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A palladium-catalyzed decarboxylative α-allylation of thiazolidinones and azlactones with aza-π-allylpalladium zwitterionic intermediates, in situ generated from sulfonamido-substituted allylic carbonates, is successfully developed. This method allows the formation of a series of structurally diverse 5-alkylated thiazolidinones and 2-piperidones under mild conditions in moderate to high yields (up to 99% yield).
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We aimed to assess the quality of life for head and neck carcinoma (HNC) patients who underwent soft tissue resection and reconstruction with double-paddle peroneal artery perforator (DPAP) free flap. The quality of life was assessed by means of the University of Washington quality of life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14) questionnaires at 12 months postoperatively. Data from 57 patients were retrospectively analysed. Out of these, 51 patients were at TNM stage III or IV. Finally, 48 patients finished and returned the two questionnaires. In the UW-QOL questionnaire, the mean (SD) higher scores were pain 76.5 (6.4), shoulder 74.3 (9.6), and activity 71.6 (6.1), whereas the lower scores were chewing 49.7 (5.2), taste 51.1 (7.7), and saliva (56.7 (7.4). In the OHIP-14 questionnaire, the higher-scoring domains were psychological discomfort (69.3 (9.6) and psychological disability 65.2 (5.8), whereas the lower-scoring domains were handicap 28.7 (4.3) and physical pain 30.4 (8.1). The DPAP free flap significantly improved appearance, activity, shoulder, mood, psychological discomfort, and handicap compared with pedicled pectoralis major myocutaneous flap reconstruction. In conclusion, DPAP free flap for reconstruction of tissue defects after soft tissue resection of HNC significantly improved the patients' QOL compared to pedicled pectoralis major myocutaneous flap reconstruction.
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Carcinoma , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Qualidade de Vida , Estudos Retrospectivos , Dor , ArtériasRESUMO
INTRODUCTION: Hypertrophic scar (HS), a fibroproliferative disorder of the skin with some tumor-like properties, is closely related to dysregulated inflammation. PD-1/PD-L1 inhibitor is a promising medication for cancer therapy as its potent functions on adaptive immune response; whether it could be a candidate for HS therapy has aroused our interest. This study aimed to explore the effect and the mechanism of BMS-202, a PD-1/PD-L1 inhibitor, in HS. METHODS: Ten HS and adjacent normal skin tissues collected from HS patients were used to detect α-SMA, collagen I, and PD-L1 expression by Quantitative reverse transcription-polymerase chain reaction and western blot (WB) analysis. Fibroblasts derived from HS tissues (HFBs) were exposed to diverse concentrations of BMS-202, of which proliferation, migration, apoptosis, and collagen synthesis were evaluated by Cell Counting Kit-8, wound healing, terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End labeling, and [3 H]-proline incorporation assays, respectively. The effect of BMS-202 on α-SMA and collagen I expression, and transforming growth factor beta 1 (TGFß1)/Smad signaling in HFBs was also determined by WB and enzyme-linked immunosorbent assay. RESULTS: The expression level of PD-L1 was significantly elevated in both HS tissues and HFBs, which was positively correlated with α-SMA and collagen I expressions. BMS-202 exerted a significant suppression effect on the cell proliferation, migration, collagen synthesis, and α-SMA and collagen I expression of HFBs in a concentration-dependent way; but did not affect apoptosis. Finally, BMS-202 could reduce the phosphorylation of ERK1/2, Smad2, and Smad3, and the TGFß1 expression once its concentration reached 2.5 nM. CONCLUSION: BMS-202 effectively suppressed proliferation, migration, and extracellular matrix deposition of HFBs, potentially through the regulation of the ERK and TGFß1/Smad signaling pathways.
