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1.
Sci Rep ; 14(1): 10647, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724510

ABSTRACT

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.


Subject(s)
Body Weight , Moringa oleifera , Rats, Sprague-Dawley , Animals , Moringa oleifera/chemistry , Rats , Male , Body Weight/drug effects , Eating/drug effects , Female , Animal Feed/analysis , Diarrhea/chemically induced , Diarrhea/veterinary
2.
ACS Sens ; 8(12): 4737-4746, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38008917

ABSTRACT

Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at ∼720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at ∼800 nm, resulting in the PA800/PA720 ratio. In vitro, a linear relationship is successfully established between PA800/PA720 values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo. Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.


Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Prodrugs , Humans , Prodrugs/chemistry , Prodrugs/pharmacokinetics , Prodrugs/therapeutic use , Drug Liberation , Photoacoustic Techniques/methods , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Disulfides/chemistry
3.
Bioorg Chem ; 130: 106220, 2023 01.
Article in English | MEDLINE | ID: mdl-36347088

ABSTRACT

Photothermal therapy (PTT) has gained extensive interest in tumor treatments due to its non-invasive and low-toxic nature. However, the currently available photothermal agents (PTAs) mostly show unsatisfactory photothermal conversion efficiency (PCE). Besides, as a local cancer treatment modality, PTT fails to inhibit metastasis of tumors. To address these issues, in this study, two aza-boron-dipyrromethene (aza-BODIPY)-based organic photothermal agents (OPTAs), Fc-aza-BODIPY and TPA-aza-BODIPY, were rationally coined by introducing two strong electron-donating ferrocene (Fc) moieties and two triphenylamine (TPA) rotors, which could boost intramolecular photo-induced electron transfer (PET) and molecular rotation respectively, thereby improving the PCE of aza-BODIPY dyes. After encapsulation of hydrophobic Fc-aza-BODIPY (or TPA-aza-BODIPY) and quercetin with biodegradable PLGA and DSPE-mPEG2000, the resulting nanoparticles (FAQ NPs and TAQ NPs) showed excellent optical properties with PCE of ∼72.0% and ∼79.7% and specific tumor accumulations through enhanced permeability and retention (EPR) effects. Consequently, these two NPs possessed prominent antitumor effects under 880 nm laser irradiation. Moreover, both FAQ NPs and TAQ NPs loaded with quercetin could inhibit tumor metastasis efficiently. These two multifunctional nanomaterials integrating OPTAs and anti-metastasis agents constructed a cooperative treatment program, which may provide a potential opportunity for future clinical cancer treatment.


Subject(s)
Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Quercetin , HeLa Cells , Nanoparticles/chemistry , Neoplasms/drug therapy
4.
Cancer Med ; 12(3): 2312-2324, 2023 02.
Article in English | MEDLINE | ID: mdl-36016484

ABSTRACT

BACKGROUND: Liver transplantation (LT), resection (LR), and ablation (LA) are three curative-intent treatment options for patients with early hepatocellular carcinoma (HCC). We aimed to develop a prognostic calculator to compare the long-term outcomes following each of these therapies. METHODS: A total of 976 patients with HCC within the Milan criteria who underwent LT, LR, and LA between 2009 and 2019 from four institutions were evaluated. Multistate competing risks prediction models for recurrence-free survival (RFS), recurrence within the Milan criteria (RWM), and HCC-specific survival (HSS) were derived to develop a prognostic calculator. RESULTS: During a median follow-up of 51 months, 420 (43%) patients developed recurrence. In the multivariate analysis, larger tumor size, multinodularity, older age, male, higher alpha-fetoprotein (AFP), higher albumin-bilirubin (ALBI) grade, and the presence of portal hypertension were significantly associated with higher recurrence and decreased survival rates. The RFS and HSS were both significantly higher among patients treated by LT than by LR or LA and significantly higher between patients treated by LR than by LA (all p < 0.001). For multinodular HCC ≤3 cm, although LT had better RFS and HSS than LR or LA, LA was noninferior to LR. An online prognostic calculator was then developed based on the preoperative clinical factors that were independently associated with outcomes to evaluate RFS, RWM, and HSS at different time intervals for all three treatment options. CONCLUSIONS: Although LT resulted in the best recurrence and survival outcomes, LR and LA also offered durable long-term alternatives. This prognostic calculator is a useful tool for clinicians to guide an informed and personalized discussion with patients based on their tumor biology and liver function.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Humans , Male , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Hepatectomy/methods , Liver Transplantation/methods , Prognosis , Retrospective Studies , Neoplasm Recurrence, Local/pathology
5.
ACS Appl Mater Interfaces ; 14(36): 40546-40558, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36059107

