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Polychlorinated diphenyl ethers (PCDEs) are detected in aquatic environments and demonstrate adverse effects in aquatic organisms. However, data regarding the environmental behavior of PCDEs in aquatic ecosystems are lacking. In the present study, a simulated aquatic food chain (Scenedesmus obliquus-Daphnia magna-Danio rerio) was constructed in a lab setting, and the bioaccumulation, trophic transfer, and biotransformation of 12 PCDE congeners were quantitatively investigated for the first time. The log-transformed bioaccumulation factors (BCFs) of PCDEs in S. obliquus, D. magna, and D. rerio were in the range of 2.94-3.77, 3.29-4.03, and 2.42-2.89 L/kg w.w., respectively, indicating the species-specific bioaccumulation of PCDE congeners. The BCF values increased significantly with the increasing number of substituted Cl atoms, with the exception of CDE 209. The number of Cl atoms at the para and meta positions were found to be the major positive contributing factors for BCFs in the case of the same number of substituted Cl. The lipid-normalized biomagnification factors (BMFs) of S. obliquus to D. magna, D. magna to D. rerio, and the whole food chain for the 12 PCDE congeners ranged at 1.08-2.27, 0.81-1.64, and 0.88-3.64, respectively, suggesting that some congeners had BMFs comparable to PBDEs and PCBs. Dechlorination was the only metabolic pathway observed for S. obliquus and D. magna. For D. rerio, dechlorination, methoxylation, and hydroxylation metabolic pathways were observed. 1H nuclear magnetic resonance (NMR) experiments and theoretical calculations confirmed that methoxylation and hydroxylation occurred at the ortho position of the benzene rings. In addition, reliable quantitative structure-property relationship (QSPR) models were constructed to qualitatively describe the relationships between molecular structure descriptors and BCFs for PCDEs. These findings provide insights into the movement and transformation of PCDEs in aquatic ecosystems.
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Éteres Difenilos Halogenados , Contaminantes Químicos del Agua , Animales , Éteres Difenilos Halogenados/química , Cadena Alimentaria , Bioacumulación , Ecosistema , Pez Cebra , Biotransformación , Contaminantes Químicos del Agua/metabolismoRESUMEN
OBJECTIVE: To elucidate the role of preoperative serum bilirubin and sodium levels, along with the duration of surgery, in predicting postoperative gastrointestinal dysfunction (POGD) following gynecological cancer surgery, informing tailored perioperative strategies. METHODS: We conducted a retrospective analysis of 281 patients undergoing gynecological cancer surgery between 2018 and 2023. This analysis focused on preoperative serum bilirubin and sodium levels and intraoperative factors (surgical duration) as potential predictors of POGD. Logistic regression models were utilized for analysis, controlling for relevant confounders. RESULTS: Elevated preoperative serum bilirubin was associated with a reduced risk of POGD (mean level in non-POGD cases: 14.172 ± 4.0701, vs. POGD cases: 9.6429 ± 3.5351; p < 0.001), suggesting a protective role. Lower preoperative sodium levels were identified in the POGD group (136.26 mEq/L [IQR: 135.2-137.63]) compared to the non-POGD group (139.32 mEq/L [IQR: 137.7-140.75]; p < 0.001), highlighting its predictive value. Additionally, longer surgical duration was associated with increased POGD incidence, with POGD cases experiencing surgeries lasting 6.1547 ± 1.9426 hours compared to 4.5959 ± 1.5475 hours in non-POGD cases (p < 0.001). CONCLUSION: Our findings underscore the importance of serum bilirubin, sodium levels, and surgical duration as significant predictors of POGD in patients undergoing gynecological cancer surgery. These indicators should be integrated into a predictive model, aiding clinicians in identifying high-risk patients, allowing for personalized perioperative care adjustments, potentially mitigating POGD risks.
