Ultraviolet (UV) radiation, particularly in the UVA spectrum (320–400 nm), induces significant damage to both dermal and epidermal layers of skin, generating reactive oxygen species (ROS) and triggering apoptotic pathways that compromise skin health. Selaginella tamariscina (P. Beauv.), a traditional medicinal plant widely used throughout Asia, contains numerous flavonoid compounds with recognized therapeutic value in Chinese medicine. Through comprehensive molecular analyses including Western blotting, RT-qPCR, and flow cytometry, we demonstrated that the Selaginella tamariscina (P. Beauv.) extract (STE) significantly reduces UVA-induced apoptosis while simultaneously activating protective autophagic responses. Mechanistically, STE modulates AKT phosphorylation to regulate two critical downstream pathways: (1) the JNK-mediated apoptotic cascade and (2) the AKT/mTOR autophagic axis. In vivo experiments revealed that topical STE application provided substantial protection against UVA-induced photodamage in murine dorsal skin models. Liquid chromatography analysis identified amentoflavone as the principal bioactive component responsible for these protective properties. These findings collectively establish STE as a promising therapeutic agent against UVA photodamage, functioning through its dual capacity to attenuate apoptosis while promoting cytoprotective autophagy.
紫外线(UV)辐射,特别是UVA光谱(320-400 nm),会对皮肤真皮层和表皮层造成严重损伤,产生活性氧(ROS)并引发损害皮肤健康的细胞凋亡途径。卷柏(Selaginella tamariscina, P. Beauv.)是一种在亚洲广泛使用的传统药用植物,其含有大量的类黄酮化合物,具有公认的中药治疗价值。通过Western blotting、RT-qPCR和流式细胞术等综合分子分析,我们发现卷柏(Selaginella tamariscina, P. Beauv.)提取物(STE)可显著降低uva诱导的细胞凋亡,同时激活保护性自噬反应。从机制上讲,STE通过调节AKT磷酸化来调节两个关键的下游通路:(1)jnk介导的凋亡级联;(2)AKT/mTOR自噬轴。体内实验表明,局部STE应用对小鼠背部皮肤模型uva诱导的光损伤具有实质性的保护作用。液相色谱分析确定了阿门托黄酮是负责这些保护特性的主要生物活性成分。这些发现共同证明STE是一种很有前景的抗UVA光损伤治疗剂,通过其双重能力来减轻细胞凋亡,同时促进细胞保护性自噬。
{"title":"Selaginella Tamariscina extract reduces UVA-induced skin photodamage via regulating apoptosis and autophagy by AKT phosphorylation","authors":"Nan Zhao, Xiandong Zhou, Zhiwei Li, Ling Liang, Jinjing Bao, Xueyi Chen, Peng Shu, Jiangming Zhong","doi":"10.1016/j.jphotobiol.2025.113343","DOIUrl":"10.1016/j.jphotobiol.2025.113343","url":null,"abstract":"<div><div>Ultraviolet (UV) radiation, particularly in the UVA spectrum (320–400 nm), induces significant damage to both dermal and epidermal layers of skin, generating reactive oxygen species (ROS) and triggering apoptotic pathways that compromise skin health. <em>Selaginella tamariscina</em> (P. Beauv.), a traditional medicinal plant widely used throughout Asia, contains numerous flavonoid compounds with recognized therapeutic value in Chinese medicine. Through comprehensive molecular analyses including Western blotting, RT-qPCR, and flow cytometry, we demonstrated that the <em>Selaginella tamariscina</em> (P. Beauv.) extract (STE) significantly reduces UVA-induced apoptosis while simultaneously activating protective autophagic responses. Mechanistically, STE modulates AKT phosphorylation to regulate two critical downstream pathways: (1) the JNK-mediated apoptotic cascade and (2) the AKT/mTOR autophagic axis. In vivo experiments revealed that topical STE application provided substantial protection against UVA-induced photodamage in murine dorsal skin models. Liquid chromatography analysis identified amentoflavone as the principal bioactive component responsible for these protective properties. These findings collectively establish STE as a promising therapeutic agent against UVA photodamage, functioning through its dual capacity to attenuate apoptosis while promoting cytoprotective autophagy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113343"},"PeriodicalIF":3.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, we report the development of multifunctional CQ-dot@HA-Gd/Fe(III) microgels that can be readily simultaneously used in fluorescence/MR dual-mode imaging and photodynamic therapy as theragnostic agents. Nitrogen (N-) and sulfur (S-) heteroatom-doped carbon quantum dots (CQ-dot) were prepared in one step microwave treatment within 3 min as a fluorescence and photoinduced antipathogenic nanomaterial. The N/S-doped CQ-dots were spherical shaped and < 50 nm via TEM images and showed high fluorescence intensity with 420 nm emission wavelength at maximum λex:350 nm. The N/S-doped CQ-dots were embedded into ionically crosslinked hyaluronic acid (HA) microgels, employing trivalent metal ions Gd(III) or Fe(III) ions. The prepared CQ-dot@HA-Gd/Fe(III) microgels <5 mm size range are injectable for possible intravenous administration and possess high fluorescent properties. The isoelectric point (IEP) of CQ-dot@HA-Gd and CQ-dot@HA-Fe(III) microgels was determined as pH 1.45. The CQ-dot@HA-Gd/Fe(III) microgels exhibit excellent hemocompatibility without causing noticeable hemolysis and blood clotting at concentrations up to 500 mg/mL. Furthermore, the toxicity of CQ-dot@HA-Gd/Fe(III) microgels on L929 fibroblast cells was found as 100 mg/mL concentration and provide brilliant cell imaging under DAPI filter without any fluorescence dye. Also, the CQ-dot@HA-Gd/Fe(III) microgel suspension afforded great MRI contrast enhancement ability. Photoinduced anticancer activity was observed for CQ-dot@HA-Gd/Fe(III) microgels even at 50 mg/mL against SK-MEL 30 melanoma cells under UV-A light treatment for 30 min. In addition, high reactive oxygen species (ROS) generation was obtained for the pathogenic bacteria cells by light-sensitive CQ-dot@HA-Gd/Fe(III) microgels upon 30 min UV-A light treatment that triggered the destruction of the Staphylococcus aureus (ATCC 6538).
