Rhizoviticin is an alphaproteobacterial tailocin that mediates biocontrol of grapevine crown gall disease.

Tailocins are headless phage tail structures that mediate interbacterial antagonism. Although the prototypical tailocins, R- and F-pyocins, in Pseudomonas aeruginosa, and other predominantly R-type tailocins have been studied, their presence in Alphaproteobacteria remains unexplored. Here, we report the first alphaproteobacterial F-type tailocin, named rhizoviticin, as a determinant of the biocontrol activity of Allorhizobium vitis VAR03-1 against crown gall. Rhizoviticin is encoded by a chimeric prophage genome, one providing transcriptional regulators and the other contributing to tail formation and cell lysis, but lacking head formation genes. The rhizoviticin genome retains a nearly intact early phage region containing an integrase remnant and replication-related genes critical for downstream gene transcription, suggesting an ongoing transition of this locus from a prophage to a tailocin-coding region. Rhizoviticin is responsible for the most antagonistic activity in VAR03-1 culture supernatant against pathogenic A. vitis strain, and rhizoviticin deficiency resulted in a significant reduction in the antitumorigenic activity in planta. We identified the rhizoviticin-coding locus in eight additional A. vitis strains from diverse geographical locations, highlighting a unique survival strategy of certain Rhizobiales bacteria in the rhizosphere. These findings advance our understanding of the evolutionary dynamics of tailocins and provide a scientific foundation for employing rhizoviticin-producing strains in plant disease control.

A NitroPure Nitrocellulose Membrane-Based Grapevine Virus Sampling Kit: Development and Deployment to Survey Japanese Vineyards and Nurseries.

We developed a NitroPure Nitrocellulose (NPN) membrane-based method for sampling and storing grapevine sap for grapevine virus detection. We devised an efficient nucleic acid extraction method for the NPN membrane, resulting in 100% amplification success for grapevine leafroll-associated virus 2 (GLRaV2) and 3 (GLRaV3), grapevine rupestris stem pitting-associated virus (GRSPaV), grapevine virus A, grapevine virus B, and grapevine red blotch virus (GRBV). This method also allowed the storage of recoverable nucleic acid for 18 months at room temperature. We created a sampling kit to survey GLRaV2, GLRaV3, and GRBV in Japanese vineyards. We tested the kits in the field in 2018 and then conducted mail-in surveys in 2020-2021. The results showed a substantial prevalence of GLRaV3, with 48.5% of 132 sampled vines being positive. On the other hand, only 3% of samples tested positive for GLRaV2 and none for GRBV.

Insight into the population dynamics of pathogenic bacteria causing grapevine crown gall in snowfall areas: snow cover protects the proliferation of pathogenic bacteria.

Grapevine crown gall (GCG) is a significant bacterial disease caused by tumorigenic Allorhizobium vitis (TAV) and is prevalent worldwide. TAV infects grapevines through wounds such as freezing injuries. Although grapevines typically avoid being wounded under snow cover, GCG occurs in many commercial vineyards in snowy regions. This study investigated the TAV population in GCG gall tissues, grapevine skins, and snow on grapevine skins from six infected vineyards located in Hokkaido, Japan, an area known for heavy snowfall. TAV was isolated not only from gall tissues but also from skins and snow on skins throughout the year. Hierarchical Bayesian model (HBM) analysis revealed that the number of TAV cells in gall tissues was affected by cultivar and low temperature, while those in skins were affected by location and low temperature. Additionally, Bayesian changepoint detection (BCD) showed that the number of TAV cells in gall and skin tissues increased during winter, including the snowfall season. Furthermore, the TAV population in grapevine skins under the snow was significantly higher than those above the snow, indicating that TAV under the snow is protected by the snow and can survive well during the snowfall season. This study highlights the ability of TAV to overwinter on/in galls and skins under the snow and act as inoculum for the next season.

Characteristic features of statistical models and machine learning methods derived from pest and disease monitoring datasets.

While many studies have used traditional statistical methods when analysing monitoring data to predict future population dynamics of crop pests and diseases, increasing studies have used machine learning methods. The characteristic features of these methods have not been fully elucidated and arranged. We compared the prediction performance between two statistical and seven machine learning methods using 203 monitoring datasets recorded over several decades on four major crops in Japan and meteorological and geographical information as the explanatory variables. The decision tree and random forest of machine learning were found to be most efficient, while regression models of statistical and machine learning methods were relatively inferior. The best two methods were better for biased and scarce data, while the statistical Bayesian model was better for larger dataset sizes. Therefore, researchers should consider data characteristics when selecting the most appropriate method.

