Postoperative Mechanomodulation Decreases T-Junction Dehiscence After Reduction Mammaplasty: Early Scar Analysis From a Randomized Controlled Trial.

BACKGROUND: Soft tissue and cutaneous tension is an important contributor to complicated wound healing and poor scar cosmesis after surgery and its mitigation is a key consideration in aesthetic and reconstructive procedures. OBJECTIVES: The study objective was to assess the efficacy of the force modulating tissue bridge (FMTB) ("Brijjit", Brijjit Medical Inc., Atlanta, GA) in reducing mechanical tension on postoperative wounds. METHODS: A prospective, single-center, randomized, within-subject clinical trial was conducted to evaluate wound healing and nascent scar formation after 8 weeks of postoperative wound support with the FMTB. Patients received standard of care (SOC) subcuticular closure on the vertical incision of 1 breast and experimental closure with the FMTB on the contralateral incision after Wise-pattern reduction mammaplasty. Three-dimensional wound analysis and rates of T-junction dehiscence were evaluated by clinical assessment at 2, 4, 6, and 8 weeks postsurgery. RESULTS: Thirty-four patients (n = 68 breasts) completed 8 weeks of postoperative FMTB application. There was a reduced rate of T-junction wound dehiscence in FMTB breasts (n = 1) vs SOC breasts (n = 11) (P < .01). The mean vertical incision wound area during the intervention period was significantly decreased in the FMTB breast (1.5 cm2) vs the SOC breast (2.1 cm2) (P < .01) and was significantly lower at 2-, 4-, and 8-week follow-up (P < .01). Only the closure method was significantly associated with variations in Week 8 wound area (P < .01) after linear regression modeling. CONCLUSIONS: FMTBs decrease nascent scar dimensions and reduce the occurrence of wound dehiscence. This study provides evidence that the use of continuous mechanomodulation significantly reduces postoperative wound complications after skin closure.

Investigating the Efficacy of Modified Lipoaspirate Grafting to Improve the Appearance of Atrophic Acne Scars: A Pilot Study.

BACKGROUND: Processed lipoaspirate grafting describes several techniques theorized to leverage the inflammatory and regenerative capacities of mechanically processed adipocytes to rejuvenate and correct skin pathology. Although lipoaspirate grafting is typically leveraged to fill visible defects such as depressed scars and dermal lines, additional fat processing allows grafts to stimulate mechanisms of wound healing, including the promotion of fibroblast activation, neovascularization, and neocollagenesis. OBJECTIVES: This study intends to assess the efficacy and tolerability of processed lipoaspirate grafting monotherapy to improve the clinical appearance of atrophic acne scars. METHODS: Patients underwent a single autologous processed lipoaspirate grafting procedure at the site of atrophic acne scars. Objective and subjective scar analysis was performed at 3 and 6 months posttreatment. Scars were assessed with standard photography, topographic analysis, and noninvasive skin measurements. In addition, microbiopsies were obtained before and after treatment to assess histological or genetic changes. Clinical improvement was assessed with patient and clinician Global Aesthetic Improvement Scales (GAIS) and blinded photographic evaluation. RESULTS: Ten patients between ages 18 and 60 completed the study. Clinical evaluation demonstrated that fat grafting improved the appearance of atrophic acne scars. Clinician GAIS and patient GAIS scores showed clinical improvement at both 3- and 6-month follow-up compared with baseline (P < .05). Blinded clinician GAIS scores also showed statistically significant improvement when clinicians compared clinical photographs taken at 6-month follow-up to baseline (P < .0001). The attenuation coefficient increased at 6-month follow-up, suggesting collagen remodeling and reorganization over the study period. Patients experienced anticipated posttreatment symptoms including transient erythema and edema; however, no unexpected adverse events were reported. CONCLUSIONS: Micronized lipoaspirate injection is a viable and effective option to improve the appearance of facial acne scarring. Favorable improvements in atrophic acne scarring were captured by objective analysis of skin ultrastructure as well as improvement in subjective assessments of scarring.

Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption.

