Journal of photochemistry and photobiology. B, Biology最新文献_第5页

Intermittent blue light-dark cycles: A new strategy for enhancing triterpenoid production in medicinal Sanghuangporus vaninii 间歇性蓝-暗循环：提高药用桑黄茯苓三萜产量的新策略。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-11 DOI: 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.

药用真菌中的三萜具有显著的生物活性和工业潜力，但其产量低，限制了其大规模生产。桑黄孢是一种广泛种植的药用真菌，是一种很有前途的三萜来源，但光暗循环在其三萜生物合成中的调节作用尚不清楚。在这项研究中，我们证明了间歇性强蓝光-暗循环（IB/D; ~ 110 μmol/m2·s, 10 h/14 h）显著提高了s . vaninii MF5的三萜产量。与黑暗对照相比，IB/D处理增加了154%的三萜产量，也优于恒定光照或白光-黑暗方案。在机制上，IB/D与：(i)超分枝形态（节间长度减少42%）；（ii）通过脂肪酸去饱和酶和转运蛋白上调的膜重塑，使通透性提高2.88倍；（iii）甲羟戊酸途径的转录激活，这伴随着内源性3-羟基-3-甲基戊二酰辅酶a合成酶（HMGS）表达的显著诱导4497倍。随后，通过与桑黄孢子属已知HMGS基因的序列同源性、鉴定保守的HMGS结构域以及预测其与甲羟戊酸（MVA）途径的关联，对SvHMGS基因进行了克隆和鉴定，表明其在三萜生物合成中可能具有保守功能。这种光周期策略代表了从恒定的光抑制到有节奏的诱导的范式转变，提供了一种可扩展的、低成本的方法来促进这种药用真菌的三萜生产。

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引用次数: 0

Molecular mechanism underlying the modulated toxicity of differently charged and sized nanoplastics by bovine serum albumin 牛血清白蛋白调节不同电荷和大小纳米塑料毒性的分子机制。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-11 DOI: 10.1016/j.jphotobiol.2025.113337

Xingren Pan , Xiaozhang Yu , Pengfei Qin , Wanni Yu

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.

纳米塑料的广泛存在引起了人们对其对生态系统和人类健康的危害的关注。它们在运输过程中容易吸收血清白蛋白形成电晕。然而，血清白蛋白对不同电荷和大小的纳米塑料毒性的调节尚不清楚。我们研究了聚苯乙烯纳米塑料（PS-NPs）对牛血清白蛋白（BSA）的分子机制以及电晕如何调节小鼠原发性肝细胞损伤。在无bsa的条件下，暴露于100 mg/L大的PS-NH2-NPs和PS-COOH-NPs的细胞活力分别显著降低27%和22%。相比之下，在BSA存在的情况下，减少的幅度被限制在17%和13%。此外，与单独使用两种改性PS-NPs （200 nm）相比，BSA预处理还降低了活性氧（ROS）水平。然而，BSA的加入并没有显著改变小PS-NPs （80 nm）的细胞活力和ROS水平。分子研究表明，PS-NPs主要通过中等疏水力与BSA的疏水腔结合，结合亲合力约为105 M-1。冠状结构的形成不仅引起牛血清白蛋白构象的改变，而且改变了其酯酶活性。分子和细胞实验都揭示了纳米塑料的尺寸和表面电荷特异性毒性模式。大的PS-NPs （200 nm）比小的纳米塑料（80 nm）与蛋白质的结合更紧密，PS-NH2-NPs比PS-COOH-NPs对BSA的风险更大。本研究阐明了BSA电晕形成如何以尺寸和电荷依赖的方式调节纳米塑性毒性。

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引用次数: 0

Effects of wavelength, fluence, irradiance, and irradiation mode of visible light on melanogenesis in B16F10 melanoma cells 可见光波长、通量、辐照度和照射方式对B16F10黑色素瘤细胞黑色素生成的影响

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-06 DOI: 10.1016/j.jphotobiol.2025.113335

Tianxiu Lu, Diya Shen, Yu Tian, Zihao Zheng, Fusheng Li, Qiuyi Han, Shanduan Zhang

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.

