Emerging role of syndecans in maintaining homeostasis of colon epithelium during inflammation.

The syndecans are a family of transmembrane proteoglycans that are widespread in mammalian tissues. Located at the cell surface membrane, they contribute to modulating the composition of the extracellular matrix via glycosaminoglycan chains (GAGs) attached to their extracellular domains. Syndecans can interact with a variety of extracellular ligands through their core proteins and GAGs, and may also transmit signals through their transmembrane domain to regulate intracellular functions. These properties enable syndecan to modulate glycocalyx formation, epithelial cell-to-cell connections for cell barrier formation, and epithelial cell-lamina propria interactions in the colon epithelium, all of which are crucial for the homeostasis of this tissue. Inflammation induces structural alterations of the colon epithelium, and accumulating evidence suggests that syndecan expression might play important regulatory functions during inflammation. This review summarizes the possible roles of syndecans in maintaining tissue homeostasis in the colon epithelium, especially under inflammation.

Multiplex SNP Genotyping Using SWITCH: Sequence-Specific Nanoparticle with Interpretative Toehold-Mediated Sequence Decoding in Hydrogel.

Single nucleotide polymorphisms (SNPs) that can alter phenotypes of individuals play a pivotal role in disease development and, more importantly, responses to therapy. However, SNP genotyping has been challenging due to the similarity of SNP alleles and their low concentration in biological samples. Sequence-specific nanoparticle with interpretative toehold-mediated sequence decoding in hydrogel (SWITCH) for multiplex SNP genotyping is presented. The encoding with gold nanoparticle probes transduces each SNP target to ≈1000 invaders with prominently different sequences between wild and mutant types, featuring polymerase chain reaction (PCR)-free amplification. Subsequently, the toehold-mediated DNA replacement in hydrogel microparticles decodes the invaders via SNP-specific fluorescence signals. The 4-plex detection of the warfarin-associated SNP targets spiked in commercially validated human serum (S1-100ML, Merck) is successfully demonstrated with excellent specificity. This work is the first technology development presenting PCR-free, multiplex SNP genotyping with a single reporting fluorophore, to the best of knowledge.

Veganism during the COVID-19 pandemic: Vegans' and nonvegans' perspectives.

Although the COVID-19 pandemic has triggered growing public interest in veganism, veganism's conceptualization remains ambiguous. Moreover, vegans' and nonvegans' different perspectives have rarely been addressed. Hence, this study involved the opinions of both vegans and nonvegans in the COVID-19 context to understand their attitudes, motivations, and opinions related to veganism. We analyzed online discourses in vegan and antivegan online communities using Word2Vec analysis and qualitative analysis. We identified lists of terms associated with three key veganism dimensions (i.e., lifestyle, animal rights, and food). Moreover, we compared actual online discussions among vegans to those among nonvegans regarding specific veganism attributes. This study preliminarily identifies specific attributes associated with veganism in online discourse among vegans. The issues addressed in this study can be tested in future research. Our findings can also be useful for people in various stages of veganism-such as active vegans, people who are interested in veganism, or even nonvegans who are uninterested in veganism-to comprehend the different perceptions prevailing in each group.

How does COVID-19 differ from previous crises? A comparative study of health-related crisis research in the tourism and hospitality context.

The importance of the risk to tourism and hospitality operations from pandemic-related crises has increased. Therefore, the current study offers a literature review targeting tourism and hospitality stakeholders' perceptions of past diseases and has three objectives: (1) Explore major topics from previous research on infectious diseases using topic modeling; (2) compare non-COVID-19 and COVID-19 crises; (3) investigate research topics in the tourism and hospitality industries. To meet our research objectives, we reviewed published pandemic-related articles in the tourism and hospitality literature since the year 2000. Based on the results, we first identified nine key topics related to infectious diseases (i.e., policy, human resources, branding, resilience, technology, global or community change, risk perception, disease impact, and lifestyle). Second, we suggest the application of different topic weights in non-COVID-19 and COVID-19 research. Third, we found that it is appropriate to apply different topic weights in tourism and hospitality research.

Goal-directed interaction of stimulus and task demand in the parahippocampal region.

The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The "dual-stream model" was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual-stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal-directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal-directed Interaction of Stimulus and Task-demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices-the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects-with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non-navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non-navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.

