Sweat glands (SGs) play pivotal roles in systemic and skin homeostasis. However, due to the extremely limited regenerative capacity of SGs, burns and traumas often result in irreversible SGs loss. Recent advancements in three-dimensional (3D) cell culture technology and stem cell research have highlighted the potential of organoid technology in regenerative medicine. This review summarizes the molecular regulatory mechanisms underlying SG development and focuses on the latest progress in sweat gland organoid (SGO) construction. By examining various cell sources, including SG stem cells, mesenchymal stem cells (MSCs), and reprogrammed cells, as well as the influence of 3D culture microenvironments on SGO assembly, we highlighted the promising applications of SGOs in post-burn SG regeneration. Despite challenges in cell induction efficiency and functional reconstruction, SGO technology offers a novel therapeutic strategy for restoring SG function in burn patients.
Bacterial wound infection has emerged as a pivotal threat to human health worldwide, and the situation has worsened owing to the gradual increase in antibiotic-resistant bacteria caused by the improper use of antibiotics. To reduce the use of antibiotics and avoid the increase in antibiotic-resistant bacteria, researchers are increasingly paying attention to photodynamic therapy, which uses light to produce reactive oxygen species to kill bacteria. Treating bacteria-infected wounds by photodynamic therapy requires fixing the photosensitizer (PS) at the wound site and maintaining a certain level of wound humidity. Hydrogels are materials with a high water content and are well suited for fixing PSs at wound sites for antibacterial photodynamic therapy. Therefore, hydrogels are often loaded with PSs for treating bacteria-infected wounds via antibacterial photodynamic therapy. In this review, we systematically summarised the antibacterial mechanisms and applications of PS-loaded hydrogels for treating bacteria-infected wounds via photodynamic therapy. In addition, the recent studies and the research status progresses of novel antibacterial hydrogels are discussed. Finally, the challenges and future prospects of PS-loaded hydrogels are reviewed.
Background: Effective management of cutaneous nocardiosis is hampered by the lack of defined treatment recommendations and frequently requires prolonged antibiotic therapy. Case presentation: This report describes a case of cutaneous nocardiosis who was effectively treated in a brief amount of time with three sessions of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in conjunction with antibiotics. Conclusion: ALA-PDT combined with antibiotics may effectively treat refractory cutaneous nocardiosis.
BACKGROUND:Frequently, recurrence of genital herpes imposes significant physical and psychological burdens on patients, and existing treatments are often ineffective in preventing recurrence. Previous studies have indicated that photodynamic therapy (PDT) showed promising outcomes in the treatment of labial herpes simplex virus (HSV) infections; however, its efficacy for genital herpes remained unclear. METHOD:The study screened patients with genital herpes at Daping Hospital from July 2020 to May 2024. Patients were divided into two groups based on whether they received PDT treatment. Over a one-year follow-up period, patients' healing time and recurrence rates were compared between the two groups. The cumulative incidence of recurrence and restricted mean survival time (RMST) were used to assess outcomes. Propensity score matching (PSM) was employed to minimize bias. RESULT:A total of 41 patients enrolled in our study, with 8 (19.5 %) received PDT. The non-PDT group exhibited a slower skin lesion healing time, averaging at 7.2 days compared to 5.4 days in the PDT group. A significant difference was observed in the cumulative incidence of recurrence between the PDT and non-PDT groups (37.5 % versus 71.4 %) after PSM. The RMST in the PDT group was 9.94 days, compared to 5.13 days in the non-PDT group before PSM, and 4.14 after PSM. CONCLUSION:Our study demonstrated that the PDT effectively reduced lesion recovery time and delayed recurrences of genital herpes. We recommend considering PDT as a potential treatment option for patients with recurrent genital herpes.
We report two cases of chronic skin ulcers that were misdiagnosed as skin and soft tissue infections and as an inflammatory myofibroblastic tumour before the final diagnosis of epithelioid sarcoma at our institution. Our coverage of this rare but fatal tumour that can cause chronic skin ulcers is critical because early diagnosis and treatment can reduce morbidity and mortality.
