The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on elimin...The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).展开更多
Objective: Pregnancy in a scarred uterus is considered to be high-risk, especially during parturition. Nevertheless, the literature favours vaginal delivery as long as obstetric conditions are favourable. The aim of o...Objective: Pregnancy in a scarred uterus is considered to be high-risk, especially during parturition. Nevertheless, the literature favours vaginal delivery as long as obstetric conditions are favourable. The aim of our study was to contribute to the improvement of delivery management for women with scar uteri at the CHU Communautaire. Methodology: This was a cross-sectional study conducted over an 18-month period from 01 January 2020 to 30 June 2021 on women with scar uterus who came to give birth at the CHU Communautaire maternity unit. The sample was exhaustive;any parturient with a history of scarred uterus of more than one year with a clinically normal pelvis and whose fetus was in cephalic presentation. The following were excluded from the study: pregnant women with a uterine scar of less than one year, fetuses in a non-cephalic vertex presentation, pregnant women with antecedent complicated childbirth at the previous cesarean section, large fetuses informed consent had been obtained from the pregnant women. Anomynia was respected throughout the study. Results: During this period, we recorded 205 parturients with a scar uterus. The incidence of delivery with a scar uterus was 9.5%. Uterine testing was attempted in 85.9% of cases, with a success rate of 75.6%. Factors predictive of a successful uterine test was: maternal age less than 35 years (P = 0.0027), entry into labour at the reference maternity hospital (P Conclusion: Delivery with a scarred uterus is an increasingly frequent occurrence at the Maternity Unit of the CHU Communautaire in Bangui. Uterine testing is the first option if conditions allow, but careful selection of candidates during antenatal care or at the very beginning of labour is necessary for this type of delivery.展开更多
Objective To verify the therapeutic effect of abdominal acupuncture combined with scarring moxibustion at Qìhǎi（气海 CV 6） on periarthritis of shoulder.Methods Thirty cases of periarthritis of shoulder were ra...Objective To verify the therapeutic effect of abdominal acupuncture combined with scarring moxibustion at Qìhǎi（气海 CV 6） on periarthritis of shoulder.Methods Thirty cases of periarthritis of shoulder were randomly divided into an acup-moxibustion group and an acupuncture group,15 cases in each group.The patients in the two groups were treated with abdominal acupuncture at Zhōngwǎn（中脘 CV 12）,Xiàwǎn（下脘 CV 10）,Shāngqǔ（商曲 KI 17）,Huáròumén（滑肉门 ST 24）,with scarring moxibustion at Qìhǎi（气海 CV 6） added in the acup-moxibustion group,5 treatments each week,altogether 15 treatments.The therapeutic effects were assessed on the 20th day of acupuncture.Results The effective rate was 93.3%（14/15） in both the acup-moxibustion group and the acupuncture group,and the cured and markedly effective rate in the acup-moxibustion group and the acupuncture group was 86.7%（13/15） and 53.3%（8/15）,respectively,the acup-moxibustion group being better than that in the acupuncture group（P〈0.01）;after treatment the cumulative score of pain and the cumulative score of shoulder joint active function were significantly increased in the two groups（all P〈0.05）,with more significantly increased in the acup-moxibustion group（both P〈0.05）.Conclusion The therapeutic effect of abdominal acupuncture combined with scarring moxibustion on periarthritis of shoulder is better than that of the simple abdominal acupuncture.展开更多
Objective:To explore the influence of scarring moxibustion on the changes of serum melatonin(MT)and neuropeptide Y(NPY)expressions in the insomnia model rats.Methods:A total of 40 SD rats were randomly divided into a ...Objective:To explore the influence of scarring moxibustion on the changes of serum melatonin(MT)and neuropeptide Y(NPY)expressions in the insomnia model rats.Methods:A total of 40 SD rats were randomly divided into a blank group,a model group,a scarring moxibustion group,an embedding needling group and a mild moxibustion group,8 rats in each group.The intraperitoneal injection of p-chlorophenylalanine(PCPA)was adopted to establish the insomnia model rats and the corresponding interventions were given,consecutively for 6 days.Separately,before modeling and the first intervention as well as before sample collection,the body weight was measured and the serum was collected in the insomnia model rats.The enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum MT and NPY.Results:Compared with the blank group,the body weight of rat in the model group was lower(P<0.01)and the levels of MT and NPY were lower in the model group(both P<0.05).Compared with the model group,in the scarring moxibustion group,the embedding needling group and the mild moxibustion group,the body weight and the levels of MT and NPY of the insomnia model rats were all higher(all P<0.05).Compared with the embedding needling group and the mild moxibustion group,the body weight and the levels of MT and NPY the insomnia model rats were all higher in the scarring moxibustion group(all P<0.05).In comparison between the embedding needling group and the mild moxibustion group,there were no statistical differences in the body weight and the levels of MT and NPY(all P>0.05).Conclusion:The regulation mechanism of sleep-wake circadian rhythm may be related to the levels of serum MT and NPY in the insomnia model rats.Scarring moxibustion increases the levels of MT and NPY more effectively and displays the effect in the intervention as compared with embedding needling and mild moxibustion in the insomnia model rats.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 alpha -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
Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand wh...Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed （about 15 d post wounding）. For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results： Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 （p〈0.05）. Scar thickness, measured by scar elevation index （SEI） at Day 35 post wounding, was significantly reduced in the intervention group （1.09±0.19） compared with the controls （1.36±0.28）. Microvessel density （MVD） observed in the intervention group （1.73±0.94） was significantly lower than that of the control group （5.63±1.78） on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions： Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-dedved growth factor （PDGF） and fibroblast growth factor （FGF）, thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.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
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
This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Re...This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation.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
Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features ...Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features of human RCT scars,characterized by disruption of tendon architecture,disorganized collagen fibrils,and imbalance in type Ⅰ/Ⅲ collagen ratios and fibril diameters.Using single-cell RNA sequencing of tendon stumps from patients with RCT,we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment.Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation,including tendon stem cell,senescent tenocyte,SOX9-driven pro-fibrotic macrophage,and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition(EndoMT).Furthermore,we found that osteopontin and TGF-βsignaling were key drivers of extracellular matrix deposition,and their blockade ameliorated fibrotic scarring after RCT.Collectively,our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.展开更多
Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacte...Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].展开更多
Objective： To investigate the relationship between fester capacity and clinical efficacy on allergic asthma treated by scarring moxibustion. Methods： The patients were randomly divided into scarring moxibustion 9-co...Objective： To investigate the relationship between fester capacity and clinical efficacy on allergic asthma treated by scarring moxibustion. Methods： The patients were randomly divided into scarring moxibustion 9-cone group, 3-cone group and 6-cone group. The biggest area, scab-lost time, first-festering time and scarring time of moxibustion sore, and the clinical efficacy in each group was observed. Results： The biggest post-moxibustion sore area in 9-cone group was larger than that in 3-cone group, but had no difference in comparison with 6-cone group; the scab-lost time, first-festering time and scarring time ofpost-moxibustion sore in each group were of no difference. The clinical efficacy was better in 9-cone group than in 3-cone group, but had no difference in comparison with the 6-cone group. Conclusion： Fester capacity in treating allergic asthma by scarring moxibustion is related to the clinical efficacy and definite fester capacity is the key to good results on allergic asthma.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecul...Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.展开更多
The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a ...The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a nanocomposite system constructed through the metal-phenolic network-mediated self-assembly of molybdenum polyoxometalate({Mo 154})and epigallocatechin gallate(EGCG),followed by chitosan encapsulation,to generate chitosan-encapsulated{Mo 154}/EGCG(CME)nanoparticles.These nanoparticles were integrated into dissolvable microneedles(CME@MN)to enable transdermal administration.Under near-infrared laser irradiation,CME exhibited a three-pronged therapeutic effect:suppression of collagen overproduction and excessive extracellular matrix(ECM)deposition in human keloid fibroblasts,regulation of proliferation and migration in human umbilical vein endothelial cells,and reprogramming of macrophages toward a proinflammatory M1 phenotype.In vivo,CME@MN patches preferentially accumulated within scar tissue,where they normalized ECM organization,improved collagen fiber rearrangement,and attenuated fibroblast activity through photothermal-enhanced mechanisms while maintaining an excellent safety profile.The CME@MN system represents a potentially transformative approach to HS management by offering a unified platform that simultaneously targets the fibrotic,angiogenic,and inflammatory components of scar pathogenesis.展开更多
文摘The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).
