Pulmonary thrombotic microangiopathy caused by gastric carcinoma.

Pulmonary tumour thrombotic microangiopathy (PTTM) is characterised by wide spread tumour emboli along with fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles. PTTM is a rare but fatal complication of carcinoma, but the pathogenesis remains to be clarified. An autopsy case of PTTM caused by gastric adenocarcinoma is described, in which tumour cells in the PTTM lesion had positive immunoreactivity for platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR), and proliferating fibromuscular intimal cells also showed expression of PDGFR. In addition, the overexpression of PGDF was detected in the alveolar macrophages. These findings suggest that PDGF derived from alveolar macrophages and from tumour cells may act together in promoting fibrocellular intimal proliferation. To the best of the authors\u27 knowledge, the possible involvement of activated alveolar macrophages in PTTM has not been previously reported

Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway.

OBJECT: The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action. RESULT: When the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-alpha, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-alpha-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-alpha inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-alpha inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-alpha, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-alpha alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication. CONCLUSION: IFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Pulmonary thrombotic microangiopathy caused by gastric carcinoma

Pulmonary tumour thrombotic microangiopathy (PTTM) is characterised by wide spread tumour emboli along with fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles. PTTM is a rare but fatal complication of carcinoma, but the pathogenesis remains to be clarified. An autopsy case of PTTM caused by gastric adenocarcinoma is described, in which tumour cells in the PTTM lesion had positive immunoreactivity for platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR), and proliferating fibromuscular intimal cells also showed expression of PDGFR. In addition, the overexpression of PGDF was detected in the alveolar macrophages. These findings suggest that PDGF derived from alveolar macrophages and from tumour cells may act together in promoting fibrocellular intimal proliferation. To the best of the authors' knowledge, the possible involvement of activated alveolar macrophages in PTTM has not been previously reported

Mixed-Ligand Approach to Palladium-Catalyzed Direct Arylation Polymerization: Effective Prevention of Structural Defects Using Diamines

This paper reports a novel mixed ligand catalyst for palladium-catalyzed direct arylation polymerization (DArP) of 2,6-diiodo­dithienosilole (DTS-I₂) and thieno­pyrroledione (TPD-H₂) to give poly­(DTS-<i>alt</i>-TPD). It has been documented that this monomer combination has a marked tendency to form homocoupling and branching defects in polymer chains, and the latter defects eventually lead to the formation of insoluble materials. This paper demonstrates that the combined use of P­(<i>o</i>-MeOC₆H₄)₃ and TMEDA ligands effectively prevents the defect formation. The side reactions that afford structural defects constitute a sequential process triggered by the reduction of DTS-I units. TMEDA as a simple diamine effectively inhibits the reduction of DTS-I units, giving poly­(DTS-<i>alt</i>-TPD) (<i>M</i>_n^GPC = 20 000) in high cross-coupling selectivity (99%)

Mixed-Ligand Approach to Palladium-Catalyzed Direct Arylation Polymerization: Synthesis of Donor–Acceptor Polymers with Dithienosilole (DTS) and Thienopyrroledione (TPD) Units

This paper reports the synthesis of an alternating copolymer consisting of dithienosilole (DTS) and thienopyrroledione (TPD) units via palladium-catalyzed direct arylation polymerization (DArP). Although DArP has recently attracted much attention as an easy synthetic method of π-conjugated polymers without the need for prepreparation of organometallic monomers, there are two major problems that must be eliminated. One is homocoupling producing structural defects in the polymer chain, and the other is byproduction of insoluble materials. In this study, we have found that the combined use of P­(2-MeOC₆H₄)₃ and P­(2-Me₂NC₆H₄)₃ ligands effectively prevents these side reactions, resulting in poly­(DTS-<i>alt</i>-TPD) (<i>M</i>_n^GPC = 15000, <i>M</i>_w/<i>M</i>_n = 2.57) with good solubility in high yield (84%)

Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis

Gallbladder (GB) disease is classified into two broad categories: GB wall-thickening and protuberant lesions, which include various lesions, such as adenomyomatosis, cholecystitis, GB polyps, and GB carcinoma. This review summarizes recent advances in the differential diagnosis of GB lesions, focusing primarily on endoscopic ultrasound (EUS) and related technologies. Fundamental B-mode EUS and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of GB diseases because they can evaluate the thickening of the GB wall and protuberant lesions in detail. We also outline the current status of EUS-guided fine-needle aspiration (EUS-FNA) for GB lesions, as there have been scattered reports on EUS-FNA in recent years. Furthermore, artificial intelligence (AI) technologies, ranging from machine learning to deep learning, have become popular in healthcare for disease diagnosis, drug discovery, drug development, and patient risk identification. In this review, we outline the current status of AI in the diagnosis of GB