Chemistry & Biology[JOURNAL]
Sun
200 papers
Optical and random laser properties of the novel multifunctional endoxifen derivative (FLTX3) and its potential for the diagnosis of breast cancer resistance.
Diaz M, de Armas-Rillo S, Lobo F … +10 more , Pereda de Pablo D, Soler-Carracedo K, Delgado P, Rodriguez M, Canerina-Amaro A, Valdes-Baizabal C, Marín R, Hernández D, Boto A, Lahoz F
J Photochem Photobiol B · 2026 Jan · PMID 41421057 · Publisher ↗
Endoxifen is the most powerful metabolite of tamoxifen (TX), the main endocrine therapy administered worldwide for the treatment of estrogen-receptor (ER) positive metastatic breast cancer. Tamoxifen itself is a prodrug...
Endoxifen is the most powerful metabolite of tamoxifen (TX), the main endocrine therapy administered worldwide for the treatment of estrogen-receptor (ER) positive metastatic breast cancer. Tamoxifen itself is a prodrug with weak affinity for ER, but it is converted into endoxifen, with up to 100-fold higher affinity for ER than TX. In this study, we introduce the first fluorescent endoxifen derivative (FLTX3), formed by covalent attachment of the small fluorophore NBD to the basic side chain of endoxifen. We have characterized the optical properties of FLTX3, demonstrating its ability as a laser dye. FLTX3 is an efficient target-directed fluorescent probe for the cellular labelling of ER in MCF7 breast cancer cell line as well as in uterine tissues. FLTX3 is also endowed with an intrinsic photodynamic effect when irradiated at the optimal excitation wavelength of FLTX3. Further, we show that FLTX3 has an optical gain behaviour that leads to random laser (RL) when the light emitted by the drug is scattered in the cell cultures. Indeed, analyses of coherent spectra by power function Fourier transform revealed a RL dominant cavity in the range of average cell sizes. As one of the main causes for tamoxifen treatment failure is resistance, we explored the potential discriminative value of FLTX3-induced RL between tamoxifen-resistant and tamoxifen-sensitive MCF7 cells. Using multivariate approaches, we unravelled significant differences in the RL signal between tamoxifen-sensitive and tamoxifen-resistant cells. These findings indicate that FLTX3-generated RL might provide a target-directed diagnostic tool for tamoxifen resistance in metastatic ER+ breast cancer.
Curcumin-mediated photodynamic action disturbs TOM70-depedent MIC60 import to damage mitonchondria against breast cancer.
Zhao XY, Yan M, Zheng L … +10 more , Gou CL, Huang Q, Li LG, Yu XR, Lu JY, Hu C, Zhang SH, Kong C, Leng F, Li TF
J Photochem Photobiol B · 2026 Jan · PMID 41418387 · Publisher ↗
The regulation of mitochondrial membrane proteins is of crucial significance for breast cancer therapy. TOM70, which located in mitochondria outer membrane, could import MIC family molecules to preserve mitochondrial hom...
