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The study aimed to explore the role and mechanism of unfolded protein response (UPR) in methylmercury (MeHg)-induced Mouse Spermatocytes (GC-2spd[ts]) apoptosis. Methods such as MTT, flow cytometry, and Western Blot were used to evaluate the cell viability, membrane potential (MMP), reactive oxygen species (ROS), calcium ion (Ca2+ ), rate of cell apoptosis, and the expression of apoptosis-related and UPR-related protein. The results showed that with the increase of MeHg concentration, cell viability and MMP decreased, ROS, Ca2+ , rate of cell apoptosis, and the expression of apoptosis-related protein and UPR-related protein increased. To further explore the effect of ROS-induced oxidative damage on it, the ROS inhibitor N-acetyl-L-cysteine (NAC) was used. The effects of MeHg on germ cell (GC-2) cells were partially inhibited after NAC pretreatment. Our present study proved that MeHg might induce cell apoptosis by activating the UPR signaling pathway in GC-2 cells and affect normal reproductive function.
Asunto(s)
Compuestos de Metilmercurio , Espermatocitos , Masculino , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Espermatocitos/metabolismo , Compuestos de Metilmercurio/toxicidad , Estrés Oxidativo , Apoptosis , Respuesta de Proteína Desplegada , Transducción de SeñalRESUMEN
Methylmercury (MeHg) is an environmental neurotoxic substance, which can easily cross the blood-brain barrier, causing irreversible damage to the human central nervous system. Reactive oxygen species (ROS) are involved in various ways of intracellular physiological or pathological processes including neuronal apoptosis. This study attempted to explore the role of ROS-mediated poly ADP-ribose polymerase (PARP)/apoptosis-inducing factor (AIF) apoptosis signaling pathway in the process of MeHg-induced cell death of human neuroblastoma cells (SH-SY5Y). Here, we found that SH-SY5Y cells underwent apoptosis in response to MeHg, which was accompanied by the increased levels of ROS and calcium ion, and the activation of caspase cascades and PARP. Inhibiting the production of ROS can reduce the apoptosis rate to a certain extent. PARP/AIF apoptotic pathway is independent of caspase dependent signaling pathway and regulates it. In conclusion, these results suggest that ROS mediated activation of caspase pathway and PARP/AIF signaling pathway are involved in MeHg induced apoptosis, and these two pathways interact with each other.
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Compuestos de Metilmercurio , Neuroblastoma , Adenosina Difosfato Ribosa/farmacología , Apoptosis , Factor Inductor de la Apoptosis/metabolismo , Factor Inductor de la Apoptosis/farmacología , Caspasas/metabolismo , Humanos , Compuestos de Metilmercurio/toxicidad , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The application of silica nanoparticles (SiNPs) in areas of agriculture and medicine has raised great concerns for the potential adverse effects of SiNPs. The increasing toxicological studies focused mainly on the lung and cardiovascular system, but the adverse effects of SiNPs on nervous system have not been well explored. This study aimed to evaluate the role and mechanism of unfolded protein reaction (UPR) in SiNPs-induced cell injury on nerve cells in vitro. We investigated the UPR-mediated apoptosis caused by SiNPs in human neuroblastoma (SH-SY5Y) cell line. The size of SiNPs and its effect on cell ultrastructure were observed by transmission electron microscopy (TEM). Cell growth, mitochondrial membrane potential (MMP), calcium ion (Ca2+ ), apoptosis rate, and the expression level of related proteins were evaluated using MTT, flow cytometry, and western blot in SH-SY5Y cells exposed to SiNPs. The results showed that with the increase of SiNPs concentration, cell viability decreased, MMP decreased, active oxygen (ROS), and Ca2+ levels increased in a dose-dependent manner. In addition, protein expression of PERK, GRP78, and other related proteins in the unfolded protein response increased in a dose-response manner together with the expression of apoptosis proteins. Conclusively, this study confirmed that SiNPs can affect the neural system by interfering structure and functional and inducing apoptosis in nerve cells through unfolded protein response.
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Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Nanopartículas/toxicidad , Dióxido de Silicio/toxicidad , Respuesta de Proteína Desplegada/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Electrónica de Transmisión , Mitocondrias/metabolismo , Nanopartículas/química , Neuroblastoma/metabolismo , Neuroblastoma/patología , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/químicaRESUMEN
Organic mechanoluminescence materials, featuring dual emission and ultralong phosphorescence characteristics, exhibit significant potential for applications in real-time stress sensing, pressure-sensitive lighting, advanced security marking techniques, and material breakage monitoring. However, due to immature molecular design strategies and unclear luminescence mechanisms, these materials remain rarely reported. In this study, we propose a valuable molecular design strategy to achieve dual-channel mechano-phosphorescence. By introducing the arylphosphine oxide group into a highly twisted molecular framework, enhanced intra- and intermolecular interactions could be achieved within rigid structures, leading to dual-channel mechanoluminescence with greatly promoted ultralong phosphorescence. Further investigations reveal the substantial boosting effect of intra- and intermolecular interactions on mechanoluminescence and ultralong phosphorescence properties by locking the highly twisted molecular skeleton. This work provides a concise and guiding route to develop novel smart responsive luminescence materials for widespread applications in material science.
