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Drug Discoveries & Therapeutics

Makiya Nishikawa
Nucleic acids are biologically active materials, and chemically modified nucleic acids are now being used in nucleic acid drugs. DNA, one of the two types of nucleic acids, can also be used as a material to construct DNA-based delivery systems, such as DNA hydrogel, for therapeutic compounds. Use of chemically modified nucleic acids would greatly increase the therapeutic potency of such DNA-based delivery systems. However, attention should be paid to the differences in the physicochemical properties of natural and chemically modified nucleic acids...
October 23, 2016: Drug Discoveries & Therapeutics
Pham Thi Be Tu, Binh Cao Quan Nguyen, Shinkichi Tawata, Cheong-Yong Yun, Eung Gook Kim, Hiroshi Maruta
We previously demonstrated that the oncogenic kinase PAK4, which both melanomas and normal melanocytes express at a very high level, is essential for their melanogenesis. In the present study, using the highly sensitive "Macaroni-Western" (IP-ATP-Glo) kinase assay, we investigated the melanogenic potential of another oncogenic kinase PAK1, which melanoma (B16F10) cells express only at a very minute level. After transfecting melanoma cells with PAK1-shRNA for silencing PAK1 gene, melanin content, tyrosinase activity, and kinase activity of PAK1 were compared between the wild-type and transfectants...
October 17, 2016: Drug Discoveries & Therapeutics
Kanjiro Miyata
In recent decades, nucleic acid therapeutics have been attracting much attention because of their potential as treatments for various diseases that require high target specificity. Nevertheless, the number of approved nucleic acid drugs is very limited due to substantially poor bioavailability, thereby generating the need for nucleic acid delivery carriers. A variety of delivery formulations have been reported so far. This review particularly describes polymer-based delivery carriers for systemic administration, highlighting the potential of biological environment-responsive chemistry for overcoming the biological barriers to nucleic acid delivery...
October 17, 2016: Drug Discoveries & Therapeutics
Raja A H Kuchay
Administration of chemotherapy often leads to gastrointestinal mucositis (GIM). GIM manifests as nausea, abdominal pain and diarrhoea in recipients of chemotherapy. GIM is a major complication occurring in approximately 80% of patients receiving 5-flurouracil treatment. These side-effects may become so severe that significant dose reductions are required, ultimately affecting treatment efficacy and patient survival. Complementary and alternative medicine (CAM) is a growing area of public interest. This review will provide an overview of current knowledge of complementary medicinal therapies for chemotherapy induced GIM...
October 17, 2016: Drug Discoveries & Therapeutics
Mehmet Emin Önger, Burcu Delibaş, Aysın Pınar Türkmen, Erkan Erener, Berrin Zuhal Altunkaynak, Süleyman Kaplan
Nerve injuries result in functional loss in the innervated organ or body parts, and recovery is difficult unless surgical treatment has been done. Different surgical treatments have been suggested for nerve repair. Tissue engineering related to growth factors has arisen as an alternative approach for triggering and improving nerve regeneration. Therefore, the aim of this review is to provide a comprehensive analysis related to growth factors as tools for optimizing the regeneration process. Studies and reviews on the use of growth factors for nerve regeneration were compiled over the course of the review...
October 17, 2016: Drug Discoveries & Therapeutics
Zhiliang Hu, Yongfeng Yang, Jian Cheng, Cong Cheng, Yun Chi, Hongxia Wei
Cryptococcal meningitis (CM) is a common opportunistic infection with a high mortality rate in human immunodeficiency virus (HIV)-infected patients. It is unclear whether mannitol could be used to manage neurological symptoms in HIV-associated CM. Here, we retrospectively analyzed the clinical data of 33 patients with HIV-associated symptomatic CM at our hospital where mannitol was used to relieve neurologic symptoms. With the empirical mannitol therapy, patients had a median of 2 episodes (range, 1-6 episodes) of headaches the day at the starting of anti-cryptococcal therapy...