The cervical epithelium undergoes changes in proliferation, differentiation, and function that are critical to ensure fertility and maintain pregnancy. Here, we identify cervical epithelial subtypes in non-pregnant, pregnant, and in labor mice using single-cell transcriptome and spatial analysis. We identify heterogeneous subpopulations of epithelia displaying spatial and temporal specificity. Notably in pregnancy, two goblet cell subtypes are present in the most luminal layers with one goblet population expanding earlier in pregnancy than the other goblet population. The goblet populations express novel protective factors and distinct mucosal networks. Single-cell analysis in a model of cervical epithelial barrier disruption indicates untimely basal cell proliferation precedes the expansion of goblet cells with diminished mucosal integrity. These data demonstrate how the cervical epithelium undergoes continuous remodeling to maintain dynamic states of homeostasis in pregnancy and labor, and provide a framework to understand perturbations in epithelial health that increase the risk of premature birth.

Use of Optical Coherence Tomography (OCT) in Assessment of Diabetic Skin Wound Characteristics and Blood Flow.

Optical coherence tomography allows for various measurements of skin but the utility of the device in determining properties of normal and wounded skin in diabetic patients is unknown. This single-site, non-randomized, observational study used an optical coherence tomography device to acquire skin images at 1305 nm, creating real-time image of 17 patient's skin and wounds 1 to 2 mm under the skin surface. Vertical B-scan, en-face and 3-D images were produced to calculate surface and dermal-epidermal junction roughness, the optical attenuation coefficient, a measure of light absorption and scattering, and blood flow metrics. In subjects with diabetes there was an increase in both the Ra (p < .02) and Rz (p < .001) of the wounded versus the control skin. In subjects without diabetes, there was an increase in both the Ra (p < .001) and Rz (p < .03) values of the wounded versus the control skin. At a depth of 0.6 mm across all subjects, there was an average decrease in blood flow of 63% from control to wounded skin. In subjects with diabetes, this decrease was 76%. In subjects without diabetes the decrease was 55%. The change in vasculature between control and wounded skin was associated with a p < .005. There was an increase in the Ra and Rz values and a decrease in blood flow between the wounded skin and control. The device determined a difference in the Ra and Rz values of both diabetic and healthy subjects' skin and a more pronounced decrease in blood flow in the wounds of patients with diabetes as opposed to those without.

Efficacy and tolerability of a microneedling device for treating wrinkles on the face.

OBJECTIVES: A microneedling pen has been cleared by the US Food and Drug Administration, indicated for improving the appearance of adult facial acne scars. The objective of this study was to assess the device's effectiveness for treating wrinkles of the face area. MATERIALS AND METHODS: Healthy adults seeking to improve the appearance of face wrinkles were enrolled (N = 35), receiving four monthly microneedling procedures by a trained aesthetician who treated the face skin per manufacturer instructions. Wrinkle assessments were performed by two trained blinded raters by comparing baseline images of each subject with images obtained at 90 days post-procedure. Subsequently, the two raters were unblinded for the Clinician's Global Aesthetic Improvement Scale (CGAIS) assessment. Subjects completed the Subject's Global Aesthetic Improvement Scale (SGAIS) and a Satisfaction Questionnaire at 30 and 90 days post-treatment. RESULTS: The study was completed by 32 subjects with a mean (SD) age of 56.3 (5.0) years. Wrinkle assessments demonstrated significant improvement in the face areas (p < 0.001). The SGAIS scores showed significant improvements after 30 and 90 days post-treatment (for each, p < 0.001). The CGAIS scores also showed significant improvements at 90 days post-treatment (p < 0.001). Most subjects reported some level of improvement in their appearance at 30 days (73.3%) and 90 days (68.8%) post-treatment. The satisfaction questionnaire showed high levels of improvement in wrinkles (93.8%), satisfaction with the treatment procedure (87.5%) and would recommend microneedling to friends and family members (80.6%) on the face and neck. CONCLUSION: Microneedling is a viable, minimally invasive option for treating wrinkles of the face. CLINICALTRIALS: gov Identifier: NCT03803059.

A Randomized, Placebo-Controlled Trial Evaluating the Single and Combined Efficacy of Radiofrequency and Hybrid Fractional Laser for Nonsurgical Aesthetic Genital Procedures in Post-Menopausal Women.