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Enfermedades Gastrointestinales , Neoplasias , Humanos , Estudios Retrospectivos , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Bilirrubina , SodioRESUMEN
Formation of protein-polymer conjugates (PPCs) is critical for many studies in chemical biology, biomedicine, and enzymatic catalysis. Polymers with coordinated physicochemical properties confer synergistic functions to PPCs that overcome the inherent limitation of proteins. However, application of PPCs has been synthetically restricted by the limited modification sites and polymer grafting method. Here, we present a versatile strategy for site-selective PPC synthesis. The initiator was specifically tethered to the preoxidized glycan moieties through oxime chemistry. Polymer brushes were grown in situ from the glycan by atom-transfer radical polymerization to generate well-controlled PPCs. Notably, the modification is site-specific, multivalent, and alterable depending on protein glycosylation. Additionally, we demonstrated that the cytocompatible method enabled the growth of polymer chains from the surface of living yeast cells. These results verified a facile technology for surface modification of biomacromolecules by desired polymers for various biomedical applications.
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Polímeros , Polisacáridos , Glicoproteínas , Polimerizacion , Propiedades de SuperficieRESUMEN
A recoverable and thermoresponsive polymer-protein bioconjugate is synthesized and employed in the purification of protein with free sulfhydryl groups. Initiator with disulphide was modified on the cysteine residue of the target protein. Poly(N-isopropylacrylamide) exhibiting a lower critical solution temperature was grown from the protein. The resulting protein-polymer conjugate was successfully thermoprecipitated and separated from other proteins. The approach was demonstrated with bovine serum albumin with the recycling yield of 76.4%. Enzyme activity test with papain verified the reversible polymer modification protected protein under extreme environments without affecting the functionality of the protein. This study implies the favorable potential of chemo-selective enriching and purification of proteins.
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Precipitación Química , Polímeros/química , Proteínas/aislamiento & purificación , Temperatura , Bromelaínas/metabolismo , Electroforesis en Gel de Poliacrilamida , Papaína/metabolismoRESUMEN
The regional industry network (RIN) is a type of financial network derived from industry networks that possess the capability to describe the connections between specific industries within a particular region. For most investors and financial analysts lacking extensive experience, the decision-support information provided by industry networks may be too vague. Conversely, RINs express more detailed and specific industry connections both within and outside the region. As RIN analysis is domain-specific and current financial network analysis tools are designed for generalized analytical tasks and cannot be directly applied to RINs, new visual analysis approaches are needed to enhance information exploration efficiency. In this study, we collaborated with domain experts and proposed V4RIN, an interactive visualization analysis system that integrates predefined domain knowledge and data processing methods to support users in uploading custom data. Through multiple views in the system panel, users can comprehensively explore the structure, geographical distribution, and spatiotemporal variations of the RIN. Two case studies were conducted and a set of expert interviews with five domain experts to validate the usability and reliability of our system.
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Objective: The rise of online platforms like Douyin, Baidu, and other Chinese search engines has changed how gynecologic oncology patients seek information about their diagnosis or condition. This study aimed to investigate the factors associated with information seeking among these patients and to evaluate their predictive performance. Methods: A cross-sectional study was conducted among 199 gynecologic oncology patients at a single hospital in China. The patients' demographic characteristics and scores on the State-Trait Anxiety Inventory (STAI-S and STAI-T) and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) were compared between those who sought information online and those who did not. Logistic regression analyses and receiver operating characteristic (ROC) curve analyses were performed. Results: The patients' age, marital status, STAI-S scores, and HADS-A scores were significantly associated with online information seeking. The combined model that included these factors showed good predictive performance with an area under the ROC curve of 0.841. Conclusion: The combination of demographic and psychological factors can be used to predict the likelihood of gynecologic oncology patients seeking information online. These findings can help healthcare providers understand their patients' information-seeking behaviors and tailor their communication strategies accordingly.
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In view of the biological significance and micro-heterogeneity of protein glycosylation for human health, specific enrichment of N-glycosylated proteins/peptides from complex biological samples is a prerequisite for the discovery of disease biomarkers and clinical diagnosis. In this work, we propose a "grafting-from" N-glycoprotein enriching method based on the in-situ growth of thermoresponsive polymer brushes from the N-glycosylated site of proteins. The initiator was first attached to the pre-oxidized glycan moieties by hydrazide chemistry, from which the thermoresponsive polymers can be grown to form giant protein-polymer conjugates (PPC). The thermosensitive PPC can be precipitated and separated by raising the temperature to above its lower critical solubility temperature (LCST). Mass spectrometry verified 210 N-glycopeptides corresponding to 136 N-glycoproteins in the rabbit serum. These results demonstrate the capability of the tandem thermoprecipitation strategy to enrich and separate N-glycoprotein/glycopeptide. Due to its simplicity and efficiency specifically, this method holds the potential for identifying biomarkers from biological samples in N-glycoproteome analysis.