据报道，高通量可见光（VL）与紫外线辐射类似，可诱导皮肤色素沉着。然而，VL是由不同波长组成的多色光。VL参数对黑色素合成的影响还需要更多的实验研究来阐明。本研究以小鼠B16F10黑色素瘤细胞为体外模型，系统研究了波长、辐照度、辐照度和辐照方式如何共同影响VL对黑色素生成的影响。我们发现，448 nm的蓝光刺激黑色素生成，而560-733 nm的光在整体上抑制黑色素生成，其中595 nm的黄光抑制作用最强。此外，观察到双相反应：560 nm和595 nm黄光在3-12 J/cm2时抑制黑素生成，但在48 J/cm2时显著增强黑素生成。595 nm光在5-20 mW/cm2时抑制黑色素合成，但在≥40 mW/cm2时转为刺激。此外，我们的研究结果表明，595 nm脉冲PBM （3000 Hz， 40% - 80%占空比）优于连续PBM，而20%占空比（峰值辐照度为25 mW/cm2）消除了抑制作用，表明高辐照度激活了促黑色素生成防御途径。实验数据表明，这些差异主要是由于光照参数对酪氨酸酶活性和小眼相关转录因子（MITF）、TYR、TRP1和TRP2 mRNA水平的不同影响。综上所述，VL对黑色素形成的调控作用取决于这些参数的选择。这些数据为优化LED光疗参数提供了实验基础，并支持后续在人类皮肤黑色素细胞中的深入机制研究。在未来，优化的VL参数可能会平衡光疗在白癜风和黄褐斑等色素沉着失调引起的皮肤疾病中的疗效和安全性。

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引用次数: 0

Femtosecond laser and bee venom as promising anti-arthritic treatments: Modulation of JAK/STAT and PI3K/AKT/mTOR signaling pathways in vivo 飞秒激光和蜂毒作为有前景的抗关节炎治疗：体内JAK/STAT和PI3K/AKT/mTOR信号通路的调节

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-05 DOI: 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.

类风湿性关节炎（RA）是一种以关节退化和全身表现为特征的慢性疾病，它增加了死亡和残疾的风险。本研究比较了蜂毒（BV；皮下注射剂量为1mg /kg）和飞秒激光照射（FSL； 830nm波长，200mw功率，120s照射时间，0.8 cm2光束面积，0.5 cm半径，0.25 W/cm2功率密度，30 J/cm2能量剂量）单独或联合对关节炎大鼠的影响。将42只成年雄性Wistar大鼠分为7组。1 ~ 3组分别作为阴性对照组、BV组和FSL组，4组作为关节炎模型组，右后爪给予100 μL/大鼠完全弗氏佐剂（CFA）。5-7组分别用BV、FSL或两者联合治疗关节炎大鼠。类风湿关节炎的组织学检查显示滑膜炎、细胞浸润和软骨变性。BV注射和FSL照射治疗可显著减轻右后足水肿，改善组织学异常，降低血清c反应蛋白（CRP）和类风湿因子（RF）水平，同时降低受影响踝关节组织中TNF-α、NF-KB和IL-6的表达。此外，这两种处理都减轻了氧化应激，减少了DNA损伤，并调节了PI3K/AKT/mTOR和JAK/STAT信号通路。总的来说，无论是单独使用FSL还是与BV联合使用FSL，都显示出更强的软骨再生和组织修复能力。这突出了BV和FSL作为一种有希望的RA治疗方法，解决了症状缓解之外的潜在机制。

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引用次数: 0

Effects of red light-emitting diode therapy in imiquimod-induced psoriasis in mice 红色发光二极管治疗吡喹莫德诱导的小鼠银屑病的效果。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-05 DOI: 10.1016/j.jphotobiol.2025.113333

Mab P. Corrêa , Rebeca D. Correia-Silva , Diego D. Santos , Nathália Rodrigues-Silva , Pâmela P. Borges , Silvana Sandri , Karin V. Greco , Cristiane D. Gil