BACKGROUND:Mycobacterium abscessus skin infections have emerged as a major medical issue. Traditional antibiotic treatments are challenging, prolonged, and often lead to recurrence, creating an urgent need for new therapies. This study investigates the effectiveness of aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics in treatmenting M. abscessus, using both in vitro and in vivo methods. METHODS:We treated eight patients with M. abscessus skin infections following cosmetic surgery, using ALA-PDT (ALA concentration: 20 %; red light: 80 J/cm2) combined with oral or intravenous antibiotics,including clarithromycin, moxifloxacin and amikacin, to treat 8 patients with M. abscessus skin infection after medical cosmetic surgery, and assessed the treatment outcomes. Additionally, four bacterial strains (MAB-A1, MAB-A2, MAB-B1, and MAB-B2) isolated from patients were tested in vitro for ALA-PDT efficacy to determine the optimal ALA-PDT dosage. Furthermore, the strains' single colony morphology, biofilm formation, and genome characteristics of were analyzed to explore the factors influencing ALA-PDT's bactericidal effects. Finally, a combined ALA-PDT and antibiotics sterilization experiment was conducted in vitro. RESULTS:Clinically, ALA-PDT combined with antibiotics showed strong efficacy in treating M. abscessus skin infections, with no recurrence observed during follow-up. In vitro, ALA-PDT effectively killed M. abscessus, although MAB-B1 and MAB-B2 required a higher ALA-PDT dose compared with MAB-A1 and MAB-A2. Compared to MAB-A1 and MAB-A2, MAB-B1 and MAB-B2 exhibited stronger biofilm formation capabilities and bacterial virulence as well as genome mutations primarily affecting fatty acid synthesis and metabolism, potentially explaining their increased ALA-PDT dosage requirement. Notably, the combination of ALA-PDT and antibiotics exerted markedly higher bactericidal effects in vitro compared with antibiotics alone. CONCLUSIONS:ALA-PDT combined with antibiotics emerged as an effective treatment for M. abscessus skin infections. However, optimal dosage and antibiotic combinations should be tailored to the characteristics of specific clinical strains.
Background: Recently, the number of cases of Mycobacterium marinum infection has increased. Due to the nonspecific clinical manifestations and lack of standardized treatment guidelines, these infections are often misdiagnosed and are challenging to treat. Methods: In this study, four patients had M. marinum skin infections accompanied by a high-risk exposure history and were diagnosed by bacterial culture and gene chip. Two patients were treated with antibiotic therapy alone, and the other two patients were treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics.Results: All four patients enrolled in the study were cured with 100 % efficacy. Two patients were cured after receiving two active antibiotics for 4 months. The other two patients, having considered the drug resistance and intolerance described above, were cured after receiving two active antibiotics for 1-1.5 months along with combination therapy with ALA-PDT.Conclusion: Combination therapy with ALA-PDT and antibiotics was chosen to shorten the duration of antibiotic treatment and reduce the occurrence of adverse reactions.
Objective To determine the effect of low-dose 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the polarity switch of M1 macrophages and explore its mechanism primarily. Methods RAW264.7 cells were cultured with 100 ng/mL lipopolysaccharide (LPS) for 24 h to induce M1 macrophages.The control group was cultured in the medium without LPS for 24 h.CCK-8 assay was used to detect the toxic effect of low-dose ALA-PDT therapy with different light doses on M1 macrophages, and the expression of M1 type marker, inducible nitric oxide synthase (iNOS) was measured with Western blotting.Then M1 macrophages were divided into M1 group, ALA group, red light group and ALA-PDT group (ALA treatment followed by red light irradiation).The mRNA expression levels of inducible M1 type markers iNOS and interleukin 6(IL-6), and M2 type markers interleukin 10(IL-10) and arginase 1(Arg-1) were detected by real-time fluorescent quantitative PCR, and the secretions of IL-6 and IL-10 were detected by ELISA.Western blotting was applied to detect the protein levels of iNOS, interleukin 1β(IL-1β), Arg-1, and autophagy-related proteins, ubiquitin-binding protein P62 and tubule-associated protein 1 light chain 3(LC3). Results Compared with the control group, the mRNA levels of iNOS and IL-6 were higher (P < 0.05), the protein levels of iNOS and IL-1β were higher (P < 0.05), and that of Arg-1 was lower (P < 0.05), and the secretion level of IL-6 was higher in the M1 group (P < 0.05).With the increase of light intensity, the toxic effect of ALA-PDT therapy on M1 macrophages was gradually increased (P < 0.05), and when the intensity higher than 2 J/cm2, the expression of iNOS was inhibited.The mRNA levels of Arg-1 and IL-10 were increased, while that of iNOS was decreased (P < 0.05), the protein expression of Arg-1 was elevated while those of iNOS and IL-1β were decreased (P < 0.05), the secretion level of IL-10 was increased (P < 0.05) but that of IL-6 decreased (P < 0.05), and the protein level of P62 was decreased (P < 0.05) and the ratio of LC3Ⅱ/LC3Ⅰ was increased (P < 0.05) in the ALA-PDT group when compared with the M1 group, ALA group and red light group. Conclusion Low-dose ALA-PDT therapy can promote the conversion of M1-type macrophages to M2-type macrophages, and its mechanism may be related to autophagy.
