AIM:To evaluate the effectiveness of knock-down of heat shock protein 47(HSP47)on conjunctival bleb scarring in a rat model and its possible mechanism.METHODS:Male Sprague–Dawley rats were used for glaucoma filtratio...AIM:To evaluate the effectiveness of knock-down of heat shock protein 47(HSP47)on conjunctival bleb scarring in a rat model and its possible mechanism.METHODS:Male Sprague–Dawley rats were used for glaucoma filtration surgery(GFS)and were treated with either phosphate buffered solution,shControl,mitomycin C,or sh-HSP47 using a microsyringe immediately after GFS.The morphology of filtering blebs was observed postoperatively.The levels of HSP47 were analyzed at 2,5,8,and 11d after GFS via real‑time quantitative polymerase chain reaction(PCR)and Western blot.The silencing effect of HSP47,the expression of collagen I and III,and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS.The protein levels of transforming growth factor-β1(TGF-β1),phospho-Smad2(pSmad2),phospho-Smad3(p-Smad3),and phospho-p38(p-p38)were also analyzed using Western blot.RESULTS:Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention.The levels of HSP47 were increased significantly at 5,8,and 11d postoperatively compared to the control group(P<0.05,P<0.01,and P<0.001).The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection(P<0.01).Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47(P<0.01).Moreover,the protein levels of TGF-β1,p-Smad2/3,and p-p38 were dramatically inhibited after treatment with sh-HSP47(P<0.01).CONCLUSION:The inhibitory effects of HSP47 knockdown on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.展开更多
AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin-binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit model. The aim of this study was to prepare a novel lo...AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin-binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit model. The aim of this study was to prepare a novel local delivery system for the sustained and controllable release of 5-Fu.METHODS: Twenty-four Japanese white rabbits were randomized into three groups: the experimental group (ocular trabeculectomy in combination with 5-Fu loaded freeze-dried bilayered fibrin-binding amniotic membrane transplantation), the control group (ocular trabeculectomy in combination with 5-Fu) and the blank group (single trabeculectomy). HE staining, massion staining and immunohistochemistry for α-SMA were performed on days 7, 14, 21 and 30 following surgery. The concentration of 5-Fu in rabbit aqueous humor was examined by high performance liquid chromatography (HPLC) 3 days after the surgery. RESULTS: Statistical differences were noted in intraocular pressure among groups on day 7, 14, 21 and 30 following surgery. Histology further demonstrated that trabeculectomy in combination with freeze-dried bilayered fibrin-binding amniotic membrane yielded well wound healing and no scar formation and was beneficial for long term effect. CONCLUSION: HPLC showed a good slow-release effect with freeze-dried bilayered fibrin-binding amniotic membrane.展开更多
Aim: The sternal region, cervico-mandibular region and the intra-mammary region have been the bane of many cutaneous surgeons, with a higher propensity for poor scarring and wound complications. In this article, the a...Aim: The sternal region, cervico-mandibular region and the intra-mammary region have been the bane of many cutaneous surgeons, with a higher propensity for poor scarring and wound complications. In this article, the author undertakes a review of different methods of breaking up scars by utilizing zigs and zags, and conducts a pigskin study to measure the reduction in tension that can be achieved by using a simple zigzag technique while performing excisions. Methods: A pigskin study conducted into the use of the simple zigzag to reduce the tension (and thereby scarring) of surgical wounds is reported here, and comparison and review is undertaken of the biomechanics of elliptical excisions and traditional Z-plasties. Results: Using a simple zigzag reduces tension across the midpoint of the scar more effectively than a Z-plasty or a simple elliptical excision. Conclusion: The techniques of breaking up a scar or incision line by using zigs and zags, in a means to reduce scarring, are not new. However, each of these techniques has specific advantages and disadvantages that need consideration by the surgeon. In this paper, a pigskin study is conducted into the use of the simple zigzag to reduce the tension (and thereby reduce the risk of poor scarring) of surgical wounds.展开更多
Purpose: The transforming growth factor beta1 (TGFB1) pathway has been linked to fibrosis in several tissues including skin, liver, kidney and the cornea. In this study, a RNA interference-based approach using siRNAs ...Purpose: The transforming growth factor beta1 (TGFB1) pathway has been linked to fibrosis in several tissues including skin, liver, kidney and the cornea. In this study, a RNA interference-based approach using siRNAs targeting three critical scarring genes, TGFB1, TGFB receptor 2 (TGFBR2) and connective tissue growth factor (CTGF), was tested for effects on reducing alpha smooth muscle actin (SMA) and corneal scarring (haze) in excimer laser ablated rabbit corneas. Methods: Levels of TGFB1 and CTGF mRNAs were measured using qRT-PCR in the epithelial and endothelial cell layers of normal and excimer ablated rabbit corneas at 30 minutes, 1 day and 2 days after ablation. Two different scarring models were