Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Volume 17, Issue 3
Displaying 1-10 of 10 articles from this issue
Review
  • Chan Hum Park, Jeong Sook Noh, Jin Pyeong Jeon, Takako Yokozawa
    Article type: review-article
    2023 Volume 17 Issue 3 Pages 151-156
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: May 27, 2023
    JOURNAL FREE ACCESS

    Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22phox. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-β1, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.

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  • Jun Zhu, Jiaxi Jin, Qing Qi, Lisha Li, Jing Zhou, Liwen Cao, Ling Wang
    Article type: review-article
    2023 Volume 17 Issue 3 Pages 157-169
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: June 25, 2023
    JOURNAL FREE ACCESS

    The steady-state gut microbiome not only promotes the metabolism and absorption of nutrients that are difficult to digest by the host itself, but also participates in systemic metabolism. Once the dynamic balance is disturbed, the gut microbiome may lead to a variety of diseases. Recurrent pregnancy loss (RPL) affects 1-2% of women of reproductive age, and its prevalence has increased in recent years. According to the literature review, the gut microbiome is a new potential driver of the pathophysiology of recurrent abortion, and the gut microbiome has emerged as a new candidate for clinical prevention and treatment of RPL. However, few studies have concentrated on the direct correlation between RPL and the gut microbiome, and the mechanisms by which the gut microbiome influences recurrent miscarriage need further investigation. In this review, the effects of the gut microbiome on RPL were discussed and found to be associated with inflammatory response, the disruption of insulin signaling pathway and the formation of insulin resistance, maintenance of immunological tolerance at the maternal-fetal interface due to the interference with the immune imbalance of Treg/Th17 cells, and obesity.

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  • Akihiro Matsumoto, Masahiro Murakami
    Article type: review-article
    2023 Volume 17 Issue 3 Pages 170-176
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: May 27, 2023
    JOURNAL FREE ACCESS

    The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations. However, harmful solvents must be used to produce certain formulations. For instance, methylene chloride has been used in the fabrication of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) microspheres. This review highlights the latest advances in the strategy of PLA or PLGA microsphere production from non-halogenated solvents and describes advantages and limitations of these methods. The study also discusses the development of dry fabrication techniques for microsphere fabrication and the positioning of conventional and dry fabrication in the containment concept for workers' safety.

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  • Meirong Wang, Juan Qi, Yujuan Liu
    Article type: review-article
    2023 Volume 17 Issue 3 Pages 177-182
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: June 16, 2023
    JOURNAL FREE ACCESS

    The coronavirus disease 2019 (COVID-19) vaccines have been shown to be effective in protecting people from severe disease progression, hospitalisation and death. However, a wide range of side effects have been reported worldwide. New onset or flare-up of autoimmune hepatitis (AIH) is an extremely rare adverse event following COVID-19 vaccination, with the majority of cases presenting with mild symptoms. Unfortunately, there have been cases of fatal complications. In this mini-review, we have summarised the clinical characteristics of a total of 35 currently reported cases of AIH after COVID-19 vaccination and suggest that patients with autoimmune diseases may be at higher risk of developing AIH after vaccination.

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Original Article
  • Hiroyuki Tanaka, Mitsutoshi Satoh, Masaki Takigawa, Toshihisa Onoda, T ...
    Article type: research-article
    2023 Volume 17 Issue 3 Pages 183-190
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: June 16, 2023
    JOURNAL FREE ACCESS