The regulation of mitochondrial membrane proteins is of crucial significance for breast cancer therapy. TOM70, which located in mitochondria outer membrane, could import MIC family molecules to preserve mitochondrial homeostasis. However, there are few agents targeting TOM70. Therein, the effects of curcumin and it's mediated photodynamic therapy (PDT) on the TOM70 and mitochondrial function for breast cancer treatment were investigated. The 4 T1 and MDA-MB-231 cells were utilized as the breast cancer cells. The 4 T1 cell-bearing mice were constructed as the breast cancer animal model. The anti-cancer efficacy was validated using the CCK-8, Annexin-V/PI staining, colony formation. The associated molecules were detected by Western blots (WB), RT-qPCR, and Immunohistochemistry (IHC). The target was verified by molecular docking, CETSA, and DARTS. The mitochondrial proteins and DNA were extracted for the MIC60 and mtDNA damage detection. Curcumin treatment showed poor efficacy in the breast cancer model, as characterized by cell viability, apoptosis, proliferation of breast cancer cells, and the growth of tumor grafts in mice. However, curcumin-mediated PDT inhibited breast cancer in vitro and in vivo. Further exploration identified curcumin bond to TOM70, which is highly expressed in breast cancer, thereby activating it. But curcumin-induced PDT inactivated TOM70 through generated reactive oxygen species (ROS), which in turn interfered with the binding of MIC60 and its translocation into mitochondria. Curcumin-triggered PDT led to severe mitochondrial damage compared with the curcumin treatment, which could be blocked by the N-Acetylcysteine (NAC). Additional TOM70 rescue dampened curcumin PDT-mediated mitochondrial damage and anti-breast cancer efficacy. To summarize, the present research identifies curcumin-induced PDT inactivated TOM70, thereby attenuating MIC60 import, leading to mitochondrial damage against breast cancer. We propose a novel approach to tumor treatment through the regulation of mitochondrial membrane proteins using the phytomedicine-driven PDT.
Aging-related peroxisomal dysregulation disrupts intestinal stem cell differentiation through alterations of very long-chain fatty acid oxidation.
Guo X, Du G, Zhou J … +7 more , Fu F, Yuan Y, Liu X, Chen H, Wan Q, Gong B, Chen H
PLoS Biol · 2025 Dec · PMID 41417787 · Full text
Aging disrupts intestinal stem cell (ISC) lineage fidelity, impairing epithelial barrier function and then promoting systemic health decline. In this study, we identify peroxisomal dysfunction as a critical driver of age...
Aging disrupts intestinal stem cell (ISC) lineage fidelity, impairing epithelial barrier function and then promoting systemic health decline. In this study, we identify peroxisomal dysfunction as a critical driver of age-associated ISC mis-differentiation. Using Drosophila and mouse colonic organoids, we demonstrate that reduced PEX5 expression in aged ISCs impairs peroxisomal matrix protein import, leading to very long-chain fatty acids (VLCFAs) accumulation. In addition, we found that RAB7-dependent late endosome maturation and SOX21A were downstream of the peroxisome in controlling aged ISC differentiation. Aspirin, a classic anti-inflammatory drug, restores ISC lineage fidelity by enhancing PEX5-mediated peroxisomal β-oxidation of VLCFAs. Taken together, these findings highlight peroxisomal dysfunction and VLCFA metabolism as pivotal regulators of ISC aging and suggest new therapeutic strategies for combating age-related intestinal decline.
The master virulence regulator PhoP dictates carbon metabolism by controlling cyclic AMP synthesis in Salmonella.
Pokorzynski ND, Sams-Dodd EC, Esneault C … +3 more , Jones KA, Campagna SR, Groisman EA
PLoS Biol · 2025 Dec · PMID 41411317 · Full text
The intracellular pathogen Salmonella enterica serovar Typhimurium confronts cytoplasmic Mg2+ starvation inside macrophages. This stress alters carbon metabolism and subverts canonical carbon source preferences by reduci...
The intracellular pathogen Salmonella enterica serovar Typhimurium confronts cytoplasmic Mg2+ starvation inside macrophages. This stress alters carbon metabolism and subverts canonical carbon source preferences by reducing synthesis of 3', 5'-cyclic adenosine monophosphate (cAMP), the essential allosteric activator of the cAMP receptor protein (CRP), master regulator of carbon utilization. How, then, does S. Typhimurium preferentially utilize CRP-cAMP-dependent carbon sources inside macrophages? We now report that the virulence and Mg2+ homeostasis regulator PhoP controls CRP-cAMP-dependent transcription, metabolism, and growth on a mixture of carbon sources during low cytoplasmic Mg2+. We determine that the PhoP-activated MgtA and MgtB proteins promote CRP-cAMP activity by importing Mg2+, indispensable cofactor of the cAMP-synthesizing adenylate cyclase CyaA. Significantly, the PhoP-activated MgtC preserves cAMP amounts despite reducing abundance of CyaA substrate adenosine triphosphate (ATP) because ATP at high concentrations inhibits CyaA. Restoring CRP activity by supplementation of cAMP or introduction of the constitutively active crp* allele corrected CRP-dependent transcriptional and growth behaviors of the mgtA mgtB mutant. By controlling cAMP synthesis, PhoP dictates the amounts of active CRP, thereby reprogramming S. Typhimurium's metabolism.