{"title":"Gd(III) and Fe(III) ion crosslinked hyaluronic acid microgels composites embedding hetero atom doped carbon quantum dots render photodynamic therapy with improved bioimaging capability","authors":"Selin Sagbas Suner , Mehtap Sahiner , Evrim Umut , Nurettin Sahiner","doi":"10.1016/j.jphotobiol.2025.113342","DOIUrl":"10.1016/j.jphotobiol.2025.113342","url":null,"abstract":"<div><div>In this study, we report the development of multifunctional CQ-dot@HA-Gd/Fe(III) microgels that can be readily simultaneously used in fluorescence/MR dual-mode imaging and photodynamic therapy as theragnostic agents. Nitrogen (N-) and sulfur (S-) heteroatom-doped carbon quantum dots (CQ-dot) were prepared in one step microwave treatment within 3 min as a fluorescence and photoinduced antipathogenic nanomaterial. The N/S-doped CQ-dots were spherical shaped and < 50 nm via TEM images and showed high fluorescence intensity with 420 nm emission wavelength at maximum λ<sub>ex</sub>:350 nm. The N/S-doped CQ-dots were embedded into ionically crosslinked hyaluronic acid (HA) microgels, employing trivalent metal ions Gd(III) or Fe(III) ions. The prepared CQ-dot@HA-Gd/Fe(III) microgels <5 mm size range are injectable for possible intravenous administration and possess high fluorescent properties. The isoelectric point (IEP) of CQ-dot@HA-Gd and CQ-dot@HA-Fe(III) microgels was determined as pH 1.45. The CQ-dot@HA-Gd/Fe(III) microgels exhibit excellent hemocompatibility without causing noticeable hemolysis and blood clotting at concentrations up to 500 mg/mL. Furthermore, the toxicity of CQ-dot@HA-Gd/Fe(III) microgels on L929 fibroblast cells was found as 100 mg/mL concentration and provide brilliant cell imaging under DAPI filter without any fluorescence dye. Also, the CQ-dot@HA-Gd/Fe(III) microgel suspension afforded great MRI contrast enhancement ability. Photoinduced anticancer activity was observed for CQ-dot@HA-Gd/Fe(III) microgels even at 50 mg/mL against SK-MEL 30 melanoma cells under UV-A light treatment for 30 min. In addition, high reactive oxygen species (ROS) generation was obtained for the pathogenic bacteria cells by light-sensitive CQ-dot@HA-Gd/Fe(III) microgels upon 30 min UV-A light treatment that triggered the destruction of the <em>Staphylococcus aureus</em> (ATCC 6538).</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113342"},"PeriodicalIF":3.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.jphotobiol.2025.113340
Biao Guo , Meiyun Wu , Liying Tong , Jiahui Yu , Ruoyun Liu , Meng Deng , Yijing Ma , Hao Li , Zile Yang , Xiyun Ye , Yongyan Dang
Safflower (Carthamus tinctorius L.) is a traditional Chinese medicinal herb that has long been used to promote blood circulation. Its major active component, hydroxysafflor yellow A (HSYA), exhibits potent antioxidant and anti-photoaging properties. However, the mechanisms underlying HSYA's protective effects against skin photoaging remain largely unclear. This study aimed to elucidate how HSYA mitigates skin aging induced by UVA- and UVB-triggered apoptosis and the senescence-associated secretory phenotype (SASP) in keratinocytes and fibroblasts. Damage models were established by exposing BALB/c nude mice, HaCaT keratinocytes, and HSF fibroblasts to either combined or individual UVA and UVB irradiation. Network pharmacology analysis was subsequently performed to explore the molecular mechanisms underlying the anti-photoaging effects of HSYA. The predicted targets and signaling pathways were validated through both in vitro and in vivo experiments. HSYA reduced apoptosis in UVB-damaged keratinocytes and UVA-damaged fibroblasts by regulating the expression of Bcl-2 and Bax and reducing cleavage of PARP and caspase 3. It also suppressed ROS accumulation in both cell types. Furthermore, HSYA inhibited SASP by downregulating the expression of TNF-α, IL-6, IL-8, and matrix metalloproteinases (MMPs). It significantly enhanced type I procollagen expression of skin fibroblasts and promoted collagen fiber deposition in mouse skin, suggesting a reversal of UV-induced senescence of skin fibroblasts. Mechanistically, HSYA exerted its protective effects by inhibiting the activation of the p38 and JNK pathways. Notably, the inhibitory effects of HSYA on p38 and JNK phosphorylation were comparable to those of specific MAPK inhibitors. These findings identify that HSYA exerts the protective effects against UV-induced skin damage through coordinated regulation of oxidative stress, inflammation, apoptosis, and collagen remodeling, in part by targeting the JNK/p38 MAPK pathway. Thus, HSYA emerges as a promising active ingredient for the development of anti-photoaging and skin-rejuvenation products in the future.
