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Fulltext Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19

Yap JKY, Moriyama M, Iwasaki A

J Immunol, 2020 Jul 15;205(2):307-312.
PMID: 32493814 DOI: 10.4049/jimmunol.2000513

The inflammatory response to severe acute respiratory syndrome-related coronavirus 2 infection has a direct impact on the clinical outcomes of coronavirus disease 2019 patients. Of the many innate immune pathways that are engaged by severe acute respiratory syndrome-related coronavirus 2, we highlight the importance of the inflammasome pathway. We discuss available pharmaceutical agents that target a critical component of inflammasome activation, signaling leading to cellular pyroptosis, and the downstream cytokines as a promising target for the treatment of severe coronavirus disease 2019-associated diseases.
Fulltext Impact of a Novel Oblique-Tip Papillotome for Biliary Cannulation during ERCP: A Nonrandomized Coarsened Exact Matching Study

Imazu H, Ho SH, Hino S, Goh KL, Moriyama M, Sumiyama K, et al.

Gastroenterol Res Pract, 2020;2020:2417841.
PMID: 32454813 DOI: 10.1155/2020/2417841

Background: We developed a novel oblique-tip papillotome (OT-papillotome) to facilitate biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP). This study was performed to evaluate the utility of the OT-papillotome for contrast-guided cannulation (CGC) and wire-guided cannulation (WGC) during ERCP, compared with standard cannulation by WGC using a standard-tip papillotome (ST-papillotome).
Methods: A prospective study was performed at two centers. CGC with the OT-papillotome (OT-CGC group) was performed at Jikei University Hospital, while WGC was done with the OT-papillotome and ST-papillotome (OT-WGC and ST-WGC groups, respectively) at the University of Malaya Medical Centre. The results of the OT-CGC and OT-WGC groups were compared with those of the ST-WGC group after performing coarsened exact matching (CEM) to reduce bias due to nonrandomized and center-based patient allocation.
Results: Eighty patients were enrolled in each of the OT-CGC, OT-WGC, and ST-WGC groups. After CEM, the successful biliary cannulation rate was significantly higher in the OT-CGC and OT-WGC groups than in the ST-WGC group, while rescue cannulation was reduced. The mean number of unintended pancreatic access events in the OT-WGC and OT-CGC groups was similar to the ST-WGC group. However, it was significantly lower in the OT-WGC group than in the OT-CGC group. Multivariate analysis revealed that the OT-papillotome was independently associated with less frequent rescue cannulation and a higher successful biliary cannulation rate.
Conclusions: Although use of the OT-papillotome in biliary cannulation did not reduce unintended pancreatic access events or PEP compared to the ST-papillotome, the OT-papillotome increased the successful biliary cannulation rate, while reducing the frequency of rescue cannulation procedures. Combining the OT-papillotome with WGC might be the best cannulation technique for minimizing unintended pancreatic access.
Fulltext IMiD/CELMoD-induced growth suppression of adult T-cell leukemia/lymphoma cells via cereblon through downregulation of target proteins and their downstream effectors

Wang Y, Shimosaki S, Ikebe E, Iha H, Yamamoto JI, Fife N, et al.

Front Oncol, 2023;13:1272528.
PMID: 38344143 DOI: 10.3389/fonc.2023.1272528

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasia associated with human T-cell leukemia virus type 1 (HTLV-1) infection and has an extremely poor prognosis. Lenalidomide (LEN; a second-generation immunomodulatory drug [IMiD]) has been employed as an additional therapeutic option for ATL since 2017, but its mechanism of action has not been fully proven, and recent studies reported emerging concerns about the development of second primary malignancies in patients treated with long-term IMiD therapy. Our purpose in this study was to elucidate the IMiD-mediated anti-ATL mechanisms. Thirteen ATL-related cell lines were divided into LEN-sensitive or LEN-resistant groups. CRBN knockdown (KD) led to a loss of LEN efficacy and IKZF2-KD-induced LEN efficacy in resistant cells. DNA microarray analysis demonstrated distinct transcriptional alteration after LEN treatment between LEN-sensitive and LEN-resistant ATL cell lines. Oral treatment of LEN for ATL cell-transplanted severe combined immunodeficiency (SCID) mice also indicated clear suppressive effects on tumor growth. Finally, a novel cereblon modulator (CELMoD), iberdomide (IBE), exhibited a broader and deeper spectrum of growth suppression to ATL cells with efficient IKZF2 degradation, which was not observed in other IMiD treatments. Based on these findings, our study strongly supports the novel therapeutic advantages of IBE against aggressive and relapsed ATL.
Fulltext Complete Sequences of the Human T-Cell Leukemia Virus Type 1 Proviral Genomes from Newly Established Adult T-Cell Leukemia Cell Lines in Oita Prefecture, Japan

Fukumoto T, Ikebe E, Ogata M, Kohno K, Kuramitsu M, Sato Y, et al.

Genome Announc, 2018 Jun 21;6(25).
PMID: 29930027 DOI: 10.1128/genomeA.00090-18

We report two complete proviral genome sequences of human T-cell leukemia virus type 1 (HTLV-1) isolated from the peripheral blood specimens of acute type adult T-cell leukemia (ATL) patients in Oita Prefecture, Japan.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.