Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Current issue
Displaying 1-9 of 9 articles from this issue
Original Article
  • Takeaki Okamoto, Sayaka Yokoyama, Hinako Ushimaru, Mamoru Tanaka
    Article type: research-article
    2024 Volume 18 Issue 3 Pages 143-149
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: June 06, 2024
    JOURNAL FREE ACCESS

    This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced β-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced β-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-α production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extract-treated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects.

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  • Soraya Rodwattanagul, Mathurada Sasarom, Pornthida Riangjanapatee, Son ...
    Article type: research-article
    2024 Volume 18 Issue 3 Pages 150-159
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: May 22, 2024
    JOURNAL FREE ACCESS

    Sophora exigua (SE) was sequentially extracted using hexane, ethyl acetate, and ethanol. The obtained extracts were tested for antioxidant activity. Among them, the fractionated ethyl acetate extract (SE-EA) showed the highest potential in free radical scavenging and ferric-reducing properties. The chemical analysis identified sophoraflavanone G as one of the active ingredients in SE-EA. According to SE-EA solubility, SE-EA liposomes were developed using a sonication-assisted thin film method. Cholesterol and phospholipids were used as the main compositions of the liposomes. The obtained liposomes were spherical with different nano-size ranges, size distribution, and zeta potential depending on SE-EA and total lipid concentrations. SE-EA liposomes were slightly bigger than their empty liposomes. All liposomes exhibited a phospholipid crystalline structure. Cholesterol and SE-EA existed in the liposomes as an amorphous state. SE-EA liposomes with high total lipid content exhibited high entrapment efficiency and sustained release behavior. Whereas liposomes with low total lipid content showed low entrapment efficiency and fast-release behavior. All SE-EA liposomes showed stronger antioxidant activity than the non-entrapped SE-EA. In conclusion, SE-EA is a natural source of potent antioxidants. The developed SE-EA liposomes are a promising pharmaceutical formulation to efficiently deliver the active ingredients of SE-EA and are suitable for further study in vivo.

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  • Motoko Kitada, Shigeo Yamamura, Etsuro Hori
    Article type: research-article
    2024 Volume 18 Issue 3 Pages 160-166
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: June 15, 2024
    JOURNAL FREE ACCESS

    Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications that affect future treatment. Older inpatients, in particular, are expected to be prone to these catheter-related complications. However, the impact of peripheral PN on older inpatients has been rarely investigated. In the current study, the impact of PN on short peripheral catheters (SPCs) was evaluated by comparing signs and symptoms at the time of catheter removal between 22 patients with PN and 27 without. In addition to external clinical assessment, sonographic investigations of the SPC site were performed. The prevalence of external signs and symptoms of complications was similar between the patients (all P > 0.05). However, subcutaneous edema was found by ultrasound in > 80% of patients with PN, compared with 55.6% of those without PN (P = 0.051). Unlike cases without PN, all patients with PN who presented with external signs and symptoms developed subcutaneous edema (P = 0.022). Multivariate analysis demonstrated that administration of PN was independently associated with subcutaneous edema (adjusted odds ratio = 6.88, 95% confidence interval = 1.083-75.486, P = 0.040). For several decades, phlebitis has been the primary focus of complications related to peripheral PN in clinical settings. However, our results imply that peripheral PN causes subcutaneous edema, which can lead to catheter failure in older inpatients. This study contributes to understanding the etiology of catheter failure during peripheral PN in this population.

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  • Mathurada Sasarom, Phenphichar Wanachantararak, Pisaisit Chaijareenont ...
    Article type: research-article
    2024 Volume 18 Issue 3 Pages 167-177
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: June 28, 2024
    JOURNAL FREE ACCESS

    Synthesis of metal nanoparticles using plant extracts is environmentally friendly and of increasing interest. However, not all plant extracts can meet successfully on the synthesis. Therefore, searching for the high potential extracts that can reduce the metal salt precursor in the synthesis reaction is essential. The present study explores the synthesis of copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract. Phytochemical analysis and determination of the total phenolic content of the extract were performed before use as a reducing agent. Under the suitable synthesized condition, a color change in the color of the solutions to brown confirmed the formation of CuONPs. The obtained CuONPs were confirmed using ultraviolet-visible spectroscopy, photon correlation spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray, and Fourier transform infrared analysis. The synthesized CuONPs investigated for antioxidant, antiglycation, and antibacterial activities. CuONPs possessed antioxidant activities by quenching free radicals with an IC50 value of 63.35 µg/mL and reducing activity with an EC range of 3.19-10.27 mM/mg. CuONPs also inhibited the formation of advanced glycation end products in the bovine serum albumin/ribose model with an IC50 value of 17.05 µg/mL. In addition, CuONPs showed inhibition of human pathogens, including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, and prevention of biofilm formation and biofilm eradication, with maximum inhibition of approx. 75%. Our findings suggest that C. sappan extract can be used to obtain highly bioactive CuONPs for the development of certain medical devices and therapeutic agents.