A PHLID Model for Tomato Bacterial Canker Predicting on Epidemics of the Pathogen.

A pathogen, healthy, latently infected, infectious, and diseased plant (PHLID) model for botanical epidemics was defined for tomato bacterial canker (TBC) caused by the pathogenic plant bacteria, Clavibacter michiganensis subsp. michiganensis (Cmm). First, the incubation period had to be defined to develop this type of model. To estimate the parameter of incubation period, inoculation experiments were conducted in which it was assumed that infection is transferred to healthy plants by cutting with contaminated scissors after cutting infected plants with early symptoms or symptomless. The concentration of Cmm was increased over 1 × 106 cells/g plant tissue at 20 cm away from the inoculated point on the stem 10 days after inoculation, and then the approximate incubation period of TBC in symptomless infected plants was defined as 10 days. The developed PHLID model showed the dynamics of diseased plants incidence and fitted the curve of the proportion of diseased plants observed in fields well. This model also contains the factors of pathogen and disease control, and it was able to simulate the control effects and combined two different control methods, which were the soil and scissors disinfections to prevent primary and secondary transmissions, respectively. Thus, this PHLID model for TBC can be used to simulate not only the increasing number of diseased plants but also suppressing disease increase.

Biological Control for Grapevine Crown Gall Evaluated by a Network Meta-Analysis.

Grapevine crown gall (GCG), which is caused by Allorhizobium vitis (=Rhizobium vitis) tumorigenic strains, is the most important disease of grapevine around the world. Previously, nonpathogenic A. vitis strains VAR03-1, ARK-1, ARK-2, and ARK-3 were identified as promising biological control agents, but the control effects of each strain were not directly compared and assessed in the field because field trials were conducted in different fields and years. Thus, the results of the control effects obtained from 16 field trials in 12 years from 2006 to 2017 were analyzed and evaluated by a linear mixed model (LMM) and a network meta-analysis (NMA). The results of the LMM strongly indicate that the factor "antagonistic strain" was significantly related to the biological control activity in this study, but the other factors, "concentration of cell suspension", "field", and "year", were not. Then, the results of 16 field trials were combined in an NMA. The estimated relative risk (RR) after treatment with ARK-1, ARK-2, ARK-3, VAR03-1, and K84 were 0.16, 0.20, 0.22, 0.24, and 0.74, respectively. In conclusion, strain ARK-1 was the best antagonist regardless of the concentration of the cell suspension, field, and year differences, and it can be recommended to control GCG.

A synthetic porphyrin as an effective dual antidote against carbon monoxide and cyanide poisoning.

Simultaneous poisoning by carbon monoxide (CO) and hydrogen cyanide is the major cause of mortality in fire gas accidents. Here, we report on the invention of an injectable antidote against CO and cyanide (CN-) mixed poisoning. The solution contains four compounds: iron(III)porphyrin (FeIIITPPS, F), two methyl-ß-cyclodextrin (CD) dimers linked by pyridine (Py3CD, P) and imidazole (Im3CD, I), and a reducing agent (Na2S2O4, S). When these compounds are dissolved in saline, the solution contains two synthetic heme models including a complex of F with P (hemoCD-P) and another one of F with I (hemoCD-I), both in their iron(II) state. hemoCD-P is stable in its iron(II) state and captures CO more strongly than native hemoproteins, while hemoCD-I is readily autoxidized to its iron(III) state to scavenge CN- once injected into blood circulation. The mixed solution (hemoCD-Twins) exhibited remarkable protective effects against acute CO and CN- mixed poisoning in mice (~85% survival vs. 0% controls). In a model using rats, exposure to CO and CN- resulted in a significant decrease in heart rate and blood pressure, which were restored by hemoCD-Twins in association with decreased CO and CN- levels in blood. Pharmacokinetic data revealed a fast urinary excretion of hemoCD-Twins with an elimination half-life of 47 min. Finally, to simulate a fire accident and translate our findings to a real-life scenario, we confirmed that combustion gas from acrylic cloth caused severe toxicity to mice and that injection of hemoCD-Twins significantly improved the survival rate, leading to a rapid recovery from the physical incapacitation.

