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The interplay between LHCSR and PSBS proteins provides photoprotection in Chlamydomonas reinhardtii pgr5 mutant under high light LHCSR 和 PSBS 蛋白之间的相互作用为强光下的衣藻 pgr5 突变体提供了光保护。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.jphotobiol.2024.113060
Ranay Mohan Yadav , Nisha Chouhan , Jerome Xavier Gunasekaran , Sai Kiran Madireddi , Aparna Nerusu , Rajagopal Subramanyam
Cyclic electron transport (CET) is a vital alternative route that protects against photodamage and aids in energy production. This process depends on proton gradient regulation 5 (PGR5) and PGRL1-dependent pathways associated with CET. The exact roles of these proteins in photosystem I photochemistry under prolonged high light conditions are not fully understood. Continuous light adaptation hinges on two critical mechanisms: alterations in the proton motive force (pmf) and adjustments in the ratio of proteins activated by high light that dissipate excess light through non-photochemical quenching (NPQ). To explore this, we studied pgrl1 and pgr5 mutants to gauge their roles in balancing photochemistry and photoacclimation. These mutants showed inhibited growth, reduced photosynthetic efficiency, and a lowered pmf, leading to diminished non-photochemical energy quenching (qE) under high light. Prolonged high light exposure slowed down unregulated energy losses Y(NO), and relaxation helped regulate photosynthetic activity by increasing photoinhibitory quenching (qI), thus preventing further damage to the photosystem. The precise balance between the two pmf components, ΔpH and Δψ, is critical for controlling photochemistry and photoacclimation, yet remains elusive. In pgr5 reduced pmf led to an accumulation of cytochrome b6f under high light, and a decrease in the ΔpH component and increased the Δψ component's role in photosynthetic acclimation. Notably, light-harvesting complex stress response protein 3 (LHCSR3) showed decreased expression in pgrl1, whereas pgr5 exhibited no expression of both LHCSR3 and LHCSR1 under high-light conditions. Moreover, continuous increase in PSBS protein accumulation in pgr5 suggests enhanced photoprotection in the absence of LHCSR3 under high light. The study provides significant insights into how CET regulates photoprotective proteins LHCSR and PSBS, influencing Chlamydomonas' survival strategies.
循环电子传递(CET)是一种重要的替代途径,可防止光损伤并帮助产生能量。这一过程依赖于与 CET 相关的质子梯度调节 5(PGR5)和 PGRL1 依赖性途径。在长期强光条件下,这些蛋白质在光系统 I 光化学中的确切作用尚不完全清楚。持续的光适应取决于两个关键机制:质子动力(pmf)的改变和通过非光化学淬灭(NPQ)消散过量光的被强光激活的蛋白质比例的调整。为了探讨这个问题,我们研究了 pgrl1 和 pgr5 突变体,以衡量它们在平衡光化学和光螯合作用方面的作用。这些突变体在强光下表现出生长受抑制、光合效率降低和pmf降低,导致非光化学能量淬灭(qE)减弱。长时间的强光照射减缓了非调控能量损失 Y(NO),而弛豫则通过增加光抑制淬灭(qI)来帮助调节光合作用活性,从而防止光系统进一步受损。pmf的两个成分ΔpH和Δψ之间的精确平衡对于控制光化学和光螯合至关重要,但至今仍难以捉摸。在 pgr5 中,pmf 的减少导致细胞色素 b6f 在强光下的积累、ΔpH 成分的减少以及Δψ成分在光合适应中作用的增加。值得注意的是,采光复合体应激反应蛋白 3(LHCSR3)在 pgrl1 中的表达量减少,而 pgr5 在高光条件下 LHCSR3 和 LHCSR1 均无表达。此外,pgr5 中 PSBS 蛋白积累的持续增加表明,在强光下 LHCSR3 缺失的情况下,光保护作用增强。这项研究为了解 CET 如何调控光保护蛋白 LHCSR 和 PSBS,从而影响衣藻的生存策略提供了重要启示。
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引用次数: 0
In vitro and in vivo investigation of the inhibitory effects of Sinoporphyrin sodium-mediated Sonodynamic therapy on human oral squamous cell carcinoma 体外和体内研究卟啉钠介导的声动力学疗法对人类口腔鳞状细胞癌的抑制作用。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.jphotobiol.2024.113061
Guogang Dong , Limin Jia , Shuhua Gao , Monan Lin , Ruilin Wang , Fuyu Yang , Juanjuan Ruan , Yanhong Lv

Objective

Sonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo.

