{"title":"Beyond DNA interactions: Insights into idarubicin's binding dynamics with tRNA using spectroscopic and computational approaches","authors":"Sonika Charak , Chandra Mohan Srivastava , Dhruv Kumar , Lovika Mittal , Shailendra Asthana , Ranjana Mehrotra , Manish Shandilya","doi":"10.1016/j.jphotobiol.2025.113147","DOIUrl":"10.1016/j.jphotobiol.2025.113147","url":null,"abstract":"<div><div>Idarubicin (4-demethoxydaunomycin), a structural analogue of daunomycin derived from <em>Streptomyces peucetius</em>, exhibits enhanced anticancer efficacy due to the substitution of a methoxy group with a hydrogen atom. This study investigates the binding interactions of idarubicin with RNA using a multifaceted approach, including infrared (IR) spectroscopy, absorption spectroscopy, circular dichroism (CD), molecular docking, and molecular dynamics (MD) simulations. The IR results demonstrate significant binding to guanine and uracil, indicated by spectral shifts, while MD simulations reveal additional interactions with adenine, highlighting a flexible binding mechanism. <strong>The binding constant of the idarubicin-RNA complex was calculated to be K = 2.1 × 10</strong><sup><strong>3</strong></sup> <strong>M</strong><sup><strong>−1</strong></sup><strong>, reflecting a strong affinity and stable interaction.</strong> Thermodynamic analysis shows that the negative Gibbs free energy (ΔG ∼ −4.57 kcal/mol) signifies spontaneous binding under physiological conditions. The binding free energy estimation was carried out to check the binding affinity, stability and interactions of the complex which was assessed through molecular dynamics simulations. The stability of the idarubicin-RNA complex is further supported by a hyperchromic effect observed in absorption spectroscopy, suggesting effective intercalation that enhances base exposure. The binding is driven by hydrogen bonding, π-π stacking interactions, and electrostatic forces, which collectively stabilize the complex. Notably, the conformational integrity of RNA is largely preserved, with key structural features remaining unchanged in both IR and CD analyses. Comparatively, idarubicin's interactions with RNA differ from those with DNA, where the latter shows more substantial conformational perturbations. These findings enhance our understanding of anthracycline functionality and provide valuable insights for developing novel analogues with improved efficacy and reduced side effects, informing future therapeutic strategies targeting RNA in cancer treatment.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"266 ","pages":"Article 113147"},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642282","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}
Jia-Ming Sun , Yu-Xin Liu , Yi-Tung Tsai , Yang-Dan Liu, Chia-Kang Ho, Dong-Sheng Wen, Ting-Yu Tsai, Dan-Ning Zheng, Ya Gao, Yi-Fan Zhang, Li Yu
{"title":"Salvianolic acid B protects against UVB-induced HaCaT cell senescence and skin aging through NRF2 activation and ROS scavenging","authors":"Jia-Ming Sun , Yu-Xin Liu , Yi-Tung Tsai , Yang-Dan Liu, Chia-Kang Ho, Dong-Sheng Wen, Ting-Yu Tsai, Dan-Ning Zheng, Ya Gao, Yi-Fan Zhang, Li Yu","doi":"10.1016/j.jphotobiol.2025.113139","DOIUrl":"10.1016/j.jphotobiol.2025.113139","url":null,"abstract":"<div><h3>Background</h3><div>Prolonged sunlight exposure can cause skin photoaging. The epidermis, the outermost layer of the skin, protects the body from the environment. This study explored the protective effect of salvianolic acid B (Sal-B), a bioactive compound from <em>Salvia miltiorrhiza</em>, against photoaging and examined its specific mechanism.</div></div><div><h3>Methods</h3><div><em>In vitro</em>, HaCaT cells were treated with various doses of Sal-B before ultraviolet B (UVB) light exposure. Assessments in HaCaT cells included cellular senescence, apoptotic cell ratio, reactive oxygen species (ROS) levels, mitochondrial function, superoxide dismutase activity, and gene and protein expression. Immunofluorescence labeling, nuclear factor erythroid 2-related factor 2 (NRF2) knockdown, and Western blotting analysis were used. To assess Sal-B's protective effects on skin photoaging <em>in vivo</em>, we employed a nude mouse model and an <em>ex vivo</em> human skin model.</div></div><div><h3>Results</h3><div><em>In vitro</em>, Sal-B significantly activated NRF2, scavenged ROS, protected mitochondrial function, and inhibited nuclear factor kappa B and mitogen-activated protein kinase pathways. Ultimately, Sal-B prevented UVB-induced photoaging and keratinocyte apoptosis. <em>In vivo</em>, we confirmed that Sal-B improved skin wrinkles and epidermal thickness in nude mice following UVB irradiation, displaying greater efficacy than tretinoin.</div></div><div><h3>Conclusion</h3><div>We identified the preventive implications of Sal-B against UVB-induced senescence in skin photoaging and revealed its potential as a regulator of the NRF2 signaling pathway.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"266 ","pages":"Article 113139"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580651","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}
