Scar Model Research Articles

Effectiveness of artesunate combined with fractional CO2 laser in a hypertrophic scar model with underlying mechanism

Background and objectivesBoth artesunate and fractional CO2 laser have been proved effective in the treatment of hypertrophic scars, yet little data are available for the efficacy of artesunate combined with fractional CO2 laser. In order to assess the pre-clinical significance and the underlying mechanism of this combined treatment profile, we attempted to observe the effectiveness of this therapy in rabbit models through determining the expression of BMP-7 and Fas. Materials and methodsTwenty-Four New Zealand white rabbits with established hypertrophic scar samples were randomly divided into control group and three treatment groups. Artesunate (20 μl/cm2) was injected into the rat’s scar of artesunate and combination groups, while fractional CO2 laser (Combo mode, deep energy:10 mJ, super energy: 50 mJ) was applied to rats in fractional CO2 laser and combination groups at week 4 after model establishment. All rabbits underwent a total of 3 sessions of treatment once every 2 weeks. Histological and immunohistochemistry study, Western blot assay, cell viability, ELISA and RT-QPCR were performed at week 10 to observe the aspects of hypertrophic scar sample changes and expression of BMP-7 and Fas in the scar tissues. ResultsCompared with control group, hypertrophic scars and the collagen fibers were significantly inhibited after treatment, and higher inhibition was seen in the samples in combination group compared to that in artesunate and fractional CO2 laser groups (P < 0.01). Meanwhile, BMP-7 and Fas expressions were both notably increased in all treatment groups, and upregulation of the two proteins was dominant in combination group (P < 0.01). ConclusionsArtesunate combined with fractional CO2 laser is effective in hypertrophic scarring in this rabbit model. Our findings can serve as a potential alternative strategy to treatment of hypertrophic scar in clinical practice.

162 An Examination of Scar Modelling and Assessment Methods for the Evaluation of Scar Treatments

Abstract Introduction Scarring is the final common pathway for healing within the skin. Scars can be itchy, painful, tight, and disfiguring. Despite advances in surgery there is currently no reliably effective treatment for reducing or preventing scarring. The primary aim of this research is to assess the currently available models for scarring and evaluate/further develop the utility of current assessment tools, in an effort to design a pilot randomised control trial (RCT) for silicone gel treatment of scars. Method A systematic review of scar models in humans and animals. Examination of currently used subjective and objective scar assessment tools in a plastic surgery scar clinic. A retrospective cohort study assessing long-term scar outcomes in paediatric burn patients. Results Limitations and drawbacks of many existing methods to assess scar treatments were found. No statistically significant difference in long-term scarring outcomes was found between paediatric burns patients treated surgically versus conservatively. A RCT for silicone gel sheeting in the treatment of scars was set up and successful in recruitment. Conclusions Here, we have demonstrated difficulties in establishing a scientific scar treatment model; and created a pilot study that will help to provide high-quality evidence for the efficacy of silicone gel sheeting as a treatment for scars.

Corilagin alleviates hypertrophic scars via inhibiting the transforming growth factor (TGF)-β/Smad signal pathway

AimsExploring the effects of corilagin on hypertrophic scar (HS) and its underlying mechanisms. Main methodsHuman HS-derived fibroblasts (HSFs) were isolated and treated with corilagin. To investigate the effects of corilagin on HSFs, quantitative real time polymerase chain reaction (qRT-PCR), western blotting, wound healing, and immunofluorescence assays were performed. These effects were confirmed in a rabbit ear scar model by histological and immunohistochemical studies. Lastly, western blot assay was performed to detect the protein levels of several components of the transforming growth factor (TGF)-β/Smad signaling pathway, as well as the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). Key findingsCorilagin showed multiple effects on HSFs, including does-dependent inhibition of collagen production, cell proliferation, and migration, besides suppression of the activation of HSFs. Moreover, corilagin suppressed HS formation and collagen deposition in a rabbit ear scar model. Corilagin also inhibited fibroblast proliferation and α-smooth muscle actin (α-SMA) expression in vivo. Finally, western blot analysis revealed that corilagin downregulated the protein levels of TGF-β1 and TGF-β receptor type I (TGFβRI), thus lowering the level of p-smad2/3, also affected the protein levels of MMPs and TIMP1. SignificanceCorilagin could be a potential agent for HS treatment through the inhibition of extracellular matrix (ECM) deposition and multiple functions of fibroblasts.