utilized to assess the effects of the triple siRNA combination on corneal scarring. In the first model, rabbit corneas were unevenly ablated creating a mesh pattern then treated immediately with the triple siRNA combination. After 1 day the ablated areas of corneas were collected and levels of mRNAs for TGFB1, TGFBR2 and CTGF were measured. After 14 days, levels of mRNA for SMA were measured and SMA protein immunolocalized in frozen sections. In the second model, rabbit corneas were uniformly ablated to a depth of 155 microns followed by three daily doses of the triple combination of siRNA. After 14 days, corneas were photographed and images were analyzed using Image J software to assess corneal scarring. Corneas were also analyzed for levels of SMA mRNA. Results: In both unwounded and wounded corneas, levels of TGFB1 and CTGF mRNA were always significantly higher in endothelial cells than in epithelial cells (10 to 30 fold). Thirty minutes after injury, levels of both TGFB1 and CTGF mRNAs increased approximately 20-fold in both epithelial and endothelial cells, and further increased approximately 60-fold in 2 days. In the first therapeutic experiment with a single siRNA dose, two of three rabbits showed substantial reductions of all three target genes after 1 day with a maximum knock down of 80% of TGFb 1, 50% reduction of TGFBR2 and 40% reduction of CTGF mRNA levels and reduced SMA mRNA at day 14. In the second therapeutic experiment with multiple doses of siRNA treatment, both rabbits showed a ~22% reduction in scar formation at day 14 as calculated by image analysis. There was also a corresponding 70% and 60% reduction of SMA RNA expression. Conclusion: These results demonstrate that both TGFB1 and CTGF dramatically increase in rabbit corneal epithelial and endothelial cells after injury. Treatment of excimer ablated rabbit corneas with a triple combination of siRNAs effectively reduced levels of the target genes and SMA, leading to reduced corneal scarring at 14 days, suggesting that this triple siRNA combination may be an effective new approach to reducing scarring in cornea and other tissues.展开更多
Regenerative medicine has brought about refreshing new thinking about age old problems. However, some problems remain mostly untouched and are not being addressed. A point in question is the track of scar tissue left ...Regenerative medicine has brought about refreshing new thinking about age old problems. However, some problems remain mostly untouched and are not being addressed. A point in question is the track of scar tissue left behind post-operatively, which reveals the surgeon’s line of invasive incision. This confers on the patient an adverse psychological reminder and burden for the rest of his/her life. Most patients cannot afford corrective plastic surgery to ameliorate this skin defect. This paper seeks to ask whether biomedical scientists could play a role in arriving at a more pleasing cosmetic result, using a simple cell culture procedure of isolating un-manipulated autologous primary epidermal and dermal cells from a small skin tissue segment in close proximity to the surgeon’s incision line.展开更多
AIM:To evaluate the safety,visual and anatomic outcomes of fourier-domain optical coherence tomography(FD-OCT)-guided excimer laser phototherapeutic keratectomy(PTK)combined with photorefractive keratectomy(PRK)surger...AIM:To evaluate the safety,visual and anatomic outcomes of fourier-domain optical coherence tomography(FD-OCT)-guided excimer laser phototherapeutic keratectomy(PTK)combined with photorefractive keratectomy(PRK)surgery in treating anterior corneal scarring.METHODS:Clinical data of 23 eyes of 21 patients with anterior corneal scarring underwent FD-OCT-guided PTK and PRK from Dec.2014 to Jul.2016 were reviewed.Patients were assessed for preoperative and postoperative uncorrected visual acuity(UCVA),best spectacle-corrected visual acuity(BSCVA),contrast sensitivity(CS),FD-OCT,corneal topography and colour figures of anterior segments.RESULTS:The preoperative corneal pathologic conditions included viral keratitis(7 patients,7 eyes),band keratopathy(2 patients,4 eyes),corneal dystrophy(4 patients,4 eyes),traumatic corneal disease(2 patients,2 eyes)and corneal chemical injury(6 patients,6 eyes).Mean follow-up time was 10.65(range,3-19)mo.UCVA(in IogMAR)improved from a mean of 0.79(95%Cl,0.281.29)preoperatively to a mean of 0.45(95%Cl,0.29-0.62)postoperatively(P=0.021).BSCVA(in IogMAR)improved from 0.57(95%Cl,0.27-0.88)preoperatively to a mean of 0.28(95%Cl,0.15-0.41)postoperatively(P=0.001).Corneal topographic indices postoperatively showed significant improvement in corneal cylinder(P=0.009),the surface regularity index(P=0.007)and surface asymmetry index(P=0.00).Postoperative spherical equivalent averaged-0.53 diopters(-1.49 to 0.42).No complications were associated with the treatment.CONCLUSION:FD-OCT-guided PTK combined with PRK is safe and effective for the treatment of anterior corneal scarring by eliminating or reducing corneal opacities.展开更多
