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1.
Skin Res Technol ; 30(4): e13693, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38572573

ABSTRACT

BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.


Subject(s)
Acne Vulgaris , Artificial Intelligence , Adult , Humans , Female , Acne Vulgaris/epidemiology , Acne Vulgaris/complications , Skin , China/epidemiology
2.
Plast Reconstr Surg ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38616321

ABSTRACT

BACKGROUND: The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma. METHODS: Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale. RESULTS: There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05). CONCLUSION: In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction.

3.
Quant Imaging Med Surg ; 14(3): 2466-2474, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38545057

ABSTRACT

Background: Facial anthropometry based on 3-dimensional (3D) imaging technology, or 3D photogrammetry, has gained increasing popularity among surgeons. It outperforms direct measurement and 2-dimensional (2D) photogrammetry because of many advantages. However, a main limitation of 3D photogrammetry is the time-consuming process of manual landmark localization. To address this problem, this study developed a U-NET-based deep learning algorithm to enable automated and accurate anatomical landmark detection on 3D facial models. Methods: The main structure of the algorithm stacked 2 U-NETs. In each U-NET block, we used 3×3 convolution kernel and rectified linear unit (ReLU) as activation function. A total of 200 3D images of healthy cases, acromegaly patients, and localized scleroderma patients were captured by Vectra H1 handheld 3D camera and input for algorithm training. The algorithm was tested to detect 20 landmarks on 3D images. Percentage of correct key points (PCK) and normalized mean error (NME) were used to evaluate facial landmark detection accuracy. Results: Among healthy cases, the average NME was 1.4 mm. The PCK reached 90% when the threshold was set to the clinically acceptable limit of 2 mm. The average NME was 2.8 and 2.2 mm among acromegaly patients and localized scleroderma patients, respectively. Conclusions: This study developed a deep learning algorithm for automated facial landmark detection on 3D images. The algorithm was innovatively validated in 3 different groups of participants. It achieved accurate landmark detection and improved the efficiency of 3D image analysis.

4.
Quant Imaging Med Surg ; 14(2): 1891-1903, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38415131

ABSTRACT

Background: Localized scleroderma (LoS) is an autoimmune disease in which craniofacial lesions can cause severe facial deformities with brain involvement. Objective evaluation of craniofacial LoS is challenging. Magnetic resonance imaging (MRI) may be used as a damage assessment tool. This study aimed to analyze the tissue involvement of craniofacial LoS based on MRI and evaluate MRI for craniofacial LoS assessment. Methods: This cross-sectional study included patients with craniofacial LoS from September 2021 to August 2022 in Peking Union Medical College Hospital. Patients who were clinically assessed in a stable phase were enrolled; patients with previous surgical treatment or contraindications to MRI were excluded. Participants underwent clinical, MRI, and ultrasound assessments. MRI was compared with ultrasound by correlation analysis and Bland-Altman analysis. The involvement of different tissues and different facial subunits was compared. The accumulated soft tissue atrophy index (ASTAI) was compared with clinical scores by correlation analysis. Results: A total of 28 patients were included (13 female; mean age, 18 years). MRI showed a good correlation and agreement with ultrasound (r=0.916, P<0.001). In different facial subunits, a significant negative correlation between the forehead and chin was found (r=-0.593, P=0.001). The ASTAI correlated well with the facial LoS damage index (r=0.580, P=0.001) and the Peking Union Medical College LoS facial aesthetic index (PUMC LoSFAI) (r=0.921, P<0.001). A total of 38.6% of clinical scores were inaccurate based on MRI. Neurological changes were found in one patient. Conclusions: MRI can reliably quantify damage in craniofacial LoS, and may serve as a useful and objective tool for overall craniofacial LoS evaluation.

5.
Asian J Surg ; 47(1): 222-228, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37596215

ABSTRACT

BACKGROUND: Minimally invasive access and fast recovery are trends of gynecomastia surgery. We placed great importance on liposuction and modified original pull-through technique. The purpose of this study was to present a refined surgical strategy for gynecomastia in grade I and II. METHODS: The refined strategy embraced enhanced liposuction to remove the intraglandular fat sufficiently, followed by open resection of gland using the pull-through and bottom-up technique with adjuvant liposuction in the end. Surgical data were recorded and satisfactory questionnaires with 5-point scales were administered during follow-up. RESULTS: Between January 2017 and May 2022, 165 patients underwent enhanced liposuction combined with the pull-through and bottom-up technique for gland excision. Age ranged from 12 to 56 years. The median length of surgery was 100 min. A median of 300 ml of fat was aspirated and a median of 20.8 g of gland was excised. Seventy-seven patients (46.7%) responded the questionnaires at least 6 months postoperatively, and the average overall satisfaction was 4.68 ± 0.52 points. Thirteen sides of breasts developed complications with a rate of 4.0%. CONCLUSION: Enhanced liposuction combined with pull-through and bottom-up technique proved effective to treat grade I and II gynecomastia with minimal scarring and high satisfaction. The refined strategy was simple and safe, and would obtain optimal outcomes even for inexperienced surgeons.


