Article
Gastroenterology & Hepatology
Kazuhiko Uchiyama, Tomohisa Takagi, Katsura Mizushima, Yasuko Hirai, Kohei Asaeda, Takeshi Sugaya, Mariko Kajiwara-Kubota, Saori Kashiwagi, Yuki Minagawa, Yuma Hotta, Makoto Tanaka, Ken Inoue, Kazuhiro Katada, Kazuhiro Kamada, Takeshi Ishikawa, Hiroaki Yasuda, Hideyuki Konishi, Mitsuo Kishimoto, Yuji Naito, Yoshito Itoh
Summary: This study found that MAdCAM-1 expression in UC patients is associated with mucosal inflammation and subsequent relapse, suggesting it may serve as a marker for both relapse and therapeutic effectiveness in UC.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Gastroenterology & Hepatology
Geert R. D'Haens, Walter Reinisch, Scott D. Lee, Dino Tarabar, Edouard Louis, Maria Klopocka, Jochen Klaus, Stefan Schreiber, Dong Il Park, Xavier Hebuterne, Peter Nagy, Fabio Cataldi, Steven W. Martin, Satyaprakash Nayak, Anindita Banerjee, Kenneth J. Gorelick, William J. Sandborn
Summary: Ontamalimab is a potential novel treatment for Crohn's disease, with sustained treatment responses observed over 72 weeks in patients. Disease activity index gradually decreased during the study period.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Pharmacology & Pharmacy
Amin Kamel, Tate Owen, Izaiah Cole, Tania Valencia, Edmund C. Lee
Summary: PK and ADME properties of RGLS4326 were characterized in vivo and in vitro in mice and monkeys. RGLS4326 showed similar properties across different species, both in vivo and in vitro. Subcutaneous administration resulted in preferential exposure to the kidney, the intended target organ, for maximum target engagement. These findings support the interpretation of toxicology and efficacy studies and provide insight into the disposition of RGLS4326 in humans.
DRUG METABOLISM AND DISPOSITION
(2023)
Review
Oncology
Hiroaki Taniguchi, Yasunori Suzuki, Kohzoh Imai, Yasushi Adachi
Summary: Oligonucleotide therapeutics, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), have great potential in targeting specific DNA or RNA sequences or proteins. However, their clinical application is still challenging and needs to be compatible with next-generation sequencing for diagnosis.
Article
Oncology
Irene Marafini, Carmine Stolfi, Edoardo Troncone, Elisabetta Lolli, Sara Onali, Omero Alessandro Paoluzi, Massimo C. Fantini, Livia Biancone, Emma Calabrese, Antonio Di Grazia, Ivan Monteleone, Marco Vincenzo Lenti, Antonio Di Sabatino, Giovanni Monteleone
Summary: This study confirmed the clinical benefit of Mongersen in active Crohn's disease and revealed variations in the inhibitory effect on Smad7 expression among different batches of Mongersen.
Article
Pharmacology & Pharmacy
Tsuyoshi Yamamoto, Yahiro Mukai, Fumito Wada, Chisato Terada, Yukina Kayaba, Kaho Oh, Asako Yamayoshi, Satoshi Obika, Mariko Harada-Shiba
Summary: Development of clinically relevant anti-microRNA antisense oligonucleotides remains a major challenge. One promising configuration called tiny LNA, highly chemically modified with high activity and specificity, shows enhanced in vivo activity with the introduction of N-acetylgalactosamine (GalNAc). GalNAc improves pharmacokinetics, and the ligand should be introduced at the 5' terminus for optimal impact. This strategy may pave the way for clinical application of miRNA-targeting small ASO therapy.
