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Studies in human subjects have revealed that autonomic responses provide objective and biologically relevant information about cognitive and affective states. Measures of autonomic responses can also be applied to studies of non-human primates, which are neuro-anatomically and physically similar to humans. Facial temperature and pupil size are measured remotely and can be applied to physiological experiments in primates, preferably in a head-fixed condition. However, detailed guidelines for the use of these measures in non-human primates are lacking. Here, we review the neuronal circuits and methodological considerations necessary for measuring and analyzing facial temperature and pupil size in non-human primates. Previous studies have shown that the modulation of these measures primarily reflects sympathetic reactions to cognitive and emotional processes, including alertness, attention, and mental effort, over different time scales. Integrated analyses of autonomic, behavioral, and neurophysiological data in primates are promising methods that reflect multiple dimensions of emotion and could provide tools for understanding the mechanisms underlying neuropsychiatric disorders and vulnerabilities characterized by cognitive and affective disturbances.

Cold atmospheric pressure plasmas are promising medical tools that can assist in cancer treatment. While the medical pathology mechanism is substantially understood, knowledge of the contribution of reactive species formed in plasma and the mode of activation of biochemical pathways is insufficient. Herein, we present a concept involving antitumoral plasma-activated organics, which is envisaged to increase cytotoxicity levels against cancer cells. Ringer′s acetate solution was irradiated by low-temperature plasma at atmospheric pressure and possible reaction pathways of the compound generation are presented. The chemical compounds formed by plasma treatment and their effects on non-tumorigenic breast epithelial cells (MCF-10A) and breast cancer cells (MCF-7) were investigated. The cell viability results have shown that plasma-derived compounds have both, stimulatory and inhibitory effects on cell viability, depending on the concentration of the generated compounds in the irradiated liquids. Previous studies have shown that oxidative stresses involving reactive oxygen and nitrogen species (RONS) can be used to kill cancer cells. Hence, while RONS offers promising first-step killing effects, cell viability results have shown that plasma-derived compounds, such as acetic anhydride and ethyl acetate, have the potential to play important roles in plasma-based cancer therapy.

Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro co-culturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon co-culturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks. This article is protected by copyright. All rights reserved.

A congenital left atrial appendage aneurysm (LAAA) is a rare cardiac malformation that is usually diagnosed in adulthood. It is rarely diagnosed prenatally. In most cases, surgical resection is recommended soon after the diagnosis has been made due to the risk of arrhythmia and thrombotic events. The present report describes a case of LAAA which was prenatally diagnosed and was asymptomatic postnatally. Imaging revealed the relation of the cardiac and airway structures around the LAAA in detail. The patient underwent surgical resection of the LAAA successfully at 7 months of age and is currently healthy at 5 years of age.

Low-temperature plasma is being widely used in the various fields of life science, such as medicine and agriculture. Plasma-activated solutions have been proposed as potential cancer therapeutic reagents. We previously reported that plasma-activated Ringer’s lactate solution exhibited selective cancer-killing effects, and that the plasma-treated L-sodium lactate in the solution was an anti-tumor factor; however, the components that are generated through the interactions between plasma and L-sodium lactate and the components responsible for the selective killing of cancer cells remain unidentified. In this study, we quantified several major chemical products, such as pyruvate, formate, and acetate, in plasma-activated L-sodium lactate solution by nuclear magnetic resonance analysis. We further identified novel chemical products, such as glyoxylate and 2,3-dimethyltartrate, in the solution by direct infusion-electrospray ionization with tandem mass spectrometry analysis. We found that 2,3-dimethyltartrate exhibited cytotoxic effects in glioblastoma cells, but not in normal astrocytes. These findings shed light on the identities of the components that are responsible for the selective cytotoxic effect of plasma-activated solutions on cancer cells, and provide useful data for the potential development of cancer treatments using plasma-activated L-sodium lactate solution.