Growing evidence supports the therapeutic potential of phototherapies, particularly light-emitting diodes (LEDs), in modulating inflammation and restoring tissue homeostasis. Here, we evaluated the effects of red LED irradiation (660 nm) in a murine model of psoriasis induced by imiquimod (IMQ). C57BL/6 mice were treated with IMQ for 12 consecutive days and exposed to LED on alternate days from day 4, totalling five sessions. Macroscopic evaluation showed a significant reduction in skin-fold thickness and Psoriasis Area and Severity Index (PASI) scores in LED-treated mice. Histological analyses confirmed that IMQ induced epidermal thickening, erythema, mast cell infiltration, and collagen alterations. LED exposure attenuated epidermal changes (p < 0.0001, IMQ + LED versus IMQ), reduced mast cell numbers (p < 0.05, IMQ + LED versus IMQ), and modulated collagen fiber distribution, although it did not reverse dermal thickening. At the systemic level, IMQ increased spleen weight and white pulp expansion, effects not prevented by LED. In skin samples, IMQ markedly elevated interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels, which were significantly reduced by LED treatment (p < 0.05). In plasma, IL-22 was elevated in IMQ-treated animals but decreased in the IMQ + LED group (p < 0.05), while no significant changes were detected for IL-1β, IL-17A, IL-23, TNF-α, or macrophage inflammatory protein (MIP)-3α. Together, these results suggest that red LED phototherapy reduces clinical severity and partially modulates both local and systemic inflammation in IMQ-induced psoriasis, supporting its potential as a complementary therapeutic approach.

越来越多的证据支持光疗法，特别是发光二极管（led）在调节炎症和恢复组织稳态方面的治疗潜力。在这里，我们评估了红色LED照射（660 nm）对咪喹莫特（IMQ）诱导的银屑病小鼠模型的影响。C57BL/6小鼠IMQ连续治疗12天，从第4天开始隔天暴露于LED，共5个疗程。宏观评价显示，led治疗小鼠的皮肤褶皱厚度和银屑病面积和严重程度指数（PASI）评分显著降低。组织学分析证实IMQ诱导表皮增厚、红斑、肥大细胞浸润和胶原蛋白改变。LED照射可减弱表皮变化(p

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引用次数: 0

Scalable fabrication of polymeric dissolving microneedles for optimized ALA delivery in photodynamic therapy 聚合物溶解微针的可扩展制造，用于优化光动力治疗中ALA的输送

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-04 DOI: 10.1016/j.jphotobiol.2025.113319

Dianeth Sara Lima Bejar , Michelle Barreto Requena , Mirian Denise Stringasci , Marlon Rodrigues Garcia , Erika Toneth Ponce Ayala , Juliana Cristina Barreiro , Sebastião Pratavieira , Vanderlei Salvador Bagnato

Topical photodynamic therapy (PDT) is a minimally invasive, clinically approved treatment for non-melanoma skin cancer that relies on the conversion of photosensitizer (PS) precursors such as 5-aminolevulinic acid (ALA) into protoporphyrin IX (PpIX), followed by light activation. However, the low skin penetration of topically applied ALA cream remains a major limitation, restricting effective PpIX accumulation in deeper tumor layers. To address this challenge, we produced dissolving microneedles (DMN) as an alternative intradermal delivery platform. Two mold types were evaluated for DMN fabrication, one with a slight edge (DMNe) and another without edges (DMNf), both maintaining a conical tip geometry. DMN were prepared with a formulation containing initially 10% ALA and 20% Gantrez® AN-139 polymer in water, produced in a few steps, and characterized. In vitro insertion studies demonstrated consistent penetration depths of approximately

250 μ m

with minimal tip deformation. DMNf showed a better penetration efficiency than the DMNe and cream groups, and mass spectrometry confirmed uniform ALA distribution. In vitro assays in darkness confirmed the formulation’s biocompatibility with tumor cells. In a murine xenograft model of nodular epidermoid carcinoma, DMN-mediated ALA delivery generated up to twice the amount of PpIX in deeper tumor regions and also caused greater PDT damage compared to cream application. These findings highlight DMN as a promising approach to enhance PDT efficacy, especially for thicker or nodular skin lesions, by enabling superior and uniform intradermal drug delivery.