BACKGROUND: The efficacy of interventions that provide long-term relief of genitourinary symptoms of menopause has not been determined. OBJECTIVES: The authors sought to evaluate radiofrequency and hybrid fractional laser (HFL) treatments for menopausal vulvovaginal symptoms. METHODS: Thirty-one postmenopausal women completed all treatments and at least 1 follow-up. Outcomes included the Vulvovaginal Symptom Questionnaire (VSQ), Vaginal Laxity Questionnaire (VLQ), Urogenital Distress Short Form, Incontinence Impact Questionnaire (IIQ), Female Sexual Function Index (FSFI), laxity measurements via a vaginal biometric analyzer probe, and gene expression studies. RESULTS: Mean VSQ score decreased 2.93 (P = 0.0162), 4.07 (P = 0.0035), and 4.78 (P = 0.0089) among placebo, dual, and HFL groups 3 months posttreatment and decreased to 3.3 (P = 0.0215) for dual patients at 6 months. FSFI scores increased in the desire domain for placebo and dual groups and in arousal, lubrication, orgasm, satisfaction, and pain domains for the HFL group 3 and 6 months posttreatment. An increase of 1.14 in VLQ score (P = 0.0294) was noted 3 months and 2.2 (P = 0.002) 6 months following dual treatment. There was also a mean decrease of 15.3 (P = 0.0069) in IIQ score for HFL patients at 3 months. Dual, HFL, and RF treatments resulted in statistically significant decreases in collagen I, elastin, and lysyl oxidase expression. CONCLUSIONS: Several self-reported improvements were noted, particularly among HFL, dual, and placebo groups 3 and 6 months posttreatment. Objective biopsy analysis illustrated decreased gene expression, suggesting that treatments did not stimulate new extracellular matrix production.

A Correlation of the Glogau Scale With VISIA-CR Complexion Analysis Measurements in Assessing Facial Photoaging for Clinical Research.

BACKGROUND: Historically, standard evaluations for photoaging have involved subjective analysis; recently, however, investigators have turned to noninvasive systems for more objective evaluation of facial aging. OBJECTIVES: The aim of this study was to establish a clinical correlation between the Glogau Photoaging Scale and the VISIA-CR Complexion Analysis System (Canfield Imaging Systems, Fairfield, NJ), and thereby reduce intra- and interobserver variability when assessing photodamage. METHODS: In total, 117 subjects aged between 18 and 89 years were included. Two-dimensional facial photographs were analyzed by 3 independent reviewers and assigned Glogau scores. Images were also captured and analyzed with VISIA software. Data were grouped by median Glogau score and compared between groups. RESULTS: All groups were statistically different (P < 0.05) for Spots, Wrinkles, and Remasked Wrinkles, except for Glogau 1 and 2 for Spots and Remasked Wrinkles. Scores for Wrinkles were plotted against age, and an exponential regression model was noted to be a better fit (R2 = 0.5) than a linear model (R2 = 0.47). The same was true for Spots with an exponential model (R2 = 0.36) compared with a linear model (R2 = 0.33). Scores were also evaluated based on sun exposure history, but no significant differences were observed. CONCLUSIONS: The results illustrate that an imaging system can be used to reliably determine objective scores correlating to Glogau photoaging evaluations, and indicate that aging appears to be an exponential process. Collectively, these findings will assist future investigations of facial aging and the therapeutic options available for facial skin rejuvenation, and enable objective assessment of treatment outcomes.

Efficacy and Tolerability of a Microneedling Device for Treating Wrinkles on the Neck.

BACKGROUND: A microneedling pen has been cleared by the US FDA and is indicated for improving the appearance of facial acne scars in adults. OBJECTIVES: The aim of this study was to assess the effectiveness of this microneedling pen for treating wrinkles. This paper focuses on the results on the neck, an area of recent importance with video meetings placing physical stress on the neck area, leading to wrinkles. METHODS: Healthy adult men and women were enrolled (N = 35). Subjects received 4 monthly microneedling procedures at depths of up to 2.5 mm. Wrinkle assessments were performed by 2 trained blinded raters by comparing images of each subject at baseline and at 90 days postprocedure. The 2 raters were unblinded for the Clinician's Global Aesthetic Improvement Scale assessment. Subjects completed the Subject's Global Aesthetic Improvement Scale and a questionnaire regarding satisfaction with the treated areas of the face and neck at 30 and 90 days posttreatment. RESULTS: The study was completed by 32 subjects. Wrinkle assessments demonstrated significant improvement in the neck areas (P < 0.001). Both Global Aesthetic Improvement Scales showed significant improvements at 90 days posttreatment (P < 0.001). Most subjects reported some level of improvement in their appearance at 30 days (73.3%) and 90 days (68.8%) posttreatment. The satisfaction questionnaire showed high levels of improvement in wrinkles (93.8%), satisfaction with the results (87.5%), and would recommend microneedling to friends and family members (80.6%). CONCLUSIONS: Microneedling is a viable, minimally invasive option for treating wrin kles of the neck.

Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis.

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma HA. Instead, an HA-driven systemic substrate redistribution and adipose tissue-liver crosstalk contributes to the systemic glucose improvements. In summary, we demonstrate an unexpected improvement in glucose metabolism as a consequence of HA overproduction in adipose tissue, which argues against the use of systemic HA synthesis inhibitors to treat obesity and T2D.

Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes.

Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS. The result is compensatory antioxidant signaling in the heart that protects cardiomyocytes from acute oxidative stress, consistent with a preconditioning paradigm. As such, a single injection of sEVs from energetically stressed adipocytes limits cardiac ischemia/reperfusion injury in mice. This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of "inter-organ mitohormesis." Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardio-protection against the inevitable lipotoxic or ischemic stresses elicited by obesity.

Bipolar Fractional Radiofrequency Treatment of Suprapatellar Skin Assessment Using Noninvasive Devices and Microbiopsy.

BACKGROUND: Noninvasive treatments for skin tightening are gaining popularity. However, no studies have assessed bipolar fractional radiofrequency treatment on suprapatellar skin. OBJECTIVES: The purpose of this study was to evaluate the efficacy of bipolar fractional radiofrequency treatment on suprapatellar skin. METHODS: Twenty patients received 1 bilateral suprapatellar bipolar fractional radiofrequency treatment. They returned 7 days, 3 weeks, 3 months, and 6 months posttreatment. Noninvasive measurements were obtained at each visit, including high-resolution ultrasonography, optical coherence tomography, transepidermal water loss and skin elasticity. Microbiopsies were collected in the treatment area for histologic and gene expression analyses. Three clinicians completed photographic evaluations comparing texture and laxity at baseline vs 6 months posttreatment. RESULTS: Fifteen subjects completed all 6 visits. Both transepidermal water loss and dermal-epidermal junction roughness were increased at 3 weeks and 3 months posttreatment. Both attenuation coefficient and stiffness were increased significantly at 3 and 6 months posttreatment. Blood flow 0.5 mm below the surface and expression of epidermal hyaluronic acid and inflammatory genes IL-1b and IL-6 were significantly higher at 7 days posttreatment compared with pretreatment and 3 months posttreatment. There were no statistically significant changes in collagen- or elastin-related genes and proteins at 7 days or 3 months posttreatment. An improvement in texture and laxity was observed at 6 months posttreatment in 17.7% and 24.4% of photographs, respectively. CONCLUSIONS: Radiofrequency treatment by microneedling of suprapatellar skin shows limited effects in decreasing skin laxity and improving skin appearance. At a molecular level, the treatment resulted in lower elastin and hyaluronic acid levels and increased dermal-epidermal junction roughness based on histology and optical coherence tomography imaging.

A Single-Center Trial to Evaluate the Efficacy and Tolerability of Four Microneedling Treatments on Fine Lines and Wrinkles of Facial and Neck Skin in Subjects With Fitzpatrick Skin Types I-IV: An Objective Assessment Using Noninvasive Devices and 0.33-mm Microbiopsies.

