Proceedings of the Japan Academy. Series B, Physical and Biological Sciences最新文献

Syntheses and biological evaluation of M-COPA analogs derived from pentadienoic Weinreb amide. 五二烯Weinreb酰胺衍生M-COPA类似物的合成及生物学评价。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-10-10 Epub Date: 2025-07-18 DOI: 10.2183/pjab.101.029

Hisazumi Tsutsui, Daiki Usukura, Fumiya Watabe, Hiroki Okano, Ryo Hirata, Ryunosuke Shiogama, Yamato Kanai, Saki Kato, Yuki Asahara, Sayaka Chogi, Yingjia Lu, Haruka Hirai, Mai Kitamoto, Miho Kojima, Yuuki Obata, Motoyuki Shimonaka, Takatsugu Murata, Isamu Shiina

{"title":"Syntheses and biological evaluation of M-COPA analogs derived from pentadienoic Weinreb amide.","authors":"Hisazumi Tsutsui, Daiki Usukura, Fumiya Watabe, Hiroki Okano, Ryo Hirata, Ryunosuke Shiogama, Yamato Kanai, Saki Kato, Yuki Asahara, Sayaka Chogi, Yingjia Lu, Haruka Hirai, Mai Kitamoto, Miho Kojima, Yuuki Obata, Motoyuki Shimonaka, Takatsugu Murata, Isamu Shiina","doi":"10.2183/pjab.101.029","DOIUrl":"10.2183/pjab.101.029","url":null,"abstract":"M-COPA (1), which contains diene and 3-picolylamine moieties in its side chain and seven stereogenic centers in a multisubstituted octalin skeleton, strongly inhibits the growth of several cancer cell lines. Expecting the improvement of conformational flexibility of basic and coordinating 3-pyridylmethylamino group on M-COPA and its physical properties, we efficiently synthesized its amine analogs by replacing its amide group with an amino group through the Weinreb amide-type Horner-Wadsworth-Emmons reaction. The cytotoxic properties of 1 and its analogs were evaluated against NCI-H226, a lung cancer cell line, HeLa, a cervical cancer cell line, and GIST-T1, a gastrointestinal stromal tumor cell line. The evaluation results indicated that the structural alteration from amide moiety to amine moiety lowered the pharmacological activity but remained strong cytotoxicity.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"510-518"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical properties and biological activities of three highly purified major tetrodotoxin analogues. 三种高度纯化的主要河豚毒素类似物的化学性质和生物活性。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-10-10 Epub Date: 2025-09-05 DOI: 10.2183/pjab.101.033

Mari Yotsu-Yamashita, Yuta Kudo, Kyoka Sato, Osamu Chiba, Yuko Cho, Ryuichi Watanabe, Toshiyuki Suzuki, Keiichi Konoki

{"title":"Chemical properties and biological activities of three highly purified major tetrodotoxin analogues.","authors":"Mari Yotsu-Yamashita, Yuta Kudo, Kyoka Sato, Osamu Chiba, Yuko Cho, Ryuichi Watanabe, Toshiyuki Suzuki, Keiichi Konoki","doi":"10.2183/pjab.101.033","DOIUrl":"10.2183/pjab.101.033","url":null,"abstract":"Tetrodotoxin (TTX), the pufferfish toxin, has the potential to cause fatal food poisoning because of its potent voltage-gated sodium channel (Nav) blocking activity. 4-epiTTX, 11-norTTX-6(S)-ol, and 11-oxoTTX are the major TTX analogues found in marine animals; thus, their chemical properties and biological activities should be determined. In this study, these three TTX analogues were purified to a high level (purity >97%) from pufferfish and newts. The ratios of the hemilactal to the 10,7-lactone forms were determined using 1H NMR, and 13C NMR data were also obtained. 4-epiTTX underwent considerable transformation to TTX in physiological conditions. The Nav blocking activity of these analogues was evaluated by whole-cell patch-clamp recording using a human Nav1.2, colorimetric cell-based assay and mouse bioassay. The toxicity equivalency factors (TEFs setting TTX 1) of the three analogues were estimated; 4-epiTTX (0.06), 11-norTTX-6(S)-ol (0.02), and 11-oxoTTX (1.2) using patch-clamp recording, and 11-norTTX-6(S)-ol (0.50) and 11-oxoTTX (0.42) using the mouse bioassay. These data confirmed the low Nav blocking activity of 4-epiTTX and high activity of 11-oxoTTX.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"519-533"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unconstrained deep learning-based sleep stage classification using cardiorespiratory and body movement activities in adults with suspected sleep apnea. 基于无约束深度学习的睡眠阶段分类，使用疑似睡眠呼吸暂停的成人心肺和身体运动活动。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-08-30 DOI: 10.2183/pjab.101.032