Background Predicting the postnatal biventricular physiology of fetuses with borderline left ventricle remains challenging. This study clarified fetal echocardiographic predictors of successful postnatal biventricular physiology establishment. Methods Forty-nine fetuses with a left ventricular (LV) width (LVw) z-score

Visual vertical (VV), visually perceived direction of gravity, is widely measured to assess the vestibular function and visuospatial cognition. VV has been assessed by comparing orientation and variability of measured values separately between subject groups. However, changes in orientation and variability often differ in patients with unilateral spatial neglect (USN). Here, we developed a novel classification of VV that combines orientation and variability and characterized the effects of USN on VV. Forty-three subacute stroke patients with or without USN (USN+, n = 17; USN-, n = 26) and 33 age-matched controls were included in the study. In darkness, a luminous line, initially tilted at 30° either to the left or right, gradually rotated towards the vertical. The VV was defined as the deviation of the subjectively-perceived vertical from the true vertical. The new classification demonstrated that, while the majority of USN + patients (14/17) exhibited large variability, nine showed normal orientation and five showed greater contra-lesional deviation of orientation, suggesting different underlying mechanisms for orientation and variability. Further analyses revealed VV deviation to the initial tilt in all groups. However, the deviation in USN + was larger and more variable, indicating attentional disorders. Such characterization would contribute to individually specified clinical rehabilitation.

In normal development, the rate of cell differentiation is tightly controlled and critical for normal development and stem cell differentiation. However, the underlying mechanisms regulating the rate of the differentiation are unknown, and manipulation of the rate of the stem cell differentiation is currently difficult. Here we show that activation of protein kinase A (PKA) accelerates the rate of mouse embryonic stem cell (ESC) differentiation through an early loss of ESC pluripotency markers and early appearance of mesodermal and other germ layer cells. The activation of PKA hastened differentiation by increasing the expression of a histone H3 lysine 9 (H3K9) dimethyltransferase, G9a protein, and the level of a negative epigenetic histone mark, H3K9 dimethylation (H3K9me2), in the promoter regions of the pluripotency markers Nanog and Oct4. These results elucidate a novel role of PKA on ESC differentiation and offer an experimental model for controlling the rate of ESC differentiation.

Metastasis is a major challenge in the treatment of cervical cancer patients. This study was aimed to identify a novel metastasis-promoting molecule and elucidate its functional role in cervical cancer. Multiple databases was used to identify molecules associated with metastasis of cervical cancer. DDIT4 (DNA-damage-inducible transcript 4), a hypoxia-inducible gene, was identified in this analysis. Correlation between DDIT4 expression and lymph node metastasis was evaluated by immunohistochemistry. Transwell® assay and wound-healing assay to determine cell migration and invasion was performed. DDIT4 was knocked down using siRNA and lentiviral vectors. The potential downstream effects of DDIT4 were explored and verified by a gene set enrichment analysis and western blotting. The in vivo metastatic capability of cervical cancer regulated by DDIT4 was determined with the use of an intraperitoneal-injection mouse model. DDIT4 was an independent prognostic factor for patients with early-stage cervical cancer, according to both public database and our cohort. In our clinical samples, the expression of DDIT4 in immunohistochemistry was strongly associated with metastasis and hypoxia. The knockdown of DDIT4 attenuated the migration and invasion activity of tumor cells in vitro, and reduced the expression of epithelial–mesenchymal transition (EMT) related proteins and the NF-κB pathway in cervical cancer cells. DDIT4 also promoted metastasis in the mouse model. Our results define the DDIT4 as a novel metastasis-promoting pathway of EMT and NF-κB pathway that mediates cancer migration and invasion. DDIT4 may thus become a prognostic marker and a potential target for cervical cancer metastasis.

Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell‐to‐cell crosstalk or phenotypic alterations including the acquisition of platinum‐resistance in OvCa cells. Herein, we report how OvCa‐associated mesothelial cells (OCAMs) induce platinum‐resistance in OvCa cells through direct cell‐to‐cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF‐β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum‐sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell‐to‐cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF‐β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell‐to‐cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum‐resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination., What's new? The clinical characteristics of refractory advanced ovarian cancer suggest that the peritoneum acts as an anchoring point for metastatic tumors, enabling persistent ovarian cancer (OvCa) cell survival. This study shows that ovarian cancer‐associated mesothelial cells (OCAMs) and OvCa cells invade the extracellular matrix of the peritoneum. OCAMs were further found to directly influence persistent OvCa cell survival via FN1 signaling. FN1 on the surface of OCAMs induced activation of the Akt signaling pathway, thereby fueling platinum resistance in OvCa cells. The findings highlight the potential for targeting OCAMs as a novel therapeutic strategy for preventing peritoneal dissemination of ovarian cancer.

At each time in our life, we choose one or few behaviors, while suppressing many other behaviors. This is the basic mechanism in the basal ganglia, which is done by tonic inhibition and selective disinhibition. Dysfunctions of the basal ganglia then cause 2 types of disorders (difficulty in initiating necessary actions and difficulty in suppressing unnecessary actions) that occur in Parkinson’s disease. The basal ganglia generate such opposite outcomes through parallel circuits: The direct pathway for initiation and indirect pathway for suppression. Importantly, the direct pathway processes good information and the indirect pathway processes bad information, which enables the choice of good behavior and the rejection of bad behavior. This is mainly enabled by dopaminergic inputs to these circuits. However, the value judgment is complex because the world is complex. Sometimes, the value must be based on recent events, thus is based on short-term memories. Or, the value must be based on historical events, thus is based on long-term memories. Such memory-based value judgment is generated by another parallel circuit originating from the caudate head and caudate tail. These circuit-information mechanisms allow other brain areas (e.g., prefrontal cortex) to contribute to decisions by sending information to these basal ganglia circuits. Moreover, the basal ganglia mechanisms (i.e., what to choose) are associated with cerebellum mechanisms (i.e., when to choose). Overall, multiple levels of parallel circuits in and around the basal ganglia are essential for coordinated behaviors. Understanding these circuits is useful for creating clinical treatments of disorders resulting from the failure of these circuits.

Epithelial ovarian cancer (EOC) is considered to secrete various factors in order to promote peritoneal dissemination through cell-to-cell interaction between cancer and mesothelial cells. We previously revealed that TGF-β secreted from EOC induces normal human peritoneal mesothelial cells (HPMCs) to differentiate into cancer-associated mesothelial cells (CAMCs). However, the relationship between tumor cells and CAMCs in EOC is still unclear. We hypothesized that CAMCs also secrete chemokines that attract cancer cells and induce peritoneal dissemination of EOC. We examined chemokines secreted from HPMCs and CAMCs by human chemokine array, and revealed that conditioned medium of CAMCs (CAMCs-CM) included many types of chemokines. The signals of CCL2 were the highest compared with other chemokines. The secretion and relative expression of CCL2 were significantly higher in CAMCs. Recombinant CCL2 promoted trans-mesothelial migration of HPMCs and the migration and invasion by EOC cells. In addition, CCL2 secreted from CAMCs promoted invasion of EOC cells. Furthermore, the neutralizing antibody of CCL2 reduced invasion by EOC. Clinical outcomes of patients whose tissue expressed higher CCR2 were significantly poorer than in patients whose tissue expression was lower. CCL2 activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK). In addition, CAMCs-CM activated the p38 MAPK pathway. Phosphorylation of p38 MAPK reduced with the presence of neutralizing antibody of CCL2. In conclusion, these data indicate CCL2 in CAMCs-CM promoted the malignant potential of EOC. CCL2 plays a crucial role in the tumor microenvironment of EOC.