Article
Medicine, Research & Experimental
Hong Kyu Lee, Min-Woo Nam, Ryeo-Eun Go, Jihye Koo, Tae Hun Kim, Jun-Eui Park, Kyung-Chul Choi
Summary: In this study, a human immune system mouse model was generated to investigate the role of TGF-β2 in T-cell-mediated anti-tumor immunity against PDAC. Results showed that inhibiting TGF-β2 production delays pancreatic cancer growth and enhances the infiltration of cytotoxic T lymphocytes (CTLs). TGF-β2 inhibition also suppresses regulatory T-cells and induces pro-inflammatory cytokines. This suggests that TASO combined with IL-2 may be a promising immunotherapeutic intervention for PDAC.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Christopher L. Barkau, Daniel O'Reilly, Seth B. Eddington, Masad J. Damha, Keith T. Gagnon
Summary: CRISPR-based therapeutics have entered clinical trials, but methods to inhibit Cas enzymes in a clinical setting have not yet been demonstrated. The ability to inhibit CRISPR-based gene editing or gene targeting drugs is crucial for establishing safety standards for these therapies, and inhibitors can serve as a failsafe against off-target effects. Among the existing inhibitor technologies, CRISPR SNuBs, small nucleic acid-based CRISPR inhibitors, show promise for clinical application in the near-term.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Dermatology
Claudio Bonifati, Aldo Morrone, Antonio Cristaudo, Dario Graceffa
Summary: New biologic drugs targeting interleukin-17 have shown quick effectiveness in treating psoriasis, but there is limited real-life data on switching to biologics targeting interleukin-23 in patients who have failed previous treatments.
DERMATOLOGIC THERAPY
(2021)
Article
Immunology
Yangyihua Zhou, Guiqi Quan, Yujun Liu, Ning Shi, Yahui Wu, Qiuju Liu, Xiang Gao, Ran Zhang, Longlong Luo
Summary: An antibody-fusion protein drug, IMAB362-mIL-21, has been developed to achieve tumor targeting and activate local anti-tumor immune response more effectively. It shows stronger anti-tumor effects without obvious hematological toxicity, suggesting better application prospects than single drugs or their combination.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Zhichao Tang, Junxing Zhao, Zach J. Pearson, Zarko V. Boskovic, Jingxin Wang
Summary: RNA splicing is crucial in producing mature mRNA, and leveraging splicing modifiers as a pharmacological modality shows promising potential in treating diseases caused by aberrant splicing. Approved drugs include antisense oligonucleotide splicing modifiers and a small-molecule splicing modifier risdiplam, targeting mRNA precursors.
Review
Chemistry, Multidisciplinary
Shalakha Hegde, Zhichao Tang, Junxing Zhao, Jingxin Wang
Summary: The ongoing COVID-19 pandemic has had a significant impact on global public health and society, with research on targeting conserved SARS-CoV-2 RNA structures and sequences emerging as a promising new approach to inhibit viral infection. These RNA-targeting molecules could serve as an emerging class of antiviral drug candidates for future viral outbreaks.
FRONTIERS IN CHEMISTRY
(2021)
Article
Health Care Sciences & Services
Malgorzata Galecka, Katarzyna Blizniewska-Kowalska, Agata Orzechowska, Janusz Szemraj, Michael Maes, Michael Berk, Kuan-Pin Su, Piotr Galecki
Summary: This research study found that in depressed patients without coexisting inflammatory diseases, the gene expression levels of specific immune-inflammatory factors such as IL-17, IL-21, IL-23, and IL-35 were higher, while Foxp3 expression was lower. The duration of the disease appears to be more important than the severity of depression in relation to the expression of these genes. These findings suggest that specific inflammatory genes may play a role in the etiopathogenesis of depressive disorders.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Misa Yoshida, Chihiro Oda, Keishiro Mishima, Itsuki Tsuji, Satoshi Obika, Masahito Shimojo
Summary: A study has found that the growth of cancer cells can be inhibited by specific nucleotides, and the detailed mechanism involves the regulation of REST splicing to affect cell viability. This research is of great significance for refractory tumors such as small cell lung cancer and prostate cancer.
CANCER CELL INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Rei Kawashima, Shun Tamaki, Yusuke Hara, Tatsunori Maekawa, Fumitaka Kawakami, Takafumi Ichikawa
Summary: Non-steroidal anti-inflammatory drugs (NSAIDs) can cause gastrointestinal disorders, but their mechanism of small intestinal mucosal injury is not well understood. This study used an animal model to induce small intestinal mucosal injury with NSAIDs and found that IL-13 production from CD4-positive T cells is involved in the injury. These results are important for understanding NSAID-induced mucosal injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