Prostate cancer risk-associated single-nucleotide polymorphisms impact the conformational dynamics of prostate-specific antigen.
Srinivasan S, Hayes BK, Costa MGS … +9 more , Riley BT, Wilson E, Marijanovic EM, Kass I, Koistinen H, Hoke DE, Clements J, Buckle AM, Batra J
BMC Biol · 2025 Dec · PMID 41402853 · Full text
BACKGROUND: Two non-synonymous single-nucleotide polymorphisms (SNPs) rs61752561 (D95N substitution) and rs17632542 (I163T substitution) in the KLK3 gene encoding prostate-specific antigen (PSA), a chymotrypsin-like seri...
BACKGROUND: Two non-synonymous single-nucleotide polymorphisms (SNPs) rs61752561 (D95N substitution) and rs17632542 (I163T substitution) in the KLK3 gene encoding prostate-specific antigen (PSA), a chymotrypsin-like serine protease, are associated with prostate cancer risk and have been shown to reduce the activity of PSA. However, the structural impact of these SNPs on PSA, which may underlie the observed risk associations and functional alterations, has not been fully explored. RESULTS: Computational modelling predicted that the variants D95N and I163T do not cause drastic structural changes in PSA. However, molecular dynamics simulations suggested that while the two prominent loops of wild-type PSA remain tethered to their initial conformations over 500 ns of simulation, they are disrupted in both variants, leading to increased loop dynamics. Frustration analysis, normal mode analysis (NMA) and perturbation response scanning identified dynamic links between mutation sites and increased loop dynamics that trigger long-range conformational changes, disrupting the active site and potentially hindering catalytic activity. Thermal denaturation stability assays using recombinant protein show the impact of D95N and I163T substitution on the protein stability. CONCLUSIONS: These data show that KLK3 SNPs disrupt dynamic communication of the key loops required for proteolytic activity of PSA, which may explain the association of these SNPs with prostate cancer risk and/or progression.
Molecular mechanism underlying the modulated toxicity of differently charged and sized nanoplastics by bovine serum albumin.
Pan X, Yu X, Qin P … +1 more , Yu W
J Photochem Photobiol B · 2026 Jan · PMID 41401635 · Publisher ↗
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 seru...
The extensively presence of nanoplastics raises concerns about their harm to ecosystems and human health. They are easy to absorb serum albumin to form corona during the transport process. However, the regulation of serum albumin to the toxicity of nanoplastics with differing charges and sizes remains unknown. We examined the molecular mechanism of polystyrene nanoplastics (PS-NPs) to bovine serum albumin (BSA) and how corona modulates the mouse primary hepatocyte damage. In cells exposed to 100 mg/L of large PS-NH-NPs and PS-COOH-NPs, a significant reduction in cell viability of 27 % and 22 % was noted, respectively, under BSA-free conditions. In contrast, the reductions were limited to 17 % and 13 % in the presence of BSA. Additionally, BSA pretreatment also lowered the reactive oxygen species (ROS) levels compared to the use of two modified PS-NPs (200 nm) alone. However, the addition of BSA did not significantly alter the cell viability or the levels of ROS in small PS-NPs (80 nm). Molecular investigations demonstrated that PS-NPs mainly bound to the hydrophobic cavity of BSA through moderate hydrophobic forces with the binding affinity approximately 10 M. The formation of corona not only induced conformational changes in BSA but also modified its esterase activity. The molecular and cellular experiments both revealed the size and surface charge-specific toxicity pattern of nanoplastics. Big PS-NPs (200 nm) bound more tightly to the protein compared to small nanoplastics (80 nm), and PS-NH-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.
Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.
Radrizzani S, Rivas-Santisteban J, Han N … +1 more , Hurst LD
PLoS Biol · 2025 Dec · PMID 41397037 · Full text
Despite early assumptions of neutrality, numerous mechanisms are now thought to cause selection on synonymous mutations, commonly supported by a low evolutionary rate at synonymous sites (Ks). This has been best evidence...
Despite early assumptions of neutrality, numerous mechanisms are now thought to cause selection on synonymous mutations, commonly supported by a low evolutionary rate at synonymous sites (Ks). This has been best evidenced in the first ~10 codons of genes in E. coli, where Ks is less than around half that of the gene body. Diverse lines of evidence support the hypothesis that these first ~10 codons are under selection for high AT content which causes low mRNA stability that in turn enables ribosomal initiation. There remains one enigmatic discrepancy, however, namely that the low Ks domain extends far beyond the first 10 codons. Here we ask why this is. As we see no evidence that the zone influencing protein levels has been misestimated, we consider three further hypotheses: that reduced Ks is a) owing to overlapping genes, b) reflects an extended slow translational "ramp," and c) is mutational. We reject the first two as in both E. coli and Bacillus sp. the extended low Ks domain persists on analysis of non-overlapping genes and in Bacillus, where fast optimal codons tend to be A/T-ending, a fast-to-slow codon trend is seen. We fail to falsify the third hypothesis. Employing mutation accumulation data for E. coli we show that the 5' end has a lower mutation rate, with the first 10 codons having a rate around half that of the gene body, this then steadily increasing following the trend seen for Ks. Compositional variation is likely to explain some of the difference, the 5' end lacking GC-rich runs while these are most mutagenic. We conclude that even a highly reduced Ks is not always adequate to substantiate selection on synonymous mutations. This result has broad implications for inference of the causes of evolutionary rate variation.
Intermittent blue light-dark cycles: A new strategy for enhancing triterpenoid production in medicinal Sanghuangporus vaninii.
Ma Y, Li R, Li J … +4 more , Song Z, She F, Ma X, Zhu X
J Photochem Photobiol B · 2026 Jan · PMID 41391213 · Publisher ↗
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 pr...
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/m·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.
Priming cancer cells via photobiomodulation at NIR wavelength to enhance photodynamic action: Insights into mechanistic alterations and cellular migration.
Sirek B, Topaloğlu N
J Photochem Photobiol B · 2026 Jan · PMID 41389731 · Publisher ↗
Photodynamic therapy (PDT) is a successful therapy for cancer treatment, especially for the superficial and easily reachable types, such as prostate cancer. During photodynamic activation, the light-sensitive chemical, w...
Photodynamic therapy (PDT) is a successful therapy for cancer treatment, especially for the superficial and easily reachable types, such as prostate cancer. During photodynamic activation, the light-sensitive chemical, which generally does not have a toxic effect on cells, can induce oxidative stress by producing reactive oxygen species (ROS). Nevertheless, the outcome of the therapy may be diminished by certain drawbacks. For this, PDT can be coupled with other therapies. Different light therapies can also serve as effective anticancer strategies. The combination of photobiomodulation (PBM) with PDT has become increasingly popular in cancer management. In the present study, PBM, which lacks anticancer activity, was combined with Chlorin e6 (Ce6)-mediated PDT. Underlying causes of additional deaths were elucidated by various mechanistic analyses, including ROS, nitric oxide (NO), mitochondrial membrane potential (ΔΨm), etc. PBM priming at an energy density of 5 J/cm resulted in up to 64 % additional cell death, as demonstrated by colorimetric and dual-staining analyses, and nearly a 100 % decrease in cell migration compared to PDT alone. Besides, PBM priming induced an additional 0.5-fold reduction in NO levels, a 19.4 % increase in ROS levels, and a 1.2 % reduction in ΔΨm compared to only PDT applications. Thus, combining PDT with PBM priming can provide a more effective therapeutic approach and significantly diminish the invasiveness of cancer cells.