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Cicatriz Hipertrófica , Inibidores de Checkpoint Imunológico , Antígeno B7-H1/metabolismo , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/terapia , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacologia , DNA Nucleotidilexotransferase/metabolismo , DNA Nucleotidilexotransferase/farmacologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Prolina/metabolismo , Prolina/farmacologia , Transdução de SinaisRESUMO
RNA polymerase mitochondrial (POLRMT) expression and the potential biological functions in skin squamous cell carcinoma (SCC) were explored. We showed that POLRMT is significantly elevated in skin SCC. Genetic depletion of POLRMT, using shRNA-induced knockdown or CRISPR/Cas9-mediated knockout (KO), resulted in profound anti-skin SCC cell activity. In patient-derived primary skin SCC cells or immortalized lines (A431 and SCC-9), POLRMT shRNA or KO potently suppressed mitochondrial DNA (mtDNA) transcription and suppressed cell viability, proliferation and migration. POLRMT shRNA or KO impaired mitochondrial functions in different skin SCC cells, leading to production of ROS (reactive oxygen species), depolarization of mitochondria and depletion of ATP. Moreover, mitochondrial apoptosis cascade was induced in POLRMT-depleted skin SCC cells. IMT1, a POLRMT inhibitor, largely inhibited proliferation and migration, while inducing depolarization of mitochondria and apoptosis in primary skin SCC cells. Contrarily, ectopic overexpression of POLRMT increased mtDNA transcription and augmented skin SCC cell growth. Importantly, POLRMT shRNA adeno-associated virus injection robustly hindered growth of the subcutaneous A431 xenografts in mice. In the POLRMT shRNA virus-treated A431 xenograft tissues, POLRMT depletion, mtDNA transcription inhibition, cell apoptosis, lipid peroxidation and ATP depletion were detected. Together, overexpressed POLRMT increases mtDNA transcription and promotes skin SCC growth.
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Hyperpigmentation is a common complaint and distressing problem in dermatology, and tranexamic acid (TA) is an effective treatment agent but limited by the delivery to melanocytes in the epidermis. Herein, a novel TA naogels (named HA/TA-LP), combining the advantages of liposomes and hyaluronic acid (HA), are prepared and assessed for topical hyperpigmentation treatment with targeting delivery and minimizing epidermal diffusion. Morphological characteristics indicate numerous TA-loaded liposomes packed in HA gels. In vitro cell studies using human A375 melanoma cells show that HA/TA-LP can promote the uptake of TA by targeting delivery with resulting inhibition of tyrosinase activity and melanin production. Guinea pigs are used to construct hyperpigmentation models and investigate the topical delivery and treatment efficacy of HA/TA-LP. In vivo topical delivery studies indicate HA/TA-LP realize the effective delivery into melanocytes with an ideal balance of effective permeability and minimizing epidermal diffusion. Subsequently, hyperpigmentation treatment assessments reveal that HA/TA-LP inhibit tyrosinase activity and melanin production under the radiation of UVB. Our study identifies favorable properties of HA/TA-LP for treating hyperpigmentation, and provides an experimental basis for further clinical application.
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Hiperpigmentação/tratamento farmacológico , Lipossomos/química , Melanócitos/efeitos dos fármacos , Nanogéis/química , Ácido Tranexâmico/farmacologia , Administração Cutânea , Animais , Ascomicetos/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Portadores de Fármacos/química , Cobaias , Humanos , Ácido Hialurônico/química , Monofenol Mono-Oxigenase/efeitos dos fármacos , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/farmacocinéticaRESUMO
The development of hydrogels that support vascularization to improve the survival of skin flaps, yet establishing homogeneous angiogenic niches without compromising the ease of use in surgical settings remains a challenge. Here, pressure-driven spreadable hydrogels were developed utilizing beta-sheet rich silk nanofiber materials. These silk nanofiber-based hydrogels exhibited excellent spreading under mild pressure to form a thin coating to cover all the regions of the skin flaps. Deferoxamine (DFO) was loaded onto the silk nanofibers to support vascularization and these DFO-laden hydrogels were implanted under skin flaps in rats to fill the interface between the wound bed and the flap using the applied pressure. The thickness of the spread hydrogels was below 200 µm, minimizing the physical barrier effects from the hydrogels. The distribution of the hydrogels provided homogeneous angiogenic stimulation, accelerating rapid blood vessel network formation and significantly improving the survival of the skin flaps. The hydrogels also modulated the immune reactions, further facilitating the regeneration of the skin flaps. Considering the homogeneous distribution at the wound sites, improved vascularization, reduced barrier effects and low inflammation, these hydrogels appear to be promising candidates for use in tissue repair where a high blood supply is in demand. The pressure-driven spreading properties should simplify the use of the hydrogels in surgical settings to facilitate clinical translation.
