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Depth of DNA photodamage in human corneas exposed to 222 nm or 254 nm UV. 222 nm和254 nm紫外线对人角膜DNA光损伤深度的影响。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-23 DOI: 10.1111/php.70093
Manuela Buonanno, Istvan R Boldogh, Raabia Hashmi, Camryn Petersen, David Welch, Theresa C Swayne, David J Brenner

Within the ultraviolet C (UVC) spectrum, the wavelengths in the 200-235 nm range, here named far-UVC, have been shown to effectively inactivate a variety of pathogens. Because of their limited penetration in biological materials, far-UVC wavelengths are anticipated to be minimally damaging to human skin and eyes. The germicidal efficacy of these wavelengths combined with a predicted low health hazard for humans suggests that far-UVC sources could operate continuously in indoor locations to reduce the risk of transmission of airborne diseases among occupants. While it is well-established that exposure to far-UVC light is minimally damaging to skin, concerns remain on the safety of exposed eyes. Scientific bodies overseeing UV radiation protection recommend eye safety limits based on published peer-reviewed data. To support this goal, our previous work used a 3D model of the human cornea to assess the wavelength dependence of corneal damage induced by UVC radiation; unlike relatively longer wavelengths, far-UVC wavelengths induced DNA dimers only in the uppermost layers of the corneal epithelium. Here, similar eye safety studies were extended to excised human corneas. The depth of DNA photodamage into the corneal epithelium was evaluated after exposure of the anterior surface to 50 mJ/cm2 or 100 mJ/cm2 from 222 nm or 254 nm light.

在紫外线C (UVC)光谱中,波长在200-235 nm范围内的远紫外线已被证明可以有效地灭活多种病原体。由于远紫外线在生物材料中的穿透力有限,预计远紫外线波长对人体皮肤和眼睛的伤害最小。这些波长的杀菌效果,加上对人类健康危害较低的预测,表明远紫外线源可以在室内持续工作,以减少居住者之间空气传播疾病的风险。虽然人们已经确定,暴露在远紫外线下对皮肤的伤害最小,但人们仍然担心暴露在远紫外线下的眼睛的安全。监督紫外线防护的科学机构根据已发表的同行评议数据推荐眼部安全限值。为了支持这一目标,我们之前的工作使用了人类角膜的3D模型来评估UVC辐射引起的角膜损伤的波长依赖性;与相对较长的波长不同,远紫外线波长仅在角膜上皮的最上层诱导DNA二聚体。在这里,类似的眼睛安全性研究扩展到切除的人类角膜。在222 nm或254 nm光照射前表面50 mJ/cm2或100 mJ/cm2后,评估角膜上皮DNA光损伤深度。
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引用次数: 0
Effects of photobiomodulation on inflammatory factors during skeletal muscle regeneration: A systematic review with meta-analysis of animal studies. 光生物调节对骨骼肌再生过程中炎症因子的影响:动物研究荟萃分析的系统综述。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-17 DOI: 10.1111/php.70092
Jia-Ming Yang, Fang Liu, Zeng-Cheng Ai, Hao Hu, Ze-Qin Li, Yan-Biao Zhong, Hua-Chao Luo, Hai Li, Wen-Juan Wu, Xin-Ye Ouyang, Mao-Yuan Wang

Skeletal muscle injury is a common sports injury and photobiomodulation (PBM) therapy has been recognized as a potential treatment for it. However, the optimal intervention timing for PBM to suppress inflammatory factor expression during muscle regeneration remains unclear. The study is a systematic review with meta-analysis to summarize the effect of PBM on the expression levels of inflammatory factors during skeletal muscle regeneration in animals. The PubMed, Cochrane Library, Scopus, and Web of Science databases were searched to obtain the studies about the effects of PBM on the inflammatory factors during muscle regeneration in animals. Two authors independently extracted the data, and the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool was used to assess the risk of bias for the included studies. Review manager 5.4 software was used to analyze the data, and subgroup and sensitivity analyses were performed. A total of 18 studies were included in this study. The results show that PBM treatment reduces levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 during skeletal muscle regeneration, especially in the early stage of skeletal muscle injury (6 and 12 h), but its effects on IL-4 and IL-10 need to be validated in higher-quality studies. In conclusion, PBM therapy primarily reduces inflammatory factor levels in the early stage of skeletal muscle injury, thereby accelerating skeletal muscle regeneration.

