Review
Medicine, General & Internal
Geoffrey P. Dobson, Jodie L. Morris, Hayley L. Letson
Summary: This review provides an update on the effect of ALM therapy on increasing survival and blunting secondary injury after trauma and infection. ALM therapy resuscitates the body at permissive hypotensive blood pressures and confers neuroprotection. It resets the body's baroreflex and improves cardiovascular function, reduces inflammation, corrects coagulopathy, and reduces energy demand. ALM therapy has potential applications in stroke, muscle trauma, REBOA, burn polytrauma, damage control surgery, and orthopedic surgery.
FRONTIERS IN MEDICINE
(2023)
Article
Multidisciplinary Sciences
Magdalena Nueesch-Inderbinen, Andrea Treier, Marc J. A. Stevens, Roger Stephan
Summary: The study assessed the presence of pathogenic bacteria, specifically Shiga toxin-producing Escherichia coli (STEC), in game meat samples from different European countries. PCR analysis detected Shiga-toxin encoding genes in 84% of the samples, with 25% of the same samples containing isolated STEC strains. Various serotypes and sequence types were identified, with some strains carrying virulence factors associated with both STEC and extra-intestinal pathogenic E. coli (ExPEC). The findings suggest that game meat may serve as a potential source of STEC infections in humans, highlighting the importance of safe handling and preparation of such meat to prevent foodborne illnesses.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Naazneen Khan, Aniruddha Sasmal, Zahra Khedri, Patrick Secrest, Andrea Verhagen, Saurabh Srivastava, Nissi Varki, Xi Chen, Hai Yu, Travis Beddoe, Adrienne W. Paton, James C. Paton, Ajit Varki
Summary: This study found that the evolution paths of A and B subunits of AB5 toxins are different and proposed a nomenclature for B subunits based on bacterial species names. The study also found poor correlation between phylogenetic trees of B subunits and species phylogeny, indicating ongoing lateral gene transfers between different species. These findings help explain the host range and pathogenesis of Yersinia pestis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Editorial Material
Hematology
Jecko Thachil
Summary: Coagulopathy is closely connected to the field of hemostasis and thrombosis, and it may be associated with bleeding or clot formation depending on the circumstances. However, the use of the term coagulopathy to denote two clinically distinct presentations can create confusion. As specialists in hemostasis and thrombosis, it is our responsibility to clarify this ambiguity and promote the proper usage of coagulopathy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Toxicology
Katharina Sessler, Panagiotis Papatheodorou, Fanny Wondany, Maike Krause, Sabrina Noettger, Denise Bernhard, Jens Michaelis, Herbert Schmidt, Holger Barth
Summary: The study found that in the absence of SubB, SubA is internalized into the endoplasmic reticulum (ER) and cleaves the chaperone GRP78, leading to cytotoxic effects. By analyzing a SubA mutant, the C-terminal SEEL motif was identified as an ER-targeting signal.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Clinical Neurology
Sebastiaan M. Bossers, Stephan A. Loer, Frank W. Bloemers, Dennis Den Hartog, Esther M. M. Van Lieshout, Nico Hoogerwerf, Joukje van der Naalt, Anthony R. Absalom, Saskia M. Peerdeman, Lothar A. Schwarte, Christa Boer, Patrick Schober
Summary: The study suggests that prehospital administration of tranexamic acid is associated with increased mortality in patients with isolated severe traumatic brain injury, indicating caution in its use when there is no evidence of extracranial hemorrhage.
