Evaluation of Ornidazole Tablets Bioequivalence in Chinese Healthy Participants Under Fasted and Fed Conditions Using Pharmacokinetic Parameters.

BACKGROUND AND OBJECTIVE: Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters. PATIENTS AND METHODS: Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (Cmax), time to Cmax (Tmax), the area under the curve (AUC) from t = 0 to infinity (AUC0-∞), AUC from t = 0 to the last quantifiable concentration (AUC0-t), half-life (t1/2), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure). RESULTS: For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (Cmax, AUC0-72, and AUC0-∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles. CONCLUSION: The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics. TRIAL REGISTRATION: CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023.

CRABR-Net: A Contextual Relational Attention-Based Recognition Network for Remote Sensing Scene Objective.

Remote sensing scene objective recognition (RSSOR) plays a serious application value in both military and civilian fields. Convolutional neural networks (CNNs) have greatly enhanced the improvement of intelligent objective recognition technology for remote sensing scenes, but most of the methods using CNN for high-resolution RSSOR either use only the feature map of the last layer or directly fuse the feature maps from various layers in the "summation" way, which not only ignores the favorable relationship information between adjacent layers but also leads to redundancy and loss of feature map, which hinders the improvement of recognition accuracy. In this study, a contextual, relational attention-based recognition network (CRABR-Net) was presented, which extracts different convolutional feature maps from CNN, focuses important feature content by using a simple, parameter-free attention module (SimAM), fuses the adjacent feature maps by using the complementary relationship feature map calculation, improves the feature learning ability by using the enhanced relationship feature map calculation, and finally uses the concatenated feature maps from different layers for RSSOR. Experimental results show that CRABR-Net exploits the relationship between the different CNN layers to improve recognition performance, achieves better results compared to several state-of-the-art algorithms, and the average accuracy on AID, UC-Merced, and RSSCN7 can be up to 96.46%, 99.20%, and 95.43% with generic training ratios.

Development and validation of prognostic nomograms based on De Ritis ratio and clinicopathological features for patients with stage II/III colorectal cancer.

BACKGROUND: Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility. METHODS: A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses. RESULTS: Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging. CONCLUSIONS: De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.

Prognostic scoring system based on eosinophil- and basophil-related markers for predicting the prognosis of patients with stage II and stage III colorectal cancer: a retrospective cohort study.

Background: Systemic inflammation is associated with the prognosis of colorectal cancer (CRC). The current study aimed to construct a comprehensively inflammatory prognostic scoring system named risk score (RS) based on eosinophil- and basophil-related markers and assess its prognostic value in patients with stage II and stage III CRC. Patients and methods: A total of 3,986 patients were enrolled from January 2007 to December 2013. The last follow-up time was January 2019. They were randomly assigned to the training set and testing set in a 3:2 split ratio. Least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to select the optimal prognostic factors in the construction of RS. The Kaplan-Meier curve, time-dependent receiver operating characteristic (ROC), and Cox analysis were used to evaluate the association between RS and overall survival (OS). Results: In the training set, all inflammatory markers showed certain prognostic values. Based on LASSO-Cox analysis, nine markers were integrated to construct RS. The Kaplan-Meier curve showed that a higher RS (RS > 0) had a significantly worse prognosis (log-rank p< 0.0001). RS (>0) remained an independent prognostic factor for OS (hazard ratio (HR): 1.70, 95% confidence interval (CI), 1.43-2.03, p< 0.001). The prognostic value of RS was validated in the entire cohort. Time-dependent ROC analysis showed that RS had a stable prognostic effect throughout the follow-up times and could enhance the prognostic ability of the stage by combination. Nomogram was established based on RS and clinicopathological factors for predicting OS in the training set and validated in the testing set. The area under the curve (AUC) values of the 3-year OS in the training and testing sets were 0.748 and 0.720, respectively. The nomogram had a satisfactory predictive accuracy and had better clinical application value than the tumor stage alone. Conclusions: RS might be an independent prognostic factor for OS in patients with stage II and III CRC, which is helpful for risk stratification of patients. Additionally, the nomogram might be used for personalized prediction and might contribute to formulating a better clinical treatment plan.

