3D Facial Analysis in Acromegaly: Gender-Specific Features and Clinical Correlations

Objective: Quantitative investigations of facial changes in acromegaly are rare. A new imaging technique, three-dimensional (3D) stereophotography, can accurately quantify whole facial changes. We aimed to measure facial characteristics in acromegaly patients using 3D stereophotography, analyze gender-specific features, and explore clinical influencing factors.Design: Single-center case-control study.Methods: Thirty-nine acromegaly patients and 39 age- and gender-matched healthy subjects were prospectively enrolled. 3D stereophotography was performed, and facial lines and angles were quantified for each subject. Clinical information for each acromegaly patient was acquired.Results: The nose width, length, height and depth were longer; the upper and lower lips were thicker; the face length, face width and gonion-gnathion distances were longer; and the nasofrontal and columella-labial angles were smaller in the acromegaly patients, especially in males, than in the healthy controls, with statistical significance (p < 0.05). No differences were found in the face breadth, columella-labial angle, or nose length, height or depth between the female patient and healthy control groups. The insulin-like growth factor 1 (IGF-1) levels in the acromegaly patients were linearly and positively correlated with the nose width (p = 0.006) and gonion-gnathion distance (p = 0.029) and linearly and negatively correlated with the nasofrontal angle (p = 0.026).Conclusions: The acromegaly patients' facial changes exhibit a unique trend, and the characteristics are not identical between genders. 3D stereophotography is an accurate and reliable tool for investigating facial characteristics. Recognizing the above facial features might be potential to assist in the early diagnosis and timely treatment of acromegaly and aid in predicting the severity of systemic complications

Reduction of Methyltransferase-like 3-Mediated RNA N6-Methyladenosine Exacerbates the Development of Psoriasis Vulgaris in Imiquimod-Induced Psoriasis-like Mouse Model

N6-methyladenosine (m6A) methylation is the most pervasive and intensively studied mRNA modification, which regulates gene expression in different physiological processes, such as cell proliferation, differentiation, and inflammation. Studies of aberrant m6A in human diseases such as cancer, obesity, infertility, neuronal disorders, immune diseases, and inflammation are rapidly evolving. However, the regulatory mechanism and physiological significance of m6A methylation in psoriasis vulgaris are still poorly understood. In this study, we found that m6A methylation and Methyltransferase-like 3 (METTL3) were both downregulated in psoriatic skin lesions and were negatively correlated with Psoriasis Area and Severity Index (PASI) scores. Inhibiting m6A methylation by knocking down Mettl3 promoted the development of psoriasis and increased its severity in imiquimod-induced psoriasis-like model mice. Our results indicate a critical role of METTL3- mediated m6A methylation in the pathogenesis of psoriasis vulgaris

Genetic Inheritance Models of Non-Syndromic Cleft Lip with or without Palate: From Monogenic to Polygenic

Non-syndromic cleft lip with or without palate (NSCL/P) is a prevalent birth defect that affects 1/500–1/1400 live births globally. The genetic basis of NSCL/P is intricate and involves both genetic and environmental factors. In the past few years, various genetic inheritance models have been proposed to elucidate the underlying mechanisms of NSCL/P. These models range from simple monogenic inheritance to more complex polygenic inheritance. Here, we present a comprehensive overview of the genetic inheritance model of NSCL/P exemplified by representative genes and regions from both monogenic and polygenic perspectives. We also summarize existing association studies and corresponding loci of NSCL/P within the Chinese population and highlight the potential of utilizing polygenic risk scores for risk stratification of NSCL/P. The potential application of polygenic models offers promising avenues for improved risk assessment and personalized approaches in the prevention and management of NSCL/P individuals

Prediction of immunotherapy responsiveness in melanoma through single-cell sequencing-based characterization of the tumor immune microenvironment