The inflammatory and fibrous responses to injuries are painful and are inhibitory to the regeneration of specialized cells. The fibrous scarring of skin injuries can also be disfiguring. Cells obtain energy not only f...The inflammatory and fibrous responses to injuries are painful and are inhibitory to the regeneration of specialized cells. The fibrous scarring of skin injuries can also be disfiguring. Cells obtain energy not only from the metabolism of food, but also via the alternative cellular energy (ACE) pathway. The ACE pathway is reflected in a dynamic (kinetic) quality of the body’s fluids. It is postulated to result from the absorption of an environmental force called KELEA (kinetic energy limiting electrostatic attraction). The body’s ACE pathway can be enhanced by the parental administration and even the oral consumption of products comprising KELEA activated water. One of these products, termed Enercel, was originally considered a complex homeopathic remedy. Another product is water containing electrolysis-generated, copper-silver-citrate (CSC) complexes. This product was initially formulated to be bacteriocidal, especially for Gram positive bacteria. This article describes the independent successful use of each of these two products in achieving essentially painless, scar-free healing of skin injuries. The skin injuries were due to a variety of causes including: vascular insufficiency from diabetes;hot water burn;penetrating object;chronic infection;and surgical incision. It is proposed that the ACE pathway increases the resilience of cells of the innate immune system to the triggering of an inflammatory reaction by “danger signals” released from damaged tissues. KELEA activated water should be widely available for the urgent therapy of burns and other traumatic injuries to the skin. ACE pathway enhancing modalities also need to be evaluated in the repair of cellular damage occurring to the heart, brain and other internal organs of the body.展开更多
Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of f...Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.展开更多
Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogr...Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.展开更多
We are pleased to announce that“The 11th SCAR Open Science Conference”will take place in Pucón,Chile from 19-23 August 2024,hosted by the Chilean Antarctic Institute.Detailed information at https://www.scar2024...We are pleased to announce that“The 11th SCAR Open Science Conference”will take place in Pucón,Chile from 19-23 August 2024,hosted by the Chilean Antarctic Institute.Detailed information at https://www.scar2024.org/.The 11th SCAR Open Science Conference theme“Antarctic Science:Crossroads for a New Hope”,recognizes the importance of Antarctica as a unique and fragile ecosystem.With increasing concerns about climate change and its impact on the polar regions,this theme aims to highlight the significance of Antarctic research in shaping our understanding of global environmental challenges.By fostering collaboration and knowledge exchange,the SCAR Open Science conference hopes to inspire new solutions and a renewed sense of hope for the future of our planet.展开更多
Though survival rate following severe thermal injuries has improved,the incidence and treatment of scarring have not improved at the same speed.This review discusses the formation of scars and in particular the format...Though survival rate following severe thermal injuries has improved,the incidence and treatment of scarring have not improved at the same speed.This review discusses the formation of scars and in particular the formation of hypertrophic scars.Further,though there is as yet no gold standard treatment for the prevention or treatment of scarring,a brief overview is included.A number of natural therapeutics have shown beneficial effects both in vivo and in vitro with the potential of becoming clinical therapeutics in the future.These natural therapeutics include both plant-based products such as resveratrol,quercetin and epigallocatechin gallate as examples and includes the non-plant-based therapeutic honey.The review also includes potential mechanism of action for the therapeutics,any recorded adverse events and current administration of the therapeutics used.This review discusses a number of potential'treatments'that may reduce or even prevent scarring particularly hypertrophic scarring,which is associated with thermal injuries without compromising wound repair.展开更多
Background:To present a method,alternative to penetrating keratoplasty,for the restoration of impaired corneal clarity with anterior stromal scarring following long-standing corneal graft failure.Case presentation:A 4...Background:To present a method,alternative to penetrating keratoplasty,for the restoration of impaired corneal clarity with anterior stromal scarring following long-standing corneal graft failure.Case presentation:A 48-year old female who had previously underwent Descemet stripping automated endothelial keratoplasty(DSAEK)for the treatment of pseudophakic bullous keratopathy,presented with longstanding corneal oedema and anterior corneal scarring.A significant improvement in corrected distance visual acuity was demonstrated,as corneal clarity was restored following graft exchange and phototherapeutic keratectomy(PTK).Conclusions:The combination of corneal graft exchange and phototherapeutic keratectomy may represent an effective therapeutic option for long-standing corneal oedema with concomitant anterior corneal scarring after failure of a DSAEK graft.展开更多
