Article
Biochemistry & Molecular Biology
Ken Asada, Fumika Sakaue, Tetsuya Nagata, Ji-Chun Zhang, Kie Yoshida-Tanaka, Aya Abe, Makiko Nawa, Kazutaka Nishina, Takanori Yokota
Summary: The development of a new drug, Toc-HDO, has shown more potency and stability compared to traditional ASO therapy. Through the identification of several binding proteins regulating Toc-HDO activity, new insights for disease therapy based on HDO have been provided.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Aristides D. Tagalakis, Vignesh Jayarajan, Ruhina Maeshima, Kin H. Ho, Farhatullah Syed, Lin-Ping Wu, Ahmad M. Aldossary, Mustafa M. Munye, Talisa Mistry, Olumide Kayode Ogunbiyi, Arturo Sala, Joseph F. Standing, Seyed M. Moghimi, Andrew W. Stoker, Stephen L. Hart
Summary: This study introduces a novel formulation of siRNA nanoparticles, termed RTNs, which can target tumors effectively while minimizing clearance by the liver, resulting in predominant accumulation in tumors rather than other organs in the body. The experiment demonstrates that these siRNA nanoparticles significantly retard the growth of xenograft tumors and improve survival rates, showing promise for delivering targeted siRNA therapeutics for cancer treatment.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Multidisciplinary Sciences
Shoko Itakura, Ayaka Shohji, Sayaka Amagai, Masashi Kitamura, Kozo Takayama, Kenji Sugibayashi, Hiroaki Todo
Summary: In this study, siRNAs were loaded into grapefruit-derived extracellular vesicles (GEVs) using a microfluidic device (MD), resulting in the formation of GEVs-siRNA-GEVs. The morphology of GEVs and siRNA-GEVs was observed using cryogenic transmission electron microscopy, and the cellular uptake and intracellular trafficking of these vesicles were evaluated in human keratinocytes. The study demonstrates the potential of MDs for the preparation of siRNA-loaded EV formulations.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Sandrine Pelofy, Hugo Bousquet, Laure Gibot, Marie-Pierre Rols, Muriel Golzio
Summary: The ability to modulate deregulated genes by RNAi shows promise for treating certain diseases, including cancers. While in vitro studies have shown the direct transfer of negatively charged siRNA across the plasma membrane, understanding the efficiency of siRNA electrotransfer into 3D tissues remains a challenge. Nonetheless, the asymmetrical distribution of siRNA within multicellular spheroids is a key finding and suggests that spheroids could be a valuable alternative to animal experimentation.
BIOELECTROCHEMISTRY
(2021)
Article
Engineering, Biomedical
Shrusti S. Patel, Ella N. Hoogenboezem, Fang Yu, Carlisle R. DeJulius, R. Brock Fletcher, Alex G. Sorets, Fiona K. Cherry, Justin H. Lo, Mariah G. Bezold, Nora Francini, Richard d'Arcy, Jordan E. Brasuell, Rebecca S. Cook, Craig L. Duvall
Summary: This study explores the use of ternary siRNA nanoparticles (si-NPs) for gene silencing in tumors. By optimizing the molecular weight and ratio of the core and surface polymer components, safe and effective si-NPs with strong inhibitory effects were developed. This work provides new insights into the structure-function relationships of ternary si-NPs and identifies strategies for safe and potent oncogene silencing.
