Enhancing Philtrum Morphology Using Fat Grafting Combined with Percutaneous Rigottomy in Repaired Unilateral Cleft Lip.

BACKGROUND: Improving the philtrum morphology of patients with a secondary cleft lip deformity has been a challenge in cleft care. Combining fat grafting with percutaneous rigottomy has been advocated for treatment of volumetric deficiency associated with a scarred recipient site. This study assessed the outcome of synchronous fat grafting and rigottomy for improvement of cleft philtrum morphology. METHODS: Consecutive young adult patients ( n = 13) with a repaired unilateral cleft lip who underwent fat grafting combined with rigottomy expansion technique for enhancement of philtrum morphology were included. Preoperative and postoperative three-dimensional facial models were used for three-dimensional morphometric analyses including philtrum height, projection, and volume parameters. Lip scar was qualitatively judged by a panel composed by two blinded external plastic surgeons using a 10-point visual analogue scale. RESULTS: Three-dimensional morphometric analysis revealed a significant (all P < 0.05) postoperative increase of the lip height-related measurements for cleft philtrum height, noncleft philtrum height, and central lip length parameters, with no difference ( P > 0.05) between cleft and noncleft sides. The postoperative three-dimensional projection of the philtral ridges was significantly ( P < 0.001) larger in cleft (1.01 ± 0.43 mm) than in noncleft sides (0.51 ± 0.42 mm). The average philtrum volume change was 1.01 ± 0.68 cm 3 , with an average percentage fat graft retention of 43.36% ± 11.35%. The panel assessment revealed significant ( P < 0.001) postoperative scar enhancement for the qualitative rating scale, with mean preoperative and postoperative scores of 6.69 ± 0.93 and 7.88 ± 1.14, respectively. CONCLUSION: Synchronous fat grafting and rigottomy improved philtrum length, projection, and volume and lip scar in patients with repaired unilateral cleft lip. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Comparison of Facial Growth between Two Nasoalveolar Molding Techniques in Patients with Unilateral Complete Cleft Lip.

BACKGROUND: Nasoalveolar molding (NAM) has become standard treatment in the authors' craniofacial center. There are two types of presurgical NAM: the Grayson and Figueroa techniques. The Grayson method involves active alveolar molding, and the Figueroa method involves passive alveolar molding. The authors previously found no differences in number of clinic visits, costs, or 6-month postoperative outcome between the two techniques. The authors extended the previous study to evaluate facial growth between these two groups. METHODS: In this randomized single-blind study, conducted between May of 2010 and March of 2013, the authors recruited 30 patients with unilateral complete cleft lip and palate and randomized them for Grayson or Figueroa presurgical NAM. Standard lateral cephalometric measurements at 5 years were used to determine facial growth. RESULTS: Twenty-nine patients completed 5 years of follow-up. There were no statistically significant differences in facial cephalometric measurements between the two groups. CONCLUSION: Presurgical NAM using either a passive or active NAM technique produced similar facial growth patterns after unilateral cleft lip and palate repair. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Refining Orthognathic Surgery Results by Synchronous Cheek Fat Compartment Augmentation with Fat Grafting in Adult Females with Class III Skeletal Profiles.

SUMMARY: Patients with maxillomandibular disharmony may present with a flat to concave midface. The effects of orthognathic surgery concomitant with midface fat grafting on facial appearance and midface volumetric and positional change have not formally been assessed to date. The authors' approach for synchronous orthognathic surgery and fat grafting is described and evaluated. Adult female patients (n = 20) who underwent synchronous two-jaw orthognathic surgery and cheek-specific fat grafting (1.9 ± 0.6 cm3 per side) for correction of skeletal class III deformity and anteromedial cheek deficiency were prospectively included. Preoperative and postoperative photographs were appraised by 42 blinded raters using facial appearance scales for beauty, attractiveness, and pleasantness parameters. The three-dimensional midface soft-tissue volume change and postoperative cheek mass position were computed. Facial imaging data from gender-, ethnic-, and facial pattern-matched adult patients (n = 20) who underwent isolated two-jaw orthognathic surgery (n = 20) were included for comparison. The three-dimensional facial norms database-derived cheek mass position information (2.19 ± 1.31mm) was also adopted for analysis. Patients treated with the synchronous procedure had significantly (p < 0.001) increased facial appearance-related perception change for beauty (2.9 ± 1.6), attractiveness (2.8 ± 1.8), and pleasantness (3.0 ± 1.5) parameters, three-dimensional midface volume change (1.8 ± 0.5 cm3), and postoperative cheek mass position (2.16 ± 0.47 mm) in comparison with those treated with the isolated procedure (2.0 ± 1.5, 1.9 ± 1.6, 2.3 ± 1.6, 0.6 ± 0.2 cm3, and 1.84 ± 0.43 mm, respectively). Healthy female individuals had similar and larger cheek mass position than patients treated with synchronous (p > 0.05) and isolated (p < 0.001) procedures, respectively. Synchronous orthognathic surgery and check-specific fat grafting resulted in superior enhancement of facial appearance and midface volume and position compared with isolated orthognathic surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Botulinum Toxin to Improve Lower Blepharoplasty Scar: A Double-Blinded, Randomized, Vehicle-Controlled Clinical Trial.

