Evaluation of the Treatment Effects of Conditioned Medium from Human Orbital Adipose-Derived Stem Cells in a Corneal Alkali Burn Rabbit Model.

Purpose: This study aimed to evaluate the effects of a new treatment-conditioned medium from human orbital adipose-derived stem cells (OASC-CM)-on corneal recovery after alkali burns in a rabbit model. Methods: The corneal alkali burn rabbit model was established and treated with OASC-CM, conditioned medium from human abdominal subcutaneous adipose-derived stem cells (ABASC-CM), and fresh control culture medium (con-CM) three times a day for 7 days, respectively. Subsequently, the treatment effects were evaluated and compared through clinical, histological, immunohistochemical, and cytokine evaluations. Results: Clinically, OASC-CM alleviated corneal opacity and edema and promoted recovery of corneal epithelium defect. Histologically and immunohistochemically, OASC-CM inhibited neovascularization, conjunctivalization, and immuno-inflammatory reaction, while promoting corneal regeneration and rearrangement. Increased secretion of interleukin-10 and inhibited protein levels of cluster of differentiation 45, interferon-γ, and tumor necrosis factor-α were observed in the alkali-burned cornea after OASC-CM treatment, which might be the relevant molecular mechanism. Conclusions: OASC-CM showed significant effects on the recovery of rabbit corneal alkali burns and eliminated immunological and ethical limitations, representing a new option for corneal wound treatment.

The Efficacy of Magnesium Sulfate (MgSO4) Wet Dressing in Reducing Eyelid Swelling and Bruising after Blepharoplasty: A Randomized, Controlled, and Observer-Blinded Assessment Study.

The purpose of this study was to evaluate the effects of wet dressing with 50% magnesium sulfate (MgSO4) solution on decreasing eyelid swelling and bruising after blepharoplasty. Fifty-eight patients (23 male and 35 female) who underwent bilateral blepharoplasty were enrolled in our randomized clinical trial. One side of the periorbital area (upper and lower eyelids) per patient received a wet dressing with 50% MgSO4 solution randomly, and the other side was cooled with an ice pack from the first postoperative day for two consecutive days (30 minutes per time and twice a day). The eyelid edema and ecchymosis were evaluated and classified using respective graded scales. Degrees of eyelid edema were similar after surgery in both groups (p > 0.05) and were significantly decreased with time. Compared with the cooled ones, less swelling was observed in the eyelids treated by MgSO4 wet compress on postoperative day 5 (p < 0.01). Both the incidence and area of ecchymosis were lower in the MgSO4 group than those in the cooling group (p < 0.01 and p < 0.05, respectively). Moreover, the majority of patients (39/58, 67.2%) indicated a preference for MgSO4 wet dressing over ice cooling. MgSO4 wet dressing can be conveniently applied to alleviate eyelid swelling and reduce recovery time after blepharoplasty.

Trends in Adipose-Derived Stem Cell-Conditioned Medium: A Bibliometric and Visualized Review.

Adipose-derived stem cell-conditioned medium (ADSC-CM) has been widely studied and used as a stem cell-based cell-free therapy. Due to the explosion of scientific publications in this field, it is difficult to review all relevant publications systematically, not mention quantitively. In this study, we combined bibliometrics with the conventional review method to summarize, analyze, and visualize the characteristics of nearly all published articles related to ADSC-CM using CiteSpace-a bibliometrics software. We applied this software to quantitively and vividly show (a) annual publications and citations; (b) distributions and co-occurrence networks of countries/regions, authors, journals, and institutions; (c) keyword co-occurrence networks and clusters in different time periods; (d) cocitation networks of references; and (e) ongoing challenges and new topics in ADSC-CM. Altogether, we found that ADSC-CM is at a hot stage with an increasing number of publications and citations, extensive and close scientific collaborations, and dense cocited networks. Impact statement To our best knowledge, it is the first bibliometric and visualized review in the field of adipose-derived stem cell-conditioned medium (ADSC-CM). This review systematically and quantitatively revealed the developments, challenges, and emerging hot spots of ADSC-CM, providing a panoramic view to assist researchers to decide the direction of their future study in the fields of ADSCs and CM derived from stem cells.

Anoikis patterns via machine learning strategy and experimental verification exhibit distinct prognostic and immune landscapes in melanoma.