骨骼肌损伤是一种常见的运动损伤,光生物调节(PBM)治疗已被认为是一种潜在的治疗方法。然而,在肌肉再生过程中,PBM抑制炎症因子表达的最佳干预时机仍不清楚。本研究是一项系统综述和荟萃分析,旨在总结PBM对动物骨骼肌再生过程中炎症因子表达水平的影响。检索PubMed、Cochrane Library、Scopus和Web of Science数据库,获得关于PBM对动物肌肉再生过程中炎症因子影响的研究。两位作者独立提取数据,并使用实验动物实验系统评价中心(sycle)工具评估纳入研究的偏倚风险。采用Review manager 5.4软件对数据进行分析,并进行亚组分析和敏感性分析。本研究共纳入18项研究。结果表明,PBM治疗可降低骨骼肌再生过程中肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-1β和IL-6的水平,特别是在骨骼肌损伤早期(6和12 h),但其对IL-4和IL-10的影响需要在更高质量的研究中验证。总之,PBM治疗主要是降低骨骼肌损伤早期的炎症因子水平,从而加速骨骼肌的再生。
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引用次数: 0
Synergistic cytotoxic activity on breast cancer cells by tetrahydroxyquinone and photothermal therapy. 四羟基醌与光热疗法对乳腺癌细胞的协同细胞毒活性。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-12 DOI: 10.1111/php.70089
Ximena A Flores-Arevalo, M Eduardo Cano, Zaira López, Antonio Topete, Francisco A Cholico, Nayeli Saraí Melendez-Checa, Rodolfo Hernandez-Gutierrez, Peter Knauth

In this work, the potential synergistic antineoplastic activity of tetrahydroxyquinone (THQ) in combination with photothermal therapy using gold nanoshells (AuNSHs) as photosensitizers and applying NIR light at 808 nm has been analyzed. To synthesize the AuNSHs, a core of PLGA and PVA was coated with oligochitosan, which was then mixed with a solution of gold seeds. The core-shell particles were obtained by a seeded-growth process in the presence of K-gold and ascorbic acid. These gold structures underwent an Ostwald ripening process and were subsequently PEGylated to increase their biocompatibility and colloidal stability. The diameter of these AuNSHs has an average of 131 ± 10 nm, a zeta potential of -20 ± 1 mV at physiological pH, a hydrodynamic diameter of 188 ± 2 nm, and a power absorption density of up to 93 W/cm3. Cell biology assays, using BT-474 breast cancer cell line, revealed a negligible decrease in metabolic activity when the cells were exposed to up to 1 mg/mL AuNSH, 100 μg/mL THQ or were irradiated for 15 min with an optical power (OP) of 2.0 W. The simultaneous administration of 1 mg/mL AuNSH and 100 μg/mL THQ reduced the cell viability only by ~17%. However, when following a photothermal therapy (AuNSH irradiated an OP of 2.0 W), 100 μg/mL THQ were added to the cells, their viability decreased significantly by ~61%, indicating a synergistic effect of the treatment. Using the Annexin V assay, it could be revealed that the majority of cells underwent apoptosis and only few died by necrosis.

本研究分析了四羟基醌(THQ)与以金纳米壳(AuNSHs)为光敏剂并在808 nm近红外光照射下进行光热治疗的潜在协同抗肿瘤活性。为了合成AuNSHs,在PLGA和PVA的核心上涂上低聚壳聚糖,然后将其与金种子溶液混合。在k金和抗坏血酸存在下,通过种子生长过程获得核壳颗粒。这些金结构经历了奥斯特瓦尔德成熟过程,随后被聚乙二醇化,以增加它们的生物相容性和胶体稳定性。这些AuNSHs的平均直径为131±10 nm,生理pH下的zeta电位为-20±1 mV,流体动力学直径为188±2 nm,功率吸收密度高达93 W/cm3。使用BT-474乳腺癌细胞系进行细胞生物学试验,发现当细胞暴露于高达1 mg/mL的AuNSH, 100 μg/mL的THQ或以2.0 W的光功率(OP)照射15 min时,代谢活性的降低可以忽略不计。同时给药1 mg/mL AuNSH和100 μg/mL THQ仅使细胞活力降低约17%。然而,在光热治疗(AuNSH照射OP为2.0 W)后,加入100 μg/mL THQ,细胞活力显著下降~61%,表明处理具有协同作用。Annexin V检测显示,大部分细胞发生凋亡,少数细胞坏死死亡。
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引用次数: 0
Photoprotective potential of gadusol against ultraviolet B radiation in melanocytes. gadusol对黑色素细胞紫外线B辐射的光保护作用。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-11 DOI: 10.1111/php.70090
Andressa Mai Matsumoto, Rocío Isla Naveira, Andy Joel Taipe Huisa, Marcelo Augusto Germani Marinho, Lais Zortéa, José María Monserrat, Agueda Elena Massa, María Sandra Churio, Ana Paula de Souza Votto