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BACKGROUND: Acne vulgaris (AV) is a common adolescent skin condition which is mainly caused by Cutibacterium acnes overcolonization and subsequent inflammation. OBJECTIVE: Our previous studies demonstrated that ethanol extracts of Meconopsis quintuplinervia Regel (EMQ) possess significant antimicrobial properties. However, their protective effects and potential mechanisms against AV remain unclear. METHODS: In the present study, the EMQ treatment potential for AV was evaluated in a C. acnes-induced mouse ear edema model, and the EMQ anti-inflammatory mechanism was evaluated in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. RESULTS: The results showed that EMQ alleviated edema formation and inflammatory cell infiltration in an acne mouse model by suppressing inflammatory cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor α expression. Moreover, EMQ inhibited the phosphorylation of MAP kinases (MAPKs) such as p38, JNK, and ERK, the phosphorylation and degradation of IκB-α and the nuclear translocation of nuclear factor kappa B (NF-κB) p65 in LPS-induced RAW264.7 cells. CONCLUSION: These findings suggest the potent anti-inflammatory activity of EMQ is possibly through the regulation of the MAPKs and NF-κB signaling pathways. Inhibition of C. acnes activity combined with a powerful anti-inflammatory effect of EMQ indicated its potential as a novel therapeutic option for AV.
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Organic mechanoluminescent (ML) materials possessing photophysical properties that are sensitive to multiple external stimuli have shown great potential in many fields, including optic and sensing. Particularly, the photoswitchable ML property for these materials is fundamental to their applications but remains a formidable challenge. Herein, photoswitchable ML is successfully realized by endowing reversible photochromic properties to an ML molecule, namely 2-(1,2,2-triphenylvinyl) fluoropyridine (o-TPF). o-TPF shows both high-contrast photochromism with a distinct color change from white to purplish red, as well as bright blue ML (λML = 453 nm). The ML property can be repeatedly switched between ON and OFF states under alternate UV and visible light irradiation. Impressively, the photoswitchable ML is of high stability and repeatability. The ML can be reversibly switched on and off by conducting alternate UV and visible light irradiation in cycles under ambient conditions. Experimental results and theoretical calculations reveal that the change of dipole moment of o-TPF during the photochromic process is responsible for the photoswitchable ML. These results outline a fundamental strategy to achieve for the control of organic ML and pave the way to the development of expanded smart luminescent materials and their applications.
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Photoresponsive materials have been widely used in sensing, bioimaging, molecular switches, information storage, and encryption nowadays. Although a large amount of photoresponsive materials have been reported, the construction of these smart materials into precisely prescribed complex 3D geometries is rarely studied. Here we designed a novel photoresponsive material methyl methacrylate containing triphenylethylene (TrPEF2-MA) that can be directly used for digital light processing (DLP) 3D printing. Based on TrPEF2-MA, a series of photoresponsive 3D structures with reversible color switching under ultraviolet/visible light irradiations were fabricated. These complex photoresponsive 3D structures show high resolutions (50 µm), excellent repeatability (25 cycles without fatigue), and tunable saturate color degrees. Multicomponent DLP 3D printing processes were also carried out to demonstrate their great properties in information hiding and information-carrying properties. This design strategy for constructing photoresponsive 3D structures is attractive in the area of adaptive camouflage, information hiding, information storage, and flexible electronics.
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In this work, a new series of 2-hydroxybenzophenone (BPOH) derivatives, BPOH-TPA, BPOH-PhCz, and BPOH-SF substituting with different electron-donating groups are designed and synthesized. Dual-emission spectra are observed in solutions indicating their excited-state intramolecular proton transfer (ESIPT) character. In solid states, all compounds exhibit a broad emission spectrum when excited at low excitation energy, deriving from the enol-type form stabilized by intramolecular hydrogen bonds. Compound BPOH-TPA shows a clear excitation wavelength dependence. However, such behavior is absent in BPOH-PhCz and BPOH-SF, as the rigid and weaker donor moieties may restrict this process. Furthermore, by increasing the excitation energy, dual emission with a high-energy band ranging from 550 to 582 nm and a low-energy band ranging from 625 to 638 nm is obtained in all three molecules. The photophysical studies and single-crystal analyses are performed to further illustrate the excitation-dependent emission. Higher excitation energies can promote more excitons to keto forms via ESIPT, giving a stronger redshifted emission. BPOH-TPA with a stronger donor strength exhibits an obvious color change gradually from yellow to orange-red with the increasing excitation power from 1 to 15 mW/cm2. This study provides a novel example of ESIPT materials with tunable emission colors.
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The rational lifetime-tuning strategy of ultralong organic phosphorescence is extraordinarily important but seldom reported. Herein, a series of multi-host/guest ultralong organic phosphorescence materials with dynamic lifetime-tuning properties were reported. By doping a non-room-temperature phosphorescence emitter into various solid host matrices with continuously reduced triplet energy levels, a wide-range lifetime (from 3.9 ms gradually to 376.9 ms) phosphorescence with unchangeable afterglow colors were realized. Further studies revealed that the host matrices were employed to afford rigid environment and proper energy levels to generate and stabilize the long-live triplet excitons. Meanwhile, these multi-host/guest ultralong organic phosphorescence materials also exhibited excitation-dependent phosphorescence and temperature-controlled afterglow on/off switching properties, according to the virtue of various photophysical and thermal properties of the host matrices. This work provides a guiding strategy to realize lifetime-tuning ultralong organic phosphorescence with lifetime-order encoding characteristic towards widespread applications in time-resolved information displaying, higher-level security protection, and dynamic multi-dimensional anti-counterfeiting.