Keloid Patient Plasma-Derived Exosomal hsa_circ_0020792 Promotes Normal Skin Fibroblasts Proliferation, Migration, and Fibrogenesis via Modulating miR-193a-5p and Activating TGF-ß1/Smad2/3 Signaling.

Background: Keloids are fibroproliferative disorders, which seriously affect the quality of life of patients with keloids. Additionally, circRNAs are enriched within exosomes derived from human blood samples, whereas their relationship with keloids remains largely unknown. It has been reported that hsa_circ_0020792 was abnormally upregulated in keloid tissues. However, the role of keloid patient plasma-derived exosomal hsa_circ_0020792 in the formation and development of keloids is not well understood. Methods: Exosomes were isolated from the peripheral blood plasma of the patients with keloids (keloid patient-Exo) and healthy controls (Healthy control-Exo). The hsa_circ_0020792 and miR-193a-5p levels in keloid patient-Exo and healthy control-Exo, as well as in keloid fibroblasts and normal skin fibroblasts (NFs) were evaluated by RT-qPCR. Results: The level of hsa_circ_0020792 was remarkably increased in keloid patient-Exo and keloid fibroblasts compared with that in Healthy control-Exo and NFs, respectively. In addition, keloid patient-Exo obviously enhanced the viability, migration, and extracellular matrix (ECM) synthesis, but reduced the apoptosis of NFs. Moreover, keloid patient-Exo notably promoted the fibrogenesis of NFs, as characterized by enhanced TGF-ß signaling, increased expressions of phosphorylated Smad2/3. However, downregulation of hsa_circ_0020792 markedly reversed the promoting effects of keloid patient-Exo on cell growth, migration, and myofibroblast activation and fibrogenesis. Furthermore, downregulation of hsa_circ_0020792 significantly reduced the viability, migration, and fibrogenesis in NFs, whereas these phenomena were reversed by miR-193a-5p inhibitor. Conclusion: Collectively, keloid patient plasma-derived exosomal hsa_circ_0020792 could promote the proliferation, migration, and fibrogenesis of NFs via modulating miR-193a-5p and activating TGF-ß1/Smad2/3 signaling.

An Application of a Negative-Pressure Wound Dressing for Partial- or Full-Thickness Burn Wounds.

Negative-pressure wound therapy is widely used in burn populations. Traditionally, negative-pressure devices use persistent vacuum suction, requiring a longer hospital stay. In this study, we applied a novel negative-pressure wound dressing for burn wounds, which eliminates the hospital stay. The medical records of 39 patients with partial-/full-thickness burns treated by negative-pressure wound dressing were retrospectively analyzed. The average burn area, burn degree, healing duration, cost, and incidents during treatment were determined and compared with previous data for conventional therapies. In conclusion, for patients diagnosed with partial-thickness or full-thickness burns and a burn area <34.6 ± 2.21 cm2, the negative-pressure wound dressing is a reliable option, especially for burnt children. Moreover, the negative-pressure wound dressing treatment was not only much cheaper than conventional therapies, but also eliminated hospital stay in patients with small-area deep burn wounds.

Structure-based discovery and redesign of TGF-ß1 Elbow epitope recognition by its type-II receptor in hypertrophic scarring biotherapy.

Transforming growth factor-ß1 (TGF-ß1) signaling pathway has been implicated in the fibroblast activation of hypertrophic scarring (HS). Previously, we proposed a new biotherapeutic strategy to combat HS by disrupting the intermolecular interaction of TGF-ß1 with its cognate type-II receptor (TßR-II). Here, we further demonstrate that the binding site of TGF-ß1 to TßR-II is not overlapped with the conformational wrist epitope and linear knuckle epitope that are traditionally recognized as the functional binding sites of bone morphogenetic protein-2 (BMP-2) to its type-II receptor (BMPR-II), which can thus be regarded as a new functional site we called elbow epitope. Structural, energetic, and dynamic investigations reveal that the elbow epitope consists of two sequentially discontinuous, spatially vicinal segments Loop30-34 and Turn90-95 ; they cannot work effectively to independently interact with TßR-II. Rational redesign of the epitope is performed using an integrated in silio-in vitro method based on crystal and modeled structure data. In the procedure, the two epitope segments are split from the interface of TGF-ß1-TßR-II complex and then connected with each other in a head-to-tail manner by adding a flexible poly-(Gly)n linker between them, thus resulting in a series of combined peptides. We found that the peptide affinity reaches maximum at n = 2, which shares a consistent binding mode with the elbow epitope at native complex interface. The linker of either too long (n > 2) or too short (n < 2) cannot properly place the gap space between the two segments, thus impairing the binding compatibility of designed peptides with TßR-II active site.