Background: It is commonly accepted that burns taking longer than 3 weeks to heal have a much higher rate of hypertrophic scarring than those which heal more quickly. However, some of our patients develop hypertrophic...Background: It is commonly accepted that burns taking longer than 3 weeks to heal have a much higher rate of hypertrophic scarring than those which heal more quickly. However, some of our patients develop hypertrophic scars despite healing within this 3-week period. Methods: We performed a prospective study of 383 paediatric burns treated non-operatively at a regional burns centre over a 2-year period from May 2011 to April 2013. Scar assessment was performed by a senior burns therapist using the Vancouver Scar Scale. Results: Overall rates of hypertrophic scarring were 17.2%. Time to healing was the strongest predictor of developing hypertrophic scarring, and the earliest hypertrophic scar developed in a patient who was healed after 8 days. The risk of hypertrophic scarring was multiplied by 1.138 for every additional day taken for the burn wound to heal. There was a trend towards higher rates of hypertrophic scarring in non-white skin types but this did not reach statistical significance. Conclusions: The risk of hypertrophic scarring increases with every day and, therefore, every effort should be made to get the wound healed as quickly as possible, even within the traditional 3-week period usually allowed for healing. We believe that the traditional dogma of aiming for healing within 3 weeks is overly simplistic and should be abandoned: in paediatric burns, every day counts.展开更多
Background:Chronic total occlusion(CTO)is a critical and unique subgroup of coronary lesions.This study aimed to investigate the correlation between the Selvester QRS score and late gadolinium enhancement cardiac magn...Background:Chronic total occlusion(CTO)is a critical and unique subgroup of coronary lesions.This study aimed to investigate the correlation between the Selvester QRS score and late gadolinium enhancement cardiac magnetic resonance imaging(LGE-CMRI)in quantifying myocardial scarring to provide a simple and feasible method for treating CTO.Methods:The medical records of 134 patients with absolute CTO who underwent coronary angiography between May 1,2014 and December 30,2017 were retrospectively reviewed.All patients were grouped according to the CTO location(right coronary artery[RCA]CTO,left artery descending[LAD]CTO,left circumflex[LCX]CTO,and multivessel CTO groups).The degree of myocardial scarring was determined according to the Selvester QRS score and using the LGE-CMRI.All patients were followed up for at least 12 months.Results:Among the 62 CTO patients,55 had occlusion of a single vessel and seven had occlusion of multiple vessels,of which 27(43.55%)were in the RCA CTO group,16(25.81%)in the LAD CTO group,12(19.35%)in the LCX CTO group,and 7(11.29%)in the multivessel CTO group.The area under the receiver operating characteristic curve for the QRS score that was used to determine the degree of myocardial scarring was 0.806,with a sensitivity and specificity of 94.7%and 42.1%,respectively.The Selvester QRS score and LGE-CMRI measures of scar size were correlated in the RCA CTO,LCX CTO,and multivessel CTO groups(r=0.466,0.593,and 0.775,respectively).Conclusion:The Selvester QRS score was feasible for detecting myocardial scarring in patients with CTO.展开更多
A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithel...A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithelialstromal defects.Currently,the etiology and pathogenesis of these defects remain inadequately understood,necessitating further investigation through experimental research.Various modeling methods exist both domestically and internationally,each with distinct adaptive conditions,advantages,and disadvantages.This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury,including mechanical modeling,chemical alkali burns,post-refractive surgery infections,and genetic engineering.The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.展开更多
Background:Damage to the skin and underlying tissues due to thermal burns is relevant.Despite the success of modern medicine,repairing thermal damage to the skin is a difficult task in reconstructive plastic surgery b...Background:Damage to the skin and underlying tissues due to thermal burns is relevant.Despite the success of modern medicine,repairing thermal damage to the skin is a difficult task in reconstructive plastic surgery because of the nature of the damage and the regenerative features.Characteristic post-burn changes are associated with different depths of damage when areas of deep damage are combined with more superficial areas.Methods:We described a clinical case of the staged surgical treatment of a cicatricial deformity of the buccalperiorbital-perioral region resulting from a childhood burn injury from a hot object.The 44-year-old patient complained of an aesthetic and functional deformity of the buccal-periorbital-perioral region and had previously undergone repeated nonsurgical corrections.Results:A comprehensive approach to the surgical treatment of a patient with post-burn deformities using a diplene adhesive membrane directly affected the stage of the surgical treatment and contributed to improved functional and aesthetic results.Conclusion:The positive treatment results with preserved contraction and relaxation processes of the facial muscles as well as satisfactory aesthetic results allow us to recommend the use of a biodegradable diplene film during facial reconstructive operations.展开更多
Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatm...Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.展开更多
Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein...Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.展开更多
基金Supported by the National Natural Science Foundation of China(No.81500719)Shaanxi Science and Technology Project(No.2022SF-434)Xi’an Science and Technology Project(No.21YXYJ0044).