局部光动力疗法（PDT）是一种微创、临床批准的非黑色素瘤皮肤癌治疗方法，它依赖于光敏剂（PS）前体如5-氨基乙酰丙酸（ALA）转化为原卟啉IX (PpIX)，然后进行光激活。然而，局部应用ALA霜的皮肤渗透性低仍然是一个主要限制，限制了PpIX在更深肿瘤层的有效积累。为了解决这一挑战，我们生产了溶解微针（DMN）作为另一种皮内给药平台。评估了DMN制造的两种模具类型，一种带有轻微边缘（DMNe），另一种没有边缘（DMNf），两者都保持锥形尖端几何形状。DMN的配方最初含有10% ALA和20% Gantrez®AN-139聚合物在水中，通过几个步骤生产，并表征。体外插入研究表明，穿透深度约为250μm，尖端变形最小。DMNf的穿透效率优于DMNe组和乳膏组，质谱分析证实ALA分布均匀。体外暗室实验证实了该制剂与肿瘤细胞的生物相容性。在小鼠结节性表皮样癌异种移植模型中，dmn介导的ALA递送在更深的肿瘤区域产生的PpIX量高达两倍，并且与乳霜相比，也造成了更大的PDT损伤。这些发现突出了DMN作为一种有希望的方法来提高PDT的疗效，特别是对于较厚或结节性皮肤病变，通过实现优越和均匀的皮内给药。

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引用次数: 0

Photobiomodulation-driven cardiomyogenic differentiation and endothelial vascularization: A dual approach with Aloe Vera 光生物调节驱动的心肌分化和内皮血管化：芦荟的双重途径。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-12-02 DOI: 10.1016/j.jphotobiol.2025.113331

Tuğçe Gültan, Menemşe Gümüşderelioğlu

Cardiomyogenic differentiation plays a critical role in cardiac tissue engineering. It enables the transformation of precursor cells into functional cardiomyocytes capable of contraction and pumping. This study investigates the synergistic effects of Aloe vera (AV) and photobiomodulation (PBM) on cardiomyogenic differentiation in rat cardiomyoblast cell line derived from embryonic ventricular heart tissue (H9C2). It also examines the vascularization potential of primary rat cardiac microvascular endothelial cells (CMECs). Given their natural interaction in cardiac tissue, H9C2 and CMECs were co-cultured at a 6:1 ratio. Cytotoxicity assays established 10 mg/mL AV as a safe concentration, with cell viabilities exceeding 80 % across both monocultures and co-cultures. In the culture, PBM was applied every other day for 10 days, using a polychromatic light source (600–1200 nm) placed 20 cm away from the cells, at an irradiance of 0.04 W/cm² for 3 min per day. Neither AV nor PBM negatively affected cell viability. Fluorescence imaging indicated enhanced alignment and nuclear fusion in H9C2 cells, suggesting cardiomyogenic differentiation, particularly under combined AV–PBM treatment. Moreover, both AV and AV–PBM treatments significantly improved CMECs vascularization potential by day 14. RT-qPCR revealed a 7-fold and 9-fold increase in FGF2 gene expression following PBM and AV–PBM treatment, respectively. Anti-von Willebrand factor staining and imaging confirmed that CMECs formed lumen-like structures beneath H9C2 cells under all treatment conditions. These results demonstrate that the combined application of AV and PBM effectively promotes cardiomyogenic differentiation in H9C2 cells and enhances CMEC-mediated vascularization. This suggests a promising strategy for optimizing biosignaling and tissue integration in cardiac tissue engineering.

