Journal of photochemistry and photobiology. B, Biology最新文献

Exploring antioxidant potential of flavonoid derivatives after ESIPT process provides a theoretical basis for discovering compounds with higher antioxidant capacity. In this work, employing the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods, the antioxidant potential of two citrus-derived naringenin flavonoids after ESIPT process is explored. Based on studies of ESIPT process including IMHB intensity variations, potential energy curves, and transition state, these molecules exist only in enol and keto^⁎ forms due to ultra-fast ESIPT. The HOMOs are utilized to explore electron-donating capacity, demonstrating that the molecules in keto^⁎ form is stronger than that in enol form. Furthermore, the atomic dipole moment corrected Hirshfeld population (ADCH) and Fukui functions indicate that the sites attacked by the electrophilic free radical of the two molecules in the keto^⁎ form are O₃ and O_5’ respectively, and both are more active than in the enol form. Overall, a comprehensive consideration of the ESIPT process and antioxidant potential of flavonoid derivatives will facilitate the exploration and design of substances with higher antioxidant capacity.

Depression, a multifactorial mental disorder, characterized by cognitive slowing, anxiety, and impaired cognitive function, imposes a significant burden on public health. Photobiomodulation (PBM), involving exposure to sunlight or artificial light at a specific intensity and wavelength for a determined duration, influences brain activity, functional connectivity, and plasticity. It is recognized for its therapeutic efficacy in treating depression, yet its molecular and cellular underpinnings remain obscure. Here, we investigated the impact of PBM with 468 nm light on depression-like behavior and neuronal damage in the chronic unpredictable mild stress (CUMS) murine model, a commonly employed animal model for studying depression. Our results demonstrate that PBM treatment ameliorated behavioral deficits, inhibited neuroinflammation and apoptosis, and notably rejuvenates the hippocampal synaptic function in depressed mice, which may be mainly attributed to the up-regulation of brain-derived neurotrophic factor signaling pathways. In addition, in vitro experiments with a corticosterone-induced hippocampal neuron injury model demonstrate reduced oxidative stress and improved mitochondrial function, further validating the therapeutic potential of PBM. In summary, these findings suggest PBM as a promising, non-invasive treatment for depression, offering insights into its biological mechanisms and potential for clinical application.

Endogenous hypochlorous acid (HOCl) is one of the most important reactive oxygen species (ROS) and acts as a distinct biomarker that is involved in various inflammatory responses including rheumatoid arthritis (RA). Therefore, it's crucial to develop an efficient method for the tracking and analysis of HOCl levels in vivo. Natural products continue to be compounds of interest, because they not only offer diverse and specific molecular scaffolds but also provide invaluable sources for new drug discovery. Herein, we firstly demonstrated harmaline (HML), a natural alkaloid mainly found in Peganum harmala L, could be acted as a novel fluorescent probe for HOCl with exceptional precision and responsiveness. Remarkably, this probe not only specifically tracked HOCl levels in cells and inflammatory RA mouse models, but also exhibited effective anti-inflammatory effects on RAW264.7 cells and anti-proliferative effects on fibroblast-like synoviocytes. Furthermore, HML has the potential to alleviate LPS-induced inflammation by inhibiting the NF-κB signaling pathway. This study represents the first example of a natural product that can simultaneously act as a fluorescent probe for specific ROS and a promising therapeutic candidate for a specific disease, which will undoubtedly extend the application of fluorophore-rich natural products.

We investigated the deoxyribonucleic acid (DNA) damage induced by laser filamentation, which was generated by focusing femtosecond near-infrared Ti:Sapphire laser light in water at several repetition rates ranging from 1000 Hz to 10 Hz. Using plasmid DNA (pUC19), the single-strand break, double-strand break, nucleobase lesions, and the fragmented DNA were analyzed and quantified by agarose gel electrophoresis. Additionally, the H₂O₂ concentration after irradiation was determined. We observed that (1) the DNA damage per laser shot and (2) the enzyme-sensitive base lesions per total DNA damage decreased as the laser repetition rate increased. Furthermore, (3) extraordinarily short DNA fragments were likely to be produced, compared with those produced using X-rays, and (4) most OH radicals could be eliminated by recombination to generate H₂O₂, preventing them from damaging the DNA. The Monte-Carlo simulation of the strand break formation implies that the observed dependency of strand break efficiency on the laser repetition rate is mainly due to diffusion of DNA molecules. These findings quantitatively and qualitatively revealed that an intense laser pulse induces a specific DNA damage profile that is not induced by X-rays, a sparsely ionizing radiation source.

Introduction

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis. Photobiomodulation (PBM) has been utilized in experimental models of cardiac hypoxia to enhance mitochondrial response and ameliorate biochemical changes in injured tissue. However, the effects of PBM on cultured cardiomyocytes subjected to hypoxia/reoxygenation are not yet well established.