The increasing incidence of skin cancer, including melanoma, combined with the need for ultraviolet (UV) filters that are safe for human health and marine ecosystems, is driving the search for new photoprotective agents. Gadusol, a natural metabolite present in marine organisms, has been identified as a compound capable of absorbing UV radiation and exerting antioxidant functions. In this study, we investigated the photoprotective effects of gadusol on non-tumorigenic murine melanocyte cell line exposed to UVB radiation. Cell viability was assessed by trypan blue exclusion, and parameters of cell death, reactive oxygen species (ROS) generation, and proliferation were also analyzed. The results showed that gadusol (50 μM) did not exhibit cytotoxicity and, when administered during exposure to 15 and 30 mJ/cm2 of UVB, protected cells against reduced cell viability and viable cell count. Furthermore, gadusol also protected against apoptosis, attenuated ROS production, and maintained the proliferative rate at levels similar to the control, even under high UVB doses (30 mJ/cm2). We conclude that gadusol exerts effective photoprotective action, attenuating the effects of UVB radiation on melanocytes without compromising cell viability or proliferation. These findings reinforce the potential of gadusol as a safe, effective, and environmentally sustainable alternative for skin photoprotection applications.

皮肤癌(包括黑色素瘤)发病率的增加,加上对对人类健康和海洋生态系统安全的紫外线过滤器的需求,正在推动寻找新的光保护剂。Gadusol是一种存在于海洋生物体内的天然代谢物,具有吸收紫外线和发挥抗氧化功能。在这项研究中,我们研究了gadusol对暴露于UVB辐射下的非致瘤性小鼠黑素细胞系的光保护作用。台盼蓝法测定细胞活力,分析细胞死亡、活性氧(ROS)生成和增殖等参数。结果表明,gadusol (50 μM)没有表现出细胞毒性,当暴露于15和30 mJ/cm2的UVB时,可以保护细胞免受细胞活力和活细胞计数的降低。此外,gadusol还可以防止细胞凋亡,减少ROS的产生,即使在高UVB剂量(30 mJ/cm2)下,也能将增殖率维持在与对照组相似的水平。我们得出结论,gadusol具有有效的光保护作用,在不影响细胞活力或增殖的情况下减弱UVB辐射对黑素细胞的影响。这些发现加强了gadusol作为一种安全、有效和环境可持续的皮肤光防护替代品的潜力。
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引用次数: 0
Spectral characterization of three wearable electronic ultraviolet radiation dosimeters. 三种可穿戴电子紫外辐射剂量计的光谱特性。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-06 DOI: 10.1111/php.70085
Leevi August, Gregor Hülsen, Juha Peltoniemi, Petri Kärhä, Erkki Ikonen

Excessive exposure to ultraviolet (UV) radiation poses significant public health risks, including DNA damage and skin-related pathologies. This necessitates accurate studies and quantification of UV-radiation exposure. Various wearable UV dosimeters have been developed to address these needs, particularly for outdoor workers. For measuring erythemal irradiance, recommendations from the World Meteorological Organization exist but standardized methods for characterization and calibration of wearable UV dosimeters are currently limited. At Aalto University and at Physikalisch-Meteorologisches Observatorium Davos, three commercial electronic UV dosimeters were evaluated for their spectral responsivities using conventional measurement methods and traceability chains. The first device closely mimicked erythemal action in UV-A and UV-B regions. Two of the measured devices were found to have a higher relative responsivity of over 0.9 in the 300 nm to 310 nm range. Results were used to calculate correction factors for measuring erythemal radiance at varying solar zenith angles and ozone levels under cloud-free conditions. Typical correction factors ranged from 0.98 to 1.2. The results of the two laboratories were in good agreement for the most accurate device but deviated due to the properties of the two other devices. The measurements revealed challenges posed by these devices in terms of data management, measurement times, and deployment, highlighting the need for standardized characterization methods.

