Proteomic analysis illustrates the potential involvement of motor proteins in cleft palate development.

Cleft palate (CP) is a congenital condition characterized by a complex etiology and limited diagnostic and therapeutic options. In this study, we delved into the molecular mechanisms associated with retinoic acid (RA)-induced CP in Kun Ming mice. Proteomic analysis of control and RA-induced CP samples at embryonic day 15.5 revealed 25 upregulated and 19 downregulated proteins. Further analysis identified these differentially expressed proteins (DEPs) as being involved in extracellular matrix organization, actin cytoskeleton, and myosin complex. Moreover, these DEPs were found to be enriched in pathways related to motor protein activity and extracellular matrix-receptor interaction. Protein-protein interaction network analysis identified 10 hub proteins, including motor proteins and ECM-related proteins, which exhibited higher expression levels in CP compared to control tissues. These findings provide insights into the molecular mechanisms underlying CP and highlight potential targets for diagnostic and therapeutic purposes.

Single-cell sequencing analysis and bulk-seq identify IGFBP6 and TNFAIP6 as novel differential diagnosis markers for postburn pathological scarring.

BACKGROUND: If not accurately diagnosed and treated, postburn pathological scars, such as keloids and hypertrophic scars, can lead to negative clinical outcomes. However, differential diagnosis at the molecular level for postburn pathological scars remains limited. Using single-cell sequencing analysis, we investigated the genetic nuances of pathological scars at the cellular level. This study aimed to identify molecular diagnostic biomarkers to distinguish between postburn keloids and hypertrophic scars. METHODS: Single-cell sequencing, differential expression, and weighted co-expression network analyses were performed to identify potential key genes for discriminating between keloids and hypertrophic scars. Postburn clinical samples were collected from our centre to validate the expression levels of the identified key genes. RESULTS: Single-cell sequencing analysis unveiled 29 and 30 cell clusters in keloids and hypertrophic scars, respectively, predominantly composed of fibroblasts. Bulk differential gene analysis showed 96 highly expressed genes and 69 lowly expressed genes in keloids compared to hypertrophic scars. By incorporating previous research, Gene Set Enrichment Analysis was conducted to select fibroblasts as the focus of research. According to the single-cell data, 301 genes were stably expressed in fibroblasts from both types of pathological scars. Consistently, Weighted Gene Co-expression Network Analysis revealed that the blue module genes were mostly hub genes associated with fibroblasts. After intersecting fibroblast-related genes in single-cell data, Weighted Gene Co-expression Network Analysis-hub module genes, and bulk differential expression genes, insulin-like growth factor binding protein 6 and tumour necrosis factor alpha-induced protein 6 were identified as key genes to distinguish keloids from hypertrophic scars, resulting in diagnostic accuracies of 1.0 and 0.75, respectively. Immunohistochemical Staining and Quantitative Reverse Transcription PCR revealed that the expression levels of tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6 were significantly lower in postburn keloids than in hypertrophic scars- CONCLUSIONS: Tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6, exhibiting high diagnostic accuracy, provide valuable guidance for the differential diagnosis and treatment of postburn pathological scars.

GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. METHODS: SiRNA transfection, wound - healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. RESULTS: The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. CONCLUSION: In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA-mRNA functional network and a new potential therapeutic target for SKCM.

Academic visualization study of aesthetic medicine management and related legal research since 2000.

BACKGROUND: Aesthetics medicine, a controversial branch of clinical medicine known for its high degree of commercialization, faces numerous conflicts, particularly in some developing countries. The global aesthetics medicine industry requires enhancements of its legal and supervision framework and risk management systems. AIMS: This paper aimed to provide a comprehensive visual analysis of academic achievements related to regulatory and legal issues in the field of aesthetic medicine and to identify its development trends and research hotspots. METHODS: The Web of Science Core Collection was employed to retrieve relevant studies, resulting in a total of 602 research articles after selection. Utilizing bibliometric methods and CiteSpace, this study analyzed the primary countries, institutions, authors, journals, hotspots, frontiers, and trends in this domain. RESULTS: The findings indicated rapid increases in the number of published papers. The United States emerged as the leading contributor with 131 research papers and the highest intermediate centrality. Eleven keyword clusters were identified, with "adolescence" and "office-based surgery" being the most recent topics. We also analyzed the trends and frontiers of legal research in medical aesthetics. CONCLUSION: The importance of informed consent has been increasingly emphasized, and research in the field of medical aesthetics has been gradually expanding beyond individual cosmetic procedures. The management system has become more comprehensive, moreover, guidelines and medical laws have been continually published, with research shifting toward a holistic perspective that encompasses patients, medical aesthetic providers, and regulatory authorities in the study of medical aesthetics regulation and legislation. This paper also proposes some innovative directions for future research and applications.

