Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Advance online publication
Displaying 1-9 of 9 articles from this issue
  • Yoko Hasegawa, Katsunori Kato, Kazuhiro Ogai, Chizuko Konya, Takeo Min ...
    Article type: review-article
    Article ID: 2024.01014
    Published: 2024
    Advance online publication: April 25, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    Dehydration is common in older adults and impacts their clinical outcomes. Chronic dehydration is especially important as it has been under-recognized. This scoping review aimed to summarize the available definitions of chronic dehydration to identify gaps between each definition and discuss future research needs. Four databases (Pubmed, CINAHL, Cochrane Library, Science Direct) were systematically searched for peer-reviewed articles that clearly described the definition of chronic dehydration published from inception to June 8th, 2023. Two researchers reviewed the articles independently, and any disagreement was solved upon discussion. We identified five articles with a wide range of subjects from children to older adults. Chronic dehydration was defined as a state of persistently elevated blood urea levels; weight loss ≥ 1% as a result of fluid loss; a ratio of blood urea nitrogen to creatinine > 20; serum osmolarity ≥ 295 mOsm/kg; and a dehydrated state lasting 72 hours or longer. The definition varied among studies, indicating the need to establish an international consensus on the definition of chronic dehydration.

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  • Li Jin, Huan Fang, Jie Shen, Zhigao He, Yi Li, Liang Dong, Jiali Feng, ...
    Article type: research-article
    Article ID: 2024.01012
    Published: 2024
    Advance online publication: April 24, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    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.

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  • Yiwen Jiang, Hong Liu, Lingrui Yang, Chen Wu, Feng Jiang, Yaosheng Wan ...
    Article type: research-article
    Article ID: 2024.01023
    Published: 2024
    Advance online publication: April 24, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    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.

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  • Jing Wang, Lisha Li, Jing Zhou, Xinyao Pan, Qing Qi, Hongmei Sun, Ling ...
    Article type: research-article
    Article ID: 2024.01003
    Published: 2024
    Advance online publication: April 19, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    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.

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  • Hongmei Sun, Qing Qi, Xinyao Pan, Jing Zhou, Jing Wang, Lisha Li, Daji ...
    Article type: research-article
    Article ID: 2024.01006
    Published: 2024
    Advance online publication: April 17, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    Limited studies are associated with premature ovarian insufficiency (POI)-related osteoimmune disorder currently. Bu-Shen-Ning-Xin decoction (BSNXD) displayed a favorable role in treating postmenopausal osteoporosis. However, its impact on the POI-related osteoimmune disorder remains unclear. The study primarily utilized animal experiments and network pharmacology to investigate the effects and underlying mechanisms of BSNXD on the POI-related osteoimmune disorder. First, a 4-vinylcyclohexene dioxide (VCD)-induced POI murine model was conducted to explore the therapeutical action of BSNXD. Second, we analyzed the active compounds of BSNXD and predicted their potential mechanisms for POI-related osteoimmune disorder via network pharmacology, further confirmed by molecular biology experiments. The results demonstrated that VCD exposure led to elevated follicle-stimulating hormone (FSH) levels, a 50% reduction in the primordial follicles, bone microstructure changes, and macrophage activation, indicating an osteoimmune disorder. BSNXD inhibited macrophage activation and osteoclast differentiation but did not affect serum FSH and estradiol levels in the VCD-induced POI model. Network pharmacology predicted the potential mechanisms of BSNXD against the POI-related osteoimmune disorder involving tumor necrosis factor α and MAPK signaling pathways, highlighting BSNXD regulated inflammation, hormone, and osteoclast differentiation. Further experiments identified BSNXD treatment suppressed macrophage activation via downregulating FSH receptor (FSHR) expression and inhibiting the phosphorylation of ERK and CCAAT enhancer binding proteins β. In conclusion, BSNXD regulated POI-related osteoimmune disorder by suppressing the FSH/FSHR pathway to reduce macrophage activation and further inhibiting osteoclastogenesis.

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  • Wenli Cao, Xiayan Fu, Haiyang Li, Jialu Bei, Lisha Li, Ling Wang
    Article type: review-article
    Article ID: 2024.01007
    Published: 2024
    Advance online publication: April 17, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    Tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis infection. In the world, tuberculosis is an important factor affecting women's reproductive health, which can cause reproductive tract anatomy abnormalities, embryo implantation obstacles, ovarian reserve and ovulation dysfunction, leading to female infertility. This group of women usually need to seek assisted reproductive technology to conceive. Latent tuberculosis infection during pregnancy has no clinical manifestation, but may develop into active tuberculosis, leading to adverse pregnancy outcomes. Most pregnant women do not need to be treated for latent tuberculosis infection, unless they are combined with high-risk factors for tuberculosis progress, but they need close follow-up. Early diagnosis and treatment of active tuberculosis in pregnancy can reduce the incidence rate and mortality of pregnant women and newborns, and treatment needs multidisciplinary cooperation.

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  • Satoru Mizuhashi, Azusa Miyashita, Haruka Kuriyama, Toshihiro Kimura, ...
    Article type: letter
    Article ID: 2024.01017
    Published: 2024
    Advance online publication: April 17, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    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.

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  • Hiroshi Maruta, Hong He
    Article ID: 2023.01097
    Published: 2024
    Advance online publication: April 04, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    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.

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  • Atsushi Miyashita, Masanobu Miyauchi, Fumiaki Tabuchi
    Article ID: 2024.01013
    Published: 2024
    Advance online publication: April 04, 2024
    JOURNAL FREE ACCESS ADVANCE PUBLICATION

    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.

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