过度暴露于紫外线辐射会造成重大的公共健康风险,包括DNA损伤和皮肤相关疾病。这就需要对紫外线照射进行精确的研究和量化。已经开发了各种可穿戴紫外线剂量计来满足这些需求,特别是对于户外工作者。对于红斑辐照度的测量,有世界气象组织的建议,但可穿戴紫外线剂量计的表征和校准的标准化方法目前有限。在阿尔托大学和达沃斯物理气象观测站,使用传统的测量方法和可追溯链对三个商用电子紫外线剂量计的光谱响应进行了评估。第一个装置紧密地模拟了UV-A和UV-B区域的红斑作用。两个被测量的器件被发现在300纳米至310纳米范围内具有高于0.9的相对响应度。结果用于计算在无云条件下不同太阳天顶角和臭氧水平下测量红斑辐射的校正因子。典型的修正系数在0.98到1.2之间。两个实验室的结果是在很好的协议,最准确的设备,但偏离由于其他两个设备的性质。测量结果揭示了这些设备在数据管理、测量时间和部署方面带来的挑战,强调了对标准化表征方法的需求。
{"title":"Spectral characterization of three wearable electronic ultraviolet radiation dosimeters.","authors":"Leevi August, Gregor Hülsen, Juha Peltoniemi, Petri Kärhä, Erkki Ikonen","doi":"10.1111/php.70085","DOIUrl":"https://doi.org/10.1111/php.70085","url":null,"abstract":"<p><p>Excessive exposure to ultraviolet (UV) radiation poses significant public health risks, including DNA damage and skin-related pathologies. This necessitates accurate studies and quantification of UV-radiation exposure. Various wearable UV dosimeters have been developed to address these needs, particularly for outdoor workers. For measuring erythemal irradiance, recommendations from the World Meteorological Organization exist but standardized methods for characterization and calibration of wearable UV dosimeters are currently limited. At Aalto University and at Physikalisch-Meteorologisches Observatorium Davos, three commercial electronic UV dosimeters were evaluated for their spectral responsivities using conventional measurement methods and traceability chains. The first device closely mimicked erythemal action in UV-A and UV-B regions. Two of the measured devices were found to have a higher relative responsivity of over 0.9 in the 300 nm to 310 nm range. Results were used to calculate correction factors for measuring erythemal radiance at varying solar zenith angles and ozone levels under cloud-free conditions. Typical correction factors ranged from 0.98 to 1.2. The results of the two laboratories were in good agreement for the most accurate device but deviated due to the properties of the two other devices. The measurements revealed challenges posed by these devices in terms of data management, measurement times, and deployment, highlighting the need for standardized characterization methods.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Measurement and modeling of diffuse ultraviolet radiation: A review. 漫射紫外线辐射的测量和建模:综述。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-02 DOI: 10.1111/php.70084
Alfio V Parisi, Joanna Turner, Abdurazaq Amar, Damien P Igoe, Peter Schouten, Nawin Raj, Nathan Downs, Harry Butler

The ultraviolet (UV) radiation environment consists of direct UV and diffuse UV components. The ratios of diffuse-to-direct UV for the UVB, UVA, and the erythema UV wavebands are influenced by clouds, aerosols, albedo, and surface reflectance, Rayleigh scattering, and solar zenith angle. At times, the relative proportion of diffuse UV may be higher than the direct UV, for example, on cloudy days or days with high atmospheric aerosols. Consequently, exposures due to diffuse UV radiation play a significant role in the UV exposure received by human subjects. Diffuse UV radiation contributes to the risk of skin cancer and sun-related eye disorders. Reducing personal exposure to diffuse UV by physical protection, including tree shade, purpose-built shade structures, protection by hats, and eyewear, is more difficult than reducing direct UV exposure due to the diffuse UV being incident from all directions. The UV index reported to the public represents the sum of the direct and the diffuse erythema UV, with no information provided specifically on the diffuse UV component. This paper reviews the factors that contribute to diffuse UV exposures affecting human populations. It examines diffuse UV modeling techniques, and broadband and spectral component measurements.