Subject(s)
Gynecomastia , Lipectomy , Male , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Gynecomastia/surgery , Lipectomy/methods , Minimally Invasive Surgical Procedures , Esthetics , Patients , Retrospective Studies
6.
Skin Res Technol ; 29(11): e13492, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38009029

ABSTRACT

BACKGROUND: To better compare the progression of dark circles and the aging process in Chinese skin. A total of 100 589 Chinese males and 1 838 997 Chinese females aged 18 to 85, without facial skin conditions, and who had access to a smartphone with a high-resolution camera all took selfies. METHOD: Using a smartphone application with a built-in artificial intelligence algorithm, facial skin diagnostic evaluated the selfies and score the severity of the dark circles with four other facial indicators (including skin type, Pores, Acne vulgaris, and Blackheads). Basic information was collected with online questionnaire, including their age, gender, skin sensitivity, and dietary habits. RESULTS: In users between the age of 18 and 59, the prevalence of comprehensive, pigmented, and structural type of dark circles all rose with age. However, between the age of 60 and 85, the intensity of all types of dark circles diminished. Besides, vascular dark circles progressively worsen from the age of 18 to their peak at 39, and then gradually decline with age. Females typically have more pronounced black circles under their eyes than males in China. Bad eating habits, urbanization, regular cosmetics use, and sensitive skin positively correlate with severe dark circles. Vascular, comprehensive dark circles were worse in spring. Both pigmented and structural dark circles were worse in the summer. The results indicated that the intensity of dark circles was influenced by oily skin, wide pores, severe blackheads, and severe acne. CONCLUSIONS: Chinese men and women differed noticeably in the prevalence of each face aging indicator and the appearance of aging dark circles. Selfies could be automatically graded and examined by artificial intelligence, which is a quick and private method for quantifying signs of facial aging and identifying major problems for different populations. Artificial intelligence would assist in the development of individualized preventive and therapeutic interventions.


Subject(s)
Artificial Intelligence , Face , Skin Aging , Female , Humans , Male , Acne Vulgaris , East Asian People , Skin , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over
7.
J Plast Reconstr Aesthet Surg ; 87: 117-130, 2023 12.
Article in English | MEDLINE | ID: mdl-37837945

ABSTRACT

BACKGROUND: Autologous fat transplantation has become a common treatment for facial deformities. However, facial deformities are the result of complex diseases with different causes, and there has been no review on the effectiveness of autologous fat transplantation for facial deformities of different aetiologies. METHODS: A systematic literature search of the Web of Science, Embase, and Medline Ovid databases was performed up to December 2022. Two investigators independently performed screening and data extraction according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, followed by a meta-analysis using random-effects model for surgeon and patient satisfaction, facial symmetry, and complication rates. Twelve-month postoperative fat graft retention was estimated by meta-regression. RESULTS: Thirty-one studies met the criteria, including 13 case series studies, 14 cohort studies, and four randomized clinical trials, with a total of 1572 patients. Follow-up visits within 6-12 months were performed in most of the studies. The results of the meta-analysis showed high overall surgeon satisfaction of 97% (95% CI: 92%-100%) and patient satisfaction of 95% (95% CI: 89%-99%), with a low complication rate of 3.4% (95% CI: 1.9%-5.9%). At 12 months postoperatively, a lower retention rate of 43% (95% CI: 28%-58%) was estimated in cases of acquired atrophic deformities compared with 64% (95% CI: 57%-71%) in cases of mixed deformities. Overall, autologous fat transplantation improved facial symmetry by 13% (95% CI: 8.4%-18%). CONCLUSION: Autologous fat transplantation is generally a safe and effective procedure that can compensate for facial volume deficits and improve facial symmetry but may be less effective in cases of acquired atrophic facial deformities.