Methods

Fluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm2 in vitro and 3 W/cm2 in vivo) in conjunction with DVDMS also being examined.

Results

The findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy.

Conclusion

DVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis.
目的:声动力疗法(SDT)是一种创新的非侵入性癌症治疗方法,它利用低强度超声波触发激活癌细胞内的声敏化剂。本研究旨在探索一种新型声波增敏剂--卟啉钠(DVDMS)在超声照射下对口腔鳞状细胞癌(OSCC)衍生的 SCC-154 细胞的体外和体内疗效:方法:检测 DVDMS 在 SCC-154 细胞系中的荧光光谱、细胞毒性评估、吸收机制和亚细胞分布。此外,该研究还全面评估了在体外和体内使用低强度超声波(1.0 MHz,体外为 1 W/cm2,体内为 3 W/cm2)处理 SCC-154 细胞后,DVDMS 的抗肿瘤效果、氧化应激反应、细胞凋亡、凋亡相关蛋白、自噬过程和超微结构变化:结果:研究结果表明,与 SAS 和 HSC-3 细胞系相比,SCC-154 细胞对 DVDMS 的敏感性更高。在 SCC-154 细胞内,DVDMS 主要定位于线粒体和溶酶体。基于 DVDMS 的 SDT 能明显提高细胞内活性氧(ROS)的水平,诱导线粒体肿胀和自溶酶体形成等形态学变化,并表现出明显的剂量依赖性降低体外细胞活力。此外,DVDMS-SDT 还能显著抑制异种移植的生长,且无明显不良反应。从机理上讲,DVDMS-SDT上调了Bax的表达,同时下调了Bcl-2的表达,这导致了Bax/Bcl-2比率的下降,并诱导了自噬:结论:与5-ALA和原卟啉IX(PpIX)不同,DVDMS-SDT可引发SCC-154细胞的线粒体依赖性凋亡。此外,DVDMS与超声刺激相结合可诱导自噬,自噬过程的开始先于细胞凋亡。
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引用次数: 0
Synthesis of heavy-atom-free thienoisoindigo dye as near-infrared photosensitizer for type I photodynamic therapy and photoacoustic imaging 合成不含重原子的噻吩异靛蓝染料,作为 I 型光动力疗法和光声成像的近红外光敏剂。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-05 DOI: 10.1016/j.jphotobiol.2024.113052
Feng Zhang , Hao Cai , Leichen Wang , Jinjun Shao
Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-AD) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O2-•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.
噻吩异靛蓝(TIIG)已被广泛用作近红外(NIR)染料和有机半导体材料的重要组成部分。本文报道了无重原子 TIIG 基近红外染料 TIIGTPA 作为光敏剂用于光动力和光热疗法以及光声成像(PAI)。通过在缺电子 TIIG 内核的外围位点引入两个甲氧基取代的三苯基胺作为转子和电子供体,构建了具有高强度近红外吸收的供体-受体-供体(D-AD)结构的染料 TIIGTPA。通过与两性离子 F-127 共同组装,制备出了水溶性 TIIGTPA NPs,在 730 纳米光照射下,该 NPs 具有良好的超氧阴离子自由基(O2--)生成能力和 59.0 % 的高光热转换效率(PCE)。此外,卓越的光热效应还能通过 PAI 实现肿瘤血管可视化的卓越光声响应。所有结果都表明,TIIGTPA NPs 在 PAI 介导的组合光疗中具有良好的潜力。
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引用次数: 0
Light and phytochrome PHY control the production of edible fungus Flammulina filiformis by regulating the morphogenesis of fruiting bodies and l-lysine accumulation 光和植物色素 PHY 通过调控子实体的形态发生和赖氨酸的积累来控制食用菌丝状木耳的生产
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.jphotobiol.2024.113051
Yizhao Chen , Huimin Ju , Hui Li , Chang Xu , Hui Jia , Lijun Xian , Chengjin Yuan , Zexuan Guo , Xijin Zhang , Yilin Yu , Yongxin Tao
Flammulina filiformis, a representative umbelliferous fungus, has a long stipe and high l-lysine content, thus is widely cultivated and consumed. Currently, there is a lack of theoretical guidance on how to better use light to cultivate edible fungi without photosynthesis such as F. filiformis in industrialized cultivation. Previous studies have found that blue light can affect the yield and l-lysine content of F. filiformis. The primary focus of this work was the phytochrome PHY in the light signaling pathway and its role in F. filiformis production. Unlike plants in which the expression of PHY was activated by only red light, it was found that different visible lights (including red, blue, green, and white light) can stimulate the up-regulation of FfPhy transcript levels. Throughout the developmental stages of F. filiformis, the transcript level of FfPhy was significantly up-regulated during the formation of fruiting body and in the stipe in the elongation stage. Further, FfPhy knockdown strain showed the markedly shorter stipe length than WT, resulting in