文摘Objective: Pregnancy in a scarred uterus is considered to be high-risk, especially during parturition. Nevertheless, the literature favours vaginal delivery as long as obstetric conditions are favourable. The aim of our study was to contribute to the improvement of delivery management for women with scar uteri at the CHU Communautaire. Methodology: This was a cross-sectional study conducted over an 18-month period from 01 January 2020 to 30 June 2021 on women with scar uterus who came to give birth at the CHU Communautaire maternity unit. The sample was exhaustive;any parturient with a history of scarred uterus of more than one year with a clinically normal pelvis and whose fetus was in cephalic presentation. The following were excluded from the study: pregnant women with a uterine scar of less than one year, fetuses in a non-cephalic vertex presentation, pregnant women with antecedent complicated childbirth at the previous cesarean section, large fetuses informed consent had been obtained from the pregnant women. Anomynia was respected throughout the study. Results: During this period, we recorded 205 parturients with a scar uterus. The incidence of delivery with a scar uterus was 9.5%. Uterine testing was attempted in 85.9% of cases, with a success rate of 75.6%. Factors predictive of a successful uterine test was: maternal age less than 35 years (P = 0.0027), entry into labour at the reference maternity hospital (P Conclusion: Delivery with a scarred uterus is an increasingly frequent occurrence at the Maternity Unit of the CHU Communautaire in Bangui. Uterine testing is the first option if conditions allow, but careful selection of candidates during antenatal care or at the very beginning of labour is necessary for this type of delivery.
文摘Objective To verify the therapeutic effect of abdominal acupuncture combined with scarring moxibustion at Qìhǎi（气海 CV 6） on periarthritis of shoulder.Methods Thirty cases of periarthritis of shoulder were randomly divided into an acup-moxibustion group and an acupuncture group,15 cases in each group.The patients in the two groups were treated with abdominal acupuncture at Zhōngwǎn（中脘 CV 12）,Xiàwǎn（下脘 CV 10）,Shāngqǔ（商曲 KI 17）,Huáròumén（滑肉门 ST 24）,with scarring moxibustion at Qìhǎi（气海 CV 6） added in the acup-moxibustion group,5 treatments each week,altogether 15 treatments.The therapeutic effects were assessed on the 20th day of acupuncture.Results The effective rate was 93.3%（14/15） in both the acup-moxibustion group and the acupuncture group,and the cured and markedly effective rate in the acup-moxibustion group and the acupuncture group was 86.7%（13/15） and 53.3%（8/15）,respectively,the acup-moxibustion group being better than that in the acupuncture group（P〈0.01）;after treatment the cumulative score of pain and the cumulative score of shoulder joint active function were significantly increased in the two groups（all P〈0.05）,with more significantly increased in the acup-moxibustion group（both P〈0.05）.Conclusion The therapeutic effect of abdominal acupuncture combined with scarring moxibustion on periarthritis of shoulder is better than that of the simple abdominal acupuncture.
基金Supported by Youth Fund of National Natural Science Foundation of China:No.81704183Henan Science and Technology Public relations program project:No.172102310014+1 种基金Special project of Henan province for Scientific Research of Traditional Chinese Medicine:No.2017ZY1021Special project of Henan Province for Scientific Research of Traditional Chinese Medicine:No.2018ZY1015.
文摘Objective:To explore the influence of scarring moxibustion on the changes of serum melatonin(MT)and neuropeptide Y(NPY)expressions in the insomnia model rats.Methods:A total of 40 SD rats were randomly divided into a blank group,a model group,a scarring moxibustion group,an embedding needling group and a mild moxibustion group,8 rats in each group.The intraperitoneal injection of p-chlorophenylalanine(PCPA)was adopted to establish the insomnia model rats and the corresponding interventions were given,consecutively for 6 days.Separately,before modeling and the first intervention as well as before sample collection,the body weight was measured and the serum was collected in the insomnia model rats.The enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum MT and NPY.Results:Compared with the blank group,the body weight of rat in the model group was lower(P<0.01)and the levels of MT and NPY were lower in the model group(both P<0.05).Compared with the model group,in the scarring moxibustion group,the embedding needling group and the mild moxibustion group,the body weight and the levels of MT and NPY of the insomnia model rats were all higher(all P<0.05).Compared with the embedding needling group and the mild moxibustion group,the body weight and the levels of MT and NPY the insomnia model rats were all higher in the scarring moxibustion group(all P<0.05).In comparison between the embedding needling group and the mild moxibustion group,there were no statistical differences in the body weight and the levels of MT and NPY(all P>0.05).Conclusion:The regulation mechanism of sleep-wake circadian rhythm may be related to the levels of serum MT and NPY in the insomnia model rats.Scarring moxibustion increases the levels of MT and NPY more effectively and displays the effect in the intervention as compared with embedding needling and mild moxibustion in the insomnia model rats.