{"title":"Boron dipyrromethene fungicide for anti-microbial photodynamic therapeutics","authors":"Aoqing Jia , Min Zheng , Zhigang Xie","doi":"10.1016/j.jphotobiol.2025.113137","DOIUrl":"10.1016/j.jphotobiol.2025.113137","url":null,"abstract":"<div><div>Due to inadequate light transmission into the subsurface, one of the key challenges for conventional photodynamic therapy (PDT) is realizing successful treatment of deep-skin pathogenetic bacterial infectious wounds. Preparation of near-infrared (NIR) photosensitizers (PSs) with potent antibacterial activity is a potential solution to address this issue. In the present work, a boron dipyrromethene (BDP) derivative was synthesized, which had red light absorption and NIR fluorescence. Under 635 nm of irradiation, BDP could generate massive reactive oxygen species (ROS) for sterilization, which exhibited robust photodynamic antiseptic property against Gram-positive bacteria (<em>S. aureus</em>), with a minimum inhibitory concentration of only 240 nM (140 mW cm <sup>−2</sup>). More importantly, BDP was capable of efficiently suppressing the development of bacterial biofilms and even eliminate established biofilms, thereby facilitating the enhancement of sterilizing efficacy. Furthermore, the promising antibacterial capability of BDP was validated in the treatment of <em>S. aureus</em>-infected abscess. The present work presents an antibiotic-free strategy for highly effective light-triggered abscess therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113137"},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528788","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}
Ang Liu , Tong Xia , Siyuan Cao , He Zhao , Yubin Hou , Xuejing Duan , Li Li , Ke Wang , Pu Wang , Chaowu Yan
{"title":"Comparative analysis of femtosecond, picosecond, and nanosecond laser techniques for transseptal puncture: An in vitro study with pathological correlation","authors":"Ang Liu , Tong Xia , Siyuan Cao , He Zhao , Yubin Hou , Xuejing Duan , Li Li , Ke Wang , Pu Wang , Chaowu Yan","doi":"10.1016/j.jphotobiol.2025.113138","DOIUrl":"10.1016/j.jphotobiol.2025.113138","url":null,"abstract":"<div><h3>Background</h3><div>Advanced precision laser technologies for transseptal puncture are still under exploration. Femtosecond lasers, renowned for their high precision and minimal collateral damage, exhibit significant potential in transseptal puncture applications.</div></div><div><h3>Objective</h3><div>This study investigated the feasibility, effectiveness and pathological effects of femtosecond, picosecond, and nanosecond lasers for transseptal puncture in vitro.</div></div><div><h3>Methods</h3><div>Three different pulsed laser systems (femtosecond, picosecond, and nanosecond) were utilized for atrial septal puncture in fresh porcine hearts. The femtosecond laser operated at 1064 nm wavelength with 179 fs pulse width and 500 kHz repetition rate; the picosecond laser at 1962 nm with 52 ps pulse width and 60 MHz repetition rate; and the nanosecond laser at 1064 nm with 70 ns pulse width and 60 kHz repetition rate. With a focused spot size of approximately 100 μm, the power density ranged from 25.50 to 51.00 kW/cm<sup>2</sup> (corresponding to energy densities of 0.05–0.10 J/cm<sup>2</sup> for femtosecond, 424.40–848.80 μJ/cm<sup>2</sup> for picosecond, and 0.42–0.85 J/cm<sup>2</sup> for nanosecond lasers). Scanning diameters varied from 0.50 to 3.00 mm at a constant speed of 1 mm/s. Measurements of puncture diameter and thermal damage were taken using a digital optical microscope, with pathological examination evaluating tissue structure and injury extent. Multiple linear regression models were used to evaluate the effects of laser types, power, and scanning diameter on puncture outcomes. <em>P</em> < 0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Using a focused spot size of 100 μm at power densities of 25.50–51.00 kW/cm<sup>2</sup> (2.0–4.0 W), the femtosecond laser (500 kHz, 0.05–0.10 J/cm<sup>2</sup>) and picosecond laser (60 MHz, 424.40–848.80 μJ/cm<sup>2</sup>) achieved complete penetration across 0.50–3.00 mm scanning