Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive im...Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.展开更多
Endoscopic resection(ER)of colorectal polyps has become a daily practice in most endoscopic units providing a colorectal cancer screening program and requires the availability of local experts and high-end endoscopic ...Endoscopic resection(ER)of colorectal polyps has become a daily practice in most endoscopic units providing a colorectal cancer screening program and requires the availability of local experts and high-end endoscopic devices.ER procedures have evolved over the past few years from endoscopic mucosal resection(EMR)to more advanced techniques,such as endoscopic submucosal dissection and endo-scopic full-thickness resection.Complete resection and disease eradication are the ultimate goals of ER-based techniques,and novel devices have been developed to achieve these goals.The EndoRotor®Endoscopic Powered Resection System(Interscope Medical,Inc.,Northbridge,Massachusetts,United States)is one such device.The EndoRotor is a powered resection tool for the removal of alimentary tract mucosa,including post-EMR persistent lesions with scarring,and has both CE Mark and FDA clearance.This review covers available published evidence documenting the usefulness of EndoRotor for the management of recurrent colorectal polyps.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be e...BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.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
Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis eval...Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis evaluates the efficacy of tamanu oil in acne treatment with a specific focus on its impact on inflammation and scar reduction. The novelty of this research lies in its comprehensive analysis of tamanu oil’s dual mechanism of action: reducing acne-related inflammation and promoting the healing of acne scars. Clinical trials and laboratory analyses were conducted to assess the oil’s effectiveness in diminishing erythema, swelling, and post-acne scarring compared to conventional treatments. Preliminary findings demonstrate that tamanu oil significantly reduces inflammation and accelerates wound healing, potentially offering a promising adjunct or alternative to standard acne therapies. Future research should aim to optimize formulation and application protocols, long-term effects, and comparative therapeutic efficacy with other anti-inflammatory agents. Tamanu oil offers a novel and effective approach to acne management, with potential advantages that go beyond inflammation reduction to include enhanced scar reduction, making it a subject that warrants further investigation.展开更多
The objective is to report a clinical case of vaginal cesarean section performed to expel a dead fetus in scarred uterus. For this indication, vaginal hysterectomy constitutes an alternative to vaginal expulsion with ...The objective is to report a clinical case of vaginal cesarean section performed to expel a dead fetus in scarred uterus. For this indication, vaginal hysterectomy constitutes an alternative to vaginal expulsion with a high risk of uterine rupture and to classic abdominal cesarean section with risk of significant surgical trauma, particularly adhesions. However, this surgical technique, described since the 19th century, remains unknown to many practitioners and few publications exist on the subject throughout the world. Considered obsolete by some practitioners, it retains all its advantages in the practice of modern obstetrics. We report this case of expulsion of fetal death on a tri-scarred uterus performed by vaginal cesarean section at the Health District Reference Health Center (District Hospital) of Commune I in Bamako, Mali in a 37-year-old patient with a pregnancy of 27 weeks of amenorrhea.展开更多
Scars, when in good evolution, result in a smooth, thin and discreet tissue. Keloid scars, however, are a type of abnormal and exacerbated repair response to tissue injury, whether in surgical interventions or in vari...Scars, when in good evolution, result in a smooth, thin and discreet tissue. Keloid scars, however, are a type of abnormal and exacerbated repair response to tissue injury, whether in surgical interventions or in various injuries, which present in a prominent and gross way. In this context, there is an excess of collagen deposition in the tissue repair process, which can lead to the formation of keloids. The diagnosis of the condition presented is made by the medical professional or by the patient himself after the surgical intervention or skin injury. Under this analysis, protruding, rough and bad-looking scars are identified. In addition, we highlight the existence of keloids similar to large tumors, described as Jorge Lobo disease. The treatment encompasses massages, compressions, corticosteroids, chemotherapy, collagenase and cryotherapy. At first, we used corticosteroid-based massages, and then we started using compressive dressings until we started intrakeloid infiltrations with injectable triamcinolone. Triamcinolone 10 mg injectable—1/10—in 0.9% saline, with syringe and fixed needle 0.3 mm × 8 mm, intralesional infiltrate, in this context, proved to be effective for its treatment when applied sequentially and linearly. In cases where the medication was applied, there was an improvement after 21 days of application and a definitive improvement 2 months after the injury. In comparison, on the other hand, patients who were not subjected to the application of the medication may improve after 4 months of the injury or worsen compared to the initial case. We have come to the conclusion that this procedure may be one of the chosen ones for the treatment of keloid scars, being one of the most recommended for cases of keloid already installed.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
In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly unders...In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.展开更多
The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial...The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.展开更多
After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astr...After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.展开更多