October 11, 2016: Drug Discoveries & Therapeutics
Yuko Wada, Yukie Takaoka, Mitsuru Nozawa, Miho Goto, Ken-Ichi Shimokawa, Fumiyoshi Ishii
We measured the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time of medicinal and over-the-counter (OTC) tape preparations containing felbinac. When measuring the pH of each preparation, Felnabion (pH 4.5) was weakly acidic, and EMEC and Tokuon (pH 7.0) were neutral. When measuring the water-vapor permeability of each preparation, that of a generic product, EMEC (380 g/m(2)/24h), was twice as high as that of a brand-name product, Seltouch (189 g/m(2)/24 h)...
October 4, 2016: Drug Discoveries & Therapeutics
Kimihito Usui, Satoshi Nishida, Takuya Sugita, Takuro Ueki, Yasuhiko Matsumoto, Hidenobu Okumura, Kazuhisa Sekimizu
This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible...
February 2016: Drug Discoveries & Therapeutics
Satoshi Nishida, Yasuo Ono, Kazuhisa Sekimizu
Lactic acid bacteria (LAB) have been thought to be helpful for human heath in the gut as probiotics. It recently was noted that activity of LAB stimulating immune systems is important. Innate immune systems are conserved in mammals and insects. Silkworm has innate immunity in response to microbes. Microbe-associated molecular pattern (ex. peptidoglycan and β-glucan) induces a muscle contraction of silkworm larva. In this study, we established an efficient method to isolate lactic acid bacteria derived from natural products...
February 2016: Drug Discoveries & Therapeutics
Ryuji Uchida, Shingo Namiguchi, Hiroyuki Ishijima, Hiroshi Tomoda
The silkworm infection assay is a useful method for directly evaluating the in vivo therapeutic effects of drug candidates. In the present study, 3 known trichothecenes, trichodermin, epiisororidin E, and verrucarin A, were evaluated as antifungal agents in the silkworm-Candida albicans assay. Trichodermin and epiisororidin E yielded effective therapeutic effects, while verrucarin A exhibited no efficacy in this assay system. These results strongly suggest that trichodermin and epiisororidin E are the lead compounds for developing a new antifungal agent...
February 2016: Drug Discoveries & Therapeutics
Yoshinori Inagaki, Yasuhiko Matsumoto, Kazuhisa Sekimizu
Evaluation of tissue injury induced by chemicals is crucial to drug development. Mice and rats, which are effectively used to analyze drug-induced tissue injury, present problems in terms of cost and ethical issues. Although alternative methods have been developed using in vitro techniques or invertebrates, evaluation of ADME and the size of animals are still issues that need to be addressed. Use of silkworms can resolve these problems. Silkworms have pharmacokinetic characteristics similar to those of mammals...
February 2016: Drug Discoveries & Therapeutics
Kohji Itoh, Isao Kobayashi, So-Ichiro Nishioka, Hideki Sezutsu, Hiroaki Machii, Toshiki Tamura
Since 2000, transgenic silkworms have been developed to produce recombinant proteins with therapeutic potential for future clinical use, including antibody preparations. Lysosomal storage diseases (LSDs) are inherited metabolic disorders caused by mutations of lysosomal enzymes associated with excessive accumulation of natural substrates and neurovisceral symptoms. Over the past few years, enzyme replacement therapy (ERT) with human lysosomal enzymes produced by genetically engineered mammalian cell lines has been used clinically to treat several patients with an LSD involving multi-organ symptoms...
February 2016: Drug Discoveries & Therapeutics
Chikara Kaito
We have used silkworms, larva of Bombyx mori, to investigate host-pathogen interactions. Silkworms have several advantages, such as high availability of a large number of animals and ease of injection of quantitative amounts of samples. Human pathogenic bacteria such as Staphylococcus aureus, Streptococcus pyogenes, or Pseudomonas aeruginosa kill silkworms. In this review, I would like to summarize our approach identifying S. aureus virulence factors by using the silkworm infection model.