High dispersion dendritic fibrous morphology nanospheres for electrochemical CO2 reduction to C2H4.

The electrochemical CO2 reduction to specific multi-carbon product on copper-based catalysts is subjected to low activity and poor selectivity. Herein, catalyst structure, morphology, and chemical component are systematically studied for bolstering the activity and selectivity of as-prepared catalyzers in this study. Dendritic fibrous nano-silica spheres favor the loading of active species and the transport of reactant from the central radial channel. Cu/DFNS with high dispersion active sites are fabricated through urea-assisted precipitation way. The coexistence of Cu(I)/Cu(II) induces a close combination of Cu active sites and CO2 on the Cu/DFNS interface, promoting the CO2 activation and CC coupling. The Cu-O-Si interface (Cu phyllosilicate) can improve CO2 and CO attachment. Cu/DFNS show the utmost Faradaic efficiency of C2H4 with a value of 53.04% at -1.2 V vs. RHE. And more importantly, in-situ ATR-SEIRAS reveals that the CC coupling is boosted for effectively producing C2H4 as a consequence of the existence of *COL, *COOH, and *COH intermediates. The mechanism reaction path of Cu/DFNS is inferred to be *CO2 â†’ *COOH â†’ *CO â†’ *CO*COH â†’ C2H4. Our findings will be helpful to gain insight into the links between morphology, texture, chemical component of catalyzers, and electrochemical reduction of CO2, providing valuable guidance in the design of more efficient catalysts.

Decreased Serum Exosomal microRNA-134 Expression and Its Prognostic Value in Gastric Cancer.

OBJECTIVE: Identification of reliable biomarkers for the diagnosis and prognosis of gastric cancer (GC) is very important for achieving early cancer detection and improving clinical outcomes. The aim of the present study was to explore the clinical significance of serum exosomal miR-134 in GC. METHODS: A total of 133 GC cases were enrolled in this study, and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to measure the relative serum exosomal miR-134 expression level. The association between serum exosomal miR-134 expression and clinicopathological characteristics was investigated. RESULTS: Our results showed that serum exosomal miR-134 expression was significantly lower in GC patients than in controls. In addition, serum exosomal miR-134 discriminated GC cases from healthy controls with high accuracy. Moreover, reduced serum exosomal miR-134 expression was closely associated with aggressive clinical variables including TNM stage, lymph node metastasis and invasion depth. Furthermore, Kaplan-Meier analysis revealed that GC patients with low serum exosomal miR-134 expression tended to have shorter overall survival and relapse free survival. In multivariate analysis, serum exosomal miR-134 was an independent prognostic marker for GC. CONCLUSION: In conclusion, serum exosomal miR-134 might serve as a promising diagnostic and prognostic biomarker for GC.

Corrigendum: Polymeric immunoglobulin receptor suppresses colorectal cancer through the AKT-FOXO3/4 axis by downregulating LAMB3 expression.

[This corrects the article DOI: 10.3389/fonc.2022.924988.].

Polymeric immunoglobulin receptor suppresses colorectal cancer through the AKT-FOXO3/4 axis by downregulating LAMB3 expression.

Colorectal cancer (CRC) remains one of the most common malignancies worldwide and its mechanism is unclear. Polymeric immunoglobulin receptor (PIGR) which plays an important role in mucosal immunity is widely expressed in the mucosal epithelium and is dysregulated in different tumors. However, the role and underlying mechanisms of PIGR in CRC remain unclear. Here, we demonstrated that PIGR was hypermethylated and downregulated in our cohort (N = 272), and these features were associated with reduced overall survival in patients (HRmethylation 1.61, 95% CI [1.11-2.33]). These findings were validated by external TCGA and GEO data. Moreover, PIGR overexpression inhibits CRC cell malignant phenotypes in vitro and impedes CRC cells growth in male BALB/c nude mice. Mechanistically, PIGR physically associates with RE1 silencing transcription factor (REST) and blocks the transcription of laminin subunit beta 3 (LAMB3). Subsequently, the AKT-FOXO3/4 axis was suppressed by downregulated LAMB3. In the drug sensitive assay, PIGR-overexpressing cells were more sensitive to cisplatin and gemcitabine. Together, PIGR may serve as a powerful prognostic biomarker and putative tumor suppressor by suppressing the AKT-FOXO3/4 axis by downregulating LAMB3 in CRC. Our study may offer a novel therapeutic strategy for treating CRC patients who highly express PIGR with cisplatin and gemcitabine.

Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer.

Early and specific detection of cancer provides an opportunity for appropriate treatment. Although studies have suggested that QKI is a tumor suppressor gene, no studies have evaluated the diagnostic utility of QKI methylation in colorectal cancer (CRC). Here, we evaluated the methylation status of QKI by integrating the methylation data of tissues and cell lines of multiple cancer types. The diagnostic performance of QKI was analyzed in the discovery dataset from the TCGA CRC 450K array (n = 440) and tested in the test sets (n = 845) from the GEO. The methylation level of QKI was further validated in our independent dataset (n = 388) using targeted bisulfite sequencing. All detected CpG sites in the QKI promoter showed CRC-specific hypermethylation in 31 types of tumor tissues. In the discovery dataset, six consecutive CpG sites achieved high diagnostic performances, with AUCs ranging from 0.821 to 0.930. In the test set, a region (chr6: 163,834,452-163,834,924) including four consecutive CpG sites had robust diagnostic ability in distinguishing CRC and adenoma from normal samples. In the validation dataset, similar robust results were observed in both early- and advanced-stage CRC patients. In addition, QKI exhibited hypermethylation in the cfDNA of patients with CRC (n = 14). Collectively, the QKI promoter is a CRC-specific methylation biomarker and holds great promise for improving the diagnosis using minimally invasive biopsy.

Monodisperse perovskite CoSn(OH)6 in-situ grown on NiCo hydroxide nanoflowers with strong interfacial bonds to boost broadband visible-light-driven photocatalytic CO2 reduction.

Heterojunction engineering is a very prospective approach to modulate the photocatalytic behaviors of semiconductors. Herein, Venus flytrap-like NiCo hydroxide nanoflowers (HNF) with surface modification by different contents of CoSn(OH)6 were fabricated in situ for the first time. Interestingly, CoSn(OH)6 nanocubes (NC) are monodispersed on the nanosheet surface of NiCo HNF. Experimental characterizations and theoretical calculations comprehensively demonstrate the surface Sn atoms of CoSn(OH)6 are effectively embedded into the NiCo HNF interlayers, and co-sharing of the hydroxyl enables intimate contact in the heterointerface of NiCo HNF/CoSn(OH)6 hybrids and thereby largely shortens the charge migrating distance, contributing to an efficient interfacial charge migration and promoting charge separation. The optimized NiCo HNF/CoSn(OH)6 exhibits the remarkably enhanced photocatalytic efficiency for CO2 reduction with a TON of 601.2 and the CO and CH4 yield is about 3 folds that over CoSn(OH)6 NC. DRIFTS reveals the reaction intermediates in the CO2 photocatalytic process and proposes a possible mechanism for photocatalytic CO2 reaction. These findings may pave the way for rational engineering design of non-precious highly-dispersed broadband visible-light-driven CO2 reduction heterostructure catalysts.

Schisandrin A protects against isoproterenol­induced chronic heart failure via miR­155.