{"title":"Hydroxysafflower yellow a protects against UVA- and UVB-induced skin aging by suppressing cell apoptosis and SASP via targeting JNK and p38 MAPK pathway","authors":"Biao Guo , Meiyun Wu , Liying Tong , Jiahui Yu , Ruoyun Liu , Meng Deng , Yijing Ma , Hao Li , Zile Yang , Xiyun Ye , Yongyan Dang","doi":"10.1016/j.jphotobiol.2025.113340","DOIUrl":"10.1016/j.jphotobiol.2025.113340","url":null,"abstract":"<div><div>Safflower (<em>Carthamus tinctorius L.</em>) is a traditional Chinese medicinal herb that has long been used to promote blood circulation. Its major active component, hydroxysafflor yellow A (HSYA), exhibits potent antioxidant and anti-photoaging properties. However, the mechanisms underlying HSYA's protective effects against skin photoaging remain largely unclear. This study aimed to elucidate how HSYA mitigates skin aging induced by UVA- and UVB-triggered apoptosis and the senescence-associated secretory phenotype (SASP) in keratinocytes and fibroblasts. Damage models were established by exposing BALB/c nude mice, HaCaT keratinocytes, and HSF fibroblasts to either combined or individual UVA and UVB irradiation. Network pharmacology analysis was subsequently performed to explore the molecular mechanisms underlying the anti-photoaging effects of HSYA. The predicted targets and signaling pathways were validated through both <em>in vitro</em> and <em>in vivo</em> experiments. HSYA reduced apoptosis in UVB-damaged keratinocytes and UVA-damaged fibroblasts by regulating the expression of Bcl-2 and Bax and reducing cleavage of PARP and caspase 3. It also suppressed ROS accumulation in both cell types. Furthermore, HSYA inhibited SASP by downregulating the expression of <em>TNF-α, IL-6, IL-8</em>, and matrix metalloproteinases (MMPs). It significantly enhanced type I procollagen expression of skin fibroblasts and promoted collagen fiber deposition in mouse skin, suggesting a reversal of UV-induced senescence of skin fibroblasts. Mechanistically, HSYA exerted its protective effects by inhibiting the activation of the p38 and JNK pathways. Notably, the inhibitory effects of HSYA on p38 and JNK phosphorylation were comparable to those of specific MAPK inhibitors. These findings identify that HSYA exerts the protective effects against UV-induced skin damage through coordinated regulation of oxidative stress, inflammation, apoptosis, and collagen remodeling, in part by targeting the JNK/p38 MAPK pathway. Thus, HSYA emerges as a promising active ingredient for the development of anti-photoaging and skin-rejuvenation products in the future.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113340"},"PeriodicalIF":3.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.jphotobiol.2025.113339
Xiang-Yi Zhao , Min Yan , Liang Zheng , Chang-Long Gou , Qi Huang , Liu-Gen Li , Xin-Ran Yu , Jing-Yu Lu , Cui Hu , Si-Han Zhang , Cunqing Kong , Fan Leng , Tong-Fei Li
The regulation of mitochondrial membrane proteins is of crucial significance for breast cancer therapy. TOM70, which located in mitochondria outer membrane, could import MIC family molecules to preserve mitochondrial homeostasis. However, there are few agents targeting TOM70. Therein, the effects of curcumin and it's mediated photodynamic therapy (PDT) on the TOM70 and mitochondrial function for breast cancer treatment were investigated. The 4 T1 and MDA-MB-231 cells were utilized as the breast cancer cells. The 4 T1 cell-bearing mice were constructed as the breast cancer animal model. The anti-cancer efficacy was validated using the CCK-8, Annexin-V/PI staining, colony formation. The associated molecules were detected by Western blots (WB), RT-qPCR, and Immunohistochemistry (IHC). The target was verified by molecular docking, CETSA, and DARTS. The mitochondrial proteins and DNA were extracted for the MIC60 and mtDNA damage detection. Curcumin treatment showed poor efficacy in the breast cancer model, as characterized by cell viability, apoptosis, proliferation of breast cancer cells, and the growth of tumor grafts in mice. However, curcumin-mediated PDT inhibited breast cancer in vitro and in vivo. Further exploration identified curcumin bond to TOM70, which is highly expressed in breast cancer, thereby activating it. But curcumin-induced PDT inactivated TOM70 through generated reactive oxygen species (ROS), which in turn interfered with the binding of MIC60 and its translocation into mitochondria. Curcumin-triggered PDT led to severe mitochondrial damage compared with the curcumin treatment, which could be blocked by the N-Acetylcysteine (NAC). Additional TOM70 rescue dampened curcumin PDT-mediated mitochondrial damage and anti-breast cancer efficacy. To summarize, the present research identifies curcumin-induced PDT inactivated TOM70, thereby attenuating MIC60 import, leading to mitochondrial damage against breast cancer. We propose a novel approach to tumor treatment through the regulation of mitochondrial membrane proteins using the phytomedicine-driven PDT.