Transplantation of human amniotic epithelial cells promotes morphological and functional regeneration in a rat uterine scar model

BackgroundCesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. Human amniotic epithelial cells (hAECs) have shown great promise in tissue regeneration. This study aims to investigate whether hAEC transplantation has the therapeutic effects on the rat uterine scar following full-thickness injury.MethodsA rat uterine scar model was established by excising the full-thickness uterine wall of about 1.0 cm in length and 1/2–2/3 of the total circumference in width. At day 30 post-surgery, hAECs were transplanted into the uterine scar. At day 30 and 60 post-transplantation, hematoxylin and eosin (H&E) staining, Masson staining, and IHC staining for vWF, VEGFA, α-SMA, and MMP-8 were performed to evaluate the regeneration of the scarred uterus and the underlying mechanism. Pregnancy outcomes were assessed at day 60 after hAEC transplantation. Finally, hAECs were incubated with hydrogen peroxide to verify the paracrine effect of hAECs.ResultsCollagen deposition, thin myometrium, and injured endometrium were observed in the rat uterine scar model. After hAEC transplantation, collagen deposition in the uterine scar decreased, and myometrial and endometrial recovery was facilitated. hAEC transplantation also increased the fetus number implanted within the scarred area. Moreover, we found hAECs promoted angiogenesis via upregulation of VEGFA and decreased collagen deposition by upregulating MMP-8 in the uterine scar. The in vitro studies further demonstrated an increase in the expression level of MMP-8 in hAECs cultured with hydrogen peroxide.ConclusionsThese results suggested that hAEC transplantation may be efficacious in the functional repair and collagen degradation of uterine scars, which provides a new therapeutic strategy to CSD.

Establishment of a long-term hypertrophic scar model by injection of anhydrous alcohol: A rabbit model.

The processes of hypertrophic scar formation are extremely complex, and current animal models have limitations in terms of the complete characterization of lesions. An ideal animal model is indispensable for exploring the complex progression of scar formation to elucidate its pathophysiology and to perform therapeutic testing. This study aimed to establish a long-term, consistent and easily testable animal model by injecting anhydrous alcohol into the dorsal trunk dermis of rabbits. The rabbits were injected with different amounts of anhydrous alcohol. Anhydrous alcohol was infiltrated into the subcutaneous and superficial fascia. The optimal amount of anhydrous alcohol was determined by measuring the area and thickness of the scar. The typical model was established by determining the optimum dosage, and then we analysed the histological characteristics and fibrosis-associated protein expression. The dermal scar was generated by treating with 2ml/kg anhydrous alcohol and displayed histopathologic features that characterize human hypertrophic scarring, including a parallel collagen fibre orientation, dermal and epidermal thickening, broad collagen deposition and the loss of dermal adnexal structures. The expression of fibrotic pan-markers was also enhanced. Moreover, the scar features and duration were compared between the anhydrous alcohol model and the rabbit ear model. Our results show that injecting anhydrous alcohol in the rabbit model thickened the dermal tissue, stimulated dermal fibroproliferation and resulted in hypertrophic scars with protein and histologic features similar to those seen in humans. Taken together, the findings from this study show that our model could be a feasible and useful tool for further research on the pathogenesis of hypertrophic scars.

Inhibition of hypertrophic scar formation with oral asiaticoside treatment in a rabbit ear scar model.