Photobiomodulation-driven cardiomyogenic differentiation and endothelial vascularization: A dual approach with Aloe Vera.
Gültan T, Gümüşderelioğlu M
J Photochem Photobiol B · 2026 Jan · PMID 41385894 · Publisher ↗
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 investiga...
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/cm 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.
Prolonged grazing reduces the diversity and weakens virus-host links of metagenome-assembled viral community in acidic karst soil.
Xue R, Li Z, Qin W … +4 more , Wang Y, Zhao K, Liu L, Bai Y
BMC Biol · 2025 Dec · PMID 41382192 · Full text
BACKGROUND: Soil viruses are fundamental yet often overlooked components of terrestrial ecosystems, where they profoundly influence microbial diversity, community assembly, and biogeochemical cycling through predator-pre...
BACKGROUND: Soil viruses are fundamental yet often overlooked components of terrestrial ecosystems, where they profoundly influence microbial diversity, community assembly, and biogeochemical cycling through predator-prey dynamics and the carriage of auxiliary metabolic genes (AMGs). However, the impact of human-driven land use change on viral communities and their functional potential remains poorly understood. RESULTS: In this study, we analyzed viral diversity, virus-host linkage, and functional profiles of AMGs across different land management regimes in acidic karst soil after reclamation. The results showed that both bacterial and viral communities significantly differ across the four land management regimes, which are unused land, grazing pastureland, abandoned pastureland, and fertilized grazing pastureland. Grazing led to a lower viral diversity, a decrease in lysogenic viral abundance, and fewer virus-host linkages. The diversity and function of AMGs were also significantly affected by land management regimes, with grazing leading to a reduction in both AMGs diversity and relative abundance. Furthermore, both the bacterial community and soil physiochemical properties were essential factors that shaped viral diversity and lifestyle. CONCLUSIONS: Overall, our findings indicate that inappropriate land use (long-term grazing) disrupts the virus-host balance, thereby altering the functional profiles of the soil viral community.
Structures of G-protein coupled receptor HCAR3 in complex with selective agonists reveal the basis for ligand recognition and selectivity.
Ye F, Zhang Z, Zhang B … +16 more , Li X, Deng J, Miao Q, Ning P, Chi Y, Chen G, Wu Z, Wang Q, Xu L, Gong N, Cheng B, Ma Z, Qian C, Zhu L, Pan X, Du Y
PLoS Biol · 2025 Dec · PMID 41359625 · Full text
The hydroxycarboxylic acid receptors (HCAR2 and HCAR3), also known as prototypical metabolite-sensing receptors, are key targets for treating dyslipidemia and metabolic disorders. While HCAR2 activation, but not HCAR3 ac...
The hydroxycarboxylic acid receptors (HCAR2 and HCAR3), also known as prototypical metabolite-sensing receptors, are key targets for treating dyslipidemia and metabolic disorders. While HCAR2 activation, but not HCAR3 activation, is associated with side effects of cutaneous flushing, the structural features and ligand preferences of HCAR3 remain less understood. Here, we used Sf9 cells to express HCAR3-Gi and HCAR2-Gi complexes, and present cryo-EM structures of HCAR3-Gi complexes with agonists compound 6O (3.31 Å), D-phenyllactic acid (3.05 Å), IBC293 (3.26 Å), and acifran (3.18Å), as well as HCAR2-Gi complex with agonist acifran (2.72 Å). Our findings reveal the mechanism behind 6O's highest affinity to HCAR3, attributed to its full occupation of both R1 and R2 regions of the orthosteric binding pocket. Moreover, combined with cAMP assay in HEK-293 cells, we have elucidated that the ligand selectivity between HCAR3 and HCAR2 depended on π-π interaction with F1073.32 (L1073.32 in HCAR2) and ligand-binding pocket size difference, facilitated by key residues difference V/L832.60, Y/N862.63, and S/W9123.48. Collectively, these structural insights lay the groundwork for developing HCAR3-specific drugs, potentially avoiding HCAR2-induced adverse effects.
