Novel prospects for scarless wound healing: The roles of myofibroblasts and adipocytes.

Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

Insight into the role of dermal white adipose tissue loss in dermal fibrosis.

The loss of dermal white adipose tissue (dWAT) is vital to the formation of dermal fibrosis (DF), but the specific mechanism is not well understood. A few studies are reviewed to explore the role of dWAT in the formation of DF. Recent findings indicated that the adipocytes-to-myofibroblasts transition in dWAT reflects the direct contribution to the DF formation. While adipose-derived stem cells (ADSCs) contained in dWAT express antifibrotic cytokines, the loss of ADSCs leads to skin protection decreased, which indirectly exacerbates DF and tissue damage. Therefore, blocking or reversing the adipocytes-to-myofibroblasts transition or improving the survival of ADSCs in dWAT and the expression of antifibrotic cytokines may be an effective strategy for the treatment of DF.

Emerging Effects of Resveratrol on Wound Healing: A Comprehensive Review.

Resveratrol (RSV) is a natural extract that has been extensively studied for its significant anti-inflammatory and antioxidant effects, which are closely associated with a variety of injurious diseases and even cosmetic medicine. In this review, we have researched and summarized the role of resveratrol and its different forms of action in wound healing, exploring its role and mechanisms in promoting wound healing through different modes of action such as hydrogels, fibrous scaffolds and parallel ratio medical devices with their anti-inflammatory, antioxidant, antibacterial and anti-ageing properties and functions in various cells that may play a role in wound healing. This will provide a direction for further understanding of the mechanism of action of resveratrol in wound healing for future research.

Insights into the role of adipose-derived stem cells: Wound healing and clinical regenerative potential.

The incidence of acute and chronic wound diseases is rising due to various reasons. With complicated pathogenesis, long course, difficult treatment and high disability, wound diseases have become a major burden for patients, their families, and society. Therefore, the focus of research is to identify new ideas and methods for treatment. Fat grafting has gained increased attention because of its effectiveness in wound treatment, and further analysis has uncovered that the stem cells derived from fat may be the main factor affecting wound healing. We summarize the function of adipose stem cells and analyze their possible mechanisms in tissue repair, helping to provide new ideas for the treatment of wound healing.

Simultaneous measurement of gas absorption and path length based on the dual-sideband heterodyne phase-sensitive detection of dispersion spectroscopy.

We present a novel approach based on dual-sideband heterodyne phase-sensitive detection of dispersion spectroscopy to realize simultaneous measurement of the gas absorption signal and corresponding path length. The details of heterodyne phase-sensitive detection of dispersion spectroscopy are derived. A standard Mach-Zehnder intensity modulator (MZM) is adopted to generate a spectrum of a carrier and two sidebands. Phase shift of the beatnote signal generated by the two sidebands is detected to retrieve the path length as well as the gas absorption signal. The measurement range of the path length can be adapted by changing the modulation frequency. Proof-of-principle experiments are conducted with methane (CH4) as the absorber which is filled into a gas cell with a variable path length. We also utilize this approach to evaluate the path length of a White cell and meanwhile calibrate the experimental system with different concentrations of methane. The proposed method has a great potential for detecting the path length and gas absorption in multipass cells and the open path environment.

m6 A facilitates YTHDF-independent phase separation.

N6-methyladenosine (m6 A) is one of the most abundant messenger RNA (mRNA) modifications in eukaryotes and is involved in various key processes of RNA metabolism. In this issue of Nature, Ries et al (2019) described the fundamental features of m6A modification of mRNAs in regulating the composition of the phase-separated transcriptome on the basis of number and distribution, and provide strong evidence that m6A plays a role in regulating phase separation in cells.

Acetylene sensing system based on wavelength modulation spectroscopy using a triple-row circular multi-pass cell.

A sensitive acetylene (C2H2) sensing system based on a novel triple-row circular multi-pass cell (CMPC) was demonstrated. This CMPC has an effective optical length of 21.9 m within an extremely small volume of 100.1 mL. We utilized wavelength modulation spectroscopy (WMS) for absorption spectroscopy detection of C2H2. The distance between the two minima of the second harmonic was used to normalize the maximum value of it, which makes the time to obtain stable output for continuous detection shorten dramatically. A fiber-coupled distributed feedback (DFB) diode laser emitting at 1.5316 µm was employed as a light source. An Allan deviation analysis yielded a detection sensitivity of 76.75 ppb with a normalized noise equivalent absorption coefficient of 8.8 × 10-10 cm-1 Hz-1/2 during an average time of 340 s. With a fast stable time, reduced size and high detection sensitivity, the proposed sensing system is suitable for trace gas sensing in a weight-limited unmanned aerial vehicle (UAV) and an exhalation diagnosis for smoking test.