Hypertrophic scar (HS) is a fibrotic skin disease characterised by over‐productive collagen and excessive inflammatory reaction, which can be functionally and cosmetically problematic. A scar‐prone constitute will accelerate HS formation and functional disorder, which deserves systemic therapy with oral medicine. To examine the oral therapeutic effectiveness on HS with convincing evidence of gross view and histological improvement, a rabbit ear HS model was employed with oral administration of asiaticoside (AS) at the doses of 12 and 24 mg kg−1 d−1 daily for 60 consecutive days. Gross observation and histological findings showed that oral AS treatment could significantly inhibit HS formation in a dose dependent manner. Semi‐quantification of scar elevation index at days 7, 15, 30, and 60, and quantitative polymerase chain reaction at days 30 and 60 also provided the evidences of reduced scar thickness and inhibited fibrotic gene expressions of collagens I, III, TGF‐β1, interleukins 1β, 6 and 8, and enhanced gene expression of SMAD 7 and PPAR‐γ with a dose‐dependent manner. These results indicated that AS is likely to serve as a systemic therapeutic agent of HS treatment for those who may have scar‐prone constitute via anti‐inflammation, inhibiting fibrotic process, and enhancing matrix degradation.

ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts.

Background: Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this study was to explore whether ABT-263 could target apoptosis of overactivated myofibroblasts in hypertrophic scar. Methods: In vivo, we used ABT-263 to treat scars in a rabbit ear scar model. Photographs and ultrasound examination were taken weekly, and scars were harvested on day 42 for further Masson trichrome staining. In vitro, the expression levels of BCL-2 family members, including prosurvival proteins, activators, and effectors, were detected systematically in hypertrophic scar tissues and adjacent normal skin tissues, as well as in human hypertrophic scar fibroblasts (HSFs) and human normal dermal fibroblasts (HFBs). The roles of ABT-263 in apoptosis and proliferation of HSFs and HFBs were determined by annexin V/PI assay, CCK-8 kit, and cell cycle analysis. Mitochondrial membrane potential was evaluated by JC-1 staining and the expression of type I/III collagen and α-SMA was measured by PCR, western blotting, and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism. Results: In vivo, ABT-263 could significantly improve the scar appearance and collagen arrangement, decrease scar elevation index (SEI), and induce cell apoptosis. In vitro, the expression levels of BCL-2, BCL-XL, and BIM were significantly higher in scar tissues and HSFs than those in normal skin tissues and HFBs. ABT-263 selectively induced HSFs apoptosis by releasing BIM from binding with prosurvival proteins. Moreover, ABT-263 inhibited HSFs proliferation and reduced the expression of α-SMA and type I/III collagen in a concentration- and time- dependent manner. Conclusion: HSFs showed increased mitochondrial priming with higher level of proapoptotic activator BIM and were primed to death. ABT-263 showed great therapeutic ability in the treatment of hypertrophic scar by targeting HSFs.

Depression and executive functioning bidirectionally impair one another across 9years: Evidence from within-person latent change and cross-lagged models.

Scar and vulnerability models assert that increased psychopathology may predict subsequent executive functioning (EF) deficits (and vice versa) over protracted timescales, yet most prior work on this topic has been cross-sectional. Thus, we tested the within- and between-person relations between EF, depression, and anxiety. Older adult participants (n=856) were assessed across four waves, approximately 2years apart. Performance-based EF and caregiver-rated symptom measures were administered. Bivariate latent change score and random-intercept cross-lagged panel models were conducted. Within persons, random-intercept cross-lagged panel models revealed that prior greater depression forecasted lower subsequent EF, and vice versa (d=-0.292 vs. -0.292). Bivariate dual latent change score models showed that within-person rise in depression predicted EF decreases, and vice versa (d=-0.245 vs. -0.245). No within-person, cross-lagged, EF-anxiety relations emerged. Further, significant negative between-person EF-symptom relations were observed (d=-0.264 to -0.395). Prospective, within-person findings offer some evidence for developmental scar and vulnerability models.

