Thickness of melanocytes in giant congenital melanocytic nevus for complete surgical excision: clinicopathological evaluation of 117 lesions according to the area and size.

BACKGROUND: Giant congenital melanocytic nevi (GCMN) are usually defined as nevi that exceed 20 cm in maximal diameter or 15% of the total body surface area. There have been reports of life-long malignant change risks arising from GCMN, leading to surgical excision of GCMN. This study aims to evaluate the thickness of melanocytes based on clinical factors in order to provide objective information for the complete resection of the lesion. METHODS: Overall, 75 patients diagnosed with GCMN between 2000 and 2021 were included, and their clinical records were collected retrospectively. 117 pathologic slides obtained during excision were reviewed to measure nevus thickness. Clinical factors were assessed with a generalized estimated equation model for association with nevus thickness. RESULTS: The thickness of nevus was significantly associated with the location and size. Nevus thickness was more superficial in the distal extremity than in the head and trunk (P = 0.003 [head]; P < 0.001 [trunk]; P = 0.091 [Proximal extremity]). Nevi sized 60 cm or more were significantly deeper than those measuring 20-29.9 cm (P = 0.035). An interaction between size and location existed (P < 0.001). Trunk and distal extremity lesions consistently exhibited uniform thickness regardless of lesion size, whereas head and proximal extremity lesions showed variations in thickness based on lesion size. CONCLUSION: GCMNs have differences in thickness according to location and size. Therefore, it is necessary to devise an approach optimized for each patient to treat GCMN. In the study, it was emphasized that the thickness of GCMN is correlated with clinical factors, specifically the location and size of the nevus. Consequently, these findings underscore the need for individualized treatment plans for effective surgical intervention.

Histochemical Identification of Motor Fascicles Using Cholinesterase Staining in Rats Using a Mixed Nerve Model.

BACKGROUND: Inappropriate matching of motor and sensory fibers after nerve repair or grafting can lead to nerve recovery failure. Identifying the motor and sensory fascicles enables surgeons to match them accurately and correctly align nerve stumps, which is crucial for neural regeneration. Very few methods have been reported to differentiate between the sensory and motor nerve fascicles, and the replicability of these techniques remains unestablished. In this study, we aimed to assess the accuracy of axonal cholinesterase (CE) histochemical staining in distinguishing motor and sensory nerve fibers. METHODS: The femoral and sciatic nerves were harvested from rats. The specimens were immediately cut, frozen in isopentane, and cooled with liquid nitrogen. Nerve serial cross-sections were processed for hematoxylin and eosin staining, followed by CE histochemistry. The staining protocol solutions included acetylthiocholine iodide, phosphate buffer, cobalt sulfate hydrate, potassium phosphate monobasic, sulfuric acid, sodium bicarbonate, glutaraldehyde, and ammonium sulfide. RESULTS: Cross-sections of nerves containing efferent and afferent nerve fibers in segregated fascicles showed that CE activity was confined to motor neurons. A histochemical study revealed that motor fibers with high cholinesterase activity can be differentiated from sensory fibers. The motor branches of the femoral and sciatic nerves showed specific axonal staining, whereas the sensory branch did not show any specific staining. CONCLUSION: CE histochemical staining is a useful technique for distinguishing between motor and sensory nerve fibers. It can be potentially useful in improving the outcomes of nerve grafts or extremity allotransplantation surgery.

Gene Ex Vivo Transduction Effects on Flap Survival and MicroRNAs Expression Analysis in Rat Allotransplantation Model.

BACKGROUND: The lack of noninvasive biomarkers for graft rejection remains a challenge for the accurate monitoring of vascularized composite allotransplants. Viral vector-mediated gene transfer is a promising method for preventing graft rejection. In this study, we aimed to establish the expression profile of microRNAs (miRNAs) in skin flap allotransplantation, with or without gene transfer, and determine the potential role of several miRNAs as biomarkers of acute rejection and immune tolerance. METHODS: An abdominal epigastric flap was transplanted from SD (RT1a) to Wistar rats (RT1Au). The adenoviral interleukin 10 (vIL-10) gene was transferred to the experimental group via flap pedicle injection. Postoperatively, flap appearance, hematoxylin and eosin staining, immunohistochemical staining, and miRNA expression analyses were performed. RESULTS: The viral IL-10 gene-treated group showed improved flap survival and reduced acute rejection response compared with the control group. On postoperative day 7, IL-10 expression in the flap was identified using immunohistochemistry and real-time polymerase chain reaction. The expression of miR-191a, miR-31a, miR-16, and miR-3473 was upregulated in the skin tissue, and that of miR-484, miR-132, miR-139, miR-150, and miR-6216 was upregulated in the serum. CONCLUSION: AV IL-10 gene transfer could be an effective immunosuppressive strategy for the prevention of skin flap allograft rejection. Additionally, some miRNAs were upregulated in the experimental group, serving as potential biomarkers of immune tolerance.