Method

H9C2 cardiomyocytes were exposed to hypoxia with concentrations of 300 μM CoCl₂ for 24 h, followed by 16 h of reoxygenation through incubation in a normoxic medium. Treatment was conducted using GaAIAs Laser (850 nm) after hypoxia at an intensity of 1 J/cm². Cells were divided into three groups: Group CT (cells maintained under normoxic conditions), Group HR (cells maintained in hypoxia and reoxygenation conditions without treatment), Group HR + PBM (cells maintained in hypoxia and reoxygenation conditions that underwent PBM treatment). Cell viability was analyzed using MTT, and protein expression was assessed by western blot. One-way ANOVA with the Tukey post hoc test was used for data analysis. Differences were significant when p < 0.05.

Results

PBM at an intensity of 1 J/cm² mitigated the alterations in cell survival caused by hypoxia/reoxygenation. Additionally, it significantly increased the expression of proteins Nrf2, HSP70, mTOR, LC3II, LC3II/I, and Caspase-9, while reducing the expression of PGC-1α, SOD2, xanthine oxidase, Beclin-1, LC3I, and Bax.

Conclusion

PBM at intensities of 1 J/cm² reverses the changes related to oxidative stress, mitochondrial biogenesis, autophagy, and apoptosis caused by hypoxia and reoxygenation in a culture of cardiomyocytes.

To increase the therapeutic efficacy of nanoparticle (NP)-assisted photothermal therapy (PTT) and allow for a transition toward the clinical setting, it is pivotal to characterize the thermal effect induced in cancer cells and correlate it with the cell biological response, namely cell viability and cell death pathways. This study quantitatively evaluated the effects of gold nanorod (GNR)-assisted near-infrared (NIR) PTT on two different cancer cell lines, the 4T1 triple-negative breast cancer cells and the Pan02 pancreatic cancer cells. The interaction between nanomaterials and biological matrices was investigated in terms of GNR internalization and effect on cell viability at different GNR concentrations. GNR-mediated PTT was executed on both cell lines, at the same treatment settings to allow a straightforward comparison, and real-time monitored through thermographic imaging. A thermal analysis based on various parameters (i.e., maximum absolute temperature, maximum temperature change, temperature variation profile, area under the time-temperature change curve, effective thermal enhancement (ETE), and time constants) was performed to evaluate the treatment thermal outcome. While GNR treatment and NIR laser irradiation alone did not cause cell toxicity in the selected settings, their combination induced a significant reduction of cell viability in both cell lines. At the optimal experimental condition (i.e., 6 μg/mL of GNRs and 4.5 W/cm² laser power density), GNR-assisted PTT reduced the cell viability of 4T1 and Pan02 cells by 94% and 87% and it was associated with maximum temperature changes of 25 °C and 29 °C (i.e., ∼1.8-fold increase compared to the laser-only condition), maximum absolute temperatures of 55 °C and 54 °C, and ETE values of 78% and 81%, for 4T1 and Pan02 cells, correspondingly. Also, the increase in the GNR concentration led to a decrease in the time constants, denoting faster heating kinetics upon irradiation. Furthermore, the thermal analysis parameters were correlated with the extent of cell death. Twelve hours after NIR exposure, GNR-assisted PTT was found to mainly trigger secondary apoptosis in both cell lines. The proposed study provides relevant insights into the relationship between temperature history and biological responses in the context of PTT. The findings contribute to the development of a universal methodology for evaluating thermal sensitivity upon NP-assisted PTT on different cell types and lay the groundwork for future translational studies.

Photobiomodulation (PBM) has widely been used to effectively treat complications associated with cancer treatment, including oral mucositis, radiation dermatitis, and surgical wounds. However, the safety of PBM against cancer still needs to be validated as the effects of PBM on cancer cells and their mechanisms are unclear. The current study investigated the wavelength-dependent PBM effects by examining four different laser wavelengths (405, 532, 635, and 808 nm) on B16F10 melanoma tumor cells. In vitro tests showed that PBM with 808 nm promoted both proliferation and migration of B16F10 cells. In vivo results demonstrated that PBM with 808 nm significantly increased the relative tumor volume and promoted angiogenesis with overexpression of VEGF and HIF-1α. In addition, PBM induced the phosphorylation of factors closely related to cancer cell proliferation and tumor growth and upregulated the related gene expression. The current result showed that compared to the other wavelengths, 808 nm yielded a significant tumor-stimulating effect the malignant melanoma cancer. Further studies will investigate the in-depth molecular mechanism of PBM on tumor stimulation in order to warrant the safety of PBM for clinical cancer treatment.