BACKGROUND: Lower blepharoplasty is a common cosmetic operation that relies on minimal postoperative scarring, but Asian patients are at higher risk than Caucasians for hypertrophic and/or widened scars. Botulinum toxin type A (BTX) injections are widely employed to alleviate dynamic facial rhytids and also can improve scar quality by reducing scar tension. The authors assessed whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. OBJECTIVES: The objective of this study was to assess whether simultaneous transcutaneous lower blepharoplasty and BTX injections could improve subciliary scar quality. METHODS: This is a prospective, randomized, vehicle-controlled, double-blinded clinical trial. Between May 2015 and May 2018, 40 adults who underwent bilateral transcutaneous lower blepharoplasties were randomized to receive BTX (n = 20) or vehicle (normal saline; n = 20) injections into the lateral orbicularis oculi muscle immediately after wound closure. Vancouver Scar Scale, Visual Analogue Scale, and photographic scar width measurements at 3 reference points were recorded at the final clinical follow-up. RESULTS: Thirty-seven patients completed the trial. Vancouver Scar Scale and Visual Analogue Scale scores in the experimental and vehicle control groups were similar, but scar widths in the experimental group at all measured points were significantly narrower than in the vehicle control group (P < 0.001, P = 0.027, and P < 0.001 at each measured point, respectively). CONCLUSIONS: Transcutaneous lower blepharoplasty scars in Asians can be significantly narrowed by simultaneous BTX injections without additional complications.

Impact of One Versus Two Consecutive Doses of Endothelial Cells (EPCs) and EPCs-Derived Condition Medium on Protecting Myocardium from Acute Ischemia-Reperfusion Injury in Rat.

This study tested the impact of single dose and two doses of endothelial progenitor cells (EPCs) and EPCs-derived condition medium (CM) on protecting the left-ventricular myocardium (LVM) from acute ischemia-reperfusion (IR) injury. In vitro study showed EPCs and CM had comparably higher capacity for enhancement of angiogenesis as compared with the controls (all P < .001). Adult-male SD rats (n = 36) were equally categorized into groups 1 (sham-operated control), 2 (IR+vehicle), 3 [IR+EPCs/1.2 × 106/intravenous administration at 3 h after IR procedure), 4 (IR+EPCs/1.2 × 106/at 3 h/24 h after IR), 5 (IR+CM/3.0cc/intravenous administration at 3 h after IR), 6 (IR+EPCs/3.0cc/at 3h/24 h after IR), and euthanized by day 3 after IR. The left-ventricular-ejection-fraction, protein and cellular expressions of endothelial-cell markers (CD31/vWF), small vessel number and protein expression of mitochondrial (mitochondrial-cytochrome-C) integrity were highest in group 1, lowest in group 2, significantly higher in group 4 than in groups 3/5/6 and significantly higher in groups 3/6 than in group 5 but they showed no differences in groups3/6, whereas the protein expressions of apoptotic (cleaved-caspase 3/cleaved-PARP), fibrotic (Smad3/TGF-ß), mitochondrial-damaged (cytosolic-cytochrome-C), heart-failed/pressure-overload (BNP), oxidative-stress (p47phox/NOX-1/NOX-2/oxidized protein), and autophagic (LCB3-II/LCB3-I) biomarkers and fibrotic/collagen-deposition areas exhibited an opposite pattern to endothelial-cell markers (all P < .0001). The protein expressions of angiogenesis (VEGF/SDF-1α/CXCR4/HIF-1α) were lowest in group 1, highest in group 4, significantly higher in groups 3/6 than in groups 2/5, significantly higher in group 5 than in group 2, but they showed no difference between groups 3/6 (all P < .0001). These results demonstrate that two consecutive doses of EPC/CM were superior to just one at protecting LVM against IR injury.