An HLD Model for Tomato Bacterial Canker Focusing on Epidemics of the Pathogen Due to Cutting by Infected Scissors.

A healthy, latently infected, diseased (HLD) plant model for botanical epidemics was defined for tomato bacterial canker (TBC) caused by the pathogenic plant bacteria, Clavibacter michiganensis subsp. michiganensis (Cmm). To estimate the infection probability parameter, inoculation experiments were conducted in which it was assumed that infection is transferred to healthy plants through contaminated scissors used to cut symptomless infected plants. The approximate concentration of Cmm in symptomless infected plants was 1 × 106 cells/mL, and the probability of infection of healthy tomato plants was approximately 0.75 due to cutting with scissors soaked in a cell suspension of Cmm at 1 × 106 cells/mL. Three different HLD models were developed by changing some parameters, and the D curve calculated by the developed HLD model A was quite similar to the curve of the proportion of diseased plants observed in fields that had a severe disease incidence. Under a simulation of disease incidence using this model, the basic reproduction number (R0) was 2.6. However, if the infected scissors were disinfected using ethanol, R0 was estimated as 0.3. The HLD model for TBC can be used to simulate the increasing number of diseased plants and the term of disease incidence.

Transplantation of Fibroblast Sheets with Blood Mononuclear Cell Culture Exerts Cardioprotective Effects by Enhancing Anti-Inflammation and Vasculogenic Potential in Rat Experimental Autoimmune Myocarditis Model.

Fulminant myocarditis causes impaired cardiac function, leading to poor prognosis and heart failure. Cell sheet engineering is an effective therapeutic option for improving cardiac function. Naïve blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. Herein, we investigated whether autologous cell sheet transplant with QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM). Fibroblast sheets (F-sheet), prepared from EAM rats, were co-cultured with or without QQMNCs (QQ+F sheet) on temperature-responsive dishes. QQ+F sheet induced higher expression of anti-inflammatory and vasculogenic genes (Vegf-b, Hgf, Il-10, and Mrc1/Cd206) than the F sheet. EAM rats were transplanted with either QQ+F sheet or F-sheet, and the left ventricular (LV) hemodynamic analysis was performed using cardiac catheterization. Among the three groups (QQ+F sheet, F-sheet, operation control), the QQ+F sheet transplant group showed alleviation of end-diastolic pressure-volume relationship on a volume load to the same level as that in the healthy group. Histological analysis revealed that QQ+F sheet transplantation promoted revascularization and mitigated fibrosis by limiting LV remodeling. Therefore, autologous QQMNC-modified F-sheets may be a beneficial therapeutic option for EAM.

A case of α-chain variant hemoglobin (Hb Chad) with falsely high HbA1c levels measured by immunoassay.

Variant hemoglobin is often detected during the diagnosis and treatment of diabetes mellitus. We here describe a case of α2-chain variant hemoglobin (Hb Chad) that was identified as a result of differences in HbA1cs values determined by different assays. HbA1c measured by immunoassay was thus falsely high, whereas that measured by high-performance liquid chromatography (HPLC) was slightly low. Sequencing analysis revealed a heterozygous GAG (glutamic acid) → AAG (lysine) mutation at amino acid position 23 of the α2-globin gene. This residue is located at the surface of the α-chain in the crystal structure of hemoglobin. The high HbA1c value determined by immunoassay might have been the result of increased antigenicity of the variant hemoglobin, whereas the low value measured by HPLC reflected differential fractionation of the variant relative to the wild-type protein. Hb Chad has been reported in only three cases to date, and HbA1c was measured for the first time. This is the first case where falsely high HbA1c measured by immunoassay due to increased antigenicity in α-chain variant hemoglobin. This case highlights the importance of comparison with other parameters related to plasma glucose such as glycated albumin if an HbA1c abnormality is suspected. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00529-y.

Origin of Pathogens of Grapevine Crown Gall Disease in Hokkaido in Japan as Characterized by Molecular Epidemiology of Allorhizobium vitis Strains.