Article
Chemistry, Multidisciplinary
David Vetvicka, Ladislav Sivak, Chinmay M. Jogdeo, Raj Kumar, Rubayat Khan, Yu Hang, David Oupicky
Summary: Despite extensive research and development in anticancer drugs, patient survival for pancreatic cancer has seen limited improvement. Gene silencing shows promise in inhibiting tumor-promoting genes in both tumor cells and stromal cells. Non-viral delivery systems for small RNAs and potential immunological implications are important in gene silencing therapy for pancreatic cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Alyssa C. Hill, Daniel van Leeuwen, Verena Schlosser, Alok Behera, Bogdan Mateescu, Jonathan Hall
Summary: RNA interference (RNAi) mediated by siRNA-3WJ, which is a fusion of siRNA with the phi29 3WJ motif, can enter the RNAi pathway through Dicer cleavage and achieve gene silencing. It has been found that siRNA-3WJs are effective even in Dicer-deficient or Argonaute 2-deficient cells, and they work best when the antisense strand of the siRNA duplex is positioned 5' of the 3WJ.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biotechnology & Applied Microbiology
Yifei Wang, Chunxi Wang, Justin Sylvers, Tatiana Segura, Fan Yuan
Summary: Electrotransfection (ET) is a non-viral approach used for delivering nucleic acids, but its efficiency is often low in vivo. In this study, we developed nanoenhancers that diffuse slowly in tissues and are poorly absorbed by blood and lymph microvessels. These nanoenhancers were found to enhance ET efficiency both in vitro and in vivo, and their mechanism of action was related to the inhibition of lysosomal functions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julien Ouvrard, Lisa Muniz, Estelle Nicolas, Didier Trouche
Summary: siRNAs can induce transcriptional silencing of chromatin-associated noncoding RNA through base-pairing with the target sequence. Transcriptional silencing occurs only in cis, and both Ago1 and Ago2 are involved.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Christian Berk, Gianluca Civenni, Yuluan Wang, Christian Steuer, Carlo V. Catapano, Jonathan Hall
Summary: The study shows that basic phosphorothioate modification of siRNA targeting Lin28B can increase metabolic stability. In vitro experiments demonstrated that it had stability exceeding patisiran and liver tritosome extracts, but not reaching the stability of the fitusiran siRNA core structure. After subcutaneous administration, the siRNA primarily accumulated in the liver and kidney.
NUCLEIC ACID THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Seo Jun Bae, Do Jin Im
Summary: This study systematically compared the delivery and expression efficiencies of RNA and DNA using a digital electroporation system in different cell types. The results showed that RNA is generally more favorable for expression than DNA, although RNA delivery efficiency may vary among different cell types. The compatibility between the cell type and nucleic acids used also affects the expression efficiency.
BIOELECTROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alexander H. van Asbeck, Jurgen Dieker, Rik Oude Egberink, Lennard van den Berg, Johan van der Vlag, Roland Brock
Summary: The study found a linear correlation between dose, uptake, and expression under different delivery vehicles, cell lines, and incubation times, and differences in expression levels can be explained by the number of mRNAs packaged per delivery vehicle. Using mRNA provides excellent quantitative control over protein expression over extended periods of time.
Article
Plant Sciences
Veli Vural Uslu, Athanasios Dalakouras, Victor A. Steffens, Gabi Krczal, Michael Wassenegger
Summary: Transitivity in plants relies on RDR6-mediated dsRNA synthesis and DCL endonuclease activity to reinforce target RNA cleavage through the formation of an RNA-induced silencing complex. This study found that the primary target site influences gene silencing and transitivity, with dsRNA synthesis generally initiated at the 3MODIFIER LETTER PRIME-end of the target RNA.
Review
Medicine, Research & Experimental
Sepideh Mirzaei, Mahmood Khaksary Mahabady, Amirhossein Zabolian, Alireza Abbaspour, Peyman Fallahzadeh, Maedeh Noori, Farid Hashemi, Kiavash Hushmandi, Salman Daneshi, Alan Prem Kumar, Amir Reza Aref, Saeed Samarghandian, Pooyan Makvandi, Haroon Khan, Michael R. Hamblin, Milad Ashrafizadeh, Ali Zarrabi
Summary: GBM is a serious brain tumor with no cure, requiring new genetic approaches for treatment. The use of siRNA can target and silence genes responsible for disease progression in GBM cells.