Review
Veterinary Sciences
Kelly Hall, Kenneth Drobatz
Summary: Resuscitation of acutely hemorrhaging small animal patients, such as dogs and cats, should prioritize hemorrhage control and judicious crystalloid administration followed by early consideration for blood component therapy to minimize blood loss, ameliorate coagulopathy, restore oxygen delivery, and correct changes in the glycocalyx.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Veterinary Sciences
Helen S. Philp, Kate S. Farrell, Ronald H. L. Li
Summary: Disseminated intravascular coagulation following melarsomine therapy for Dirofilaria immitis (D. immitis) is reported in a 9-year-old female intact pit bull-type dog. The dog had been diagnosed with D. immitis and treated with various medications, but the coagulopathy persisted and resulted in euthanasia.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Sebastien Larreche, Jean-Philippe Chippaux, Lucie Chevillard, Simon Mathe, Dabor Resiere, Virginie Siguret, Bruno Megarbane
Summary: Toxins from Bothrops venoms target hemostasis, causing bleeding, vascular damage, and complications. These toxins include enzymatic and non-enzymatic proteins, affecting vessels, platelets, and coagulation factors leading to hemorrhage and thrombosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Paul Vulliamy, Lucy Z. Kornblith, Matthew E. Kutcher, Mitchell J. Cohen, Karim Brohi, Matthew D. Neal
Summary: Platelets play a crucial role in the initial response to tissue injury, with altered responsiveness observed in both acutely injured patients and survivors. Aside from their role in coagulation, platelets contribute to the sterile inflammatory response to injury and can impact multiple-organ dysfunction syndromes.
Article
Cell Biology
Kinnosuke Yahiro, Kohei Ogura, Hiroyasu Tsutsuki, Sunao Iyoda, Makoto Ohnishi, Joel Moss
Summary: The study found that SubAB toxin induces cell apoptosis by significantly upregulating KLHDC7B expression. Knockdown of KLHDC7B inhibits the apoptotic pathway stimulated by SubAB, reducing cytotoxicity. Additionally, KLHDC7B regulates the expression of the HRK gene, affecting apoptosis caused by toxin-mediated ER stress.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Shinichiro Hama, Miki Nakahara, Miho Watanabe-Takahashi, Eiko Shimizu, Hiroyasu Tsutsuki, Kinnosuke Yahiro, Kiyotaka Nishikawa
Summary: A series of multivalent peptides that efficiently bind to the receptor-binding region of SubAB were identified, and these peptides competitively inhibited the binding of SubAB to receptor molecules. One specific peptide, FFP-tet, was able to absorb SubAB cytotoxicity through direct binding to the toxin. These findings suggest that FFP-tet-beads may be an effective therapeutic agent for complications arising from eae-negative STEC infection.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Medicine, General & Internal
Yuki Itagaki, Mineji Hayakawa, Yuki Takahashi, Kazuma Yamakawa
Summary: This systematic review and meta-analysis will evaluate the use of fibrinogen concentrate (FC) for hemorrhages in emergency situations. The primary outcome is in-hospital mortality. The study aims to provide physicians with updated information on the efficacy and safety of using FC for hemorrhage in emergency settings.
Article
Critical Care Medicine
Jason B. Brill, Megan Brenner, Juan Duchesne, Derek Roberts, Paula Ferrada, Tal Horer, David Kauvar, Mansoor Khan, Andrew Kirkpatrick, Carlos Ordonez, Bruno Perreira, Artai Priouzram, Bryan A. Cotton
Summary: Trauma-induced coagulopathy is associated with high mortality, and viscoelastic testing like TEG and ROTEM can predict massive transfusion and coagulopathy earlier than conventional testing, guiding resuscitation efforts after trauma.
Article
Critical Care Medicine
Taleen A. MacArthur, Grant M. Spears, Rosemary A. Kozar, Jing-fei Dong, Matthew Auton, Donald H. Jenkins, Kent R. Bailey, Aneel A. Ashrani, Mike J. Ferrara, Joseph M. Immermann, Timothy M. Halling, Myung S. Park
Summary: This study found that trauma patients with decreased arrival systolic blood pressure, increased INR, and decreased time to peak are at higher risk of requiring a high rate of packed red blood cell transfusions. Patients with accelerated thrombin generation have an increased risk of requiring transfusions.