diameters, with puncture diameters of 0.51–3.02 mm and 0.51–3.01 mm respectively. The nanosecond laser (60 kHz, 0.42–0.85 J/cm<sup>2</sup>) penetrated only at 0.50 mm scanning diameter and partially at 1.00 mm (3 W–4 W), with significantly smaller diameters (<em>P</em> < 0.001). Multiple regression showed scanning diameter primarily determined puncture size (β = 0.992, P < 0.001), while both power (β = 1.798, <em>P</em> = 0.002) and scanning diameter (β = 2.604, P < 0.001) affected thermal damage, with nanosecond (β = 6.515, <em>P</em> = 0.017) and picosecond lasers (β = 5.595, <em>P</em> = 0.039) showing greater thermal effects than femtosecond laser. Histologically, thermal damage progressed from minimal carbonization at 2 W to moderate-severe eosinophilic degeneration at 4 W…</div></div><div><h3>Conclusions</h3><div>Transseptal puncture using laser systems demonstrated feasibility, particularly with femtosecond laser showing favorable outcomes in precision and therma","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"266 ","pages":"Article 113138"},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563242","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}
Cailing Fan , Kaifu Ma , Ran Chen , Tianyu Zhang , Yonghao Song , Lei Liu , Weijie Chi , Qinxi Dong , Wei Shu , Chaoyuan Zeng
{"title":"Construction of a NIR fluorescent probe for tracking mitochondrial HOCl during liver injury","authors":"Cailing Fan , Kaifu Ma , Ran Chen , Tianyu Zhang , Yonghao Song , Lei Liu , Weijie Chi , Qinxi Dong , Wei Shu , Chaoyuan Zeng","doi":"10.1016/j.jphotobiol.2025.113136","DOIUrl":"10.1016/j.jphotobiol.2025.113136","url":null,"abstract":"<div><div>The inappropriate or excessive drug and alcohol consumption is a major cause of liver injuries. The development of a tool capable of visualizing the liver injury process with high precision, and in real time is particularly urgent. In this study, we designed and synthesized a novel HOCl-responsive fluorescent probe, <strong>PTZ-NS</strong>, for tracking mitochondrial HOCl during liver injury. <strong>PTZ-NS</strong> exhibits excellent sensitivity and selectivity for HOCl, with a detection limit of 158 nM. It can specifically target mitochondria, and successfully distinguishing between HepG2 and L-02 cells. The probe was also effective in tracking changes of endogenous HOCl levels in cells and zebrafish, and it was used to capture the increase in HOCl content during ferroptosis. Crucially, <strong>PTZ-NS</strong> was successfully employed to monitor HOCl during alcohol-induced liver disease (AID) and drug-induced liver injury (DILI) in mice liver tissue. Overall, <strong>PTZ-NS</strong> not only facilitate the real-time and precise observation of liver injury but also open up promising avenues for future disease prevention and research.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113136"},"PeriodicalIF":3.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508303","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}
Tiantian Sun , Sijia Wang , Xiao Liu , Dongliang Ji , Xudong Xie , Ruiqi Yang , Lei Wang , Yong Ling , Chang-Chun Ling
{"title":"Novel ꞵ-carboline/cyanoisoflavone photosensitizers for ferroptosis-induced efficient chemo-photodynamic synergistic cancer therapy","authors":"Tiantian Sun , Sijia Wang , Xiao Liu , Dongliang Ji , Xudong Xie , Ruiqi Yang , Lei Wang , Yong Ling , Chang-Chun Ling","doi":"10.1016/j.jphotobiol.2025.113135","DOIUrl":"10.1016/j.jphotobiol.2025.113135","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is an emerging therapeutic modality to selectively eradicate pathological cells, such as cancer cells. Hence, we designed and synthesized a series of novel ꞵ-carboline/cyanoisoflavone photosensitizers <strong>A1</strong>-<strong>A3</strong>. All compounds possessed potent type-I/-II photodynamic properties. Especially, the optimized compound <strong>A2</strong> produced large amounts of •O<sub>2</sub><sup>−</sup>, •OH, and <sup>1</sup>O<sub>2</sub> under irradiation, and exhibited a higher quantum yield of singlet oxygen (Φ<sub>Δ</sub> = 0.92) than others. Furthermore, <strong>A2</strong> not only exhibited potent cytotoxicity in HT29 cells, but also demonstrated prominent chemo-photodynamic effects with IC<sub>50</sub> values of 3.9–4.1 μM under normoxic and hypoxic conditions in HT29 cells, while exhibited minimal toxicity to normal cells, suggesting its tumor-selective and hypoxia-tolerant efficacy. Most importantly, <strong>A2</strong> significantly promoted mitochondrial damage and ferroptosis, through depleting GSH/GPX-4 levels and increasing malondialdehyde (MDA) expression. Finally, in vivo studies showed that <strong>A2</strong> achieved a high colonic tumor-inhibitory rate of 84.6 % through chemo-photodynamic therapy. These findings provide a promising framework for the development of novel photosensitizers for chemo-photodynamic therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113135"},"PeriodicalIF":3.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511029","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}