Immune checkpoint inhibitors (ICB) therapy have emerged as effective treatments for melanomas. However, the response of melanoma patients to ICB has been highly heterogenous. Here, by analyzing integrated scRNA-seq datasets from melanoma patients, we revealed significant differences in the TiME composition between ICB-resistant and responsive tissues, with resistant or responsive tissues characterized by an abundance of myeloid cells and CD8+ T cells or CD4+ T cell predominance, respectively. Among CD4+ T cells, CD4+ CXCL13+ Tfh-like cells were associated with an immunosuppressive phenotype linked to immune escape-related genes and negative regulation of T cell activation. We also develop an immunotherapy response prediction model based on the composition of the immune compartment. Our predictive model was validated using CIBERSORTx on bulk RNA-seq datasets from melanoma patients pre- and post-ICB treatment and showed a better performance than other existing models. Our study presents an effective immunotherapy response prediction model with potential for further translation, as well as underscores the critical role of the TiME in influencing the response of melanomas to immunotherapy

Therapeutic applications of exosomes from adipose-derived stem cells in antifibrosis

Fibrosis is a condition in which connective tissue replaces normal parenchymal tissue, resulting in significant tissue remodeling. Fibrosis can affect several organs and pose a serious threat to human health and life. Adipose-derived stem cells (ASCs) have been suggested as promising candidates for antifibrotic therapies. Paracrine secretion is one of the key processes in stem cell therapy due to its critical function in cellular communication. ASC-derived exosomes (ASC-exos) are used as tools for restoring and regenerating damaged tissue, and they are now thought to orchestrate antifibrosis-related events. In this review, we summarize the recent findings and present an extensive view of the therapeutic applications of ASC-exos in fibrotic diseases

Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu

Abstract Background Human adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether the exosome-derived miRNAs secreted by hADSCs are capable of influencing angiogenesis, a key step in tissue regeneration. Methods Exosomes were purified from hADSCs followed by the characterization of their phenotype and angiogenic potential in vitro. RNA sequencing was performed to detect the miRNAs that were enriched in the hADSC-derived exosomes. A miRNA-mimic experiment was used to detect the key miRNAs in the proangiogenic activity of hADSC-derived exosomes. Results Exosomes isolated from hADSCs were characterized as round membrane vesicles with a size of approximately 100 nm and were positive for CD9 and flotillin. The exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs) and stimulated HUVEC proliferation and migration. Remarkably, the exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10 μg/mL) was comparable with that of 5% FBS. The RNA-seq bioinformatics analysis predicted 1119 gene targets of the top 30 exosomal miRNAs in Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the pathway involved in the angiogenesis was among the top KEGG pathways. Moreover, intact miR-423-5p was further demonstrated to be transferred into HUVECs via exosomes and to exert its angiogenic function by targeting Sufu. Conclusions Exosomal miR-423-5p mediated the proangiogenic activity of hADSCs by targeting Sufu, which may contribute to the exploitation of exosomes from hADSCs as a therapeutic tool for regenerative medicine

Vaginoplasty with Acellular Dermal Matrix after Radical Resection for Carcinoma of the Uterine Cervix

<p>Various methods are available for vaginoplasty, but many of them have the drawbacks including surgical complexity and postoperative pain at the donor site. We herein evaluated the outcomes of vaginoplasty using tissue-engineered biomaterial graft. This study included 16 early stage cervical cancer patients who received curative surgery in combination with radiotherapy. They underwent vaginoplasty with tissue-engineered biological material, acellular dermal matrix (ADM). After treatment, a vaginal dilator was advised to be used for 6 months to prevent contraction of vagina. The effectiveness of the treatment was evaluated by the anatomic changes of vagina before and after treatment, and the sexual outcomes at 12-month after treatment. The procedure was safe with no intra-operative complications reported. The mean operation time was 1.7 ± 0.3 hours, with 11/16 patients had blood loss < 50 mL during surgery. Generally, epithelialization was observed in 2-week after treatment. At the 1-year follow-up visit, the mean vaginal width was increased significantly from 1.31 ± 0.4 cm before surgery to 4.13 ± 0.43 cm after surgery (p = 0.034). The vaginal length was also increased from 5.97 ± 0.59 cm to 9.25 ± 0.66 cm (p < 0.001). Majority of the patients (12/16) reported satisfactory sexual life. The use of ADM in vaginoplasty was a safe and effective procedure that provided satisfactory sexual function for patients with vaginal abnormalities after cervical cancer treatment.</p