文摘AIM:To evaluate the effectiveness of knock-down of heat shock protein 47(HSP47)on conjunctival bleb scarring in a rat model and its possible mechanism.METHODS:Male Sprague–Dawley rats were used for glaucoma filtration surgery(GFS)and were treated with either phosphate buffered solution,shControl,mitomycin C,or sh-HSP47 using a microsyringe immediately after GFS.The morphology of filtering blebs was observed postoperatively.The levels of HSP47 were analyzed at 2,5,8,and 11d after GFS via real‑time quantitative polymerase chain reaction(PCR)and Western blot.The silencing effect of HSP47,the expression of collagen I and III,and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS.The protein levels of transforming growth factor-β1(TGF-β1),phospho-Smad2(pSmad2),phospho-Smad3(p-Smad3),and phospho-p38(p-p38)were also analyzed using Western blot.RESULTS:Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention.The levels of HSP47 were increased significantly at 5,8,and 11d postoperatively compared to the control group(P<0.05,P<0.01,and P<0.001).The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection(P<0.01).Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47(P<0.01).Moreover,the protein levels of TGF-β1,p-Smad2/3,and p-p38 were dramatically inhibited after treatment with sh-HSP47(P<0.01).CONCLUSION:The inhibitory effects of HSP47 knockdown on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.
基金Natural Science Foundation of Hubei Province, China (No.2008cda055)
文摘AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin-binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit model. The aim of this study was to prepare a novel local delivery system for the sustained and controllable release of 5-Fu.METHODS: Twenty-four Japanese white rabbits were randomized into three groups: the experimental group (ocular trabeculectomy in combination with 5-Fu loaded freeze-dried bilayered fibrin-binding amniotic membrane transplantation), the control group (ocular trabeculectomy in combination with 5-Fu) and the blank group (single trabeculectomy). HE staining, massion staining and immunohistochemistry for α-SMA were performed on days 7, 14, 21 and 30 following surgery. The concentration of 5-Fu in rabbit aqueous humor was examined by high performance liquid chromatography (HPLC) 3 days after the surgery. RESULTS: Statistical differences were noted in intraocular pressure among groups on day 7, 14, 21 and 30 following surgery. Histology further demonstrated that trabeculectomy in combination with freeze-dried bilayered fibrin-binding amniotic membrane yielded well wound healing and no scar formation and was beneficial for long term effect. CONCLUSION: HPLC showed a good slow-release effect with freeze-dried bilayered fibrin-binding amniotic membrane.
文摘Aim: The sternal region, cervico-mandibular region and the intra-mammary region have been the bane of many cutaneous surgeons, with a higher propensity for poor scarring and wound complications. In this article, the author undertakes a review of different methods of breaking up scars by utilizing zigs and zags, and conducts a pigskin study to measure the reduction in tension that can be achieved by using a simple zigzag technique while performing excisions. Methods: A pigskin study conducted into the use of the simple zigzag to reduce the tension (and thereby scarring) of surgical wounds is reported here, and comparison and review is undertaken of the biomechanics of elliptical excisions and traditional Z-plasties. Results: Using a simple zigzag reduces tension across the midpoint of the scar more effectively than a Z-plasty or a simple elliptical excision. Conclusion: The techniques of breaking up a scar or incision line by using zigs and zags, in a means to reduce scarring, are not new. However, each of these techniques has specific advantages and disadvantages that need consideration by the surgeon. In this paper, a pigskin study is conducted into the use of the simple zigzag to reduce the tension (and thereby reduce the risk of poor scarring) of surgical wounds.