Article
Oncology
Aya Sugyo, Atsushi B. Tsuji, Hitomi Sudo, Kanako Takano, Moriaki Kusakabe, Tatsuya Higashi
Article
Biochemistry & Molecular Biology
Honoka Obata, Atsushi B. Tsuji, Hitomi Sudo, Aya Sugyo, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Ming-Rong Zhang
Summary: Research has shown that the use of no-carrier-added radio-cisplatin can cause severe DNA damage without chemical harm, by releasing Auger electrons very close to the DNA target. Although uptake is low, this method can still induce DNA double-strand breaks effectively. Efficient delivery of radio-drugs to DNA is crucial for the successful clinical application of Auger electrons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Winn Aung, Atsushi B. Tsuji, Aya Sugyo, Masayuki Fujinaga, Ming-Rong Zhang, Tatsuya Higashi
Summary: Photoimmunotherapy (PIT) combined with chemotherapy shows improved efficacy in cancer treatment. By evaluating the super-enhanced permeability and retention effect of different molecular weight drugs, promising candidates for combined PIT treatment were identified, leading to increased drug accumulation in tumors. Further preclinical and clinical studies are encouraged to develop combination therapy of PIT with conventional anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Tomoko Tachibana, Tomoko Gowa Oyama, Yukie Yoshii, Fukiko Hihara, Chika Igarashi, Atsushi B. Tsuji, Tatsuya Higashi, Mitsumasa Taguchi
Summary: This study established a xenograft mouse model of subcutaneous submillimeter tumors with human colorectal cancer HT-29 cells. The use of radiation-crosslinked gelatin hydrogel microwells (rGHMs) as a culture base and transplantation scaffold allowed for the formation of uniform spheroids and creation of consistent xenografted submillimeter tumors. The model provides a useful platform for the development of medicines and methods for detection and treatment of small nodules of colorectal cancer.
APPLIED SCIENCES-BASEL
(2021)
Article
Cell Biology
Hitomi Sudo, Atsushi B. Tsuji, Aya Sugyo, Mika K. Kaneko, Yukinari Kato, Kotaro Nagatsu, Hisashi Suzuki, Tatsuya Higashi
Summary: The study demonstrated that alpha-radioimmunotherapy with the newly developed NZ-16 antibody is a promising therapeutic option for malignant mesothelioma, showing higher antitumor effects compared to the previous antibody NZ-12.
Article
Cardiac & Cardiovascular Systems
Kazunari Maekawa, Atsushi B. Tsuji, Atsushi Yamashita, Aya Sugyo, Chietsugu Katoh, Minghui Tang, Kensaku Nishihira, Yoshisato Shibata, Chihiro Koshimoto, Ming-Rong Zhang, Ryuichi Nishii, Keiichiro Yoshinaga, Yujiro Asada
Summary: This study demonstrated that F-18-FEDAC-PET can visualize atherosclerotic lesions in rabbit models and human coronary arteries, with higher TSPO expression in areas with more macrophages. TSPO expression may serve as a marker for high-risk coronary plaques.
Article
Cell Biology
Kinnosuke Yahiro, Kohei Ogura, Hiroyasu Tsutsuki, Sunao Iyoda, Makoto Ohnishi, Joel Moss
Summary: The study found that SubAB toxin induces cell apoptosis by significantly upregulating KLHDC7B expression. Knockdown of KLHDC7B inhibits the apoptotic pathway stimulated by SubAB, reducing cytotoxicity. Additionally, KLHDC7B regulates the expression of the HRK gene, affecting apoptosis caused by toxin-mediated ER stress.