Ammonia and Particulate Matter Emissions at a Korean Commercial Pig Farm and Influencing Factors.

Quantifying emission factors of ammonia and particulate matter (PM) in livestock production systems is crucial for assessing and mitigating the environmental impact of animal production and for ensuring industry sustainability. This study aimed to determine emission factors of ammonia, total suspended particles (TSPs), PM10, and PM2.5 for piglets and growing-finishing pigs at a commercial pig farm in Korea. It also sought to identify factors influencing these emission factors. The research found that the emission factors measured were generally lower than those currently used in Korea, but were consistent with findings from individual research studies in the literature. Seasonal variations were observed, with ammonia emissions peaking in spring and autumn, and PM emissions rising in summer. Correlation analyses indicated that the number of animals and their average age correlated positively with both ammonia and PM emission factors. Ventilation rate was also positively correlated with PM emissions. Future extended field measurements across diverse pig farms will offer deeper insights into the emission factors of pig farms in Korea, guiding the development of sustainable livestock management practices.

Outcomes After Rotator Cuff Repair With Transverse Scapular Ligament Release in Patients With Severe Fatty Degeneration of the Infraspinatus.

BACKGROUND: In some large to massive rotator cuff tears (RCTs), fatty degeneration (FD) is more severe in the infraspinatus than the supraspinatus muscle, and in such cases, suprascapular neuropathy is highly suspected. Nerve release at the suprascapular notch might alleviate this problem. PURPOSE: To evaluate the effects of the transverse scapular ligament (TSL) release in patients with large to massive RCTs with more severe FD of the infraspinatus than the supraspinatus. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between September 2017 and January 2022, arthroscopic TSL release with rotator cuff repair was performed in patients with large to massive RCTs and more severe FD of the infraspinatus muscle than the supraspinatus muscle (TSL group). Cuff integrity, FD, and atrophy of cuff muscles were evaluated using preoperative and 1-year postoperative magnetic resonance imaging. In addition, results were compared with those of patients who did not undergo TSL release during arthroscopic large to massive rotator cuff repair (NTSL group). RESULTS: A total of 103 patients-20 in the TSL group and 83 in the NTSL group-were included. Group preoperative characteristics, including tear size and supraspinatus FD, were not significantly different, but infraspinatus FD (TSL vs NTSL; grade, 0-4, 0/0/5/10/5 vs 1/33/42/4/3) and atrophy (grade, 1-3. 3/9/8 vs 56/20/7) differed significantly (P < .001). Healing failure occurred in 13 of 20 (65%) patients in the TSL group and 30 of 83 (36%) patients in the NTSL group, which was a statistically significant difference (P = .019). Postoperatively, infraspinatus FD and atrophy were more severe in the TSL group than in the NTSL group (P < .001), and supraspinatus FD was more severe in the TSL group (P = .029). Seven patients in the TSL group achieved healing, but FD and atrophy of the supraspinatus and the infraspinatus showed no improvement in this group (all, P > .05). CONCLUSION: In patients with more FD in the infraspinatus than the supraspinatus muscle, TSL release appeared to have no benefit for cuff healing or FD reversal in cuff muscles. The possibility of suprascapular nerve entrapment remains in patients with more FD in the infraspinatus than the supraspinatus, and this potential nerve problem is not properly addressed by TSL release alone.

Surgical delay increases the survival of expanded random-pattern flap in pediatric patients.