a significantly reduced yield. RNA-Seq analysis showed that the most genes in MAPK signaling pathway and its downstream regulatory processes, mainly focusing on cell division and cell wall remodeling, were down-regulated after FfPhy knockdown. It suggested that FfPhy regulates the fruiting body elongation through acting on cell division and cell wall remodeling, thereby affecting the morphological development of the stipe rather than the pileus. Interestingly, FfPhy knockdown also inhibits the accumulation of l-lysine content by promoting l-lysine degradation instead of inhibiting l-lysine biosynthesis, indicating that its influence extends to metabolic processes related to l-lysine metabolism. These findings provide new insights into photobiological effect of FfPhy in macrofungus F. filiformis, and have potential guiding significance for cultivation and breeding to increase mushroom yield and l-lysine content.
丝状木耳(Flammulina filiformis)是伞形科真菌的代表,具有菌柄长、赖氨酸含量高等特点,因此被广泛栽培和食用。目前,在工业化栽培中,如何更好地利用光来栽培丝状木耳等无光合作用的食用菌还缺乏理论指导。之前的研究发现,蓝光会影响丝状真菌的产量和赖氨酸含量。这项工作的主要重点是光信号途径中的植物色素 PHY 及其在丝核菌生产中的作用。与仅红光能激活 PHY 表达的植物不同,研究发现不同的可见光(包括红光、蓝光、绿光和白光)都能刺激 FfPhy 转录本水平的上调。在丝核菌的整个发育阶段中,FfPhy的转录水平在子实体形成期和伸长期的柄部明显上调。此外,FfPhy基因敲除菌株的果柄长度明显短于WT菌株,导致产量明显降低。RNA-Seq分析表明,FfPhy敲除后,MAPK信号通路及其下游调控过程中的大部分基因下调,主要集中在细胞分裂和细胞壁重塑方面。这表明FfPhy通过作用于细胞分裂和细胞壁重塑来调控子实体的伸长,从而影响柄而不是绒毛的形态发育。有趣的是,FfPhy 基因敲除还能通过促进赖氨酸降解而不是抑制赖氨酸的生物合成来抑制赖氨酸含量的积累,这表明其影响延伸到了与赖氨酸代谢相关的代谢过程。这些发现为了解 FfPhy 在丝状真菌中的光生物效应提供了新的视角,对提高蘑菇产量和赖氨酸含量的栽培和育种具有潜在的指导意义。
{"title":"Light and phytochrome PHY control the production of edible fungus Flammulina filiformis by regulating the morphogenesis of fruiting bodies and l-lysine accumulation","authors":"Yizhao Chen ,&nbsp;Huimin Ju ,&nbsp;Hui Li ,&nbsp;Chang Xu ,&nbsp;Hui Jia ,&nbsp;Lijun Xian ,&nbsp;Chengjin Yuan ,&nbsp;Zexuan Guo ,&nbsp;Xijin Zhang ,&nbsp;Yilin Yu ,&nbsp;Yongxin Tao","doi":"10.1016/j.jphotobiol.2024.113051","DOIUrl":"10.1016/j.jphotobiol.2024.113051","url":null,"abstract":"<div><div><em>Flammulina filiformis</em>, a representative umbelliferous fungus, has a long stipe and high <span>l</span>-lysine content, thus is widely cultivated and consumed. Currently, there is a lack of theoretical guidance on how to better use light to cultivate edible fungi without photosynthesis such as <em>F. filiformis</em> in industrialized cultivation. Previous studies have found that blue light can affect the yield and <span>l</span>-lysine content of <em>F. filiformis</em>. The primary focus of this work was the phytochrome PHY in the light signaling pathway and its role in <em>F. filiformis</em> production. Unlike plants in which the expression of PHY was activated by only red light, it was found that different visible lights (including red, blue, green, and white light) can stimulate the up-regulation of <em>FfPhy</em> transcript levels. Throughout the developmental stages of <em>F. filiformis</em>, the transcript level of <em>FfPhy</em> was significantly up-regulated during the formation of fruiting body and in the stipe in the elongation stage. Further, <em>FfPhy</em> knockdown strain showed the markedly shorter stipe length than WT, resulting in a significantly reduced yield. RNA-Seq analysis showed that the most genes in MAPK signaling pathway and its downstream regulatory processes, mainly focusing on cell division and cell wall remodeling, were down-regulated after <em>FfPhy</em> knockdown. It suggested