Article
Microbiology
Maria E. Cilento, Aaron B. Reeve, Eleftherios Michailidis, Tatiana Ilina, Eva Nagy, Hiroaki Mitsuya, Michael A. Parniak, Philip R. Tedbury, Stefan G. Sarafianos
Summary: The study demonstrates that EFdA exhibits exceptional potency against HIV-1, with M184V and A114S/M184V identified as key mutations contributing to EFdA resistance. These mutations show higher sensitivity to tenofovir and are suitable for use in treatment of naive, AZT, FTC/3TC, and tenofovir-treated patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Meika Kaneko, Yoshie Reien, Hanae Morio, Tomoko Fukuuchi, Kiyoko Kaneko, Yuri Hirayama, Hirofumi Hashimoto, Nobuyo Kuwata, Hiroaki Mitsuya, Naohiko Anzai
Summary: The study indicates that Islatravir is unlikely to cause kidney damage in clinical settings due to its concentration levels not being high enough to harm tubular cells. Organic anion transporters OAT1 and OAT3 may not be involved in the injury caused by Islatravir to tubular cells.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Jiao Hou, Youmei Peng, Bingjie Liu, Qianqian Zhang, Jian-Hua Wang, Wenquan Yu, Junbiao Chang
Summary: 2'-Deoxy-2'-β-fluoroadenosines with 4'-azido or 4'-ethynyl groups have been synthesized for the treatment of HIV-1 infection. These compounds exhibit nanomolar anti-HIV-1 activity, with the 4'-ethynyl-2-fluoroadenosine analog 1c (CL-197) being the most potent and least cytotoxic (EC50 = 0.9 nM, CC50 > 100 μM). It shows strong inhibitory activity against drug resistant and clinical HIV-1 strains. Oral administration of 1c in Beagle dogs results in high levels of the bioactive form 1c-TP in peripheral blood mononuclear cells, where it exhibits long-term intracellular retention and prevents HIV-1 infection for an extended time. 1c displays low in vivo toxicity and favorable pharmacokinetic profiles in Sprague-Dawley rats. The preclinical data support the further development of 1c as a highly potent and orally bioavailable clinical candidate for treating HIV-1 infection. Currently, CL-197 is in clinical trials in China (registration number: CXHL2200529).
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shingo Hirashima, Hiroshi Sugiyama, Soyoung Park
Summary: This study characterized 2FA-containing DNA molecules and found that they have similar structure and properties to native adenine due to their small size, but exhibit unique features due to their high electronegativity. This provides valuable information for future applications of 2FA-modified DNA.
Article
Chemistry, Organic
Yasufumi Fuchi, Miho Kawaguchi, Yuta Ito, Yoshiyuki Hari
Summary: In this study, two adenosine-like C-nucleosides bearing thieno[3,2-d]pyrimidine rings were synthesized and investigated as monomer nucleosides. The synthesized C-nucleosides were not recognized by adenosine deaminase (ADA) and exhibited fluorescence emissions. Furthermore, when incorporated into oligonucleotides, these modified C-nucleosides formed stable duplexes with DNA and RNA and showed fluorescence emission.
Article
Microbiology
Julia C. LeCher, Keivan Zandi, Vivian Vasconcelos Costa, Franck Amblard, Sijia Tao, Dharmeshkumar Patel, Sujin Lee, Felipe Rocha da Silva Santos, Matheus Rodrigues Goncalves, Celso Martins Queroz-Junior, Fernanda Martins Marim, Katie Musall, Shu Ling Goh, Tamara McBrayer, Jessica Downs-Bowen, Ramyani De, Niloufar Azadi, James Kohler, Mauro Martins Teixeira, Raymond F. Schinazi
Summary: This study reports potential antiviral drugs against yellow fever virus, showing low toxicity, high intracellular metabolism, and strong anti-YFV activity in different models. The findings provide a new therapeutic option for treating yellow fever virus infections.