Schisandrin A (Sch A) has a protective effect on cardiomyocytes. Circulating miR­155 levels are related to chronic heart failure (CHF). The present study aimed to clarify the role and the molecular mechanism of Sch A in CHF. C57BL/6JGpt mice were used for an isoproterenol (ISO)­induced CHF model to collect heart samples. Echocardiography was employed to detect heartbeat indicators. The degree of myocardial hypertrophy was evaluated based on the measurement of heart weight (HW), body weight (BW) and tibia length (TL) and the observation using hematoxylin­eosin staining. Sprague­Dawley rats were purchased for the separation of neonatal rat ventricular myocytes (NRVMs), which were treated with ISO for 24 h. Transfection regulated the level of miR­155. The viability of NRVMs was detected via MTT assay. The mRNA and protein levels were measured via reverse transcription­quantitative PCR and western blotting and immunofluorescence was used to detect the content of α­smooth muscle actin (α­SMA). Treatment with ISO resulted in rising left ventricular posterior wall thickness, intra­ventricular septum diastole, left ventricular end diastolic diameter, left ventricular end systolic diameter, HW/BW, HW/TL and falling ejection fraction and fractional shortening, the trend of which could be reversed by Sch A. Sch A ameliorated myocardial hypertrophy in CHF mice. In addition, Sch A inhibited ISO­induced upregulated expressions of atrial natriuretic peptide, B­type natriuretic peptide, B­myosin heavy chain and miR­155 in myocardial tissue. Based on the results in vitro, Sch A had no significant effect on the viability of NRVMs when its concentration was <24 µmol/l. Sch A inhibited the levels of miR­155, α­SMA and the phosphorylation levels of AKT and cyclic AMP response­element binding protein (CREB) in ISO­induced NRVMs, which was reversed by the upregulation of miR­155. Schisandrin A mediated the AKT/CREB signaling pathway to prevent CHF by regulating the expression of miR­155, which may shed light on a possible therapeutic target for CHF.

Mir-204 Regulates LPS-Induced A549 Cell Damage by Targeting FOXK2.

Objective: To assess whether miR-204 and HA affect A549 cell injury induced by lipopolysaccharide. Material and Methods. A549 cells were treated with hirsutanol A, and cell damage was induced by LPS followed by analysis of cell proliferation by CCK-8, cell apoptosis by flow cytometry, apoptosis-related protein expression by western blot, downstream target of miR-20 by dual-luciferase reporter gene, and inflammatory factors by ELISA and PCR. Results: LPS can significantly inhibit the viability of A549 cells, induce cell apoptosis, and promote the release of IL-6, IL-1ß, and TNF-α, while HA pretreatment can target FOXK2 by upregulating miR-204 levels, thereby alleviating apoptosis and promoting cell viability and at the same time inhibiting the release of inflammatory factors by inhibiting the activation of NF-κB. Conclusions: miR-204 participates in the protection of HA acute lung injury by targeting FOXK2.

Simple acupuncture combined with fluoxetine in the treatment of poststroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Poststroke depression is a common secondary mental disorder after stroke, which increases the recurrence rate and mortality rate after stroke and hinders the recovery of function. As a combination therapy, simple acupuncture combined with fluoxetine has achieved good clinical effect, but there is a lack of evidence-based medicine. The purpose of this study is to evaluate the efficacy and safety of acupuncture combined with fluoxetine in the treatment of poststroke depression by meta-analysis. METHODS: Search Chinese and English databases: China national knowledge infrastructure, VP information Chinese Journal Service Platform, Wanfang, the China Biomedical Database, PubMed, Embase, the Cochrane Library, and web of science. A randomized controlled trial of simple acupuncture combined with fluoxetine in the treatment of poststroke depression will be selected. The retrieval time is of the establishment of the database in January 2021. Selected literature is extracted and deleted by 2 researchers, and the quality of the included literature is evaluated. The included literature is analyzed by Meta with RevMan5.3 software. RESULTS: In this study, the efficacy and safety of acupuncture combined with fluoxetine in the treatment of post-stroke depression are evaluated by Hamilton Depression scale (HAMD) and its reduction rate, Treatment Emergency Symptom Scale, Self-rating Depression Scale, and Activities of Daily living scale. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of acupuncture combined with fluoxetine in the treatment of post-stroke depression. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/5J896.

Prognostic Inflammatory Index Based on Preoperative Peripheral Blood for Predicting the Prognosis of Colorectal Cancer Patients.