Non-thermal atmospheric pressure plasma has been widely used for preclinical studies in areas such as wound healing, blood coagulation, and cancer therapy. We previously developed plasma-activated medium (PAM) and plasma-activated Ringer’s lactate solutions (PAL) for cancer treatments. Many in vitro and in vivo experiments demonstrated that both PAM and PAL exhibit anti-tumor effects in several types of cancer cells such as ovarian, gastric, and pancreatic cancer cells as well as glioblastoma cells. However, interestingly, PAM induces more intracellular reactive oxygen species in glioblastoma cells than PAL. To investigate the differences in intracellular molecular mechanisms of the effects of PAM and PAL in glioblastoma cells, we measured gene expression levels of antioxidant genes such as CAT, SOD2, and GPX1. Microarray and quantitative real-time PCR analyses revealed that PAM elevated stress-inducible genes that induce apoptosis such as GADD45α signaling molecules. PAL suppressed genes downstream of the survival and proliferation signaling network such as YAP/TEAD signaling molecules. These data reveal that PAM and PAL induce apoptosis in glioblastoma cells by different intracellular molecular mechanisms.

The mesothelium, covered by a continuous monolayer of mesothelial cells, is the first protective barrier against metastatic ovarian cancer. However, mesothelial cells release tumor-promoting factors that accelerate the process of peritoneal metastasis. We identified cancer-associated mesothelial cells (CAMs) that had tumor-promoting potential. Here, we found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Moreover, PAI-1 correlated with peritoneal metastasis in ovarian cancer patients and indicated a poor prognosis. In both ex vivo and in vivo models, after PAI-1 expression was knocked down, the metastasis of ovarian cancer cells decreased significantly. Therefore, targeting PAI-1 may provide a potential target for future therapeutics to prevent the formation of CAMs and alleviate peritoneal metastasis in ovarian cancer patients., ファイル公開：2020-02-01

A fingerprint reader based on epitaxial PbTiO3 (PTO) transducer array operating thickness extensional mode in GHz range was fabricated. The device consisted of nine square transducers with 0.1 mm per side arranged 1.3 mm apart in a 3 × 3 array. Minimum conversion loss of the fabricated transducer was 2.5 dB at 0.8 GHz, and electromechanical coupling coefficient kt2 was estimated to be 28.9%. In contrast to MHz range ultrasonic fingerprint readers such as those based on piezoelectric micromachined ultrasonic transducers using a piezoelectric transducer and ScAlN, a GHz range transducer enables imaging in higher spatial resolution. Furthermore, PTO transducers have a high dielectric constant and electromechanical coupling coefficient kt2. A high dielectric constant realizes 50 Ω impedance matching with small electrode area. The small acoustic source is expected to improve the spatial resolution of a fingerprint reader. We achieved the fingerprint imaging by evaluating the acoustic reflectance of the medium/transducer interface. Furthermore, piezostage that allows mechanical movement in the 100 nm order was introduced to image a 12 × 12 μm2 area with total of 3600 data points.

A double-barrelled aorta was detected in a female newborn with 22q11.2 deletion syndrome. Double-barrelled aorta had been previously described as persistence of the fifth pharyngeal arch, but its existence continues to be debated. Recent embryologic studies suggest that double-barrelled aorta is more likely explained by other developing processes in the majority of cases. In our case, catheter angiography confirmed the presence of the high aortic arch and double-barrelled aorta. The upper lumen was located above the level of the clavicles. These findings suggested that the persistence of the segment of dorsal aorta between the third and fourth embryonic arches and the double-barrelled aorta was more likely a consequence of persistence of the third and fourth pharyngeal arches. Detailed imaging and embryologic considerations played an important role in accurate assessment of the origin of the double-barrelled aorta. Learning objective: Double-barrelled aorta is a rare congenital anomaly. Its etiology had been previously described as persistence of the fifth pharyngeal arch, but recent embryologic studies suggest that it is more likely explained by other several developing processes. We report a case of double-barrelled aorta with high aortic arch likely arose from the third and fourth pharyngeal arches. Although the therapeutic approaches remain the same, accurate description and classification are important.