The role of FGF-21 in promoting diabetic wound healing by modulating high glucose-induced inflammation.

Background: Wound healing is a complex biological process that can be impaired in individuals with diabetes. Diabetic wounds are a serious complication of diabetes that require promoting diagnosis and effective treatment. FGF-21, a member of the endocrine FGF factors family, has caught the spotlight in the treatment of diabetes for its beneficial effects on accelerating human glucose uptake and fat catabolism. However, the therapeutic efficacy of FGF-21 in promoting diabetic wounds remains unknown. This study aims to evaluate the therapeutic potential of FGF-21 in promoting diabetic wound healing. Methods: we investigated the effects of FGF-21 on wound healing related-cells under high-glucose conditions using various assays such as CCK8, scratch assay, flow cytometry analysis, endothelial tube-formation assay, and transmission electron microscopy. Furthermore, we used db/db mice to verify the healing-promoting therapeutic effects of FGF-21 on diabetic wounds. We also conducted qRT-PCR, Western blot, and immunofluorescence staining analyses to elucidate the underlying mechanism. Result: Our results indicate that FGF-21 treatment restored hyperglycemic damage on endothelial cell proliferation, migration, and tube-forming ability. It also reduced endothelial cell death rates under high-glucose conditions. TEM analysis showed that FGF-21 treatment effectively restored mitochondrial damage and morphological changes in endothelial cells caused by glucose. Additionally, qRT-PCR and Western blot analysis indicated that FGF-21 treatment restored inflammatory responses caused by hyperglycemic damage. Animal experiments confirmed these findings, suggesting that FGF-21 may be a promising candidate for the treatment of non-healing diabetic wounds due to its effectiveness in stimulating angiogenesis and anti-inflammatory function. Conclusion: Our study provides evidence that FGF-21 is an essential regulator of wound-related cells under high-glucose conditions and has the potential to be a novel therapeutic target for accelerating diabetic wound healing.

Enhancing cellular behavior in repaired tissue via silk fibroin-integrated triboelectric nanogenerators.

Triboelectric nanogenerators (TENGs) have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic devices. Despite their potential benefits, the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and efficacy. Therefore, further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical applications. In this study, we present a flexible silk fibroin-based triboelectric nanogenerator (SFB-TENG) that features an on-skin substrate and is characterized by excellent skin compliance and air/water permeability. The range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926, NIH-3T3 and RSC96 cells. However, apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 Hz. In addition, the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 cells. This research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design, as well as its safe operating conditions for use in biomedical applications. These findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration.

Exploration of the Changes in Facial Microbiota of Maskne Patients and Healthy Controls Before and After Wearing Masks Using 16 S rRNA Analysis.

Whether in the field of medical care, or in people's daily life and health protection, the importance of masks has been paid more and more attention. Acne, the most common complication after wearing masks, which is also called maskne, has been successfully introduced into the common language as a common topic of dermatologist consultations. This study aims to study the changes of microflora in maskne patients and healthy controls before and after wearing masks. In the summer of 2023, we collected a total of 50 samples from 15 maskne patients and 10 healthy controls before and after wearing surgical masks for a long time. 16 S ribosomal DNA sequencing and identification technology with V3-V4 variable region were adopted to explore the microbiome changes caused by mask wearing, analyze the changes in microbial diversity, and make interaction network. LDA effect size analysis was used to identify which bacteria showed significant changes in their relative abundance from phylum to genus. After wearing a mask, the microbiome of the maskne patients changed significantly more than that of the healthy controls, with both α diversity and ß diversity lower than those of maskne patients before wearing masks and those of healthy controls after wearing masks. Co-occurrence network analysis showed that compared with other groups, the network of maskne patients after wearing masks for a long time had the lowest connectivity and complexity, but the highest clustering property, while the opposite was true for healthy controls. Many microbes that are potentially beneficial to the skin decreased significantly after wearing a mask. There was almost no difference in healthy controls before and after wearing a mask.

Elastic parameter identification of three-dimensional soft tissue based on deep neural network.