Subject(s)
Adipose Tissue , Plastic Surgery Procedures , Humans , Adipose Tissue/transplantation , Transplantation, Autologous/methods , Patient Satisfaction , Face/surgery , Postoperative Complications/etiology
8.
Clin Cosmet Investig Dermatol ; 16: 2375-2379, 2023.
Article in English | MEDLINE | ID: mdl-37671405

ABSTRACT

In this study, we report a rare case of en coup de sabre with hyperplasia of the left frontal bone beneath skin lesion, which is detected during magnetic resonance imaging screening and preoperative evaluation. A 27-year-old woman with 13-year history of progressive soft tissue depression in the forehead and scalp, and was treated by traditional Chinese herb before the disease went into stationary stage. The patient underwent serial long-pulsed laser treatments and autologous fat grafting with satisfactory outcome. To our knowledge, this is the first time that bony hyperplasia beneath the soft tissue lesion was found in a patient with en coup de sabre.

9.
J Dermatol Sci ; 112(1): 31-38, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37743142

ABSTRACT

BACKGROUND: Inflammation and fibrosis of the skin are characteristics of localized scleroderma (LS). Emerging evidence has demonstrated that exosomes from human adipose tissue-derived mesenchymal stem cells (ADSC-Exo) could alleviate skin fibrosis. OBJECTIVE: The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. METHODS: ADSC-Exo was isolated and identified. The effects of ADSC-Exo on the abilities of proliferation and migration of LS-derived fibroblasts (LSFs) were assessed by CCK-8 and scratch assays, respectively. qRT-PCR, western blot, and immunofluorescence were conducted to detect LSFs stimulated with ADSC-Exo, ADSC-ExoAnti-let-7a-5p, let-7a-5p mimic/TGF-ßR1 shRNA virus, and negative controls. The impact of ADSC-Exo on C57BL/6j LS mice was evaluated by photographic morphology, hematoxylin-eosin (H&E), Masson's trichrome, and immunohistochemical staining. RESULTS: The verified ADSC-Exo limited the proliferation and migration of LSFs and reduced the expression of COL1, COL3, α-SMA, TGF-ßR1, and p-Smad2/ 3 in vitro and in vivo. TGF-ßR1 knockdown and let-7a-5p mimic in LSFs reduced the expression of COL1, COL3, α-SMA, and p-Smad2/3. However, compared with the ADSC-ExoNC group, the dermal thickness was increased, collagen arrangement was disordered, and α-SMA and TGF-ßR1 levels were increased after exposure to ADSC-ExoAnti-let-7a-5p. CONCLUSIONS: In this study, it might show that ADSC-Exo may successfully prevent LSF bioactivity, collagen deposition, and myofibroblast trans-differentiation. Additionally, we confirmed that let-7a-5p in ADSC-Exo could directly target TGF-R1 to control the Smad pathway and reduce fibrosis in LSFs. Our work offered a brand-new therapeutic approach and clarified the unique mechanism for the clinical management of LS.


Subject(s)
Exosomes , Mesenchymal Stem Cells , MicroRNAs , Scleroderma, Localized , Animals , Humans , Mice , Collagen/metabolism , Exosomes/metabolism , Fibrosis , Mesenchymal Stem Cells/metabolism , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Scleroderma, Localized/metabolism , Receptor, Transforming Growth Factor-beta Type I/metabolism , Smad Proteins/metabolism
10.
Aesthetic Plast Surg ; 47(5): 1759-1770, 2023 10.
Article in English | MEDLINE | ID: mdl-37500904

ABSTRACT

BACKGROUND: Data on the value of magnetic resonance imaging (MRI) in the preoperative evaluation and surgery planning of gynecomastia are limited. The purpose of this study is to reveal MRI features and categories of gynecomastia and compare surgical outcomes following MRI and sonography as well as their diagnostic accuracy. METHODS: The area of the gland and the whole breast on the transverse plane via nipple of MRI were measured to calculate the ratio between them. Areola, mass and branch patterns were categorized to represent three different gynecomastia type on MRI. 183 patients were included, with 38 in MRI group and 145 in sonography group. Diagnostic accuracy was assessed by the level of agreement between preoperative imaging findings and intraoperative observations. Surgical data, patients' satisfaction and complications were compared between the two groups. RESULTS: MRI in 75 gynecomastic breasts demonstrated the average ratio of the gland to the whole breast was 10.6%±13.3%. The most common MRI categories were branch patterns (45.3%). The diagnostic concordance rate of MRI was higher than sonography (100% vs. 86.8%, p = 0.001). Among those junior surgeons, the length of surgery was reduced in MRI group (100 min vs. 115 min, p = 0.048). There was no difference in terms of patient's satisfaction and complication rate between MRI and sonography. CONCLUSION: MRI was superior to sonography in diagnostic accuracy to assess the tissue components of gynecomastia and provided informative guidance especially for junior surgeons. Surgical outcomes were comparable regardless of the use of MRI or sonography for evaluation. LEVEL OF EVIDENCE IV: IThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Gynecomastia , Mammaplasty , Male , Humans , Gynecomastia/diagnostic imaging , Gynecomastia/surgery , Retrospective Studies , Treatment Outcome , Nipples/surgery , Magnetic Resonance Imaging , Esthetics , Mammaplasty/methods
11.
Clin Exp Rheumatol ; 41(8): 1659-1669, 2023 08.
Article in English | MEDLINE | ID: mdl-37382451