Scalable fabrication of polymeric dissolving microneedles for optimized ALA delivery in photodynamic therapy.
Bejar DSL, Requena MB, Stringasci MD … +5 more , Garcia MR, Ayala ETP, Barreiro JC, Pratavieira S, Bagnato VS
J Photochem Photobiol B · 2026 Jan · PMID 41352277 · Publisher ↗
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)...
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 250μm 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.
Photodamaged PSII does not accumulate in the non-appressed thylakoid membranes in the absence of PSII repair.
Bagchus C, Ramakers LAI, Verhoeven D … +2 more , van Amerongen H, Wientjes E
J Photochem Photobiol B · 2026 Jan · PMID 41352276 · Publisher ↗
Photosystem II (PSII) is highly sensitive to light-induced damage. Photoinhibition, the light-dependent inactivation of PSII, is associated with an increase of excitation-energy quenching. Recovery from photoinhibition i...
Photosystem II (PSII) is highly sensitive to light-induced damage. Photoinhibition, the light-dependent inactivation of PSII, is associated with an increase of excitation-energy quenching. Recovery from photoinhibition involves migration of PSII complexes from the appressed to the non-appressed region of the thylakoid membrane, where D1 (the PSII core protein most sensitive to photodamage) is degraded and repair occurs. However, it remains unclear whether damaged PSII core complexes accumulate in the stroma lamellae when repair is blocked. Here, we combined confocal Fluorescence Lifetime Imaging Microscopy (FLIM) with biochemical fractionation of the thylakoid membrane to investigate the localization of damaged PSII following photoinhibition in the presence of lincomycin, an inhibitor of D1 synthesis. This condition mimics natural stress scenarios such as heat, where D1 synthesis is impaired. FLIM analysis of structured, intact thylakoid membranes, segmented into grana- and stroma-lamellae-enriched regions, revealed a decrease in PSII fluorescence lifetime upon photoinhibition, consistent with increased excitation-energy quenching. Surprisingly, no significant difference in fluorescence lifetime components was observed between membrane domains, suggesting that damaged, quenched PSII does not accumulate in the stroma lamellae under these conditions. Western blot analysis of biochemically isolated membrane fractions confirmed a uniform decrease in D1 levels across grana and stroma lamellae upon photoinhibition. Our results indicate that when D1 synthesis is blocked, the relocation and degradation of photodamaged PSII proceed efficiently enough to prevent its accumulation in the stroma lamellae. This reveals new aspects of PSII repair and demonstrates the strength of FLIM for spatially resolved analysis of the thylakoid membrane.
Photodynamic therapy and argon laser treatment of white spot lesions: Effects on enamel remineralization and orthodontic bracket bond strength.
Alnazeh AA, Kamran MA, Alshahrani A … +2 more , Amer OM, Anzi RAK
J Photochem Photobiol B · 2026 Jan · PMID 41349299 · Publisher ↗
AIM: Effect of different prophylactic regimes, i.e., Fluoride, Methylene blue (MB) activated photodynamic therapy (PDT), Argon laser, and photopolymerized resin infiltration, on the microhardness (MH), calcium/phosphorus...