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Hidrogéis , Nanofibras , Pele , Retalhos Cirúrgicos , Animais , Desferroxamina/farmacologia , Ratos , Seda , CicatrizaçãoRESUMO
Hypertrophic Scar (HS) is a complicated fibrotic disease. In addition, its pathogenesis is still to be further explored. Long non-coding RNAs (lncRNAs) have been proved to be participated in multiple diseases, including HS. However, the role of lncRNA TUG1 in HS remains unclear. The expression level of RNA and protein in cells were detected by q-PCR and western blot, respectively. MTT assay was performed to test the cell proliferation. Cell migration was detected by transwell assay. Cell apoptosis was measured by flow cytometry. Dual luciferase report assay and RNA pull down were used to verify the relationship between TUG1, miR-27b-3p and TAK1.TUG1 and TAK1 were upregulated in HS, while miR-27b-3p was downregulated. Knockdown of TUG1 significantly suppressed the proliferation and migration and induced the apoptosis of HS fibroblasts (HSF). In addition, silencing of TUG1 notably inhibited the extracellular matrix (ECM) biosynthesis in HSF. Overexpression of miR-27b-3p has the same effect on HS as that of TUG1 knockdown. Meanwhile, TUG1 could sponge miR-27b-3p, and TAK1 was the direct target of miR-27b-3p. Furthermore, knockdown of TUG1 significantly suppressed the fibrosis in HS via miR-27b-3p/TAK1/YAP/TAZ axis mediation. LncRNA TUG1 promotes the fibrosis in HS via sponging miR-27b-3p and then activates TAK1/YAP/TAZ pathway, which may serve as a potential target for treatment of HS.
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Proteínas de Ciclo Celular/metabolismo , Cicatriz Hipertrófica/patologia , Fibrose/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MAP Quinase Quinase Quinases/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição/metabolismo , Apoptose , Biomarcadores/metabolismo , Proteínas de Ciclo Celular/genética , Movimento Celular , Proliferação de Células , Células Cultivadas , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Fibrose/genética , Fibrose/metabolismo , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , MAP Quinase Quinase Quinases/genética , MicroRNAs/genética , Prognóstico , Fatores de Transcrição/genética , Proteínas com Motivo de Ligação a PDZ com Coativador TranscricionalRESUMO
BACKGROUND: Auricular concha has been widely used as a supporting material in rhinoplasty or repairing of auricular defects. However, complications, trauma or iatrogenic excision often result in concha defects which destroy the normal structure of the external ear and further influence daily life. Local flaps are often applied to repair the defects because of their safety and satisfactory functional and aesthetic results. CASE PRESENTATION: We report a 24-year-old female who presented with a concha defect that resulted from a complication of concha cartilage graft for rhinoplasty. The anterior concha defect was covered by a revolving-door (RD) flap as a single-stage procedure. The aesthetic and functional outcomes were satisfactory at 6 months post operation. CONCLUSION: We recommend the RD flap as an excellent choice for conchal defect reconstruction. Satisfactory aesthetic and functional results can be achieved by this easy-to-learn technique in relatively short surgical time.
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Orelha Externa , Procedimentos de Cirurgia Plástica , Adulto , Pavilhão Auricular/cirurgia , Orelha Externa/cirurgia , Feminino , Humanos , Doença Iatrogênica , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Retalhos Cirúrgicos , Adulto JovemRESUMO
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous malignancy with an incidence rate increasing each year. Glutathione S-transferase A3 (GSTA3), a member of the glutathione S-transferase family, is considered an antioxidative protease, but its role in cSCC remains unclear. AIM: The present study was designed to explore the effect of GSTA3 on cSCC. PATIENTS/METHODS: Through previous systematic studies, we screened GSTA3 to be a key gene with lower expression in cSCC. In the present study, we selected cSCC tissues and para-carcinoma tissue specimens from 20 patients in plastic surgery department. A431 cells were treated with GSTA3 transfection. The cell proliferation, apoptosis, colony formation, and cell migration as well as invasion were examined, respectively. And the expressions of