A Rodent Model of Hypertrophic Scarring: Splinting of Rat Wounds.

Human hypertrophic scars are the result of imperfect healing of skin, which is particularly evident from the scars developing after severe burns. In contrast, mouse and rat full-thickness skin wounds heal normally without forming visible scar tissue, which reduces the suitability of rodent models for the study of skin scarring. We here provide a simple procedure to splint the edges of full-thickness rodent skin with a sutured plastic frame that prevents wound closure by granulation tissue contraction. The resulting mechanical tension in the wound bed and the lack of neo-epithelium amplify myofibroblast formation and generate hypertrophic features, not unlike those of human skin. In addition to producing scar tissue, the splint provides a reservoir that can be used for the delivery of cellular and acellular wound treatment regimen. Despite being simple and almost historical, wound splinting is a robust and reliable model to study myofibroblast biology.

Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagen-based biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model.

Hypertrophic scarring (HS) is an intractable complication associated with cutaneous wound healing. Although transforming growth factor β1 (TGF-β1) has long been documented as a central regulatory cytokine in fibrogenesis and fibroplasia, there is currently no cure. Gene therapy is emerging as a powerful tool to attenuate the overexpression of TGF-β1 and its signaling activities. An effective approach may require transferring multiple genes to regulate different aspects of TGF-β1 signaling activities in a Spatio-temporal manner. Herein we report the additive anti-fibrotic effects of two plasmid DNAs encoding interleukin 10 (IL-10) and decorin (DCN) co-delivered via a biphasic 3D collagen scaffold reservoir platform. Combined gene therapy significantly attenuated inflammation and extracellular matrix components' accumulation in a rabbit ear ulcer model; and suppressed the expressions of genes associated with fibrogenesis, including collagen type I, as well as TGF-β1 and TGF-β2, while enhancing the genes commonly associated with regenerative healing including collagen type III. These findings may serve to provide a non-viral gene therapy platform that is safe, optimized, and effective to deliver multiple genes onto the diseased tissue in a wider range of tissue fibrosis-related maladies.

Efficacy and safety of a dual-scan protocol for carbon dioxide laser in the treatment of split-thickness skin graft contraction in a red Duroc pig model.

BackgroundFractional CO2 laser plays an important role in scar management post split-thickness skin graft by loosening the graft contracture and restoring the smoothness of the surface. However, the optimal treatment protocol remains unknown. This study applied a dual-scan protocol to achieve both releasing and ablation of contracted skin graft. We comprehensively describe this treatment method and compare the efficacy and safety between this dual-scan method and the conventional mono-scan mode.MethodsA hypercontracted scar model after split-thickness skin grafting in red Duroc pigs was established. All scars meeting the inclusion criteria were randomly divided into four groups: high fluence–low density (HF–LD), low fluence–high density (LF–HD), combined group and control group. The energy per unit area was similar in the HF–LD and LF–HD groups. Two laser interventions were performed at a 6-week interval. The efficacy of the treatment was evaluated by objective measures of scar area, release rate, elasticity, thickness and flatness, while the safety was evaluated based on adverse reactions and melanin index. Collagen structure was observed histologically. The animals were followed up for a maximum of 126 days after modeling.ResultsA total of 28 contracted scars were included, 7 in each group. At 18 weeks postoperatively, the HF–LD and the combined groups showed significantly increased scar release rate (p = 0.000) and elasticity (p = 0.036) and decreased type I/III collagen ratio (p = 0.002) compared with the control and LF–HD groups. In terms of flatness, the combined group was significantly better than the HF–LD group for elevations <1 mm (p = 0.019). No significant skin side effects, pigmentation or scar thickness changes were observed at 18 weeks.ConclusionsDual-scan protocol could achieve superficial ablation and deep release of contracted split-thickness skin graft in a single treatment, with similar contraction release and texture improvement compared to a single deep scan. Its main advantage is to restore a smoother scar appearance. Adequate laser penetration was necessary for the release of contracted scars.