Despite the aid of tissue expansion, the ideal design of random pattern flap is not always available in patients with extensive skin lesions. We investigated the effectiveness of surgical delay on expanded flaps in pediatric patients. Retrospective cohort study was performed on patients who underwent tissue expansion surgery for extensive skin lesions at Seoul National University Children's Hospital. The surgical delay technique was employed for patients with unfavorable flap conditions related to location or transposition angles. The dimensions of skin lesions and flaps were measured based on medical photographs. Fifty patients underwent a total of 66 tissue expansion procedures (49 conventional procedures among 41 patients, 17 surgical delay procedures among 15 patients) from January 2016 to September 2019. Although flaps in the surgical delay group were more narrow-based (p < 0.001), the partial flap loss rate and excised area-to-inflation amount ratio was comparable between the two groups (p = 0.093 and p = 0.194, respectively). Viable flaps, excluding postoperative necrosis, in the surgical delay group were significantly more narrow-based in terms of the length-to-base width ratio and the area-to-base width ratio compared to conventional group (p < 0.01, p < 0.01). Surgical delay can result in outcomes comparable to well-designed random flaps, even in disadvantageous conditions. Patients with large skin lesions but limited areas for expansion may benefit from surgical delay.

Chest wall depression caused by tissue expander use in breast reconstruction with recoiling following expander removal: a case report.

Background: While the number of implant-based immediate breast reconstructions has increased, two-stage reconstructions still comprise a significant proportion. Some studies have reported chest wall depression (CWD) following tissue expander insertion; however, there have been no reports on chest wall recoiling following expander removal. Here, we present a case of CWD resulting from tissue expander use for breast reconstruction, with subsequent chest wall recoiling following expander removal. Case Description: A 40-year-old woman had previously undergone skin-sparing mastectomy and tissue expander insertion at another hospital 7 months previously. She presented to our institute and complained of pain and restricted shoulder movement, desiring the removal of the tissue expander. A preoperative computed tomography (CT) scan showed CWD on the expander-inserted side; the antero-posterior (AP) length of the right chest wall was 127.2 mm and that of the left side was 150.2 mm. During the surgical procedure, a capsulectomy was performed, followed by the reconstruction of the right breast using a free transverse rectus abdominis myocutaneous flap. The patient exhibited symptom improvement immediately after the surgery and a 12-month follow-up CT scan revealed recoiling of the chest wall (right side, 147.4 mm; left side, 153.7 mm). Conclusions: This case highlights the potential for CWD and recoil following tissue expander use in breast reconstruction. It is essential for surgeons to be aware of this phenomenon and to provide thorough explanations to patients who have undergone expander insertion, particularly those who have received radiation therapy.

Evaluation of Actual Ventilation Rates and Efficiency in Research-Scale Pig Houses Based on Ventilation Configurations.

Accurate ventilation control is crucial for maintaining a healthy and productive environment in research-specialized pig facilities. This study aimed to evaluate actual ventilation rates and ventilation efficiency by investigating different inlet and exhaust configurations. The research was conducted in two pig rooms, namely pig room A and pig room B, in the absence of animals and workers to focus solely on evaluating the ventilation system's performance. Actual ventilation rates were measured using hood-type anemometers, and the local air change per hour was analyzed at various measurement points via tracer gas decay experiments. The results demonstrated that specific inlet and exhaust combinations, such as side inlet/chimney outlet and ceiling inlet/side outlet, exhibited higher ventilation rates. However, the measured ventilation rates were much lower than the manufacturer's specifications. The side exhaust fan closer to the pig activity space demonstrated better ventilation effectiveness for the animals than the chimney exhaust fan. Additionally, the ceiling inlet exhibited superior air distribution and uniformity. Lower ventilation rates and higher infiltration ratios resulted in reduced ventilation efficiency, with the difference between pig and worker activity spaces being pronounced. This study emphasizes the importance of selecting optimal inlet and exhaust configurations to achieve efficient ventilation and create a healthy environment for both pigs and workers.

Long-term outcomes after core extirpation of fibrous dysplasia of the zygomaticomaxillary region.

BACKGROUND: Fibrous dysplasia (FD) is a localized bone disorder in which fibro-osseous tissue replaces the normal bone structure. Patients with craniofacial FD often present with gradual swelling, deformity, and compromised vision or hearing. We previously introduced "the core extirpation method," a novel surgical technique that is minimally invasive like traditional bone shaving but has longer-lasting effects. This study presents the long-term outcomes of our core extirpation method. METHODS: We conducted a retrospective analysis of patients who underwent core extirpation for FD of the zygomaticomaxillary region from 2012 through 2021. Computed tomography (CT) scans were performed 6 to 12 months before the operation, immediately before and after the operation, and during follow-up visits. We performed all operations using the upper gingivobuccal approach, and we extirpated the core of the lesion while preserving the cortical structures of the zygoma and the maxilla to maintain symmetrical facial contour. RESULTS: In 12 patients with lesions in the growth phase, anteroposterior/mediolateral (AP/ML) length discrepancies and the volume increased between preoperative and immediate postoperative CT scans. All patients' immediate postoperative AP/ML discrepancies were stable up to 12-17 months postoperatively. Postoperative volume showed continuous lesion growth; the median volume growth rate was 0.61 cc per month. CONCLUSION: In this article, we present our experiences managing FD using the minimally invasive core extirpation technique, which entails small expected blood loss and can be performed as day surgery. It provides similar cosmetic outcomes as traditional bone shaving but with longer-lasting results. Although there are some limitations with the study's retrospective nature and small sample size, our 4-year follow-up results show promising results of the core extirpation method in well-indicated patients.