Background: The skin infection caused by Mycobacterium abscessus (M. abscessus) is extremely difficult to treat in clinical practice. PDT (photodynamic therapy) is a promising antibacterial treatment. We evaluated the effect of photodynamic therapy using 5-aminolevulinic acid (ALA) as a photosensitizer on M. abscessus and its antibiotic resistance in this study. Methods: M. abscessus and biofilm were treated with different concentrations of ALA and then irradiated with LED light (635 nm, 80 J/cm(2)), while there were ALA-only group, light-only group, and negative control group. The effects were observed by colony counting, crystal violet staining, confocal laser scanning microscope (CLSM), and scanning electron microscope (SEM). The changes of drug susceptibility of M. abscessus at sublethal doses were detected by micro-broth dilution method, and the possible mechanism was explored by fluorometer and real-time fluorescence quantitative Polymerase Chain Reaction (RT-qPCR). Results: ALA-PDT showed a significant killing effect on M. abscessus at ALA concentrations greater than 50 mu g/ml and the effect increased with increasing photosensitizer concentrations. ALA-PDT also showed a notable scavenging effect on M. abscessus biofilm, which was also enhanced with increasing ALA concentrations. At sublethal doses, the susceptibility of M. abscessus to antibiotics was increased, and ALA-PDT greatly increased the cell wall permeability of M. abscessus and decreased the mRNA expression of drug resistance genes whiB7 and erm (41), as well as efflux pump genes MAB_1409c and MAB_3142c at the transcriptional level. Conclusions: ALA-PDT has a significant killing effect on M. abscessus and can increase its antibiotic susceptibility.
BACKGROUND:Recently, the number of nontuberculous mycobacterium (NTM) infections caused by iatrogenic procedures, especially rapid NTM skin infections, has been increasing. Due to the nonspecific clinical manifestations and nonstandard treatment guidelines, these infections are often misdiagnosed and challenging to treat.METHODS:In this study, eight patients had NTM skin infections caused by iatrogenic procedures, and were diagnosed by bacterial culture and flight mass spectrometry tests. They were treated with 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) combined with antibiotic therapy.RESULTS:All eight patients enrolled in the study were cured with 100% efficacy after receiving combination therapy with ALA-PDT and antibiotics for 3-6 months. All patients experienced redness and pain during treatment but no other discomfort and were satisfified with the results of their treatments.CONCLUSION:Local ALA-PDT combined with antibiotics is a safe and effective method of treating NTM skin infections.
目的 探讨皮肤病患者感染病原菌分布及耐药菌情况,为临床医师治疗皮肤感染提供治疗依据.方法 收集该科室2014年1月至2019年12月患者来源的细菌,菌株鉴定和药敏实验采用法国生物梅里埃公司VITEK-60全自动微生物分析仪及其配套的相应鉴定卡与药敏卡,按照美国临床实验室标准化协会(CLSI)M100-S27标准进行判定.采用WHONET5.6软件进行数据分析.结果 共分离出517株细菌,其中革兰阳性菌、革兰阴性菌、真菌分别占51.45%、41.39%、7.16%.检出耐甲氧西林金黄色葡萄球菌(MRSA)39株,占金黄色葡萄球菌的23.64%.检出碳青霉烯类耐药铜绿假单胞菌4株,占铜绿假单胞菌的6.35%.结论 皮肤感染病原菌种类繁多,细菌耐药率逐渐升高,皮肤科临床医师要更加重视病原菌变化,合理使用抗生素.
目的 探讨复方甘草酸苷和他克莫司软膏联合薇诺娜舒敏保湿修复霜治疗面部激素依赖性皮炎的临床效果.方法 收集于2017年12月~2019年12月期间收治的98例面部激素依赖性皮炎患者为研究对象,随机分为观察组(49例)和对照组(49例).对照组给予凡士林治疗,观察组采用复方甘草酸苷、他克莫司软膏、薇诺娜舒敏保湿修复霜联合治疗.对两组患者的总有效率、皮肤屏障功能、不良反应发生率、复发率进行统计对比.结果 观察组总有效率为89.80%(44/49),高于对照组患者的73.47%(36/49)(P<0.05).治疗后观察组患者的经皮水丢失(TEWL)低于对照组,角质层含水量、皮脂量高于对照组(P<0.05).治疗期间观察组、对照组不良反应发生率分别为18.37%(9/49)、12.24%(6/49),组间对比差异无统计学意义(P>0.05).随访6个月期间观察组复发率为8.17%(4/49),低于对照组的24.49%(12/49)(P<0.05).结论 复方甘草酸苷和他克莫司软膏联合薇诺娜舒敏保湿修复霜治疗面部激素依赖性皮炎的疗效显著,能够提升患者的皮肤屏障功能,降低复发率,治疗安全性良好.