文摘Purpose: The transforming growth factor beta1 (TGFB1) pathway has been linked to fibrosis in several tissues including skin, liver, kidney and the cornea. In this study, a RNA interference-based approach using siRNAs targeting three critical scarring genes, TGFB1, TGFB receptor 2 (TGFBR2) and connective tissue growth factor (CTGF), was tested for effects on reducing alpha smooth muscle actin (SMA) and corneal scarring (haze) in excimer laser ablated rabbit corneas. Methods: Levels of TGFB1 and CTGF mRNAs were measured using qRT-PCR in the epithelial and endothelial cell layers of normal and excimer ablated rabbit corneas at 30 minutes, 1 day and 2 days after ablation. Two different scarring models were utilized to assess the effects of the triple siRNA combination on corneal scarring. In the first model, rabbit corneas were unevenly ablated creating a mesh pattern then treated immediately with the triple siRNA combination. After 1 day the ablated areas of corneas were collected and levels of mRNAs for TGFB1, TGFBR2 and CTGF were measured. After 14 days, levels of mRNA for SMA were measured and SMA protein immunolocalized in frozen sections. In the second model, rabbit corneas were uniformly ablated to a depth of 155 microns followed by three daily doses of the triple combination of siRNA. After 14 days, corneas were photographed and images were analyzed using Image J software to assess corneal scarring. Corneas were also analyzed for levels of SMA mRNA. Results: In both unwounded and wounded corneas, levels of TGFB1 and CTGF mRNA were always significantly higher in endothelial cells than in epithelial cells (10 to 30 fold). Thirty minutes after injury, levels of both TGFB1 and CTGF mRNAs increased approximately 20-fold in both epithelial and endothelial cells, and further increased approximately 60-fold in 2 days. In the first therapeutic experiment with a single siRNA dose, two of three rabbits showed substantial reductions of all three target genes after 1 day with a maximum knock down of 80% of TGFb 1, 50% reduction of TGFBR2 and 40% reduction of CTGF mRNA levels and reduced SMA mRNA at day 14. In the second therapeutic experiment with multiple doses of siRNA treatment, both rabbits showed a ~22% reduction in scar formation at day 14 as calculated by image analysis. There was also a corresponding 70% and 60% reduction of SMA RNA expression. Conclusion: These results demonstrate that both TGFB1 and CTGF dramatically increase in rabbit corneal epithelial and endothelial cells after injury. Treatment of excimer ablated rabbit corneas with a triple combination of siRNAs effectively reduced levels of the target genes and SMA, leading to reduced corneal scarring at 14 days, suggesting that this triple siRNA combination may be an effective new approach to reducing scarring in cornea and other tissues.
文摘Regenerative medicine has brought about refreshing new thinking about age old problems. However, some problems remain mostly untouched and are not being addressed. A point in question is the track of scar tissue left behind post-operatively, which reveals the surgeon’s line of invasive incision. This confers on the patient an adverse psychological reminder and burden for the rest of his/her life. Most patients cannot afford corrective plastic surgery to ameliorate this skin defect. This paper seeks to ask whether biomedical scientists could play a role in arriving at a more pleasing cosmetic result, using a simple cell culture procedure of isolating un-manipulated autologous primary epidermal and dermal cells from a small skin tissue segment in close proximity to the surgeon’s incision line.
基金Supported by Grants from National Natural Science Foundation of China(No.81900830)National Key Research&Development Intensification Key Project(No.2016YFC1101103,No.2018YFA0107302)Basic Science and Frontier Technology Project in Chongqing Science and Technology Commission(No.cstc2016jcyjA0297).
文摘AIM:To evaluate the safety,visual and anatomic outcomes of fourier-domain optical coherence tomography(FD-OCT)-guided excimer laser phototherapeutic keratectomy(PTK)combined with photorefractive keratectomy(PRK)surgery in treating anterior corneal scarring.METHODS:Clinical data of 23 eyes of 21 patients with anterior corneal scarring underwent FD-OCT-guided PTK and PRK from Dec.2014 to Jul.2016 were reviewed.Patients were assessed for preoperative and postoperative uncorrected visual acuity(UCVA),best spectacle-corrected visual acuity(BSCVA),contrast sensitivity(CS),FD-OCT,corneal topography and colour figures of anterior segments.RESULTS:The preoperative corneal pathologic conditions included viral keratitis(7 patients,7 eyes),band keratopathy(2 patients,4 eyes),corneal dystrophy(4 patients,4 eyes),traumatic corneal disease(2 patients,2 eyes)and corneal chemical injury(6 patients,6 eyes).Mean follow-up time was 10.65(range,3-19)mo.UCVA(in IogMAR)improved from a mean of 0.79(95%Cl,0.281.29)preoperatively to a mean of 0.45(95%Cl,0.29-0.62)postoperatively(P=0.021).BSCVA(in IogMAR)improved from 0.57(95%Cl,0.27-0.88)preoperatively to a mean of 0.28(95%Cl,0.15-0.41)postoperatively(P=0.001).Corneal topographic indices postoperatively showed significant improvement in corneal cylinder(P=0.009),the surface regularity index(P=0.007)and surface asymmetry index(P=0.00).Postoperative spherical equivalent averaged-0.53 diopters(-1.49 to 0.42).No complications were associated with the treatment.CONCLUSION:FD-OCT-guided PTK combined with PRK is safe and effective for the treatment of anterior corneal scarring by eliminating or reducing corneal opacities.