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Glicopéptidos , Polímeros , Humanos , Animales , Conejos , GlicoproteínasRESUMEN
[This corrects the article DOI: 10.3389/fphys.2022.907906.].
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Considering the frequent detection of polychlorinated dibenzothiophenes (PCDTs) in various environmental matrices and the potential ecological health risks, the environmental behavior of such compounds needs to be elucidated further. In this work, the sorption behavior of 2,3,7,8-tetrachlorodibenzothiophene (2,3,7,8-TCDT) onto three sediments and paddy soil from Chaohu Lake were investigated via batch equilibration experiments. From the perspective of sorption kinetics and isotherms, the sorption characteristics and mechanism of 2,3,7,8-TCDT on the above four carriers were compared, and the relationship between their structural characteristics and soil sorption capacity was discussed. Results suggested that rapid sorption played the primary role during the sorption process of 2,3,7,8-TCDT and the corresponding sorption isotherms were well fitted using the Freundlich logarithmic model. Moreover, the effects of pH and dissolved organic matter (DOM) on the sorption of 2,3,7,8-TCDT were investigated. The maximum sorption capacity of 2,3,7,8-TCDT on sediment was under acidic pH condition (pH = 4.0). Meanwhile, DOM at a low level promoted the sorption capacity of sediment toward 2,3,7,8-TCDT, while the high concentration of DOM inhibited this effect. In addition, the values of logKoc were obtained using high-performance liquid chromatography (HPLC) and did not show any significant correlation with organic carbon (OC) contents, thereby indicating that the partition effect was the dominating influencing factor for the sorption of 2,3,7,8-TCDT both on sediments and soil. This work provides useful data to understand the sorption behavior of 2,3,7,8-TCDT on sediments and soil and assess its potential environmental risk.
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Contaminantes del Suelo , Suelo , Adsorción , Carbono/química , Sedimentos Geológicos/química , Lagos , Suelo/química , Contaminantes del Suelo/análisisRESUMEN
Polychlorinated diphenyl ethers (PCDEs) have been detected in various aquatic matrices, which pose potential threats to aquatic ecosystem security. In this work, both micro and macro analysis methods were used to assess the toxicity of PCDEs to zebrafish. Results indicated that after in vivo PCDE exposure, the oxidative stress and related gene of Danio rerio were significantly changed. The higher concentration or longer exposure time could cause more severe oxidative stress in zebrafish tissues. Compared with among the five tested compounds, more obvious changes in the level of oxidative biomarkers of lower chlorinated PCDEs' (4-mono-CDE and 4,4'-di-CDE) exposure groups were observed. The integrated biomarker response analysis and gene expression results also indicate a similar trend. Histopathological observation suggested that 4,4'-di-CDE could render liver nuclei enlargement and necrosis, hepatocyte vacuolation, and the development inhibition of ovarian cells. Transmission electron microscope photos showed that 4,4'-di-CDE caused organelle damage in the liver and ovary, including the rupture of the endoplasmic reticulum, swelling of mitochondria, and condensation of chromatin in the liver and mitochondria disappeared significantly in the ovary. The degree of damage is enhanced with the increasing exposure doses. In addition, PCDEs also significantly altered vitellogenin content and related gene (vtg1) expression, suggesting that PCDEs may be estrogen endocrine disruptors. Overall, these results provided some valuable toxicological data of PCDEs on aquatic species.