Seiichi Morokuma, Toshinari Hayashi, Naoyuki Motomura, Masatomo Kanegae, Yoshihiko Mizukami, Shinji Asano, Ichiro Kimura, Kenji Fujita, Yutaka Kohda, Hiroshi Imai, Yuji Tateizumi, Hitoshi Ueno, Subaru Ikeda, Kyuichi Niizeki

{"title":"Unconstrained deep learning-based sleep stage classification using cardiorespiratory and body movement activities in adults with suspected sleep apnea.","authors":"Seiichi Morokuma, Toshinari Hayashi, Naoyuki Motomura, Masatomo Kanegae, Yoshihiko Mizukami, Shinji Asano, Ichiro Kimura, Kenji Fujita, Yutaka Kohda, Hiroshi Imai, Yuji Tateizumi, Hitoshi Ueno, Subaru Ikeda, Kyuichi Niizeki","doi":"10.2183/pjab.101.032","DOIUrl":"https://doi.org/10.2183/pjab.101.032","url":null,"abstract":"This study assessed the feasibility of unconstrained deep-learning-based sleep stage classification using cardiorespiratory and body movement activities derived from piezoelectric sensors installed under a bed mattress. Heart and respiratory rates and their respective variabilities, cardiorespiratory coupling index, and body movement were simultaneously acquired through polysomnography (PSG) for 106 untreated participants with suspected sleep apnea. We used a bidirectional long short-term memory network to predict the five sleep stages using five different input feature combinations. The best performance was achieved with a model comprising six parameters, including cardiorespiratory variability features, with a balanced accuracy of 0.70 ± 0.05, Cohen's κ of 0.40 ± 0.12, and an F1 score of 0.62 ± 0.08. Deming regression and Bland-Altman analyses of the six major sleep parameters estimated by the model and those determined by PSG showed significant correlations (r = 0.426-0.695) with a low bias. These results demonstrate the effectiveness of the proposed approach and its potential to expand opportunities for in-home sleep monitoring.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel glomerulopathy model demonstrates renal counterbalance via local angiotensin II regulation. 一种新的肾小球疾病模型显示肾脏平衡通过局部血管紧张素II调节。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-07-29 Epub Date: 2025-06-20 DOI: 10.2183/pjab.101.025

Kazuo Sakamoto, Kunio Kawanishi, Jun-Dal Kim, Masahiro Koizumi, Shin-Ichi Muroi, Saori Tabara, Akiyoshi Fukamizu, Taiji Matsusaka, Michio Nagata

{"title":"A novel glomerulopathy model demonstrates renal counterbalance via local angiotensin II regulation.","authors":"Kazuo Sakamoto, Kunio Kawanishi, Jun-Dal Kim, Masahiro Koizumi, Shin-Ichi Muroi, Saori Tabara, Akiyoshi Fukamizu, Taiji Matsusaka, Michio Nagata","doi":"10.2183/pjab.101.025","DOIUrl":"10.2183/pjab.101.025","url":null,"abstract":"Renal counterbalance, involving compensatory hypertrophy of the healthy kidney and atrophy of the injured one, remains incompletely understood, particularly at the glomerular level. In this study, we employed NEP25 mice, which selectively express human CD25 in podocytes, enabling precise induction of unilateral podocyte injury through the administration of LMB2, a CD25-targeted immunotoxin. Using a two-kidney, one-nephropathy (2K1N) model, we demonstrated that asymmetric changes in renal blood flow and proteinuria, with histological and transcriptomic analyses uncovering distinct pathological and molecular features between the injured and contralateral healthy kidneys. Notably, an imbalance in intrarenal angiotensin (Ang) II levels was observed, and angiotensin-converting enzyme inhibition ameliorated the glomerular damage and restored perfusion. These findings indicate that local Ang II dysregulation is a key factor in renal counterbalance. Our study provides the first glomerulopathy-based experimental platform to dissect asymmetric renal adaptation, offering fundamental insight into the homeostatic mechanisms of renal function in health and disease.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"431-444"},"PeriodicalIF":4.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The shifting paradigm of chromatin structure: from the 30-nm chromatin fiber to liquid-like organization. 染色质结构的转变范式：从30纳米染色质纤维到液体状组织。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-06-11 Epub Date: 2025-06-05 DOI: 10.2183/pjab.101.020