Uremic toxic substances are essential elements for enhancing carotid artery stenosis after balloon-induced endothelial denudation: worsening role of the adventitial layer.

This study tested the hypothesis that uremic-toxic substances play a crucial role in enhancing left-common carotid artery (LCCA) stenosis after balloon-denudation of LCCA endothelium (BDLCCAE), and that the adventitial layer plays a complementary role in worsening LCCA stenosis. In vitro results showed the protein expressions of inflammation (IL-1ß/TNF-α/IL-6), apoptosis (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and autophagy (beclin/Atg5/LC3B-II to LC3B-I ratio) as well as protein (NOX-1/NOX-2/p22phox/oxidized-protein), total cellular (H2DCFDA) and mitochondrial (Mitosox) levels of oxidative stress were significantly increased in p-Cresol-treated umbilical vein endothelial cells (HUVECs) as compared with control, whereas angiogenesis capacity (i.e., Matrigel-assay for HUVECs) exhibited an opposite pattern to inflammation between the two groups (all P < 0.001). Animals (n = 60) were categorized into group 1 (sham-operated control), group 2 (BDLCCAE), group 3 [BDLCCAE + ESRD patient's serum (1 cc/injection into deprived CA adventitia)], group 4 [BDLCCAE + ESRD patient's serum (1 cc/injection from peri-adventitia)], and group 5 [BDLCCAE + ESRD patient's serum (2 cc/by intravenous injection at days 1/3/7/10/14 after BDLCCADE)] and LCCA was harvested by day-21 after BDLCCAE procedure. Nitric-oxide release from LCCA and the LCCA cross-section area significantly and progressively reduced, whereas intimal and medial layers of LCCA significantly and progressively increased from groups 1 to 5 (all P < 0.001). The cellular expressions of inflammation (CD14+) and DNA-damage biomarker (γ-H2AX+) were significantly and progressively increased, whereas endothelial surface markers (CXCR4/vWF+) were significantly and progressively reduced from groups 1 to 5 (all P < 0.0001). Uremic toxins played an essential role in LCCA remodeling and obstruction. LCCA adventitia facilitated the initiation and propagation of LCCA proliferative obstruction.

Early intramyocardial implantation of exogenous mitochondria effectively preserved left ventricular function in doxorubicin-induced dilated cardiomyopathy rat.

This study tested the hypothesis that early implantation of mitochondria (Mito) into left myocardium could effectively protect heart against doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) in rat. Adult-male SD rats (n = 18) were equally categorized into group 1 (sham control), group 2 (DCM) and group 3 [DCM + Mito (500 µg/rat intramyocardial injection by day-21 after DCM induction)] and euthanized by day 60. In vitro studies showed that exogenously-transferred Mito was abundantly identified in H9C2 cells. The q-PCR showed significant increase in relative number of mitDNA in Mito-transferred H9C2 cells than in control group (P<0.001). The mRNA-gene and protein expressions of NRF1/NRF2/Tfam/PGC-1α/ERRα/Mfn2 were significantly increased in low-dose Mito-transferred and more significantly increased in high-dose Mito-transferred H29C2 cells than in control group (all P<0.01). Day-60 left-ventricular-ejection-fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1 (P<0.0001). The ratios of lung and heart weights to tibial length and myocardial histopathological findings of fibrotic area/myocardial injured score/γ-H2AX+ cells exhibited an opposite pattern to LVEF among the three groups (all P<0.0001). The myocardial protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein/p22phox), autophagic (beclin-1/Atg-5/ratio of CL3B-II/CL3B-I), and apoptotic/mitochondrial-damaged (cleaved-caspase-3/mitochondrial Bax/cleaved-PARP/cytosolic-cytochrome-C/DRP1/cyclophilin D1) biomarkers exhibited an opposite pattern, whereas the protein expressions of mitochondrial integrity (mitochondrial-cytochrome-C/mitochondrial-complex I/II/III/IV and Mfn2/PGC-1) exhibited an identical pattern to LVEF among the groups (all P<0.001). In conclusion, early Mito therapy effectively preserved LVEF and myocardial integrity in DCM rat.