BACKGROUND: Anoikis is a cell death programmed to eliminate dysfunctional or damaged cells induced by detachment from the extracellular matrix. Utilizing an anoikis-based risk stratification is anticipated to understand melanoma's prognostic and immune landscapes comprehensively. METHODS: Differential expression genes (DEGs) were analyzed between melanoma and normal skin tissues in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data sets. Next, least absolute shrinkage and selection operator, support vector machine-recursive feature elimination algorithm, and univariate and multivariate Cox analyses on the 308 DEGs were performed to build the prognostic signature in the TCGA-melanoma data set. Finally, the signature was validated in GSE65904 and GSE22155 data sets. NOTCH3, PIK3R2, and SOD2 were validated in our clinical samples by immunohistochemistry. RESULTS: The prognostic model for melanoma patients was developed utilizing ten hub anoikis-related genes. The overall survival (OS) of patients in the high-risk subgroup, which was classified by the optimal cutoff value, was remarkably shorter in the TCGA-melanoma, GSE65904, and GSE22155 data sets. Low-risk patients exhibited low immune cell infiltration and high expression of immunophenoscores and immune checkpoints. They also demonstrated increased sensitivity to various drugs, including dasatinib and dabrafenib. NOTCH3, PIK3R2, and SOD2 were notably associated with OS by univariate Cox analysis in the GSE65904 data set. The clinical melanoma samples showed remarkably higher protein expressions of NOTCH3 (P = 0.003) and PIK3R2 (P = 0.009) than the para-melanoma samples, while the SOD2 protein expression remained unchanged. CONCLUSIONS: In this study, we successfully established a prognostic anoikis-connected signature using machine learning. This model may aid in evaluating patient prognosis, clinical characteristics, and immune treatment modalities for melanoma.

On the role of vertical resolution for resolving mesoscale eddy dynamics and the prediction of ocean sound speed variability.

This work investigates how vertical resolution affects the prediction of ocean sound speed through a suite of regional simulations covering the DeSoto Canyon in the Gulf of Mexico. Simulations have identical horizontal resolution of 0.5 km, partially resolving submesoscale dynamics, and vertical resolution from 30 to 200 terrain-following layers. The focus is on mesoscale eddies and how modeled sound speeds vary whenever more vertical baroclinic modes are resolved. While domain-averaged sound speed profiles do not differ substantively, the standard deviation increases for increasing resolution due to the sharper representation of mesoscale circulations underneath the mixed layer and their associated density anomalies.

Subcutaneous and Orbital Adipose Tissues: Intrinsic Differences in Carotenoid Contents and Lipidomic Compositions.

The color difference in human subcutaneous fat (SF) and orbital fat (OF) is apparent, but the reasons have been rarely elaborated. We speculate that differences in carotenoid and lipid contents may account for the discrepancy in color. In this study, the intrinsic differences in SF and OF were analyzed using ultrahigh-performance liquid chromatography coupled with Q-Exactive liquid chromatography mass spectrometry/mass spectrometry (UPLC-QE Plus LC-MS/MS). Lipid profiling was performed in an independent batch. The morphology between orbital septum and SF differed statistically in the size of adipocytes and the distribution area of adipocytes. We compared carotenoid contents between two groups (seven samples) and found that lutein was more abundant in SF than that in OF with a p-value of 0.0409, suggesting that lutein could be mainly responsible for the yellow color of adipose tissue. Lipidomic results proved that SF and OF were well differentiated. Totally, 402 lipid features were detected, with 349 features in the positive ion mode and 53 features in the negative ion mode. Features (99.9%) in the positive ion mode and features (98.7%) in the negative ion mode well described various separation patterns in principal component analysis. Thirty-two features selected by variable importance in projection might account for the diversity of compounds in SF and OF. In conclusion, SF and OF differed from each other in carotenoids and lipidome. It is helpful to study the metabolism process of lipid droplets in adipocytes.

Photoactive conjugated microporous polymer@C60 with quencher on tailed Y-triangular DNA structure for high-performance signal-off photoelectrochemical biosensing.