Generalized optical design of the multiple-row circular multi-pass cell with dense spot pattern.

We present a generalized method for designing a novel circular multi-pass cell (MPC) with multifold overall optical path length, or alternatively enlarged path-to-volume ratio in the same magnification compared to traditional version, by exploiting the vertical dimension of cavity mirrors. Multiple rows of reflection spots can be generated on arbitrary number of different horizontal planes within the cell that consists of two easy-fabricating circular spherical mirrors. Base on this method, one can arbitrarily determine the interval of reflection spots in both horizontal and vertical directions, so that almost seamless and regular distributed dense spot pattern, and consequently large path-to-volume ratio can be achieved. A series of q-preserving configurations of the multiple-row circular multi-pass cell are calculated and simulated, in which the q-parameters of probe Gaussian beams can be approximately unchanged after the whole transmission within the cells. The maximum optical path length among these simulation cases is 201.8 m within 427.2 mL volume. Furthermore, we demonstrate a practical optical setup with 21.9 m optical path length within 100.1 mL, which is the smallest volume case among the existing actual MPCs with similar overall optical path lengths.

Generalized method for seeking q-preserving configurations of multi-pass cells.

A method is presented for seeking specified multi-pass cell (MPC) configurations with q-parameters of the input and output Gaussian beams that remain the same (q-preserving configurations). The Frobenius norm (F-norm) is chosen as the quantitative criterion of the deviation between the transfer matrix of the MPC configurations and identity matrix. When the deviation is down near to zero, the corresponding configuration is close to an ideal q-preserving configuration. In contrast to common 2 × 2 transfer matrixes that are only applicable to MPCs with negligible astigmatism, we adopt 4 × 4 transfer matrixes that are also workable for multi-pass systems with astigmatism. To demonstrate the validation of the method, several q-preserving structures of four-objective multi-pass matrix system (FO-MMS) and double-row circular MPC (DR-CMPC), which are two fundamentally different MPC types, are illustrated. The variation tendencies of the quantitative deviation between the transfer matrix and the identity matrix are discussed in detail for each structure as functions of structural parameters. The optimal q-preserving structures are found for FO-MMS and DR-CMPC, with the matrix deviation of 0.0047 and 0.0051, while the corresponding total optical path length (OPL) are 33.6 m and 67.8 m, respectively. The OPL of the optimal DR-CPMC is longer than the traditional CMPC in the state of the art, and the deviation is three orders of magnitude smaller if the similar spherical reflecting surfaces are adopted.

Dual-Channel Spectral Domain Optical Coherence Tomography Based on a Single Spectrometer Using Compressive Sensing.

Dual-channel spectral domain optical coherence tomography (SD-OCT) is one of the effective methods for improving imaging depth and imaging speed. In this paper, we design a dual-channel SD-OCT system based on a single spectrometer that can operate in two modes: (1) Increasing imaging speed and (2) expanding imaging depth. An optical path offset is preintroduced between the two channels to separate the two-channel data. However, this offset increases the requirement for the spectral resolution of the spectrometer in mode (1), so compressive sensing (CS) technology is used herein to overcome this problem. Consequently, in mode (1), when the spectral resolution of the spectrometer is the same as that used in the single-channel system, we use a dual-channel SD-OCT system combined with CS technology to double the imaging speed. In mode (2), when the spectral resolution of the spectrometer is only half of that used in a single-channel system, the imaging depth can be nearly doubled. We demonstrate the feasibility and effectiveness of the method proposed in this work by imaging a mirror, a fish fin, a fish eye, and an onion.

Progress about the fibro-adipose vascular anomaly: A review.