Protective effect of combined therapy with hyperbaric oxygen and autologous adipose-derived mesenchymal stem cells on renal function in rodent after acute ischemia-reperfusion injury.

BACKGROUND: This study tested the hypothesis that combined hyperbaric oxygen (HBO) and autologous adipose-derived mesenchymal stem cell (ADMSC) therapy was superior to either alone at protecting renal function in rodents after acute ischemia-reperfusion (IR) injury. METHODS AND RESULTS: Adult-male SD rats (n = 40) were equally categorized: group 1 (sham-operated control); group 2 (IR + 50 µg medium intra-renal artery administration); group 3 [IR + HBO (at 1.5 h and days 1 and 2 after IR)]; group 4 [IR + ADMSC (2.0×106 cells/5.0×105/per each renal artery and 1.0×106 by intravenous injection at 1.5 h after IR]; and group 5 (IR + HBO-ADMSC). By 72 hr after IR, the circulating levels of BUN/creatinine and ratio of urine protein/creatinine were significantly highest in group 2, lowest in group 1, significantly increased in group 5 than in groups 3 and 4, but not different between latter two groups, whereas the circulating levels of EPCs and soluble-angiogenesis biomarkers (SDF-1α/HIF-1α) exhibited an opposite pattern to BUN/creatinine among the five groups (all P<0.001). The kidney injury score, ROS (fluorescent intensity of H2DCFDA dye in kidney), inflammation (F4/80+, CD14+ cells) and glomerular-tubular injury score (WT-1/KIM-1) displayed an identical pattern whereas the integrity of podocyte components exhibited an opposite pattern to BUN/creatinine among the five groups (all P<0.0001). The protein expressions of inflammatory (MMP-9/TNF-α/NF-κB/ICAM-1), oxidative-stress (NOX-1/NOx-2/oxidized protein) and apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) markers showed an identical pattern to BUN/creatinine (all P<0.001). CONCLUSION: Combined ADMSC-HBO therapy was superior to either one alone at protecting the kidney from acute IR injury.

Intravenous administration of iPS-MSCSPIONs mobilized into CKD parenchyma and effectively preserved residual renal function in CKD rat.

This study traced intravenously administered induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSC) and assessed the impact of iPSC-MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrack™Direct contrast particles (ie intracellular magnetic labelling) in the iPSC-MSC (ie iPS-MSCSPIONs ) were clearly identified by Prussian blue stain. Adult-male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS-MSCSPIONs (1.0 × 106 cells)/intravenous administration post-day-14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS-MSCSPIONs (0.5 × 106 cells)] and group 5 [CKD + iPS-MSCSPIONs (1.0 × 106 cells)]. By day-15 after CKD induction, abdominal MRI demonstrated that iPS-MSCSPIONs were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule-1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO-1/synaptopodin) and protein levels of anti-apoptosis ((Bad/Bcl-xL/Bcl-2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell-proliferation signals (PI3K/p-Akt/m-TOR, p-ERK1/2, FOXO1/GSK3ß/p90RSK), apoptotic/DNA-damage (Bax/caspases8-10/cytosolic-mitochondria) and inflammatory (TNF-α/TNFR1/TRAF2/NF-κB) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS-MSCSPIONs that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.

Human induced pluripotent stem cell-derived mesenchymal stem cell therapy effectively reduced brain infarct volume and preserved neurological function in rat after acute intracranial hemorrhage.