Varvara G. Kubenko, Vladimir A. Pomogaev, Andrey A. Buglak, Alexei I. Kononov
{"title":"Photophysics of 5,6,7,8-tetrahydrobiopterin on a femtosecond time-scale","authors":"Varvara G. Kubenko, Vladimir A. Pomogaev, Andrey A. Buglak, Alexei I. Kononov","doi":"10.1016/j.jphotobiol.2025.113134","DOIUrl":"10.1016/j.jphotobiol.2025.113134","url":null,"abstract":"<div><div>Pterins are naturally occurring compounds widespread in living organisms. 5,6,7,8-Tetrahydrobiopterin (H<sub>4</sub>Bip) is a cofactor of several key enzymes, including NO-synthases and phenylalanine hydroxylase, whereas tetrahydrocyanopterin is a photoreceptor molecule in cyanobacteria. In this regard, tetrahydropterins (H<sub>4</sub>pterins) photochemistry and photophysics have been attracting our attention. H<sub>4</sub>pterins photodegrade in presence of molecular oxygen yielding dihydropterins (H<sub>2</sub>pterins) and oxidized pterins. Meanwhile, the excited states dynamics of H<sub>4</sub>pterins on a femto- and picosecond time-scale remains unclear. To shed light on this area, we perform time-resolved spectroscopy of H<sub>4</sub>Bip using fluorescence up-conversion as well as transient absorption spectroscopy techniques along with TD-DFT non-adiabatic molecular dynamics. We show that the lowest H<sub>4</sub>Bip exited state has a lifetime of ca. 200 fs. Using the BHandHLYP functional and multireference spin-flip (MRSF) method we demonstrate that starting from the S<sub>4</sub> state, H<sub>4</sub>Bip passes to the S<sub>1</sub> state within 50 fs, and after 200 fs a conical intersection with the ground S<sub>0</sub> state is achieved. As a whole, the excited state behavior of H<sub>4</sub>Bip is similar to DNA nucleobases, in particular guanine. These findings allow us to make some speculations about the biochemical role of H<sub>4</sub>pterins photophysics.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113134"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479198","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}
Alysson Benite de Freitas , Hanstter Hallison Alves Rezende , Guilherme Rocha Lino de Souza , Pablo José Gonçalves
{"title":"Photodynamic inactivation of KPC-producing Klebsiella pneumoniae difficult-to-treat resistance (DTR) by a cationic porphyrin","authors":"Alysson Benite de Freitas , Hanstter Hallison Alves Rezende , Guilherme Rocha Lino de Souza , Pablo José Gonçalves","doi":"10.1016/j.jphotobiol.2025.113133","DOIUrl":"10.1016/j.jphotobiol.2025.113133","url":null,"abstract":"<div><div>The global rise of difficult-to-treat resistance (DTR) bacteria, such as <em>Klebsiella pneumoniae</em> carbapenemase-producing <em>Klebsiella pneumoniae</em> (KPC-Kp), poses a critical challenge in controlling infections and curbing the spread of antimicrobial resistance genes. Antimicrobial photodynamic inactivation (aPDI) offers a promising alternative to traditional antimicrobials by effectively targeting extensively drug-resistant pathogens and mitigating antimicrobial resistance. This study investigated the <em>in vitro</em> photodynamic efficacy of the cationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) against planktonic cultures of KPC-Kp. The minimum effective concentration (MEC) of TMPyP for significant photodynamic activity was determined to be 0.8 μM under an irradiance of 314 ± 11 mW/cm<sup>2</sup>, delivering a total light dose of 189 J/cm<sup>2</sup>. At the same concentration, bacterial suspensions exposed to a lower irradiance of 107 ± 7 mW/cm<sup>2</sup> achieved a > 99.997 % reduction in viability with a lethal light dose of 51.4 J/cm<sup>2</sup>. Scanning electron microscopy (SEM) revealed oxidative damage to the bacterial cell wall induced by aPDI. Hemolysis assays confirmed the safety of TMPyP, with no significant cytotoxicity or photocytotoxicity observed, and a selectivity index (SI) greater than 8, indicating a favorable therapeutic window. These findings underscore the potential of TMPyP-based aPDI as a therapeutic strategy to combat KPC-Kp infections. Further studies are warranted to explore its clinical applications and optimize treatment protocols for DTR bacterial infections.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113133"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464635","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}
