Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
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Showing 1-10 articles out of 10 articles from the selected issue
Original Articles
  • Yasuhiko Matsumoto, Miki Takahashi, Masahiro Umehara, Masato Asano, Hi ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 244-247
    Published: October 31, 2019
    Released: November 14, 2019
    [Advance publication] Released: October 14, 2019
    JOURNALS FREE ACCESS

    Silkworms are useful for evaluating substances that suppress postprandial hyperglycemia by oral administration. In this study, orally administered whey protein hydrolysate (WPH), obtained by enzymatic treatment of whey protein, suppressed sucrose-induced hyperglycemia in silkworms in a dose-dependent manner. WPH also inhibited glucose-induced hyperglycemia in silkworms. These findings suggest that WPH contains a bioactive peptide that inhibits glucose uptake from the intestinal tract and thereby suppresses sucrose-induced hyperglycemia.

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  • Rene Hennig, Alia Albawardi, Saeeda Almarzooqi, Shoja Haneefa, Edward ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 248-255
    Published: October 31, 2019
    Released: November 14, 2019
    [Advance publication] Released: October 27, 2019
    JOURNALS FREE ACCESS

    More than 90% of human pancreatic cancers carry the oncogenic mutant of Ki-RAS and their growth depends on its downstream kinase PAK1, mainly because PAK1 blocks the apoptosis of cancer cells selectively. We developed a highly cell-permeable PAK1-blocker called 15K from an old pain-killer (ketorolac), that is shown here to inhibit the growth of three pancreatic cancer cell lines with IC50 values ranging 41-88 nM in vitro. The anti-cancer effect of 15K was further investigated in an orthotopic xenograft model with gemcitabine (GEM)-resistant human pancreatic cancer cell lines (AsPC-1 and BxPC-3) expressing luciferase in athymic mice. During 4 weeks, 15K blocks total burden (growth) of both AsPC-1 and BxPC-3 tumors (measured as radians/sec) with the IC50 below daily dose of 0.1 mg/kg, i.p. In a similar manner 15K reduced both their invasion and metastases as well, while it had no effect on either body weight or hematological parameters even at 5 mg/kg/day. To the best of our knowledge, 15K is so far the most potent among synthetic PAK1-blockers in vivo, and could be potentially useful for therapy of GEM-resistant cancers.

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  • Naoyoshi Nagata, Mari Tohya, Fumihiko Takeuchi, Wataru Suda, Suguru Ni ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 256-260
    Published: October 31, 2019
    Released: November 14, 2019
    [Advance publication] Released: October 11, 2019
    JOURNALS FREE ACCESS

    How long fecal samples can withstand a period of refrigeration or room temperature, and the appropriate preservative, are largely unknown. Cary-Blair transport medium has been used for many years because it is inexpensive and prevents bacterial overgrowth. However, its effectiveness for metagenomic analyses has never been tested. We found that the microbial compositions using a 16S rRNA sequence of samples left at 4°C for 3 or 7 days or at 25°C for 1, 3, or 7 days differed significantly from samples stored at −80°C in no-preservative method. Whereas samples stored in Cary-Blair medium remained unchanged for longer periods. The relative abundances of phylum Bacteroidetes and Actinobacteria, changed significantly at 25°C, whereas Cary-Blair medium inhibited the reduction in Bacteroidetes and the increase in Actinobacteria. The bacterial survival counts were significantly lower in the RNAlater samples than in the Cary-Blair samples under aerobic and anaerobic culture conditions. In conclusion, storage time and storage temperature significantly affect the gut microbial composition in fecal samples. Given the low cost, inhibitory effect on bacterial changes, and potential utility in bacterial isolation, Cary-Blair medium containers are suitable for large-scale or hospital-based microbiome studies, especially if direct freezing at −80°C is unavailable.

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  • Siska Andrina Kusumastuti, Dwi Aris Agung Nugrahaningsih, Mae Sri Hart ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 261-267
    Published: October 31, 2019
    Released: November 14, 2019
    JOURNALS FREE ACCESS