We tested the hypothesis that human induced pluripotent stem cell-derived mesenchymal stem cell (iPSC-MSC) therapy could effectively reduce brain-infarct volume (BIV) and improve neurological function in rat after acute intracranial hemorrhage (ICH) induced by a weight-drop device. Adult-male SD rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH + hyaluronic acid (HA)/intracranial injection at 3 h after ICH), group 4 [ICH + HA + iPSC-MSC (1.2 × 106 cells/intracranial injection at 3 h after ICH)] and euthanized by day 28 after ICH procedure. In vitro study showed that hemorrhagic-brain tissue augmented protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/TNF-α/iNOS/IL-1ß) in cultured neurons that were significantly inhibited by iPSC-MSC treatment (all P<0.001). By days 7 and 14 after ICH procedure, circulating inflammatory levels of TNF-α/IL-6/MPO expressed were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all P<0.0001). By day 14 after ICH procedure, neurological function and BIV expressed an opposite pattern, whereas protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/I-kB/TNF-α/iNOS/IL-1ß/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved-caspase-2/PARP) in brain exhibited an identical pattern to circulating inflammation among the four groups (all P<0.001). Microscopy demonstrated that the number of vascular remodeling and GFAP+/53BP1+/γ-H2AX+ cells displayed an identical pattern of inflammation, whereas the NeuN+ cells displayed an opposite pattern of inflammation among the four groups (all P<0.001). In conclusion, iPSC-MSC therapy markedly reduced BIV and preserved neurological function mainly by inhibiting inflammatory/oxidative-stress generation.

Direct implantations of erythropoietin and autologous EPCs in critical limb ischemia (CLI) area restored CLI area blood flow and rescued remote AMI-induced LV dysfunction.

BACKGROUND: This study tested the hypothesis that intramuscular injections of erythropoietin (EPO) and endothelial progenitor cells (EPC) to critical limb ischemia (CLI; primary treatment site) could also improve heart function in rat after acute myocardial infarction (AMI; remote ischemic organ). METHOD: Adult-male SD rats (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI-AMI), group 3 [CLI-AMI + EPO (10 mg/kg)], group 4 [CLI-AMI + EPCs (1.2 × 106)] and group 5 (CLI-AMI + EPCs + EPO). RESULTS: By day 21 (end of study period), 2-D echo and Laser doppler showed that left-ventricular injection fraction (LVEF) and the ratio of ischemic to normal blood flow were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but not different in the latter two groups (all p < 0.0001). Flow cytometry and ELISA demonstrated that circulating angiogenesis factors were significantly progressively increased from groups 1 to 5 (all p < 0.001). The number of small vessels and protein (CD31/eNOS)/cellular (vWF) expressions reflecting integrity of endothelium exhibited an identical pattern to LVEF whereas protein (VEGF/SDF-1α)/cellular (VEGF) expressions were significantly progressively increased from groups 1 to 5 in quadriceps and heart tissues (all p < 0.0001). Protein expressions of apoptotic (Bax/caspase-3/PARP)/inflammatory (MMP-9) and microscopic findings of ischemic/fibrotic/collagen-deposition areas and DNA-damage marker (γ-H2AX+) were lowest in group 1 and significantly progressively decreased from groups 2 to 5 in quadriceps and heart tissues (all p < 0.0001). CONCLUSIONS: Direct injection of EPO-EPC into CLI effectively restored blood flow in the CLI area and also preserved remote heart function.

Combined Therapy With Hyperbaric Oxygen and Melatonin Effectively Reduce Brain Infarct Volume and Preserve Neurological Function After Acute Ischemic Infarct in Rat.

This study tested the hypothesis that combined hyperbaric oxygen (HBO) and melatonin (Mel) was superior to either one for protecting the brain functional and parenchymal integrity from acute ischemic stroke (IS) injury. Adult-male Sprague-Dawley rats were divided into groups 1 (sham-operated control), 2 (IS), 3 (IS + HBO), 4 (IS + Mel), and 5 (IS + HBO-Mel). By day 28 after IS, the brain infarct area (BIA) was lowest in group 1, highest in group 2, significantly higher in groups 3 and 4 than in group 5, but not different between groups 3 and 4. The neurological function at day 7, 14, and 28 exhibited an opposite pattern to BIA among the 5 groups. The protein expressions of inflammatory (IL-1ß/IL-6/iNOS/TNF-α/p-NF-κB), apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial Bax), mitochondrial/DNA-damaged (cytochrome-C/γ-H2AX), oxidative stress (NOX-1/NOX-2), and autophagy (i.e. ratio of CL3B-II/CL3B-I) biomarkers displayed an identical pattern of BIA among 5 groups. Cellular expressions of inflammation (F4/80+/GFAP+) and DNA-damaged biomarker (γ-H2AX+) exhibited an identical pattern, whereas the integrities of myelin sheath/neuron (MPB+/NeuN+), endothelial cell (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIA among the 5 groups. Combined HBO-Mel therapy offered an additional benefit in protecting the brain against IS injury.