Host inflammation is a critical component of tumor progression and its status can be indicated by peripheral blood cell counts. We aimed to construct a comprehensively prognostic inflammatory index (PII) based on preoperative peripheral blood cell counts and further evaluate its prognostic value for patients with colorectal cancer (CRC). A total of 9315 patients with stage II and III CRC from training and external validation cohorts were included. The PII was constructed by integrating all the peripheral blood cell counts associated with prognosis in the training cohort. Cox analyses were performed to evaluate the association between PII and overall survival (OS) and disease-free survival (DFS). In the training cohort, multivariate Cox analyses indicated that high OS-PII (>4.27) was significantly associated with worse OS (HR: 1.330, 95% CI: 1.189-1.489, p < 0.001); and high DFS-PII (>4.47) was significantly associated with worse DFS (HR: 1.366, 95% CI: 1.206-1.548, p < 0.001). The prognostic values of both OS-PII and DFS-PII were validated in the external validation cohort. The nomograms achieved good accuracy in predicting both OS and DFS. Time-dependent ROC analyses showed that both OS-PII and DFS-PII have a stable prognostic performance at various follow-up times. The prognostic value of tumor-node-metastasis staging could be enhanced by combining it with either OS-PII or DFS-PII. We demonstrated that PIIs are independent prognostic predictors for CRC patients, and the nomograms based on PIIs can be recommended for personalized survival prediction of patients with CRC.

Chemical fixation of CO2 into cyclic carbonates catalyzed by bimetal mixed MOFs: the role of the interaction between Co and Zn.

Bimetal mixed MOFs of [CoZn][(BDC)(DABCO)0.5] (CZ-BDO), [CoNi][(BDC)(DABCO)0.5] (CN-BDO), and [NiZn][(BDC)(DABCO)0.5] (NZ-BDO) were prepared under solvothermal conditions and further employed as highly active accelerants for converting carbon dioxide into cyclic carbonates. The characteristics of the bimetal compounds were revealed via various techniques, including ICP-OES, XRD, FT-IR, Raman, XPS, SEM, EDS maps, N2 adsorption, TG-DTG, and CO2/NH3-TPD. The catalytic results revealed that CZ-BDO is superior to the other samples for obtaining a satisfactory chloropropene carbonate (CPC) yield. The excellent catalytic activity may be owing to the presence of a solid solution within the Co and Zn bimetal sample, which provides synergistic catalysis in the carbon dioxide cycloaddition. In addition, the synergistic catalysis was further confirmed by the NH3-TPD profiles, whereby the amount of CZ-BDO basic sites was obviously enhanced compared to the other samples. Furthermore, DFT calculations were also performed to reveal the synergistic catalysis between Co and Zn for the coupling reaction. Additionally, when the coupling reaction was carried out at 100 °C for 5 h in the presence of 0.5 wt% epichlorohydrin (ECH) as a catalyst at 3.0 MPa, 99.31% conversion of ECH and 97.05% yield of CPC were obtained over the optimal CZ-BDO sample. Moreover, the bimetal sample can also efficiently convert other epoxides into the corresponding cyclic carbonates.

Synchronous Response Analysis of Features for Remote Sensing Crop Classification Based on Optical and SAR Time-Series Data.

Accurate crop classification is the basis of agricultural research, and remote sensing is the only effective measuring technique to classify crops over large areas. Optical remote sensing is effective in regions with good illumination; however, it usually fails to meet requirements for highly accurate crop classification in cloud-covered areas and rainy regions. Synthetic aperture radar (SAR) can achieve active data acquisition by transmitting signals; thus, it has strong resistance to cloud and rain interference. In this study, we designed an improved crop planting structure mapping framework for cloudy and rainy regions by combining optical data and SAR data, and we revealed the synchronous-response relationship of these two data types. First, we extracted geo-parcels from optical images with high spatial resolution. Second, we built a recurrent neural network (RNN)-based classifier suitable for remote sensing images on the geo-parcel scale. Third, we classified crops based on the two datasets and established the network. Fourth, we analyzed the synchronous response relationships of crops based on the results of the two classification schemes. This work is the basis for the application of remote sensing data for the fine mapping and growth monitoring of crop planting structures in cloudy and rainy areas in the future.

Catalytic pyrolysis of natural algae over Mg-Al layered double oxides/ZSM-5 (MgAl-LDO/ZSM-5) for producing bio-oil with low nitrogen content.

