Negative Pressure Wound Therapy for Chronic Wounds.

ABSTRACT: Chronic wounds, including those caused by venous and arterial insufficiency, diabetic complications, and pressure-induced ulcers, pose significant treatment challenges. Negative pressure wound therapy has been increasingly used for managing these wounds. This treatment aims to promote wound healing, prepare the wound bed for further surgical intervention, minimize the risk of infection, and potentially shorten the time to wound healing. Considering variances in techniques applied in different regions globally, there is an emerging need to comprehensively evaluate the effectiveness of negative pressure wound therapy on chronic wounds. Unfortunately, detailed descriptions of the techniques applied to achieve negative pressure are often lacking in existing literature abstracts, posing challenges for direct comparisons. This review aims to analyze the application of negative pressure wound therapy in the treatment of chronic wounds, summarize its advantages and disadvantages, and further explore the potential value and future research direction of negative pressure wound therapy in the repair of chronic wounds.

Associations between temporal eating patterns and body composition in young adults: a cross-sectional study.

PURPOSE: The aim of this study was to examine the associations between body composition and temporal eating patterns, including time of first eating occasion, time of last eating occasion, eating window, and eating jet lag (the variability in meal timing between weekdays and weekends). METHODS: A total of 131 participants were included in the study. Temporal eating pattern information was collected through consecutive 7-day eat timing questionnaires and photographic food records. Body composition was assessed by bioelectrical impedance analysis. Multiple linear regression models were used to evaluate the relationships of temporal eating patterns with body composition, and age was adjusted. Eating midpoint was additionally adjusted in the analysis of eating window. RESULTS: On weekdays, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with lower body fat percentage. On weekends, both later first eating occasion and last eating occasion were associated with lower lean mass, and longer eating window was associated with higher FFMI. Longer first eating occasion jet lag was associated with lower lean mass. CONCLUSION: Our study suggested that earlier and more regular eating patterns may have a benefit on body composition.

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.

The efficacy and safety of Rhodiola formulation for the treatment of ischemic heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Ischemic heart disease is the main cause of heart failure, which seriously endangers the health of people and puts a huge burden on health care resources all over the world. We propose the current protocol to evaluate the effectiveness and safety of Rhodiola on ischemic heart disease, providing a reference for clinical use. METHODS: Two research members will electronically and independently search 4 English databases (EMBASE, PubMed, National Guideline Clearinghouse, and Cochrane Central Register of Controlled Trials) and 4 Chinese databases (Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP Database) from their inception to October 2020. Quality assessment of the included randomized controlled trial was assessed using the Cochrane Collaboration's tool. All calculations were carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, United Kingdom). RESULTS: A synthesis of current evidence of Rhodiola formulation for ischemic heart disease will be provided in this protocol. CONCLUSION: This study will provide a theoretical basis for the clinical use of Rhodiola formulation for treating ischemic heart disease.

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.

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.

Rise of cyborg microrobot: different story for different configuration.

By integrating organic parts achieved through evolution and inorganic parts developed by human civilisation, the cyborg microrobot is rising by taking advantage of the high flexibility, outstanding energy efficiency, extremely exquisite structure in the natural components and the fine upgradability, nice controllability in the artefact parts. Compared to the purely synthetic microrobots, the cyborg microrobots, due to the exceptional biocompatibility and biodegradability, have already been utilised in in situ diagnosis, precise therapy and other biomedical applications. In this review, through a thorough summary of recent advances of cyborg microrobots, the authors categorise the cyborg microrobots into four major classes according to the configuration between biomaterials and artefact materials, i.e. microrobots integrated inside living cell, microrobots modified with biological debris, microrobots integrated with single cell and microrobots incorporated with multiple cells. Cyborg microrobots with the four types of configurations are introduced and summarised with the combination approaches, actuation mechanisms, applications and challenges one by one. Moreover, they conduct a comparison among the four different cyborg microrobots to guide the actuation force promotion, locomotion control refinement and future applications. Finally, conclusions and future outlook of the development and potential applications of the cyborg microrobots are discussed.

Untethered microgripper-the dexterous hand at microscale.

Untethered microgrippers that can navigate in hard-to-reach and unpredictable environments are significantly important for biomedical applications such as targeted drug delivery, micromanipulation, minimally invasive surgery and in vivo biopsy. Compared with the traditional tethered microgrippers, the wireless microgrippers, due to the exceptional characteristics such as miniaturized size, untethered actuation, dexterous and autonomous motion, are projected to be promising microtools in various future applications. In this review, we categorize the untethered microgrippers into five major classes, i.e. microgrippers responsive to thermal, microgrippers actuated by magnetic fields, microgrippers responsive to chemicals, light-driven microgrippers and hybrid actuated microgrippers. Firstly, the actuation mechanisms of these microgrippers are introduced. The challenges faced by these microgrippers are also covered in this part. With that, the fabrication methods of these microgrippers are summarized. Subsequently, the applications of microgrippers are presented. Additionally, we conduct a comparison among different actuation mechanisms to explore the advantages and potential challenges of various types of microgrippers. In the end of this review, conclusions and outlook of the development and potential applications of the microgrippers are discussed.

CTHRC1 promotes wound repair by increasing M2 macrophages via regulating the TGF-ß and notch pathways.