Short-interval exposure to ambient fine particulate matter (PM2.5) exacerbates the susceptibility of pulmonary damage in setting of lung ischemia-reperfusion injury in rodent: Pharmacomodulation of melatonin.

This study tested the hypothesis that exposure to ambient fine particulate matter (PM2.5) pollution increased susceptibility of rat lung to damage from acute ischemia-reperfusion (IR) injury that was reversed by melatonin (Mel) treatment. Male-adult SD rats (n = 30) were categorized into group 1 (normal control), group 2 (PM2.5 only), group 3 (IR only at day 8 after PM2.5 exposure), group 4 (PM2.5 + IR) and group 5 (PM2.5 + IR + Mel), and all animals were sacrificed by day 10 after PM2.5 exposure. Oxygen saturation (%) was significantly higher in group 1 than in other groups and significantly lower in group 4 than in groups 2, 3 and 5 but it did not differ among the latter three groups (p < 0.01). Pulmonary protein expressions of inflammation (MMP-9/TNF-α/NF-kB), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (mitochondrial-Bax/caspase-3/PARP) and fibrosis were lowest in group 1, highest in group 4, significantly higher in group 5 than in groups 2 and 3 (all p < 0.0001), but they did not differ between groups 2 and 3. Inflammatory cell infiltration in lung parenchyma, specific inflammatory cell surface markers (CD14+, F4/88+), allergic inflammatory cells (IgE+, eosinophil+), number of goblet cells, thickness of tracheal epithelial layer and fibrotic area exhibited an identical pattern of protein expressions to inflammation among the five groups (all p < 0.0001). In conclusion, lung parenchymal damage and a rigorous inflammatory response were identified in rodent even with short-term PM2.5 exposure.

Therapeutic effects of adipose derived fresh stromal vascular fraction-containing stem cells versus cultured adipose derived mesenchymal stem cells on rescuing heart function in rat after acute myocardial infarction.

We tested the hypothesis that adipose-derived fresh stromal vascular fraction (SVF) is non-inferior to conventional adipose-derived mesenchymal stem cell (ADMSC) therapy for improving left-ventricular ejection fraction (LVEF) in rat after acute myocardial infarction (AMI). Male-adult SD rats (n = 48) were categorized into group 1 (sham control), AMI, AMI + ADMSCs (1.2 × 106) cells] and AMI + SVF (1.2 × 106) cells]. Flow cytometric and qPCR analyses showed that the expressions of surface biomarkers for endothelial progenitor cells, and cardiac-stem cells were significantly higher in the SVF population than in the ADMSC population, whereas MSCs showed a reversed pattern between these two groups (all P < 0.001). By day-42 after AMI, LVEF was highest in SC, lowest in AMI, and significantly higher in AMI + SVF than in AMI + ADMSCs (P < 0.0001). Protein expression indicating angiogenesis, anti-inflammatory/anti-apoptotic, mitochondrial/bioenergy-integrity and antifibrotic biomarkers showed an identical pattern, whereas protein expressions for inflammatory, apoptotic and pressure-overload/heart failure biomarkers exhibited an opposite pattern to LVEF among the four groups (all P < 0.001). Histopathology displayed that LV infarction/fibrotic area/collagen-deposition areas, cellular expressions of DNA-damage, and inflammatory biomarkers exhibited an opposite pattern, whereas cellular expressions of endothelial/gap-junction biomarkers showed an identical pattern to LVEF among the four groups (all P < 0.0001). Cellular expression of angiogenesis biomarkers significantly and progressively increased from groups 1 to 4 (all P < 0.0001). In conclusion, SVF may be better than ADMSC at improving LVEF in rat after AMI.

Simultaneous auricular reconstruction and transcutaneous bone conduction device implantation in patients with microtia.