Article
Chemistry, Medicinal
Armin Hofmeister, Kerstin Jahn-Hofmann, Bodo Brunner, Mike Helms, Christiane Metz-Weidmann, Arne Krack, Michael Kurz, Christoph Heubel, Sabine Scheidler
Summary: Investigated the destabilizing properties of dioxane-and morpholino-based nucleotide analogues in siRNAs, and found that their application in siRNAs can improve non-specific targeting.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Nutrition & Dietetics
Akio Tanaka, Makoto Yamaguchi, Takuji Ishimoto, Takayuki Katsuno, Hironobu Nobata, Shiho Iwagaitsu, Hirokazu Sugiyama, Hiroshi Kinashi, Shogo Banno, Takahiro Imaizumi, Masahiko Ando, Yoko Kubo, Yasuhiko Ito
Summary: This study found that daily higher alcohol consumption in women was significantly associated with a higher incidence of proteinuria and low eGFR. However, no significant association between alcohol consumption and primary outcomes was observed in men.
Article
Multidisciplinary Sciences
Shun Minatoguchi, Shoji Saito, Kazuhiro Furuhashi, Yuriko Sawa, Masaki Okazaki, Yuko Shimamura, Ahmad Baseer Kaihan, Yusaku Hashimoto, Yoshinari Yasuda, Akitoshi Hara, Yasuyuki Mizutani, Ryota Ando, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Nobutoshi Esaki, Makoto Matsuyama, Yukihiro Shiraki, Hiroki Kobayashi, Naoya Asai, Atsushi Enomoto, Shoichi Maruyama
Summary: This study reveals a subset of PMC marked by Meflin, which is functionally distinct from classic pericytes and myofibroblasts. The findings highlight the importance of elucidating PMC heterogeneity.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, General & Internal
Akihito Tanaka, Kazuhiro Furuhashi, Kumiko Fujieda, Kayaho Maeda, Shoji Saito, Tetsushi Mimura, Yosuke Saka, Tomohiko Naruse, Takuji Ishimoto, Tomoki Kosugi, Fumie Kinoshita, Yachiyo Kuwatsuka, Shinobu Shimizu, Yasuhiro Nakai, Shoichi Maruyama
Summary: This study aims to evaluate the safety and efficacy of ADR-001 in adult patients with refractory IgA nephropathy.
FRONTIERS IN MEDICINE
(2022)
Article
Medicine, General & Internal
Yuki Kuroyanagi, Asami Takeda, Hiroshi Kinashi, Yoshiyuki Kuroyanagi, Minako Murata, Kenta Futamura, Norihiko Goto, Yoshihiko Watarai, Takuji Ishimoto, Kunio Morozumi, Yasuhiko Ito
Summary: The deposition of Galactose-deficient IgA1 (Gd-IgA1) was found in all transplanted kidneys, with latent IgA deposition noted in otherwise healthy kidneys. IgA deposition disappeared 1 year after kidney transplantation in most cases, but re-deposition was observed in a few cases. The deposition of Gd-IgA1 may indicate the initial stage of IgA nephropathy, but additional factors such as IgG deposition are required for the ultimate development of IgA nephropathy.
Article
Medicine, Research & Experimental
Shunnosuke Kunoki, Hideki Tatsukawa, Yukinao Sakai, Hiroshi Kinashi, Tetsuyoshi Kariya, Yasuhiro Suzuki, Masashi Mizuno, Makoto Yamaguchi, Hiroyuki Sasakura, Masashi Ikeno, Kosei Takeuchi, Takuji Ishimoto, Kiyotaka Hitomi, Yasuhiko Ito
Summary: Long-term peritoneal dialysis is often associated with peritoneal dysfunction characterized by fibrosis, inflammation, and angiogenesis. In this study, transglutaminase 2 (TG2) was identified as a potential therapeutic target for peritoneal injury. TG2 activity and protein expression were found to increase during the development of peritoneal fibrosis, and TGF-β and TG2 interaction played a role in regulating peritoneal fibrosis, angiogenesis, and inflammation. Inhibition of TG2 showed promising results in reducing peritoneal injuries associated with PD.