Oncologic Safety and Efficacy of Cell-Assisted Lipotransfer for Breast Reconstruction in a Murine Model of Residual Breast Cancer.

BACKGROUND: Cell-assisted lipotransfer (CAL) is a novel technique for fat grafting that combines the grafting of autologous fat and adipose-derived stromal cells (ASCs) to enhance fat graft retention; however, its oncologic safety is controversial. METHODS: Herein, we investigated the oncologic safety of CAL for breast reconstruction using a murine model of residual breast cancer. Various concentrations of 4T1 cells (murine breast cancer cells) were injected into female mastectomized BALB/c mice to determine the appropriate concentration for injection. One week after injection, mice were divided into control (100 µL fat), low CAL (2.5 × 105 ASCs/100 µL fat), and high CAL (1.0 × 106 ASCs/100 µL fat) groups, and fat grafting was performed. The injection of 5.0 × 103 4T1 cells was appropriate to produce a murine model of residual breast cancer. RESULTS: The weight of the fat tumor mass was significantly higher in the high CAL group than in the other groups (p < 0.05). However, the estimated tumor weight was not significantly different between the groups. Additionally, the fat graft survival rate was significantly higher in the high CAL group than in the control and low CAL groups (p < 0.05). No significant difference was noted in the percentage of Ki-67-positive cells, suggesting that tumor proliferation was not significantly different between the groups. CONCLUSION: In summary, CAL significantly improved fat graft survival without affecting tumor size and proliferation in a murine model of residual breast cancer. These results highlight the oncologic safety of CAL for breast reconstruction. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Thermo-mechanical properties of 3D printed photocurable shape memory resin for clear aligners.

To overcome the limitations of the conventional vacuum thermoforming manufacturing method, direct 3D printing of clear aligners has been developed. The present study investigated the thermo-mechanical and viscoelastic properties of a photocurable resin TC-85, which is a new material for the direct 3D printed clear aligners, comparing to a conventional thermoplastic material polyethylene terephthalate glycol. Dynamic mechanical analysis was performed to analyse the mechanical behaviours of the two materials at 37 °C and 80 °C, respectively. Furthermore, the shape memory property of the two materials was evaluated using a U-shape bending test, and the shape recovery ratio for 60 min at 37 °C was calculated. The results indicate that TC-85 can constantly apply a light force to the teeth when used for the 3D printed clear aligners, owing to its flexibility and viscoelastic properties. In addition, it is expected that the force decay induced by repeated insertion of the clear aligners will be reduced and a constant orthodontic force will be maintained. Furthermore, its geometric stability at high temperatures and the shape memory properties provide advantages for the clinical application.

Comparison of Liquid and Solid-State Fermentation Processes for the Production of Enzymes and Beta-Glucan from Hulled Barley.

Solid-state fermentation using hulled barley was carried out to produce enzymes and ß-glucan. The one-factor-at-a-time experiments were carried out to determine the optimal composition of the basal medium. The modified synthetic medium composition in liquid-state fermentation was determined to be 70 g/l hulled barley, 0 g/l rice bran, 5 g/l soytone, and 6 g/l ascorbic acid. Optimal pretreatment conditions of hulled barley by solid-state fermentation were evaluated in terms of maximum production of fungal biomass, amylase, protease, and ß-glucan, which were 1.26 mg/g, 31310.34 U/g, 2614.95 U/g, and 14.6% (w/w), respectively, at 60 min of pretreatment condition. Thus, the solid-state fermentation process was found to enhance the overall fermentation yields of hulled barley to produce high amounts of enzymes and ß-glucan.