Herein, we synthesized a conjugated microporous polymer (CMP) decorated C60 (CMP@C60) with high photoelectric conversion efficiency, in which continuously repeated donor-acceptor (D-A) π electron unit within one molecule of CMP on C60 could not only effectively increase the mobility of photogenerated carriers with improved electron transmission, but also constitute the cascade energy band matching with reduced electron-hole recombination. Based on the high-performance of CMP@C60 for producing exciting initial photoelectrochemical (PEC) signal, a sensitive signal-off sensing platform was designed for lead ion (Pb2+) assay by coupling with quencher methylene blue (MB) interacting on efficient long tailed Y-triangular DNA structure (LYTD). The proposed LYTD with a tripod structure could generate six long tails in situ on its side at the same time via a simple hybridization chain reaction (HCR), providing notably grooves on electrode to accommodate quencher MB to significantly depress the signal for sensitive detection of Pb2+. As a result, the proposed PEC biosensor revealed excellent analysis capability with a low detection limit of 0.3 fM (S/N = 3). Additionally, it also showed satisfactory stability in the detection of tap water samples, lake water samples and clinical serum samples, manifesting great application prospect in the areas of environmental pollutant detection.

Area four technique: An effective injection approach to the posterior facial frame aesthetic treatment with injectable hyaluronic acid fillers.

BACKGROUND: Defined as a contour line from the hairline, the zygomatic arch, to the ramus and gonial angle area of the mandible, posterior facial frame (PFF) is an important aesthetic units of the face. With the development of hyaluronic acid fillers and the improvement of injection techniques, minimally invasive injection has become one of the first options to improve PFF. However, effective and systematic injection methods to improve PFF are rarely reported in the literature. METHODS: We retrospectively analyzed 200 patients treated with area four technique for PFF. According to the clinical manifestations, PFF was divided into four types, and the injection strategies of the different types were described. GAIS (Global Aesthetic Improvement Scale) at 1 month and 3 months by patients after treatment was evaluated as primary end point. Nine-item aesthetic assessment scores reviewed by two independent observers with experience were performed. RESULTS: GAIS showed that patients' profile was remarkably improved for 90% of total number of subjects. Before and 3 months after treatment, the assessed scores of the lateral cheek lifting (3.17 ± 0.21 vs. 2.56 ± 0.31) and PFF (3.78 ± 0.56 vs. 2.19 ± 0.48) were statistically significant reduced (p < 0.01). The jawline contouring scale (2.32 ± 0.45 vs. 1.23 ± 0.31) and the lateral cheek fullness scale (3.01 ± 0.23 vs. 2.09 ± 0.17) showed a statistically moderate decrease (p < 0.05). CONCLUSION: Area four technique provides a safe and convenient method for classifying and treating patients with insufficent PFF, which makes up for the multisite systematic injection of the face.

The incidence of vasovagal reactions during earlobe piercing.

Background: Vasovagal reactions are common amongst patients with a fear of needles receiving injections or during venipuncture, but they are rarely studied in healthy people undergoing earlobe piercing. The purpose of this prospective study was to evaluate the incidence and the features of vasovagal reactions observed during earlobe piercing. Methods: Thousand eight hundred and sixty six participants aged older than 13 years had their earlobes pierced in our department from January 2020 to January 2022. When vasovagal reactions occurred during the procedure (e.g., dizziness, pallor, diaphoresis, and faintness, etc.), they were recorded and more detailed demographic information was collected. Results: A total of 196 cases of vasovagal reactions were reported in females amongst 1,866 participants, including 58 who actually lost consciousness during earlobe piercing. The incidence of vasovagal reactions and vasovagal syncope was 10.5 and 3.11% respectively. All syncopal reactions occurred in persons younger than 30 years. Conclusion: Vasovagal syncope is often very sudden and occurs without warning. Practitioners need to be familiar with these reactions, and prevent people from an unpredictable fall and subsequent injury during ear piercing.

Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model.

BACKGROUND: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa characterized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchymal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti- inflammatory potential in treating AR. OBJECTIVE: The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model. MATERIAL AND METHODS: The AR murine model was induced by repeated sensitization and challenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated. RESULTS: Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symptoms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (STAT6) at messenger RNA and protein levels in the nasal mucosa. CONCLUSION: BMSC-CM could ameliorate allergic inflammation and regulate the balance of Th cells, and the underlying mechanism was closely related to STAT6 signaling pathway. The immunoregulatory effects of BMSCs could be achieved through paracrine function, and nasal dripping of BMSC-CM might be a novel approach for the treatment of AR.

Anti-Parkinson's Disease Activity of Sanghuangprous vaninii Extracts in the MPTP-Induced Zebrafish Model.

