The temporal redistribution pattern of NK cells under acute stress based on CD62L adhesion molecule expression

Recent studies demonstrated that an acute psychological stressor elicited transient changes in lymphocyte redistribution. Earlier studies had established that CD3-CD16+CD56+ natural killer cells (NK cells) increased remarkably in peripheral blood circulation and that the amount of lymphocyte redistribution in NK cells was dependent on the CD62L expression density. Specifically, CD62L- cells were mobilized more pronouncedly than were CD62L+ cells. These results led us to hypothesize that such different reactivity causes different temporal characteristics between CD62L+ and CD62L- lymphocyte subsets. The present study was conducted to examine this issue. Ten female participants experienced a 10-minute baseline period and performed a 10-minute mental arithmetic task as an acute psychological stressor. Blood samples for measuring the proportions of CD62L+ or CD62L- NK cells and CD62L+ or CD62L- T cells were obtained immediately after each period and every 2 min during the task. As expected, CD62L+ and CD62L- NK cells showed different reactivity in response to the stressor and showed different temporal characteristics. That is, the elevation of CD62L- NK cells reached a significant level at 1 min after the initiation of the stressor, while CD62L+ NK cells took 8 min to show a tendency of elevation. Although CD3+ T cells showed different reactivity between CD62L cell types, they did not show different temporal characteristics. These findings suggest that the expression of CD62L modulates not only the amount of redistribution but also the temporal characteristics of the redistribution of NK cells.     

Oral administration of Jumihaidokuto inhibits UVB-induced skin damage and prostaglandin E2 production in HR-1 hairless mice

Journal of Natural Medicines - This study was conducted to investigate whether and how Jumihaidokuto (JHT), a traditional Chinese medicine, prevents UVB-induced skin damage in male HR-1 hairless...     

PD‐1+ TIM‐3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer

The liquid biopsy of ascites fluid could be an excellent source of tumor and microenvironment for the study of prognostic biomarkers because of its accessibility. Tumor‐infiltrating lymphocytes (TILs) can predict prognosis in multiple malignancies, including the response to immune checkpoint inhibitors, a breakthrough cancer therapy. However, TILs’ profiles from malignant ascites have not been extensively studied. Using flow cytometric analysis, we quantified the proportion of exhausted T cells and memory/naive/effector T‐cell subsets, among the CD4+ and CD8+ T‐cell populations of paired TILs and peripheral blood T cell samples (n = 22). The correlation between CD4+ and CD8+ subset profiles suggested that the combined analysis of CD4+ and CD8+ cells in malignant ascites was clinically significant. We found that cells positive for the exhaustion markers programmed cell death‐1 (PD‐1), and T‐cell immunoglobulin and mucin domain 3 (TIM‐3), and cells coexpressing PD‐1 and TIM‐3 abundantly exist among malignant ascites TILs. Furthermore, patients with high frequency of PD‐1+ TIM‐3+ cells among the CD4+ and CD8+ T‐cell population showed worse clinical outcome in multivariate analysis (n = 27). We propose that exhausted ascites TILs represent a clinically significant prognostic biomarker in advanced gastrointestinal cancer and represent an important target for immune checkpoint inhibitors.     

Scanning electron microscopic studies on coronary microvascular architecture in diabetic human hearts by corrosion cast

Microvascular architecture of 13 diabetic human hearts and 5 nondiabetic control subjects were studied by scanning electron microscopy of corrosion casts. The following results were obtained in the diabetic and nondiabetic hearts. (1) Arterial branches running with remarkable tortuosity were observed in 10 of 13 diabetic hearts, and showed an acute angle, a hairpin turn, a wavelike form, a spiral configuration, a twist, or complex tortuosity. (2) Microaneurysms were found in 11 of 13 diabetic hearts and were observed as spherical, oval, or fusiform. (3) Capillary microaneurysms were found in all diabetic hearts, and observed as saccular form or fusiform. (4) Veins running with remarkable tortuosity or dilations and stenosis were observed in 7 of 13 diabetic hearts. (5) Arterial branches running with remarkable tortuosity were observed in 3 of 5 nondiabetic hearts. (6) Microaneurysms and capillary microaneurysms were not found in nondiabetic hearts. (7) Veins running with remarkable tortuosity were observed in 1 of 5 nondiabetic hearts.     

Efficient gene transfer via retrograde transport in rodent and primate brains using a human immunodeficiency virus type 1-based vector pseudotyped with rabies virus glycoprotein

The primate lentiviral vector system based on human immunodeficiency virus type 1 (HIV-1) has been used for a wide range of gene therapy trials in animal models. Axonal transport in the retrograde direction, which is observed with some viral vectors, confers a considerable advantage to gene transfer into neuronal cell bodies that are localized in regions remote from the injection site of the vectors. However, retrograde axonal transport of the HIV-1-based lentiviral vector pseudotyped with vesicular stomatitis virus glycoprotein is reported to be inefficient. In the present study, we developed an efficient gene transfer system through retrograde transport in the brain with the HIV-1-based vector pseudotyped with rabies virus glycoprotein (RV-G). Injection of the RV-G-pseudotyped HIV-1 vector into the dorsal striatum of mice yielded an increase in gene transfer into neuronal populations in the cerebral cortex, thalamus, and ventral midbrain, each of which innervates the striatum. In addition, injection of the RV-G-pseudotyped vector into the monkey striatum (putamen) resulted in highly efficient transfer into neurons in the ventral midbrain (nigrostriatal dopamine neurons). Our results indicate that pseudotyping of the HIV-1 vector with RV-G enhances the efficiency of gene transfer through retrograde axonal transport in both mouse and monkey brains. This primate lentiviral vector system will provide a powerful approach to gene therapy for neurological and neurodegenerative diseases by means of enhanced retrograde transport.     

Clinical impact of additional therapy for residual pancreatic cancer

Surgery Today - This study aimed to explore the prognostic significance of the resection margin (R) status of pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant therapy (NAT) or...