BACKGROUND Cesarean scar pregnancy(CSP)is rare but may result in uterine rupture during pregnancy or massive hemorrhage during abortion procedures.Awareness of this condition is increasing,and most patients with CSP a...BACKGROUND Cesarean scar pregnancy(CSP)is rare but may result in uterine rupture during pregnancy or massive hemorrhage during abortion procedures.Awareness of this condition is increasing,and most patients with CSP are now diagnosed early and can be managed safely.However,some atypical patients are misdiagnosed,and their surgical risks are underestimated,increasing the risk of fatal hemorrhage.CASE SUMMARY A 27-year-old Asian woman visited our institution because of abnormal pregnancy,and she was diagnosed with a hydatidiform mole through transvaginal ultrasound(TVS).Under hysteroscopy,a large amount of placental tissue was found in the scar of the lower uterine segment,and a sudden massive hemorrhage occurred during the removal process.The bilateral internal iliac arteries were temporarily blocked under laparoscopy,and scar resection and repair were rapidly performed.She was discharged in good condition 5 d after the operation.CONCLUSION Although TVS is widely used in the diagnosis of CSP,delays in the diagnosis of atypical CSP remain.Surgical treatment following internal iliac artery temporary occlusion may be an appropriate management method for unanticipated massive hemorrhage during CSP surgery.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
BACKGROUND Hypertrophic scars(HSs)formation is a complication that occurs after wounds heal with secondary intention and sometimes after clean surgical incisions.Many treatments are in vogue now with varying successes...BACKGROUND Hypertrophic scars(HSs)formation is a complication that occurs after wounds heal with secondary intention and sometimes after clean surgical incisions.Many treatments are in vogue now with varying successes.Although the mechanism or mechanisms that cause a HS to form are not clearly understood,one thing that is clear is that once scar tissue matures,any intervention will not be successful.In this paper,we report on a case where a patient who was known to develop HS was treated with a new combination of ingredients(Phyto-chemicals+Silicone JUMI)to suppress HS formation.CASE SUMMARY A 68-year-old female of African descent presented a severe HS post total knee replacement(TKR),which the patient describes as itchy and painful.Due to complications caused by the scar,she was apprehensive about undergoing TKR on her other knee.However,after the TKR of the contralateral side post-removal of skin clips,JUMI anti-scar cream(JASC)was used to suppress excessive scar formation.CONCLUSION JASC appears potent and efficacious at suppressing excessive scar formation.We believe that this warrants further studies on larger patient groups and on different surgical sites.展开更多
基金supported by grants PICT 2019-08512017-2203,UBACYT and PIP CONICET(to AJR).
文摘Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.
文摘Endoscopic resection(ER)of colorectal polyps has become a daily practice in most endoscopic units providing a colorectal cancer screening program and requires the availability of local experts and high-end endoscopic devices.ER procedures have evolved over the past few years from endoscopic mucosal resection(EMR)to more advanced techniques,such as endoscopic submucosal dissection and endo-scopic full-thickness resection.Complete resection and disease eradication are the ultimate goals of ER-based techniques,and novel devices have been developed to achieve these goals.The EndoRotor®Endoscopic Powered Resection System(Interscope Medical,Inc.,Northbridge,Massachusetts,United States)is one such device.The EndoRotor is a powered resection tool for the removal of alimentary tract mucosa,including post-EMR persistent lesions with scarring,and has both CE Mark and FDA clearance.This review covers available published evidence documenting the usefulness of EndoRotor for the management of recurrent colorectal polyps.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金Supported by the 2022 Shaoxing City Health Science and Technology Program(Health Science and Technology Program),No.2022KY050。
文摘BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.
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Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis evaluates the efficacy of tamanu oil in acne treatment with a specific focus on its impact on inflammation and scar reduction. The novelty of this research lies in its comprehensive analysis of tamanu oil’s dual mechanism of action: reducing acne-related inflammation and promoting the healing of acne scars. Clinical trials and laboratory analyses were conducted to assess the oil’s effectiveness in diminishing erythema, swelling, and post-acne scarring compared to conventional treatments. Preliminary findings demonstrate that tamanu oil significantly reduces inflammation and accelerates wound healing, potentially offering a promising adjunct or alternative to standard acne therapies. Future research should aim to optimize formulation and application protocols, long-term effects, and comparative therapeutic efficacy with other anti-inflammatory agents. Tamanu oil offers a novel and effective approach to acne management, with potential advantages that go beyond inflammation reduction to include enhanced scar reduction, making it a subject that warrants further investigation.
文摘The objective is to report a clinical case of vaginal cesarean section performed to expel a dead fetus in scarred uterus. For this indication, vaginal hysterectomy constitutes an alternative to vaginal expulsion with a high risk of uterine rupture and to classic abdominal cesarean section with risk of significant surgical trauma, particularly adhesions. However, this surgical technique, described since the 19th century, remains unknown to many practitioners and few publications exist on the subject throughout the world. Considered obsolete by some practitioners, it retains all its advantages in the practice of modern obstetrics. We report this case of expulsion of fetal death on a tri-scarred uterus performed by vaginal cesarean section at the Health District Reference Health Center (District Hospital) of Commune I in Bamako, Mali in a 37-year-old patient with a pregnancy of 27 weeks of amenorrhea.