ABSTRACT

OBJECTIVES: Systemic sclerosis (SSc) is characterised by vasculopathy and progressive fibrosis of the skin. The aim of this article is to analyse and summarise the efficacy and safety of autologous fat (AF), stromal vascular fraction (SVF) and adipose-derived stem cell (ADSC) grafting in the treatment of SSc, providing evidence for clinical application. METHODS: The research involves the efficacy and safety of AF, SVF and ADSC grafting in the treatment of patients with SSc. The studies were screened and selected independently by two authors based on pre-specified criteria. The data extraction and quality assessment were also performed independently by two authors. RESULTS: Fifteen studies were eligible for inclusion. Skin thickness reduced following SVF or AF therapy, but there was no significant difference. All measures used to assess fingertip symptoms revealed a significant improvement. Notably, SVF and AF were found to have the most impact on Raynaud's phenomenon improvement. The ADSC group improved the most in terms of finger pain alleviation. SVF reported the highest proportion of adverse events, accounting for approximately half of the cases. CONCLUSIONS: AF, SVF, and ADSC all displayed therapeutic effects of improving SSc, but differences existed in the effects on different symptoms. Plastic surgeons should choose the most suitable treatment strategy after comprehensively evaluating the patient's clinical manifestations.


Subject(s)
Scleroderma, Systemic , Stem Cell Transplantation , Humans , Stem Cell Transplantation/adverse effects , Obesity , Scleroderma, Systemic/therapy , Adipose Tissue/transplantation
12.
Int J Mol Sci ; 20(12)2019 Jun 19.
Article in English | MEDLINE | ID: mdl-31248165

ABSTRACT

Actin filaments are a major component of the cytoskeleton in eukaryotic cells and play an important role in cancer metastasis. Dynamics and reorganization of actin filaments are regulated by numerous regulators, including Rho GTPases, PAKs (p21-activated kinases), ROCKs (Rho-associated coiled-coil containing kinases), LIMKs (LIM domain kinases), and SSH1 (slingshot family protein phosphate 1). Ubiquitination, as a ubiquitous post-transcriptional modification, deceases protein levels of actin cytoskeleton regulatory factors and thereby modulates the actin cytoskeleton. There is increasing evidence showing cytoskeleton regulation by long noncoding RNAs (lncRNAs) in cancer metastasis. However, which E3 ligases are activated for the ubiquitination of actin-cytoskeleton regulators involved in tumor metastasis remains to be fully elucidated. Moreover, it is not clear how lncRNAs influence the expression of actin cytoskeleton regulators. Here, we summarize physiological and pathological mechanisms of lncRNAs and ubiquitination control mediators of actin cytoskeleton regulators which that are involved in tumorigenesis and tumor progression. Finally, we briefly discuss crosstalk between ubiquitination and lncRNA control mediators of actin-cytoskeleton regulators in cancer.


Subject(s)
Actin Cytoskeleton/genetics , Actin Cytoskeleton/metabolism , Gene Expression Regulation, Neoplastic , Neoplasms/genetics , Neoplasms/metabolism , RNA, Long Noncoding/genetics , Animals , Cytoskeleton/metabolism , Disease Progression , Humans , Neoplasms/pathology , Phosphorylation , Signal Transduction , Ubiquitination
13.
Cell Death Dis ; 10(3): 192, 2019 02 25.
Article in English | MEDLINE | ID: mdl-30804330

ABSTRACT

Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy in cancer metastasis is still controversial. Redox-dependent autophagy largely relies on the magnitude and the rate of ROS generation. Thus, we aimed to explore the role of GLDC in cellular autophagy during HCC progression. We showed that a high GLDC expression level is associated with better overall survival and is an independent factor for the favorable prognosis of HCC patients. GLDC overexpression significantly induced cell autophagy, whereas GLDC downregulation reduced cell autophagy. Of note, GLDC is the post-transcriptional target of miR-30d-5p. GLDC overexpression could rescue miR-30d-5p-mediated cell metastasis and increase autophagy. Furthermore, upregulation of GLDC could significantly decrease p62 expression and impair intrahepatic metastasis in vivo. Taken together, our results suggest that GLDC may play an important role to increasing miR-30d-5p-reduced autophagy to suppress HCC progress.