    Insulin resistance in obese condition is related to chronic low-grade inflammation which leads to insulin signaling impairment. Centella asiatica (L.) is an herb that exhibits anti-inflammatory and blood sugar-lowering activity (hypoglycemia). The study aims to investigate the molecular mechanism of C. asiatica extract in insulin sensitivity improvement in a coculture of lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes and RAW 264.7 macrophages. A coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages were incubated with LPS to induce insulin resistance in the adipocytes. An extract of C. asiatica was added to coculture cells and after 24 hours, insulin sensitivity and inflammatory response were determined, including glucose consumption, glucose transporter-4 (GLUT-4), insulin receptor substrate-1 (IRS-1), and interleukin-6 (IL-6) mRNA expression. C. asiatica extract at a concentration of 500 µg/mL increased glucose consumption and induced GLUT-4 and IRS-1 mRNA expression significantly in a coculture of LPS-induced 3T3-L1 adipocytes and RAW 264.7 macrophages. The pro-inflammatory cytokines IL-6 mRNA expression was decreased in the coculture cells after treatment with C. asiatica extract at a concentration of 500 µg/mL. This result indicates that C. asiatica has an effect to stimulate glucose consumption in the coculture cells that might be mediated via GLUT-4/IRS-1 pathway as a result of IL-6 inhibition. These findings suggest that the C. asiatica extract inhibits inflammation and improves insulin sensitivity in a coculture of LPS-induced 3T3-L1 adipocytes and RAW 264.7 macrophages.

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  • Yuya Kawano, Katsunari Makino, Masatoshi Jinnin, Soichiro Sawamura, Sh ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 268-273
    Published: October 31, 2019
    Released: November 14, 2019
    JOURNALS FREE ACCESS

    Although royal jelly is believed to prevent skin aging, the underlying mechanism is not known in detail. In the present study, we investigated the plausibility of the involvement of microRNAs in the manifestation of this effect of royal jelly. The expression of microRNAs was determined by PCR array analysis and real-time PCR and the number of cells was counted with a cell counter. Using PCR array, we identified four microRNAs that were downregulated by royal jelly in cultured human dermal microvascular endothelial cells (HDMEC). Upon comparison of the expression of the four microRNAs between young and senescent facial skin, miR-129-5p was found to be significantly upregulated in senescent skin. Consistently, the expression of miR-129-5p in HDMEC was significantly increased by UVB radiation, suggesting that this microRNA is related to photoaging. The royal jelly treatment increased the number of HDMEC. Furthermore, forced overexpression of miR-129-5p resulted in significant decrease in the number of HDMEC, and its forced downregulation increased the number of cells. The number and density of vessels is reported to be decreased in aged skin. Our results indicate that miR-129-5p is induced in damaged endothelial cells upon exposure to UV radiation, which decreases the cell number. Furthermore, administration of royal jelly downregulated the expression of miR-129-5p in endothelial cells, and might prevent skin aging by maintaining the number of cells. The present study elucidates the mechanism of vessel aging caused by UV exposure and the anti-aging effects of royal jelly through the involvement of microRNA.

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  • Ammara Lodhi, Ashif Sajjad, Khalid Mehmood, Ayesha Lodhi, Sabeena Rizw ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 274-279
    Published: October 31, 2019
    Released: November 14, 2019
    JOURNALS FREE ACCESS

    Hemodialysis (HD) is the most commonly used treatment in patients with end-stage renal failure or disease (ESRD) worldwide. Blood-borne viral diseases are the major causes of mortality and morbidity in patients on HD. This study aims to analyze the prevalence and to concentrate on the key risk factors that are responsible for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection in patients on HD visiting two dialysis centers in the city of Quetta in southwestern Pakistan. The overall incidence of HBV was found to be 16.1%, the overall incidence of HCV was found to be 43.2%, and two patients (1.6%) were found to be positive for both HBV and HCV. HIV was not found among patients seen at both hospitals during the study period. The main risk factors for development of a viral infection were the length of time on HD (p = 0.007), number of sessions (p = 0.001), and level of education (p = 0.092). Biochemical and hematological parameters including urea, creatinine, uric acid, and calcium levels, red blood cell count, white blood cell count, hemoglobin levels, and platelet count were also studied in patients on HD. HD is becoming one of the major factors causing a viral infection because a patient can possibly become infected during an HD session via a blood transfusion, dialysis machines, instruments and/or other contaminated equipment. In order to control the spread of viral infections, increased public awareness, vaccinations, and health education programs for both health care providers and patients are needed, and proper screening programs should be instituted before dialysis is performed.