BACKGROUND: Although ablative techniques are the standard of care for the treatment of fine lines and wrinkles, microneedling offers a minimally invasive alternative. OBJECTIVES: The purpose of this study was to assess the efficacy of microneedling on facial and neck fine lines and wrinkles. METHODS: Thirty-five subjects between 44 and 65 years old with Fitzpatrick skin types I to IV received 4 monthly microneedling treatments over the face and neck. Subjects returned 1 and 3 months posttreatment. At every visit, high-resolution ultrasonography and optical coherence tomography were performed, and transepidermal water loss and skin elasticity were measured. Microbiopsies (0.33 mm) were collected pretreatment, before the fourth treatment and 3 months posttreatment. RESULTS: Thirty-two subjects (30 females, 2 males) completed all 7 visits. Facial dermal and epidermal density increased 101.86% and 19.28%, respectively, from baseline at 3 months posttreatment. Facial elasticity increased 28.2% from baseline at 3 months posttreatment. Facial attenuation coefficient increased 15.65% and 17.33% at 1 and 3 months posttreatment, respectively. At study completion, blood flow at a depth of 300 µm decreased 25.8% in the face and 42.3% in the neck. Relative collagen type III and elastin gene expression was statistically higher 3 months posttreatment. However, total elastin protein levels were unchanged from baseline values. Dermal muscle formation was observed in 58% of biopsies extracted 3 months posttreatment compared with 15.3% at baseline. CONCLUSIONS: The results illustrate the effects of microneedling treatments. Noninvasive measurements and biopsy data showed changes in skin architecture and collagen/elastin gene expression, suggesting skin rejuvenation, with new extracellular matrix production and muscle formation.

Clinical Translation of Scarless 0.33-mm Core Microbiopsy for Molecular Evaluation of Human Skin.

BACKGROUND: Skin scarring can occur after punch biopsies, prohibiting their routine utilization, especially in the central face. OBJECTIVES: This paper describes a scarless, 0.33-mm-diameter skin microbiopsy for molecular analysis of skin. METHODS: This is was single-center, randomized, prospective study with 15 patients receiving no biopsy or biopsy on the left or right nasolabial fold. Six blinded raters assessed participant photos at baseline, 1 month, and 3 months post biopsy to evaluate for a visualized scar. Patient and Observer Scar Assessment Scale was completed. Additionally, biopsies from various skin regions of body along with arm skin after treatment with a single Erbium-YAG laser were processed for molecular analysis. RESULTS: No patients exhibited scar formation based on evaluation of photographs and patient feedback. There was no mark at the biopsy site 7 days post-procedure. Optical coherence tomography showed a complete closing of the biopsy-punch wound 48 hours post-biopsy. One month post-biopsy, photography reviewers were unable to identify a scar, on average, 90% of the time at 3-month follow-up. Microbiopsies from various anatomical regions were successfully extracted for histology, electron microscopy, and gene expression analysis. Selected skin rejuvenation markers in the biopsies from Erbium-YAG-treated forearm skin resulted in significant gene upregulation in extracellular matrix molecules at 1 month posttreatment compared with untreated skin. CONCLUSIONS: A core microbiopsy of 0.33 mm can be extracted reproducibly for histological, ultrastructural, and gene expression analysis without scarring. This allows repeated sampling for assessment of skin treatments and diseases, including aesthetics and wound-healing progress.

The effect of continuous diffusion of oxygen treatment on cytokines, perfusion, bacterial load, and healing in patients with diabetic foot ulcers.

To evaluate continuous diffusion of oxygen therapy (CDO) on cytokines, perfusion, and bacterial load in diabetic foot ulcers we evaluated 23 patients for 3 weeks. Tissues biopsies were obtained at each visit to evaluate cytokines and quantitative bacterial cultures. Perfusion was measured with hyperspectral imaging and transcutaneous oxygen. We used paired T tests to compare continuous variables and independent T tests to compare healers and nonhealers. There was an increase from baseline to week 1 in TGF-ß (P = .008), TNF-α (P = .014), VEGF (P = .008), PDGF (P = .087), and IGF-1 (P = .058); baseline to week 2 in TGF-ß (P = .010), VEGF (P = .051), and IL-6 (P = .031); and baseline to week 3 with TGF-ß (P = .055) and IL-6 (P = .054). There was a significant increase in transcutaneous oxygen after 1 week of treatment on both medial and lateral foot (P = .086 and .025). Fifty-three percent of the patients had at least a 50% wound area reduction (healers). At baseline, there were no differences in cytokines between healers and nonhealers. However, there was an increase in CXCL8 after 1 week of treatment (P = .080) and IL-6 after 3 weeks of treatment in nonhealers (P = .099). There were no differences in quantitative cultures in healers and nonhealers.

Novel Use of Non-Invasive Devices and Microbiopsies to Assess Facial Skin Rejuvenation Following Laser Treatment.