A six-herb Chinese medicine composition ointment as a promising candidate for treatment of hypertrophic scars

ObjectiveTo study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition (SCMC) ointment on the rabbit ear hypertrophic scar models. MethodsThe optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests. The SCMC ointment was prepared through emulsifying method. The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment. ResultsOur results demonstrated that all the quality control indications of the SCMC ointment met the requirements. Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading, and took an unobvious but palpable shift from hard to soft texture with the low, middle and high concentration SCMC ointments treatments in vivo. Additionally, on 21st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group, in a concentration-dependent manner. The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation. ConclusionThe SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues. Our research has demonstrated the Chinese medicine composition ointment with good anti-hypertrophic scar properties that could be used to treat hypertrophic scars. Meanwhile, it provides a theoretical basis for further clinical application.

Scaffolding Augmented Reality Model to Enhance Deep Reading Skill

Deep Reading (DR) is an advance reading skill which requires the learners to immerse themselves in what they read to get its concept and details. For new learners it's difficult to acquire DR skill. This research designs Scaffolding Augmented Reality Model (SC-AR Model) as a scaffolding tool to create an immersive learning environment to enhance DR skill for new learners. The process of SC-AR Model consists of: 1) teaching about the theory of DR; 2) using Augmented Reality (AR) as visual media overlaying on the text while reading; and 3) testing after reading. The researcher implements SC-AR Model to the sample group and the result shows that the progress scores of learners are significantly higher, and higher than the group that read only the text, without SC-AR. The conclusion, therefore, is that SC-AR Model effectively improves learner's DR skill. This Model can also be applied to improve DR skill in any other foreign languages.

ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts

Background: Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great anti-tumor characteristics by targeting tumor cells apoptosis. The objective of this study was to explore the potential therapeutical effects of ABT-263 on hypertrophic scar formation in vivo and in vitro. Methods: In vivo, we used ABT-263 to treat scars in a rabbit ear scar model. Photographs and ultrasound examination were taken weekly, and scars were harvested on day 42 for further Masson trichrome staining. In vitro, the expression levels of BCL-2 family members, including pro-survival proteins, activators and effectors, were detected systematically in human hypertrophic scar fibroblasts (HSFs) and human normal dermal fibroblasts (HFBs). The roles of ABT-263 in apoptosis and proliferation of HSFs and HFBs were determined by Annexin V/PI assay, CCK-8 kit and cell cycle analysis. Mitochondrial membrane potential was evaluated by JC-1 staining and the expression of type I/III collagen and α-SMA were measured by PCR, western blotting and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism. Findings: In vivo, ABT-263 could significantly improve the scar appearance and collagen arrangement, and decrease scar elevation index (SEI). In vitro, the expression levels of BCL-2, BCL-XL and BIM were significantly higher in HSFs than that in HFBs. ABT-263 selectively induced HSFs apoptosis by releasing BIM from binding with pro-survival proteins. Moreover, ABT-263 inhibited HSFs proliferation and reduced the expression of α-SMA and type I/III collagen in a concentration- and time- dependent manner. Interpretation: HSFs showed increased mitochondrial priming with higher level of pro-apoptotic activator BIM and were primed to death. ABT-263 showed great therapeutic ability in the treatment of hypertrophic scar by targeting HSFs. Funding Statement: This work was supported by National Key RD Youth Incubation Plan of the Military Medical Science and Technology (20QNPY035)；the National Nature Science Foundation of China (81701905, 81772076, 81871559, 81571897); and Shanghai health system excellent talent training program (2017BR037). Declaration of Interests: The authors declare no competing interests with relevance to this study. Ethics Approval Statement: All experimental procedures have been approved by the Ethics Committee of Changhai Hospital, Shanghai, China. Informed consent was obtained. All animal studies were approved by the Animal Center of the Naval Military Medical University, Shanghai, China.

