Radioprotective Effect of Vitamin C as an Antioxidant

Vitamin C is known as a potent antioxidant. We studied vitamin C as a radioprotective agent, focusing on its antioxidative effect. When the body is exposed to radiation, free radicals and reactive oxygen species (ROS) are produced and oxidize cell components, resulting in cell damage. Vitamin C has the potential to scavenge these radical products, thereby protecting against radiation-induced cell damage. We investigated the effects of vitamin C on radiation-induced gastrointestinal (GI) syndrome in mice. The mice received whole-body irradiation followed by bone marrow transplantation 24 h after exposure. Despite avoiding bone marrow failure, the mice eventually died of GI syndrome. Pretreatment with per os administration of high-dose vitamin C effectively mitigated radiation-induced GI syndrome and improved mouse survivals, while per os post-treatment with vitamin C was ineffective, presumably due to impaired absorption from the radiation-damaged intestine. We also investigated the effect of post-exposure treatment with intraperitoneal administration of vitamin C on radiation-induced bone marrow dysfunction in mice. Intraperitoneal administration with high-dose vitamin C, even at 24 h after whole-body irradiation, was still effective in avoiding bone marrow dysfunction, thereby increasing mouse survival after radiation. In conclusion, administration of high-dose vitamin C effectively reduced the radiation lethality in mice

Antitumor Immunity Produced by the Liver Kupffer Cells, NK Cells, NKT Cells, and CD8+ CD122+ T Cells

Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like receptor (TLR) ligands and an NKT cell ligand (α-galactocylceramide), activate liver Kupffer cells, which produce IL-1, IL-6, IL-12, and TNF. IL-12 activates hepatic NK cells and NKT cells to produce IFN-γ, which further activates hepatic T cells, in turn activating phagocytosis and cytokine production by Kupffer cells in a positive feedback loop. These immunological events are essentially evoked to protect the host from bacterial and viral infections; however, these events also contribute to antitumor and antimetastatic immunity in the liver by activated liver NK cells and NKT cells. Bystander CD8+CD122+ T cells, and tumor-specific memory CD8+T cells, are also induced in the liver by α-galactocylceramide. Furthermore, adoptive transfer experiments have revealed that activated liver lymphocytes may migrate to other organs to inhibit tumor growth, such as the lungs and kidneys. The immunological mechanism underlying the development of hepatocellular carcinoma in cirrhotic livers in hepatitis C patients and liver innate immunity as a double-edged sword (hepatocyte injury/regeneration, septic shock, autoimmune disease, etc.) are also discussed

Role of Kupffer Cells in Systemic Anti-Microbial Defense

The liver has long been recognized as important in digestion. However, the liver’s abundance of innate immune cells strongly suggests that it has specific defense mechanisms. A characteristic anatomical feature of the liver is its large blood flow. The blood flowing out from the whole alimentary tract is transported to the liver via the portal vein and distributed to peripheral structures called sinusoids. Kupffer cells, a typical example of resident macrophages, are located in sinusoids and are in continuous contact with various portal blood components. They have vigorous phagocytic activity and eliminate bacteria coming from the gut before they enter systemic circulation. Based on this framework, Kupffer cells were considered a filter for portal blood pathogens. However, recent evidence reveals that they exert crucial functions in systemic host defense against bacterial infection. To defend against various sources of bacterial pathogens, Kupffer cells construct an efficient surveillance system for systemic circulation, cooperating aggressively with other immune cells. They collaborate with non-immune cells such as hepatocytes and platelets to potentiate defense function. In conclusion, Kupffer cells coordinate immune cell activity to efficiently defend against infections, making them crucial players in systemic antibacterial immunity

Appearance of fluid content in Rathke’s cleft cyst is associated with clinical features and postoperative recurrence rates

The version of record of this article, first published in Pituitary, is available online at Publisher’s website: https://doi.org/10.1007/s11102-024-01395-y.Purpose: The contents of Rathke’s cleft cysts (RCCs) vary from clear and slightly viscous to purulent. Surgical treatment of symptomatic RCCs involves removing the cyst contents, whereas additional cyst-wall opening to prevent reaccumulation is at the surgeon’s discretion. The macroscopic findings of the cyst content can reflect the nature of RCCs and would aid in surgical method selection. Methods: We retrospectively reviewed the records of 42 patients with symptomatic RCCs who underwent transsphenoidal surgery at our institute between January 2010 and March 2022. According to the intraoperative findings, cyst contents were classified into type A (purulent), type B (turbid white with mixed semisolids), or type C (clear and slightly viscous). Clinical and imaging findings and early recurrence rate (within two years) were compared according to the cyst content type. Results: There were 42 patients classified into three types. Patients with type C were the oldest (65.4 ± 10.4 years), and type A included more females (92.9%). For magnetic resonance imaging, type-A patients showed contrast-enhanced cyst wall (92.9%), type-B patients had intracystic nodules (57.1%), and all type-C patients showed low T1 and high T2 intensities with larger cyst volumes. Fewer asymptomatic patients had type C. Preoperative pituitary dysfunction was most common in type A (71.4%). Early recurrence was observed in types A and C, which were considered candidates for cyst-wall opening. Conclusion: The clinical characteristics and surgical prognosis of RCCs depend on the nature of their contents

Behavior of vascular resistance undergoing various pressure insufflation and perfusion on decellularized lungs