文摘The inflammatory and fibrous responses to injuries are painful and are inhibitory to the regeneration of specialized cells. The fibrous scarring of skin injuries can also be disfiguring. Cells obtain energy not only from the metabolism of food, but also via the alternative cellular energy (ACE) pathway. The ACE pathway is reflected in a dynamic (kinetic) quality of the body’s fluids. It is postulated to result from the absorption of an environmental force called KELEA (kinetic energy limiting electrostatic attraction). The body’s ACE pathway can be enhanced by the parental administration and even the oral consumption of products comprising KELEA activated water. One of these products, termed Enercel, was originally considered a complex homeopathic remedy. Another product is water containing electrolysis-generated, copper-silver-citrate (CSC) complexes. This product was initially formulated to be bacteriocidal, especially for Gram positive bacteria. This article describes the independent successful use of each of these two products in achieving essentially painless, scar-free healing of skin injuries. The skin injuries were due to a variety of causes including: vascular insufficiency from diabetes;hot water burn;penetrating object;chronic infection;and surgical incision. It is proposed that the ACE pathway increases the resilience of cells of the innate immune system to the triggering of an inflammatory reaction by “danger signals” released from damaged tissues. KELEA activated water should be widely available for the urgent therapy of burns and other traumatic injuries to the skin. ACE pathway enhancing modalities also need to be evaluated in the repair of cellular damage occurring to the heart, brain and other internal organs of the body.
文摘Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.
基金supported by the National Natural Science Foundation of China,No.82073783(to YY)the Natural Science Foundation of Beijing,No.7212160(to YY).
文摘Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.
文摘We are pleased to announce that“The 11th SCAR Open Science Conference”will take place in Pucón,Chile from 19-23 August 2024,hosted by the Chilean Antarctic Institute.Detailed information at https://www.scar2024.org/.The 11th SCAR Open Science Conference theme“Antarctic Science:Crossroads for a New Hope”,recognizes the importance of Antarctica as a unique and fragile ecosystem.With increasing concerns about climate change and its impact on the polar regions,this theme aims to highlight the significance of Antarctic research in shaping our understanding of global environmental challenges.By fostering collaboration and knowledge exchange,the SCAR Open Science conference hopes to inspire new solutions and a renewed sense of hope for the future of our planet.
文摘Though survival rate following severe thermal injuries has improved,the incidence and treatment of scarring have not improved at the same speed.This review discusses the formation of scars and in particular the formation of hypertrophic scars.Further,though there is as yet no gold standard treatment for the prevention or treatment of scarring,a brief overview is included.A number of natural therapeutics have shown beneficial effects both in vivo and in vitro with the potential of becoming clinical therapeutics in the future.These natural therapeutics include both plant-based products such as resveratrol,quercetin and epigallocatechin gallate as examples and includes the non-plant-based therapeutic honey.The review also includes potential mechanism of action for the therapeutics,any recorded adverse events and current administration of the therapeutics used.This review discusses a number of potential'treatments'that may reduce or even prevent scarring particularly hypertrophic scarring,which is associated with thermal injuries without compromising wound repair.
文摘Background:To present a method,alternative to penetrating keratoplasty,for the restoration of impaired corneal clarity with anterior stromal scarring following long-standing corneal graft failure.Case presentation:A 48-year old female who had previously underwent Descemet stripping automated endothelial keratoplasty(DSAEK)for the treatment of pseudophakic bullous keratopathy,presented with longstanding corneal oedema and anterior corneal scarring.A significant improvement in corrected distance visual acuity was demonstrated,as corneal clarity was restored following graft exchange and phototherapeutic keratectomy(PTK).Conclusions:The combination of corneal graft exchange and phototherapeutic keratectomy may represent an effective therapeutic option for long-standing corneal oedema with concomitant anterior corneal scarring after failure of a DSAEK graft.