心肌分化在心脏组织工程中起着至关重要的作用。它使前体细胞转化为能够收缩和泵送的功能性心肌细胞。本研究探讨芦荟（AV）和光生物调节（PBM）对大鼠胚胎心室组织（H9C2）成心肌细胞分化的协同作用。它还检测了原代大鼠心脏微血管内皮细胞（CMECs）的血管化潜能。考虑到H9C2和cmec在心脏组织中的天然相互作用，以6:1的比例共培养。细胞毒性试验确定10 mg/mL AV为安全浓度，在单培养和共培养中细胞存活率均超过80%。在培养中，每隔一天使用PBM，持续10天，使用多色光源（600-1200 nm），放置在距离细胞20厘米的地方，辐照度为0.04 W/cm2，每天使用3分钟。AV和PBM均未对细胞活力产生负面影响。荧光成像显示H9C2细胞的排列和核聚变增强，提示心肌分化，特别是在AV-PBM联合治疗下。此外，AV和AV- pbm治疗在第14天显著改善了cmec的血管化潜力。RT-qPCR显示，PBM和AV-PBM治疗后，FGF2基因表达分别增加了7倍和9倍。Anti-von Willebrand factor染色和成像证实，在所有处理条件下，cmec在H9C2细胞下形成管腔样结构。这些结果表明，AV和PBM联合应用可有效促进H9C2细胞的成心分化，增强cmec介导的血管化。这为优化心脏组织工程中的生物信号和组织整合提供了一个有前途的策略。

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引用次数: 0

UVB enhances SLC6A15-mediated phenylalanine transport to promote melanogenesis UVB增强slc6a15介导的苯丙氨酸转运，促进黑色素生成

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-11-30 DOI: 10.1016/j.jphotobiol.2025.113329

Shu Zhou , Yujie Ouyang , Yibo Hu , Xixia Dai , Ling Jiang , Chuhan Fu , Yaqing Wen , Jiangfeng Huang , Keyi Zhang , Jing Chen , Qinghai Zeng

Background

Abnormal melanogenesis is a fundamental biological process underlying pigmentary disorders. While several solute carrier (SLC) transporters have been implicated in its regulation, the functions of many SLCs members remain poorly characterized.

Methods

We delineated transcriptional features of melanocytes with high melanogenic activity using single-cell and bulk RNA sequencing. Key SLC genes associated with melanogenesis were identified and prioritized using machine learning and Mendelian randomization analyses, followed by in vitro functional validation.

Results

Integrated multi-omics analysis identified SLC6A15 as a potential regulator of melanogenesis. SLC6A15 knockdown in MNT1 cells and primary melanocytes reduced melanin synthesis and downregulated key melanogenesis-related genes (e.g., MITF, TYR, DCT). Fontana–Masson staining and tyrosinase activity assays confirmed a marked decrease in melanin deposition and TYR activity in SLC6A15-depleted cells. UVB exposure upregulated SLC6A15, whereas SLC6A15 silencing abrogated the UVB-induced increase in pigmentation. Mechanistically, SLC6A15 knockdown reduced intracellular phenylalanine levels, indicating a role for SLC6A15-mediated phenylalanine transport in melanogenesis. Mendelian randomization further suggested that genetically higher phenylalanine levels are associated with an increased risk of melasma (OR = 6.02).

Conclusions

Our findings identify SLC6A15 as a potential key regulator of melanogenesis through the transport of phenylalanine.

背景：异常黑色素形成是色素紊乱的一个基本生物学过程。虽然一些溶质载体（SLC）转运体参与了其调控，但许多SLC成员的功能仍然缺乏表征。方法利用单细胞和大体积RNA测序技术，对具有高黑色素生成活性的黑素细胞的转录特征进行了描述。通过机器学习和孟德尔随机化分析，确定了与黑色素形成相关的关键SLC基因，并对其进行了优先排序，随后进行了体外功能验证。结果综合多组学分析发现SLC6A15是黑色素形成的潜在调节因子。SLC6A15在MNT1细胞和原代黑素细胞中的敲低降低了黑色素合成，下调了关键的黑素形成相关基因（如MITF、TYR、DCT）。Fontana-Masson染色和酪氨酸酶活性测定证实，slc6a15缺失的细胞中黑色素沉积和TYR活性显著降低。UVB暴露上调了SLC6A15，而SLC6A15沉默消除了UVB诱导的色素沉着增加。在机制上，SLC6A15敲除降低了细胞内苯丙氨酸水平，表明SLC6A15介导的苯丙氨酸运输在黑色素形成中的作用。孟德尔随机化进一步表明，遗传上较高的苯丙氨酸水平与黄褐斑风险增加相关（OR = 6.02）。结论研究结果表明，SLC6A15可能是通过苯丙氨酸转运介导黑色素形成的关键调控因子。