Platelet-Rich Plasma for Treating Androgenic Alopecia: A Systematic Review.

BACKGROUND: Platelet-rich plasma (PRP) contains a variety of growth factors and proteins that can accelerate tissue repair. Androgenic alopecia is a genetic disorder characterized by atrophy of hair follicles and hair loss. At present, PRP injections for hair restoration have become a popular though controversial practice. We conducted a meta-analysis to compare the differences between patients treated with local injections of PRP and control group subjects to explore the effectiveness of PRP treatment for androgenic alopecia. MATERIALS AND METHODS: We searched PubMed, EMBASE and the Cochrane Library until Jan 2019 for human studies evaluating the efficacy of PRP for the treatment of androgenic alopecia. RESULTS: We retrieved 132 papers; 11 articles matched our inclusion criteria and comprised 262 androgenic alopecia patients. Through a meta-analysis, we found a significantly locally increased hair number per cm2 after PRP injections in the treatment group versus the control group (mean difference 38.75, 95% CI 22.22-55.28, P < .00001). Similarly, a significantly increased terminal hair density was found in the PRP group compared with the control group (mean difference 22.83, 95% CI 0.28-45.38, P = 0.05). CONCLUSION: Most studies suggest that subcutaneous injection of PRP is likely to reduce hair loss, increase hair diameter and density in patients with androgenic alopecia. Because of the low quality of the studies, small sample sizes, different treatment regimens and possible publication bias, the results of this meta-analysis should be interpreted with caution. Furthermore, more randomized controlled studies should be performed. 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 .

Structure-based derivation of peptide inhibitors to target TGF-ß1 receptor for the suppression of hypertrophic scarring fibroblast activation.

The intermolecular recognition and interaction between human transforming growth factor ß-1 (TGF-ß1) and its cognate receptor TßRII have been implicated in the pathological condition of hypertrophic scarring (HS). Here, we attempted to rationally derive peptide inhibitors from the complex interface of TGF-ß1 with TßRII to disrupt such interaction for the suppression of fibroblast activation involved in HS. A synthetic strategy that integrated computational design and fluorescence-based assay was described to examine the structural basis and energetic property of TGF-ß1-TßRII crystal structure, from which a small peptide segment in the complex binding site was stripped artificially. Molecular dynamics simulations revealed that the linear peptide possesses a large intrinsic disorder that would incur considerable entropy penalty upon binding to TßRII; the peptide segment was then extended and cyclized by introducing a disulfide bond across its terminal residues that were premutated to cysteine. Normal mode analysis indicated that, as expected, the peptide flexibility was largely reduced upon the cyclization, and thus, the entropy penalty was minimized substantially, consequently promoting the spontaneous binding of peptide to TßRII. Fluorescence polarization assay confirmed that all linear peptides are typical non-binders of TßRII (Kd  = ND), while the designed cyclic peptides exhibit moderate or high affinity with Kd at micromolar level.

Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation.

Hypertrophic scarring (HS) is a type of fibrosis that occurs in the skin, and is characterized by fibroblast activation and excessive collagen production. However, at present, therapeutic strategies for this condition are ineffective. Previous studies have identified that the mutual regulation of chronic inflammation, mechanical force and fibroblast activation leads to the formation of HS. Induced pluripotent stem cells (iPSCs) are novel bioengineered embryonic­like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC­conditioned medium (iPSC­CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC­CM, the level of collagen I was markedly reduced and α­smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force­induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor­ß1. Additionally, iPSC­CM attenuated the local inflammatory cell response by blocking the adhesion of human acute monocytic leukemia cell monocytes and fibroblasts in vitro. In addition, the contractile ability of HDFs may be reduced by iPSC­CM. These observations suggest that iPSC­CM may protect against processes leading to hypertrophic scarring by attenuating fibroblast activation, blocking inflammatory cell recruitment and adhesion and reducing the contractile ability of fibroblasts.