文摘Background: It is commonly accepted that burns taking longer than 3 weeks to heal have a much higher rate of hypertrophic scarring than those which heal more quickly. However, some of our patients develop hypertrophic scars despite healing within this 3-week period. Methods: We performed a prospective study of 383 paediatric burns treated non-operatively at a regional burns centre over a 2-year period from May 2011 to April 2013. Scar assessment was performed by a senior burns therapist using the Vancouver Scar Scale. Results: Overall rates of hypertrophic scarring were 17.2%. Time to healing was the strongest predictor of developing hypertrophic scarring, and the earliest hypertrophic scar developed in a patient who was healed after 8 days. The risk of hypertrophic scarring was multiplied by 1.138 for every additional day taken for the burn wound to heal. There was a trend towards higher rates of hypertrophic scarring in non-white skin types but this did not reach statistical significance. Conclusions: The risk of hypertrophic scarring increases with every day and, therefore, every effort should be made to get the wound healed as quickly as possible, even within the traditional 3-week period usually allowed for healing. We believe that the traditional dogma of aiming for healing within 3 weeks is overly simplistic and should be abandoned: in paediatric burns, every day counts.
文摘Background:Chronic total occlusion(CTO)is a critical and unique subgroup of coronary lesions.This study aimed to investigate the correlation between the Selvester QRS score and late gadolinium enhancement cardiac magnetic resonance imaging(LGE-CMRI)in quantifying myocardial scarring to provide a simple and feasible method for treating CTO.Methods:The medical records of 134 patients with absolute CTO who underwent coronary angiography between May 1,2014 and December 30,2017 were retrospectively reviewed.All patients were grouped according to the CTO location(right coronary artery[RCA]CTO,left artery descending[LAD]CTO,left circumflex[LCX]CTO,and multivessel CTO groups).The degree of myocardial scarring was determined according to the Selvester QRS score and using the LGE-CMRI.All patients were followed up for at least 12 months.Results:Among the 62 CTO patients,55 had occlusion of a single vessel and seven had occlusion of multiple vessels,of which 27(43.55%)were in the RCA CTO group,16(25.81%)in the LAD CTO group,12(19.35%)in the LCX CTO group,and 7(11.29%)in the multivessel CTO group.The area under the receiver operating characteristic curve for the QRS score that was used to determine the degree of myocardial scarring was 0.806,with a sensitivity and specificity of 94.7%and 42.1%,respectively.The Selvester QRS score and LGE-CMRI measures of scar size were correlated in the RCA CTO,LCX CTO,and multivessel CTO groups(r=0.466,0.593,and 0.775,respectively).Conclusion:The Selvester QRS score was feasible for detecting myocardial scarring in patients with CTO.
基金Supported by the National Key Research and Development Program of China(No.2020YFE0204400)the National Natural Science Foundation of China(No.82271042)the Zhejiang Province Key Research and Development Program(No.2023C03090).
文摘A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithelialstromal defects.Currently,the etiology and pathogenesis of these defects remain inadequately understood,necessitating further investigation through experimental research.Various modeling methods exist both domestically and internationally,each with distinct adaptive conditions,advantages,and disadvantages.This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury,including mechanical modeling,chemical alkali burns,post-refractive surgery infections,and genetic engineering.The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.
文摘Background:Damage to the skin and underlying tissues due to thermal burns is relevant.Despite the success of modern medicine,repairing thermal damage to the skin is a difficult task in reconstructive plastic surgery because of the nature of the damage and the regenerative features.Characteristic post-burn changes are associated with different depths of damage when areas of deep damage are combined with more superficial areas.Methods:We described a clinical case of the staged surgical treatment of a cicatricial deformity of the buccalperiorbital-perioral region resulting from a childhood burn injury from a hot object.The 44-year-old patient complained of an aesthetic and functional deformity of the buccal-periorbital-perioral region and had previously undergone repeated nonsurgical corrections.Results:A comprehensive approach to the surgical treatment of a patient with post-burn deformities using a diplene adhesive membrane directly affected the stage of the surgical treatment and contributed to improved functional and aesthetic results.Conclusion:The positive treatment results with preserved contraction and relaxation processes of the facial muscles as well as satisfactory aesthetic results allow us to recommend the use of a biodegradable diplene film during facial reconstructive operations.
文摘Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, Chamomilla recutita (chamomile) oil, Helianthus annuus (sunflower) oil, and Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.
基金supported by the Natural Science Foundation of Guangdong Province,No.2020A1515010090(to ZLZ)the Science and Technology Project Foundation of Guangzhou City,No.202002030004(to HZ).
文摘Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.