Article
Chemistry, Organic
Mahendra A. Wagh, Dinesh R. Shinde, Rama Krishna Gamidi, Gangadhar J. Sanjayan
Summary: This study presents a nature-inspired Janus G-C nucleobase that contains two recognition sites: DDA (G mimic) and DAA (C mimic), resulting in a linear tape-like supramolecular polymer structure. The amino group of this self-assembling system can also be modified to create a highly stable quadruple H-bonding system and a light-cleavable masked self-assembling system.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Immunology
Anna-Lena Unterweger, Alena Ruescher, Marietta Seuss, Paula Winkelmann, Florian Beigel, Leandra Koletzko, Simone Breiteneicher, Matthias Siebeck, Roswitha Gropp, Attila Aszodi
Summary: The combined approach of patient immune-profiling and a mouse model based on NSG reconstituted with PBMC from CD patients partially reflects the human disease, showing an immune-remodeling phenotype with increased collagen deposition, elevated levels of specific immune cells, and inflammatory markers. This model provides a platform for studying fibrosis development in CD.
IMMUNITY INFLAMMATION AND DISEASE
(2021)
Article
Pharmacology & Pharmacy
M. Alkhaled, A. M. Elazzazy, O. A. Almaghrabia, R. Handgretinger
Summary: Natural killer cells have therapeutic potential in cancer immunotherapy. A reliable ex vivo expansion platform is needed to study their efficacy. A preclinical study using humanized mice showed that expanded natural killer cells extended the survival of mice and effectively killed leukemia cells.
INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Cell Biology
Henrika Jodeleit, Paula Winkelmann, Janina Caesar, Sebastian Sterz, Lesca M. Holdt, Florian Beigel, Johannes Stallhofer, Simone Breiteneicher, Eckart Bartnik, Thomas Leeuw, Matthias Siebeck, Roswitha Gropp
Summary: This study aimed to demonstrate patient stratification for oxelumab treatment using immune profiling and a humanized mouse model of UC. Results showed significant differences in OX40L expression levels between UC and non-UC donors. The efficacy of oxelumab in reducing clinical scores and inflammation was slightly better than adalimumab, suggesting a potential benefit for patients with elevated OX40L levels.
DISEASE MODELS & MECHANISMS
(2021)
Article
Pharmacology & Pharmacy
Renkai Li, Winston Wing-Shum Mak, Jingjing Li, Chengwen Zheng, Polly Ho-Ting Shiu, Sai-Wang Seto, Simon Ming-Yuen Lee, George Pak-Heng Leung
Summary: This study identified compound 3c as a selective and irreversible non-competitive inhibitor of ENT1 and ENT2, which is a derivative of FPMINT. The structure-activity relationship analysis revealed the importance of the position of benzene moiety and the addition of halogen substitutes for the inhibitory effects. These findings contribute to the development of more potent and selective drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Analytical
Yi-Da Zhang, Yan-Ping Shi
Summary: A cost-efficient and easy-to-use approach called dual molecular imprinting immunosandwich colorimetric strategy (DMI-ICS) was constructed for detection of alpha-2-macroglobulin (alpha 2MG) using janus imprinted nanoparticles. This strategy showed great performance with lower detection limit and could be a versatile tool for point-of-care diagnosis.
ANALYTICA CHIMICA ACTA
(2021)
Article
Veterinary Sciences
Yuyo Ka, Ryoji Ito, Ryoko Nozu, Kayo Tomiyama, Masami Ueno, Tomoyuki Ogura, Riichi Takahashi
Summary: Humanized mice are widely used to study the human immune system and therapeutic targets for human diseases. This study established a new model of germ-free humanized mice and found that the human gut microbiota supports T cell proliferation and maintenance in the mice. This dual-humanized mouse model may be useful for studying the role of the gut microbiota in human immunity and as a new model in cancer immunology.
EXPERIMENTAL ANIMALS
(2023)
Article
Chemistry, Physical
Jae Won Song, Jungyo Suh, Seok Won Lee, Jung Ki Yoo, Uijeong Lee, Jang Hee Han, Cheol Kwak, Minyong Kang, Yi Rang Kim, Chang Wook Jeong, Jin Woo Choi
Summary: In this study, an adenovirus was designed and tested for the detection of circulating tumor cells (CTCs). The adenovirus is able to bind to desmoglein-2, which is highly expressed in most cancer cells. By comparing the number of CTCs before and after surgery in patients with renal cell carcinoma and prostate cancer, the researchers found that the cancer cell-specific infection of the adenovirus can efficiently detect CTCs.
Article
Medicine, General & Internal
Jie Xu, Fang-Ping Xu, Zhi-Hua Liu, Qian Cui, Ke-Ping Zhang, Zhi Li
Summary: This study investigated the correlations between mutations in the TERT promoter and IDH1/2 mutations or 1p/19q deletion in human gliomas. The results showed a positive correlation between TERT promoter mutations and 1p/19q deletion, as well as a negative correlation between TERT promoter mutations and IDH gene mutations, except in certain cases. This suggests a complex inter-regulatory relationship between these mutations in human gliomas.
