests. Serum samples from 20 patients with malaria and 22 patients with Clostridioides difficile infection were also tested using FIC. The false-positive rates were 4/20 (20%) and 1/22 (4%) in patients with malaria and C. difficile infection, respectively. Combining the data from the present study with our previous study, the sensitivity and specificity of FIC were determined to be 98.5% and 95.2%, respectively. The results of the 50 samples were studied using a fluorescence scope and a fluorescence intensity reader, and the findings were compared. Disagreements were found in only two samples showing near-borderline fluorescence intensity, indicating that the use of scope was adequate for judging the results. These results demonstrate that FIC is a simple and rapid test for the serodiagnosis of amebiasis.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The eight flavonoids, apigenin, chrysin, hesperidin, kaempferol, myricetin, quercetin, rutin and luteolin were tested for the inhibition of human parainfluenza virus type 2 (hPIV-2) replication. Three flavonoids out of the eight, kaempferol, quercetin and luteolin inhibited hPIV-2 replication. Kaempferol reduced the virus release (below 1/10,000), partly inhibited genome and mRNA syntheses, but protein synthesis was observed. It partly inhibited virus entry into the cells and virus spreading, and also partly disrupted microtubules and actin microfilaments, indicating that the virus release inhibition was partly caused by the disruption of cytoskeleton. Quercetine reduced the virus release (below 1/10,000), partly inhibited genome, mRNA and protein syntheses. It partly inhibited virus entry and spreading, and also partly destroyed microtubules and microfilaments. Luteolin reduced the virus release (below 1/100,000), largely inhibited genome, mRNA and protein syntheses. It inhibited virus entry and spreading. It disrupted microtubules and microfilaments. These results indicated that luteolin has the most inhibitory effect on hPIV-2 relication. In conclusion, the three flavonoids inhibited virus replication by the inhibition of genome, mRNA and protein syntheses, and in addition to those, by the disruption of cytoskeleton in vitro.
{"title":"Inhibitory effects of kaempferol, quercetin and luteolin on the replication of human parainfluenza virus type 2 in vitro.","authors":"Kae Sakai-Sugino, Jun Uematsu, Hidetaka Yamamoto, Sahoko Kihira, Mitsuo Kawano, Miwako Nishio, Masato Tsurudome, Hidehisa Sekijima, Myles O'Brien, Hiroshi Komada","doi":"10.5582/ddt.2023.01099","DOIUrl":"10.5582/ddt.2023.01099","url":null,"abstract":"<p><p>The eight flavonoids, apigenin, chrysin, hesperidin, kaempferol, myricetin, quercetin, rutin and luteolin were tested for the inhibition of human parainfluenza virus type 2 (hPIV-2) replication. Three flavonoids out of the eight, kaempferol, quercetin and luteolin inhibited hPIV-2 replication. Kaempferol reduced the virus release (below 1/10,000), partly inhibited genome and mRNA syntheses, but protein synthesis was observed. It partly inhibited virus entry into the cells and virus spreading, and also partly disrupted microtubules and actin microfilaments, indicating that the virus release inhibition was partly caused by the disruption of cytoskeleton. Quercetine reduced the virus release (below 1/10,000), partly inhibited genome, mRNA and protein syntheses. It partly inhibited virus entry and spreading, and also partly destroyed microtubules and microfilaments. Luteolin reduced the virus release (below 1/100,000), largely inhibited genome, mRNA and protein syntheses. It inhibited virus entry and spreading. It disrupted microtubules and microfilaments. These results indicated that luteolin has the most inhibitory effect on hPIV-2 relication. In conclusion, the three flavonoids inhibited virus replication by the inhibition of genome, mRNA and protein syntheses, and in addition to those, by the disruption of cytoskeleton in vitro.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20Epub Date: 2024-02-20DOI: 10.5582/ddt.2023.01092
Shanshan Chen, Linqi Ouyang, Lian Li, Yuyang Xiao, Shengfeng Wang
To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.
{"title":"PD-1/PD-L1 inhibitors associated hypophysitis: An analysis from the FAERS database and case reports.","authors":"Shanshan Chen, Linqi Ouyang, Lian Li, Yuyang Xiao, Shengfeng Wang","doi":"10.5582/ddt.2023.01092","DOIUrl":"10.5582/ddt.2023.01092","url":null,"abstract":"<p><p>To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.</p>","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}