that <em>FfPhy</em> regulates the fruiting body elongation through acting on cell division and cell wall remodeling, thereby affecting the morphological development of the stipe rather than the pileus. Interestingly, <em>FfPhy</em> knockdown also inhibits the accumulation of <span>l</span>-lysine content by promoting <span>l</span>-lysine degradation instead of inhibiting <span>l</span>-lysine biosynthesis, indicating that its influence extends to metabolic processes related to <span>l</span>-lysine metabolism. These findings provide new insights into photobiological effect of <em>FfPhy</em> in macrofungus <em>F. filiformis</em>, and have potential guiding significance for cultivation and breeding to increase mushroom yield and <span>l</span>-lysine content.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113051"},"PeriodicalIF":3.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592667","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}
引用次数: 0
Novel synthetic UV screen compounds inspired in mycosporine-like amino acids (MAAs): Antioxidant capacity, photoprotective properties and toxicity 从类菌体氨基酸(MAAs)中获得灵感的新型合成紫外线筛选化合物:抗氧化能力、光保护特性和毒性。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.jphotobiol.2024.113050
Félix L. Figueroa , Pablo Castro-Varela , Julia Vega , Raúl Losantos , Beatriz Peñín , Leonardo López-Cóndor , María Jesús Pacheco , Sofía Latorre Redoli , Manuel Marí-Beffa , Roberto Abdala-Díaz , Diego Sampedro
The combination of environmental stress on the ozone layer, climate change and a greater sun exposure due to outdoor habits has led to an increase in skin cancer cases and other health issues related with UV radiation. Researchers are searching for new alternative UV filters that could protect our skin from the deleterious effects of UV radiation while also presenting low toxicity and biodegradable character (unlike the UV filters currently available in the market). In this work, two compounds inspired in the natural oxo-mycosporine-like amino acids (MAAs) have been synthesized and their antioxidant and photoprotective properties, as well as their in vitro and in vivo toxicity effects were evaluated. Both compounds featured a strong UV-B absorption together with a high antioxidant capacity, close to 50 μmol TE g−1 DW in the ABTS assay. Compound 1 presented an absorption peak at 285–300 nm, whereas compound 2 showed a wider band with a peak around 295–305 nm and two shoulders at 318 and 342 nm. The addition of 5 % of compound 2 to galenic formulas increased the photoprotection, reaching SPF values of 4. Both compounds were stable under UV radiation exposure. Regarding toxicity, the synthetic compounds did not show cytotoxic activity against healthy human cell lines or significant toxicity over zebrafish embryos. Compound 1 showed a complete lack of toxicity over zebrafish, although compound 2 showed slight, not-significant effects on viability, hatching, pericardial stability or body axis formation over 5 mg mL−1. Moreover, compound 1 presented relatively antitumoral activities against HCT-116 cells (selective index:1.49). The relevant antioxidant and photoprotective ability together with the great advantage provided by the reduced toxicity to health cells or zebrafish embryos, make these compounds promising candidates to be exploited as functional ingredients with specific applications in the biotechnological or pharma sector.