Article
Oncology
Jutatip Panaampon, Ryusho Kariya, Seiji Okada
Summary: Primary effusion lymphoma (PEL) is a rare and aggressive B cell non-Hodgkin's lymphoma with poor prognosis and lack of established optimal treatment. The study showed that the monoclonal antibody Daratumumab (DARA) targeting CD38 demonstrated high antibody-dependent cytotoxicity against PEL cells, suggesting it could be an effective therapeutic strategy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Natsuki Imayoshi, Makoto Yoshioka, Kuniaki Tanaka, Shyh-Ming Yang, Koshi Akahane, Yuki Toda, Shigekuni Hosogi, Takeshi Inukai, Seiji Okada, David J. Maloney, Tatsutoshi Nakahata, Junko Takita, Itaru Kato, Eishi Ashihara
Summary: This study demonstrates that the BET/CBP/p300 multi-bromodomain inhibitor, CN470, has anti-tumor activity against MLL-r ALL by inhibiting cell growth, inducing apoptosis, and showing potential therapeutic advantages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Kazuharu Kamachi, Hiroshi Ureshino, Tatsuro Watanabe, Nao Yoshida, Yuta Yamamoto, Yuki Kurahashi, Yuki Fukuda-Kurahashi, Yoshihiro Hayashi, Hideyo Hirai, Satoshi Yamashita, Toshikazu Ushijima, Seiji Okada, Shinya Kimura
Summary: Targeting DNMT1 with OR21 demonstrates anti-tumor effects and impairs leukemic stem cells in chronic myeloid leukemia (CML). Combination therapy of OR21 and TKIs represents a promising treatment strategy for CML.
Article
Infectious Diseases
Kamonnaree Chotinantakul, Surachet Woottisin, Seiji Okada
Summary: The study investigated the prevalence of ESBL-producing E. coli in fresh vegetables purchased from fresh markets in Chiang Rai, Thailand, finding that a portion of them exhibited multidrug resistance, carried various resistance genes, and belonged to different sequence types.
JAPANESE JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Oncology
Jutatip Panaampon, Ryusho Kariya, Seiji Okada
Summary: This study found that NK cells play a role in killing PEL, and Elo, which targets SLAMF7, enhances NK cell cytotoxicity against PEL through ADCC/SLAMF7 ligation.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Mikinori Ueno, Ryusho Kariya, Sittithumcharee Gunya, Kodcharat Cheevapruk, Seiji Okada
Summary: This study investigated the mechanism of action of the midkine inhibitor (iMDK) on primary effusion lymphoma (PEL). The results showed that iMDK could inhibit the proliferation of PEL by inducing cell cycle arrest and causing mitotic catastrophe, leading to apoptosis. Furthermore, iMDK had no effects on viral protein-activated signaling pathways and viral gene expression in PEL.
Article
Oncology
Orawan Suppramote, Sunisa Prasopporn, Satinee Aroonpruksakul, Ben Ponvilawan, Jiradej Makjaroen, Monthira Suntiparpluacha, Krittiya Korphaisarn, Komgrid Charngkaew, Rawisak Chanwat, Trairak Pisitkun, Seiji Okada, Somponnat Sampattavanich, Siwanon Jirawatnotai
Summary: Based on vulnerability screening, this study reveals a potential treatment option for cholangiocarcinoma by exploiting the vulnerabilities of CCA cells under CDK4/6 inhibition and their response to oxaliplatin, an anti-ribosome drug. The combination of the CDK4/6 inhibitor palbociclib and oxaliplatin shows synergistic effects in inhibiting CCA growth and inducing apoptosis, suggesting its promising potential as a treatment for cholangiocarcinoma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Hesham Nasser, Naofumi Takahashi, Youssef M. Eltalkhawy, Omnia Reda, Sameh Lotfi, Kanako Nasu, Jun-ichi Sakuragi, Shinya Suzu
Summary: IL-32 inhibits HIV-1 production in MDMs through SAMHD1, but stimulates viral production in CD4(+) T cells. IL-32 also induces the expression of immunosuppressive molecules such as IDO1 and PD-L1, and promotes MDMs' mobility.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Chihiro Motozono, Mako Toyoda, Toong Seng Tan, Hiroshi Hamana, Yoshihiko Goto, Yoshiki Aritsu, Yusuke Miyashita, Hiroyuki Oshiumi, Kimitoshi Nakamura, Seiji Okada, Keiko Udaka, Mizuki Kitamatsu, Hiroyuki Kishi, Takamasa Ueno
Summary: Mutations in the spike protein of SARS-CoV-2 can lead to escape from the neutralizing antibody response but still retain susceptibility to cellular immune response. A specific mutation, G446S, in the spike protein of the Omicron BA.1 variant affects antigen processing/presentation and enhances antiviral activity by vaccine-induced T cells.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Supawan Jamnongsong, Patipark Kueanjinda, Pongsakorn Buraphat, Phuwanat Sakornsakolpat, Kulthida Vaeteewoottacharn, Seiji Okada, Siwanon Jirawatnotai, Somponnat Sampattavanich
Summary: This study presents a comprehensive drug response profiling for cholangiocarcinoma (CCA) and identifies two major CCA subgroups with unique molecular pathways. MEK and Src inhibitors show specific cytotoxicity against one CCA subgroup without affecting normal cholangiocytes. The developed CCA45 signature accurately predicts prognosis for Asian CCA patients and provides a valuable resource for drug repurposing in CCA and rare cancers.
