VISTA is a key immune checkpoint receptor under investigation for cancer immunotherapy; however, its signaling mechanisms remain unclear. Here we identify a conserved four amino acid (NPGF) intracellular motif in VISTA that suppresses cell proliferation by constraining cell-intrinsic growth receptor signaling. The NPGF motif binds to the adapter protein NUMB and recruits Rab11 endosomal recycling machinery.
View Article and Find Full Text PDFMyxofibrosarcoma, a rare malignant tumor, predominantly affects the extremities of the elderly. Because of its invasive nature amputation is sometimes required, resulting in serious deterioration of quality of life. Therefore, cell lines established from amputated surgical specimens of myxofibrosarcoma in the upper limbs of elderly patients were used to create a myxofibrosarcoma-bearing animal model and to investigate the therapeutic effect of BNCT thereon.
View Article and Find Full Text PDFChikungunya virus (CHIKV) is a pathogenic arthritogenic alphavirus responsible for large-scale human epidemics for which a vaccine was recently approved for use. Mayaro virus (MAYV) is a related emerging alphavirus with epidemic potential with circulation overlap potential with CHIKV. We previously reported the ability of a non-replicating human adenovirus (AdV)-vectored vaccine expressing the MAYV structural polyprotein to protect against disease in mice following challenge with MAYV, CHIKV and UNAV.
View Article and Find Full Text PDFBackground: A model system described in International Organization for Standardization 9360 is the standard method for estimating the humidifying performance of heat and moisture exchangers (HMEs). However, there are no reliable bedside methods for evaluating the ongoing humidification performance of HMEs. Therefore, this study aimed to develop 2 clinically applicable methods for estimating the ongoing humidifying performance of HMEs and to evaluate their reliability in a model system.
View Article and Find Full Text PDFInt Arch Allergy Immunol
September 2024
Background: Itch is the most troublesome symptom of atopic dermatitis, and it is important to assess it appropriately for optimal treatment. We discussed issues regarding itch and the most appropriate methods of assessment at the Atopic Itch Consensus Meeting (AICOM), attended by physicians and researchers with expertise in itch treatment and research.
Methods: The AICOM participants prepared a draft consensus statement that addressed the most appropriate itch assessment methods for age groups <2 years, 2-6 years, 7-14 years, and ≥15 years.
Background: Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood.
Objective: In this study, we investigate the combined effects of NTP and MCB on PHP in mice.
Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes debilitating and persistent arthritogenic disease. While MAYV was previously reported to infect non-human primates (NHP), characterization of MAYV pathogenesis is currently lacking. Therefore, in this study we characterized MAYV infection and immunity in rhesus macaques.
View Article and Find Full Text PDFRecently, boron neutron capture therapy (BNCT) has been attracting attention as a minimally invasive cancer treatment. In 2020, the accelerator-based BNCT with L-BPA (Borofalan) as its D-sorbitol complex (Steboronine®) for head and neck cancers was approved by Pharmaceutical and Medical Devices Agency for the first time in the world. As accelerator-based neutron generation techniques are being developed in various countries, the development of novel tumor-selective boron agents is becoming increasingly important and desired.
View Article and Find Full Text PDFBackground: The effect of inverse inspiration:expiration (I:E) ratio on functional residual capacity (FRC) during pneumoperitoneum is unclear. We hypothesised that volume-targeted pressure-controlled inverse ratio ventilation (vtPC-IRV) would increase FRC by increasing the level of auto-PEEP in low respiratory compliance situations.
Methods: During robot-assisted laparoscopic radical prostatectomy, 20 obese patients were sequentially ventilated with four different settings for 30 min in each setting: (1) control, I:E ratio of 1:2 and baseline airway pressure (BAP) of 5 cm HO; (2) IRV2, I:E ratio of 2:1 and BAP off; (3) IRV3, I:E ratio of 3:1 and BAP off; and (4) IRV4, I:E ratio of 4:1 and BAP off.