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 alpha -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 the National Natural Science Foundation of China (No.81272120)the Health Department of the Zhejiang Province (No.2007B086),China
文摘Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed （about 15 d post wounding）. For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results： Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 （p〈0.05）. Scar thickness, measured by scar elevation index （SEI） at Day 35 post wounding, was significantly reduced in the intervention group （1.09±0.19） compared with the controls （1.36±0.28）. Microvessel density （MVD） observed in the intervention group （1.73±0.94） was significantly lower than that of the control group （5.63±1.78） on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions： Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-dedved growth factor （PDGF） and fibroblast growth factor （FGF）, thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.
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.
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supported by a grant from the Development of Medical Science and Technology Project of Shandong Province in China,No.2014WS0354the National Natural Science Foundation of China,No.81272099+1 种基金the Shandong Medical and Health Science and Technology Development Program Fund for Youth in China,No.2009QZ023the Natural Science Foundation of Shandong Province in China,No.BS2009YY043
文摘This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation.
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.
基金supported by the National Natural Science Foundation of China(NO.82230085,82272572,82030071)National Key Research and Development Program of China(NO.2022YFC2010204)Natural Science Foundation of Hunan Province(NO.2024JJ6637)。
文摘Irreversible fibrotic scarring after rotator cuff tear(RCT)compromises the mechanical properties of the healing tendon,yet the underlying mechanisms remain poorly understood.Here,we analyzed the histological features of human RCT scars,characterized by disruption of tendon architecture,disorganized collagen fibrils,and imbalance in type Ⅰ/Ⅲ collagen ratios and fibril diameters.Using single-cell RNA sequencing of tendon stumps from patients with RCT,we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment.Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation,including tendon stem cell,senescent tenocyte,SOX9-driven pro-fibrotic macrophage,and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition(EndoMT).Furthermore,we found that osteopontin and TGF-βsignaling were key drivers of extracellular matrix deposition,and their blockade ameliorated fibrotic scarring after RCT.Collectively,our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.
文摘Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].
文摘Objective： To investigate the relationship between fester capacity and clinical efficacy on allergic asthma treated by scarring moxibustion. Methods： The patients were randomly divided into scarring moxibustion 9-cone group, 3-cone group and 6-cone group. The biggest area, scab-lost time, first-festering time and scarring time of moxibustion sore, and the clinical efficacy in each group was observed. Results： The biggest post-moxibustion sore area in 9-cone group was larger than that in 3-cone group, but had no difference in comparison with 6-cone group; the scab-lost time, first-festering time and scarring time ofpost-moxibustion sore in each group were of no difference. The clinical efficacy was better in 9-cone group than in 3-cone group, but had no difference in comparison with the 6-cone group. Conclusion： Fester capacity in treating allergic asthma by scarring moxibustion is related to the clinical efficacy and definite fester capacity is the key to good results on allergic asthma.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
基金Ministry of Research,Innovation and Digitization,CCCDI-UEFISCDI,Grant/Award Number:PN-IV-P7-7.1-PED-2024-1578,within PNCDI Ⅳ.
文摘Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.
基金the financial support from the Fujian Provincial Youth Top-Notch Talent Support Program,China.
文摘The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a nanocomposite system constructed through the metal-phenolic network-mediated self-assembly of molybdenum polyoxometalate({Mo 154})and epigallocatechin gallate(EGCG),followed by chitosan encapsulation,to generate chitosan-encapsulated{Mo 154}/EGCG(CME)nanoparticles.These nanoparticles were integrated into dissolvable microneedles(CME@MN)to enable transdermal administration.Under near-infrared laser irradiation,CME exhibited a three-pronged therapeutic effect:suppression of collagen overproduction and excessive extracellular matrix(ECM)deposition in human keloid fibroblasts,regulation of proliferation and migration in human umbilical vein endothelial cells,and reprogramming of macrophages toward a proinflammatory M1 phenotype.In vivo,CME@MN patches preferentially accumulated within scar tissue,where they normalized ECM organization,improved collagen fiber rearrangement,and attenuated fibroblast activity through photothermal-enhanced mechanisms while maintaining an excellent safety profile.The CME@MN system represents a potentially transformative approach to HS management by offering a unified platform that simultaneously targets the fibrotic,angiogenic,and inflammatory components of scar pathogenesis.