In the field of virtual surgery and deformation simulation, the identification of elastic parameters of human soft tissues is a critical technology that directly affects the accuracy of deformation simulation. Current research on soft tissue deformation simulation predominantly assumes that the elasticity of tissues is fixed and already known, leading to the difficulty in populating with the elasticity measured or identified from specific tissues of real patients. Existing elasticity modeling efforts struggle to be implemented on irregularly structured soft tissues, failing to adapt to clinical surgical practices. Therefore, this paper proposes a new method for identifying human soft tissue elastic parameters based on the finite element method and the deep neural network, UNet. This method requires only the full-field displacement data of soft tissues under external loads to predict their elastic distribution. The performance and validity of the algorithm are assessed using test data and clinical data from rhinoplasty surgeries. Experiments demonstrate that the method proposed in this paper can achieve an accuracy of over 99% in predicting elastic parameters. Clinical data validation shows that the predicted elastic distribution can reduce the error in finite element deformation simulations by more than 80% at the maximum compared to the error with traditional uniform elastic parameters, effectively enhancing the computational accuracy in virtual surgery simulations and soft tissue deformation modeling.

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis.

Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.

The Usage of Mesh and Relevant Prognosis in Implant Breast Reconstruction Surgery: A Meta-analysis.

BACKGROUND: Although mesh-based implant breast reconstruction surgery is emerging as the primary surgical procedure for breast reconstruction, mesh use remains controversial in implant breast reconstruction surgery, especially in terms of how to select the ideal mesh. Our aim is to elaborate relevant prognosis in the mesh-based implant breast reconstruction surgery. METHODS: Relevant studies were identified from PubMed, Web of Science, EMBASE, and Cochrane library searches. Extracted data included study type, basic characteristics, mesh information, complications, etc. We analyzed the included cohort studies and randomized controlled trials that reported mesh-related implant breast reconstruction complications and breast quality scale scores. RESULTS: A total of 32 studies including 7475 subjects were included. The results showed that the overall complication rate was 2.07 times higher in the biological mesh group than in the synthetic mesh group (risk ratio [RR]: 2.07, 95% CI 1.14-3.78). The risk of seroma was 4.50 times higher in the biological mesh group than in the synthetic mesh group (RR: 4.50, 95% CI 2.27-8.95). In terms of comparing breast quality scale scores, the mesh group had scores that were 1.49 (95% CI 0.19-2.78) higher than the non-mesh group for "physical well-being" and 2.05 (95% CI 0.08-4.02) higher for "sexual well-being." CONCLUSIONS: Our study found that the risk of total complications was higher with biological mesh than with synthetic mesh in implant breast reconstruction surgery. Based on short-term cost, healthcare burden, and healthcare benefits, synthetic meshes are superior to biological meshes. LEVEL OF EVIDENCE III: This 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 .

The systemic inflammation indexes after admission predict in-hospital mortality in patients with extensive burns.

PURPOSE: To explore the clinical value of various complete blood count (CBC)-derived inflammation indicators to predict in-hospital mortality in patients with extensive burns. METHODS: Systemic inflammation indexes, including lymphocyte-platelet ratio (LPR), neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), neutrophil-to-lymphocyte * platelet (NLPR), systemic inflammation index (SII), and systemic inflammation response index (SIRI) on days 1, 3, and 7 after admission were calculated in 135 patients with extensive burns. RESULTS: We included 135 patients with extensive burns, including 97 survivors and 38 non-survivors. After adjusting for confounders, only the LPR on day 1, NLPR on days 3 and 7 were significantly associated with survival (OR= 1.237, 1.097, 1.104; 95 % CI: 1.055-1.451, 1.002-1.202, 1.005-1.212; respectively) in the analysis of multivariate logistic regression. The optimum cutoff values of the LPR on day 1 and NLPR on day 3 were 6.37 and 8.06, and the area under the curves (AUC) were 0.695 and 0.794, respectively. The AUC of NLPR on day 7 had the highest value, 0.814, and the optimum cut-off value was 3.84. The efficacy of LPR on day 1, NLPR on days 3 and 7 combined with the burn prognostic score index in predicting the prognosis of patients was higher than that of the burn index alone, and the three composite inflammatory indexes combined with PBI had the highest efficacy in predicting the prognosis (AUC = 0.994). Kaplan-Meier survival analysis showed poor prognosis in patients with higher LPR on day 1 and higher NLPR on days 3 and 7 (log-rank χ2 =9.623,31.564, 20.771, respectively; P < 0.01). CONCLUSIONS: LPR on day 1 and NLPR on days 3 and 7 after admission are reliable predictors of prognosis in patients with severe extensive burns. The combination of the burn prognostic score index, LPR on day 1, and NLPR on days 3 and 7 was superior to the burn indexes alone in predicting a patient's prognosis.

Development of pro-angiogenic skin substitutes for wound healing.

