EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin ß1 signalling axis.

Endometrial carcinoma (EC) is a common type of uterine cancer in developed countries, originating from the uterine epithelium. The incidence rate of EC in Taiwan has doubled from 2005. Cancer stem cells (CSCs) are a subpopulation of cancer cells that have high tumorigenicity and play a crucial role in the malignant processes of cancer. Targeting molecules associated with CSCs is essential for effective cancer treatments. This study delves into the role of Exosome component 5 (EXOSC5) in EC. Data from The Cancer Genome Atlas suggests a correlation between high EXOSC5 mRNA expression and unfavorable EC prognosis. EXOSC5 knockdown diminished EC-CSC self-renewal and reduced expression of key cancer stemness proteins, including c-MYC and SOX2. Intriguingly, this knockdown significantly curtailed tumorigenicity and CSC frequency in EC tumor spheres. A mechanistic examination revealed a reduction in netrin4 (NTN4) levels in EXOSC5-depleted EC cells. Moreover, NTN4 treatment amplified EC cell CSC activity and, when secreted, NTN4 partnered with integrin ß1, subsequently triggering the FAK/SRC axis to elevate c-MYC activity. A clear positive relation between EXOSC5 and NTN4 was evident in 93 EC tissues. In conclusion, EXOSC5 augments NTN4 expression, activating c-MYC via the integrin ß1/FAK/SRC pathway, offering potential avenues for EC diagnosis and treatment.

A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility.

Introduction: Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis. Methods: ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA). Results: Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation. Conclusion: ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.

Investigation of Flexible Arrayed Lactate Biosensor Based on Copper Doped Zinc Oxide Films Modified by Iron-Platinum Nanoparticles.

Potentiometric biosensors based on flexible arrayed silver paste electrode and copper-doped zinc oxide sensing film modified by iron-platinum nanoparticles (FePt NPs) are designed and manufactured to detect lactate in human. The sensing film is made of copper-doped zinc oxide (CZO) by a radio frequency (RF) sputtering system, and then modified by iron-platinum nanoparticles (FePt NPs). The surface morphology of copper-doped zinc oxide (CZO) is analyzed by scanning electron microscope (SEM). FePt NPs are analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The average sensitivity, response time, and interference effect of the lactate biosensors are analyzed by voltage-time (V-T) measurement system. The electrochemical impedance is analyzed by electrochemical impedance spectroscopy (EIS). The average sensitivity and linearity over the concentration range 0.2-5 mM are 25.32 mV/mM and 0.977 mV/mM, respectively. The response time of the lactate biosensor is 16 s, with excellent selectivity.

The Decisive Case-Control Study Elaborates the Null Association between ESR1 XbaI and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.

A rare case report: an inextricable shoulder pain as the exclusive presentation of lung adenocarcinoma with metastasis over contralateral clavicle.

BACKGROUND: Lung cancer is the fourth most common form of the tumor spreading to the bone. Among all patients of lung carcinoma, the most common sites of bone metastasis are vertebrae, ribs, and pelvis. By comparison, the clavicle is an extremely rare site of metastases not only in the population of lung cancers but among all types of tumors. Enlightened by this existing fact, we would like to share our experience of management of an uncommon clavicular metastasis and illuminate the obscure mechanism of its scarcity. CASE PRESENTATION: A 56-year-old female without any preknown systemic disease had suffered from a sole intermittent right shoulder pain without any other discomfort for 3 months. Physical examination performed at our orthopedic department showed tenderness over the right distal third of the clavicle with limited range-of-motion of the right shoulder. EGFR-mutated lung adenocarcinoma with metastasis over the right clavicle resulting in a pathological fracture was diagnosed according to the result of the incisional biopsy. Concurrent chemoradiation therapy accompanied with target therapy was performed. Eighteen months postoperatively, the clavicle pain was found to be subsided with stationary bony lesion under appropriate medication and palliative radiotherapy during the subsequent follow-up. CONCLUSIONS: The clavicle is an exceedingly unusual site with 2% of metastatic involvement of all type of tumors and only 1% among the population of carcinoma of lung due to its scanty red marrow and sparse vascular supply. Despite the unpleasant prognosis of clavicular metastasis from primary lung adenocarcinoma, promising quality of life is achievable under multidisciplinary management.

Horizontally acquired antibacterial genes associated with adaptive radiation of ladybird beetles.