环境对臭氧层造成的压力、气候变化以及户外习惯导致的更多阳光照射,导致皮肤癌病例和其他与紫外线辐射有关的健康问题增加。研究人员正在寻找新的紫外线过滤器替代品,以保护我们的皮肤免受紫外线辐射的有害影响,同时还具有低毒性和可生物降解的特点(与目前市场上销售的紫外线过滤器不同)。在这项工作中,受天然氧代霉菌素样氨基酸(MAAs)的启发,合成了两种化合物,并对它们的抗氧化和光保护特性,以及体外和体内毒性效应进行了评估。这两种化合物都具有很强的紫外线-B 吸收能力和很高的抗氧化能力,在 ABTS 试验中接近 50 μmol TE g-1 DW。化合物 1 在 285-300 纳米波长处有一个吸收峰,而化合物 2 的吸收带更宽,在 295-305 纳米波长处有一个吸收峰,在 318 和 342 纳米波长处有两个吸收肩。在 galenic 配方中添加 5% 的化合物 2 可以提高光防护能力,达到 SPF 值 4。在毒性方面,合成化合物没有显示出对健康人体细胞系的细胞毒性,也没有显示出对斑马鱼胚胎的显著毒性。化合物 1 对斑马鱼完全没有毒性,但化合物 2 对斑马鱼的存活率、孵化率、心包稳定性或体轴形成有轻微影响,但影响不显著(5 毫克/毫升-1)。此外,化合物 1 对 HCT-116 细胞具有较强的抗肿瘤活性(选择性指数:1.49)。相关的抗氧化和光保护能力,以及对健康细胞或斑马鱼胚胎的毒性降低所带来的巨大优势,使这些化合物有望成为生物技术或制药领域具有特殊用途的功能成分。
{"title":"Novel synthetic UV screen compounds inspired in mycosporine-like amino acids (MAAs): Antioxidant capacity, photoprotective properties and toxicity","authors":"Félix L. Figueroa ,&nbsp;Pablo Castro-Varela ,&nbsp;Julia Vega ,&nbsp;Raúl Losantos ,&nbsp;Beatriz Peñín ,&nbsp;Leonardo López-Cóndor ,&nbsp;María Jesús Pacheco ,&nbsp;Sofía Latorre Redoli ,&nbsp;Manuel Marí-Beffa ,&nbsp;Roberto Abdala-Díaz ,&nbsp;Diego Sampedro","doi":"10.1016/j.jphotobiol.2024.113050","DOIUrl":"10.1016/j.jphotobiol.2024.113050","url":null,"abstract":"<div><div>The combination of environmental stress on the ozone layer, climate change and a greater sun exposure due to outdoor habits has led to an increase in skin cancer cases and other health issues related with UV radiation. Researchers are searching for new alternative UV filters that could protect our skin from the deleterious effects of UV radiation while also presenting low toxicity and biodegradable character (unlike the UV filters currently available in the market). In this work, two compounds inspired in the natural oxo-mycosporine-like amino acids (MAAs) have been synthesized and their antioxidant and photoprotective properties, as well as their <em>in vitro</em> and <em>in vivo</em> toxicity effects were evaluated. Both compounds featured a strong UV-B absorption together with a high antioxidant capacity, close to 50 μmol TE g<sup>−1</sup> DW in the ABTS assay. Compound <strong>1</strong> presented an absorption peak at 285–300 nm, whereas compound <strong>2</strong> showed a wider band with a peak around 295–305 nm and two shoulders at 318 and 342 nm. The addition of 5 % of compound <strong>2</strong> to galenic formulas increased the photoprotection, reaching SPF values of 4. Both compounds were stable under UV radiation exposure. Regarding toxicity, the synthetic compounds did not show cytotoxic activity against healthy human cell lines or significant toxicity over zebrafish embryos. Compound <strong>1</strong> showed a complete lack of toxicity over zebrafish, although compound <strong>2</strong> showed slight, not-significant effects on viability, hatching, pericardial stability or body axis formation over 5 mg mL<sup>−1</sup>. Moreover, compound <strong>1</strong> presented relatively antitumoral activities against HCT-116 cells (selective index:1.49). The relevant antioxidant and photoprotective ability together with the great advantage provided by the reduced toxicity to health cells or zebrafish embryos, make these compounds promising candidates to be exploited as functional ingredients with specific applications in the biotechnological or pharma sector.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113050"},"PeriodicalIF":3.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer 氯素e6脂质体介导的光动力疗法可诱导乳腺癌细胞发生热休克并促进抗肿瘤免疫效应。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-29 DOI: 10.1016/j.jphotobiol.2024.113047
Fang Yang , Song Zhang , Xiao Zhang , Chenchen Xu , Xiaoying Hou , Jinting Shang , Binlian Sun , Xiji Shu , Yuchen Liu , Yixiang Li , Haiping Wang
Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE.
staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.
热休克是一种炎性细胞死亡形式,已被证实能引发抗肿瘤免疫反应。光动力疗法(PDT)是一种创新的非侵入性肿瘤治疗方法,可有效摧毁肿瘤细胞并增强抗肿瘤免疫反应。目前,光动力疗法引发热蛋白沉积的能力及其作用机制尚不明确。在本研究中,我们首先验证了光动力疗法能有效消灭肿瘤细胞。TEM和Western印迹分析表明,PDT治疗后肿瘤细胞发生了热解。脂质-Ce6主要积聚在4 T1细胞的线粒体中,PDT过程中产生的大量ROS严重破坏了细胞线粒体,导致线粒体DNA释放,引发炎性体caspase-1信号级联,最终导致细胞热解、此外,NAC(ROS 的清除剂)和 EB(线粒体 DNA 的清除剂)也能有效防止 PDT 引起的细胞猝灭,这表明 ROS 在 PDT 诱导的细胞猝灭中起着关键作用。此外,我们还发现 PDT 会引发免疫性细胞死亡(ICD)。此外,PDT 还能有效抑制小鼠肿瘤的生长、引发 ICD 和诱导细胞热解。引入免疫检查点抑制剂 BMS202 能显著提高肿瘤抑制率,促进免疫细胞向肿瘤浸润。体重和正常器官的 HE 染色主要表明了这种联合策略的安全性。我们的研究表明,PDT通过线粒体氧化损伤诱导细胞热休克,PDT诱导的热休克能有效提高抗癌免疫力,PDT与免疫检查点抑制剂的联合应用可能是一种很有前景的临床肿瘤治疗方法。
{"title":"Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer","authors":"Fang Yang ,&nbsp;Song Zhang ,&nbsp;Xiao Zhang ,&nbsp;Chenchen Xu ,&nbsp;Xiaoying Hou ,&nbsp;Jinting Shang ,&nbsp;Binlian Sun ,&nbsp;Xiji Shu ,&nbsp;Yuchen Liu ,&nbsp;Yixiang Li ,&nbsp;Haiping Wang","doi":"10.1016/j.jphotobiol.2024.113047","DOIUrl":"10.1016/j.jphotobiol.2024.113047","url":null,"abstract":"<div><div>Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE.</div><div>staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113047"},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590708","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}
引用次数: 0
Enhanced anticancer efficacy of photodynamic therapy in combination with immunotherapy 光动力疗法与免疫疗法相结合可增强抗癌疗效。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.jphotobiol.2024.113048
Mihyun Song , Heewon Yoon , Hyejin Yoon , Hyang-Mi Lee , Yoon-Jee Chae , Ji-Eun Chang
Photodynamic therapy (PDT) is known to trigger immunogenic cell death (ICD), leading to an anticancer effect even in untreated metastatic cancer, a phenomenon called the “abscopal effect”. Furthermore, ICD induction activates an immune response, which may synergize with immunotherapy. The objective of our research was to evaluate the anticancer efficacy of combining PDT with immunotherapy. To assess in vivo anticancer efficacy and the abscopal effect, we implanted CT26 cells on both flanks of BALB/c mice. The mice were categorized into five different groups: 1) PBS, 2) immunotherapy alone, 3) PDT alone, 4) immunotherapy administered 3 days after PDT, and 5) immunotherapy administered immediately after PDT. The observed antitumor effects on the primary tumor followed this order: immunotherapy administered immediately after PDT > immunotherapy administered 3 days after PDT > PDT alone > immunotherapy alone > PBS. In metastatic tumors that were not directly treated, immunotherapy administered immediately after PDT was also the most effective. In conclusion, our study confirms that the combination of PDT with immunotherapy enhances anticancer efficacy against both primary and metastatic tumors. Additionally, administering immunotherapy immediately after PDT is more effective than delayed administration.