    The development of new anti-HIV drugs and advances in antiretroviral therapy (ART) regimens have enabled longer and more effective treatments in people living with HIV (PLWH). However, the aging of PLWHs is another issue that needs to be addressed. In addition to ART, many PLWHs frequently receive medications for various comorbidities. However, real-world data on the occurrence of adverse events in PLWHs and their causative drugs are rare. Therefore, this study aimed to clarify the characteristics of adverse event reports among PLWHs in Japan. PLWH cases with adverse events were comprehensively searched and analyzed using the Japanese Adverse Drug Event Report database (JADER). Despite changes in guideline-recommended ART regimens, anti-HIV drugs were the main cause of adverse events in PLWHs throughout the study period. However, considerable variations have been observed in the reporting rate of anti-HIV drug classes registered as causative drugs in JADER, especially for anchor drugs. In other words, the reporting rate of integrase strand transfer inhibitors has increased in recent years, while that of protease inhibitors and non-nucleoside reverse transcriptase inhibitors has decreased. Immune reconstitution inflammatory syndrome was the most reported adverse event and was frequently noticed by healthcare providers managing patients with HIV infections. The trends in adverse event reports for female and older patients differed from those for the overall population. This study may provide insights that can help in the establishment of optimal management strategies for PLWHs.

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  • Mo Zhang, Zhi Wei, Hongbo Zhao, Sai Zhang, Jing Wu, Jing Zhou, Yan Wan ...
    Article type: research-article
    2023 Volume 17 Issue 3 Pages 191-200
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: March 09, 2023
    JOURNAL FREE ACCESS

    The majority of cervical cancer cases are contributed to chronic infection with high-risk human papillomavirus (HPV), while only a fraction of infected women finally develop cancer. It is suggested that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A), a type of mRNA editing enzyme, may be involved in the development and progression of HPV-related tumors. This study aimed to explore the role and potential mechanisms of APOBEC3A in cervical cancer. First, the expression levels, prognostic values and genetic alterations of APOBEC3A in cervical cancer were explored using various bioinformatics tools and databases. Then, functional enrichment analyses were performed. Finally, genetic polymorphisms (rs12157810 and rs12628403) of APOBEC3A were genotyped in our clinical sample of 91 cervical patients. The associations between APOBEC3A polymorphisms and clinical characteristics as well as patient overall survival were further evaluated. Compared with normal tissues, the expression level of APOBEC3A was significantly elevated in cervical cancer. High expression of APOBEC3A had better survival compared with the low expression group. The immunohistochemistry results showed that the expression of APOBEC3A protein was localized in the nucleus. APOBEC3A expression level in cervical and endocervical cancer (CESC) was negatively correlated with the infiltration level of cancer-associated fibroblasts, and positively correlated with the infiltration level of gamma delta T cells. No association was observed between APOBEC3A polymorphisms and patient survival. The expression of APOBEC3A was significantly higher in cervical cancer tissues, while high expression was associated with better prognosis in cervical cancer patients. APOBEC3A has the potential of being used in prognostic evaluation in cervical cancer patients.

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  • Dianis Wulan Sari, Takeo Minematsu, Mikako Yoshida, Aya Kitamura, Sana ...
    Article type: research-article
    2023 Volume 17 Issue 3 Pages 201-208
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: May 11, 2023
    JOURNAL FREE ACCESS

    Since itching without rash frequently among older adults' population, study about skin properties of itching without rash is important to develop prevention methods. Therefore, this study explored the skin properties related to itching without rash and the factors associated with them. A correlation, predictive designs study was conducted at Indonesian Long-term Care (LTC) facilities. Skin properties including skin barrier function and skin inflammation were examined by photographs (macroscopic and microscopic), stratum corneum (SC) hydration, skin Potential of Hydrogen (pH), and skin blotting. Itching experience and skincare behavior were obtained by questionnaire. The itching-related skin properties and associated factors were analyzed. A total of 405 residents participated in this study, with mean age was 74 years. The prevalence of itching on the whole body was 69.1%, and 50.3% of those manifesting itching on the left forearm involved itching without macroscopic abnormalities (itching without rash). SC hydration, skin pH, albumin and nerve growth factor β (NGFβ) were associated with itching without rash (p = 0.007, 0.012, < 0.001, and < 0.001, respectively). Additionally, factors associated with skin properties were age, sex, sun exposure experience, skincare, and hygiene care in the linear regression analysis. Measurement of skin biomarkers using skin blotting was a possible objective measurement of itching skin properties without rash regardless of the environmental condition.