Lumican Accelerates Wound Healing by Enhancing α2ß1 Integrin-Mediated Fibroblast Contractility.

Lumican is a dermatan sulfate proteoglycan highly expressed in connective tissue and has the ability to regulate collagen fibril assembly. Previous studies have shown that lumican is involved in wound healing, but the precise effects of lumican on reepithelialization and wound contraction, the two pivotal aspects of skin wound healing, have not been investigated. Here we explored the roles of lumican in fibroblast contractility, a main aspect of skin wound healing, by adopting mice skin wound healing model and the corresponding in vitro cellular experiments. Our results showed that lumican can promote skin wound healing by facilitating wound fibroblast activation and contraction but not by promoting keratinocyte proliferation and migration. Silencing of integrin α2 completely abolished the pro-contractility of lumican, indicating lumican enhances fibroblast contractility via integrin α2. Our study for the first time demonstrated that lumican can affect fibroblast's mechanical property, which is pivotal for many important pathological processes, such as wound healing, fibrosis, and tumor development, suggesting that lumican might have a potential to be used to modulate these processes.

Suppression of cell proliferation and collagen production in cultured human hypertrophic scar fibroblasts by Sp1 decoy oligodeoxynucleotide.

Hypertrophic scars are characterized by the abnormal proliferation of fibroblasts and an overproduction of collagen. The Sp1 transcription factor is involved in the stimulation of collagen synthesis. A decoy oligonucleotide (ODN) targeting Sp1 was designed and transfected into hypertrophic scar fibroblasts (HSFs) cells using cationic liposomes. The transfection efficiency was determined by flow cytometry and was observed to be 85±7% (n=5). Specific binding of the Sp1 decoy ODN was monitored with an electrophoretic mobility shift assay (EMSA). Following transfection with the decoy ODN to Sp1, cell viability and cell proliferation, which were examined by the cell counting kit WST­8, were decreased by 80% compared with untreated cells. Transforming growth factor­ß (TGF­ß) mRNA and collagen mRNA expression were also reduced by 48% in the transfection decoy ODN group. The cell viability of HSFs after 48 h of transfection with 25, 50, 100 and 150 nM Sp1 decoy ODN was 0.9331±0.0203, 0.7479±0.0868, 0.577±0.0347 and 0.4703±0.0147, respectively. The 100 nM dose of the Sp1 decoy ODN inhibited the expression of types I and III collagen by 32 and 28%, respectively (both P<0.01). TGF­ß mRNA expression was also effectively suppressed by the 100 nM Sp1 decoy ODN (P<0.01). The Sp1 decoy ODN inhibited cell proliferation and the expression of types I and III collagen. Therefore, Sp1 decoy ODNs may be a promising tool for developing and testing novel therapeutic applications for treating hypertrophic scars.

Projecting dynamic trends for HIV/AIDS in a highly endemic area of China: estimation models for Liangshan Prefecture, Sichuan Province.

This study describes the current situation and projects dynamic trends for HIV prevalence in a highly endemic area of China, Liangshan Prefecture, Sichuan Province. Epidemiological, behavioral, and population census data from multiple sources were analyzed to extract input for an Asian Epidemic Model (AEM). Fitting curves to historical trends in HIV prevalence were used as a baseline, and future intervention scenarios were explored using the AEM. For 2007, modeled data suggested approximately 0.5% adult HIV prevalence in Liangshan, with an estimated 17,450 people living with HIV/AIDS and 3,400 new infections. With current high risk behaviors, the model predicts that adult prevalence will rise to 1.5% by 2020. Increased condom use and clean needle exchange among injection drug users (IDUs) have slowed the epidemic. The source of new HIV infections will change from a preponderance of IDU-related infections in 2007 (65.9%) to a mixed epidemic in 2020 (general population heterosexuals 45.2%, IDU 38.6%, homosexual transmission between men 12.7%, female sex workers and their clients 3.5%). We anticipate rising prevalence, stable incidence, and higher representation of sexual transmission over time. Prevention investments should target specific interventions toward sub-groups at highest risk, given that both IDUs and men who have sex with men will likely represent a majority of cases and serve as a bridge population.