Fibro-adipose vascular anomaly (FAVA) is a rare and complex vascular malformation associated with persistent pain, limb contracture, and even restriction of activity. However, the pathophysiology of FAVA remains unclear. Although FAVA is a benign vascular malformation, it is highly misdiagnosed and often thus undergoing repeated surgical resection and interventional sclerotherapy, resulting in worsening of symptoms and irreversible dysfunction. Therefore, aggressive diagnosis and treatment are essential. There are several different treatment options for FAVA, including surgical resection, sclerotherapy, cryoablation, drug therapy, and physical therapy. This article reviews the clinical manifestations, pathological features, pathogenesis, and treatment methods of FAVA.

Expression of CXCL8 and its relationship with prognosis in patients with non-small cell lung cancer.

To determine the expression of chemokine 8 (CXCL8) in non-small cell lung cancer (NSCLC) patients and analyze its correlation with tumor characteristics and patient prognosis. We conducted a retrospective analysis of 149 NSCLC patients treated between January 2016 and April 2018, measuring serum CXCL8 expression upon admission or prior to treatment. The clinical characteristics, including lymph node metastasis and staging, based on CXCL8 expression levels, were analyzed. Receiver Operating Characteristic (ROC) curves was drawn to assess its predictive value for lymph node metastasis and staging in NSCLC patients. Furthermore, the Kaplan-Meier curve was plotted to assess the impact of CXCL8 on 5-year survival in NSCLC Patients. NSCLC patients exhibited significantly higher serum CXCL8 levels than those with benign tumors (P<0.001), with the high CXCL8 expression group showing a higher incidence of lymph node metastasis or stage III NSCLC (P<0.01). CXCL8 was identified as an independent predictor of lymph node metastasis (AUC=0.730) and higher TNM stage (AUC=0.708), as well as a validated biomarker for predicting five-year survival in NSCLC patients. This study highlights the strong association between CXCL8 expression in NSCLC and patient prognosis, particularly regarding lymph node metastasis and clinical staging, suggesting the need for further research to explore CXCL8's specific role in the tumor microenvironment and its impact on different NSCLC subtypes.

Characterizing the inherent activity of urinary bladder matrix for adhesion, migration, and activation of fibroblasts as compared with collagen-based synthetic scaffold.

The mechanism of action underlying the intriguing prominent bioactivity of urinary bladder matrix (UBM) for in situ tissue regeneration of soft tissue defects remains to be elucidated. It is speculated that the activity of UBM for cell adhesion, migration, and activation is inherent. The bioactivity of UBM for in situ tissue regeneration and its relation with the structure and intact soluble components of UBM were investigated in comparison to a collagen-based scaffold, PELNAC (PEL). We isolated the soluble component of the two materials with urea buffer, and evaluated the respective effect of these soluble components on the in vitro adhesion and migration of L929 fibroblasts. The spatiotemporal pattern of endogenous-cell ingrowth into the scaffolds and cell activation were investigated using a model of murine subcutaneous implantation. UBM is more capable of promoting the adhesion, migration, and proliferation of fibroblasts than PEL in a serum-independent manner. In vivo, as compared with PEL, UBM exhibits significantly enhanced activity for fast endogenous cell ingrowth and produces a more prominent pro-regenerative and pro-remodeling microenvironment by inducing the expression of TGF-ß1, VEGF, MMP-9, and murine type I collagen. Overall, our results suggest the prominent bioactivity of UBM for in situ tissue regeneration is inherent.

CH4/C2H6 dual-gas sensing system based on wavelength modulation spectroscopy using a single near infrared laser.

For sensitive and accurate methane (CH4) and ethane (C2H6) simultaneous detection, a near-infrared dual-gas sensing system based on wavelength modulation spectroscopy (WMS) was developed. A fiber-coupled distributed feedback (DFB) diode laser emitting at 1.684 µm was employed as light source. The scanning and modulation signals applied to the injection current of the laser were designed based on time division multiplexing (TDM) to realize the dual-gas measurement. A White cell with absorption path length of 16 m was utilized. The light intensity signal detected was processed with python based digital quadrature lock-in amplifier to obtain first and second harmonic signals. Allan deviation analysis yielded detection limits of 23.53 ppb for CH4 and 146.4 ppb for C2H6 in an average time of 100 s.

Insight into the role of DPP-4 in fibrotic wound healing.