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Polychlorinated diphenyl sulfides (PCDPSs) represent an emerging group of constituents that are persistent, bioaccumulative and toxic (PBT) substances of great concern in terms of human health and ecological integrity. However, little is known about the occurrence, environmental behaviour and ecological risks of PCDPSs in lake environments. In this study, the concentrations of 21 PCDPSs were determined in surface water, suspended particulate matter (SPM), sediments, and 8 fish species from Chaohu Lake, China. Eighteen PCDPS congeners were prevalently detected in the samples, with concentrations ranging from 0.272-1.69 ng/L (water), 0.477-2.03 ng/g d.w. (SPM), 0.719-4.07 ng/g d.w. (sediment) and 0-0.131 ng/g w.w. (fish), respectively. Medium- and high-chlorinated PCDPSs in SPM and sediment were significantly higher than those in water samples. Increased PCDPS concentrations were found in higher trophic level fishes and those with a demersal habitat preference, indicating their bioaccumulation and biomagnification potential. The logBCFs, BSSAFs, and BSAFs of PCDPS congeners in fishes were determined to be 3.91-5.18, 0.0500-2.33, and 0.0360-4.94 L/kg, respectively. The organic carbon normalized partition coefficients (logKoc) of PCDPSs in surface water-SPM (4.61-5.54 L/g) and surface water-sediment (4.38-5.69 L/g) systems were determined, and it was found that highly chlorinated PCDPSs were more prone to migrate from water to sediment and SPM. The toxic equivalent (TEQ) values of PCDPSs in the samples (lower than 10-1 pg/g or pg/L) and daily intake via fish consumption (0.180-0.340 µg/kg/day) were estimated for humans, and cumulative risk quotients (RQs) after correction at ten sampling sites (0.065-0.66) were calculated for green algae. The findings elucidated the environmental behaviour of PCDPSs in Chaohu Lake.
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Sedimentos Geológicos , Contaminantes Químicos del Agua , Animales , Bioacumulación , China , Monitoreo del Ambiente , Peces , Material Particulado , Sulfuros , Agua , Contaminantes Químicos del Agua/análisisRESUMEN
[This corrects the article DOI: 10.7150/thno.10853.].
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Sinoporphyrin sodium (DVDMS) is a newly identified photosensitizer that was isolated from Photofrin. Experimental and clinical results have demonstrated that repeated application of PDT greatly improved the therapeutic efficacy. Here, we comparatively studied two kinds of photodynamic therapy (PDT) strategies by using DVDMS (2mg/kg) in murine breast cancer 4T1 xenograft model to provide evidence which strategy exerts a better antitumor effect. Regimen (1): DVDMS was injected one time into tumor-bearing mice, which were then repeatedly exposed to 50J/cm(2) light 24h, 30h and 36h later. Regimen (2): DVDMS was injected 3 times and mice exposed to 50J/cm(2) light 24h after each injection, with 5days intervals between each DVDMS injection. On day 21 after the tumor cell injection, in regimen (1) the tumor volume inhibition ratio was reached to 85.75±7.60%. While at the same day the inhibition ratio was 65.74±8.64% of regimen (2). Additionally, regimen (1) appeared to more effectively initiate tumor tissue destruction and cancer cell apoptosis, inhibit lung metastasis, suppress cancer cell proliferation and angiogenesis. Moreover, no obvious effect on body weight and other side effects were observed in the treated mice. These results suggest that regimen (1) might be a potentially efficient strategy against breast cancer.
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Neoplasias de la Mama/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Inmunohistoquímica , Luz , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Microscopía Fluorescente , Neovascularización Patológica , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/toxicidad , Porfirinas/química , Porfirinas/toxicidad , Trasplante HomólogoRESUMEN
Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. Photosensitizers are critical components for PDT. Sinoporphyrin sodium, referred to as DVDMS, is a newly identified photosensitizer that was isolated from Photofrin. Here, we evaluated the effects of DVDMS-mediated PDT (DVDMS-PDT) on tumor cell proliferation and metastasis in the highly metastatic 4T1 cell line and a mouse xenograft model. DVDMS-PDT elicited a potent phototoxic effect in vitro, which was abolished using the reactive oxygen species (ROS) scavenger N-acetylcysteine. In addition, DVDMS-PDT effectively inhibited the migration of 4T1 cells in scratch wound-healing and transwell assays. Using an in vivo mouse model, DVDMS-PDT greatly prolonged the survival time of tumor-bearing mice and inhibited tumor growth and lung metastasis, consistent with in vitro findings. PDT with DVDMS had a greater anti-tumor efficacy than clinically used Photofrin. Moreover, preliminary toxicological results indicate that DVDMS is relatively safe. These results suggest that DVDMS is a promising sensitizer that warrants further development for use in cancer treatment with PDT or other sensitizing agent-based therapies.