Kazuhiro Maeshima

{"title":"The shifting paradigm of chromatin structure: from the 30-nm chromatin fiber to liquid-like organization.","authors":"Kazuhiro Maeshima","doi":"10.2183/pjab.101.020","DOIUrl":"10.2183/pjab.101.020","url":null,"abstract":"The organization and dynamics of chromatin are critical for genome functions such as transcription and DNA replication/repair. Historically, chromatin was assumed to fold into the 30-nm fiber and progressively arrange into larger helical structures, as described in the textbook model. However, over the past 15 years, extensive evidence including our studies has dramatically transformed the view of chromatin from a static, regular structure to one that is more variable and dynamic. In higher eukaryotic cells, chromatin forms condensed yet liquid-like domains, which appear to be the basic unit of chromatin structure, replacing the 30-nm fiber. These domains maintain proper accessibility, ensuring the regulation of DNA reaction processes. During mitosis, these domains assemble to form more gel-like mitotic chromosomes, which are further constrained by condensins and other factors. Based on the available evidence, I discuss the physical properties of chromatin in live cells, emphasizing its viscoelastic nature-balancing local fluidity with global stability to support genome functions.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"339-356"},"PeriodicalIF":4.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

f₄-statistics-based ancestry profiling and convolutional neural network phenotyping shed new light on the structure of genetic and spike shape diversity in Aegilops tauschii Coss. 基于统计分析和卷积神经网络表型分析的方法，揭示了陶氏Aegilops tauschii遗传结构和穗形多样性。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-06-11 Epub Date: 2025-05-21 DOI: 10.2183/pjab.101.023

Yoshihiro Koyama, Mizuki Nasu, Yoshihiro Matsuoka

{"title":"f4-statistics-based ancestry profiling and convolutional neural network phenotyping shed new light on the structure of genetic and spike shape diversity in Aegilops tauschii Coss.","authors":"Yoshihiro Koyama, Mizuki Nasu, Yoshihiro Matsuoka","doi":"10.2183/pjab.101.023","DOIUrl":"10.2183/pjab.101.023","url":null,"abstract":"Aegilops tauschii Coss., a progenitor of bread wheat, is an important wild genetic resource for breeding. The species comprises three genetically defined lineages (TauL1, TauL2, and TauL3), each displaying valuable phenotypes in agronomic traits, including spike shape. In the present work, we studied the relationship between population structure and spike shape variation patterns using a collection of 249 accessions. f4-statistics-based ancestry profiling confirmed the previously identified lineages and revealed a genetic component derived from TauL3 in the genomes of some southern Caspian and Transcaucasus TauL1 and TauL2 accessions. Spike shape variation patterns were analyzed using a convolutional neural network-based approach, trained on green and dry spike image datasets. This analysis showed that spike shape diversity is structured according to lineages and demonstrated the potential to distinguish the lineages based on spike shape. The implications of these findings for the origins of common wheat and the intraspecific taxonomy of Ae. tauschii are discussed.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"357-370"},"PeriodicalIF":4.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conformational dynamics and molecular interactions of natural products: unveiling functional structures in biological membranes. 天然产物的构象动力学和分子相互作用：揭示生物膜的功能结构。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-05-09 Epub Date: 2025-03-31 DOI: 10.2183/pjab.101.016

Michio Murata, Masayuki Satake, Nobuaki Matsumori

引用次数: 0

Mechanism of puberulic acid contamination in red yeast rice tablets that caused a serious food poisoning outbreak in Japan. 红曲米片剂中微嫩酸污染导致日本严重食物中毒的机理。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-05-09 Epub Date: 2025-03-31 DOI: 10.2183/pjab.101.017

Tomoya Yoshinari, Maiko Watanabe, Wataru Aoki, Seiji Tanaka, Naoko Masumoto, Michiho Ito, Takahiro Ohnishi

