Three-dimensional comparative changes in the pharyngeal airway of patients with cleft after two-jaw orthognathic surgery.

BACKGROUND: The present study evaluated the three-dimensional changes of the pharyngeal airway after orthognathic surgery (OGS) in patients with unilateral and bilateral clefts, and in unilateral cleft patients with and without pharyngeal flap (PF). METHODS: Forty-five patients with unilateral or bilateral clefts receiving OGS were enrolled. Cone-beam computed tomography images were obtained before (T0) and after (T1) OGS. We measured the pharyngeal airway volumes, minimal cross-sectional area, and the horizontal displacement of facial landmarks. RESULTS: The patients with bilateral cleft exhibited smaller initial velopharyngeal volume (unilateral: 8623 mm 3; bilateral: 7781 mm 3; p = 0.211), while the velopharyngeal volume increased significantly with median of 744 mm 3 after OGS (p = 0.031). The median horizontal displacement of A point was 2.9 and 2.6 mm among the patients with unilateral and bilateral clefts, respectively (p = 0.276), and the median horizontal displacement of B point was -2.9 and -3.3 mm among patients with unilateral and bilateral clefts, respectively (p = 0.618). The unilateral cleft patients with PF exhibited lower initial velopharyngeal volume (PF+: 7582 mm 3; PF-: 8756 mm 3; p = 0.129) and a lower increase in velopharyngeal volume (PF+: 437 mm 3; PF-: 627 mm 3; p = 0.739) after OGS. CONCLUSIONS: Midface hypoplasia and the decrease in the velopharyngeal volume were more prominent among the bilateral cleft patients and the unilateral cleft patients with PF. After OGS, the velopharyngeal volume considerably increased among the bilateral cleft patients, but no considerable differences were noted among the unilateral cleft patients with PF.

The Preferred Reconstructive Choice for a Lower Third Tibial Exposure Defect: An Online Survey of 356 Microsurgeons.

BACKGROUND: One of the most challenging yet common areas in reconstructive surgery is the closure of defects in the lower leg. Surgeons can choose from several reconstructive options including local and free flaps. The aim of this study was to understand the reconstructive strategy for lower leg defects of different microsurgeons around the world by harnessing the power of social media and online questionnaires. METHODS: A case of a patient with an exposed plate over distal tibial fracture was presented via an online questionnaire distributed on various social media platforms. A total of 369 international microsurgeons replied with their preferred treatment choice. The data were analyzed according to geographic area, microsurgical training, seniority, and subspecialty. RESULTS: Among all the respondents (n = 369), 64% would have opted for a free flap reconstruction, while the remaining 36% would have opted for a local/pedicle flap. In the group that would have opted for a free flap, 63% would reconstruct the defect using a free fasciocutaneous flap, while the remaining 37% would have used a free muscle flap. In the local flap group, 60% would have used a local perforator while 30% would have chosen a conventional local flap. While North American and European microsurgeons had a clear preference toward free flaps, Asian, Middle Eastern, African, and South American surgeons were evenly divided between local and free flaps. CONCLUSION: In this study, we provide a current global overview of the reconstructive strategies for a lower limb with skin defect and bone or prosthesis exposure. We hope that this will be able to help global microsurgeons and patients worldwide.

Inhibitory effects of the atypical antipsychotic, clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Experiences and attitudes toward aesthetic procedures in East Asia: a cross-sectional survey of five geographical regions.