This study investigated whether the repeated topical paeoniflorin inhibits postoperative pain in mice. An incision of the plantar skin and underlying muscle of the hind paw elicits acute postoperative pain. Repeated topical paeoniflorin inhibited postoperative pain.
View Article and Find Full Text PDFFunctional peptides, which are composed of proteinogenic natural amino acids, are expected to be used as biomaterials with minimal environmental impact. Synthesizing a functional peptide with a shorter amino acid sequence while retaining its function is a easy and economical strategy. Furthermore, shortening functional peptides helps to elucidate the mechanism of their functional core region.
View Article and Find Full Text PDFChikungunya virus (CHIKV) is an emerging/re-emerging mosquito-borne pathogen responsible for explosive epidemics of febrile illness characterized by debilitating polyarthralgia and the risk of lethal infection among the most severe cases. Despite the public health risk posed by CHIKV, no vaccine is currently available. Using a site-directed hydrogen peroxide-based inactivation approach, we developed a new CHIKV vaccine, HydroVax-CHIKV.
View Article and Find Full Text PDFChikungunya virus (CHIKV) has re-emerged as a significant human pathogen in the 21st century, causing periodic, and sometimes widespread, outbreaks over the past 15 years. Although mortality is very rare, a debilitating arthralgia is very common and may persist for months or years. There are no antivirals that are approved for the treatment of CHIKV infection, and current treatment options consist of supportive care only.
View Article and Find Full Text PDFFor binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle.
View Article and Find Full Text PDFBackground: We previously reported that there were no differences between the lung-protective actions of pressure-controlled inverse ratio ventilation and volume control ventilation based on the changes in serum cytokine levels. Dead space represents a ventilation-perfusion mismatch, and can enable us to understand the heterogeneity and elapsed time changes in ventilation-perfusion mismatch.
Methods: This study was a secondary analysis of a randomized controlled trial of patients who underwent robot-assisted laparoscopic radical prostatectomy.
Ultraviolet irradiation (UV) exposure is the leading factor underlying the development of skin malignancies. D-dopachrome tautomerase (D-DT), a functional homolog of macrophage migration inhibitory factor (MIF), has functional similarities to MIF. However, its role, unlike the role of MIF in photocarcinogenesis, is unknown.
View Article and Find Full Text PDFImmature neurons dominantly express the Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) rather than the K+-Cl- cotransporter isoform 2 (KCC2). The intracellular chloride ion concentration ([Cl-]i) is higher in immature neurons than in mature neurons; therefore, γ-aminobutyric acid type A (GABAA) receptor activation in immature neurons does not cause chloride ion influx and subsequent hyperpolarization. In our previous work, we found that midazolam, benzodiazepine receptor agonist, causes less sedation in neonatal rats compared to adult rats and that NKCC1 blockade by bumetanide enhances the midazolam-induced sedation in neonatal, but not in adult, rats.
View Article and Find Full Text PDFActivated microglia induce brain inflammation and neuronal death. Panaxytriol, ((3R,9R,10R)-Heptadec-1-en-4,6-diyne-3,9,10-triol), is a component of Panax ginseng C. A.
View Article and Find Full Text PDFAtopic dermatitis (AD) is a chronic inflammatory skin disease with severe pruritus. Berberine, a naturally occurring isoquinoline alkaloid, has anti-inflammatory effects. This study investigated the effects and molecular mechanisms of berberine on AD-like symptoms in mice.
View Article and Find Full Text PDFIschemia-reperfusion injury (IRI) is an important risk factor for accelerated cardiac allograft rejection and graft dysfunction . Utilizing a rat heart isogeneic transplant model, we identified inflammatory pathways involved in IRI in order to identify therapeutic targets involved in disease. Pathway analyses identified several relevant targets, including cytokine signaling by the IL-1 receptor (IL-1R) pathway and inflammasome activation.
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