GSTA3, TGF-ß/Smad, and HIF-1α signalings were measured by Western blot and qRT-PCR. RESULTS: GSTA3 was downregulated in both cSCC tissues and A431 cells. Additionally, overexpression of GSTA3 induced a phenotype with a lower degree of malignancy, while GSTA3 silencing induced more malignant phenotypes, including cell proliferation, colony formation, apoptosis, migration, and invasion. Moreover, we found that the TGF-ß/Smad2/3 and HIF-1α signalings were activated in cSCC under hypoxic conditions. CONCLUSION: GSTA3 could inhibit cSCC progression through suppression of the TGF-ß/Smad and HIF-1α signalings. Therefore, GSTA3 may prove to be a prospective therapeutic target for cSCC.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Glutationa Transferase/genética , Humanos , Estudos Prospectivos , Neoplasias Cutâneas/genéticaRESUMO
BACKGROUND: Random skin flap is widely used to repair tissue defects; however, it is often accompanied by ischemia and necrosis of the distal flap due to inferior axial vascularity. Even though different drugs, biomaterials, and stem cell therapies have been developed to improve the survival of random flap, evaluating the promotion of flap survival remains a big challenge. Based on successful clinical practice, we designed a "Pingpong racket" shape flap in the rat. Without the predetected blood vessels procedure, the "pingpong racket" flap provides a preferable option to evaluate the function of drugs and biomaterials in promoting flap survival. MATERIALS AND METHODS: "Pingpong racket" dorsal flaps with different pedicle lengths were developed in the rats. The survival area was evaluated by digital photography and computer-assisted analysis. The quantitative survival area was considered a useful indicator for analyzing drugs' applicability in improving skin flap survival. RESULTS: A new model with a pedicle width of 1 cm and a flap diameter of 3 cm, in which the length of the pedicle could be tuned, was established. No iliolumbar vessels passed through the pedicle. The necrosis ratio ( round ) of the flap was 29.88% in the 2 cm long pedicle, 74.69% in the 3 cm long pedicle, 95.52% in the 4 cm long pedicle, and in the 5 cm long pedicle; necrotic area could be found in both the round part and in the pedicle. CONCLUSION: The new 3 cm long pedicle flap is suitable for evaluating the drugs for promoting skin flap survival. Rat dorsal "Pingpong racket" flap can be easily handled, thus avoiding blood vessels' detection. The flap could achieve comparable results to clinical and alleviate the negative influence of the flap's longitudinal contraction. Besides, it is intuitive and aesthetically pleasing.
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Transplante de Pele , Retalhos Cirúrgicos , Animais , Necrose , RatosRESUMO
BACKGROUND: Burns are common traumas that cause systemic symptoms by increasing vascular permeability. OBJECTIVES: To investigate the role of miRNA-451 and to clarify the underlying mechanism of the burn process. MATERIAL AND METHODS: We established a heat-induced third-degree burn with acute lung injury (ALI) model in rats. Hematoxylin and eosin (H&E) staining and in situ hybridization were performed. Overexpressed miRNA-451 in human umbilical vascular endothelial cells (HUVEC) were carried out. The migration and proliferation of HUVEC cells were examined. RESULTS: The H&E staining showed that the burn injury caused by heat went through the dermis and damaged deep tissues. Meanwhile, the heat also induced acute lung injury, characterized by inflammatory exudation in the alveoli and significant enlargement of the alveolar septum. In situ hybridization showed that the expression of miRNA-451 increased in the lung endothelial cells. We overexpressed miRNA-451 in human umbilical vascular endothelial cells (HUVEC) and the results showed that miRNA-451 inhibited the migration and proliferation of HUVEC cells, increased HUVEC cell permeability, inhibited cell adhesion, and induced cell apoptosis. Furthermore, the expression of occludin and ZO-1, 2 key protein molecules in forming tight junction between cells, decreased, and the proteins dispersed in the cytoplasm of HUVEC cells. CONCLUSIONS: MiRNA-451 was upregulated in the lung endothelial cells of the rat model, and contributed to increase lung endothelial cell permeability. It suppresses angiogenesis of lung endothelial cells, indicating their potential as a target in the treatment of burn injuries.