Combined fascial flap and expanded skin flap for enveloping Medpor framework in microtia reconstruction.

The Medpor implant is another choice for a new auricular framework besides autogenous costal cartilage. However, its relatively frequent exposure and less-matching skin coverage discourage surgeons from using it. In this article, we present a new two-flap method, a combination of the temporoparietal fascial flap and the expanded skin flap, for wrapping the Medpor implant in microtia reconstruction. A staged surgical procedure was performed, including soft tissue expansion in the mastoid region, soft tissue expander removal, expanded skin flap and temporoparietal fascial flap formation, Medpor framework implantation, and the combined two-flap envelopment. Conventional lobule transposition and tragus reconstruction were accomplished for selected patients. In this study, a total of 22 microtias were reconstructed consecutively using this method. Eighteen patients were followed since the first surgery. The postoperative follow-up time ranged from 3 to 12 months. The draped soft tissue covering was thin enough to show the reconstructed ear with excellent, subtle contour when edema gradually vanished 3-6 months postoperatively. The new ear had a stable shape, and its skin color and texture matched the normal surrounding skin very well. No exposure or extrusion of the framework was observed in the series. The Medpor implant enveloped by both a temporoparietal fascial flap and an expanded cutaneous flap appears to be a promising alternative for the auricular framework in microtia reconstruction. Because of the wrapping tissues, auricular construction using a Medpor implant can be a safe, steady, and easily acceptable choice for both microtia patients and their physicians.

Etiology and management of axillary bromidrosis: a brief review.

BACKGROUND: Axillary bromidrosis is a distressing condition that poses significant social embarrassment in almost all the countries over the world. However, its definite etiology has not been generalized yet. There have been a lot of treatments for bromidrosis, which can be roughly divided into two types: conservative management and radical surgical therapy. In order to summarize the possible causes of axillary bromidrosis, a brief review of the literatures regarding bromidrosis was performed. METHODS: An English literature search from 1975 to June 2007 was completed with references to treatments for bromidrosis. A total of 29 papers about the treatment were selected to review. After a close reading, all the extracted information was imported into Microsoft Excel. RESULTS: Many therapies were carried out to treat bromidrosis, including nonoperative and operative ones. Almost all the authors thought that the nonoperative management, such as topical antiperspirants, systemic agents, and iontophoresis, did not have a permanent effect. Most surgeons (90%) chose surgical methods to remove axillary sweat glands for bromidrosis and 90.69% of the axillae had good results. CONCLUSION: Axillary sweat glands may play the most important role in the etiology of bromidrosis. In addition, axillary microorganism, hormone, and inherent also contribute to bromidrosis.

Aesthetic rhinoplasty of the Asian nasal tip: a brief review.

Tip surgery, the most important part of the rhinoplasty procedure, has entered a new era in the past few decades. Various treatment protocols have been attempted. To date, however, opinions on the management of the Asian tip have not been solidified. To generalize and provide appropriate guidelines for the treatment of typical Asian tips, an English literature search from 1977 to March 2007 was conducted. Finally, a total of 26 papers were selected for review. The full text of each paper was read carefully, and data were extracted. Then all extracted information was imported into Microsoft Excel. Nine articles treating 11 groups of patients described the suitable techniques for Asian nasal tips, with 81.8% of the groups advocating that the protocol include a grafting technique, 64% reporting use of the grafting technique alone, and 9% applying cartilage reduction and a suturing technique. Of the 11 (18%) groups, 2 attempted more than one technique. Because of the Asian nasal tip's innate qualities, success with nasal tip plasty for Asians depends on the combined application of appropriate suturing, grafting, and defatting, with grafting techniques contributing the most.

Increased expression of CD86 and reduced production of IL-12 and IL-10 by monocyte-derived dendritic cells from allergic asthmatics and their effects on Th1- and Th2-type cytokine balance.