BACKGROUND/PURPOSE: The Bonebridge (BB) is a newly designed transcutaneous bone conduction hearing implant. We describe, for the first time, simultaneous BB implantation and different surgical techniques of auricular reconstruction for microtia patients with aural atresia/stenosis. METHODS: Ten patients with unilateral or bilateral microtia underwent BB implantation combined simultaneously with either total auricular reconstruction using bespoke hand-carved Medpor framework or second stage auricular projection using autologous costal cartilage framework. Auditory aided and unaided sound fields were evaluated using (1) a pure-tone average (PTA4), (2) a speech reception threshold (SRT), and (3) a Speech Discrimination Score (SDS) at a sound level of 65 dB SPL. RESULTS: All patients and their families were satisfied with the aesthetic outcome of their constructed ears with no requests for further revision. No major complications were encountered. One patient developed minor partial skin graft epidermolysis that healed uneventfully, and another patient had a three month period of auditory acclimatization to the BB device that resolved. Postoperatively, the mean aided PTA4 decreased by 35.35 dB, while the SRT was 54.5 dB HL unaided and 28 dB HL with use of a BB sound processor. The SDS increased by 16.4%-65 dB SPL. CONCLUSION: Simultaneous BB implantation during either total auricular reconstruction or framework projection for microtia patients who have aural atresia/stenosis is feasible and safe. This approach reduces operative stages, thereby minimizing schooling/occupational disruption and time to total microtia reconstruction and auditory rehabilitation.

Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat.

This study tested the hypothesis that early administration of empagliflozin (Empa), an inhibitor of glucose recycling in renal tubules, could preserve heart function in cardiorenal syndrome (CRS) in rat. Chronic kidney disease (CKD) was caused by 5/6 subtotal nephrectomy and dilated cardiomyopathy (DCM) by doxorubicin (DOX) treatment. In vitro results showed that protein expressions of cleaved-caspase3 and autophagy activity at 24 h/48 h in NRK-52P cells were significantly upregulated by para-Creso treatment; these were significantly downregulated by Empa treatment. Flow cytometric analysis showed that annexin-V (i.e., early/late apoptosis) in NRK-52P cells expressed an identical pattern to cleaved-caspase3 between the two groups (all p < 0.001). Adult-male-SD rats (n = 18) were equally categorized into group 1 (sham-control), group 2 (CRS) and group 3 [CRS + Empa; 20 mg/kg/day]. By day-42 after CRS induction, left-ventricular ejection fraction (LVEF) level exhibited an opposite pattern, whereas LV end-diastolic dimension and creatinine level displayed the same pattern, to cleaved-caspase3 among the three groups (all p < 0.0001). In LV tissues, protein expressions of inflammatory (tumor-necrosis factor-α/nuclear-factor-κB/interleukin-1ß/matrix-metalloprotianse-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP), fibrotic (transforming-growth factor-ß/Smad3), DNA/mitochondrial-damage (γ-H2AX/cytosolic-cytochrome-C) and heart failure (brain natriuretic peptide (BNP) levels displayed an opposite pattern to LVEF among the three groups (all p < 0.0001). Additionally, cellular expressions of DNA-damage/heart-failure (γ-H2AX+//XRCC1+CD90+//BNP+) biomarkers and histopathological findings of fibrotic/condensed collagen-deposition areas and apoptotic nuclei showed an identical pattern, whereas connexin43 and small-vessel number exhibited an opposite pattern, to inflammation among the three groups (all p < 0.0001). In conclusion, Empa therapy protected heart and kidney against CRS injury.

Masseter Muscle Volume Changes Evaluated by 3-Dimensional Computed Tomography After Repeated Botulinum Toxin A Injections in Patients With Square Facial Morphology.

INTRODUCTION: Botulinum neurotoxin A (BoNT-A) is a minimally invasive and technically straightforward treatment of masseter muscle (MM) volume reduction and facial contouring, but the literature on its long-term effect on MM volume remains unclear. OBJECTIVE: This study aimed to assess quantitatively for progressive volume changes of lower facial contour after 3 BoNT-A injections in patients with bilateral MM hypertrophy causing square facial morphology using 3-dimensional computed tomographic scans. MATERIALS AND METHODS: Ten female patients with square facial morphology due to bilateral MM hypertrophy were recruited to, and 6 completed, this clinical study. Each received 24 U of BoNT-A into the inferior portion of each MM on both sides, repeated 6 monthly to complete 3 treatments. Masseter muscle volume changes were assessed using 3-dimensional computed tomography at pretreatment (before injections) and posttreatment (1 year after the third injection). RESULTS: Mean MM volume significantly reduced from 26.39 ± 4.18 cm before treatment to 23.26 ± 4.31 cm 1 year after treatment (P = 0.002). CONCLUSION: Three consecutive 6-monthly BoNT-A injections into the MMs reduced their volume by 12% when assessed 1 year after completion of treatment.