Bioengineering of functional lung tissue by using whole lung scaffolds has been proposed as a potential alternative for patients awaiting lung transplant. Previous studies have demonstrated that vascular resistance (Rv) could be altered to optimize the process of obtaining suitable lung scaffolds. Therefore, this work was aimed at determining how lung inflation (tracheal pressure) and perfusion (pulmonary arterial pressure) affect vascular resistance. This study was carried out using the lungs excised from 5 healthy male Sprague-Dawley rats. The trachea was cannulated and connected to a continuous positive airway pressure (CPAP) device to provide a tracheal pressure ranging from 0 to 15 cmH(2)O. The pulmonary artery was cannulated and connected to a controlled perfusion system with continuous pressure (gravimetric level) ranging from 5 to 30 cmH(2)O. Effective Rv was calculated by ratio of pulmonary artery pressure (P-PA) by pulmonary artery flow (V'(PA)). Rv in the decellularized lungs scaffolds decreased at increasing V'(PA), stabilizing at a pulmonary arterial pressure greater than 20 cmH(2)O. On the other hand, CPAP had no influence on vascular resistance in the lung scaffolds after being subjected to pulmonary artery pressure of 5 cmH(2)O. In conclusion, compared to positive airway pressure, arterial lung pressure markedly influences the mechanics of vascular resistance in decellularized lungs. (C) 2016 Elsevier Ltd. All rights reserved

Initiation of NALT Organogenesis Is Independent of the IL-7R, LTβR, and NIK Signaling Pathways but Requires the Id2 Gene and CD3−CD4+CD45+ Cells

AbstractInitiation of nasopharyngeal-associated lymphoid tissue (NALT) development is independent of the programmed cytokine cascade necessary for the formation of Peyer's patches (PP) and peripheral lymph nodes (PLN), a cytokine cascade which consists of IL-7R, LTα1β2/LTβR, and NIK. However, the subsequent organization of NALT seems to be controlled by these cytokine signaling cascades since the maturation of NALT structure is generally incomplete in those cytokine cascade-deficient mice. NALT as well as PP and PLN are completely absent in Id2−/− mice. NALT organogenesis is initiated following the adoptive transfer of CD3−CD4+CD45+ cells into Id2−/− mice, constituting direct evidence that CD3−CD4+CD45+ inducer cells can provide an IL-7R-, LTα1β2/LTβR-, and NIK-independent tissue organogenesis pathway for secondary lymphoid tissue development

New aspect of photophysics of 7,7,8,8-tetracyanoquinodimethane and its solvated complexes: intra- vs. inter-molecular charge-transfer

We performed laser-induced fluorescence (LIF) spectroscopy of 7,7,8,8-tetracyanoquinodimethane (TCNQ) and its solvated complexes with acetonitrile (ACN) and benzene (Bz), under the jet-cooled gas-phase condition. We also carried out fluorescence and its time profile measurements in TCNQ/Bz/hexane solution to compare with the gas-phase results. The LIF excitation spectrum of the S-1 (pi pi*)-S-0 electronic transition of TCNQ monomer exhibited unusual vibronic structure with the maximum intensity at similar to 3000 cm(-1) above the band origin. In addition, the fluorescence lifetime is more than 100 times longer than that in hexane solution with most of the bands showing double exponential decay. The unusual feature of the vibronic bands is intrinsic and not due to the presence of other species, as confirmed by UV-UV hole-burning (HB) spectroscopy. These unusual features of S-1 are thought to be due to the coupling with the S-2 state, where S-2 was revealed to have intramolecular charge-transfer (ICT) character. The S-1-S-0 transition of the TCNQ-ACN complex exhibited sharp vibronic bands which are red-shifted by 120 cm(-1) from those of the monomer, indicating van der Waals (vdW) interaction between them; however, the fluorescence lifetime was drastically shortened. In contrast, the TCNQ-Bz complex gave a broad electronic spectrum. The study of the fluorescence and its time profile in TCNQ/Bz/hexane solution clearly shows the formation of the CT complex between TCNQ and Bz. Based on the experimental results and density functional theory (DFT) calculations, we propose that in the TCNQ monomer and TCNQ-ACN complex the S-1 (pi pi*) state is coupled to the intramolecular CT state, while the S-1 state of TCNQ in the TCNQ-Bz complex is more strongly coupled to the intermolecular CT state

Expression of human mutant cyclin dependent kinase 4, Cyclin D and telomerase extends the life span but does not immortalize fibroblasts derived from loggerhead sea turtle (Caretta caretta)

Conservation of the genetic resources of endangered animals is crucial for future generations. The loggerhead sea turtle (Caretta caretta) is a critically endangered species, because of human hunting, hybridisation with other sea turtle species, and infectious diseases. In the present study, we established primary fibroblast cell lines from the loggerhead sea turtle, and showed its species specific chromosome number is 2n = 56, which is identical to that of the hawksbill and olive ridley sea turtles. We first showed that intensive hybridization among multiple sea turtle species caused due to the identical chromosome number, which allows existence of stable hybridization among the multiple sea turtle species. Expressions of human-derived mutant Cyclin-dependent kinase 4 (CDK4) and Cyclin D dramatically extended the cell culture period, when it was compared with the cell culture period of wild type cells. The recombinant fibroblast cell lines maintained the normal chromosome condition and morphology, indicating that, at the G1/S phase, the machinery to control the cellular proliferation is evolutionally conserved among various vertebrates. To our knowledge, this study is the first to demonstrate the functional conservation to overcome the negative feedback system to limit the turn over of the cell cycle between mammalian and reptiles. Our cell culture method will enable the sharing of cells from critically endangered animals as research materials