线粒体膜蛋白的调控对乳腺癌的治疗具有重要意义。TOM70位于线粒体外膜,可导入MIC家族分子维持线粒体稳态。然而,很少有靶向TOM70的药物。本文研究了姜黄素及其介导的光动力疗法(PDT)对乳腺癌TOM70和线粒体功能的影响。4个T1细胞和MDA-MB-231细胞作为乳腺癌细胞。构建4只T1细胞小鼠作为乳腺癌动物模型。通过CCK-8、Annexin-V/PI染色、菌落形成验证其抗癌效果。Western blots (WB)、RT-qPCR和免疫组化(IHC)检测相关分子。通过分子对接、CETSA、dart等方法对该靶点进行了验证。提取线粒体蛋白和DNA进行MIC60和mtDNA损伤检测。姜黄素治疗在乳腺癌模型中效果不佳,表现为细胞活力、凋亡、乳腺癌细胞增殖和小鼠肿瘤移植物生长。然而,姜黄素介导的PDT在体外和体内均能抑制乳腺癌。进一步探索发现姜黄素与TOM70结合,TOM70在乳腺癌中高度表达,从而激活TOM70。但姜黄素诱导的PDT通过产生活性氧(ROS)使TOM70失活,进而干扰MIC60的结合及其转运到线粒体。与姜黄素治疗相比,姜黄素引发的PDT导致严重的线粒体损伤,这可以被n-乙酰半胱氨酸(NAC)阻断。额外的TOM70救援抑制姜黄素pdt介导的线粒体损伤和抗乳腺癌疗效。综上所述,本研究发现姜黄素诱导的PDT灭活TOM70,从而减弱MIC60的输入,导致乳腺癌的线粒体损伤。我们提出了一种通过使用植物药驱动的PDT调节线粒体膜蛋白来治疗肿瘤的新方法。
{"title":"Curcumin-mediated photodynamic action disturbs TOM70-depedent MIC60 import to damage mitonchondria against breast cancer","authors":"Xiang-Yi Zhao , Min Yan , Liang Zheng , Chang-Long Gou , Qi Huang , Liu-Gen Li , Xin-Ran Yu , Jing-Yu Lu , Cui Hu , Si-Han Zhang , Cunqing Kong , Fan Leng , Tong-Fei Li","doi":"10.1016/j.jphotobiol.2025.113339","DOIUrl":"10.1016/j.jphotobiol.2025.113339","url":null,"abstract":"<div><div>The regulation of mitochondrial membrane proteins is of crucial significance for breast cancer therapy. TOM70, which located in mitochondria outer membrane, could import MIC family molecules to preserve mitochondrial homeostasis. However, there are few agents targeting TOM70. Therein, the effects of curcumin and it's mediated photodynamic therapy (PDT) on the TOM70 and mitochondrial function for breast cancer treatment were investigated. The 4 T1 and MDA-MB-231 cells were utilized as the breast cancer cells. The 4 T1 cell-bearing mice were constructed as the breast cancer animal model. The anti-cancer efficacy was validated using the CCK-8, Annexin-V/PI staining, colony formation. The associated molecules were detected by Western blots (WB), RT-qPCR, and Immunohistochemistry (IHC). The target was verified by molecular docking, CETSA, and DARTS. The mitochondrial proteins and DNA were extracted for the MIC60 and mtDNA damage detection. Curcumin treatment showed poor efficacy in the breast cancer model, as characterized by cell viability, apoptosis, proliferation of breast cancer cells, and the growth of tumor grafts in mice. However, curcumin-mediated PDT inhibited breast cancer in vitro and in vivo. Further exploration identified curcumin bond to TOM70, which is highly expressed in breast cancer, thereby activating it. But curcumin-induced PDT inactivated TOM70 through generated reactive oxygen species (ROS), which in turn interfered with the binding of MIC60 and its translocation into mitochondria. Curcumin-triggered PDT led to severe mitochondrial damage compared with the curcumin treatment, which could be blocked by the N-Acetylcysteine (NAC). Additional TOM70 rescue dampened curcumin PDT-mediated mitochondrial damage and anti-breast cancer efficacy. To summarize, the present research identifies curcumin-induced PDT inactivated TOM70, thereby attenuating MIC60 import, leading to mitochondrial damage against breast cancer. We propose a novel approach to tumor treatment through the regulation of mitochondrial membrane proteins using the phytomedicine-driven PDT.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113339"},"PeriodicalIF":3.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.jphotobiol.2025.113330
Lee So Maeng , Jung Hwan Yoon , Bom Yee Chung , Kyung Jin Seo , Hae Kyung Lee , Moon Gyu Chung , Won Sang Park , Hiun Suk Chae
Background
Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are chronic conditions influenced by genetic and environmental factors. Current treatments are costly and not universally effective. This study aimed to evaluate the therapeutic potential of refined photobiomodulation (PBM) therapy by addressing limitations in light delivery and its impact on gut microbiota using a dextran sodium sulfate (DSS)-induced colitis mouse model.
Methods
PBM therapy was administered using an 830 nm infrared LED with optimized light delivery protocols, including abdominal hair removal and a four-directional irradiation approach. DSS-induced colitis was established in mice, and therapeutic efficacy was assessed through histological analysis, transcriptomic profiling, immune marker expression, and gut microbiota diversity using 16S rRNA sequencing.