BACKGROUND: Horizontal gene transfer (HGT) has been documented in many herbivorous insects, conferring the ability to digest plant material and promoting their remarkable ecological diversification. Previous reports suggest HGT of antibacterial enzymes may have contributed to the insect immune response and limit bacterial growth. Carnivorous insects also display many evolutionary successful lineages, but in contrast to the plant feeders, the potential role of HGTs has been less well-studied. RESULTS: Using genomic and transcriptomic data from 38 species of ladybird beetles, we identified a set of bacterial cell wall hydrolase (cwh) genes acquired by this group of beetles. Infection with Bacillus subtilis led to upregulated expression of these ladybird cwh genes, and their recombinantly produced proteins limited bacterial proliferation. Moreover, RNAi-mediated cwh knockdown led to downregulation of other antibacterial genes, indicating a role in antibacterial immune defense. cwh genes are rare in eukaryotes, but have been maintained in all tested Coccinellinae species, suggesting that this putative immune-related HGT event played a role in the evolution of this speciose subfamily of predominant predatory ladybirds. CONCLUSION: Our work demonstrates that, in a manner analogous to HGT-facilitated plant feeding, enhanced immunity through HGT might have played a key role in the prey adaptation and niche expansion that promoted the diversification of carnivorous beetle lineages. We believe that this represents the first example of immune-related HGT in carnivorous insects with an association with a subsequent successful species radiation.

Tribbles Pseudokinase 3 Contributes to Cancer Stemness of Endometrial Cancer Cells by Regulating ß-Catenin Expression.

Endometrial cancer (EC) is the second most common gynecological malignancy worldwide. Tribbles pseudokinase 3 (TRIB3) is a scaffolding protein that regulates intracellular signal transduction, and its role in tumor development is controversial. Here, we investigated the biological function of TRIB3 in EC. We found that the messenger RNA (mRNA) expression level of TRIB3 was significantly and positively correlated with shorter overall survival of EC patients in The Cancer Genome Atlas database. The protein expression of TRIB3 was found to be significantly increased in EC cancer stem cells (CSCs) enriched by tumorsphere cultivation. Knockdown of TRIB3 in EC cells suppressed tumorsphere formation, the expression of cancer stemness genes, and the in vivo tumorigenesis. The expression of ß-catenin at both the protein and the mRNA levels was downregulated upon TRIB3 silencing. TRIB3 was found to interact with E74 Like ETS transcription factor 4 (ELF4) in the nucleus and bound to ELF4 consensus sites within the catenin beta 1 (CTNNB1) promoter in EC cell lines. These data indicated that TRIB3 may regulate CTNNB1 transcription by enhancing the recruitment of ELF4 to the CTNNB1 promoter. In conclusion, our results suggest that TRIB3 plays an oncogenic role in EC and positively regulates the self-renewal and tumorigenicity of EC-CSCs. Targeting TRIB3 is considered as a potential therapeutic strategy in future EC therapy.

NAD(P)H:quinone oxidoreductase 1 determines radiosensitivity of triple negative breast cancer cells and is controlled by long non-coding RNA NEAT1.

Radioresistant cells cause recurrence in patients with breast cancer after they undergo radiation therapy. The molecular mechanisms by which cancer cells obtain radioresistance should be understood to develop radiation-sensitizing agents. Results showed that the protein expression and activity of NAD(P)H:quinone oxidoreductase 1 (NQO1) were upregulated in radioresistant MDA-MB-231 triple-negative breast cancer (TNBC) cells. NQO1 knockdown inhibited the proliferation of NQO1 expressing Hs578t TNBC cells or the radioresistant MDA-MB-231 cells, whereas NOQ1 overexpression increased the survival of MDA-MB-231 cells, which lack of NQO1 expression originally, under irradiation. The cytotoxicity of ß-lapachone, an NQO1-dependent bioactivatable compound, was greater in radioresistant MDA-MB-231 cells than in parental cells. ß-lapachone displayed a radiosensitization effect on Hs578t or radioresistant MBDA-MB-231 cells. The expression of the long noncoding RNA NEAT1 positively regulated the NQO1 expression in radioresistant MDA-MB-231 cells at a translational level rather than at a transcription level. The inhibition of the NEAT1 expression through the CRISPR-Cas9 method increased the sensitivity of radioresistant MDA-MB-231 cells to radiation and decreased their proliferation, the activity of cancer stem cells, and the expression of stemness genes, including BMI1, Oct4, and Sox2. In conclusion, the NQO1 expression in triple-negative breast cancer cells determined their radiosensitivity and was controlled by NEAT1. In addition, NOQ1 bioactivatable compounds displayed potential for application in the development of radiation sensitizers in breast cancer.

Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation.

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44⁺ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G¹ phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

Three Simple Steps for Refining Transcutaneous Lower Blepharoplasty for Aging Eyelids: The Indispensability of Micro-Autologous Fat Transplantation.

BACKGROUND: Lower blepharoplasty has been used for rejuvenating lower eyelids, and diverse modifications have been used to treat conjunct deformities at the tear trough/lid-cheek junction. Strategies for recontouring prominent tear trough/lid-cheek junctions, including orbital fat manipulation, have been reported with good results in the literature. Micro-autologous fat transplantation (MAFT) is a previously unevaluated, potentially advantageous approach to blending the prominent tear trough/lid-cheek junction. OBJECTIVES: We determined the long-term results after 3-step transcutaneous lower blepharoplasty with MAFT for patients with aging eyelids and prominent tear trough/lid-cheek junctions. METHODS: We evaluated 205 patients with aging lower eyelids who underwent transcutaneous lower blepharoplasty with MAFT between October 2010 and September 2016. The 3-step procedure involved a subciliary elliptical skin excision, resection of 3 orbital fat compartments, and MAFT for the tear trough/lid-cheek junction employing a MAFT-GUN under intravenous anesthesia. RESULTS: The mean patient age was 52 years (range, 34-78 years). The mean operating time was 61 minutes. The mean fat volumes delivered to the tear trough/lid-cheek junctions were 2.80 mL and 2.76 mL for the left and right sides, respectively. The average weights of the 3 resected orbital fat compartments were 0.58 g for the left side and 0.56 g for the right side. Patients showed significant improvement and maintenance at an average follow-up of 60.2 months (range, 18-90 months). CONCLUSIONS: Three-step transcutaneous lower blepharoplasty with MAFT is an effective, reliable, and promising method with high patient satisfaction and minimal risk of complications. Long-term results demonstrated its utility for aging lower eyelid treatment.

Micro-Autologous Fat Transplantation for Treating a Gummy Smile.

BACKGROUND: A gummy smile is treated using many techniques, including botulinum toxin injection and various surgical interventions. Micro-autologous fat transplantation (MAFT) is a potentially advantageous alternative approach that has not been previously evaluated. OBJECTIVES: This study sought to determine the long-term results of MAFT in patients with a gummy smile. METHODS: Seven patients with gummy smiles were evaluated for MAFT treatment between October 2015 and April 2017. Centrifuged purified fat was micro-transplanted into the nasolabial groove, ergotrid, and upper lip areas using the MAFT-GUN while the patients were under total intravenous anesthesia. RESULTS: The mean age of the 7 patients was 31 years (range, 23-40 years). The mean operating time for MAFT was 52 minutes (range, 40-72 minutes), and the mean volume of fat delivered to the nasolabial groove, ergotrid, and upper lip was 16.1 mL. The mean decreases of gingival display in the right canine incisor, left canine incisor, right canine, and left canine teeth were 4.9, 4.6, 3.8, and 4.4 mm, respectively. The smiles of the 7 patients showed significant improvement at an average follow-up time of 12.9 months. CONCLUSIONS: Gummy smile treatment using MAFT is an effective, reliable, and relatively simple method, with high patient satisfaction and minimal risk of complications.

Long-Term Outcome of Microautologous Fat Transplantation to Correct Temporal Depression.

OBJECTIVE: Sunken temporal fossa appears oftentimes in Asians and resembles bad fortune that people wish to change. Numerous techniques and materials have been applied clinically for augmenting the sunken temporal fossa with variable results. The microautologous fat transplantation (MAFT) technique proposed by Lin et al in 2006 has demonstrated favorable results in facial rejuvenation. In the present study, the authors applied the MAFT technique with an innovative instrument in sunken temporal fossa and reported its results. METHODS: Microautologous fat transplantation was performed on 208 patients during the 4-year period starting in January 2010. Fat was harvested by liposuction, processed and refined by centrifugation at 1200 g for 3 minutes. Then purified fat was microtransplanted to the temporal fossa with the assistance of an instrument, MAFT-Gun. The patients were followed up regularly and photographs were taken for comparison. RESULTS: On average, the MAFT procedure took 48 minutes to complete. The average delivered fat was 6.8 ±â€Š0.2 mL/6.5 ±â€Š0.3 mL for the right/left side. The average follow-up period was 18 months. No complication including skin necrosis, vascular compromise, nodulation, fibrosis, and asymmetry was noted. The patient-rated satisfaction 5-point Likert scale demonstrated that 81.3% of all patients had favorable results (38.5% very satisfied and 42.8% satisfied). CONCLUSIONS: The concept and technique of MAFT along with the micro- and precise controlling instrument enabled surgeons to perform fat grafting accurately and consistently. In comparison with other strategies for volume restoration, the MAFT procedure demonstrated the patients' high satisfaction with the long-term results. Therefore, the potential of MAFT as an alternative strategy in sunken temporal fossa in Asians was emphasized.

Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the epigenetic inhibition of ZEB1 expression.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral mucosa without specific therapeutic drugs. We previously demonstrated that the zinc finger E-box binding homeobox 1 (ZEB1) plays a pathogenic role in the induction of the myofibroblast activity of buccal mucosal fibroblasts (BMFs) and contributes to the pathogenesis of OSF. Resveratrol is a natural polyphenolic flavonoid with anti-fibrosis activity in various tissues and has the capability to inhibit ZEB1 in oral cancer cells. We examined the effect of resveratrol on the myofibroblast activity of human primary fibrotic BMFs (fBMFs) derived from OSF tissues. With the collagen contraction assay, resveratrol displayed anti-myofibroblast activity in three fBMF lines. Resveratrol also inhibited the expression of fibrogenic genes at the mRNA and protein levels in a dose- and time-dependent manner. The downregulation of ZEB1 in fBMFs by resveratrol was mediated by epigenetic mechanisms, such as the upregulated expression of miR-200c and the enhancer of zeste homolog 2 (EZH2), as well as the trimethylated lysine 27 of histone H3 (H3K27me3). Resveratrol also increased the binding of H3K27me3 to the ZEB1 promoter. The knockdown of EZH2 in fBMFs caused the upregulation of ZEB1 and suppressed the inhibitory effect of resveratrol. Furthermore, the reversed expression pattern between EZH2 and ZEB1 was observed in 6/8 OSF tissues with twofold upregulation of ZEB1 expression compared with the adjacent normal mucosa. In conclusion, our data suggest that resveratrol epigenetically inhibits ZEB1 expression to suppress the myofibroblast activity of fBMFs and may serve as a dietary supplement for OSF patients.

Microautologous Fat Transplantation for Primary Augmentation Rhinoplasty: Long-Term Monitoring of 198 Asian Patients.

BACKGROUND: Numerous techniques and materials are available for increasing the dorsal height and length of the nose. Microautologous fat transplantation (MAFT) may be an appropriate strategy for augmentation rhinoplasty. OBJECTIVES: The authors sought to determine the long-term results of MAFT with the so-called one-third maneuver in Asian patients who underwent augmentation rhinoplasty. METHODS: A total of 198 patients who underwent primary augmentation rhinoplasty with MAFT were evaluated in a retrospective study. Fat was harvested by liposuction and was processed and refined by centrifugation. Minute parcels of purified fat were transplanted to the nasal dorsum with a MAFT-Gun. Patient satisfaction was scored with a 5-point Likert scale, and aesthetic outcomes were validated with pre- and postoperative photographs. RESULTS: The mean age of the patients was 45.5 years. The mean operating time for MAFT was 25 minutes, and patients underwent 1-3 MAFT sessions. The mean volume of fat delivered per session was 3.4 mL (range, 2.0-5.5 mL). Patients received follow-up for an average of 19 months (range, 6-42 months). Overall, 125 of 198 patients (63.1%) indicated that they were satisfied with the results of 1-3 sessions of MAFT. There were no major complications. CONCLUSIONS: The results of this study support MAFT as an appropriate fat-transfer strategy for Asian patients undergoing primary augmentation rhinoplasty. LEVEL OF EVIDENCE 4: Therapeutic.

A Secure Technique for Microvascular Anastomosis in Arteries with Intimal Dissection: Intimal Sleeve Fold-Over Technique.

BACKGROUND: Intimal dissection can cause an irregular internal surface with intimal flaps and subendothelial collagen exposure. This has been associated with a high risk of thrombosis. Trimming the artery to a healthy level is routinely recommended to avoid intimal dissection. However, this method is limited when there is inadequate vascular length to work with. METHODS: We dealt with an artery exhibiting severe intimal dissection by using a new suture technique: the intimal sleeve fold-over technique. Severe arterial intimal dissections were observed in 9 (6.9%) of 130 arterial microvascular anastomoses in free flap reconstruction for oral cancer patients from January 2013 to December 2013. We used this technique in 6 of the 9 patients. RESULTS: All 6 patients were discharged as scheduled without perioperative problems and complications during follow-ups. The mean diameters of the recipient and pedicle arteries with intimal dissection were 2.13 and 2.20 mm. The mean time for performing sleeve fold-over procedure of on each artery was 5.1 minutes. CONCLUSIONS: A secure intima-to-intima contact can be achieved using this technique. This technique can provide an alternative method to intimal dissection when the length of the artery is limited.