Absent pulmonary valve (APV) syndrome with tricuspid atresia or tricuspid stenosis (TA/TS) is an extremely rare malformation recently reported as a variant of APV with intact ventricular septum (VS). The condition, however, has univentricular physiology and unique structural and clinical features. The purpose of this study was to update the current knowledge about this condition by describing long-term outcomes of three new cases and reviewing the available literatures. A systematic literature search was performed to collect clinical and anatomical data of APV with TA/TS. Institutional medical records were retrospectively reviewed to identify APV with TA/TS patients. In a total of 62 (59 reported and 3 new) cases, patent ductus arteriosus was present in 98% of APV patients with TA/TS. A large ventricular septal defect, dilatation of the pulmonary arteries, which is typically found in APV with tetralogy of Fallot, and respiratory distress at birth were rarely reported. Most of the recent cases were successfully managed by the Glenn or Fontan procedure. Coronary artery anomaly and ventricular arrhythmia were more frequently reported as the cause of death or severe neurological sequelae (9/16 and 3/8, respectively). Additional surgical intervention was required in the mid/long-term period in three cases due to left-ventricular outflow obstruction and in two due to aortic dilatation. The Fontan and Glenn procedures improved the survival in the last two decades. In addition to coronary artery anomaly and ventricular arrhythmia, left-ventricular outflow tract obstruction and aortic dilatation should be carefully monitored.

Background: Children with autism spectrum disorder (ASD) may experience difficulty adapting to daily life in a preschool or school setting and are likely to develop psychosomatic symptoms. For a better understanding of the difficulties experienced daily by preschool children and adolescents with ASD, this study investigated differences in eye gaze behavior in the classroom environment between children with ASD and those with typical development (TD).Methods: The study evaluated 30 children with ASD and 49 children with TD. Participants were presented with images of a human face in a classroom setting. While they gazed at specific regions of visual stimuli, eye tracking was used with an iView X system to evaluate and compare the duration of gaze time between the two groups.Results: Compared with children with TD, children with ASD spent less time gazing at the eyes of the human face and the object to which the teacher pointed in the classroom image. Preschool children with no classroom experience and adolescents with TD spent the same amount of time looking at the human eyes and the object to which the teacher pointed in the classroom image.Conclusion: Children with ASD did not look at the human eyes in the facial image or the object pointed to in the classroom image, which may indicate their inability to analyze situations, understand instruction in a classroom, or act appropriately in a group. It is suggested that this gaze behavior of children with ASD causes social maladaptation and psychosomatic symptoms. A therapeutic approach that focuses on joint attention is desirable for improving the ability of children with ASD to adapt to the social environment.

Electricity plays an important role in modern societies, with lighting and illumination accounting for approximately one-fifth of the global demand for electricity. Haworthia obtusa has the remarkable ability to collect solar light through a so-called ‘window’ which allows it to photosynthesise in the dark. Inspired by this unique characteristic, we developed a novel lighting system that does not use electricity. The ‘window’ of H. obtusa is replicated using a scattering medium that collects solar light and guides it to an optical fibre. The optical fibre then carries the light indoors, where illumination is needed. The efficacy of this unique lighting system was confirmed both numerically and experimentally. The developed system should help in lowering energy consumption.

Ringer's lactate solution irradiated by non-thermal plasma, comprised of radicals, electrons, and ions, is defined as plasma-activated lactate (PAL). PAL exhibited antitumor effects in glioblastoma U251SP cells, which we termed PAL-specific regulated cell death. In contrast to the oxidative stress condition typical of cells incubated in plasma-activated medium (PAM), U251SP cells treated with Ringer's lactate solution or PAL exhibited changes in intracellular metabolites that were reductive in the redox state, as measured by the ratio of oxidative/reductive glutathione concentrations. In the metabolomic profiles of PAL-treated cells, the generation of acetyl-CoA increased for lipid metabolism from alanine and asparagine. PAL thus induces regulated death of U251SP glioblastoma cells in more innate microenvironments than PAM.