LABORATORY INVESTIGATION
(2023)
Article
Medicine, General & Internal
Makoto Yamaguchi, Masashi Mizuno, Fumiya Kitamura, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Shogo Banno, Akimasa Asai, Takuji Ishimoto, Takayuki Katsuno, Yasuhiko Ito
Summary: Thrombotic microangiopathy (TMA) and macrophage activation syndrome (MAS) are rare and life-threatening complications of systemic lupus erythematosus (SLE). The association between TMA and MAS in SLE patients has been rarely studied and the diagnosis of these conditions remains challenging. This case report demonstrates the efficacy of eculizumab in treating refractory TMA concurrent with SLE-associated MAS, and suggests the importance of evaluating TMA during the course of SLE-associated MAS.
FRONTIERS IN MEDICINE
(2023)
Article
Urology & Nephrology
Miyoko Kunou, Makoto Yamaguchi, Hirotake Takahashi, Yukihiro Kimura, Naoki Watanabe, Mayumi Ito, Hirokazu Sugiyama, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Takayuki Katsuno, Shogo Banno, Yasuhiko Ito, Takuji Ishimoto
Summary: Adenine phosphoribosyltransferase (APRT) deficiency, a rare genetic disorder, causes the accumulation of poorly soluble 2,8-dihydroxyadenine (DHA) in the kidneys, leading to various renal problems such as nephrolithiasis, acute kidney injury, and chronic kidney disease (CKD) due to crystal nephropathy. We present a case of a 43-year-old man with 2,8-DHA crystalline nephropathy caused by APRT deficiency, diagnosed definitively by urine gas chromatography-mass spectrometry (GC/MS)-based plasma metabolomics. This case highlights the importance of recognizing the signs, symptoms, and progression of this rare condition to CKD, which can be prevented by early administration of xanthine oxidoreductase inhibitors.
Article
Pharmacology & Pharmacy
Tomoko Mizaki, Hironobu Nobata, Shogo Banno, Makoto Yamaguchi, Hiroshi Kinashi, Shiho Iwagaitsu, Takuji Ishimoto, Yukiko Kuru, Masafumi Ohnishi, Ken-ichi Sako, Yasuhiko Ito
Summary: This study developed the first PPK model of MPA for Japanese lupus nephritis patients, and found that a double sampling strategy at 1 and 4 hours, as well as a single sampling strategy at 6 hours, were the most effective methods. These limited sampling strategies may facilitate safer, more effective, and individualized therapy.
JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES
(2023)
Article
Urology & Nephrology
Sumihisa Ono, Naoyuki Hatayama, Kanyu Miyamoto, Munekazu Naito, Takuji Ishimoto, Yasuhiko Ito
Summary: This study used a simple rat model to investigate the growth of endothelial cells on the luminal surface of arteriovenous grafts. The results showed that the formation of endothelial cells was initially more active on the venous side and then increased in number across the luminal surface. Future clinical studies could confirm whether puncture on the arterial side versus the venous side results in different infection rates.
CLINICAL AND EXPERIMENTAL NEPHROLOGY
(2023)
Article
Urology & Nephrology
Takehiko Wada, Sayaka Shimizu, Masahiro Koizumi, Tadashi Sofue, Hiroki Nishiwaki, Sho Sasaki, Izaya Nakaya, Yuji Oe, Takuji Ishimoto, Kengo Furuichi, Hirokazu Okada, Noriaki Kurita
Summary: This study examined nephrologists' adherence to the recommendations of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020. A web-based survey was conducted among certified nephrologists in Japan. The findings revealed gaps between recommendations and practices, particularly in serodiagnosis and treatment of membranous nephropathy.