BACKGROUND AND OBJECTIVE: Patient-reported outcomes and blinded observer rating scales are subjective and unreliable but are extensively utilized to evaluate cosmetic office-based treatments, including ablative lasers. This study aims to assess the practicality of using non-invasive and minimally invasive methods for objective skin assessment following a skin rejuvenation treatment. STUDY DESIGN/MATERIALS AND METHODS: Twelve patients received a single 1,470/2,940 nm laser treatment for facial rejuvenation. Assessments were performed before treatment, and 7 days, 3 weeks, and 3 months post-treatment. Images were taken with the VISIA Skin Analysis System to measure wrinkles, textures, pores, ultraviolet (UV) spots, brown spots, red areas, and porphyrins. Other non-invasive skin measurements-high-resolution ultrasonography, optical coherence tomography, transepidermal water loss and BTC 2000-were used to measure epidermal/dermal thickness, blood flow, surface roughness, wrinkle depth, attenuation coefficient, elasticity, laxity, and viscoelasticity. Microbiopsies (0.33 mm in diameter or the equivalent of a 23-gauge needle) were collected for histology and gene expression of tissue rejuvenation. RESULTS: Significant improvement in facial skin aesthetics after laser treatment was recorded in UV spots, brown spots and pores after 3 weeks and in UV spots and brown spots after 3 months. The dermal attenuation coefficient decreased significantly at 3 weeks, while blood flow 0.5 to 0.7 mm below the skin surface increased significantly between 5 days and 3 weeks following treatment. Epidermal hyaluronic acid expression assessed by immunostaining and expression of inflammatory genes were elevated at 7 days post-treatment compared with untreated or 3 months post-treatment. There were no statistically significant changes in collagen or elastin-related genes between groups at the studied parameters. CONCLUSION: Non-invasive devices can be effectively used to provide objective measurements of skin structure, pigmentation, blood flow, and elasticity to assess the efficacy of facial skin rejuvenation treatments. Furthermore, microbiopsies can objectively evaluate facial skin rejuvenation without scarring. Using non-invasive skin imaging, a single treatment with the 1,470/2,940 nm laser was observed to be effective in improving skin appearance after 3 months, namely in reducing UV spots and brown spots, without significant changes in the tissue at the molecular level, as assessed by microbiopsy. Lasers Surg. © 2020 Wiley Periodicals, Inc.

Use of Optical Coherence Tomography (OCT) in Aesthetic Skin Assessment-A Short Review.

Assessments of non-surgical office-based aesthetic treatments' efficacy including lasers are mostly based on subjective evaluation of clinical photography. Accumulating evidence suggest that non-invasive skin imaging such as optical coherence tomography (OCT) can be effectively used to assess not only the skin surface but also the underlying epidermis and dermis, providing objective and clinically relevant data. In this review, we highlight the potential of OCT imaging for the aesthetic medicine field along with OCT measurement parameters and their clinical relevance to healthy and pathological skin conditions. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization.

Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor ( IGF)-1, Insulin-like growth factor binding protein ( IGFBP)-1, and PRL gene expression at baseline and during decidualization. These effects were mediated through protease activated receptor (PAR)-1- and PAR-1-independent pathways. Thrombin decreased the secretion of a key marker of decidualization (PRL), altered the morphological transformation of decidualizing hESCs, and activated genes involved in matrix degradation and proinflammatory chemokines ( Interleukin-8 and Interleukin-6). Genes encoding factors important for matrix stability ( Col1α1, LOX) were suppressed. We suggest that intrauterine bleeding and generation of thrombin accentuates leukocyte extravasation and endometrial inflammation, impairs decidualization, and endometrial support of early pregnancy.

Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism.

Hyaluronic acid (HA, also known as hyaluronan), is a non-sulfated linear glycosaminoglycan polymer consisting of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine abundantly present in the extracellular matrix. The sizes of hyaluronic acid polymers range from 5000 to 20,000,000 Da in vivo, and the functions of HA are largely dictated by its size. Due to its high biocompatibility, HA has been commonly used as soft tissue filler as well as a major component of biomaterial scaffolds in tissue engineering. Several studies have implicated that HA may promote differentiation of adipose tissue derived stem cells in vitro or in vivo when used as a supporting scaffold. However, whether HA actually promotes adipogenesis in vivo and the subsequent metabolic effects of this process are unclear. This review summarizes some recent publications in the field and discusses the possible directions and approaches for future studies, focusing on the role of HA in the adipose tissue.