Wounds pose significant challenges to public health, primarily due to the loss of the mechanical integrity and barrier function of the skin and impaired angiogenesis, causing physical morbidities and psychological trauma to affect patients. Reconstructing the vasculature of the wound bed is crucial for promoting wound healing, reducing scar formation and enhancing the quality of life for patients. The development of pro-angiogenic skin substitutes has emerged as a promising strategy to facilitate vascularization and expedite the healing process of burn wounds. This review provides an overview of the various types of skin substitutes employed in wound healing, explicitly emphasising those designed to enhance angiogenesis. Synthetic scaffolds, biological matrices and tissue-engineered constructs incorporating stem cells and primary cells, cell-derived extracellular vesicles (EVs), pro-angiogenic growth factors and peptides, as well as gene therapy-based skin substitutes are thoroughly examined. The review summarises the existing challenges, future directions and potential innovations in pro-angiogenic dressing for skin substitutes. It highlights the need for continued research to develop new technologies and combine multiple strategies and factors, and to overcome obstacles and advance the field, ultimately leading to improved outcomes for wound patients.

POU2F2-mediated upregulation of lncRNA PTPRG-AS1 inhibits ferroptosis in breast cancer via miR-376c-3p/SLC7A11 axis.

Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC.

Triple-negative breast cancer (TNBC) is a kind of breast cancer with high recurrence and low survival rates. Activation of the ferroptosis pathway can inhibit BC proliferation and distant metastasis. Therefore, identifying effective biomarkers and molecular mechanisms of ferroptosis in TNBC is important for its earlier detection and therapy. PTPRG-AS1 is a new type of lncRNA discovered in recent years that is increased in various diseases and is related to prognosis. In the present study, the authors found that POU2F2 promoted PTPRG-AS1 transcription. PTPRG-AS1 knockdown activated ferroptosis in TNBC and inhibited proliferation. Mechanistically, PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11, thereby inhibiting ferroptosis and promoting TNBC development. These results indicate that PTPRG-AS1 is a possible therapeutic target in TNBC.

[Retracted] MicroRNA­138 suppresses proliferation, invasion and glycolysis in malignant melanoma cells by targeting HIF­1α.

[This retracts the article DOI: 10.3892/etm.2016.3220.].

A bibliometric study: Relevant studies on scar laser therapy since the 21st century.

To summarise research studies on scar laser therapy since the 21st century using bibliometric methods, and to speculate on the possible development in the future. The literature about scar laser therapy in Web of Science database was searched. CiteSpace and VOSviewer were used to analyse main countries, institutions, journals，subject hotspots and trends, etc. A total of 884 papers have been published since the 21st century. These publications were written by 653 authors from 515 institutions in 58 countries. The United States published 287 papers in this field and ranks first. Laser in Surgery and Medicine is the most widely published journal, with Shumaker as the core author. The main keyword clustering includes terms such as combination therapy, wound healing, fractional photothermolysis, experience, scar formation, etc. CiteSpace and VOSviewer were used to sort out and summarise the countries, institutions, authors, journals, research hotspots and frontier topics of related literature about scar laser therapy since the 21st century. The current situation of its application and basic scientific research in clinical treatments were summarised briefly. This provides a new idea for the development and research of scar laser therapy in the future.

Astragaloside IV promotes exosome secretion of endothelial progenitor cells to regulate PI3KR2/SPRED1 signaling and inhibit pyroptosis of diabetic endothelial cells.

BACKGROUND AIMS: Treating chronic non-healing diabetic wounds and achieving complete skin regeneration has always been a critical clinical challenge. METHODS: In order to address this issue, researchers conducted a study aiming to investigate the role of miR-126-3p in regulating the downstream gene PIK3R2 and promoting diabetic wound repair in endothelial progenitor cell (EPC)-derived extracellular vesicles. The study involved culturing EPCs with astragaloside IV, transfecting them with miR-126-3p inhibitor or mock plasmid, interfering with high glucose-induced damage in human umbilical vein endothelial cells (HUVECs) and treating diabetic skin wounds in rats. RESULTS: The healing of rat skin wounds was observed through histological staining. The results revealed that treatment with miR-126-3p-overexpressing EPC-derived extracellular vesicles accelerated the healing of rat skin wounds and resulted in better tissue repair with slower scar formation. In addition, the transfer of EPC-derived extracellular vesicles with high expression of miR-126-3p to high glucose-damaged HUVECs increased their proliferation and invasion, reduced necrotic and apoptotic cell numbers and improved tube formation. In this process, the expression of angiogenic factors vascular endothelial growth factor (VEGF)A, VEGFB, VEGFC, basic fibroblast growth factor and Ang-1 significantly increased, whereas the expression of caspase-1, NRLP3, interleukin-1ß, inteleukin-18, PIK3R2 and SPRED1 was suppressed. Furthermore, miR-126-3p was able to target and inhibit the expression of the PIK3R2 gene, thereby restoring the proliferation and migration ability of high glucose-damaged HUVEC. CONCLUSIONS: In summary, these research findings demonstrate the important role of miR-126-3p in regulating downstream genes and promoting diabetic wound repair, providing a new approach for treating chronic non-healing diabetic wounds.

Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA.

BACKGROUND: PLAU is known as a selected serine protease converting plasminogen to plasmin. The role of PLAU in the development of pan-cancer, especially bladder urothelial carcinoma (BLCA) remains unclear. METHOD: A variety of online tools and cancer databases, including TCGA, GETx, HPA database, GSCALite, UALCAN, ESTIMATE, CIBERSORT, ssGSEA algorithms and SangerBox website, were applied to investigate the associations between PLAU expression and prognosis, genetic alterations, pathway activation, and tumor immunity in pan-cancer. Through cBioPortal and STITCH platforms, the oncogenic role of PLAU and related targeting medicines in BLCA were also explored. We verified the expression of PLAU in pan-cancer cells and its function in bladder cancer cell lines using wet-lab experiments. RESULTS: PLAU expression levels were significantly higher in most cancer tissues. PLAU had a certain accuracy in the diagnosis of various types of cancers (90 % AUC > 0.700). In BLCA, PLAU has abundant methylated sites and showed statistical differences in clinical features. PLAU was involved in tumor immune infiltration, and especially positively correlated with neutrophil infiltration. High-expressed PLAU indicated poorer prognosis in the BLCA patients receiving Atezolizumab. A high mRNA and protein expression levels of PLAU were observed in pan-cancer cell lines, especially BLCA cells. Knockdown of PLAU inhibited the invasive, proliferative, and aggressive phenotypes of bladder cancer cells. Immunohistochemical staining validated PLAU's higher expression in BLCA tissues than in adjacent non-cancerous tissues. And overexpression of PLAU was associated with more advanced TNM stage, and high infiltrating depth. CONCLUSION: Our study revealed that PLAU can serve as a potential therapeutic target and prognostic marker for various malignancies, especially BLCA.

Discovery of ß-sitosterol's effects on molecular changes in rat diabetic wounds and its impact on angiogenesis and macrophages.

Diabetes care, particularly for diabetic foot ulcers (DFUs)-related complications, increases treatment costs substantially. Failure to provide timely and appropriate treatment for severe DFUs significantly increases amputation risk. Neovascularization and macrophage polarization play an important role in diabetic wound healing during different stages of the wound repair process. Therefore, a new treatment method that promotes neovascularization and macrophage polarization may accelerate diabetic wound healing. ß-sitosterol possesses anti-inflammatory, lipid-lowering, and antidiabetic properties. However, its therapeutic potential in diabetic wound healing remains underexplored. This study evaluated the healing effects of ß-sitosterol on diabetic ulcer wounds in rats. We found that ß-sitosterol can promote angiogenesis, alternatively activated macrophages (M2 macrophage) proliferation, and collagen synthesis in diabetic wounds. Transcriptomics analysis and proteomics analysis revealed that MAPK, mTOR and VEGF signaling pathways were enriched in ß-sitosterol-treated wounds. Molecular docking revealed Ndufb5 maybe the target of ß-sitosterol-treated wounds. Our findings confirm the significant diabetic wound healing effects of ß-sitosterol in a rat model. ß-sitosterol treatment to diabetic wounds accelerates wound healing through promoting M2 macrophage proliferation and angiogenesis. Interestingly, we also found that the process of M2 macrophage proliferation accompanies angiogenesis. Thus, ß-sitosterol may be a promising therapeutic approach to enhance diabetic wound healing and reduce amputation in diabetes.

Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal LINC01963 to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells.

BACKGROUND: Hyperglycemia is widespread in the world's population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. METHODS: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1ß, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. RESULTS: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1ß, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1ß, IL-18, ROS, MDA, and LDH. CONCLUSION: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

[Corrigendum] Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the ß­actin bands shown for the western blots portrayed in Fig. 4A and E on p. 2403 appeared to be strikingly similar, albeit that the bands were inverted with respect to their orientation and the dimensions of the bands differed slightly. After re­examining their original data, the authors have realized that these data in Fig. 4 had inadvertently been assembled incorrectly. The revised version of Fig. 4, showing the correct data for all the experiments in Fig. 4E, is shown on on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree to its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 53: 2397­2408, 2018; DOI: 10.3892/ijo.2018.4579].