February 2016: Drug Discoveries & Therapeutics
Kazuhisa Sekimizu, Hiroshi Hamamoto
For this special issue, we, the Editors of Drug Discoveries & Therapeutics, have asked researchers who are using silkworms to actively develop drugs and study foods to summarize their recent work. Our profound hope is that this special issue encourages researchers who are helping to develop the new field of "using silkworms as a laboratory animal to evaluate medicines and foods".
February 2016: Drug Discoveries & Therapeutics
Yasuhiko Matsumoto, Kazuhisa Sekimizu
Since diabetes patients are increasing in the world, establishment of a novel method for development of anti-diabetic drugs is desired. In this review, we describe recent results of our studies regarding diabetic model using silkworms for evaluation of anti-diabetic drugs for patients of both type I and type II diabetes. The use of the evaluation systems using silkworms is expected to contribute to reduction in cost and in the number of mammals sacrificed for screening of anti-diabetic drugs.
February 2016: Drug Discoveries & Therapeutics
Hiroshi Hamamoto, Kazuhisa Sekimizu
New antimicrobials with novel mechanisms need to be developed to combat antimicrobial-resistant pathogenic bacteria. The current authors recently reported discovery of a new antibiotic named "Lysocin E". Lysocin E was identified using a silkworm model of bacterial infection. The current review discusses the advantages of using a silkworm model of bacterial infection to identify and develop therapeutically efficacious antimicrobials. This review also discusses the discovery of lysocin E and its novel mechanism of action...
February 2016: Drug Discoveries & Therapeutics
Yasuhiko Matsumoto, Kazuhisa Sekimizu
Silkworm shows hyperglycemia after intake of diet containing large amount of glucose. The hyperglycemic silkworm model is useful for evaluation of anti-diabetic drugs. A hot water extract of Rehmanniae Radix, an herbal medicine, showed hypoglycemic effect against the hyperglycemic silkworms. This method is applicable for quick and simple evaluation of the hypoglycemic activities of different batches of Rehmanniae Radix. Our findings suggest that silkworms have a lot of merit as experimental animals for evaluation of various herbal medicines...
February 2016: Drug Discoveries & Therapeutics
Masaki Ishii, Yasuhiko Matsumoto, Kazuhisa Sekimizu
We propose Cryptococcus neoformans infection model using silkworm for understanding cryptococcosis and screening of therapeutically effective antibiotics. Silkworm is an insect whose rearing methods were established through a long history of the sericulture industry. Silkworm facilitates experiments using a large number of individuals because of low cost for rearing and few ethical problems caused by killing animals. Silkworm can be reared at 37˚C to perform infection experiments at same temperature to human body...
February 2016: Drug Discoveries & Therapeutics
Hiroko Tabunoki, Hidemasa Bono, Katsuhiko Ito, Takeshi Yokoyama
Bombyx mori (silkworm) is the most famous lepidopteran in Japan. B. mori has long been used in the silk industry and also as a model insect for agricultural research. In recent years, B. mori has attracted interest in its potential for use in pathological analysis of model animals. For example, the human macular carotenoid transporter was discovered using information of B. mori carotenoid transporter derived from yellow-cocoon strain. The B. mori carotenoid transport system is useful in human studies. To develop a human disease model, we characterized the human homologs of B...
February 2016: Drug Discoveries & Therapeutics
Adila Salih ElObeid, Ibrahim AlAbdudlkarim
Biobanking entails large-scale collection of human biological specimens that are linked to the donors' health and personal information, and has several applications in clinical research. Human biological specimens, such as blood, urine and tissue, have become immensely important to medical research: they offer a valuable source of genetic material that researchers can use to identify disease-associated genetic variation and to determine interactions between genes and environmental factors. Identification of genetic contributions to disease can lead to the development of new diagnostic tests and targeted treatments...
2016: Drug Discoveries & Therapeutics
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