Fat Grafting for Recontouring Sunken Upper Eyelids With Multiple Folds in Asians-Novel Mechanism for Neoformation of Double Eyelid Crease.

BACKGROUND: This study reviewed the mini invasive technique, microautologous fat transplantation (MAFT), as a strategy in simultaneously treating sunken upper eyelids with multiple folds and recreating a double eyelid crease in Asian people. METHODS: The MAFT was performed with the assistance of a patented medical device, the MAFT-GUN, on 34 patients who had sunken upper eyelids and multiple folds. Each delivered fat parcel was accurately and consistently maintained at 1/240 mL during placement. Follow-up was regularly performed with photography for comparison. RESULTS: Fifty-eight sunken upper eyelids with multiple folds were reconstructed. In addition to the ameliorative recontouring of hollowness, a natural eyelid crease was created postoperatively. Temporary swelling and bruising were noted several days after surgery without morbidities, such as fibrosis or nodulation. All of the patients were satisfied with the 1-time MAFT procedure. CONCLUSIONS: Fat grafting for sunken upper eyelids with multiple folds has been reported in the literature. However, temporal effects and complications, such as nodulation and irregularity, have often occurred. A new method, MAFT, demonstrated its reliability as a modality for sunken upper eyelids with multiple folds in Asians. Moreover, MAFT might serve as an alternative for neoformation of double eyelids in these candidates.

ß-catenin is O-GlcNAc glycosylated at Serine 23: implications for ß-catenin's subcellular localization and transactivator function.

BACKGROUND: We have previously reported that ß-catenin is post-translationally modified with a single O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAc). We showed that O-GlcNAc regulated ß-catenin's subcellular localization and transcriptional activity. OBJECTIVE: The objectives of this investigation were to identify the putative O-GlcNAc sites of ß-catenin and the relevance of identified sites in the regulation of ß-catenin's localization and transcriptional activity. METHOD: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-ß-catenin by site-directed mutagenesis. We determined the levels of O-GlcNAc-ß-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. RESULTS: Serine 23 of ß-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. SIGNIFICANCE: O-GlcNAcylation of Serine 23 is a novel regulatory modification for ß-catenin's subcellular localization and transcriptional activity. This study is the first report to characterize site specific regulation of ß-catenin by the O-GlcNAc modification.

The role of frontalis orbicularis oculi muscle flap for correction of blepharoptosis with poor levator function.

On the basis of the close anatomical interdigitation between the longitudinal-oriented frontalis muscle and the horizontal-oriented orbicularis oculi muscle (OOM), frontalis OOM (FOOM) flap was developed to treat blepharoptosis. Retrospective study during an 11-year period, 66 patients with 81 poor levator function ptotic eyelids accepted FOOM flap shortening (65 lids; 80.2%) or double-breasted FOOM flap advancement (16 lids; 19.8%) to correct blepharoptosis. There were 51 (77.3%) patients with unilateral ptosis and 15 (22.7%) patients with bilateral ptosis. Severity of blepharoptosis included severe type in 72 (88.9%) lids, moderate type in 5 (6.2%) lids, and mild type in 4 (4.9%) lids. The underlying etiology included congenital origin in 43 (65.1%) patients, involutional change in 19 (28.8%) patients, and neurologic origin in 4 (6.1%) patients. Marginal reflex distance 1 and lid slit distance improved from -1.6 (2.0) to 3.3 (1.2) and 3.2 (2.0) to 7.2 (1.4) mm, respectively, after operation. The postoperative outcome includes good results in 54 (81.8%) patients, fair results in 10 (15.2%) patients, and poor results in 2 (3.0%) patients. The undercorrection or recurrence rate is 14.8%, and secondary revision rate is 11.1%. Positive Hering law is 17.6% among patients with unilateral ptosis. Overall patients' satisfaction rate is 95.1%. Both FOOM flap shortening and double-breasted FOOM flap advancement are effective to treat poor levator function blepharoptosis. Double-breasted FOOM flap advancement is highly recommended because of the more natural contour and minimal lagophthalmos postoperatively, because of the maximal preservation of OOM.