紫外线辐射环境由直接紫外线和漫射紫外线组成。UVB、UVA和红斑UV波段的漫射紫外线与直射紫外线的比值受云层、气溶胶、反照率、地表反射率、瑞利散射和太阳天顶角的影响。有时,扩散紫外线的相对比例可能高于直接紫外线,例如,在阴天或大气气溶胶含量高的日子。因此,由于漫射紫外线辐射的暴露在人类受试者接受的紫外线暴露中起着重要作用。漫射紫外线辐射会增加患皮肤癌和与太阳有关的眼部疾病的风险。通过物理保护来减少个人对漫射紫外线的暴露,包括树荫、专门建造的遮阳结构、帽子和眼镜的保护,比减少直接接触紫外线要困难得多,因为漫射紫外线是从各个方向入射的。向公众报告的紫外线指数是直接和弥漫性红斑紫外线的总和,没有提供关于弥漫性紫外线成分的具体信息。本文综述了影响人类漫射紫外线照射的因素。它检查了漫射UV建模技术,以及宽带和光谱成分测量。
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引用次数: 0
Singlet oxygen generation from secondary photoproducts of benzo[a]pyrene. 苯并[a]芘次生光产物产生单线态氧。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-02 DOI: 10.1111/php.70082
David A Cagan, Nareh Ghevondian, Julia Montoya-Aguilera, Michael Zitser, Jonathan Avina, Dianlu Jiang, Dong Zhang, Olaseni Sode, Krishna L Foster, Matthias Selke

We have investigated the photosensitized generation of singlet oxygen (1Δg) from a variety of diones derived from benzo[a]pyrene (1), namely benzo[a]pyrene (6,12) dione (2), benzo[a]pyrene (1,6) dione (3), benzo[a]pyrene (3,6) dione (4), and benzo[a]pyrene (4,5) dione (5). The diones 2-4 are formed in the atmosphere as secondary photoproducts from benzo[a]pyrene. Benzo[a]pyrene (4,5) dione (5) was additionally selected for this study due to its much larger dipole moment relative to the other diones. All of these diones are excellent sensitizers with quantum yields of singlet oxygen generation (ΦΔ) ranging from 0.77 to near unity. Singlet oxygen appears to be generated primarily from the triplet excited state. Quantum yields were measured in four solvents with different polarity. The singlet oxygen quantum yield for benzo[a]pyrene decreases with increasing polarity of the solvent. By contrast, the values for ΦΔ for the diones 2-5 increase slightly with increasing polarity of the solvent. Unlike substituted anthracene derivatives, all of the diones 2-5 show very little singlet oxygen quenching, as singlet oxygen lifetimes showed no decrease compared with the literature values when diones 2-5 were used for singlet oxygen generation. The large singlet oxygen quantum yields for diones 2-5, and the lack of singlet oxygen quenching implies that, in the presence of these compounds in the environment, photosensitized generation of singlet oxygen generation could be significant.

我们研究了由苯并[a]芘(1)衍生的多种二酮光敏生成单重态氧(1Δg),即苯并[a]芘(6,12)二酮(2),苯并[a]芘(1,6)二酮(3),苯并[a]芘(3,6)二酮(4)和苯并[a]芘(4,5)二酮(5)。二酮2-4在大气中作为苯并[a]芘的次生光产物形成。本研究还选择了苯并[a]芘(4,5)二酮(5),因为它的偶极矩比其他二酮大得多。所有这些二酮都是极好的敏化剂,单线态产氧量子产率(ΦΔ)范围从0.77到接近1。单重态氧似乎主要是由三重态激发态产生的。测定了四种不同极性溶剂的量子产率。苯并[a]芘的单线态氧量子产率随溶剂极性的增加而降低。相反,随着溶剂极性的增加,二酮2-5的ΦΔ值略有增加。与取代蒽衍生物不同,所有的二酮2-5都表现出很少的单线态氧猝灭,因为当二酮2-5用于单线态氧生成时,单线态氧寿命与文献值相比没有下降。二酮2-5的单线态氧量子产率大,并且缺乏单线态氧猝灭,这意味着,在这些化合物存在的环境中,光敏生成单线态氧可能是重要的。
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引用次数: 0
Adjunctive use of Polypodium leucotomos extract in patients with erythropoietic protoporphyria: An exploratory study. 辅助使用白芍提取物治疗红细胞原卟啉症:一项探索性研究。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-02 DOI: 10.1111/php.70081
Nayha Shetty, Rebecca L Quiñonez, Marissa S Ceresnie, Sunita Ghosh, Henry W Lim, Tasneem F Mohammad