Results
PBM therapy significantly ameliorated DSS-induced colitis by reducing inflammatory cell infiltration, crypt damage, and ulceration (p < 0.05). Colon length was restored, and disease activity index scores were reduced (p < 0.001). Transcriptomic profiling revealed modulation of inflammatory pathways, including downregulation of NF-κB signaling and apoptosis-related genes. PBM decreased neutrophil activity (MPO levels) and immune cell marker expression while promoting gut microbiota richness (Chao1 index, p < 0.05). PBM-treated mice exhibited altered microbial composition with increased abundance of protective taxa such as Bacteroides.
Conclusions
Refined PBM therapy effectively alleviates DSS-induced colitis by modulating immune responses and gut microbiota composition. These findings highlight PBM as a promising non-invasive strategy for IBD management, warranting further translational studies.
{"title":"Refined photobiomodulation therapy ameliorates inflammatory bowel disease via modulation of immune pathways and gut microbiota","authors":"Lee So Maeng , Jung Hwan Yoon , Bom Yee Chung , Kyung Jin Seo , Hae Kyung Lee , Moon Gyu Chung , Won Sang Park , Hiun Suk Chae","doi":"10.1016/j.jphotobiol.2025.113330","DOIUrl":"10.1016/j.jphotobiol.2025.113330","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are chronic conditions influenced by genetic and environmental factors. Current treatments are costly and not universally effective. This study aimed to evaluate the therapeutic potential of refined photobiomodulation (PBM) therapy by addressing limitations in light delivery and its impact on gut microbiota using a dextran sodium sulfate (DSS)-induced colitis mouse model.</div></div><div><h3>Methods</h3><div>PBM therapy was administered using an 830 nm infrared LED with optimized light delivery protocols, including abdominal hair removal and a four-directional irradiation approach. DSS-induced colitis was established in mice, and therapeutic efficacy was assessed through histological analysis, transcriptomic profiling, immune marker expression, and gut microbiota diversity using 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>PBM therapy significantly ameliorated DSS-induced colitis by reducing inflammatory cell infiltration, crypt damage, and ulceration (<em>p</em> < 0.05). Colon length was restored, and disease activity index scores were reduced (<em>p</em> < 0.001). Transcriptomic profiling revealed modulation of inflammatory pathways, including downregulation of NF-κB signaling and apoptosis-related genes. PBM decreased neutrophil activity (MPO levels) and immune cell marker expression while promoting gut microbiota richness (Chao1 index, <em>p</em> < 0.05). PBM-treated mice exhibited altered microbial composition with increased abundance of protective taxa such as Bacteroides.</div></div><div><h3>Conclusions</h3><div>Refined PBM therapy effectively alleviates DSS-induced colitis by modulating immune responses and gut microbiota composition. These findings highlight PBM as a promising non-invasive strategy for IBD management, warranting further translational studies.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113330"},"PeriodicalIF":3.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.jphotobiol.2025.113336
Büşra Sirek , Nermin Topaloğlu
Photodynamic therapy (PDT) is a successful therapy for cancer treatment, especially for the superficial and easily reachable types, such as prostate cancer. During photodynamic activation, the light-sensitive chemical, which generally does not have a toxic effect on cells, can induce oxidative stress by producing reactive oxygen species (ROS). Nevertheless, the outcome of the therapy may be diminished by certain drawbacks. For this, PDT can be coupled with other therapies. Different light therapies can also serve as effective anticancer strategies. The combination of photobiomodulation (PBM) with PDT has become increasingly popular in cancer management. In the present study, PBM, which lacks anticancer activity, was combined with Chlorin e6 (Ce6)-mediated PDT. Underlying causes of additional deaths were elucidated by various mechanistic analyses, including ROS, nitric oxide (NO), mitochondrial membrane potential (ΔΨm), etc. PBM priming at an energy density of 5 J/cm2 resulted in up to 64 % additional cell death, as demonstrated by colorimetric and dual-staining analyses, and nearly a 100 % decrease in cell migration compared to PDT alone. Besides, PBM priming induced an additional 0.5-fold reduction in NO levels, a 19.4 % increase in ROS levels, and a 1.2 % reduction in ΔΨm compared to only PDT applications. Thus, combining PDT with PBM priming can provide a more effective therapeutic approach and significantly diminish the invasiveness of cancer cells.