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Queimaduras , Lesão Pulmonar/genética , Animais , Permeabilidade Capilar , Células Endoteliais , Pulmão , MicroRNAs/genética , Neovascularização Patológica , Permeabilidade , RatosRESUMO
Tissue engineering cartilage is a promising strategy to reconstruct the craniofacial cartilaginous defects. It demands plenty of chondrocytes to generate human-sized craniofacial frameworks. Partly replacement of chondrocytes by adipose-derived stem cells (ADSCs) can be an alternative strategy.The study aimed at evaluating the chondrogenic outcome of ADSCs and chondrocytes in direct co-culture with transforming growth factor-beta (TGF-ß3). Porcine ADSCs and chondrocytes were obtained from abdominal wall and external ears. Four groups: ADSCs or chondrocytes monocultured in medium added with TGF-ß3; ADSCs and ACs co-cultured with or without TGF-ß3. Cell growth rate was performed to evaluate the cell proliferation. Morphological, histologic and real-time polymerase chain reaction analysis were performed to characterize the chondrogenic outcome of pellets. ADSCs had favorable multi-lineage differentiation potential. Further, when ADSCs were co-cultured with chondrocytes in medium added with TGF-ß3, the cell proliferation was promoted and the chondrogenic differentiation of ADSCs was enhanced. We demonstrate that pellet co-culture of ADSCs and chondrocyte with TGF-ß3 could construct high quantity cartilages. It suggests that this strategy might be useful in future cartilage repair.
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Adipócitos/citologia , Tecido Adiposo/citologia , Condrócitos/citologia , Células-Tronco/citologia , Fator de Crescimento Transformador beta3/farmacologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Animais , Diferenciação Celular , Proliferação de Células , Condrócitos/efeitos dos fármacos , Condrogênese , Técnicas de Cocultura , Células-Tronco/efeitos dos fármacos , Suínos , Engenharia TecidualRESUMO
Melanoma is a malignant skin cancer type associated with a high mortality rate, but its treatment is currently not ideal. Both microRNA (miR)214 and cell adhesion molecule 1 (CADM1) are differentially expressed in melanoma, but their role in this cancer type remains unknown. Therefore, the aim of the present study was to investigate the role of CADM1 and miR214 in melanoma to identify novel targets for its treatment. The expression levels of CADM1 and miR214 in cells were detected by reverse transcriptionquantitative PCR (RTqPCR). Moreover, cell viability, migration and invasion were measured by MTT, wound healing and Transwell assays, respectively. In addition, the relative expression levels of epithelialmesenchymal transition (EMT)related proteins in cells were detected by RTqPCR and western blotting. It was found that the expression of CADM1 was inhibited in melanoma cells, while miR214 expression was increased during melanoma tumorigenesis. Furthermore, miR214 mimics promoted the viability, migration and invasion of melanoma cells. It was also demonstrated that the downregulation of CADM1 reversed the inhibitory effect of the miR214 inhibitor in melanoma. Moreover, overexpression of CADM1 inhibited the EMT process in melanoma, while the miR214 inhibitor suppressed the EMT process. The results also indicated that miR214 promoted the EMT process by downregulating CADM1, which may represent a novel mechanism for the progression of melanoma.
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Molécula 1 de Adesão Celular/metabolismo , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , MicroRNAs/metabolismo , Neoplasias Cutâneas/metabolismo , Molécula 1 de Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Progressão da Doença , Humanos , Melanoma/patologia , MicroRNAs/genética , NF-kappa B/metabolismo , Invasividade Neoplásica/genética , Transdução de Sinais/genética , Neoplasias Cutâneas/patologia , TransfecçãoRESUMO
Clinically deficient cartilage is difficult to regenerate, and the availability of chondrocytes is very limited. However, human adipose-derived stem cells (ADSCs) can be obtained easily and in sufficient quantities. Therefore, we will find a way of replacing chondrocytes with fat stem cells to solve the problem of seed cell origin. Previous studies have revealed that transforming growth factor-ß (TGF-ß) can promote chondrocyte differentiation and maturation. In this study, we found that TGF-ß3 in the transforming growth factor family can effectively promote the transformation process from fat stem cells to chondrocytes, thus promoting chondrogenesis. At the same time, we also further reviewed and considered the mechanism of this process. Through flow cytometry, immunohistochemical, fluorescent microscopy, qRCR, Wb etc., we found that TGF-ß3 mainly plays a role through wnt5a/ß-catenin, promoting human fat stem cell growing into the cartilage. This discovery is expected to provide new ideas in the field of cartilage regeneration.