众所周知,光动力疗法(PDT)可诱发免疫性细胞死亡(ICD),甚至在未经治疗的转移性癌症中也能产生抗癌效果,这种现象被称为 "缺席效应"。此外,ICD诱导可激活免疫反应,从而与免疫疗法产生协同作用。我们的研究目的是评估光动力疗法与免疫疗法相结合的抗癌效果。为了评估体内抗癌疗效和腹水效应,我们将 CT26 细胞植入 BALB/c 小鼠的两侧腹部。小鼠被分为五组:1)PBS;2)单独免疫治疗;3)单独PDT;4)PDT三天后免疫治疗;5)PDT后立即免疫治疗。在原发肿瘤上观察到的抗肿瘤效果依次为:PDT 后立即使用免疫疗法 > PDT 3 天后使用免疫疗法 > 单独使用 PDT > 单独使用免疫疗法 > PBS。在未直接治疗的转移性肿瘤中,PDT 后立即进行免疫治疗的效果也最好。总之,我们的研究证实,光动力疗法与免疫疗法相结合可提高对原发性和转移性肿瘤的抗癌疗效。此外,在光动力疗法后立即使用免疫疗法比延迟使用更有效。
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引用次数: 0
Synergistic effect of folic acid and hypericin administration to improve the efficacy of photodynamic therapy via folate receptors 叶酸和金丝桃素协同作用,通过叶酸受体提高光动力疗法的疗效
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.jphotobiol.2024.113046
Anass Benziane , Veronika Huntošová , Viktória Pevná , Luboš Zauška , György Vámosi , Andrej Hovan , Gabriela Zelenková , Vladimír Zeleňák , Miroslav Almáši
Transport systems are developed to improve the solubility of the transported drug, increase its stability, enhance its pharmacological activity and target cancer while minimising side effects. In this work, nanoporous silica particles that can be functionalized and loaded with a large number of hydrophobic molecules are proposed. The designed system was modified with folic acid to target the folic acid receptors of cancer cells. This modification enabled a higher uptake of the drug by the cells. Hypericin was selected as a hydrophobic molecule/drug with photodynamic properties suitable for diagnosis and therapy. Fluorescence microscopy and flow cytometry were used to detect the targeting and distribution of hypericin in the cancer cells. Furthermore, the combination of folic acid and hypericin has been shown to form singlet oxygen and to have a synergistic effect in improving the efficacy of photodynamic therapy. The functionalisation of the particles proposed in this work holds great potential for the delivery of hydrophobic drugs to other types of cancer cells with increased expression of the folic acid receptor to which the particles can be attached.