Objective Exposure to chronic psychosocial stress is a risk factor for metabolic cardiovascular disorders. Given that dipeptidyl peptidase-4 (DPP-4) has an important role in human pathobiology, we investigated the role of DPP-4 in stress-related thrombosis in mice, focusing on oxidative stress and the von Willebrand factor (vWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Methods and results Male mice randomly assigned to nonstress and 2-week immobilized-stress groups underwent iron chloride3 (FeCl3)-induced carotid artery thrombosis surgery for morphological and biochemical studies at specific times. On day 14 post-stress/surgery, stress had enhanced the lengths and weights of arterial thrombi, with alterations of plasma DPP-4, plasminogen activation inhibitor-1 and ADAMTS13. The stressed mice had increased levels of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, monocyte chemoattractant protein-1, gp91phox, p22phox, matrix metalloproteinase-2 (MMP-2), MMP-9, cathepsins S and K mRNAs and/or proteins, and reduced levels of endothelial nitric oxide synthase, catalase and superoxide dismutase-1 mRNAs and/or proteins. Stress also accelerated arterial endothelial cell damage. The DPP-4 inhibitor anagliptin ameliorated the stress-induced targeted molecular and morphological changes and thrombosis. In vitro, DPP-4 inhibition also mitigated the alterations in the targeted ADAMTS13 and other oxidative and inflammatory molecules in human umbilical vein endothelial cells in response to H2O2. Conclusion DPP-4 inhibition appeared to improve the FeCl3-induced thrombosis in mice that received stress, possibly via the improvement of ADAMTS13 and oxidative stress, suggesting that DPP-4 could become a novel therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disorders.

Background Chronic psychological stress (CPS) is linked to cardiovascular disease initiation and progression. Given that cysteinyl cathepsin K (CatK) participates in vascular remodeling and atherosclerotic plaque growth in several animal models, we investigated the role of CatK in the development of experimental neointimal hyperplasia in response to chronic stress. Methods and results At first, male wild-type (CatK) mice that underwent carotid ligation injury were subjected to chronic immobilization stress. On postoperative and stressed day 14, the results demonstrated that stress accelerated injury-induced neointima hyperplasia. On day 4, stressed mice showed following: increased levels of monocyte chemoattractant protein-1, gp91phox, toll-like receptor-2 (TLR2), TLR4, and CatK mRNAs or/and proteins, oxidative stress production, aorta-derived smooth muscle cell (SMC) migration, and macrophage infiltration as well as targeted intracellular proliferating-related molecules. Stressed mice showed increased matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA expressions and activities and elastin disruption in the injured carotid arteries. Second, CatK and CatK deficiency (CatK) mice received ligation injury and stress to explore the role of CatK. The stress-induced harmful changes were prevented by CatK. Finally, CatK mice that had undergone ligation surgery were randomly assigned to one of two groups and administered vehicle or CatK inhibitor for 14 days. Pharmacological CatK intervention produced a vascular benefit. Conclusion These data indicate that CatK deletion protects against the development of experimental neointimal hyperplasia via the attenuation of inflammatory overaction, oxidative stress production, and VSMC proliferation, suggesting that CatK is a novel therapeutic target for the management of CPS-related restenosis after intravascular intervention therapies.

Ringer’s lactate solution was irradiated with non-equilibrium plasma under airtight conditions. The plasma-activated lactate (PAL) was produced with argon, oxygen, and nitrogen gases following purging of Ar. Cytotoxicity could be controlled by diluting PAL, and a killing effect was selectively obtained on cancer cells compared to normal cells for Ar+O2+N2 PALs. Nonetheless, cytotoxicity was partly reproduced by similar concentrations of H2O2 and NO2 − in the PALs. The organics produced by plasma irradiation to lactate were investigated using nuclear magnetic resonance, and the generation of methyl amino species was confirmed.