{"title":"Priming cancer cells via photobiomodulation at NIR wavelength to enhance photodynamic action: Insights into mechanistic alterations and cellular migration","authors":"Büşra Sirek , Nermin Topaloğlu","doi":"10.1016/j.jphotobiol.2025.113336","DOIUrl":"10.1016/j.jphotobiol.2025.113336","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is a successful therapy for cancer treatment, especially for the superficial and easily reachable types, such as prostate cancer. During photodynamic activation, the light-sensitive chemical, which generally does not have a toxic effect on cells, can induce oxidative stress by producing reactive oxygen species (ROS). Nevertheless, the outcome of the therapy may be diminished by certain drawbacks. For this, PDT can be coupled with other therapies. Different light therapies can also serve as effective anticancer strategies. The combination of photobiomodulation (PBM) with PDT has become increasingly popular in cancer management. In the present study, PBM, which lacks anticancer activity, was combined with Chlorin e6 (Ce6)-mediated PDT. Underlying causes of additional deaths were elucidated by various mechanistic analyses, including ROS, nitric oxide (NO), mitochondrial membrane potential (ΔΨm), etc. PBM priming at an energy density of 5 J/cm<sup>2</sup> resulted in up to 64 % additional cell death, as demonstrated by colorimetric and dual-staining analyses, and nearly a 100 % decrease in cell migration compared to PDT alone. Besides, PBM priming induced an additional 0.5-fold reduction in NO levels, a 19.4 % increase in ROS levels, and a 1.2 % reduction in ΔΨm compared to only PDT applications. Thus, combining PDT with PBM priming can provide a more effective therapeutic approach and significantly diminish the invasiveness of cancer cells.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113336"},"PeriodicalIF":3.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145747531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.jphotobiol.2025.113338
Yanjun Ma , Rong Li , Jiahui Li , Zilu Song , Fawen She , Xiaoyan Ma , Xuetai Zhu
Triterpenoids from medicinal fungi have significant biological activities and industrial potential, but their low yield limits large-scale production. Sanghuangporus vaninii, a widely cultivated medicinal fungus, is a promising source of triterpenoids, yet the regulatory role of light-dark cycles in its triterpenoid biosynthesis remains unclear. In this study, we demonstrated that intermittent intense blue light-dark cycles (IB/D; ∼110 μmol/m2·s, 10 h/14 h) dramatically enhance triterpenoid production in S. vaninii MF5. IB/D treatment increased triterpenoid yield by 154 % compared to dark controls, also outperforming constant light or white light-dark regimens. Mechanistically, IB/D was associated with: (i) hyperbranching morphology (42 % reduced internode length); (ii) membrane remodeling via upregulated fatty acid desaturases and transporters, enhancing permeability 2.88-fold; and (iii) transcriptional activation of the mevalonate pathway, which was accompanied by a dramatic induction of endogenous 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) expression 4497-fold. Subsequent cloning and characterization of the SvHMGS gene-through sequence homology with known HMGS genes from Sanghuangporus species, identification of conserved HMGS domains, and prediction of its association with the mevalonic acid (MVA) pathway-suggested its potential conserved function in triterpenoid biosynthesis. This photoperiodic strategy represents a paradigm shift from constant light suppression to rhythmic induction, offering a scalable, low-cost approach to boost triterpenoid production in this medicinal fungus.
{"title":"Intermittent blue light-dark cycles: A new strategy for enhancing triterpenoid production in medicinal Sanghuangporus vaninii","authors":"Yanjun Ma , Rong Li , Jiahui Li , Zilu Song , Fawen She , Xiaoyan Ma , Xuetai Zhu","doi":"10.1016/j.jphotobiol.2025.113338","DOIUrl":"10.1016/j.jphotobiol.2025.113338","url":null,"abstract":"<div><div>Triterpenoids from medicinal fungi have significant biological activities and industrial potential, but their low yield limits large-scale production. <em>Sanghuangporus vaninii</em>, a widely cultivated medicinal fungus, is a promising source of triterpenoids, yet the regulatory role of light-dark cycles in its triterpenoid biosynthesis remains unclear. In this study, we demonstrated that intermittent intense blue light-dark cycles (IB/D; ∼110 μmol/m<sup>2</sup>·s, 10 h/14 h) dramatically enhance triterpenoid production in <em>S. vaninii</em> MF5. IB/D treatment increased triterpenoid yield by 154 % compared to dark controls, also outperforming constant light or white light-dark regimens. Mechanistically, IB/D was associated with: (i) hyperbranching morphology (42 % reduced internode length); (ii) membrane remodeling via upregulated fatty acid desaturases and transporters, enhancing permeability 2.88-fold; and (iii) transcriptional activation of the mevalonate pathway, which was accompanied by a dramatic induction of endogenous 3-hydroxy-3-methylglutaryl-CoA synthase (<em>HMGS</em>) expression 4497-fold. Subsequent cloning and characterization of the <em>SvHMGS</em> gene-through sequence homology with known <em>HMGS</em> genes from <em>Sanghuangporus</em> species, identification of conserved HMGS domains, and prediction of its association with the mevalonic acid (MVA) pathway-suggested its potential conserved function in triterpenoid biosynthesis. This photoperiodic strategy represents a paradigm shift from constant light suppression to rhythmic induction, offering a scalable, low-cost approach to boost triterpenoid production in this medicinal fungus.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113338"},"PeriodicalIF":3.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The extensively presence of nanoplastics raises concerns about their harm to ecosystems and human health. They are easy to absorb serum albumin to form corona during the transport process. However, the regulation of serum albumin to the toxicity of nanoplastics with differing charges and sizes remains unknown. We examined the molecular mechanism of polystyrene nanoplastics (PS-NPs) to bovine serum albumin (BSA) and how corona modulates the mouse primary hepatocyte damage. In cells exposed to 100 mg/L of large PS-NH2-NPs and PS-COOH-NPs, a significant reduction in cell viability of 27 % and 22 % was noted, respectively, under BSA-free conditions. In contrast, the reductions were limited to 17 % and 13 % in the presence of BSA. Additionally, BSA pretreatment also lowered the reactive oxygen species (ROS) levels compared to the use of two modified PS-NPs (200 nm) alone. However, the addition of BSA did not significantly alter the cell viability or the levels of ROS in small PS-NPs (80 nm). Molecular investigations demonstrated that PS-NPs mainly bound to the hydrophobic cavity of BSA through moderate hydrophobic forces with the binding affinity approximately 105 M−1. The formation of corona not only induced conformational changes in BSA but also modified its esterase activity. The molecular and cellular experiments both revealed the size and surface charge-specific toxicity pattern of nanoplastics. Big PS-NPs (200 nm) bound more tightly to the protein compared to small nanoplastics (80 nm), and PS-NH2-NPs presented a greater risk to BSA than PS-COOH-NPs. This study elucidates how BSA corona formation modulates nanoplastic toxicity in a size- and charge-dependent manner.