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Neoplasias de la Mama/terapia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/efectos adversos , Porfirinas/efectos adversos , Animales , Línea Celular Tumoral , Femenino , Ratones , Ratones Endogámicos BALB C , Fotoquimioterapia/efectos adversos , Fármacos Fotosensibilizantes/química , Porfirinas/químicaRESUMEN
Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.
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Antineoplásicos/farmacología , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Terapia por Ultrasonido/métodos , Animales , Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Ratones , Ratones Endogámicos ICR , Células 3T3 NIH/efectos de los fármacos , Trasplante de Neoplasias , Neoplasias Experimentales/terapia , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/terapia , Fármacos Fotosensibilizantes/farmacocinética , Porfirinas/farmacocinética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Sono-Photodynamic therapy (SPDT), a new modality for cancer treatment, is aimed at enhancing anticancer effects by the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we investigated the antitumor effect and possible mechanisms of Chlorin e6 (Ce6) mediated SPDT (Ce6-SPDT) on breast cancer both in vitro and in vivo. MTT assay revealed that the combined therapy markedly enhanced cell viability loss of breast cancer cell lines (MDA-MB-231, MCF-7 and 4T1) compared with SDT and PDT alone. Propidium iodide/hoechst33342 double staining reflected that 4T1 cells with apoptotic morphological characteristics were significantly increased in groups given combined therapy. Besides, the combined therapy caused obvious mitochondrial membrane potential (MMP) loss at early 1 h post SPDT treatment. The generation of intracellular reactive oxygen species (ROS) detected by flow cytometry was greatly increased in 4T1 cells treated with the combination therapy, and the loss of cell viability and MMP could be effectively rescued by pre-treatment with the ROS scavenger N-acetylcysteine (NAC). Further, Ce6-SPDT markedly inhibited the tumor growth (volume and weight) and lung metastasis in 4T1 tumor-bearing mice, but had no effect on the body weight. Hematoxylin and eosin staining revealed obvious tissue destruction with large spaces in the Ce6-SPDT groups, and TUNEL staining indicated tumor cell apoptosis after treatment. Immunohistochemistry analysis showed that the expression level of VEGF and MMP were significantly decreased in the combined groups. These results indicated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, loss of MMP and generation of ROS might be involved. In addition, Ce6-mediated SPDT significantly inhibited tumor growth and metastasis in mouse breast cancer 4T1 xenograft model, in which MMP-9 and VEGF may play a crucial role.
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Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Fotoquimioterapia , Porfirinas/farmacología , Terapia por Ultrasonido , Animales , Transporte Biológico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Clorofilidas , Terapia Combinada , Femenino , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Espacio Intracelular/efectos de la radiación , Neoplasias Pulmonares/secundario , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/efectos de la radiación , Metástasis de la Neoplasia , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/farmacología , Porfirinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of this study was to evaluate the photodynamic effect of Sinoporphyrin sodium (DVDMS). In this study, Eca-109 cells were treated with DVDMS (5 µg mL(-1)) and subjected to photodynamic therapy (PDT). The uptake and subcellular localization of DVDMS were monitored by flow cytometry and confocal microscopy. The phototoxicity of DVDMS was studied by MTT assay. The morphological changes were observed by scanning electron microscopy (SEM). DNA damage, reactive oxygen species (ROS) generation and mitochondria membrane potential (MMP) changes were analyzed by flow cytometry. Studies demonstrated maximal uptake of DVDMS occurred within 3 h, with a mitochondrial subcellular localization. MTT assays displayed that DVDMS could be effectively activated by light and the phototoxicity was much higher than photofrin under the same conditions. In addition, SEM observation indicated that cells were seriously damaged after PDT treatment. Furthermore, activation of DVDMS resulted in significant increases in ROS production. The generated ROS played an important role in the phototoxicity of DVDMS. DVDMS-mediated PDT (DVDMS-PDT) also induced DNA damage and MMP loss. It is demonstrated that DVDMS-mediated PDT is an effective approach on cell proliferation inhibition of Eca-109 cells.