Ribociclib (RIB), a tyrosine kinase inhibitor, exhibits promising antitumor efficacy and controlled toxicity in HR+/HER2- breast cancer patients, which is closely related to the binding with plasma proteins. This study utilized a combination of spectroscopic techniques including UV spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) as well as molecular docking and molecular dynamic simulation to clarify the binding mechanism between bovine serum albumin (BSA) and RIB. The findings demonstrated that RIB produced a 1:1 stoichiometric complex with BSA, which quenched BSA's fluorescence in the manner of the static quenching mechanism. Site labelling experiments pinpointed Site III on BSA as the primary binding site for RIB, a finding validated by molecular docking. Van der Waals forces and hydrogen bonding interactions as key drivers in the formation of RIB-BSA complexes, a conclusion supported by molecular docking. Molecular simulation studies suggested that the insertion of RIB into the hydrophobic cavity (Site III) of BSA induced subtle conformational changes in the BSA protein, and CD measurements confirmed alterations in BSA secondary structure content. Synchronous and three-dimensional fluorescence spectroscopy further demonstrated that RIB decreased the hydrophobicity of the microenvironment surrounding tyrosine and tryptophan residues. These findings offer valuable insights into the pharmacokinetics and structural modifications of RIB.

Exposure to ultraviolet B (UVB) radiation represents a significant environmental threat to human skin. This study investigates the protective mechanism of Artemisia Capillaris Thunb. (AC) extract against UVB-induced apoptosis and inflammation in HaCaT keratinocytes. AC extract demonstrated a significant protective effect, as evidenced by reduced early apoptosis, late apoptosis, and necrosis, as well as decreased apoptotic cell status upon UVB exposure. Additionally, AC extract effectively inhibited UVB-induced DNA damage, as indicated by diminished γ-H2AX foci formation. Restoration of mitochondrial damage and normalization of mitochondrial membrane potential, along with the reduction of intracellular and mitochondrial reactive oxygen species (ROS) levels, were observed with AC extract pre-treatment. The extract also exhibited anti-inflammatory properties, evidenced by the decreased release of IL-1α, IL-6, and PGE2 from keratinocytes. Additional research on the molecular mechanisms uncovered that the AC extract alters the cGAS/STING pathway, suppressing the mRNA (cGAS, STING, IRF3, IRF7 and TBK1) and protein levels (cGAS, STING, IRF3, IRF7 and NF-κB) linked to this particular pathway. The HPLC analysis identified chlorogenic acid and its derivatives as the major components in AC, constituting up to 16.44% of the total chlorogenic acid content. The cGAS/STING signaling pathway was found to be suppressed by chlorogenic acid and its derivatives, as indicated by molecular docking studies and RT-qPCR analysis. This suppression contributes to the protective effects against cell apoptosis and inflammation induced by UVB. To summarize, AC extract, which is abundant in chlorogenic acid and its derivatives, shows potential in protecting keratinocytes from damage caused by UVB by regulating the cGAS/STING signaling pathway.

Mitochondria, central organelles pivotal for eukaryotic cell function, extend their influence beyond ATP production, encompassing roles in apoptosis, calcium signaling, and biosynthesis. Recent studies spotlight two emerging determinants of mitochondrial functionality: intramitochondrial viscosity and sulfur dioxide (SO₂) levels. While optimal mitochondrial viscosity governs molecular diffusion and vital processes like oxidative phosphorylation, aberrations are linked with neurodegenerative conditions, diabetes, and cancer. Similarly, SO₂, a gaseous signaling molecule, modulates energy pathways and oxidative stress responses; however, imbalances lead to cytotoxic sulfite and bisulfite accumulation, triggering disorders such as cancer and cardiovascular anomalies. Our research focused on development of a dual-channel fluorescent probe, applying electron-withdrawing acceptors within a coumarin dye matrix, facilitating monitoring of mitochondrial viscosity and SO₂ in live cells. This probe distinguishes fluorescence peaks at 650 nm and 558 nm, allowing ratiometric quantification of SO₂ without interference from other sulfur species. Moreover, it enables near-infrared viscosity determination, particularly within mitochondria. The investigation employed theoretical calculations utilizing Density Functional Theory (DFT) methods to ascertain molecular geometries and calculate rotational energies. Notably, the indolium segment of the probe exhibited the lowest rotational energy, quantified at 7.38 kcals/mol. The probe featured heightened mitochondrial viscosity dynamics when contained within HeLa cells subjected to agents like nystatin, monensin, and bacterial lipopolysaccharide (LPS). Overall, our innovative methodology elucidates intricate mitochondrial factors, presenting transformative insights into cellular energetics, redox homeostasis, and therapeutic avenues for mitochondrial-related disorders.