AIM: Effect of different prophylactic regimes, i.e., Fluoride, Methylene blue (MB) activated photodynamic therapy (PDT), Argon laser, and photopolymerized resin infiltration, on the microhardness (MH), calcium/phosphorus (Ca/P) ratio, bracket-enamel interface, and shear bond strength (SBS) of orthodontic adhesive adhered to demineralized enamel. METHOD: One hundred twenty-five premolars were obtained and disinfected. The buccal surface was coated with acid-resistant varnish, creating a 4 × 6-mm area uncovered for bracket bonding and MH testing. Artificial enamel demineralization mimicking white spot lesion (WSL) was developed, and specimens were allocated into five groups based on prophylactic regimes (n = 25): Group 1 (No pretreatment), Group 2 (Fluoride), Group 3 (MB-PS+ Diode Activation), Group 4 (Argon laser), and Group 5 (photopolymerized resin infiltration). Five samples from each group underwent MH assessment and EDX evaluation for Ca/P ratio. 15 samples per group were bonded with orthodontic brackets and thermocycled. Enamel orthodontic bracket interface assessment was performed using scanning electron microscope(n = 5). SBS testing was executed using universal testing machine(n = 10). Debonded samples were examined according to Adhesive Remnant Index. ANOVA and post hoc Tukey were utilized for intergroup comparisons (p < 0.05). RESULTS: Group 5- photopolymerized resin infiltration-treated groups presented the highest MH scores (273.45 ± 35.26) and maximum SBS (9.52 ± 0.92 MP). Whereas Group 3 (MB-PS-Diode Activation) displayed the lowest outcomes of MH (135.31 ± 32.11) and minimum bond integrity (5.23 ± 0.71 MPa). In terms of MH scores and SBS, the Argon laser was comparable to resin infiltration (p > 0.05). CONCLUSION: Both modalities, photopolymerized resin infiltration and argon laser, can be recommended as effective prophylactic regimens before bonding orthodontic brackets to demineralized enamel.
Subcellular proteomics of the protist Paradiplonema papillatum reveals the digestive capacity of the cell membrane and the plasticity of peroxisomes across euglenozoans.
Hammond MJ, Iorillo O, Faktorová D … +6 more , Svobodová M, Akiyoshi B, Licknack T, Poh YP, Lukeš J, Wideman JG
PLoS Biol · 2025 Dec · PMID 41336180 · Full text
Diplonemids are among the most diverse and abundant protists in the deep ocean, have extremely complex and ancient cellular systems, and exhibit unique metabolic capacities. Despite this, we know very little about this m...
Diplonemids are among the most diverse and abundant protists in the deep ocean, have extremely complex and ancient cellular systems, and exhibit unique metabolic capacities. Despite this, we know very little about this major group of eukaryotes. To establish a model organism for comprehensive investigation, we performed subcellular proteomics on Paradiplonema papillatum and localized 4,870 proteins to 22 cellular compartments. We additionally confirmed the predicted location of several proteins by epitope tagging and fluorescence microscopy. To probe the metabolic capacities of P. papillatum, we explored the proteins predicted to the cell membrane compartment in our subcellular proteomics dataset. Our data revealed an accumulation of many carbohydrate-degrading enzymes (CDZymes). Our predictions suggest that these CDZymes are exposed to the extracellular space, supporting proposals that diplonemids may specialize in breaking down carbohydrates in plant and algal cell walls. Further exploration of carbohydrate metabolism revealed an evolutionary divergence in the function of glycosomes (modified peroxisomes) in diplonemids versus kinetoplastids. Our subcellular proteome provides a resource for future investigations into the unique cell biology of diplonemids.
Photodynamic ablation of floating lung cancer cells using PVA and TPGS emulsified PLGA nanoparticles loaded with pyropheophorbide-a.
Pramual S, Arnoux P, Lirdprapamongkol K … +4 more , Frochot C, Jouan-Hureaux V, Barberi-Heyob M, Svasti J
J Photochem Photobiol B · 2026 Jan · PMID 41330308 · Publisher ↗
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 cel...