Crown gall is a globally distributed and economically important disease of grapevine and other important crop plants. The causal agent of grapevine crown gall is tumorigenic Allorhizobium vitis (Ti) strains that harbor a tumor-inducing plasmid (pTi). The epidemic of grapevine crown gall has not been widely elucidated. In this study, we investigated the genetic diversity of 89 strains of Ti and nonpathogenic A. vitis to clarify their molecular epidemiology. Multi-locus sequence analysis (MLSA) of the partial nucleotide sequences of pyrG, recA, and rpoD was performed for molecular typing of A. vitis strains isolated from grapevines with crown gall symptoms grown in 30 different vineyards, five different countries, mainly in Japan, and seven genomic groups A to F were obtained. The results of MLSA and logistic regression indicated that the population of genetic group A was significantly related to a range of prefectures and that the epidemic of group A strains originated mainly in Hokkaido in Japan through soil infection. Moreover, group E strains could have been transported by infected nursery stocks. In conclusion, this study indicates that both soil infection and transporting of infected nursery stocks are working as infection source in Hokkaido.

External administration of moon jellyfish collagen solution accelerates physiological wound healing and improves delayed wound closure in diabetic model mice.

INTRODUCTION: Artificial dermis is an effective therapeutic method for full-thickness dermal defects. However, the currently available artificial dermis made of porcine or bovine type I collagen has several limitations such as incomplete epithelialization and delayed migration of fibrogenic and angiogenic cells into the graft. We previously developed a composite dermal graft containing a mixture of moon jellyfish collagen and porcine type I collagen, and reported its stimulatory effect on both the re-epithelialization of the epidermis and the migration of fibrogenic and angiogenic cells into the graft. In the present study, we examined whether the same effect was observed by administering jellyfish collagen solution externally onto an artificial dermal graft made of bovine type I collagen. METHODS: We used a 6 mm full-thickness wound defect model. Moon jellyfish collagen was prepared as a concentrated 0.5% solution and dripped externally onto a transplanted artificial dermal graft made of bovine type I collagen. Wound repair and long-term dermal tissue remodeling were compared between mice administered jellyfish collagen solution on the bovine collagen graft and those transplanted with a composite dermal graft containing the same amounts of jellyfish and bovine collagens. The stimulatory effect of jellyfish collagen solution was also evaluated using diabetic dB/dB mice. RESULTS: External administration of jellyfish collagen solution onto the bovine collagen graft significantly accelerated wound closure compared to control saline. It also decreased the number of inflammatory cells infiltrating the wound and suppressed absorption of the transplanted graft, as well as reduced subsequent scar formation. Furthermore, external administration of jellyfish collagen solution onto the bovine collagen graft improved the delayed wound healing in diabetic model mice, and this effect was superior to that of the currently used basic fibroblast growth factor. CONCLUSIONS: External administration of moon jellyfish collagen solution onto a bovine collagen graft significantly accelerated physiological wound healing and prevented excessive scar formation. It also improved wound closure in diabetic model mice, confirming its therapeutic application for intractable skin ulcers caused by impaired wound healing.

Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.

Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, while the fact that CO accumulation in tissues is the most likely direct cause of mortality is less investigated. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was used in vivo as a CO removal agent, showing that it acts as an effective adjuvant to O2 ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning.

Complete Genome Sequence Data of Nonpathogenic and Nonantagonistic Strain of Rhizobium vitis VAR06-30 Isolated From Grapevine Rhizosphere.

Rhizobium (Agrobacterium) is one genus in the family Rhizobiaceae. Most of the species are epi- or endophytic bacteria which include tumorigenic or rhizogenic pathogens, root nodule bacteria, and commensal endosymbionts. Rhizobium vitis strain VAR06-30 is a commensal bacterium without pathogenicity which was isolated from a rootstock of grapevine in Japan. It also does not have antagonistic activity to the pathogenic strain of R. vitis. Here, we show the complete genome sequence data with annotation of R. vitis VAR06-30 which was analyzed by sequence reads obtained from both PacBio and Illumina platforms. This genome sequence would contribute to the understanding of evolutionary lineage and characteristics of Rhizobium commensal bacteria.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Complete Genome Sequence Data of Tumorigenic Rhizobium vitis Strain VAT03-9, a Causal Agent of Grapevine Crown Gall Disease.