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Condrócitos/citologia , Condrogênese , Células-Tronco Mesenquimais/citologia , Fator de Crescimento Transformador beta3/metabolismo , Agrecanas/análise , Agrecanas/metabolismo , Cartilagem/citologia , Cartilagem/metabolismo , Diferenciação Celular , Células Cultivadas , Condrócitos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Engenharia TecidualRESUMO
We report here the clinical, genetic, and molecular characteristics of type 2 diabetes in a Chinese family. There are differences in the severity and age of onset in diabetes among these families. By molecular analysis of the complete mitochondrial genome in this family, we identified the homoplasmic m.15897G>A mutation underwent sequence analysis of whole mitochondrial DNA genome, which localized at conventional position ten of tRNAThr, and distinct sets of mtDNA polymorphisms belonging to haplogroup D4b1. This mutation has been implicated to be important for tRNA identity and stability. Using cybrid cell models, the decreased efficiency of mitochondrial tRNAThr levels caused by the m.15897G>A mutation results in respiratory deficiency, protein synthesis and assembly, mitochondrial ATP synthesis, and mitochondrial membrane potential. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cell lines. These data provide a direct evidence that a novel tRNA mutation was associated with T2DM. Thus, our findings provide a new insight into the understanding of pathophysiology of maternally inherited diabetes.
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Diabetes Mellitus Tipo 2/genética , RNA de Transferência de Treonina/genética , Adulto , Idoso , Povo Asiático/genética , Northern Blotting , Western Blotting , China , Diabetes Mellitus Tipo 2/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Genoma Mitocondrial , Humanos , Masculino , Herança Materna , Potencial da Membrana Mitocondrial/genética , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Linhagem , Filogenia , Mutação Puntual , Espécies Reativas de Oxigênio/metabolismoRESUMO
Keloids are considered to be a type of benign tumor. MicroRNAs have been reported to be involved in the formation and growth of keloids. MicroRNA-4328 (miR-4328) was found to be abnormally expressed in keloids, while the role and the detailed molecular mechanism of miR-4328 in keloids remain unclear. The expression of miR-4328 and B-cell lymphoma 2 (BCL2) mRNA was detected by qRT-PCR. The proliferation, migration, invasion and apoptosis of keloid fibroblasts (KFs) was examined using Cell Counting Kit-8 assay, transwell assay or flow cytometry, respectively. Western blot was used to detect the level of proliferating cell nuclear antigen, cleaved-caspase 3, collagen I, collagen III and BCL2 protein. The interaction between miR-4328 and BCL2 was confirmed by luciferase reporter analyses. It was observed that miR-4328 was down-regulated in keloid tissues and fibroblasts, and miR-4328 restoration mediated the inhibition of proliferation, metastasis, collagen synthesis and the promotion of apoptosis in KFs. BCL2 was up-regulated in keloid tissues and fibroblasts, and BCL2 knockdown promoted the deterioration of KFs. In addition, BCL2 was confirmed to be a target of miR-4328, and the rescue experiment indicated that the inhibitory action of miR-4328 on keloid fibroblast progression was reversed by BCL2 overexpression. Thus, our results demonstrated that miR-4328 restrained the deterioration of KFs by targeting BCL2, which sheds new light on miR-4328 as a promising target for keloid development and therapeutic.
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INTRODUCTION: Diabetic foot ulcers (DFUs) are the most common foot injuries leading to lower extremity amputation in diabetic patients. Recent studies showed that long non-coding RNAs (lncRNAs) played important roles in diverse biological processes. In this study, we focused on identifying differentially expressed long non-coding RNAs (lncRNAs) in DFU. MATERIAL AND METHODS: Real-time PCR assay was performed to validate the expression pattern of lncRNAs in DFU. Moreover, co-expression networks were also constructed to identify hub lncRNAs in DFU. Specifically, gene ontology (GO) analysis was first performed to evaluate the potential roles of differentially expressed genes (DEGs) and lncRNAs in DFU. RESULTS: In the present study, we identified 58 up-regulated lncRNAs and 42 down-regulated lncRNAs in DFU samples compared to non-diabetic foot skin samples by analyzing the GSE68186 dataset. Four lncRNAs (FLJ30679, LINC01193, LINC00692, and LINC00641) were observed to be up-regulated in DFU. Furthermore, we found that the down-regulated lncRNA-mediated co-expression network contained 42 lncRNAs and 700 DEGs and the up-regulated lncRNA mediated co-expression network contained 58 lncRNAs and 688 DEGs. CONCLUSIONS: Bioinformatics analysis showed that differentially expressed lncRNAs were involved in regulating the ERK1 and ERK2 cascade, secondary alcohol biosynthetic process, centrosome duplication and DNA repair. These results suggested the potential prognostic value of lncRNAs in DFU.