Subject(s)
Autophagy/genetics , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/genetics , Glycine Dehydrogenase (Decarboxylating)/metabolism , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , MicroRNAs/metabolism , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/secondary , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation/genetics , Female , Gene Expression Regulation, Neoplastic , Glycine Dehydrogenase (Decarboxylating)/genetics , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Middle Aged , Prognosis , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Up-Regulation/genetics
14.
Liver Int ; 38(11): 2006-2017, 2018 11.
Article in English | MEDLINE | ID: mdl-29655291

ABSTRACT

BACKGROUND AND AIMS: The role of Ras guanine nucleotide-releasing protein 1 (RasGRP1) in tumourigenesis has been a subject of debate, and its functions and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we evaluated the expression of RasGRP1 in HCC and determined how it contributes to HCC cell proliferation. METHODS: RasGRP1 expression was measured by quantitative polymerase chain reaction (qPCR) and Western blotting of 24 paired HCC tissues and para-tumour tissues. RasGRP1 expression was confirmed by immunohistochemical analysis of a tissue microarray from 1 independent cohort. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and risk factors that contributed to OS or DFS were identified using Cox regression analysis. The biologic relevance of RasGRP1 was examined by small interfering RNAs and an exogenous plasmid construct. Chromatin immunoprecipitation assays were performed to examine the binding of Sp1 to the RasGRP1 promoter. RESULTS: Increased RasGRP1 expression was associated with tumour size (P = .004), tumour-node-metastasis stage (P = .032), and Barcelona Clinic Liver Cancer stage (P = .002). RasGRP1 overexpression was an independent prognostic factor in HCC patients. RasGRP1 downregulation inhibited cell proliferation, whereas RasGRP1 overexpression promoted cell proliferation. Moreover, specificity protein 1 bound to the RasGRP1 promoter and promoted RasGRP1 transcription. In addition, RasGRP1 overexpression enhanced activation of the c-Raf pathway. CONCLUSIONS: RasGRP1 is upregulated in HCC and promotes HCC cell proliferation. Thus, RasGRP1 may be a novel therapeutic target for HCC.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , DNA-Binding Proteins/genetics , Guanine Nucleotide Exchange Factors/genetics , Liver Neoplasms/genetics , Sp1 Transcription Factor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation , DNA-Binding Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Guanine Nucleotide Exchange Factors/metabolism , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Male , Middle Aged , Proto-Oncogene Proteins c-raf/genetics , RNA, Small Interfering , Survival Analysis , Up-Regulation
15.
Free Radic Biol Med ; 120: 1-12, 2018 05 20.
Article in English | MEDLINE | ID: mdl-29524606

ABSTRACT

Metabolic reprogramming is a hallmark of cancer. Glycine decarboxylase (GLDC), an oxidoreductase, plays an important role in amino acid metabolism. While GLDC promotes tumor initiation and proliferation in non-small cell lung cancer and glioma and it was reported as a putative tumor suppressor gene in gastric cancer, the role of GLDC in hepatocellular carcinoma (HCC) is unknown. In the current study, microarray-based analysis suggested that GLDC expression was low in highly malignant HCC cell lines, and clinicopathological analysis revealed a decrease in GLDC in HCC tumor samples. While the knockdown of GLDC enhanced cancer cell migration and invasion, GLDC overexpression inhibited them. Mechanistic studies revealed that GLDC knockdown increased the levels of reactive oxygen species (ROS) and decreased the ratio of glutathione/oxidized glutathione (GSH/GSSG), which in turn dampened the ubiquitination of cofilin, a key regulator of actin polymerization. Consequently, the protein level of cofilin was elevated, which accounted for the increase in cell migration. The overexpression of GLDC reversed the phenotype. Treatment with N-acetyl-L-cysteine decreased the protein level of cofilin while treatment with H2O2 increased it, further confirming the role of ROS in regulating cofilin degradation. In a tumor xenographic transplant nude mouse model, the knockdown of GLDC promoted intrahepatic metastasis of HCC while GLDC overexpression inhibited it. Our data indicate that GLDC downregulation decreases ROS-mediated ubiquitination of cofilin to enhance HCC progression and intrahepatic metastasis.


Subject(s)
Actin Depolymerizing Factors/metabolism , Carcinoma, Hepatocellular/enzymology , Glycine Dehydrogenase (Decarboxylating)/metabolism , Liver Neoplasms/enzymology , Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Down-Regulation , Heterografts , Humans , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness/pathology
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