{"title":"Mechanism of puberulic acid contamination in red yeast rice tablets that caused a serious food poisoning outbreak in Japan.","authors":"Tomoya Yoshinari, Maiko Watanabe, Wataru Aoki, Seiji Tanaka, Naoko Masumoto, Michiho Ito, Takahiro Ohnishi","doi":"10.2183/pjab.101.017","DOIUrl":"10.2183/pjab.101.017","url":null,"abstract":"In Japan, serious food poisoning among individuals who took supplement tablets for lowering plasma cholesterol levels have been publicized since late March 2024. The tablets were prepared from red yeast rice (RYR), a product of Monascus pilosus. Puberulic acid (PA) was detected as an unexpected compound in tablets that caused food poisoning. We conducted an on-site investigation at the RYR production factory to determine the cause of PA contamination of the tablets. Fungi capable of producing PA were detected in wipe samples from the factory and were identified as Penicillium adametzioides. To understand the route through which P. adametzioides contaminated RYR and produced PA, coculture experiments with M. pilosus and P. adametzioides were performed. P. adametzioides grew on rice covered with M. pilosus and produced PA. These results suggest that PA-producing P. adametzioides inhabited the RYR production factory and accidently contaminated the culture of M. pilosus. Consequently, RYR tablets contaminated with PA were manufactured and caused the food poisoning outbreak.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"302-316"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A thermostable and highly active fungal GH3 β-glucosidase generated by random and saturation mutagenesis. 一种耐热高活性真菌GH3 β-葡萄糖苷酶，由随机诱变和饱和诱变产生。

IF 4.6 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-03-11 Epub Date: 2025-02-20 DOI: 10.2183/pjab.101.011

Chiaki Matsuzaki, Masafumi Hidaka, Yukari Nakashima, Yuji Honda, Takashi Koyanagi, Kazuhiko Ishikawa, Toshihiko Katoh, Takane Katayama, Hidehiko Kumagai

{"title":"A thermostable and highly active fungal GH3 β-glucosidase generated by random and saturation mutagenesis.","authors":"Chiaki Matsuzaki, Masafumi Hidaka, Yukari Nakashima, Yuji Honda, Takashi Koyanagi, Kazuhiko Ishikawa, Toshihiko Katoh, Takane Katayama, Hidehiko Kumagai","doi":"10.2183/pjab.101.011","DOIUrl":"10.2183/pjab.101.011","url":null,"abstract":"Enhancing the thermostability of cellulose-degrading enzymes is pivotal for establishing an efficient bioconversion system from cellulosic materials to value-added compounds. Here, by introducing random and saturation mutagenesis into the Thermoascus aurantiacus β-glucosidase gene, we generated a hyperthermostable mutant with five amino acid substitutions. Analysis of temperature-induced unfolding revealed the involvement of each replacement in the increased Tm value. Structural analysis showed that all replacements are located at the periphery of the catalytic pocket. D433N replacement, which had a pronounced thermostabilizing effect (ΔTm ＝ 4.5°C), introduced an additional hydrogen bond with a backbone carbonyl oxygen in a long loop structure. The mutant enzyme expressed in Kluyveromyces marxianus exhibited a Tm of 82°C and hydrolyzed cellobiose with kcat and Km values of 200 s－1 and 1.8 mM, respectively. When combined with a thermostable endoglucanase, the mutant enzyme released 20％ more glucose than wild-type enzyme from cellulosic material. The mutant enzyme is therefore a noteworthy addition to the existing repertoire of thermostable β-glucosidases.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"177-195"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation. 凝血调节素-血管内凝血和炎症的关键调节因子，以及弥散性血管内凝血的治疗方法。

IF 4.4 3区综合性期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2025-02-10 Epub Date: 2024-12-18 DOI: 10.2183/pjab.101.006

Koji Suzuki

{"title":"Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.","authors":"Koji Suzuki","doi":"10.2183/pjab.101.006","DOIUrl":"10.2183/pjab.101.006","url":null,"abstract":"Thrombomodulin (TM) is an important regulator of intravascular blood coagulation, fibrinolysis, and inflammation. TM inhibits the procoagulant and proinflammatory activities of thrombin and promotes the thrombin-induced activation of protein C (PC) bound to the endothelial PC receptor (EPCR). Activated PC (APC) inactivates coagulation factors Va and VIIIa, thereby inhibiting blood clotting. APC bound to EPCR exerts anti-inflammatory and cytoprotective effects on vascular endothelial cells. TM promotes the activation of thrombin-activatable fibrinolysis inhibitor, and also protects cells in blood vessels from inflammation caused by pathogen-associated and damaged cell-associated molecules. Excessive anticoagulant, fibrinolytic, anti-inflammatory, and tissue regenerative effects in the TM-PC pathway are controlled by PC inhibitor. A recombinant TM drug (TM), a soluble form of natural TM developed from the cloned human TM gene, has been evaluated for efficacy in many clinical trials and approved as a treatment for disseminated intravascular coagulation (DIC) caused by diseases such as sepsis, solid tumors, hematopoietic tumors, and trauma. It is currently widely used to treat DIC in Japan.","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":" ","pages":"75-97"},"PeriodicalIF":4.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0