Cyanobacteria were catalytically pyrolyzed over Mg-Al layered double oxide/ZSM-5 composites (MgAl-LDO/ZSM-5) to produce bio-oil. MgAl-LDO/ZSM-5 with a Mg/Al molar ratio of four was proved to be the best catalyst. Under the optima condition that the final temperature was 823K, heating rate was 10K/min and catalyst/algae mass ratio was 0.75, a maximum yield of liquid (41.1%) was achieved at 823K with a heating rate of 10K/min and a catalyst/algae mass ratio of 0.75, which was much higher than the one obtained without catalyst. The element analysis results proved that this bio-oil had much lower O/C molar ratio and higher HHV. The GC-MS results showed that the bio-oil had less nitrogenous compounds. MgAl4-LDO/ZSM-5 was proved to be an applicable and effective catalyst to obtain bio-oil from catalytic pyrolysis of water-blooming algae.

Photodynamic therapy with a novel porphyrin-based photosensitizer against human gastric cancer.

The objective of the present study was to evaluate the effects of novel porphyrin-based photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid- aminophenyl]-10,15,20-triphenyl-porphyrin (DTP)-mediated photodynamic therapy (PDT) on the HGC27 and SNU-1 human gastric cancer cell lines. The absorption spectrum of DTP was analyzed using a microplate spectrophotometer. The HGC27 or SNU-1 cells were incubated with DTP and exposed to illumination by a 650-nm laser. The experiments were divided into four groups: A blank control, cells treated with DTP without light, cells exposed to laser light without DTP and cells treated with a combination of DTP and light together. The phototoxicity of DTP was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell apoptosis was detected by flow cytometry and Hoechst 33342 staining. In addition, the intracellular distribution of DTP was investigated by laser scanning confocal microscopy. DTP-PDT demonstrated marked phototoxicity towards HGC27- and SNU-1 cells. The rate of cell death increased significantly in a DTP concentration-dependent and light dose-dependent manner, with maximum mortality rates of 74.14 and 67.76%, respectively. There were significant differences between the therapeutic and control groups (P<0.01). In addition, the growth of cells treated with DTP or laser light alone was not inhibited. Further evaluation revealed that, following DTP-PDT, HGC27 and SNU-1 cells demonstrated notable apoptotic changes, including condensed chromatin, fragmented nuclei and apoptotic bodies, and the percentage of apoptotic cells was significantly higher than that of the control groups (P<0.01). Furthermore, confocal laser scanning microscopy revealed that DTP localized to the lysosomes but not mitochondria in the two types of tumor cell. In conclusion, significant phototoxicity and reduced cytotoxicity in dark conditions make the novel photosensitizer DTP a promising potential PDT drug for future use in the treatment of human gastric cancer.

Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug-resistant human gastric cancer cell lines.

Photodynamic therapy (PDT) has been considered to be a possible candidate approach in combating multidrug resistance (MDR) phenomenon during the treatment of cancer. To investigate the photocytotoxicity of a novel porphyrin-based photosensitizer, meso-5-[ρ-DTPA-aminophenyl]-10, 15, 20-triphenyl-porhyrin (DTP) (Fig. 1A), on MDR cells, the intracellular DTP uptake, phototoxicity and subcellular DTP localization were studied by using a human gastric cancer MGC803 cell line and its paclitaxel selected subline MGC803/PA expressing MDR phenotype. No significant difference was observed in intracellular DTP accumulation between sensitive and resistant cell lines after exposure to 1.56 µM concentration for 6h. DTP-PDT induced significant photocytotoxicity on both MGC803 and MGC803/PA cell lines and the photokilling was greater in MGC803 cell line in comparison to MGC803/PA. The fluence that caused 50% cell death was 4.42 and 6.29 J/cm(2) in MGC803 and MGC803/PA cell lines, respectively. The presence of Pgp inhibitors verapamil and cyclosporin A could not modify the intracellular DTP level in MGC803/PA cell line and the phototoxic effects. DTP was localized at lysosomes of MGC803 cell line but at lysosomes and mitochondria of MGC803/PA. Our results indicated that DTP-mediated PDT could eradicate gastric cancer cells whether or not they express MDR although the efficacy is slightly reduced in the MDR cells. The photokilling in MDR cells could not be altered by MDR inhibitor verapamil. The slightly different photocytotoxicity between sensitive and resistant cell lines could not explained by classical Pgp MDR and might be attributed to the differential intracellular DTP localization sites.