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.
Analysis of ROS dynamics based on dissolved oxygen sensing in upconversion nanoparticle-based photodynamic therapy.
Heydari E, Delavari S, Jafarpour M … +6 more , Hajisharifi K, Moeini M, Erdem A, Zare-Behtash H, Razzaghi M, Bai G
J Photochem Photobiol B · 2026 Jan · PMID 41330307 · Publisher ↗
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 up...
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 NaYF:Yb,Tm 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), and time to reach the maximum PL lifetime change τ 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 NaYF:Yb,Tm 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.
Polar cell membrane nanotubes containing microtubules and acidic vesicles render Drosophila eggs fertile.
Acharjee S, Saha B, Kumari N … +4 more , Nandi J, Adhya S, Karmakar PP, Prasad M
PLoS Biol · 2025 Dec · PMID 41329774 · Full text
Membrane nanotubes serve as critical cytoskeletal structures that facilitate intercellular communication and signal transmission across distances in both plants and animals. Here, we report the role of microtubule (MT) n...
Membrane nanotubes serve as critical cytoskeletal structures that facilitate intercellular communication and signal transmission across distances in both plants and animals. Here, we report the role of microtubule (MT) nanotubes in rendering the Drosophila micropyle functional, a structure essential for sperm entry during fertilization. Our study highlights that MT-nanotubes emanate from the apical end of the specialized epithelial cells called the polar cells in late oogenesis, forming a narrow channel through the eggshell. Utilizing a combination of fly genetics, live cell imaging, and tissue immunochemistry, our research elucidates the structural and functional characteristics of the polar cell nanotube. We show that tubulin is vital for the formation of these nanotubes, which are enriched in the lateral membrane marker, Fasciclin III. Moreover, the overall polarity of the migrating border cell cluster is critical for the successful development of the micropyle. Notably, both lysosomal function and lysosomal trafficking within the polar cells are essential for the opening of the vitelline layer, further facilitating the micropyle's role in fertilization.
Three-dimensional genome architecture connects chromatin structure and function in a major wheat pathogen.
Glavincheska I, Lorrain C
BMC Biol · 2025 Nov · PMID 41316293 · Full text
BACKGROUND: Genome spatial organization plays a fundamental role in biological function across all domains of life. While the principles of nuclear architecture have been well-characterized in animals and plants, their f...
BACKGROUND: Genome spatial organization plays a fundamental role in biological function across all domains of life. While the principles of nuclear architecture have been well-characterized in animals and plants, their functional relevance in filamentous fungi remains largely uncharacterized. The wheat pathogen Zymoseptoria tritici presents a unique model for genome evolution, with a compartmentalized genome comprising conserved core and highly variable accessory chromosomes linked to genome plasticity. Here, we present the first 3D genome analysis of a eukaryotic organism with an extensive set of accessory chromosomes, revealing a hierarchical genome architecture integrating core and accessory regions. RESULTS: At the nuclear level, centromere clustering defines the global genome conformation. Accessory chromosomes are spatially segregated from core arms but maintain focal contacts with pericentromeric regions of core chromosomes, contributing to mitotic stability. At finer resolution, we identify homotypic interactions among heterochromatin-rich compartments and self-interacting domains demarcated by specific histone marks, gene expression profiles, and insulator-like sequence motifs. Notably, a subset of highly insulated, transposon-rich heterochromatic domains forms strong inter-domain interactions. Additionally, domains defined under axenic conditions with coordinated transcriptional activation during wheat infection suggest a link between 3D architecture and dynamic gene regulation. CONCLUSIONS: Our study uncovers the multi-scale principles of nuclear organization in a major fungal plant pathogen and reveals how hierarchical nuclear architecture contributes to gene expression coordination and genome stability. These findings establish a conceptual framework for investigating 3D genome function and chromatin-mediated regulation in filamentous fungi and other eukaryotic microbes.
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