Nanoparticle-Mediated Blocking of Excessive Inflammation for Prevention of Heart Failure Following Myocardial Infarction.

Severe cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post-MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time-consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L-Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen-specific regulatory T cells (Tregs). Impressively, intradermal injection of L-Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory-to-reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle-mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post-MI heart failure.

Comparison of PECS II and erector spinae plane block for postoperative analgesia following modified radical mastectomy: Bayesian network meta-analysis using a control group.

The present study compared the effects of pectoral nerve block II (PECS II) and erector spinae plane (ESP) block for postoperative analgesia in patients who underwent modified radical mastectomy by performing a network meta-analysis (NMA) using indirect comparison with systemic analgesia. Studies comparing the analgesic effects of PECS II and ESP block were searched on MEDLINE, PubMed, EMBASE and the Cochrane Library. The primary outcome of this study was cumulative opioid consumption for 24 h postoperatively. Pain score during this period was also assessed. NMA was performed to compare the postoperative analgesic effects of plane blocks and systemic analgesia. A search of databases identified 17 studies, with a total of 1069 patients, comparing the analgesic efficacies of PECS II block, ESP block, and systemic analgesia. Compared with systemic analgesia, mean difference of opioid consumption was - 10 mg (95% credible interval [CrI] - 15.0 to - 5.6 mg) with PECS II block and - 5.7 mg (95% CrI - 11.0 to - 0.7 mg) with ESP block. Relative to systemic analgesia, PECS II block showed lower pain scores over the first postoperative 24 h, whereas ESP block did not. PECS II block showed the highest surface under the cumulative ranking curves for both opioid consumption and pain score. Both PECS II and ESP blocks were shown to be more effective than systemic analgesia regarding postoperative analgesia following modified radical mastectomy, and between the two blocks, PECS II appeared to have favorable analgesic effects compared to ESP block.

Changes in the Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1(APE1/Ref-1) Level during Cancer Surgery: An Observational Study.

Background and Objectives: Propofol-based total intravenous anesthesia (TIVA) is presumed to have more favorable effects on the prognosis of patients with cancer compared with volatile inhaled anesthesia (VIA). We hypothesized that these anesthetics target plasma apurinic apyrimidinic endonuclease/redox effector factor-1 (APE1/Ref-1) as a possible mechanism of action. Materials and Methods: The plasma APE1/Ref-1 level was evaluated three times during surgery for cancer, i.e., before anesthesia, immediately after cancer resection, and finally, in the recovery room. Blood (3 cc) was drawn from the radial artery catheter, and plasma APE1/Ref-1 levels were compared according to measurement time and between the two groups. Spearman's Rho correlation analysis was performed to determine relationships among body mass index, American Society of Anesthesiologists classification, age, sex, cancer type, and tumor-node-metastasis (TNM) stage. A total of 166 patients (VIA: 129; TIVA: 37) were enrolled. Results: Plasma APE1/Ref-1 level increased significantly (p = 0.028) after cancer resection compared with before surgery, but no significant difference was observed between anesthetics (p = 0.134). The post-resection plasma APE1/Ref-1 level showed a positive correlation with the NM stages, but not the T stage. Conclusions: The plasma APE1/Ref-1 level increased during surgery with more severe lymph node invasion, but there were no significant differences according to the anesthetics used.

NF-κB Activation Promotes Alphavirus Replication in Mature Neurons.