BACKGROUND: The demand for aesthetic procedures continues to grow globally, particularly in East Asian countries. The popularity of specific aesthetic procedures varies, however, depending on the particular East Asian geographical region being studied. This study aimed to evaluate the experiences of and attitudes toward aesthetic procedures in five East Asian countries/regions, including China, Japan, South Korea, Hong Kong, and Taiwan. METHODS: To recruit participants, an online questionnaire was designed and distributed on social media networks between May 2015 and March 2016. The statistical analysis was conducted using SPSS software, version 22.0. RESULTS: A total of 3,088 people responded (approximately 600 in each country/region). Of these, 940 participants (47.8%) responded that they had experienced at least one aesthetic procedure in the past. Taiwan had the highest number of participants who had experienced at least one procedure (264/940, 41%), with primarily non-surgical experiences. Only in South Korea did surgical cosmetic experiences exceed non-surgical cosmetic experiences (55.9% vs. 44.1%). The popularity of particular procedures and the motivation for undergoing aesthetic procedures varied by country. CONCLUSIONS: The popularity of aesthetic procedures continues to evolve. Similar trends were observed across the East Asian regions; however, each country had its unique demands and preferences. The information provided by this study can help aesthetic plastic surgeons further understand the patients in their corresponding region, customize their practice, and develop the requisite skills.

The Preferred Management of a Single-Digit Distal Phalanx Amputation.

BACKGROUND: Replantation of a single digit at the distal phalanx level is not routinely performed since it is technically challenging with questionable cost-effectiveness. The purpose of this study was to analyze international microsurgeons' clinical decisions when faced with this common scenario. METHODS: A survey of a right-middle finger distal phalanx transverse complete amputation case was conducted via online and paper questionnaires. Microsurgeons around the world were invited to provide their treatment recommendations. In total, 383 microsurgeons replied, and their responses were stratified and analyzed by geographical areas, specialties, microsurgery fellowship training, and clinical experiences. RESULTS: Among 383 microsurgeons, 170 (44.3%) chose replantation as their preferred management option, 137 (35.8%) chose revision amputation, 62 (16.2%) chose local flap coverage, 8 (2.1%) chose composite graft, and 6 (1.6%) favored other choices as their reconstruction method for the case study. Microsurgeons from the Asia-Pacific, Middle East/South Asia, and Central/South America regions tend to perform replantation (70.7, 68.8, and 67.4%, respectively) whereas surgeons from North America and Europe showed a lower preference toward replantation (20.5 and 26.8%, respectively p < 0.001). Having completed a microsurgery fellowship increased the attempt rate of replantation by 15.3% (p = 0.004). Clinical experience and the surgeons' specialties did not show statistical significance in clinical decision making. CONCLUSION: From the present study, the geographic preferences and microsurgery fellowship experience influence the method of reconstruction for distal phalanx amputation. Multiple factors are taken into consideration in selecting the most suitable reconstructive method for each case scenario. In addition to the technical challenges of the proposed surgery, the cost of the procedure and the type of facility needed are important variables in the decision making process.

International Microsurgery Club: An Effective Online Collaboration System.

BACKGROUND: This study aimed to determine if International Microsurgery Club (IMC) is an effective online resource for microsurgeons worldwide, in providing an avenue for timely group discussions and advice regarding complicated cases, and an avenue for collaboration and information sharing. METHODS: All posts on the IMC Facebook group from member 1 to 8,000 were analyzed according to inclusion criteria and categorized into three categories-case discussion, question, and information sharing. Posts were retrospectively analyzed for number of responses, time of responses, number of "likes," number of treatment options, time of day, and demographics of authors and responders. RESULTS: A retrospective analysis of 531 cases showed an average response rate of 75.7% within 1 hour and as membership grew. The response rate stabilized averaging between 72.5 and 78% across all times of the day. An average of 11.8 microsurgeons was involved per case discussion, and 5.7 treatment options were provided per case. CONCLUSION: IMC is shown to be an effective resource to allow microsurgeons to access timely advice from other microsurgeons without time and distance limitation, and to have interactive group discussions on complicated cases.

Impact of Social Media on Current Medical Conferences.