Pushpamali De Silva , Mohammad A. Saad , Joseph W.R. Swain , Zhiming Mai , Madeline D. Kidd , Joanna J. Choe , Assiris P. Camargo , Sanjay Anand , Vinay Chandrasekhara , Brian W. Pogue , Kenneth K. Wang , Bryan Q. Spring , Edward V. Maytin , Tayyaba Hasan
{"title":"Photodynamic priming with red light triggers adaptive immune responses in a pancreatic cancer mouse model","authors":"Pushpamali De Silva , Mohammad A. Saad , Joseph W.R. Swain , Zhiming Mai , Madeline D. Kidd , Joanna J. Choe , Assiris P. Camargo , Sanjay Anand , Vinay Chandrasekhara , Brian W. Pogue , Kenneth K. Wang , Bryan Q. Spring , Edward V. Maytin , Tayyaba Hasan","doi":"10.1016/j.jphotobiol.2025.113126","DOIUrl":"10.1016/j.jphotobiol.2025.113126","url":null,"abstract":"<div><div>The poor response of pancreatic ductal adenocarcinoma (PDAC) to treatment, including immunotherapy, is attributed to its tumor microenvironment (TME). An ongoing challenge is the desmoplastic and immunosuppressed TME that evades immune surveillance. Here, we investigate transient modulation of the TME to overcome immunosuppression using a light-activated process, termed photodynamic priming (PDP). As a first step, this study captures the temporal dynamics of variations in immune infiltrates and subsequent immune responses in the TME, spleen, and blood of the KPC mouse model of PDAC post-PDP. In response to PDP, there were transient increases in tumor infiltrating lymphocytes (TIL) in tumors. The TIL population post-PDP includes an enrichment of CD8<sup>+</sup> T cells, accompanied by temporal increases in PD-1, CTLA-4, and TIM-3 immune checkpoints on both CD8<sup>+</sup> T and CD4<sup>+</sup> T cells. Significant increases in CD11C<sup>+</sup>MHC-11<sup>+</sup> dendritic cells and proliferating lymphocytes are observed in the spleen within several hours post-tumor PDP, suggesting initiation of adaptive immune responses. These observations are followed by an expansion of CD44<sup>+</sup>CD62<sup>−</sup>CD8<sup>+</sup> effector memory T cells in the blood over several days as evidence of a systemic immune response. Post-PDP TME alterations also included the reduced formation of blood (CD31<sup>+</sup>) and lymphatic (Lyve-1<sup>+</sup>) vessels as well as decreases in PD-L1 and collagen content. Collectively, these data suggest that PDP helps to mitigate immunosuppressive mechanisms and promote enhanced tumor permeability. The temporal dynamics of the processes elucidated here pave the way to develop strategies in future work for combined PDP–immunotherapy utilizing the immune checkpoint expression dynamics for precision therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113126"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474854","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}
Ding Luo , Yanhong Mao , Shengni Zhang , Shengqiang Shen , Xiaohu Ge , Litao Zhang
{"title":"Milk-derived exosome-loaded SS31 as a novel strategy to mitigate UV-induced photodamage in skin","authors":"Ding Luo , Yanhong Mao , Shengni Zhang , Shengqiang Shen , Xiaohu Ge , Litao Zhang","doi":"10.1016/j.jphotobiol.2025.113125","DOIUrl":"10.1016/j.jphotobiol.2025.113125","url":null,"abstract":"<div><div>It is widely recognized that ultraviolet (UV) radiation primarily catalyses photodamage in the skin by generating reactive oxygen species (ROS). In this study, we developed a novel antioxidant complex, Exo-SS31, by loading the antioxidant peptide SS31 (also known as MTP-131, elamipretide) into milk-derived exosomes. Our findings indicate that Exo-SS31 is an effective antioxidant capable of mitigating Human dermal fibroblast (HDF) damage induced by ultraviolet exposure, suppressing ROS production, and achieving greater therapeutic efficacy than SS31 alone. This complex can regulate the levels of superoxide dismutase (SOD) and glutathione (GSH) within the skin, inhibit the expression of proteins in pathways such as pMAPK and AP-1 triggered by UV radiation, and reduce the expression of the matrix metalloproteinases MMP1 and MMP3. Through these mechanisms, Exo-SS31 effectively prevents collagen degradation in the dermis and inhibits ultraviolet-induced photodamage. The use of milk-derived exosomes as carriers for antioxidant peptides represents a promising strategy to increase the bioavailability of peptide-based therapeutics.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113125"},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427789","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}