开发转运系统的目的是提高转运药物的溶解度,增加其稳定性,增强其药理活性,并在减少副作用的同时以癌症为目标。在这项工作中,提出了可功能化并装载大量疏水分子的纳米多孔二氧化硅颗粒。用叶酸对所设计的系统进行了修饰,以靶向癌细胞的叶酸受体。这种改性使细胞对药物的吸收率更高。金丝桃素被选为具有光动力特性的疏水分子/药物,适用于诊断和治疗。荧光显微镜和流式细胞术用于检测金丝桃素在癌细胞中的靶向和分布。此外,叶酸和金丝桃素的结合还能形成单线态氧,并在提高光动力疗法的疗效方面产生协同效应。这项工作中提出的颗粒功能化技术具有很大的潜力,可将疏水性药物输送到叶酸受体表达量增加的其他类型的癌细胞,而颗粒可附着在叶酸受体上。
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引用次数: 0
Lysosome-localization and tumor-targeting of novel photosensitizers enhance the ablation of cancer 新型光敏剂的溶酶体定位和肿瘤靶向性增强了癌症消融效果。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.jphotobiol.2024.113045
Jiahui Li , Guodong Wang , Yuhan Mai , Wei Zhang , Hailong Zhao , Yang Zhou , Liyun Chen , Yuxin Lin , Longguang Jiang , Peng Xu , Xiaolei Zhou , Cai Yuan , Mingdong Huang
Lysosomes are promising therapeutic targets for cancer therapy due to their essential function and increased vulnerability in cancer cells. Herein, we report a new category of cationic photosensitizers (compounds 1–3) containing a quaternary ammonium group. These photosensitizers exhibited selective uptake on cancer cells (about three times compared to the normal cells), lysosome-specific localization (Pearson's coefficients greater than 0.85), remarkable phototoxicity (IC50 are in the range of dozens of nM), and at the same time, favorable biosafety. Mechanically, these tumor-targeting photosensitizers function as light-controlled “bombs”, inducing lysosomal membrane permeabilization (LMP), ultimately resulting in apoptosis of cancer cells. In vivo, compound 1 (a representative of these novel photosensitizers) accumulated predominantly in and visualized tumors implanted on mice. Upon exposure to near-infrared light irradiation (50 J/cm2), the compound effectively ablated the tumor at a low dose of 2 mg/kg. Our results demonstrate a novel class of photosensitizers showing potential for integrated cancer diagnosis and photodynamic treatment.
溶酶体具有重要功能,但在癌细胞中的脆弱性增加,因此是很有希望的癌症治疗靶点。在此,我们报告了一类含有季铵基团的新型阳离子光敏剂(化合物 1-3)。这些光敏剂表现出对癌细胞的选择性吸收(约为正常细胞的三倍)、溶酶体特异性定位(皮尔逊系数大于 0.85)、显著的光毒性(IC50 在数十 nM 的范围内),同时具有良好的生物安全性。从机理上讲,这些肿瘤靶向光敏剂具有光控 "炸弹 "的功能,可诱导溶酶体膜通透(LMP),最终导致癌细胞凋亡。在体内,化合物 1(这些新型光敏剂的代表)主要积聚在植入小鼠体内的肿瘤中,并使肿瘤可视化。经近红外光照射(50 J/cm2)后,该化合物在 2 mg/kg 的低剂量下就能有效消融肿瘤。我们的研究结果表明,一类新型光敏剂具有综合癌症诊断和光动力治疗的潜力。
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引用次数: 0
A BODIPY derivative for PDT/PTT synergistic treatment of bacterial infections 一种用于 PDT/PTT 协同治疗细菌感染的 BODIPY 衍生物。
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.jphotobiol.2024.113049
Qijia Sun , Aoqing Jia , Min Zhao , Ke Wang , Tingting Sun , Zhigang Xie
Phototherapeutic antimicrobials, including photodynamic and photothermal antimicrobials, are considered effective alternatives for antibiotic strategy due to their broad-spectrum antibacterial activity and low risk of resistance. Here, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative containing triphenylamine groups was co-assembled with Pluronic F-127 (F-127) to form nanoparticles (BICF NPs). BICF NPs have excellent photodynamic and photothermal properties and are demonstrated to be effective in inhibiting and disrupting bacterial biofilms, thereby promoting the healing of subcutaneous abscesses. This work provides a new avenue for antibiotic replacement therapy.
光疗抗菌剂,包括光动力抗菌剂和光热抗菌剂,因其广谱抗菌活性和低抗药性风险而被认为是抗生素策略的有效替代品。在这里,一种含有三苯胺基团的 4,4-二氟-4-硼-3a,4a-二氮杂-s-茚并(BODIPY)衍生物与 Pluronic F-127 (F-127)共同组装成纳米颗粒(BICF NPs)。BICF NPs 具有出色的光动力和光热特性,已被证明能有效抑制和破坏细菌生物膜,从而促进皮下脓肿的愈合。这项工作为抗生素替代疗法提供了一条新途径。
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引用次数: 0
期刊
Journal of photochemistry and photobiology. B, Biology
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