Rhizobium vitis strain VAT03-9 (MAFF 211676) is a causal agent of crown gall disease in grapevine. It is one of the pathogenic strains of R. vitis isolated from graft unions of grapevine in Okayama Prefecture, Japan. Inoculation tests verified its virulence for gall formation on grapevine, tomato, and sunflower. It harbors tumor-inducing plasmid. Here, we present the complete genome sequence with annotation of R. vitis VAR03-9 obtained by assembling reads from PacBio and Illumina-sequencers. This genome sequence should be useful for the analyses of pathogenicity and evolutionary lineage of the pathogens of crown gall disease.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Complete Genome Sequence Data of Nonpathogenic Strain Rhizobium vitis VAR03-1, a Biological Control Agent for Grapevine Crown Gall Disease.

Crown gall disease in grapevine is caused by pathogenic strains of Rhizobium vitis with a tumor-inducing (Ti) plasmids. A nonpathogenic strain, VAR03-1 of R. vitis, has been isolated from the grapevine root of nursery stock and it was shown to act as a biological control agent to crown gall disease. Its disease-suppressive effect was observed even when it was coinoculated with the pathogen in a 1:1 ratio. Here, we present the complete genome data of R. vitis VAR03-1, assembled by sequencing reads obtained by both PacBio and Illumina technologies with annotation. This genome sequence could contribute to investigations of the molecular basis underlying the biocontrol activity as well as the root-colonization ability of this bacterial strain.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Evaluating Asthma Mobile Apps to Improve Asthma Self-Management: User Ratings and Sentiment Analysis of Publicly Available Apps.

BACKGROUND: The development and use of mobile health (mHealth) apps for asthma management have risen dramatically over the past two decades. Asthma apps vary widely in their content and features; however, prior research has rarely examined preferences of users of publicly available apps. OBJECTIVE: The goals of this study were to provide a descriptive overview of asthma mobile apps that are publicly available and to assess the usability of asthma apps currently available on the market to identify content and features of apps associated with positive and negative user ratings. METHODS: Reviews were collected on June 23, 2020, and included publicly posted reviews until June 21, 2020. To characterize features associated with high or low app ratings, we first dichotomized the average user rating of the asthma app into 2 categories: a high average rating and a low average rating. Asthma apps with average ratings of 4 and above were categorized as having a high average rating. Asthma apps with average ratings of less than 4 were categorized as having a low average rating. For the sentiment analysis, we modeled both 2-word (bi-gram) and 3-word (tri-gram) phrases which commonly appeared across highly rated and lowly rated apps. RESULTS: Of the 10 apps that met the inclusion criteria, a total of 373 reviews were examined across all apps. Among apps reviewed, 53.4% (199/373) received high ratings (average ratings of 4 or 5) and 47.2% (176/373) received low ratings (average ratings of 3 or less). The number of ratings across all apps ranged from 188 (AsthmaMD) to 10 (My Asthma App); 30% (3/10) of apps were available on both Android and iOS. From the sentiment analysis, key features of asthma management that were common among highly rated apps included the tracking of peak flow readings (n=48), asthma symptom monitoring (n=11), and action plans (n=10). Key features related to functionality that were common among highly rated apps included ease of use (n=5). Users most commonly reported loss of data (n=14) and crashing of app (n=12) as functionality issues among poorly rated asthma apps. CONCLUSIONS: Our study results demonstrate that asthma app quality, maintenance, and updates vary widely across apps and platforms. These findings may call into question the long-term engagement with asthma apps, a crucial factor for determining their potential to improve asthma self-management and asthma clinical outcomes.

A Novel Composite Biomaterial Made of Jellyfish and Porcine Collagens Accelerates Dermal Wound Healing by Enhancing Reepithelization and Granulation Tissue Formation in Mice.