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引用次数: 0

Analysis of ROS dynamics based on dissolved oxygen sensing in upconversion nanoparticle-based photodynamic therapy 上转换纳米粒子光动力治疗中溶解氧传感的ROS动力学分析。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-11-29 DOI: 10.1016/j.jphotobiol.2025.113328

Esmaeil Heydari , Sepideh Delavari , Motahareh Jafarpour , Kamal Hajisharifi , Mohammad Moeini , Ahmet Erdem , Hossein Zare-Behtash , Mohammadreza Razzaghi , Gongxun Bai

Photodynamic therapy (PDT) is a promising cancer treatment approach that relies on the localized generation of reactive oxygen species (ROS) to eliminate cancer cells. In particular, the nanophotonic approach based on upconversion nanoparticles (UCNPs) offers a key advantage by enabling the use of near-infrared (NIR) light, which enhances light penetration into tissue and expands clinical applicability of PDT. Real-time monitoring of ROS generation and degradation during the PDT process offers distinct advantages over conventional endpoint assays for elucidating PDT mechanisms, optimizing photosensitizer (PS) formulations and refining treatment protocols.

In this study, we not only distinguish and quantify the relative contribution of NaYF₄:Yb³⁺,Tm³⁺ UC nano-antennas, Rose Bengal (RB) PS, NIR activation laser, and culture medium in UCNP-based PDT for the first time via real-time ROS analysis using dissolved oxygen (DO) data which cannot be achieved by endpoint assays but also introduce new and insightful concepts such as medium activation time (FWHM), maximum PL lifetime change (Δτ_max), and time to reach the maximum PL lifetime change ₍τ_max). This is realized by implementation of a 3D-printed optofluidic dissolved oxygen (DO) sensor for indirect analysis of ROS dynamics which infer from changes in the sensor's photoluminescence (PL) lifetime (τ).

Thus, performance and optimum concentrations of NaYF₄:Yb³⁺,Tm³⁺ UCNPs and RB PS are first determined via MTT assays using A375 melanoma cells, and subsequent in-vitro PDT tests using a 980 nm laser. Quantitative analyses show that, UCNPs, RB, and the cell culture medium contribute approximately 25 %, 26 %, and 4 % to the total Δτ respectively. The maximum performance occurs when all components are present and activated, resulting in the highest ROS level with the longest activation time. Interestingly, even laser excitation of the medium alone or UCNPs without PS results in partial ROS generation. These findings provide valuable insights for optimizing UCNP-based PDT drugs for cancer treatment.

光动力疗法（PDT）是一种很有前途的癌症治疗方法，它依赖于局部产生活性氧（ROS）来消除癌细胞。特别是，基于上转换纳米粒子（UCNPs）的纳米光子方法通过使用近红外（NIR）光提供了一个关键优势，它增强了光穿透组织并扩大了PDT的临床适用性。在PDT过程中，实时监测ROS的生成和降解，在阐明PDT机制、优化光敏剂（PS）配方和改进处理方案方面，比传统的终点分析具有明显的优势。在这项研究中，我们不仅通过使用溶解氧（DO）数据进行实时ROS分析，首次区分和量化了基于ucnp的PDT中NaYF4:Yb3+，Tm3+ UC纳米天线，Rose Bengal (RB) PS，近红外激活激光器和培养基的相对贡献，这是终点分析无法实现的，而且还引入了新的和有见解的概念，如介质激活时间（FWHM），最大PL寿命变化（Δτmax）和达到最大PL寿命变化的时间（τmax）。这是通过实现一个3d打印的光流体溶解氧（DO）传感器来间接分析ROS动力学，这是从传感器的光致发光（PL）寿命（τ）的变化中推断出来的。因此，首先使用A375黑色素瘤细胞通过MTT试验确定NaYF4:Yb3+，Tm3+ UCNPs和RB PS的性能和最佳浓度，然后使用980 nm激光进行体外PDT试验。定量分析表明，UCNPs、RB和细胞培养基分别约占总量的25%、26%和4% Δτ。当所有组件都存在并激活时，产生最高的ROS水平，激活时间最长。有趣的是，即使激光激发单独的介质或不含PS的UCNPs也会产生部分ROS。这些发现为优化基于ucnp的PDT药物用于癌症治疗提供了有价值的见解。