Assessment of progressive alterations in collagen organization in the postoperative conjunctiva by multiphoton microscopy.

Glaucoma filtration surgery (GFS) commonly fails due to excessive fibrosis. As collagen structure aberrations is implicated in adverse fibrotic progression, this study aims to uncover collagen organization alterations during postoperative scarring. Via quantitative second harmonic generation/two photon excitation multiphoton imaging, we reveal the scar development and phenotype in the mouse model of conjunctival scarring. We also show that multiphoton imaging corroborated the collagen ultrastructure anomaly characteristic of the SPARC-/- mouse postoperative conjunctiva. These data improve our understanding of postoperative conjunctival scarring and further enhance the utility of this model for the development of anti-fibrotic therapeutics for GFS.

BTXA Could Induce Fibroblast Apoptosis and Inhibit the Expression of α-SMA and Myosin II in Scar Tissue of Rabbit Ears

Purpose This study aims to explore the effects of BTXA on the proteins that affect the contraction of fibroblasts. Moreover, the optimal dose of BTXA on hypertrophic scars has not yet been determined. The current study investigated the effect of different doses of BTXA on scar formation. Materials and Methods 18 rabbits’ ears of New Zealand rabbits were used to establish hypertrophic scar model. These wounds were divided into four groups as group B (treated with deferent dosage of BTXA), group T (treated with TAC), group S (not treated), and group C (normal skin). Fibroblast apoptosis was detected by the method of TUNEL. Collagen I, III, and TGF-β1 expression were examined by western blotting method. The immunohistochemical staining and computerized image analysis were used to measure the optical density (OD value) of positive staining of α-SMA and myosin II. Results With increasing BTXA dose, the apoptotic rates increased. Western blot showed that Collagen fibrils and TGF-β1 proteins were expressed lower with the increasing of dose of BTXA (P < 0.05). α-SMA and myosin II in Group B were significantly decreased than those in Group T (P < 0.05), moreover, more myosin II can be reduced with high concentrations of BTXA (2.0 IU). Conclusions It was shown that BTXA could induce fibroblast apoptosis and inhibit the expression of α-SMA and myosin II, which can inhibit FB contraction. It plays a positive role in the treatment of scar.

Uterine Scarring Leads to Adverse Pregnant Consequences by Impairing the Endometrium Response to Steroids.

Uterine surgical scarring is an increasing risk factor for adverse pregnant consequences that threaten fetal-maternal health. The detailed molecular features of scar implantation remain largely unknown. We aim to study the pathologic features of uterine surgical scarring and the mechanisms of compromised pregnancy outcomes of scar implantation. We generated a mouse model of uterine surgical scarring with a uterine incision penetrating the myometrium to endometrium to examine the pathologic changes and transcriptome profiles of uterine scarring at various postsurgery (PS) time points, as well as features of the feto-maternal interface during scar implantation. We found that uterine surgical scar recovery was consistently poor at PS3 until PS90, as shown by a reduced number of endometrial glands, inhibition of myometrial smooth muscle cell growth but excessive collagen fiber deposition, and massive leukocyte infiltration. Transcriptome annotation indicated significant chronic inflammation at the scarring site. At the peri-implantation and postimplantation stages, abnormal expression of various steroid-responsive genes at the scarring site was in parallel with lumen epithelial cell hyperplasia, inappropriate luminal closure, and disorientation of the implanted embryo, restricted stromal cell proliferation, and defective decidualization. High embryonic lethality (around 70%) before E10.5 was observed, and the small amount of survival embryos at E10.5 exhibited restricted growth and aberrant placenta defects including overinvasion of trophoblast cells into the decidua and insufficient fetal blood vessel branching in the labyrinth. The findings indicate that chronic inflammation and compromised responses to steroids in uterine scar tissues are the pivotal molecular basis for adverse pregnancy consequences of scar implantation.

