Review on neutrophil migration from blood vessels, and the spatiotemporal regulation of the overall immune response.
Neutrophils are professional phagocytes that constitute the first line of defense ...in humans. The primary function of neutrophils is to eliminate invading pathogens through oxidative and nonoxidative mechanisms. Because neutrophils rapidly migrate into inflammatory foci via diapedesis and chemotaxis, neutrophil recruitment has long been considered a hallmark of inflammation. Recent advances in intravital microscopic technologies using animal model systems have enabled researchers to directly visualize neutrophil trafficking. Consequently, the specific mechanisms of neutrophil transmigration have been identified, and even the reverse migration of neutrophils can be verified visually. Moreover, the detailed phenomena of neutrophil infiltration into various organs, such as the liver, lymphoid organs, and CNS have been identified. This progress in the study of neutrophil migration from the blood vessels to organs results in a deeper understanding of these immune cells’ motility and morphology, which are closely related to the spatiotemporal regulation of the overall immune response. In this review, we discuss our current understanding of neutrophil trafficking in various organs.
Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide ...prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for
Hy
’s law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI total: 0.60%, 95% confidence interval (CI) 0.12–1.08; women: 0.95%, 95% CI 0.19–1.68 and described its features in hospitalized participants.
This letter presents transparent microstrip patch antennas made of two types of transparent conductive films, which are multilayer film (MLF; IZTO/Ag/IZTO) and metal-mesh film (MMF; Cu). The sheet ...resistance levels of the MLF and MMF are 2.52 and 0.18 Ω/□. The transparencies of the MLF and MMF are over 80% and 60% at a 550-nm wavelength, respectively. The design and dimensions of the antennas follow the conventional simple microstrip patch antenna. A transparent acryl substrate is used for the proposed transparent antennas. The conductive parts of the proposed antennas are also made of copper sheets (CS; case 1) for the performance comparison to two types of transparent antennas made of MLF (case 2) and MMF (case 3). The resonance frequency band of the antennas is 2.4-2.5 GHz for Wi-Fi service. The case-1, case-2, and case-3 antennas have peak gains of 4.75, -4.23, and 2.63 dB and have radiation efficiencies of 66.32%, 7.76%, and 42.69% at the center frequency of the Wi-Fi service band (2.45 GHz), respectively.
Background and Purpose
There is a scarcity of information regarding the role of prothrombin kringle‐2 (pKr‐2), which can be generated by active thrombin, in hippocampal neurodegeneration and ...Alzheimer's disease (AD).
Experimental Approach
To assess the role of pKr‐2 in association with the neurotoxic symptoms of AD, we determined pKr‐2 protein levels in post‐mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age‐matched controls and wild‐type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr‐2 up‐regulation.
Key Results
Our results demonstrated that pKr‐2 was up‐regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid‐β aggregation in 5XFAD mice. The up‐regulation of pKr‐2 expression was inhibited by preservation of the blood–brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up‐regulation of pKr‐2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice.
Conclusion and Implications
We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr‐2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr‐2 represents a novel target for AD therapeutic strategies and those for related conditions.
This paper aims to design, fabricate, and analyze transparent and flexible monopole antennas for an application in wearable glasses. A multilayer electrode film composed of 100-nm-thick ...indium-zinc-tin oxide (IZTO)/Ag/IZTO (IAI), a type of transparent conducting oxide electrodes, is selected as the conductors of antennas and ground planes of the wearable glasses. The average transparency of the proposed antennas is measured to be 81.1% in the visible wavelength, and the electrical conductivity of the proposed antennas is measured to be 2 000 000 S/m. The proposed antennas are fabricated with physical vapor deposition process in high vacuum. Moreover, nontransparent antennas made of a 40-nm-thick silver (Ag) thin film are designed and fabricated to compare their performances with the transparent IAI antennas. To reduce the electromagnetic field absorption of the human head, we introduced and analyzed three configurations (types A-C) of monopole antennas having different directions of radiation patterns. The fabricated IAI antennas show the average efficiency of 40% and 4-dBi peak gain at 2.4-2.5 GHz. Furthermore, they have a specific absorption rate lower than 1.6 W/kg, which complies with the Federal Communications Commission standard, when the input power is 15 dBm, which is Google Glass's.
Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also ...inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1β. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression.
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•Increased lung cancer cell proliferation in Prx5 -/- mice.•Deficiency of Prx5 in macrophages increased susceptibility to M2 macrophage polarization by lung cancer cells.•Deficiency of Prx5 in macrophages promoted lung cancer development.•Macrophage Prx5 has a pivotal role in macrophage polarization.
We previously reported the protective effects of long-term administration of ferulic acid against the in vivo toxicity of β-amyloid peptide administered intracerebroventricularly in mice. In the ...present study, we investigated the effects of ferulic acid in transgenic amyloid precursor protein (APP)swe/presenilin 1 (PS1)dE9 (APP/PS1) mouse model of Alzheimer disease (AD). Chronic (for 6 months from the age of 6 to 12 months) oral administration of ferulic acid at a dose of 5.3 mg/kg/day significantly enhanced the performance in novel-object recognition task, and reduced amyloid deposition and interleukin-1 beta (IL-1β) levels in the frontal cortex. These results suggest that ferulic acid at a certain dosage could be useful for prevention and treatment of AD.
Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. As professional phagocytes, neutrophils also produce EVs in response to various inflammatory ...stimuli during inflammatory processes. Neutrophil-derived EVs can be categorized into 2 subtypes according to the mechanism of generation. Neutrophil-derived trails (NDTRs) are generated from migrating neutrophils. The uropods of neutrophils are elongated by adhesion to endothelial cells, and small parts of the uropods are detached, leaving submicrometer-sized NDTRs. Neutrophil-derived microvesicles (NDMVs) are generated from neutrophils which arrived at the inflammatory foci. Membrane blebbing occurs in response to various stimuli at the inflammatory foci, and small parts of the blebs are detached from the neutrophils, leaving NDMVs. These 2 subtypes of neutrophil-derived EVs share common features such as membrane components, receptors, and ligands. However, there are substantial differences between these 2 neutrophil-derived EVs. NDTRs exert pro-inflammatory functions by guiding subsequent immune cells through the inflammatory foci. On the other hand, NDMVs exert anti-inflammatory functions by limiting the excessive immune responses of nearby cells. This review outlines the current understanding of the different subtypes of neutrophil-derived EVs and provides insights into the clinical relevance of neutrophil-derived EVs.
Relaxor ferroelectricity is one of the most widely investigated but the least understood material classes in the condensed matter physics. This is largely due to the lack of experimental tools that ...decisively confirm the existing theoretical models. In spite of the diversity in the models, they share the core idea that the observed features in relaxors are closely related to localized chemical heterogeneity. Given this, this review attempts to overview the existing models of importance chronologically, from the diffuse phase transition model to the random-field model and to show how the core idea has been reflected in them to better shape our insight into the nature of relaxor-related phenomena. Then, the discussion will be directed to how the models of a common consensus, developed with the so-called canonical relaxors such as Pb(Mg
1/3
Nb
2/3
)O
3
(PMN) and (Pb, La)(Zr, Ti)O
3
(PLZT), are compatible with phenomenological explanations for the recently identified relaxors such as (Bi
1/2
Na
1/2
)TiO
3
(BNT)-based lead-free ferroelectrics. This review will be finalized with a discussion on the theoretical aspects of recently introduced 0−3 and 2−2 ferroelectric/relaxor composites as a practical tool for strain engineering.
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