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引用次数: 0

Photodynamic ablation of floating lung cancer cells using PVA and TPGS emulsified PLGA nanoparticles loaded with pyropheophorbide-a PVA和TPGS乳化PLGA纳米颗粒负载焦磷-a的光动力消融漂浮肺癌细胞。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology

Pub Date : 2025-11-26 DOI: 10.1016/j.jphotobiol.2025.113318

Sasivimon Pramual , Philippe Arnoux , Kriengsak Lirdprapamongkol , Céline Frochot , Valérie Jouan-Hureaux , Muriel Barberi-Heyob , Jisnuson Svasti

Metastasis or the spread of cancer cells to other tissues is a hallmark that leads to the majority of cancer-related deaths worldwide. When metastasizing cancer cells invade into the bloodstream, they become floating cells, also known as circulating tumor cells (CTCs), which can lead to the development of metastasis-associated multidrug resistance in advanced cancer patients. Eradication of CTCs has received much attention as a strategy for preventing metastasis. Photodynamic therapy (PDT) has attracted growing interest as a minimally invasive approach for cancer treatment. Pyropheophorbide-a (PPa) is photosensitizer with advantages of relatively high wavelength absorption and high extinction coefficient; however, it has limited PDT therapeutic benefits due to poor solubility. This work aimed to employ PDT for killing CTCs by utilizing PVA and TPGS coated PLGA nanoparticles, loaded with PPa. The PPa-entrapped PLGA nanoparticles (PPa-NPs) exhibited a spherical morphology under TEM with an average size of 124.9 ± 2.3 nm and a zeta potential value of −32.0 ± 1.4 mV. The PPa-NPs enhanced singlet oxygen generation in water upon light activation. PPa-NPs successfully delivered PPa into A549 floating cells under CTC-mimicking conditions, with 21-fold increase in intracellular PPa accumulation when compared to free PPa treatment. After red light excitation, intracellular ROS level was elevated in PPa-NPs treated floating cells, in a dose-dependent manner, and correlated with photocytotoxic effect of PPa-NPs in the floating cells. Our results demonstrate that PVA and TPGS stabilized PLGA NPs efficiently preserved the photophysical properties of PPa for eradicating CTCs by PDT with red light activation.

癌细胞转移或扩散到其他组织是导致世界上大多数癌症相关死亡的一个标志。当转移性癌细胞侵入血液时，它们成为漂浮细胞，也称为循环肿瘤细胞（ctc），这可能导致晚期癌症患者发生与转移相关的多药耐药。根除ctc作为预防转移的策略已受到广泛关注。光动力疗法（PDT）作为一种微创治疗癌症的方法引起了越来越多的关注。PPa是一种波长吸收高、消光系数高的光敏剂；然而，由于溶解性差，它的PDT治疗效果有限。本工作旨在利用PVA和TPGS包被的PLGA纳米颗粒，负载PPa，利用PDT杀死ctc。在TEM下，PPa-NPs包埋的PLGA纳米颗粒呈球形，平均尺寸为124.9±2.3 nm， zeta电位值为-32.0±1.4 mV。pa - nps在光活化下增强了水中单线态氧的生成。在模拟ctc的条件下，PPa- nps成功地将PPa传递到A549漂浮细胞中，与游离PPa处理相比，细胞内PPa积累增加了21倍。红光激发后，pa - nps处理的漂浮细胞细胞内ROS水平呈剂量依赖性升高，且与pa - nps对漂浮细胞的光毒作用相关。我们的研究结果表明，PVA和TPGS稳定的PLGA NPs有效地保留了PPa的光物理性质，用于红光活化的PDT根除ctc。

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引用次数: 0