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  • Qingshan Li, Meng Feng, Hongze Zhang, Hang Zhou, Xunjia Cheng
    Article type: research-article
    2024 Volume 18 Issue 3 Pages 178-187
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: May 22, 2024
    JOURNAL FREE ACCESS

    In humans, Entamoeba histolytica is the main pathogen causing various amoebiases, while E. moshkovskii falls between being a pathogen and non-pathogen. The two species have similar behavior patterns but differ significantly in pathogenicity, with previous studies and clinical data indicating that E. moshkovskii has a low level of pathogenicity. Meaningfully, the biological characteristics of E. moshkovskii make it a potential model organism and a protein display platform for studying the functions of important Entamoeba proteins. Here, an Amoeba-pcDNA3.1 vector capable of overexpressing E. histolytica-sourced Igl-C protein was constructed and successfully transfected into E. moshkovskii. High levels of expression of the Igl-C, EGFP, and NeoR genes were identified in Igl-C-transfected trophozoites using qRT-PCR, and they were subsequently confirmed using immunoblotting. Transfection of Igl-C protein improved the adherence and phagocytosis of E. moshkovskii, demonstrating that E. histolytica Igl mediated amoebic adhesion. Moreover, as a manifestation of protein virulence, the ability of post-transfected trophozoites to induce inflammation in host macrophages was also enhanced. In conclusion, this study utilizing the characteristics of E. moshkovskii confirmed its potential to serve as a model organism. E. moshkovskii could replace E. histolytica as the target of gene editing, allowing more efficient study of amoebic pathogenicity.

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Brief Report
  • Yoshiyuki Yoshikawa, Kyoko Nagayoshi, Noriaki Maeshige, Atomu Yamaguch ...
    Article type: brief-report
    2024 Volume 18 Issue 3 Pages 188-193
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: June 15, 2024
    JOURNAL FREE ACCESS

    Wheelchair cushions are recommended to be used with wheelchair and can protect the buttocks from pain and injury by relieving interface pressure for wheelchair users. However, further investigations are required for proper use in response to the development of new types of wheelchair cushions. The objective of this study was to evaluate physical characteristics of wheelchair cushions by comparing pressure redistributing effects of four types of cushions. The participants were 16 healthy adults who consented to participate in this study. A pressure mapping system (CONFORMat, Nitta Corp.) was used for the measurements. Pressure at ischium was measured immediately after the stabilization of the sitting posture and 10 minutes after. The pressure at ischium significantly decreased with any wheelchair cushions (P < 0.01). A significant negative correlation between body mass index and pressure at ischium was observed without a wheelchair cushion (r = - 0.70), however, the correlation disappeared upon use of a wheelchair cushion. The pressure at ischium increased over time with cushions of urethane, air, and urethane-air hybrid while that with the 3D thermoplastic elastomer cushion did not, and the change in the pressure was statistically less than that in other cushions (P < 0.01). Use of wheelchair cushions was effective in redistribution of the pressure at ischium, and the overtime change in the pressure depends on the type of used cushions.

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  • Yasuhiko Matsumoto, Eri Sato, Takashi Sugita
    Article type: brief-report
    2024 Volume 18 Issue 3 Pages 194-198
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    Advance online publication: June 26, 2024
    JOURNAL FREE ACCESS

    Staphylococcus aureus, a Gram-positive bacterium, causes inflammatory skin diseases, such as atopic dermatitis, and serious systemic diseases, such as sepsis. In the skin and nasal environment, peptidoglycan (PGN)-degrading enzymes, including lysozyme and lysostaphin, affects S. aureus PGN. However, the effects of PGN-degrading enzymes on the acute innate immune-inducing activity of S. aureus have not yet been investigated. In this study, we demonstrated that PGN-degrading enzymes induce acute silkworm hemolymph melanization by S. aureus. Insoluble fractions of S. aureus treated with lysozyme, lysostaphin, or both enzymes, were prepared. Melanization of the silkworm hemolymph caused by the injection of these insoluble fractions was higher than that of S. aureus without enzyme treatment. These results suggest that structural changes in S. aureus PGN caused by PGN-degrading enzymes affect the acute innate immune response in silkworms.

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  • Xin-Yi Tien, Yean Kee Lee, Pooi-Fong Wong, Yi-Sheng Khor, Dharmani Dev ...
    Article type: brief-report
    2024 Volume 18 Issue 3 Pages 199-206
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    JOURNAL FREE ACCESS

    Senolytics are drugs that specifically target senescent cells. Flavonoids such as quercetin and fisetin possess selective senolytic activities. This study aims to investigate if chalcones exhibit anti-senescence activities. Anti-senescence effect of 11 chalcone derivatives on the replicative senescence human aortic endothelial cells (HAEC) and human fetal lung fibroblasts (IMR90) was evaluated. Compound 2 (4-methoxychalcone) and compound 4 (4-bromo-4'-methoxychalcone) demonstrated increased cytotoxicity in senescent HAEC compared to young HAEC, with significant differences on IC50 values. Their anti-senescence effects on HAEC exceeded fisetin. Higher selectivity of compound 4 toward HAEC over IMR90 could be attributed to 4-methoxy (4-OMe) substitution at ring A (R1). Chalcone derivatives have potentials as senolytics in mitigating replicative senescence, warranting further research and development on chalcones as anti-senescent agent.

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Letter to the Editor
  • Ying Zhang, Hongtao Qu, Chuanhua Li, Lanfang Li, Lu He
    Article type: letter
    2024 Volume 18 Issue 3 Pages 207-209
    Published: June 30, 2024
    Released on J-STAGE: July 09, 2024
    JOURNAL FREE ACCESS

    Aortic aneurysm and aortic dissection (AAD) are severe life-threatening cardiovascular disorders for which no approved pharmaceutical therapies are currently available. Protein S-nitrosylation (SNO) is a typical redox-dependent posttranslational modification whose role in AAD has yet to be described. Recently, Zhang et al. revealed for the first time that SNO modification of macrophage cytoskeletal protein septin2 promotes vascular inflammation and extracellular matrix degradation in aortic aneurysm. Mechanically, the TIAM1-RAC1(T lymphoma invasion and metastasis-inducing protein 1-Ras-related C3 botulinum toxin substrate 1) axis participates in the progression of AAD induced with S-nitrosylated septin2. More importantly, developing R-ketorolac and NSC23766 compounds that specifically target the TIAM1-RAC1 pathway may be new a potential strategy for alleviating AAD.

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