Human-specific gene CHRFAM7A mediates M2 macrophage polarization via the Notch pathway to ameliorate hypertrophic scar formation

Hypertrophic scars often cause great pain to patients. It is generally believed that anti-inflammatory scar therapies are the best strategies for treatment because excessive inflammation is observed in hypertrophic scar tissue. However, the results of such treatment are unsatisfactory. In recent studies, immune stimulatory therapies have been suggested to be a preferable method for ameliorating hypertrophic scars. In this study, the expression of the human-specific gene CHRFAM7A, which has been reported to be a promoter of inflammation, was found to be lower in human hypertrophic scars than in normotrophic scars. The CHRFAM7A gene was overexpressed in a hypertrophic scar mouse model using a lentivirus system. Scar fibrosis decreased in the CHRFAM7A transfection group compared to the control group, and the proportion of M2 macrophages decreased at 4 and 8 weeks after establishing the model. We also found that CHRFAM7A increased the activation of the Notch pathway, which eventually attenuated M2 polarization. In the CHRFAM7A-transfected hypertrophic scar mouse group, the number of M1 macrophages increased dramatically in the initial period. Moreover, the expression of the inflammatory gene TNFα was also increased in transfected mice. Our results demonstrate that CHRFAM7A can effectively ameliorate hypertrophic scar formation via regulation of macrophage phenotypic transition. CHRFAM7A might be a therapeutic target for hypertrophic scars.

The Relationship between Positive Youth Development and Depressive Symptoms among Chinese Early Adolescents: A Three-Year Cross-Lagged Analysis.

Based on the development assets theory and the scar model, the present study examined the relationship between positive youth development (PYD) and depressive symptoms among Chinese early adolescents using a three-year longitudinal study design. Data from three waves were collected from 1301 students (Mean age = 12.46, SD = 0.63 years and 51.2% boys at wave 1) across the junior high school period (Grades 7–9). All participants completed a questionnaire that included the Center for Epidemiologic Studies Depression Scale (CES-D) and the Chinese Positive Youth Development Scale (CPYD) once a year over three years. After controlling for age and gender, this study found that PYD significantly predicted subsequent depressive symptoms. However, depressive symptoms did not significantly predict subsequent PYD. The results indicated a unidirectional relationship between PYD and depressive symptoms, where a reduction in PYD may increase subsequent depressive symptoms, though not vice versa. Besides, the negative cross-sectional correlation between PYD and depressive symptoms remains significant and stable from first year (T1) to third year (T3). These findings suggest that promoting PYD may be a promising approach to preventing/reducing adolescent depressive symptoms.

Larger increase in trait negative affect is associated with greater future cognitive decline and vice versa across 23 years.

Trait negative affect (NA) is a central feature of anxiety and depression disorders. Neurocognitive and scar models propose that within-person increase in NA across one period of time relates to a decline in cognitive functioning at a future period of time and vice versa. Yet, there has been little research on whether a within-person change in trait NA across one time-lag precedes and is associated with a change in cognition across a future time lag and vice versa. Due to a growing aging population, such knowledge can inform evidence-based prevention. Participants were 520 dementia-free community-dwelling adults (mean age = 59.76 years [standard deviation = 8.96], 58.08% females). Trait-level NA (negative emotionality scale), spatial cognition (block design and card rotations), verbal working memory (WM; digit span backward), and processing speed (symbol digit modalities) were assessed at five time points (waves) across 23 years. Bivariate dual latent change score (LCS) approaches were used to adjust for regression to the mean, lagged outcomes, and between-person variability. Unique bivariate LCS models showed that within-person increase in trait NA across two sequential waves was related to declines in spatial cognition, verbal WM, and processing speed across the subsequent two waves. Moreover, within-person reductions in spatial cognition, verbal WM, and processing speed across two sequential waves were associated with future increases in trait NA across the subsequent two waves. Findings concur with neurobiological and scar theories of psychopathology. Furthermore, results support process-based emotion regulation models that highlight the importance of verbal WM, spatial cognition, and processing speed capacities for downregulating NA.