文摘Scars, when in good evolution, result in a smooth, thin and discreet tissue. Keloid scars, however, are a type of abnormal and exacerbated repair response to tissue injury, whether in surgical interventions or in various injuries, which present in a prominent and gross way. In this context, there is an excess of collagen deposition in the tissue repair process, which can lead to the formation of keloids. The diagnosis of the condition presented is made by the medical professional or by the patient himself after the surgical intervention or skin injury. Under this analysis, protruding, rough and bad-looking scars are identified. In addition, we highlight the existence of keloids similar to large tumors, described as Jorge Lobo disease. The treatment encompasses massages, compressions, corticosteroids, chemotherapy, collagenase and cryotherapy. At first, we used corticosteroid-based massages, and then we started using compressive dressings until we started intrakeloid infiltrations with injectable triamcinolone. Triamcinolone 10 mg injectable—1/10—in 0.9% saline, with syringe and fixed needle 0.3 mm × 8 mm, intralesional infiltrate, in this context, proved to be effective for its treatment when applied sequentially and linearly. In cases where the medication was applied, there was an improvement after 21 days of application and a definitive improvement 2 months after the injury. In comparison, on the other hand, patients who were not subjected to the application of the medication may improve after 4 months of the injury or worsen compared to the initial case. We have come to the conclusion that this procedure may be one of the chosen ones for the treatment of keloid scars, being one of the most recommended for cases of keloid already installed.
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.
基金supported by the National Natural Science Foundation of China,Nos.82171456 (to QY),81971229 (to QY)the Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0263 (to QY)the Postgraduate Research and Innovation Project of Chongqing,Nos.CYB20151 (to QY),CYS19182 (to YC)。
文摘In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82071287,81870916)the National Natural Science Foundation of China(Grant No.:81971097)+3 种基金the Basic Public Interests Research Plan of Zhejiang Province,China(Grant No.:GF18H090006)the National Natural Science Foundation of China(Grant No.:81701214)the National Natural Science Foundation of China(Grant No.:82001299)the Natural Science Foundation of Zhejiang Province,China(Grant No.:TGD23C040017).
文摘The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.
基金supported by the National Natural Science Foundation of China,Nos.82101455(to RYY),31872773(to GC),82001168(to JYP)the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC)+3 种基金the Foundation of Jiangsu Province,333 Project High-level Talents",No.BRA2020076(to GC)the Nantong Civic Science and Technology Project of China,No.JC2020028(to RYY)the Natural Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.
基金Supported by Medical Health Science and Technology Project of Zhejiang Province,China,No.2020ZH003。
文摘BACKGROUND Cesarean scar pregnancy(CSP)is rare but may result in uterine rupture during pregnancy or massive hemorrhage during abortion procedures.Awareness of this condition is increasing,and most patients with CSP are now diagnosed early and can be managed safely.However,some atypical patients are misdiagnosed,and their surgical risks are underestimated,increasing the risk of fatal hemorrhage.CASE SUMMARY A 27-year-old Asian woman visited our institution because of abnormal pregnancy,and she was diagnosed with a hydatidiform mole through transvaginal ultrasound(TVS).Under hysteroscopy,a large amount of placental tissue was found in the scar of the lower uterine segment,and a sudden massive hemorrhage occurred during the removal process.The bilateral internal iliac arteries were temporarily blocked under laparoscopy,and scar resection and repair were rapidly performed.She was discharged in good condition 5 d after the operation.CONCLUSION Although TVS is widely used in the diagnosis of CSP,delays in the diagnosis of atypical CSP remain.Surgical treatment following internal iliac artery temporary occlusion may be an appropriate management method for unanticipated massive hemorrhage during CSP surgery.
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BACKGROUND Hypertrophic scars(HSs)formation is a complication that occurs after wounds heal with secondary intention and sometimes after clean surgical incisions.Many treatments are in vogue now with varying successes.Although the mechanism or mechanisms that cause a HS to form are not clearly understood,one thing that is clear is that once scar tissue matures,any intervention will not be successful.In this paper,we report on a case where a patient who was known to develop HS was treated with a new combination of ingredients(Phyto-chemicals+Silicone JUMI)to suppress HS formation.CASE SUMMARY A 68-year-old female of African descent presented a severe HS post total knee replacement(TKR),which the patient describes as itchy and painful.Due to complications caused by the scar,she was apprehensive about undergoing TKR on her other knee.However,after the TKR of the contralateral side post-removal of skin clips,JUMI anti-scar cream(JASC)was used to suppress excessive scar formation.CONCLUSION JASC appears potent and efficacious at suppressing excessive scar formation.We believe that this warrants further studies on larger patient groups and on different surgical sites.