{"title":"Molecular mechanism underlying the modulated toxicity of differently charged and sized nanoplastics by bovine serum albumin","authors":"Xingren Pan , Xiaozhang Yu , Pengfei Qin , Wanni Yu","doi":"10.1016/j.jphotobiol.2025.113337","DOIUrl":"10.1016/j.jphotobiol.2025.113337","url":null,"abstract":"<div><div>The extensively presence of nanoplastics raises concerns about their harm to ecosystems and human health. They are easy to absorb serum albumin to form corona during the transport process. However, the regulation of serum albumin to the toxicity of nanoplastics with differing charges and sizes remains unknown. We examined the molecular mechanism of polystyrene nanoplastics (PS-NPs) to bovine serum albumin (BSA) and how corona modulates the mouse primary hepatocyte damage. In cells exposed to 100 mg/L of large PS-NH<sub>2</sub>-NPs and PS-COOH-NPs, a significant reduction in cell viability of 27 % and 22 % was noted, respectively, under BSA-free conditions. In contrast, the reductions were limited to 17 % and 13 % in the presence of BSA. Additionally, BSA pretreatment also lowered the reactive oxygen species (ROS) levels compared to the use of two modified PS-NPs (200 nm) alone. However, the addition of BSA did not significantly alter the cell viability or the levels of ROS in small PS-NPs (80 nm). Molecular investigations demonstrated that PS-NPs mainly bound to the hydrophobic cavity of BSA through moderate hydrophobic forces with the binding affinity approximately 10<sup>5</sup> M<sup>−1</sup>. The formation of corona not only induced conformational changes in BSA but also modified its esterase activity. The molecular and cellular experiments both revealed the size and surface charge-specific toxicity pattern of nanoplastics. Big PS-NPs (200 nm) bound more tightly to the protein compared to small nanoplastics (80 nm), and PS-NH<sub>2</sub>-NPs presented a greater risk to BSA than PS-COOH-NPs. This study elucidates how BSA corona formation modulates nanoplastic toxicity in a size- and charge-dependent manner.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113337"},"PeriodicalIF":3.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High-fluence visible light (VL) has been reported to induce cutaneous pigmentation similarly to ultraviolet radiation. However, VL is a polychromatic light composed of different wavelengths. More experimental studies are required to elucidate the effects of VL parameters on melanin synthesis. In this study, using murine B16F10 melanoma cells as an in vitro model, we systematically investigated how wavelength, fluence, irradiance and irradiation mode jointly determine the melanogenic response to VL. We revealed that 448 nm blue light stimulated melanogenesis, whereas 560–733 nm light globally suppressed it, with 595 nm yellow light exhibiting the strongest inhibition. Furthermore, a biphasic response was observed: both 560 nm and 595 nm yellow light inhibited melanogenesis at 3–12 J/cm2 but markedly enhanced it at 48 J/cm2. 595 nm light suppressed melanin synthesis at 5–20 mW/cm2, yet switched to stimulation at ≥ 40 mW/cm2. Additionally, our results suggested that the 595 nm pulsed PBM (3000 Hz, 40 %–80 % duty cycle) outperformed continuous PBM, whereas the 20 % duty cycle (with a peak irradiance of 25 mW/cm2) abolished the inhibitory effect, indicating that high irradiance activates pro-melanogenic defense pathways. Experimental data indicated that these differences arise primarily from the distinct effects of light parameters on tyrosinase activity and the mRNA levels of microphthalmia-associated transcription factor (MITF), TYR, TRP1, and TRP2. In conclusion, the regulatory effect of VL on melanogenesis is dependent on the selection of these parameters. These data provide an experimental basis for optimizing LED phototherapy parameters and support subsequent in-depth mechanistic studies in human cutaneous melanocytes. In the future, optimized VL parameters may balance the efficacy and safety of phototherapy in skin disorders caused by pigmentation dysregulation, such as vitiligo and melasma.