目的:探讨ALA-PDT对巨噬细胞极化的影响,并探讨相关机制.方法:采用免疫荧光、PCR、WB等试验检测巨噬细胞极化特征蛋白CD86、CD206、iNOS、ARG-1的表达水平变化,NF-kB激活-核转运检测试剂、WB试验检测NF-kB通路激活情况,WB试验检测抑制NF-kB通路后CD86、iNOS蛋白表达水平.结果:免疫荧光、PCR、WB实验结果显示,PDT处理后,巨噬细胞M1特征蛋白CD86、iNOS表达水平增高,M2特征蛋白表达水平下降(P<0.05).NF-kB激活-核转运检测、WB实验结果表明PDT处理后,NF-kB通路被激活.给予NF-kB通路抑制剂处理,PDT处理后巨噬细胞M1特征蛋白CD86、iNOS表达水平增高现象被抑制.结论:ALA-PDT通过激活NF-kB通路促进巨噬细胞向M1极化.
目的:探讨用CO2点阵激光联合光动力疗法治疗囊肿性痤疮的疗效及安全性.方法:将2018年3月至2020年3月期间陆军特色医学中心收治的92例囊肿性痤疮患者随机分为联合治疗组和常规治疗组(46例/组).为常规治疗组患者采用光动力疗法进行治疗,在此基础上为联合治疗组患者采用CO2点阵激光疗法进行治疗.治疗后,对比两组患者的临床疗效、皮损积分、DLQI评分、皮肤油脂含量和不良反应的发生率.结果:1)联合治疗组患者治疗的总有效率〔89.13%(41/46)〕高于常规治疗组患者治疗的总有效率〔71.74%(33/46)〕,P<0.05.2)治疗期间,联合治疗组患者、常规治疗组患者不良反应的发生率分别为15.22%(7/46)、8.70%(4/46),二者相比,P>0.05.3)治疗后,两组患者的皮损积分、皮肤油脂含量均较治疗前明显下降,其DLQI评分均较治疗前明显升高,P<0.05.治疗后,联合治疗组患者的皮损积分、皮肤油脂含量均低于常规治疗组患者,其DLQI评分高于常规治疗组患者,P<0.05.结论:用CO2点阵激光联合光动力疗法治疗囊肿性痤疮的疗效显著,能够改善患者的皮损症状,降低其皮肤油脂含量,提高其生活质量,且安全性较高.
目的:探讨氨基酮戊酸(5-aminolevulinic acid,5-ALA)光动力疗法(photodynamic therapy,ALA-PDT)对大鼠细菌感染创面的治疗效果和机制.方法:健康雄性Wistar大鼠18只,建立创面细菌感染模型,随机分为模型对照组、ALA-PDT治疗大肠埃希菌感染皮肤创面组、ALA-PDT治疗金黄色葡萄球菌感染皮肤创面组,每组6只.治疗后,检测各组的创面愈合率、治疗前后痂下细菌量、HE染色观察组织学愈合情况;结果:ALA-PDT能显著减少创面组织中两种细菌的数量,改善大鼠创伤组织的炎症,促进肉芽新生,加快创面愈合的速度,缩短创面愈合时间.结论:ALA-PDT可以治疗皮肤创面感染,为其临床治疗感染性皮肤病提供了进一步的实验证据.
光动力疗法(Photodynamic Therapy,PDT)是指利用光敏剂在病变组织内聚集,在特定的波长的光或者激光的照射下被激活,产生单态氧或者其他自由基,造成病变组织坏死,不损伤正常组织的疗法[1].这些年来,PDT已经得到了广泛的应用,越来越多的研究者开始关注着它的机制.近年来许多研究发现PDT对巨噬细胞吞噬活性及其极化具有重大作用.本文就拟对PDT对巨噬细胞的作用及机制进行阐述.