BACKGROUND: In allergic asthma, allergen-specific T cells have a Th2-biased phenotype, and it is thought that dendritic cells (DCs) contribute to the induction of allergic immune responses. Therefore, we hypothesized that DCs from allergic asthmatics and healthy donors differ with regard to their preference to induce Th1 or Th2 immune responses. OBJECTIVES: To investigate differences in DC-expressed costimulatory molecules and DC-secreted cytokines between allergic asthmatics and healthy donors, and their influence on the Th1- and Th2-type cytokine balance. METHODS: Circulating monocytes from patients with allergic asthma and healthy donors were cultured with GM-CSF and IL-4, respectively, for 5 days and subsequently with lipopolysaccharide for 2 days to create mature DCs (mDCs). CD1a, CD83, CD40 and CD86 expression on mDCs was examined using a fluorescence-activated cell sorter. IL-12 and IL-10 secreted by mDCs were measured by ELISA. Naïve cord blood T cells were primed by mDCs from two groups, and IL-4 and IFN-gamma production by polarized T-helper cells (Th) was measured by ELISA. RESULTS: (1) CD86 expression on mDCs from allergic asthmatics was higher than that from healthy donors. (2) IL-12, IL-12p40 and IL-10 production by mDCs from allergic asthmatics was significantly lower than that from healthy donors, respectively. (3) IL-4 production by Th cells primed by mDCs from allergic asthmatics was increased compared with that from healthy donors. CONCLUSIONS: mDCs from allergic asthmatics preferentially priming naïve T cells towards Th2-cell development might be due to increased expression of CD86 and reduced production of IL-12 and IL-10.

[A study of phenotype and function of dendritic cells and secretory cytokine in allergic asthmatic patients].

OBJECTIVE: To investigate the deficiency of the expression of the phenotypes (CD(1a), CD(83), CD(40), CD(86)) and cytokines (IL-12 and IL-10) by human peripheral blood monocyte (PBMC)-derived dendritic cell (DCs) from asthmatic subjects, and their influence on naive T cell polarization. METHODS: Adherent cells were isolated from peripheral blood samples in asthmatic patients and in healthy volunteers, and were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 as immature DC (iDC). iDCs were stimulated with lipopolysaccharide as mature DC (mDCs). Nonadherent cells were obtained from umbilical cord blood by idem methods, and naïve T cells were sorted by adding anti-CD(4) and anti-CD(45RA) in nonadherent cells respectively and magnetic microbeads. Naïve T cells and mDCs from two groups were co-cultured in complete RPMI1640 media respectively, and naive T cells polarized as T helper cells 1 (Th1) and Th2. The expression of the CD(1a), CD(83), CD(40) and CD(86) on mature DCs were examined by fluorescent activated cell sorter. IL-12 and IL-10 released by mDCs and IL-4 and IFNgamma produced by Th cells were measured by ELISA. RESULTS: (1) The expression of CD(86) on dendritic cells from atopic asthmatics was higher than that from healthy control subjects (40.75 +/- 3.99 vs 29.88 +/- 1.25, P < 0.01). (2) The levels of IL-12, IL-12p40 and IL-10 produced by DCs from asthmatic subjects were all significantly lower than those from healthy control group (217.79 +/- 118.65 vs 905.66 +/- 495.32, P < 0.01; 2072.22 +/- 1496.37 vs 5569.43 +/- 2922.75, P < 0.01; 336.89 +/- 261.52 vs 1425.00 +/- 1148.87, P < 0.05, respectively). (3) IL-4 production by Th2 cells which were primed by DCs from asthmatics was significantly increased as compared to that from control group (368.56 +/- 190.72 vs 584.91 +/- 290.13, P < 0.01); On the contrary, IFNgamma in the patient group was reduced as compared to that in the control group (425.33 +/- 164.94 vs 49.86 +/- 18.14, P < 0.05). (4) In the patient group, the level of IL-12 was positively correlated to that of IFNgamma (P < 0.05), negatively correlated to that of IL-4 (P < 0.05); IL-10 was negatively correlated to IL-4 (P < 0.05). (5) There was a positive correlation between IL-12 and IL-10 in the two groups (P < 0.01). CONCLUSION: Because of DC deficiency, naïve T cells preferentially polarize to Th2 which synthesize more Th2-type cytokine (i.e. IL-4) and T cell tolerance cannot be induced, which may be one of the important pathogenic mechanisms for allergic asthma.