Comparative Effectiveness of Collaborative Treatment with Korean and Western Medicine for Low Back Pain: A Prospective Cohort Study.

In Korea, low back pain is the ailment that is most frequently treated using collaborative care regimens that include aspects of Western and traditional Korean medicine. As part of a national pilot project on the collaboration between Western and Korean medicine, we aimed to investigate the clinical effectiveness of collaborative treatment and compare it with treatment methods that involved only Korean or Western Medicine practices for patients with low back pain. This nationwide, multicenter, prospective, observational, and comparative study spanned 8 weeks, during which patients with low back pain were evaluated at three time points (at baseline, 4 weeks, and 8 weeks). The primary outcome was low back pain-related disability measured by the Oswestry Disability Index, while the secondary outcomes included severity of low back pain (as on a numeric rating scale) and quality of life (as per a 5-level EuroQol-5 dimensions questionnaire). We analyzed 150 patients (including 129 per-protocol cases) and found that the Oswestry Disability Index and 5-level EuroQol-5 dimensions showed statistically significant differences over time between the collaborative treatment group and the sole treatment group after adjusting for sex, income level, and age. Conversely, the numeric rating and EuroQol-visual analog scales showed no significant between-group differences over time. Based on our findings, we believe that collaborative treatment that includes parallelly administered aspects of Western and Korean medicine can benefit patients with low back pain by facilitating functional improvements and lead to a better quality of life.

Selecting Effective Herbal Medicines for Attention-Deficit/Hyperactivity Disorder via Text Mining of Donguibogam.

OBJECTIVE: Several attempts have been made to reduce the harmful side effects and increase the efficacy of current drugs used to treat attention-deficit/hyperactivity disorder (ADHD). Many articles have studied medicinal herbs as an effective supplement in treating ADHD. In a similar manner, this study provides foundational data to identify herbs that are potentially effective in treating ADHD by text mining of Donguibogam, which is a comprehensive summation of the important traditional principles and practices of Korean medicine. METHODS: Text mining was performed for 3833 herbal prescriptions and 1108 medicinal herbs comprising prescriptions listed in Donguibogam. The first step was frequency analysis followed by chi-square test, which is a statistical hypothesis test. RESULTS AND CONCLUSIONS: Twelve medicinal herbs were selected for each ADHD subtype: hyperactivity ADHD type (ADHD-PHI) and attention-deficit ADHD type (ADHD-PI). Compared to previous research on traditional literature, a newer and more efficient methodology of selecting herbal medicines was developed in this process.

Validation and cross-cultural adaptation of the Korean version of the Core Outcome Measures Index in patients with degenerative lumbar disease.

PURPOSE: To translate and cross-culturally adapt the Core Outcome Measures Index (COMI) into the Korean language and to test the psychometric properties of the Korean COMI in patients with degenerative lumbar spine diseases. METHODS: A cross-cultural adaptation of the COMI into Korean was carried out using established guidelines. A total of 117 patients with lumbar spinal diseases were recruited from the spinal center of a tertiary care teaching institution and completed a baseline questionnaire including the newly translated COMI, the visual analog scale for back pain and for leg pain, the Oswestry Disability Index (ODI), and the EuroQOL-5 dimensions (EQ-5D). Within 2 weeks after the first assessment, 83 (71%) completed a second COMI questionnaire and a transition question (no change, slight change, moderate change, a lot of change) by phone to assess reproducibility. RESULTS: COMI summary scores displayed 1.7% floor effects and no ceiling effect. For construct validity, each COMI item and COMI summary score well correlated with its corresponding reference questionnaire. Therefore, the predefined hypotheses for the construct validities of each COMI item (ρ > 0.4 with the corresponding questionnaire) and the COMI summary score (ρ > 0.6 with both ODI and EQ-5D) were confirmed. Intraclass correlation coefficients of each COMI item and summary score ranged from 0.93 to 0.98. Therefore, the hypothesis for reliability (ICC > 0.8) was confirmed. CONCLUSIONS: The present study highlights that the Korean version of the COMI is a reliable and valid outcome tool for use in Korean-speaking patients with degenerative lumbar spinal disease. These slides can be retrieved under Electronic Supplementary Material.

Corrigendum: Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury.

This corrects the article DOI: 10.1038/srep23472.

Radiographic and Clinical Outcomes of Robot-Assisted Posterior Pedicle Screw Fixation: Two-Year Results from a Randomized Controlled Trial.