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) cause severe photosensitivity, resulting in significant quality of life (QoL) impairment. This study aims to evaluate the safety and efficacy of Polypodium leucotomos extract (PLE) as an adjunctive therapy in patients with persistent symptoms despite standard dosing of afamelanotide. In this prospective single-center cohort study, eight adults with confirmed EPP or XLP and ongoing symptoms despite regular afamelanotide implants every 2 months were enrolled. Participants received 480 mg oral PLE daily for 4 months. QoL and symptom severity were measured using questionnaires at baseline, Day 60, and Day 120. Six participants completed the study. Statistically significant improvements in QoL were observed on Day 60 (p = 0.014), but not at Day 120 (p = 0.152). Half of participants reported reduced reaction severity. No adverse events occurred. Adjunctive PLE improved short-term QoL in participants with incomplete symptom control on afamelanotide alone and was well tolerated. Larger studies are warranted.

红细胞生成原生卟啉症(EPP)和x连锁原生卟啉症(XLP)引起严重的光敏性,导致显著的生活质量(QoL)损害。本研究旨在评价紫堇提取物(PLE)作为一种辅助治疗的安全性和有效性,尽管标准剂量的阿麦兰肽持续症状的患者。在这项前瞻性单中心队列研究中,8名确诊为EPP或XLP的成年人,尽管每2个月定期植入阿麦兰肽,但仍有症状。参与者每天口服480毫克PLE,持续4个月。在基线、第60天和第120天使用问卷测量生活质量和症状严重程度。6名参与者完成了这项研究。在第60天观察到有统计学意义的生活质量改善(p = 0.014),但在第120天无统计学意义(p = 0.152)。一半的参与者报告反应严重程度降低。无不良事件发生。辅助PLE改善了单独使用阿麦兰肽症状控制不完全的参与者的短期生活质量,并且耐受性良好。更大规模的研究是必要的。
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引用次数: 0
Inhibition of P-glycoprotein using photoimmunotherapy in peritoneal metastasis mouse model. 光免疫疗法对腹腔转移小鼠模型p -糖蛋白的抑制作用。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-02 DOI: 10.1111/php.70075
Kaitlyn A Moore, Brian Schnoor, Kathryn L McNaughton, Idrisa Rahman, Benjamin D Powers, Dana M Roque, Huang-Chiao Huang

Up to 80%-90% of recurrent peritoneal metastasis cases exhibit resistance to multiple chemotherapy agents. A major contributor to this multidrug resistance is the active efflux of chemotherapeutics by P-glycoprotein (P-gp), also known as ATP-binding cassette subfamily B member 1 (ABCB1) transporter and multidrug resistance protein 1 (MDR1). Clinical attempts to inhibit P-gp using small molecule inhibitors have been limited by systemic toxicity or poor tumor selectivity, underscoring the need for safer, targeted strategies. To address this challenge, we demonstrated, for the first time, that intraperitoneal photoimmunotherapy (PIT) using a photoimmunoconjugate (PIC) can inhibit the function of P-gp in a mouse model of peritoneal carcinomatosis. PIC was synthesized and characterized, and a sterile filtration protocol was implemented for its in vivo administration and intraperitoneal PIT application. To assess P-gp function following low-dose PIT, in vivo tumor cells were isolated and evaluated for intracellular accumulation of a well-established P-gp substrate (Rhodamine 123). PIC-PIT significantly increased intracellular Rhodamine 123 retention, indicating effective reduction of P-gp activity. This study provides the first in vivo evidence that PIT can inhibit P-gp function, offering a promising, targeted approach to overcoming chemoresistance while avoiding the systemic toxicity associated with conventional P-gp inhibitors.