CELL DEATH DISCOVERY
(2021)
Article
Chemistry, Medicinal
Honoka Obata, Atsushi B. Tsuji, Katsushi Kumata, Hitomi Sudo, Katsuyuki Minegishi, Kotaro Nagatsu, Hideo Takakura, Mikako Ogawa, Akihiro Kurimasa, Ming-Rong Zhang
Summary: This study aims to establish new labeling methods for no-carrier-added radio-Pt (191Pt) and evaluate the in vitro properties of 191Pt-labeled agents compared with those of agents labeled with the common emitter 111In. The results showed that 191Pt labeled via DTPA or Cys had a comparable intranuclear fraction to 111In labeled via DTPA, but demonstrated a significantly higher DNA-binding/cellular uptake ratio. This suggests that 191Pt has better DNA targeting capabilities than 111In.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Hiroyasu Tsutsuki, Tianli Zhang, Kinnosuke Yahiro, Katsuhiko Ono, Yukio Fujiwara, Sunao Iyoda, Fan-Yan Wei, Kazuaki Monde, Kazuko Seto, Makoto Ohnishi, Hiroyuki Oshiumi, Takaaki Akaike, Tomohiro Sawa
Summary: SubAB inhibits the activation of the NLRP3 inflammasome and the production of interleukins in murine macrophages through ER stress signaling, which may be associated with the survival and pathogenicity of STEC strains in hosts.
Article
Engineering, Chemical
Tatsuya Higashi, Kotaro Nagatsu, Atsushi B. Tsuji, Ming-Rong Zhang
Summary: This paper reviews the research on Ac-225 production and pharmaceutical development at the National Institutes for Quantum Science and Technology (QST), discussing the current status of global Ac-225 supply and the development of new production methods. It emphasizes the challenges faced by Japan as a resource-poor country in the field of medical applications.
Article
Biochemistry & Molecular Biology
Honoka Obata, Akihiro Kurimasa, Tadanori Muraoka, Atsushi B. Tsuji, Katsuya Kondo, Yoshikazu Kuwahara, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Ming-Rong Zhang
Summary: This study evaluates the relationship between DNA damage induced by radiolabeled cisplatin and the cell cycle. The results show that radiolabeled cisplatin causes more double-strand breaks (DSBs) in the G1 phase compared to nonradioactive cisplatin and saline. This suggests that the G1 phase is a promising target for Auger electron-induced DNA damage.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Zhao-Hui Jin, Atsushi B. Tsuji, Melissa Degardin, Pascal Dumy, Didier Boturyn, Tatsuya Higashi
Summary: This study aimed to reveal the intratumoral distribution of pH (low) insertion peptides (pHLIPs) and their spatial relationship with other tumor features. The results showed that the distribution of fluorescent dye-labeled pHLIPs in tumors was not uniform, with a high degree of colocalization with necrosis. The hypoxic region was spatially contiguous but not overlapping with pHLIPs. Additionally, the proliferative activity was still detectable in the pHLIP-accumulated regions.
Article
Oncology
Hitomi Sudo, Atsushi B. Tsuji, Aya Sugyo, Yosuke Harada, Satoshi Nagayama, Toyomasa Katagiri, Yusuke Nakamura, Tatsuya Higashi
Summary: The study compared the effects of three chelates on Ac-225 labeling of OTSA101 antibody and found that DOTAGA chelate had the optimal labeling efficiency and stability, providing high absorbed doses to tumors and limited absorbed doses to bone marrow.
Article
Chemistry, Medicinal
Honoka Obata, Atsushi B. Tsuji, Hitomi Sudo, Aya Sugyo, Kaori Hashiya, Hayato Ikeda, Masatoshi Itoh, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Toshikazu Bando, Hiroshi Sugiyama, Ming-Rong Zhang
Summary: Auger electrons can efficiently damage specific DNA sites that play a key role in cancer cell survival. This study developed a Pt-191-labeled agent targeting the oncogene MYCN and demonstrated its ability to efficiently bind to DNA, cause DNA damage, and decrease MYCN gene expression and cell viability. However, the delivery of the agent to tumors needs improvement.
Article
Oncology
Aya Sugyo, Atsushi B. Tsuji, Hitomi Sudo, Yoshiya Sugiura, Mitsuru Koizumi, Tatsuya Higashi
Summary: This study provides direct evidence that Wnt1 is involved in the development of osteoblastic bone metastasis and establishes a model for further investigating the molecular mechanisms and developing effective therapies for the disease.