Article
Oncology
Ayumi Kanemaru, Satoru Shinriki, Mimi Kai, Kanae Tsurekawa, Kazuya Ozeki, Shota Uchino, Naoki Suenaga, Kou Yonemaru, Shunsuke Miyake, Takeshi Masuda, Ryusho Kariya, Seiji Okada, Hisashi Takeshita, Yuki Seki, Hiromu Yano, Yoshihiro Komohara, Ryoji Yoshida, Hideki Nakayama, Jian-Dong Li, Hideyuki Saito, Hirofumi Jono
Summary: EGFR-targeted molecular therapies, such as EGFR-TKIs, have potential as novel therapeutic agents for CYLD-negative oral squamous cell carcinoma (OSCC) patients with poor prognosis, according to this study.
CANCER CELL INTERNATIONAL
(2022)
Article
Virology
Patta Phumesin, Jutatip Panaampon, Ryusho Kariya, Thawornchai Limjindaporn, Pa-thai Yenchitsomanus, Seiji Okada
Summary: Dengue virus (DENV) infection is a serious public health problem in tropical and subtropical regions, causing a range of clinical manifestations. Currently, there is no specific antiviral drug for DENV infection. In this study, cepharanthine (CEP) was found to have inhibitory effects on DENV infection at the initial viral replication states and proinflammatory cytokine secretion, making it a potential candidate for further development as an anti-DENV treatment.
Article
Plant Sciences
Parichaya Aimvijarn, Witchuda Payuhakrit, Nisamanee Charoenchon, Seiji Okada, Prasit Suwannalert
Summary: Ultraviolet type B (UVB) radiation plays an important role in hyperpigmentation disorder by inducing cellular oxidative stress and abnormal melanin production. Phenolic compounds, which are secondary metabolites synthesized in stress conditions, have been found to have antioxidant and anti-melanogenesis properties. However, their effect on F-actin rearrangement-associated dendrite formation has not been studied. This study aimed to investigate the enhancement of phenolic compounds in riceberry rice germination under UVB radiation (RR-GR) and their potential in suppressing melanogenesis through F-actin rearrangement.
Article
Biochemistry & Molecular Biology
Piyanard Boonnate, Ryusho Kariya, Seiji Okada
Summary: Adult T cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy that develops in some elderly human T-cell leukemia virus (HTVL-1) carriers. Despite conventional and targeted therapies, ATLL has a poor prognosis, and a new safe and efficient therapy is required. This study found that Shikonin (SHK) could induce apoptosis of ATLL cells through the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and induction of endoplasmic reticulum (ER) stress. These findings suggest that SHK could be a potent anti-ATLL agent.
Article
Pediatrics
Yasuhiro Kondo, Shunsuke Watanabe, Atsuki Naoe, Toshiyuki Takeuchi, Atsuko Niimi, Motoshi Suzuki, Naoya Asai, Seiji Okada, Tomonori Tsuchiya, Mika Murayama, Toshihiro Yasui, Mikihiro Inoue, Tatsuya Suzuki
Summary: This study established a mouse model of neuroblastoma metastasis and demonstrated that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.
PEDIATRIC SURGERY INTERNATIONAL
(2022)