OBJECTIVE:To investigate low-level ALA-PDT (Aminolevulinic acid photodynamic therapy) effects on photorejuvenation in vitro and in vivo, exploring the basic mechanism of Bach2 involved in PDT treatment in photoaging.METHOD:Photoaging model was established by UVA chronic irradiation in human fibroblasts and mice skins. Cell viability was determined by MTS assay and cell senescence was detected by SA-β-gal activity. PDT treatment and Bach2 knockdown with adenovirus in fibroblasts were confirmed by Western blot.RESULTS:UVA chronic irradiation induced photoaging in vitro and in vivo. Treatment of low-level PDT reduced photoaging by decreasing SA-β-gal activity and cell senescence-related proteins levels of p16 and p21 in fibroblasts. Moreover, low-level PDT treatment accompany with Bach2 accumulation increased in fibroblasts and in mice skin tissues. Bach2 knockdown with adenovirus induced cell senescence and Bach2 depletion with PDT treatment some extent decreased SA-β-gal activity, but was with no significant change of Bach2 itself and p16 protein levels in fibroblasts.CONCLUSION:Low-level PDT treatment decreased skin photoaging which might be through up-regulating Bach2.
Background: Photodynamic therapy (PDT) is considered an important and innovative treatment for healing skin wounds. Skin ulcers with sinus tract formation are rare and difficult to treat in the field of dermatology. Herein, we utilized optical fibers as a light source to penetrate the sinus tract and applied PDT to treat the sinus tract. Objectives: To evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and provide insight into the use of ALA-PDT in the treatment of skin ulcers with sinus tracts. Methods: Seven patients with skin ulcers with sinus tract formation who were previously unsuccessfully treated with systemic antibiotics, debridement and dressing changes were examined. In the present study, these patients also received ALA-PDT treatment (the ulcers were irradiated with a red LED, and the sinus tracts were irradiated with semiconductor laser optical fibers), which was locally administered every 10 days with a total of 1-5 sessions. Results: Six patients enrolled in the study were fully cured after receiving combination therapy with ALA-PDT and antibiotics for three months. The sinus tract of one patient was cured and the ulcer area of this patient was reduced. All patients experienced varying degrees of redness and pain during treatment but no severe discomfort, and all patients were satisfied with the outcome of the treatment. Conclusion: Local ALA-PDT combined with antibiotics could be a safe and effective treatment approach for skin ulcers with sinus tract formation.
Periodontal ligament stem cells (PDLSCs) exhibit potential for osteogenesis in vitro and in vivo and are a candidate cell type for periodontal regeneration for the treatment of periodontitis. However, periodontitis is accompanied by hypoxia, and it is not clear how hypoxia affects the osteogenesis of PDLSCs. In this study, we found that the expression of hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1) is enhanced in the osteogenesis of PDLSCs under nonhypoxic conditions. TGF-β1 can induce the stabilization of HIF-1α through the phosphorylation of mothers against decapentaplegic homolog 3 (Smad3) in PDLSCs, and in turn, HIF-1α inhibits the mRNA and protein expression of TGF-β1 and inhibits the phosphorylation of Smad3 in PDLSCs. In addition, both HIF-1α and TGF-β1 reduce the expression of crucial osteogenic gene runt-related transcription factor 2 (RUNX2) and the mineralization of PDLSCs in normoxia. In conclusion, our results showed that TGF-β1 can induce the stabilization of HIF-1α in PDLSCs under nonhypoxic conditions, that HIF-1α can negatively regulate the TGF-β1/Smad3 signal pathway in PDLSCs, and that TGF-β1 and HIF-1α can synergistically inhibit the osteogenesis of PDLSCs.
OBJECTIVES:To investigate the effects of low-dose aminolevulinic acid photodynamic therapy (ALA-PDT) on photoaging in human dermal fibroblasts (HDFs) and to explore the mechanism of Nuclear factor erythroid 2-related factor 2(Nrf2)-mediated photorejuvenation in vitro.METHODS:A photoaging model was established through repeated exposure of HDFs to UVA. Total superoxide dismutase (SOD) expression was detected by a SOD activity assay. Nrf2 was knocked down through adenovirus infection, and successful knockdown was confirmed by Western blot analysis and quantitative polymerase chain reaction.RESULTS:Sustained exposure to UVA induced photoaging in HDFs. Total SOD activity was significantly increased by low-dose aminolevulinic acid (ALA)-PDT. Upon application of low doses of ALA-PDT to photoaging HDFs, Nrf2 was translocated to the nucleus; in addition, the expression of Nrf2, transforming growth factor-β1 (TGF-β1), type I and III collagen (COL1 and COL3), heme oxygenase 1 (HO-1), and p-ERK was increased, while the expression of matrix metalloproteinase 9 (MMP-9) was decreased. However, after Nrf2 was knocked down in HDFs, the expression of TGF-β1, COL1, COL3, and HO-1 was significantly decreased, while the expression of MMP-9 was increased.CONCLUSION:This study revealed that low-dose ALA-PDT decreases UVA-mediated photoaging through an Nrf2-mediated antioxidant effect.