BACKGROUND: Medical conferences are forums for research, continuing medical education, and networking. Social media is increasingly used for communication and networking due to its low cost and ability to overcome large distances. This study investigates the impact that social media brings to the current conference system. METHODS: There are three parts of this study: (1) comparing two similar brachial plexus injuries (BPIs) courses without (2009) and with (2017) social media support, and the participants' feedback; (2) sharing our experiences in the management of the 2018 International Course on SuperMicrosurgery (ICSM) conference; and (3) evaluating the studies from the social media platform International Microsurgery Club (IMC), for the consensus pertaining to social media and conference system. RESULTS: With the help of social media, international attendance increased during the 2017 BPI conference compared with the 2009 BPI course (25 nationalities in 2009 vs. 35 in 2017). At least 23% obtained their meeting information through social media. Live surgery was the overall main attraction (79%). The 2018 ICSM meeting revealed that video posts increased attendance; videos that were the most effective in attracting (viewership) were either short or pertained to surgical procedures. Facebook, Messenger, and WeChat smartphone applications were effective for immediate communication and troubleshooting among the participants. From the IMC polls, 78% believe that the social media and the conference complemented each other. 97% attended the conference to update their skills and knowledge. CONCLUSION: Social media is a quick and economic tool in promoting medical conferences and instant messenger systems offer immediate communication amongst associates. Despite the popularity of social media, the conference still has its irreplaceable role. The combination of the conference and the social media enhances the training and education of microsurgeons.

Tips for Making a Successful Online Microsurgery Educational Platform: The Experience of International Microsurgery Club.

The presence of online learning resources has grown tremendously in recent years. They provide powerful and yet easily accessible means of learning and sharing knowledge. Online learning resources now encompass all aspects of medicine, and microsurgery is no exception. International Microsurgery Club is a closed, invitation-only group based on the Facebook social media platform. It was initiated on May 6, 2016, with the primary objectives of providing a convenient forum for discussing challenging cases, sharing valuable resources, and providing opportunities for research collaboration. The membership of International Microsurgery Club has grown to over 8700 at 2 years' existence, and continues to expand. International Microsurgery Club has become one of the largest online platforms for global microsurgeons. Here, the authors share their experience on how to establish a successful online platform for medical education.

Bleomycin Inhibits Proliferation via Schlafen-Mediated Cell Cycle Arrest in Mouse Alveolar Epithelial Cells / 결핵및호흡기질환

BACKGROUND@#Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells.@*METHODS@#Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM.@*RESULTS@#BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family.@*CONCLUSION@#BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow

BACKGROUND AND OBJECTIVES: Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet well understood. METHODS: BM cells were harvested from femurs of mice and analyzed using flow cytometry. Human PVCs were cultured in serum-free α-MEM. After 24hrs, PVC-CM was collected and filtered through a 0.22 μm filter. RESULTS: In this study, we showed that hyperglycemia alters hematopoietic composition in the BM, which can partially be restored via paracrine mechanisms, including perivascular cells (PVCs) and NADPH oxidase (NOX) inhibition in mice with streptozotocin-induced diabetes. Prolonged hyperglycemic conditions resulted in an increase in the frequency and number of long-term hematopoietic stem cells as well as the number of total BM cells. The altered hematopoiesis in the BM was partially recovered by treatment with PVC-derived conditioned medium (CM). Long-term diabetes also increased the number of myeloid-derived suppressor cells in the BM, which was partially restored by the administration of PVC-CM and diphenyleneiodonium (DPI), a NOX inhibitor. We further showed the downregulation of ERK and p38 phosphorylation in BM cells of diabetic mice treated with PVC-CM and DPI. This may be associated with dysfunction of hematopoietic cells and promotion of subsequent diabetic complications. CONCLUSIONS: Our data suggested that alterations in BM hematopoietic composition due to prolonged hyperglycemic conditions might be restored by improvement of the hematopoietic microenvironment and modulation of NOX activity.

Perivascular Stem Cells Suppress Inflammasome Activation during Inflammatory Responses in Macrophages

BACKGROUND AND OBJECTIVES: Perivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated.METHODS AND RESULTS: In this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1β in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation.CONCLUSIONS: Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.

Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

Bleomycin Inhibits Proliferation via Schlafen-Mediated Cell Cycle Arrest in Mouse Alveolar Epithelial Cells / 결핵

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

Use of Social Media and an Online Survey to Discuss Complex Reconstructive Surgery: A Case of Upper Lip Reconstruction with 402 Responses from International Microsurgeons.