Extracorporeal Shock Wave-Supported Adipose-Derived Fresh Stromal Vascular Fraction Preserved Left Ventricular (LV) Function and Inhibited LV Remodeling in Acute Myocardial Infarction in Rat.

This study tested the hypothesis that extracorporeal shock wave- (ECSW-) assisted adipose-derived stromal vascular fraction (SVF) therapy could preserve left ventricular ejection fraction (LVEF) and inhibit LV remodeling in a rat after acute myocardial infarction (AMI). Adult male SD rats were categorized into group 1 (sham control), group 2 (AMI induced by left coronary artery ligation), group 3 [AMI + ECSW (280 impulses at 0.1 mJ/mm2, applied to the chest wall at 3 h, days 3 and 7 after AMI), group 4 [AMI + SVF (1.2 × 106) implanted into the infarct area at 3 h after AMI], and group 5 (AMI + ECSW-SVF). In vitro, SVF protected H9C2 cells against menadione-induced mitochondrial damage and increased fluorescent intensity of mitochondria in nuclei (p < 0.01). By day 42 after AMI, LVEF was highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, and similar between the latter two groups (all p < 0.0001). LV remodeling and infarcted, fibrotic, and collagen deposition areas as well as apoptotic nuclei exhibited an opposite pattern to LVEF among the groups (all p < 0.0001). Protein expressions of CD31/vWF/eNOS/PGC-1α/α-MHC/mitochondrial cytochrome C exhibited an identical pattern, whilst protein expressions of MMP-9/TNF-α/IL-1ß/NF-κB/caspase-3/PARP/Samd3/TGF-ß/NOX-1/NOX-2/oxidized protein/ß-MHC/BNP exhibited an opposite pattern to LVEF among five groups (all p < 0.0001). Cellular expressions of CXCR4/SDF-1α/Sca-1/c-Kit significantly and progressively increased from groups 1 to 5 (all p < 0.0001). Cellular expression of γ-H2AX/CD68 displayed an opposite pattern to LVEF among the five groups (all p < 0.0001). In conclusion, ECSW-SVF therapy effectively preserved LVEF and inhibited LV remodeling in rat AMI.

Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury.

This study tested whether inducible pluripotent stem cell (iPSC)-derived mesenchymal stem cell (MSC) therapy could effectively protect kidney from acute ischemia (1 h) - reperfusion (5 day) injury (IRI). Male-adult SD-rats (n = 24) were equally categorized into groups 1 (sham-control), 2 [sham-control + iPSC-MSC (1.2 × 106 cells/rat)], 3 (IR only) and 4 (IR + iPSC-MSC). Blood urine nitrogen/creatinine levels and ratio of urine protein to creatinine, kidney weight and expressions of inflammation (TNF-α/NF-κB), oxidative-stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved caspase-3/PARP) were significantly higher in group 3 than in groups 1, 2 and 4 and significantly higher in group 4 than in groups 1 and 2 (all P<0.0001), but showed no differences between groups 1 and 2, whereas the protein expressions of anti-inflammation (IL-4/IL-10) and endothelial (CD31/vWF) markers exhibited an opposite pattern to inflammation among the four groups (all P<0.0001). Protein expressions of angiogenesis (VEGF/CXCR4/SDF-1α) markers progressively increased from groups 1 to 4 (all P<0.0001). Cellular expressions of kidney injury score/DNA-damage (γ-H2AX)/apoptotic nuclei and glomerulus-tubular-damage (KIM/FSP-1) displayed an identical pattern to inflammation, whereas the cellular expressions of glomerulus-tubular-integrity (dystroglycan/podocin/p-cadherin/synaptopodin/ZO-1/fibronectin) revealed an opposite pattern to inflammation among the four groups (all P<0.0001). In conclusion, iPSC-derived MSC therapy effectively protected kidney against IRI.