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  • Toshiaki Takahashi, Takeo Minematsu, Ryoko Murayama, Gojiro Nakagami, ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 280-287
    Published: October 31, 2019
    Released: November 14, 2019
    JOURNALS FREE ACCESS

    Few studies have investigated the molecular mechanisms of catheter failure (CF). Herein, we performed histological and molecular biological analyses of the catheter tip to demonstrate its potential as a resource for biological investigation. Additionally, we searched for risk factors for the development of inflammation and coagulation, which are pathological conditions clarified by biological analysis. The CF group included 30 failed catheters involving thrombus and subcutaneous edema identified by ultrasonography. The No-CF group included 26 catheters with no complications. The removed catheter tips were fixed for hematoxylin-eosin (HE) staining with the application of a real-time reverse transcriptase polymerase chain reaction for eukaryotic 18S ribosomal RNA (rRNA), interleukin 1β, tumor necrosis factor α, tissue plasminogen activator, and plasminogen activator inhibitor 1 (SERPINE1). HE staining identified attached nuclear cells on the inner surfaces of both CF and No-CF catheters. The 18S rRNA was amplified in all samples. The expression level of SERPINE1 was significantly higher in the CF group than in the No-CF group (p = 0.01), whereas the expression levels of other genes did not differ between the groups. Symptoms of CF associated with the expression of SERPINE1 were analyzed. The catheter being in contact with blood vessels during placement was a suggested factor related to the high expression of SERPINE1 (p = 0.04). Catheter tips are a potential resource for biological investigation, and expression analysis of the attached cells can reflect the pathological condition of the catheterized tissue. Further studies using catheter tips are required to elucidate the molecular mechanisms of CF.

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Brief Report
  • Ryoko Murayama, Maiko Oya, Mari Abe-Doi, Makoto Oe, Chieko Komiyama, H ...
    Type: research-article
    2019 Volume 13 Issue 5 Pages 288-293
    Published: October 31, 2019
    Released: November 14, 2019
    JOURNALS FREE ACCESS

    Paclitaxel, a taxane, is frequently administered intravenously as an anticancer agent. When a peripheral intravenous catheter is used for paclitaxel infusion, clinical nurses often observe signs such as slight swelling at the catheter placement site, lack of blood return, and difficulty in continuing the infusion. However, the cause(s) of such phenomena at the puncture site has not yet been elucidated. The aim of this study was to obtain ultrasonography images of subcutaneous tissues and veins of patients undergoing paclitaxel and carboplatin chemotherapy and compare ultrasonography images taken immediately before catheter removal with those of patients receiving other types of taxanes. We studied 24 patients receiving chemotherapy, including seven receiving paclitaxel and carboplatin chemotherapy, through a peripheral intravenous catheter in a chemotherapy unit for outpatients of a university hospital in Japan. Ultrasonography images of venipuncture sites were obtained before catheter insertion and immediately before catheter removal. We observed subcutaneous edema in the absence of visible manifestations at the puncture sites of all patients undergoing paclitaxel and carboplatin chemotherapy, but not in any patients receiving other types of taxanes. When vesicant agents and vehicles have caused subclinical subcutaneous edema, clinical nurses may detect early slight extravasation by using ultrasonography.

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Case Report
  • Ayan Basu, Dyuti Basu, Arpita Chattopadhyay, Rhik Sanyal, Mehebubar Ra ...
    Type: case-report
    2019 Volume 13 Issue 5 Pages 294-296
    Published: October 31, 2019
    Released: November 14, 2019
    [Advance publication] Released: October 27, 2019
    JOURNALS FREE ACCESS

    Graham Little Piccardi Lassueur syndrome (GLPLS) is a rare dermatosis characterized by patchy cicatricial alopecia of scalp, rapidly developing keratosis pilaris like follicular papules over trunk and extremities, and noncicatricial loss of axillary and pubic hair. This syndrome which is mostly seen in middle aged post-menopausal females (between ages 30-70)has rarely ever been described in the pediatric age group. We report a case of a 15 year old girl presenting to us with this rare syndrome.

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  • Akira Kaneko, Ikko Kajihara, Azusa Miyashita, Hironobu Ihn
    Type: case-report
    2019 Volume 13 Issue 5 Pages 297-298
    Published: October 31, 2019
    Released: November 14, 2019
    JOURNALS FREE ACCESS

    Myocardial injury with systemic sclerosis (SSc) causes pericarditis and arrhythmia, and polymyositis-induced muscle inflammation causes myocarditis. We report a rare case of overlap syndrome (SSc and polymyositis) who presented with sudden chest pain secondary to myocardial fibrosis. Although the etiology of chest symptoms in collagen disease was difficult to identify, cardiac magnetic resonance imaging (MRI) revealed not myocarditis but myocardial fibrosis in our case. Synthetic judgement of serum brain natriuretic peptide/ troponin T levels and cardiac MRI is useful in the search for the cause of chest symptoms even in patients with collagen diseases.

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