CLINICAL AND EXPERIMENTAL NEPHROLOGY
(2023)
Article
Medicine, General & Internal
Reiko Muto, Yasuhiro Suzuki, Hideaki Shimizu, Kaoru Yasuda, Takuji Ishimoto, Shoichi Maruyama, Yasuhiko Ito, Masashi Mizuno
Summary: Fabry disease is a lysosomal storage disorder caused by mutations in the alpha-galactosidase A gene. In Fabry disease patients with end-stage renal disease (ESRD), cerebrovascular events are often fatal even with enzyme replacement therapy (ERT). The use of biomarkers to assess the response to ERT in such cases is unclear. A case of recurrent cerebrovascular complications under ERT in a Fabry disease patient progressing to ESRD on peritoneal dialysis is reported, suggesting that careful long-term follow-up is needed for Fabry disease patients with ESRD receiving ERT and exhibiting cerebrovascular manifestations.
Review
Biochemistry & Molecular Biology
Yasuhiko Ito, Ting Sun, Hiroya Tanaka, Makoto Yamaguchi, Hiroshi Kinashi, Fumiko Sakata, Shunnosuke Kunoki, Yukinao Sakai, Takuji Ishimoto
Summary: High salt intake contributes to over-hydration in chronic kidney disease (CKD) patients, and sodium storage in tissues, regulated by the TonEBP protein, is associated with inflammation, fibrosis, and organ dysfunction. Salt-loading subtotal nephrectomized mice showed macrophage infiltration and upregulated TonEBP expression in the heart and peritoneal wall, leading to cardiac fibrosis and peritoneal membrane dysfunction. Reducing salt intake and using anti-interleukin-6 therapy attenuated these effects. Further studies are needed to understand and regulate TonEBP activation in CKD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Kentaro Imai, Takuji Ishimoto, Tomohito Doke, Toshiki Tsuboi, Yu Watanabe, Keisuke Katsushima, Miho Suzuki, Hideto Oishi, Kazuhiro Furuhashi, Yasuhiko Ito, Yutaka Kondo, Shoichi Maruyama
Summary: This study investigated the function of lncRNAs in renal interstitial fibrosis (RIF), a common manifestation of chronic kidney diseases. The lncRNA lnc-CHAF1B-3 was found to be significantly upregulated in human renal proximal tubular cells when stimulated with TGF-β1 and hypoxia, accompanied by increased expression of EMT-related genes. Knockdown of lnc-CHAF1B-3 suppressed the upregulated expression of various genes related to RIF progression. This suggests that lnc-CHAF1B-3 may be a potential target for treating RIF.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Nutrition & Dietetics
Makoto Yamaguchi, Mayumi Ito, Hirokazu Sugiyama, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Takayuki Katsuno, Shogo Banno, Yasuhiko Ito, Masahiko Ando, Yoko Kubo, Keisuke Maeda, Yuria Ishida, Naoharu Mori, Takuji Ishimoto
Summary: A study found that malnutrition based on the GLIM criteria is associated with mortality in patients with cardiovascular disease (CVD), and the severity of malnutrition is positively correlated with mortality. Furthermore, malnutrition combined with renal dysfunction is also positively associated with mortality. These findings provide clinically relevant information for identifying high mortality risk and emphasizing the importance of addressing malnutrition with kidney dysfunction among CVD patients.
CLINICAL NUTRITION ESPEN
(2023)
Review
Rheumatology
Seika Terashima, Makoto Yamaguchi, Tomomi Ishihara, Junichiro Hagita, Takayuki Katsuno, Mayumi Ito, Hirokazu Sugiyama, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Takuji Ishimoto, Shogo Banno, Yasuhiko Ito
Summary: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by inflammation in multiple organ systems, most commonly the lungs, skin, and nervous system. Limb ulcers are a rare complication, and there are few reports on the use of mepolizumab in treating EGPA.
MODERN RHEUMATOLOGY CASE REPORTS
(2023)