The healing of acute wounds is vital to humans and is a well-orchestrated process that involves systemic and local factors. However, there is a lack of effective and safe clinical therapies. The collagen triple helix repeat containing 1 (CTHRC1) protein is a type of exocrine protein that has been recently reported to contribute to tissue repair. Our aim is to validate the promoting effects of CTHRC1 on the healing of acute wounds and to elucidate the underlying molecular mechanism. Therefore, we first established acute wound healing mouse models and confirmed that CTHRC1 accelerates the healing process of acute wounds. Then, we characterized wound macrophages using a polyvinylalcohol (PVA) sponge model and used Western blotting to investigate the molecular mechanism. We found that CTHRC1 increased the M2 macrophage population and the TGF-ß expression level as a result of the activation of the TGF-ß and Notch pathways, which eventually contributed to the promotion of wound healing. Inhibition of the Notch pathway showed attenuated M2 macrophage recruitment, and it decreased the TGF-ß expression level. These results substantiate our hypothesis that CTHRC1 promotes wound healing by recruiting M2 macrophages and regulating the TGF-ß and Notch pathways.

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.

A comparison of two different sub-dermal trimming techniques for the treatment of axillary osmidrosis.

BACKGROUND: Axillary osmidrosis is a distressing condition caused by excessive secretion by the apocrine glands. Surgical ablation of the subcutis without skin excision is the most popular solution for axillary osmidrosis. Various special operating instruments have been employed to help remove the subcutis. However, ideal results are not always achieved. This study aimed to present our experience of treating osmidrosis by two different sub-dermal trimming techniques and compare two techniques. METHODS: For the study, 150 patients were randomly divided into two groups. Eighty patients of group I were cured using the type I trimming technique: a 1-cm incision and a subcutaneous pocket were made and glandular tissue and subcutaneous tissue attaching to the dermis were removed only using a scissors by experience. Seventy patients of group II were cured using the type II trimming technique: a 4-5-cm incision and a subcutaneous pocket were made, and the elevated axillary flap was turned over with the fingertips; then, the same trimming was performed under direct vision. The post-operation follow-up time was 12-48 months. Operative complications, malodour recurrence and patient satisfaction degree were recorded. RESULTS: The type II trimming technique had significantly lower operative complication rate (2.9% vs. 11.9%) and malodour recurrence rate (2.1% vs. 10.6%), and significantly higher patient satisfaction degree (7.73 ± 0.74 vs. 7.19 ± 0.72) as compared with the type I trimming technique. Most incision scars were not obvious or were even invisible at the time of follow-up. Shoulder movement was normal in all patients, and most patients' armpit hairs became sparse. CONCLUSION: Manual sub-dermal trimming is a satisfactory solution for axillary osmidrosis. The type II trimming technique has a higher success rate with few complications.

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.

Surgical subcision as a cost-effective and minimally invasive treatment for axillary osmidrosis.

BACKGROUND: Axillary osmidrosis, characterized by unpleasant odor and occasional staining of clothing, is a personal discomfort and social impairment for people who suffer from it. Various types of surgical procedures involving instrumented-assisted tools (lasers, ultrasonic, endoscope, and others) have shown relatively positive results; however, for patients in developing countries, especially in China, these treatments are inconvenient and cost-ineffective. OBJECTIVE: To introduce a minimal incision surgical procedure with skin flap treatment that removes the apocrine sweat glands in the subcutaneous tissue through a 1-cm-long incision without instrument-assisted tools. METHOD: From July 2005 to October of 2007, 108 patients (68 women and 40 men) were treated with the minimal incision and cost-effective surgical treatment by manual excision. A 1-cm-long incision is made in the axillary crease. Subcutaneous tissue and glands were removed with scissors through this incision. This procedure is repeated throughout the entire axilla until the axilla has essentially become a super-thin flap. RESULT: Malodor elimination was good in 206 out of 215 axillae (95.8%) treated, fair in nine (4.2%), and poor in zero (0%). The resulting scar is small and virtually invisible because it is only 1-cm long and located in the axillary crease. CONCLUSION: Treatment of axillary osmidrosis by manual excision through a 1-cm incision is a convenient, efficient, cost-effective, and relatively safe technique that results in high patient satisfaction and benefits patients and surgeons in developing countries. Axillary osmidrosis, a non-life-threatening condition characterized by unpleasant odor and occasional staining of clothing, is an annoying problem, particularly in Asian societies. For many people who suffer from this problem, this condition is a personal discomfort, a social impairment, and discourages patients from enjoying social or personal activities, especially young women. They are usually embarrassed by the smell during their daily activities and communication with other people.

[Effect of recombinant Sp1 gene on the collagen expression of hypertrophic scar fibroblasts in vitro].

OBJECTIVE: To explore the feasibility of transfecting recombinant Sp1 into hypertrophic scar fibroblasts and investigate the proliferation and collagen I, III synthesis in the transfected cells. METHODS: Recombinant human Sp1 was transfected into hypertrophic scar fibroblasts with the karyocyte expressive vector. The expression of Sp1, collagen I, III mRNA was tested by real time PCR. The change of cell proliferation was observed with CCK8 colorimeter. RESULTS: About 30% of transfected hypertrophic scar fibroblasts showed green fluorescence positive. The relative expression of Sp1 mRNA in transfected cells, empty-vector cell or untransfected cells group was 5.26 +/- 0.76, 1.08 +/- 0.18, 1.09 +/- 0.15, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P <0.01, n = 5). Expression of collagen I, III mRNA was 2.49 +/- 0.40 and 1.88 +/- 0.30 in transfected cells, 0.96 +/- 0.18 and 0.95 +/- 0.18 in empty-vector cell, and 0.97 +/- 0.15 and 0.93 +/- 0.13 in untransfected cells, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P < 0.01, n = 5). CONCLUSIONS: The hypertrophic scar fibroblasts could be as the target cells of Sp1 gene transfection. Sp1 gene may play an important role in abnormal collagen metabolism in hypertrophic scar.