Background and Objective: Impaired dermal wound healing represents a major medical issue in today's aging populations. Granulation tissue formation in the dermis and reepithelization of the epidermis are both important and necessary for proper wound healing. Although a number of artificial dermal grafts have been used to treat full-thickness dermal loss in humans, they do not induce reepithelization of the wound, requiring subsequent epithelial transplantation. In the present study, we sought a novel biomaterial that accelerates the wound healing process. Approach: We prepared a composite biomaterial made of jellyfish and porcine collagens and developed a hybrid-type dermal graft that composed of the upper layer film and the lower layer sponge made of this composite biomaterial. Its effect on dermal wound healing was examined using a full-thickness excisional wound model. Structural properties of the dermal graft and histological features of the regenerating skin tissue were characterized by electron microscopic observation and immunohistological examination, respectively. Results: The composite biomaterial film stimulated migration of keratinocytes, leading to prompt reepithelization. The regenerating epithelium consisted of two distinct cell populations: keratin 5-positive basal keratinocytes and more differentiated cells expressing tight junction proteins such as claudin-1 and occludin. At the same time, the sponge made of the composite biomaterial possessed a significantly enlarged intrinsic space and enhanced infiltration of inflammatory cells and fibroblasts, accelerating granulation tissue formation. Innovation: This newly developed composite biomaterial may serve as a dermal graft that accelerates wound healing in various pathological conditions. Conclusion: We have developed a novel dermal graft composed of jellyfish and porcine collagens that remarkably accelerates the wound healing process.

Artificial oxygen carrier improves fatigue resistance in slow muscle but not in fast muscle in a rat in situ model.

The effects of liposome-encapsulated hemoglobin with high O2 affinity (h-LEH), an artificial O2 carrier in skeletal muscle, were studied by in situ fatigue resistance test in fast-type plantaris (PLT) and slow-type soleus (SOL) muscles with or without ischemia in the rat. The distal tendons of PLT and SOL muscles were isolated in situ and individually attached to the force transducers to record the developed tension in response to stimuli (80 Hz tetanus train, 1.5 minutes) to the ipsilateral sciatic nerve. The fatigue resistance test (five sets separated by 2-minute rests) was evaluated in terms of tension attenuation (fatigue) from the initial to the last tension (A) during each set, attenuation of the initial (B) or last tension (C) in each set, as compared to the first set in the presence or absence of ischemia or h-LEH (10 mL/kg). While ischemia significantly enhanced fatigue only in PLT, h-LEH showed no effect regardless of the perfusion pattern (normal/ischemia) or muscle-type (PLT/SOL) during each set (A). In parameter (B), set-by-set fatigue development was observed in PLT, whereas h-LEH-SOL showed a trend of advanced fatigue resistance. Such trends became clear in the parameter C (last tension), because h-LEH-SOL exerted, rather than decreased, the tension enhancement regardless of the presence or absence of ischemia, whereas there were no h-LEH effects in PLT. In addition, faster recovery of the nicotinamide adenine dinucleotide content in the muscle after 10 minutes of all fatigue tests was observed in h-LEH-SOL, while saline-SOL still showed a significantly higher value than that of control. These results suggested that additional O2 supply by h-LEH may accelerate the tricarboxylic acid cycle/electron transport chain in slow-type aerobic SOL muscle containing abundant mitochondria and contribute to the faster removal of muscle fatigue substances such as lactate.

Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells.

OBJECTIVE: In-stent restenosis after percutaneous transluminal angioplasty and stenting (PTAS) due to neointimal hyperplasia is a potential cause of clinical complications, including repeated revascularization and ischemic events. Neointimal hyperplasia induced by an inflammatory response to the stent strut may be a possible mechanism of in-stent restenosis. Intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) has been reported to show therapeutic efficacy for cerebral stroke, presumably by an antiinflammatory effect. This study aimed to determine whether MSCs can reduce or prevent neointimal hyperplasia induced by an endovascular stent. METHODS: In this study, two types of bare metal stents were deployed using a porcine (mini-pig) model. One stent was implanted in the common carotid artery (CCA), which is considered quite similar to the human CCA, and the other was inserted in the superficial cervical artery (SCA), which is similar in size to the human middle cerebral artery. Angiographic images, intravascular ultrasound (IVUS) imaging, and microscopic images were used for analysis. RESULTS: Angiographic images and IVUS studies revealed that intravenous infusion of MSCs immediately after deployment of stents prevented in-stent stenosis of the CCA and SCA. Histological analysis also confirmed that inflammatory responses around the stent struts were reduced in both the stented CCA and SCA in the mini-pig. CONCLUSIONS: Intravenous infusion of MSCs inhibited the inflammatory reaction to an implanted stent strut, and prevented progressive neointimal hyperplasia in the stented CCA and SCA in a porcine model. Thus, MSC treatment could attenuate the recurrence of cerebral ischemic events after stenting.