Alphaviruses are enveloped, positive-sense RNA viruses that are important causes of viral encephalomyelitis. Sindbis virus (SINV) infects the neurons of rodents and is a model for studying factors that regulate infection of neuronal cells. The outcome of alphavirus infection of the central nervous system is dependent on neuronal maturation status. Differentiated mature neurons survive and control viral replication better than undifferentiated immature neurons. The cellular factors involved in age-dependent susceptibility include higher levels of antiapoptotic and innate immune factors in mature neurons. Because NF-κB pathway activation is required for the initiation of both apoptosis and the host antiviral response, we analyzed the role of NF-κB during SINV infection of differentiated and undifferentiated rat neuronal cells. SINV infection induced canonical NF-κB activation, as evidenced by the degradation of IκBα and the phosphorylation and nuclear translocation of p65. Inhibition or deletion of the upstream IκB kinase substantially reduced SINV replication in differentiated but not in undifferentiated neuronal cells or mouse embryo fibroblasts. NF-κB inhibition did not affect the establishment of infection, replication complex formation, the synthesis of nonstructural proteins, or viral RNA synthesis in differentiated neurons. However, the translation of structural proteins was impaired, phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α) was decreased, and host protein synthesis was maintained, suggesting that NF-κB activation was involved in the regulation of translation during infection of mature neurons. Inhibition or deletion of double-stranded RNA-activated protein kinase (PKR) also decreased eIF2α phosphorylation, the translation of viral structural proteins, and virus production. Therefore, canonical NF-κB activation synergizes with PKR to promote SINV replication in differentiated neurons by facilitating viral structural protein translation.IMPORTANCE Mosquito-borne alphaviruses are a significant and growing cause of viral encephalomyelitis worldwide. The outcome of alphaviral neuronal infections is host age dependent and greatly affected by neuronal maturation status, with differentiated, mature neurons being more resistant to infection than undifferentiated, immature neurons. The biological factors that change during neuronal maturation and that influence the outcome of viral infection are currently only partially defined. These studies investigated the role of NF-κB in determining the outcome of alphaviral infection in mature and immature neurons. Inhibition of canonical NF-κB activation decreased alphavirus replication in mature neurons by regulating protein synthesis and limiting the production of the viral structural proteins but had little effect on viral replication in immature neurons or fibroblasts. Therefore, NF-κB is a signaling pathway that influences the maturation-dependent outcome of alphaviral infection in neurons and that highlights the importance of cellular context in determining the effects of signal pathway activation.

Attributes associated with person-centered care competence among undergraduate nursing students.

Person-centered care is widely recognized as a promising practice to improve patient care quality. However, little is known about the competencies of nursing students who are essential to providing high-quality person-centered care. In this study, relevant attributes, including professional nursing competence, empathy, and self-awareness, were examined in relation to person-centered care competence among South Korean nursing students while controlling for individual characteristics, including age, gender, religion, and academic performance. Data were collected from 213 senior students enrolled in four nursing schools in South Korea from November 15 to 30, 2017. The mean age of the nursing students in the sample was 23 years. Data were analyzed using multiple regression analyses while accounting for the students nested in their schools. Professional nursing competence and empathy were strongly associated with person-centered care competence among nursing students. Of the five aspects of professional nursing competence, human understanding and communication skills were the most likely to be associated with person-centered care competence. Moreover, there were few variations across nursing schools in the levels of professional nursing competence. Our findings corroborate the importance of developing better communication skills and empathy to improve and maintain person-centered care competence among nursing students who belong to a new generation.

Improved in vitro antioxidant properties and hepatoprotective effects of a fermented Inula britannica extract on ethanol-damaged HepG2 cells.

This study aimed to improve antioxidant effect and hepatoprotective effect of Inula britannica using fermentation. Epigallocatechin gallate (EGCG) in an I. britannica extract was found to be upregulated from 2.06 to 10.28 µg/mg during fermentation (p < 0.001). After fermentation, DPPH radical-scavenging ABTS radical-scavenging, and superoxide anion-scavenging abilities increased to 92.65%, 694.25 µM Trolox/mL, and 86.38%, respectively, at 500 µg/mL (p < 0.05). Cupric-ion-reducing capacity with formation of the Cu+-neocuproine complex increased by 5.88%, 6.38%, 3.24%, and 8.55% at 62.5 to 500 µg/mL. Ferric-ion-reducing capacity of the fermented extract increased by 20%, 7.16%, 3.85%, and 5.45% at each concentration (p < 0.05). Unfermented extracts yielded cell viability of 91.42%, 90.59%, 88.38%, and 79.17%, whereas the fermented extract yielded 100.28%, 99.66%, 96.15%, and 89.90%, respectively, at each concentration in ethanol-damaged HepG2 cells (p < 0.05). Additionally, the fermented extract decreased alanine transaminase activity from 117.2 to 61.7 U/mL in the ethanol-damaged HepG2 cell line (p < 0.01). Overall, both antioxidant and hepatoprotective effect increased by fermentation in I. britannica extract. These properties are expected to lead to new antioxidant agents via production of EGCG by fermentation.

Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields.