BACKGROUND: The best reconstructive strategy for upper lip defects is still in debate. The purpose of this study was to analyze the decisions made by international microsurgeons, who were participated through online questionnaire, distributed by email and social media network. MATERIALS AND METHODS: A case of a two-thirds upper lip oncologic defect was presented via an online questionnaire and 402 microsurgeons replied their treatment options. The data were then analyzed according to the geographic area, microsurgical fellowship, seniority, and subspecialty. All the data were analyzed using SPSS 22. RESULTS: A total of 27.7% of microsurgeons chose a free flap, while 72.3% chose a local/pedicle flap as their preferred method for reconstruction. The most common choice of free and local/pedicle flaps was radial forearm (73.6%) and Abbé (36.2%), respectively. The microsurgeons in Europe preferred local/pedicle flaps than free flap when compared with Middle/South America, Asia-Pacific, Africa and South Asia/Middle East (11.6% versus 50%, 43.4%, 29.3% and 27.3%, respectively, multivariant p < 0.05). The microsurgeons with microsurgical fellowships preferred to use free flaps (32.9% versus 17.5%, multivariant p = 0.021). There was no difference for the seniority and specialty of the microsurgeons. CONCLUSIONS: The online questionnaire is valuable and feasible for obtaining experts' opinions. This study provides a current global overview of surgical preferences for this common complicated clinical scenario.

Assessing the suitability of medial sural artery perforator flaps in tongue reconstruction - An outcome study.

INTRODUCTION: Oncological resection of the tongue can be reconstructed using a multitude of free flaps. The medial sural artery perforator (MSAP) flap has been well described in the literature in terms of its anatomy and harvest. However, functional outcome studies of post-reconstruction tongue defects using the MSAP flap have not been reported. This study represents the largest outcome study of patients with tongue reconstructions using MSAP flaps and a comprehensive review of its use. MATERIALS AND METHODS: From December of 2010 to October of 2015, 579 patients with subtotal glossectomy and free flap reconstructions in Chang Gung Memorial Hospital were retrospectively reviewed. 27 patients were reconstructed with MSAP flap. The pre- and intra-operative factors, as well as flap-related factors were analyzed. Post-operative complications and functional outcomes were evaluated. Donor site assessment were also conducted. RESULTS: A 96.3% flap survival rate was found with an average total operating time of 6 hours and 18 minutes. 84.6% of patients had primary closure of the donor site with and the remaining either had skin grafts or delayed closure. Donor site closure can be achieved primarily with no functional deficit. Speech intelligibility remained for most patients. 100% of patients resumed normal oral feeding. CONCLUSION: The MSAP flap is a small to medium sized flap most suited for subtotal glossectomy defects where optimal outcomes can be achieved in terms of speech clarity and restoration of oral intake.

Aesthetic Multiple-Toe Reconstruction With Combined Iliac Bone Graft and Wraparound Free Anterolateral Thigh Flap-A Case Report and Literature Review.

Compared with upper extremity injuries, toe amputations and their replantations are rare because of the difficulty of their relatively thinner soft tissue envelope. Consequently, fewer reconstructive options are available for toes and they are rarely reported in the literature. In this study, we reported a case of right third to fifth toe amputations and their subsequent reconstruction with iliac bone grafts and a free anterolateral thigh flap. After serial debulking and division procedures, 3 toes were divided successfully. Ten months after the initial operation, the patient regained pain-free functional ambulation despite some bone resorption noted on follow-up radiographs. The patient showed high satisfaction on her new toes in terms of aesthetical and functional outcomes. She was able to stand for over 30 minutes without pain. At the 2-year follow-up, the Foot Function Index was 18.3%. Although toe reconstruction is frequently considered unnecessary because of its relative high demand of surgical techniques and little gain on gait; nonetheless, in selected cases, toe reconstruction may still be beneficial if the metatarsophalangeal joints were intact and there is a strong individual desire for aesthetical restoration.

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H₂O₂-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.

Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells

Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562) in vitro using Transwell® co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.