PURPOSE: We prospectively assessed the early radiographic and clinical outcomes (minimum follow-up of 2 years) of robot-assisted pedicle screw fixation (Robot-PSF) and conventional freehand pedicle screw fixation (Conv-PSF). MATERIALS AND METHODS: Patients were randomly assigned to Robot-PSF (37 patients) or Conv-PSF (41 patients) for posterior interbody fusion surgery. The Robot-PSF group underwent minimally invasive pedicle screw fixation using a pre-planned robot-guided screw trajectory. The Conv-PSF underwent screw fixation using the freehand technique. Radiographic adjacent segment degeneration (ASD) was measured on plain radiographs, and clinical outcomes were measured using visual analogue scale (VAS) and Oswestry disability index (ODI) scores regularly after surgery. RESULTS: The two groups had similar values for radiographic ASD, including University California at Los Angeles grade, vertebral translation, angular motion, and loss of disc height (p=0.320). At final follow-up, both groups had experienced significant improvements in back VAS, leg VAS, and ODI scores after surgery (p<0.001), although inter-group differences were not significant for back VAS (p=0.876), leg VAS (p=0.429), and ODI scores (p=0.952). In the Conv-PSF group, revision surgery was required for two of the 25 patients (8%), compared to no patients in the Robot-PSF group. CONCLUSION: There were no significant differences in radiographic ASD and clinical outcomes between Robot-PSF and Conv-PSF. Thus, the advantages of robot-assisted surgery (accurate pedicle screw insertion and minimal facet joint violation) do not appear to be clinically significant.

Hot Deformation Behavior of Hot-Extruded AA7175 Through Hot Torsion Tests.

The hot deformation behavior of hot-extruded AA7175 was investigated with flow curves and processing maps through hot torsion tests. The flow curves and the deformed microstructures revealed that dynamic recrystallization (DRX) occurred in the hot-extruded AA7175 during hot working. The failure strain was highest at medium temperature. This was mainly influenced by the dynamic precipitation of fine rod-shaped MgZn2. The processing map determined the optimal deformation condition for the alloy during hot working.

microRNA-133a attenuates cardiomyocyte hypertrophy by targeting PKCδ and Gq.

During the past decade, microRNAs have continuously been suggested as a promising therapeutic tool due to their beneficial effects, such as their multi-targets and multi-functions in pathologic conditions. As a pathologic phenotype is generally regulated by multiple signaling pathways, in this study we identified a microRNA regulating multiple target genes within cardiac hypertrophic signaling pathways. microRNA-133a is known to play a crucial role in cardiac hypertrophy. However, the role of microRNA-133a, which may regulate several signaling pathways in norepinephrine-induced cardiac hypertrophy via multi-targeting, has not been investigated. In the current study, we showed that microRNA-133a can protect cardiomyocyte hypertrophy against norepinephrine stimulation in neonatal rat ventricular cardiomyocytes via new targets, PKCδ and Gq, all of which are related to downstream signaling pathways of the α1-adrenergic receptor. Taken together, these results suggest the advantages of the therapeutic use of microRNAs as an effective potential drug regulating multiple signaling pathways under pathologic conditions.

Small molecule-mediated induction of miR-9 suppressed vascular smooth muscle cell proliferation and neointima formation after balloon injury.

Pathologic proliferation and migration of vascular smooth muscle cells (VSMCs) exacerbate cardiovascular disease. MicroRNAs (miRNAs), as endogenous inhibitors of protein synthesis, are expected to modulate pathologic proliferation of VSMCs. Here we report that both platelet-derived growth factor receptor (PDGFR) targeting miR-9 and a small molecule that increases miR-9 can inhibit the serum-induced proliferation of VSMCs. First, based on miRNA-target prediction databases and empirical data, we have selected miR-9 as a potent anti-proliferative miRNA in VSMCs. Further examination indicated that miR-9 directly targets PDGFR disrupting downstream signaling cascades, and this resulted in inhibition of VSMC proliferation and migration. Exogenous delivery of miR-9 inhibited VSMC proliferation in vitro, and a small molecule that increased miR-9 expression also inhibited neointima formation following balloon injury in vivo. We provide evidence of miRNA-mediated modulation of VSMC proliferation and further demonstrate that small molecule-mediated regulation of miRNA targeting a key regulator of VSMC proliferation is a viable therapeutic strategy for treating vascular disease involving pathologic VSMC proliferation such as restenosis.