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Brief Report
  • Daisuke Miyazawa, Kinari Suzuki, Hikari Sato, Natsumi Katsurayama, Tom ...
    Article type: brief-report
    2023 Volume 17 Issue 3 Pages 209-213
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: May 27, 2023
    JOURNAL FREE ACCESS

    Docosahexaenoic acid (DHA; 22:6n-3), an n-3 polyunsaturated fatty acid, has various important roles in brain functions. Nitric oxide (NO) produced by neuronal NO synthase (nNOS) and Ca2+/calmodulindependent protein kinase II (CaMKII) is also involved in brain functions. We investigated the influence of DHA on nNOS and CaMKII protein expression in differentiated NG108-15 cells. NG108-15 cells were seeded in 12-well plates, and after 24 h, the medium was replaced with Dulbecco's modified Eagle's medium containing 1% fetal bovine serum, 0.2 mM dibutyryl cyclic adenosine monophosphate and 100 nM dexamethasone as differentiation-inducing medium. When cells were cultured in differentiation-inducing medium, neurite-like outgrowths were observed on days 5 and 6. However, no significant difference in morphology was observed in cells with or without DHA treatment. With or without DHA addition, nNOS protein expression was increased on days 5 and 6 compared with day 0. This increase tended to be enhanced by DHA. CaMKII protein expression did not change after differentiation without DHA, but was significantly increased on day 6 compared with day 0 with DHA addition. These data indicate that DHA is involved in brain functions by regulating CaMKII and nNOS protein expression.

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Correspondence
  • Motoki Inoue, Kazuhiko Nakadate, Mami Oosaki, Mikio Shirota, Takeo Yas ...
    2023 Volume 17 Issue 3 Pages 214-216
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: May 23, 2023
    JOURNAL FREE ACCESS

    The interruption of anticancer infusion processes in patients undergoing chemotherapy may affect their quality of life and the efficacy and safety of the therapy. We experienced several interruptions of carboplatin infusion in multiple patients receiving paclitaxel-carboplatin combination therapy. Therefore, we investigated the causes of these interruptions. The filter and catheter surfaces were evaluated by scanning electron microscopy. Moreover, using a texture analyzer, the mechanical strengths of catheter-attached syringes were compared pre- and post-administration. We observed that the syringe pushing force requirement was higher following dripping failure. However, precipitates were not evident on the filter surfaces, regardless of the dripping failure route. In this case, some of the drug adhered to the catheters' surfaces and interrupted the carboplatin titration. Consequently, in patients receiving combination therapy with paclitaxel and carboplatin, and experiencing interruptions in carboplatin infusion, attention should be paid to the catheter.

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Letter to the Editor
  • Yuki Ohya, Shintaro Hayashida, Akira Yoneda, Akira Tsuji, Taihei Inoue ...
    Article type: letter
    2023 Volume 17 Issue 3 Pages 217-219
    Published: June 30, 2023
    Released on J-STAGE: July 12, 2023
    Advance online publication: June 16, 2023
    JOURNAL FREE ACCESS

    Diospyrobezoar is a relatively uncommon cause of small bowel obstruction. Here we report successful treatment in a patient with small bowel obstruction due to diospyrobezoar by laparoscopic-assisted surgery. A 93-year-old woman who had undergone distal gastrectomy and laparoscopic cholecystectomy presented with nausea and anorexia. An intestinal obstruction and an intestinal intraluminal mass were discovered on abdominal enhanced computed tomography. Following a transnasal ileus tube placement, the patient underwent laparoscopic surgery to remove the diospyrobezoar from the small intestine. The postoperative course of the patient was uneventful. Laparoscopic-assisted surgery following the transnasal ileus tube was beneficial for the patient's small bowel obstruction caused by diospyrobezoar.

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