We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p.) impairs a well learned, hippocampus-dependent place avoidance behavior in rats that requires cognitive control even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium-freguency gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium-frequency and slow gamma oscillations in CA1 LFPs such that medium-frequency gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP, but the drug discoordinates the subsecond temporal organization of discharge among place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the subsecond timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation-inhibition discoordination as the root of PCP-induced cognitive impairment.SIGNIFICANCE STATEMENT Hippocampal neural discharge is temporally coordinated on timescales of theta and gamma oscillations in the LFP and the discharge of a subset of pyramidal neurons called "place cells" is spatially organized such that discharge is restricted to locations called a cell's "place field." Because this temporal coordination and spatial discharge organization is thought to represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt cognitive behavior and assess the importance of neural coordination and place fields for spatial cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal discharge without disrupting firing fields. These findings dissociate place fields from spatial cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial cognition.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

BACKGROUND: Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. METHODS: We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. RESULTS: In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. CONCLUSIONS: This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

Sector-Based Assessment of Infarct Size on Late-Gadolinium-Enhancement MRI in a Mouse Model of Acute Myocardial Infarction.

Scoring of myocardial infarction (MI) disease extent in cardiac magnetic resonance (CMR) images has been generally presented in terms of area-based infarct size. However, gradual thinning of the infarcted wall and compensatory hypertrophy of the noninfarcted remote wall during left ventricular (LV) remodeling after MI complicate the accuracy of infarct size measurement. In this study, we measured and compared infarct sizes in mice on late gadolinium enhancement (LGE) images using area-, length-, and radial sector-based methods.MI was induced by permanent ligation of the left coronary artery (n = 6). LGE images were acquired 30 minutes after intravenous injection of Gd-DTPA-BMA. Percentages of infarct size (%Area, %Length, and %Sector) on the LGE images were calculated and compared with histological findings.Infarct sizes obtained by an area-based approach were smaller than those obtained by other measurements. The area-based approach underestimated infarct size compared with the length-based approach. Most infarct sizes measured by each method demonstrated a similar trend, with maximum values determined by sector-based measurements using a mean + SD threshold. Spearman's rank correlation coefficients indicated that the 3 measurements were strongly correlated (P < 0.05) to each other. Significant differences and trends were observed between sector-based infarct sizes with different thresholds when 16 or more sectors were used.In conclusion, our study demonstrated that methods used for the histological calculation of infarct size could be applied to CMR analysis. Moreover, our results showed a similar trend to histological assessment. Sector-based CMR approaches can be useful for infarct size measurement.

Crystal structure analysis of a bacterial aryl acylamidase belonging to the amidase signature enzyme family.

The atomic structure of a bacterial aryl acylamidase (EC 3.5.1.13; AAA) is reported and structural features are investigated to better understand the catalytic profile of this enzyme. Structures of AAA were determined in its native form and in complex with the analgesic acetanilide, p-acetaminophenol, at 1.70 Å and 1.73 Å resolutions, respectively. The overall structural fold of AAA was identified as an α/ß fold class, exhibiting an open twisted ß-sheet core surrounded by α-helices. The asymmetric unit contains one AAA molecule and the monomeric form is functionally active. The core structure enclosing the signature sequence region, including the canonical Ser-cisSer-Lys catalytic triad, is conserved in all members of the Amidase Signature enzyme family. The structure of AAA in a complex with its ligand reveals a unique organization in the substrate-binding pocket. The binding pocket consists of two loops (loop1 and loop2) in the amidase signature sequence and one helix (α10) in the non-amidase signature sequence. We identified two residues (Tyr(136) and Thr(330)) that interact with the ligand via water molecules, and a hydrogen-bonding network that explains the catalytic affinity over various aryl acyl compounds. The optimum activity of AAA at pH > 10 suggests that the reaction mechanism employs Lys(84) as the catalytic base to polarize the Ser(187) nucleophile in the catalytic triad.

A novel strain of porcine epidemic diarrhea virus in Vietnamese pigs.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and dehydration in suckling pigs and has caused high rates of death among piglets and substantial economic loss in Vietnam since 2009. To investigate the genotypes of prevailing PEDVs, intestinal and fecal samples from piglets from central and northern Vietnam were collected and analyzed. Phylogenetic analysis of the nucleotide sequences of complete spike genes of PEDVs from Vietnam resulted in the identification of two divergent groups. PEDVs (HUA-PED45 and HUA-PED47) belonged to the G2b group, along with Chinese, US, and Korean strains occurring at the end of 2010, in May 2013 and in November 2013, respectively. Six strains from the Quang Tri region were assigned to the G1b group, along with Chinese and US strains. The Vietnamese PEDVs detected in infected piglets had a nationwide distribution and belonged to the G2b and G1b genotypes.