Parkinson's disease (PD) is a devastating disease of the central nervous system that occurs mainly in the elderly age group, affecting their quality of life. The PD pathogenesis is not yet fully understood and lacks the disease-modifying treatment strategies. Sanghuangprous vaninii (S. vaninii) is a perennial fungus with a plethora of pharmacological activities including anti-cancer and antioxidant activity and so on. However, no study till date has reported its neuroprotective effect against symptoms that are similar to PD in pre-clinical investigation. In the current study, we investigated anti-PD-like effects of S. vaninii mycelium extracts (SvMEs) on MPTP-induced PD in zebrafish. We observed that the loss of dopaminergic neurons and neurovascular reduction were reversed by using SvMEs in the zebrafish brain in a concentration-independent manner. Moreover, it also relieved locomotor impairments in MPTP-induced PD zebrafish. In addition, SvMEs exerted significant antioxidant activity in vitro, which was also demonstrated in vivo on ktr4:NTR-hKikGR zebrafish. Upon investigating the underlying mechanism, we found that SvMEs may alleviate oxidant stress and accelerate α-synuclein degradation and then alleviate PD-like symptoms. Antioxidant-related genes (sod1, gss, gpx4a, gclm, and cat) implied that the SvMEs exhibited anti-PD activity due to the antioxidation mechanism. Finally, upon analysis of chemical composition of SvMEs by liquid chromatography-mass spectrometry, we identified 10 compounds that are plausibly responsible for the anti-PD-like effect of SvMEs. On the limiting part, the finding of the study would have been more robust had we investigated the protein expression of genes related to PD and oxidative stress and compared the effects of SvMEs with any standard anti-PD therapy. Despite this, our results indicated that SvMEs possess anti-PD effects, indicating SvMEs as a potential candidate that is worth exploring further in this avenue.

Glabellar wrinkle correction by autologous fat transplantation and evidence of human adipose tissue regeneration in a nude mouse model.

BACKGROUND: Fat grafts are increasingly applied in augmenting soft tissue defects and correcting static wrinkles, but the outcome is always unpredictable because of high absorption rate. Perilipin1 (Plin1) and perilipin2 (Plin2), two perilipin family proteins on lipid droplets in adipocytes, are reported to be used as biomarkers to evaluate adipocyte regeneration in vivo. AIMS: The aim of this study was to assess the efficacy of glabellar wrinkle correction with autologous fat grafting and to observe human adipose regeneration in a nude mouse model. PATIENTS/METHODS: Ten patients with 16 moderate or severe glabellar wrinkles underwent wrinkle correction by subcutaneously injecting autologous lipoaspirates obtained from the abdomen. The injection dose was 0.05 ml per 5 mm. The aspirated adipose tissue (0.05 ml) was also injected under the scalps of nude mice. Fat grafts were explanted at 3, 7, 15, 30, and 120 days after transplantation and the dynamic cellular changes were evaluated by HE staining and immunostaining of Plin1 and Plin2. RESULTS: Among the sixteen wrinkle lines, thirteen were obviously improved 4 months after procedure. Eight of the ten patients were satisfied with their wrinkle correction effects. The fat grafts demonstrated a continuous changing process from degeneration to regeneration in the mouse model without significant absorption and necrosis. It was Plin1, not Plin2 that was expressed in mature adipocytes. After transplantation, Plin1 expression was lost in dead fat cells while Plin2 expression was activated in newly regenerated adipocytes. After 120 days, all the surviving adipocytes were negative for Plin2 but positive for Plin1 again. CONCLUSIONS: Micro-volume fat transplantation was an easy and safe method to improve glabellum wrinkle lines, and the regenerative process of human adipose tissue could be verified in the mouse model.

Perilipin2 is an Earlier Marker Than Perilipin1 for Identifying Adipocyte Regeneration in Fat Grafts.

BACKGROUND: Both perilipin1 (Plin1) and perilipin2 (Plin2) play a crucial role in regulating lipid droplet (LD) formation in fat cells. Plin2 is expressed early in the adipocyte differentiation process but is replaced by Plin1 after cell maturation. In free fat grafts, only a small number of adipocytes remain alive or are replaced by newly regenerated fat cells. It is known that Plin1-positive adipocytes participate in regeneration, but the characteristics of Plin2 expression during this process are still poorly understood. OBJECTIVES: The aim of this study was to investigate whether Plin2 is a more precise early marker for detecting adipocyte regeneration in fat grafts than Plin1. METHODS: Autologous fat tissue (120 mg) harvested from inguinal fat pads was injected under the scalps of C57 mice. Samples were explanted at days 3, 7, 15, and 30 after transplantation. Changes in sample size and weight were evaluated. Hematoxylin-eosin staining, real-time polymerase chain reaction, and immunostaining of Plin1 and Plin2 expression were performed. RESULTS: Plin1, but not Plin2, expression was detected in the freshly harvested fat, but the latter was activated after grafting. Newly regenerated Plin2-positive adipocytes increased from day 3 to day 7 and then declined, whereas the number of Plin1-positive fat cells decreased first and began to increase after day 15. The expression levels of Plin1 and Plin2 mRNA demonstrated similar changes over time. At day 30, adipocytes lost Plin2 expression and were positive for Plin1 again. CONCLUSIONS: Our experiments showed convincing evidence that Plin2 expression could be used to detect early adipocyte regeneration in grafted fat tissue.