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OBJECTIVE: To investigate the effectiveness of free-style perforator flap in repairing the soft tissue defect of knee. METHODS: Between December 2011 and October 2017, 13 patients with the soft tissue defects of knees were repaired with the free-style perforator flaps. There were 9 males and 4 females, with an average age of 40 years (range, 14-65 years). The injuries were caused by traffic accident in 7 cases, crushing in 4 cases, and falling from height in 2 cases. The soft tissue defects in 9 cases formed after 2 weeks-2 months (mean, 1 month) of lower extremity fractures fixation. The other 4 cases were urgently admitted to the hospital after injury, and the time from injury to admission was 0.5-18.0 hours (mean, 8 hours). The size of soft tissue defect ranged from 3 cm×2 cm to 12 cm×8 cm after debridement. Nine propeller flaps, 6 rotating flaps, and 2 V-Y advanced flaps were used; and 9 cases were repaired by single flap and 4 cases were repaired by combined flaps. The size of flap ranged from 7.5 cm×2.5 cm to 20.0 cm×6.0 cm. The donor sites were sutured directly. RESULTS: The flaps survived smoothly and incisions healed by first intention in 12 cases. The congestion occurred in 1 case, which obtained delayed healing after symptomatic treatment. All incisions at donor sites healed by first intention. All patients were followed up 3-24 months with an average of 6 months. The shape and motions of knee were satisfactory. CONCLUSION: The free-style perforator flap can maximize the utilization of the donor area around the knee wound, with reliable blood supply, small trauma, and easy operation. It is an ideal flap for the soft tissue defect of knee.
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Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pele , Resultado do Tratamento , Adulto JovemRESUMO
Here we report on the interventions taken to treat a patient exposed to high-dose radiation and provide a protocol for treating such patients in the future. The patient, Mr. Wang, was a 58-year-old male janitor who was accidentally exposed to a 192Ir source with an activity of 966.4 GBq or 26.1 Ci. The dose estimated to the lower right limb was 4,100 Gy, whereas the whole-body effective dose was 1.51 Gy. The diagnosis was made according to the results of the patient dose estimation and clinical manifestations. Systemic treatment included stimulating bone marrow hematopoietic cells, enhancing immunity, anti-infection and vitamin supplements. The treatment of radiation-induced skin lesions consisted of several debridements, two skin-flap transplantations and application of mesenchymal stem cells (MSCs). Skin-flap transplantations and MSCs play important roles in the recovery of skin wound. A combination of antibiotics and antimycotic was useful in reducing inflammation. The application of vacuum sealing drainage was effective in removing necrotic tissue and bacteria, ameliorating ischemia and hypoxia of wound tissue, providing a fresh wound bed for wound healing and improving skin or flap graft survival rates. The victim survived the accident without amputation, and function of his highly exposed right leg was partially recovered. These results demonstrate the importance of collaboration among members of a multidisciplinary team in the treatment of this patient.
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Acidentes , Radioisótopos de Irídio/efeitos adversos , Doses de Radiação , Exposição à Radiação/efeitos adversos , Lesões por Radiação/terapia , China , Humanos , Lesões por Radiação/etiologiaRESUMO
Tumescent anesthesia makes it feasible to perform liposuction in an office setting. There are often patients who desire extensive liposuction on approximately 30% of total body surface area, which means the potential of fluid overload. In this study, the charts of 83 patients undergoing extensive liposuction were retrospectively reviewed. The intra-operative fluid ratio was 1.66 for the extensive liposuction. There were no episodes of pulmonary edema, congestive heart failure exacerbation, or other major complications. The average urine output in the operating room, the recovery room, and while on the floors was 1.35, 2.3, and 1.4âmL/kg/hour respectively. Intravenous (IV) fluid administration during operation was minimized to approximately 300 to 500âmL. The total volume of IV injection was also reduced to less than 1500 mL when the patient was in the recovery room and on the hospital floor. Our fluid management strategy in extensive liposuction reflects minimal risk of volume overload. Foley catheters are not applied and patients could resume oral intake in usual, so they can discharge after 6âhours of recovery room stay in our daily practice.