Oral immunization of mice with lily pollen expressing HBsAg.

Lily pollen was developed to express HBsAg by Agrobacterium-mediated transformation. A double prime-boost strategy combining parenteral and oral HBsAg boosters was found to increase antibody titer levels 10-fold, as compared to a single process of priming and boosting. Lily pollen may prove a tool for oral vaccine development.

Do Place Cells Dream of Deceptive Moves in a Signaling Game?

We consider the possibility of applying game theory to analysis and modeling of neurobiological systems. Specifically, the basic properties and features of information asymmetric signaling games are considered and discussed as having potential to explain diverse neurobiological phenomena; we focus on neuronal action potential discharge that can represent cognitive variables in memory and purposeful behavior. We begin by arguing that there is a pressing need for conceptual frameworks that can permit analysis and integration of information and explanations across many scales of biological function including gene regulation, molecular and biochemical signaling, cellular and metabolic function, neuronal population, and systems level organization to generate plausible hypotheses across these scales. Developing such integrative frameworks is crucial if we are to understand cognitive functions like learning, memory, and perception. The present work focuses on systems neuroscience organized around the connected brain regions of the entorhinal cortex and hippocampus. These areas are intensely studied in rodent subjects as model neuronal systems that undergo activity-dependent synaptic plasticity to form neuronal circuits and represent memories and spatial knowledge used for purposeful navigation. Examples of cognition-related spatial information in the observed neuronal discharge of hippocampal place cell populations and medial entorhinal head-direction cell populations are used to illustrate possible challenges to information maximization concepts. It may be natural to explain these observations using the ideas and features of information asymmetric signaling games.

Antifungal Activity of Bulgarian Rose Damascena Oil against Vaginitis-Causing Opportunistic Fungi.

Since Bulgarian rose damascena oil is known for its anti-inflammatory, antioxidant, and antimicrobial properties, we investigated its antifungal activity against the species of Candida, which are among the most common opportunistic fungal pathogens. Our disk-diffusion assay revealed that Bulgarian rose damascena oil effectively inhibited the growth of Candida albicans along with various bacteria. The minimum inhibitory and fungicidal concentrations against Candida albicans and Candida glabrata were all 0.25%. Under our experimental conditions, Bulgarian rose damascena oil showed better inhibitory effects on Candida glabrata and Candida albicans than several popular essential oils reported to have antifungal activity other than Origanum vulgare oil. Interestingly, Bulgarian rose damascena oil showed better antifungal activity against Candida species at acidic pH and induced cell death of Candida species in the culture medium, with cell death seen in 25-35% of the cells exposed to 0.05% Bulgarian rose damascena oil. Furthermore, Bulgarian rose damascena oil inhibited the hyphal growth of Candida albicans cultured in the RPMI medium with fetal bovine serum. These findings collectively suggest that Bulgarian rose damascena oil has antifungal activity against Candida species and thus could potentially be developed in novel therapies for vaginitis-causing pathogenic fungi.

Effects of Mesenchymal Stem Cell Injection into Healed Myocardial Infarction Scar Border Zone on the Risk of Ventricular Tachycardia.

The scar border zone is a main source of reentry responsible for ischemic ventricular tachycardia (VT). We evaluated the effects of mesenchymal stem cell (MSC) injection into the scar border zone on arrhythmic risks in a post-myocardial infarction (MI) animal model. Rabbit MI models were generated by left descending coronary artery ligation. Surviving rabbits after 4 weeks underwent left thoracotomy and autologous MSCs or phosphate-buffered saline (PBS) was administered to scar border zones in two rabbits in each group. Another rabbit without MI underwent a sham procedure (control). An implantable loop recorder (ILR) was implanted in the left chest wall in all animals. Four weeks after cell injections, ventricular fibrillation was induced in 1/2 rabbit in the PBS group by electrophysiologic study, and no ventricular arrhythmia was induced in the MSC group or control. Spontaneous VT was not detected during ILR analysis in any animal for 4 weeks. Histologic examination showed restoration of connexin 43 (Cx43) expression in the MSC group, which was higher than in the PBS group and comparable to the control. In conclusion, MSC injections into the MI scar border zone did not increase the risk of VT and were associated with favorable Cx43 expression and arrangement.