高达80%-90%的腹膜转移复发病例表现出对多种化疗药物的耐药性。这种多药耐药的一个主要因素是p -糖蛋白(P-gp)的主动外排,p -糖蛋白也被称为atp结合盒亚家族B成员1 (ABCB1)转运蛋白和多药耐药蛋白1 (MDR1)。使用小分子抑制剂抑制P-gp的临床尝试受到全身毒性或肿瘤选择性差的限制,强调需要更安全、更有针对性的策略。为了解决这一挑战,我们首次证明,在腹膜癌小鼠模型中,使用光免疫偶联物(PIC)的腹腔光免疫疗法(PIT)可以抑制P-gp的功能。合成并表征了PIC,并采用无菌过滤方案进行体内给药和腹腔PIT应用。为了评估低剂量PIT后P-gp的功能,分离了体内肿瘤细胞,并评估了P-gp底物在细胞内的积累(Rhodamine 123)。PIC-PIT显著增加细胞内罗丹明123的保留,表明P-gp活性有效降低。该研究首次提供了PIT可以抑制P-gp功能的体内证据,为克服化疗耐药提供了一种有希望的、有针对性的方法,同时避免了与常规P-gp抑制剂相关的全身毒性。
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引用次数: 0
Evaluation of the disulfide bond positions in recombinant Gaussia luciferase expressed in Escherichia coli cells by site-directed mutagenesis. 利用定点诱变技术对大肠杆菌中表达的重组高斯荧光素酶二硫键位置的评价。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-06-16 DOI: 10.1111/php.70003
Satoshi Inouye, Yuiko Sahara-Miura, Jun-Ichi Sato

Gaussia luciferase (GLase) is a secreted enzyme composed of 168 amino acids, including 10 cysteine residues, and catalyzes the oxidation of coelenterazine to emit light. To evaluate the disulfide bond positions in GLase, we generated 10 cysteine-to-serine substituted GLase genes, in which each cysteine residue was replaced with a serine residue (C52S, C56S, C59S, C65S, C77S, C120S, C123S, C127S, C136S, and C148S), using site-directed mutagenesis. In both bacterial and mammalian expression systems, four disulfide bonds formed between eight cysteine residues (C52, C56, C65, C77, C123, C127, C136, and C148) were found to be essential for luminescence activity. In bacterial cells, the single mutants C59S and C120S, as well as the double mutant C59S/C120S, exhibited luminescence activities of 258%, 2.8%, and 42.8%, respectively, relative to wild-type GLase (100%). Notably, all three mutants could be efficiently refolded by dialysis after treatment with 2-mercaptoethanol. In mammalian cells, only the double mutant C59S/C120S was secreted and showed luminescence activity of 11% in the culture medium, relative to wild-type GLase (100%). By integrating previously reported NMR-based structural data of recombinant GLase purified from bacterial cells with our experimental findings, we conclude that GLase contains five disulfide bonds: C52-C127, C56-C123, C59-C120, C65-C77, and C136-C148, which are consistent with those reported in PDB ID: 7D2O.

高斯荧光素酶(GLase)是一种由168个氨基酸组成的分泌酶,其中包括10个半胱氨酸残基,它催化coelenterazine氧化发光。为了评估GLase中的二硫键位置,我们生成了10个半胱氨酸-丝氨酸取代的GLase基因,其中每个半胱氨酸残基都被丝氨酸残基取代(C52S, C56S, C59S, C65S, C77S, C120S, C123S, C127S, C136S和C148S),使用位点定向诱变技术。在细菌和哺乳动物的表达系统中,发现8个半胱氨酸残基(C52、C56、C65、C77、C123、C127、C136和C148)之间形成的4个二硫键对发光活性至关重要。在细菌细胞中,单突变体C59S和C120S以及双突变体C59S/C120S的发光活性分别为野生型的258%、2.8%和42.8%(100%)。值得注意的是,所有三种突变体都可以在2-巯基乙醇治疗后通过透析有效地重新折叠。在哺乳动物细胞中,仅分泌双突变体C59S/C120S,在培养基中显示11%的发光活性,而野生型GLase的发光活性为100%。通过整合先前报道的从细菌细胞中纯化的重组玻璃酶的核磁共振结构数据和我们的实验结果,我们得出结论,玻璃酶含有5个二硫键:C52-C127、C56-C123、C59-C120、C65-C77和C136-C148,这与PDB ID: 7D2O报道的结果一致。
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Photochemistry and Photobiology
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