Wound healing is a complex and long-term process consisting of hemostasis, inflammation, proliferation, and maturation/remodeling. These four stages overlap and influence each other; they affect wound healing in different ways, and if they do not function perfectly, they may cause scarring, proliferative scarring and keloid formation. A therapeutic target affecting wound healing in multiple ways will help the healing process proceed more effectively. DPP-4/CD26 is a multifunctional dimorphic glycoprotein widely distributed on the surface of a variety of cells, including fibroblasts and keratin-forming cells. It has been found to affect periwound inflammation, re-epithelialization, extracellular matrix secretion and skin fibrosis and is a potential target for promoting wound healing and inhibiting scar formation. After presenting a brief introduction of the wound healing process and DPP-4/CD26, this paper summarizes the effects of DPP-4/CD26 on cells involved in different stages of wound healing and discusses the feasibility of DPP-4/CD26 as a multifunctional target for the treatment of wound healing and inhibition of scar formation.

The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis.

Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor ß1 (TGF-ß1), thereby producing an ASIC3-M-CSF-TGF-ß1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.

Dual-Action Icariin-Containing Thermosensitive Hydrogel for Wound Macrophage Polarization and Hair-Follicle Neogenesis.

Bone morphogenetic protein (BMP) pathway is essential for M2 macrophage polarization and hair-follicle neogenesis. Icariin, a flavonoid derived from Epimedium, is a mediator of the BMP pathway. Here, we develop a hydrogel formulation functionalized with icariin for regulation of macrophage polarization to accelerate wound healing and hair-follicle neogenesis. Compared to skin defects without icariin treatment, those treated with icariin+PEG hydrogel healed faster and had new hair follicles. Results in vivo showed that icariin+PEG hydrogel induced a higher level of M2 phenotypic transformation of macrophages. Moreover, icariin+PEG hydrogel significantly accelerated wound-repair process by reducing the invasion of inflammation, excessive deposition of collagen, immoderate activation of myofibroblasts, and increasing the regeneration of hair follicles. Furthermore, studies in vitro demonstrated that the icariin+PEG hydrogel induced macrophages to polarize to the M2 phenotype and dermal papilla cell to hair follicles. Finally, molecular analysis demonstrated that the icariin+PEG hydrogel increased the expression of BMP4 and Smad1/5 phosphorylation in skin wounds. These results demonstrate the therapeutic potential of icariin-containing thermosensitive hydrogels for inducing M2 macrophage polarization to accelerate wound healing and promote hair-follicle neogenesis by regulating the BMP pathway.

The uPA System Differentially Alters Fibroblast Fate and Profibrotic Ability in Skin Fibrosis.

Skin fibrosis is a common pathological feature of various diseases, and few treatment strategies are available because of the molecular pathogenesis is poorly understood. The urokinase-type plasminogen activator (uPA) system is the major serine protease system, and its components uPA, urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1(PAI-1) are widely upregulated in fibrotic diseases, including hypertrophic scars, keloids, and scleroderma. Here, we found that the successful binding of uPA and uPAR activates the downstream peroxisome proliferator-activated receptor (PPAR) signalling pathway to reduce the proliferation, migration, and contraction of disease-derived fibroblasts, contributing to the alleviation of skin fibrosis. However, increased or robust upregulation of the inhibitor PAI-1 inhibits these effects, suggesting of the involvement of PAI-1 in skin fibrosis. Subsequent in vivo studies showed that uPAR inhibitors increased skin fibrosis in mouse models, while uPA agonists and PAI-1 inhibitors reversed these effects. Our findings demonstrate a novel role for the uPA system and highlights its relationships with skin fibrosis, thereby suggesting new therapeutic approaches targeting the uPA system.

The m6A RNA Modification Modulates Gene Expression and Fibrosis-Related Pathways in Hypertrophic Scar.

Purpose: To systematically analyze the overall m6A modification pattern in hyperplastic scars (HS). Methods: The m6A modification patterns in HS and normal skin (NS) tissues were described by m6A sequencing and RNA sequencing, and subsequently bioinformatics analysis was performed. The m6A-related RNA was immunoprecipitated and verified by real-time quantitative PCR. Results: The appearance of 14,791 new m6A peaks in the HS sample was accompanied by the disappearance of 7,835 peaks. The unique m6A-related genes in HS were thus associated with fibrosis-related pathways. We identified the differentially expressed mRNA transcripts in HS samples with hyper-methylated or hypo-methylated m6A peaks. Conclusion: This study is the first to map the m6A transcriptome of human HS, which may help clarify the possible mechanism of m6A-mediated gene expression regulation.