{"title":"Effects of wavelength, fluence, irradiance, and irradiation mode of visible light on melanogenesis in B16F10 melanoma cells","authors":"Tianxiu Lu, Diya Shen, Yu Tian, Zihao Zheng, Fusheng Li, Qiuyi Han, Shanduan Zhang","doi":"10.1016/j.jphotobiol.2025.113335","DOIUrl":"10.1016/j.jphotobiol.2025.113335","url":null,"abstract":"<div><div>High-fluence visible light (VL) has been reported to induce cutaneous pigmentation similarly to ultraviolet radiation. However, VL is a polychromatic light composed of different wavelengths. More experimental studies are required to elucidate the effects of VL parameters on melanin synthesis. In this study, using murine B16F10 melanoma cells as an in vitro model, we systematically investigated how wavelength, fluence, irradiance and irradiation mode jointly determine the melanogenic response to VL. We revealed that 448 nm blue light stimulated melanogenesis, whereas 560–733 nm light globally suppressed it, with 595 nm yellow light exhibiting the strongest inhibition. Furthermore, a biphasic response was observed: both 560 nm and 595 nm yellow light inhibited melanogenesis at 3–12 J/cm<sup>2</sup> but markedly enhanced it at 48 J/cm<sup>2</sup>. 595 nm light suppressed melanin synthesis at 5–20 mW/cm<sup>2</sup>, yet switched to stimulation at ≥ 40 mW/cm<sup>2</sup>. Additionally, our results suggested that the 595 nm pulsed PBM (3000 Hz, 40 %–80 % duty cycle) outperformed continuous PBM, whereas the 20 % duty cycle (with a peak irradiance of 25 mW/cm<sup>2</sup>) abolished the inhibitory effect, indicating that high irradiance activates pro-melanogenic defense pathways. Experimental data indicated that these differences arise primarily from the distinct effects of light parameters on tyrosinase activity and the mRNA levels of microphthalmia-associated transcription factor (MITF), TYR, TRP1, and TRP2. In conclusion, the regulatory effect of VL on melanogenesis is dependent on the selection of these parameters. These data provide an experimental basis for optimizing LED phototherapy parameters and support subsequent in-depth mechanistic studies in human cutaneous melanocytes. In the future, optimized VL parameters may balance the efficacy and safety of phototherapy in skin disorders caused by pigmentation dysregulation, such as vitiligo and melasma.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113335"},"PeriodicalIF":3.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.jphotobiol.2025.113334
Jihad M. El-Sayed , Sally M. Khadrawy , Hanaa M. Mohamed , Magdy Sayed Aly , Abdelwahab Khalil , Dina Sabry , Tarek Mohamed
Rheumatoid arthritis (RA) is a chronic condition characterized by joint degradation and systemic manifestations, which increase the risk of mortality and disability. This study compared the effects of bee venom (BV; subcutaneously administered at 1 mg/kg) and femtosecond laser irradiation (FSL; 830 nm wavelength, 200 mW power, 120 s exposure time, 0.8 cm2 beam area with a 0.5 cm radius, 0.25 W/cm2 power density, and 30 J/cm2 energy dose), either individually or in combination, on arthritic rats. Forty-two adult male Wistar rats were allocated into seven groups. Groups 1–3 served as the negative control, BV, and FSL groups, respectively, while group 4 functioned as the arthritic model group that received 100 μL/rat of complete Freund's adjuvant (CFA) in the right hind paw. Groups 5–7 included arthritic rats treated with BV, FSL, or their combination, respectively. Histological examination of RA development, showing synovitis, cellular infiltration, and cartilage degeneration. Treatment with BV injections and FSL irradiation significantly reduced right hind paw edema, improved histological abnormalities, and reduced serum levels of C-reactive protein (CRP) and rheumatoid factor (RF), alongside decreased tissue expressions of TNF-α, NF-KB, and IL-6 in the affected ankle joints. Moreover, both treatments mitigated oxidative stress, reduced DNA damage, and regulated PI3K/AKT/mTOR and JAK/STAT signaling pathways. Collectively, FSL, either alone or in combination with BV, demonstrated a superior capacity for cartilage regeneration and tissue repair. This highlights BV and FSL as a promising RA therapy, addressing underlying mechanisms beyond symptom relief.
{"title":"Femtosecond laser and bee venom as promising anti-arthritic treatments: Modulation of JAK/STAT and PI3K/AKT/mTOR signaling pathways in vivo","authors":"Jihad M. El-Sayed , Sally M. Khadrawy , Hanaa M. Mohamed , Magdy Sayed Aly , Abdelwahab Khalil , Dina Sabry , Tarek Mohamed","doi":"10.1016/j.jphotobiol.2025.113334","DOIUrl":"10.1016/j.jphotobiol.2025.113334","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic condition characterized by joint degradation and systemic manifestations, which increase the risk of mortality and disability. This study compared the effects of bee venom (BV; subcutaneously administered at 1 mg/kg) and femtosecond laser irradiation (FSL; 830 nm wavelength, 200 mW power, 120 s exposure time, 0.8 cm<sup>2</sup> beam area with a 0.5 cm radius, 0.25 W/cm<sup>2</sup> power density, and 30 J/cm<sup>2</sup> energy dose), either individually or in combination, on arthritic rats. Forty-two adult male Wistar rats were allocated into seven groups. Groups 1–3 served as the negative control, BV, and FSL groups, respectively, while group 4 functioned as the arthritic model group that received 100 μL/rat of complete Freund's adjuvant (CFA) in the right hind paw. Groups 5–7 included arthritic rats treated with BV, FSL, or their combination, respectively. Histological examination of RA development, showing synovitis, cellular infiltration, and cartilage degeneration. Treatment with BV injections and FSL irradiation significantly reduced right hind paw edema, improved histological abnormalities, and reduced serum levels of C-reactive protein (CRP) and rheumatoid factor (RF), alongside decreased tissue expressions of TNF-α, NF-KB, and IL-6 in the affected ankle joints. Moreover, both treatments mitigated oxidative stress, reduced DNA damage, and regulated PI3K/AKT/mTOR and JAK/STAT signaling pathways. Collectively, FSL, either alone or in combination with BV, demonstrated a superior capacity for cartilage regeneration and tissue repair. This highlights BV and FSL as a promising RA therapy, addressing underlying mechanisms beyond symptom relief.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"274 ","pages":"Article 113334"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}