Subcutaneous Fat in the Upper Eyelids of Asians: Application to Blepharoplasty.

The Asian eyelid has distinctive anatomical properties. Although the upper eyelid is reported in the literature to have no subcutaneous fat layer, we have often noticed adipose tissue below the upper eyelid skin during ophthalmic plastic surgeries. The aim of the present study was to examine the anatomical and histological features of subcutaneous adipose tissue in Asian upper eyelids using biopsies and microscopic morphological analysis. A total of 30 Chinese patients (60 upper eyelids) undergoing upper blepharoplasty were evaluated. The subcutaneous fat in the upper eyelids was surgically harvested and examined histologically. This study yielded two main findings. First, upper eyelid subcutaneous fat was found in 28 of the 30 patients. This fat layer was the inferior extension of the eyebrow subcutaneous fat layer, which descended and covered the superior half of the upper eyelid. Second, the lobules of subcutaneous fat in the upper eyelid were surrounded by dense fibrous tissues, and the fat cells were smaller than abdominal adipocytes but similar in size to orbital fat cells. Subcutaneous fat tissue is prominent in the upper eyelids of most Asians and is one important contributor to the bulky appearance of those eyelids. Clin. Anat. 33:338-342, 2020. © 2019 Wiley Periodicals, Inc.

Influence of Recipient Site on the Function and Survival of Fat Grafts.

BACKGROUND: Autologous fat grafting has become an increasingly common procedure for soft tissue augmentation throughout the body. However, the long-term outcome is always unpredictable because of inconsistent graft survival. Based on the "law of use and disuse," we speculate that the volume loss of fat grafts will occur when transferred into a site where there is less fat. The purpose of this study is to investigate the cause of high resorption rate from the perspective of fat function after transplantation. METHODS: Adipose aspirates obtained from routine liposuction were injected into the dorsal site of athymic mice, which have no subcutaneous fat layer. The fat grafts were explanted at days 7, 15, and 30 after transplantation. Changes in fat function were evaluated by measuring the adipocyte size and the expression level of adipose differentiation-related protein. RESULTS: After grafting, adipose tissue was replaced by fibrosis, inflammation, and vacuolar tissues gradually over time. The size of fat cells decreased sharply from day 0 to day 7, increased at day 15, and further declined at day 30. Adipose differentiation-related protein expression experienced a dramatic increase at day 7 and then continuously decreased until day 30. CONCLUSIONS: Assuming that the extrinsic factors influencing fat function and distribution remain stable, capabilities of the redistributed fat to handle free fatty acid and store lipid substance are reduced, leading to substantial tissue atrophy and volume decline after grafting.

Secretome from bone marrow mesenchymal stem cells: A promising, cell-free therapy for allergic rhinitis.

Allergic rhinitis (AR), characterized by the symptoms of sneezing, rhinorrhea, itchiness and nasal blockage, is a type I allergic disease of nasal mucosa, which is mainly mediated by IgE after exposure to allergens. At present, general drug therapy is limited to alleviating allergic symptoms but fails to regulate the allergic reaction; the recurrence of symptoms and the side effects of the drugs make many patients with AR resist treatments and bring serious impacts on the quality of life. Bone marrow mesenchymal stem cells (BMSCs) are a population of adult stem cells with multipotential differentiation capability, low immunogenicity, and immunoregulatory effects. The unique immunoregulatory properties of BMSCs make them hold great promise in the treatment of chronic inflammation and immune disorders through a paracrine mechanism of anti-inflammatory and anti-allergic effects. The stem cell secretome is defined as the set of molecules secreted to the extracellular space. The secretome such as conditioned media (CM) obtained from BMSCs contains various bioactive molecules and vesicular elements, which may act as therapeutic mediators to support their immunoregulatory effects. Therefore, we hypothesize that the BMSCs secretome may represent a promising treatment for AR by anti-allergic effects via the paracrine mechanism.