ABSTRACT

Hypoxia-activated prodrugs (HAPs) have drawn increasing attention for improving the antitumor effects while minimizing side effects. However, the heterogeneous distribution of the hypoxic region in tumors severely impedes the curative effect of HAPs. Additionally, most HAPs are not amenable to optical imaging, and it is difficult to precisely trace them in tissues. Herein, we carefully designed and synthesized a multifunctional therapeutic BAC prodrug by connecting the chemotherapeutic drug camptothecin (CPT) and the fluorescent photothermal agent boron dipyrromethene (BODIPY) via hypoxia-responsive azobenzene linkers. To enhance the solubility and tumor accumulation, the prepared BAC was further encapsulated into a human serum albumin (HSA)-based drug delivery system to form HSA@BAC nanoparticles. Since the CPT was caged by a BODIPY-based molecule at the active site, the BAC exhibited excellent biosafety. Importantly, the activated CPT could be quickly released from BAC and could perform chemotherapy in hypoxic cancer cells, which was ascribed to the cleavage of the azobenzene linker by overexpressed azoreductase. After irradiation with a 730 nm laser, HSA@BAC can efficiently generate hyperthermia to achieve irreversible cancer cell death by oxygen-independent photothermal therapy. Under fluorescence imaging-guided local irradiation, both in vitro and in vivo studies demonstrated that HSA@BAC exhibited superior antitumor effects with minimal side effects.


Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Prodrugs , Azo Compounds , Boron , Boron Compounds , Camptothecin/chemistry , Cell Line, Tumor , Humans , Hypoxia , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Phototherapy , Photothermal Therapy , Porphobilinogen/analogs & derivatives , Prodrugs/chemistry
6.
Eur J Med Chem ; 243: 114749, 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-36115207

ABSTRACT

Herein, we fabricate a multifunctional molecular prodrug BAC where the chemotherapeutical agent camptothecin (CPT) is linked with a boron dipyrromethene (BODIPY)-based photosensitizer by an azobenzene chain which is sensitive to over-expressed azoreductase in hypoxic tumor cells. This prodrug was further loaded into biodegradable monomethoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) to improve its solubility and tumor accumulation. The formed BAC nanoparticles (BAC NPs) can destroy aerobic tumor cells with relatively short distance from blood vessels by photodynamic therapy (PDT) under illumination. The PDT action inevitably leads to consumption of O2, and subsequently acute hypoxia which can induce cleavage of azobenzene linkage to boost release of CPT killing the other hypoxic interior tumor cells survived from PDT. Both in vitro and in vivo studies have verified that BAC NPs possess remarkable antitumor activity by a synergistic action of PDT and chemotherapy.


Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Prodrugs , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic use , Neoplasms/drug therapy , Camptothecin/therapeutic use , Hypoxia/drug therapy , Cell Line, Tumor
7.
Chempluschem ; 87(9): e202200158, 2022 09.
Article in English | MEDLINE | ID: mdl-36148971

ABSTRACT

Increasing Investigations show that photosensitizers (PSs) which target mitochondria are useful for enhancing photodynamic therapy (PDT) efficacy. Herein, we carefully designed and synthesized four triphenylphosphonium (TPP)-modified boron dipyrromethene (BDP)-based PSs through Cu(I)-assisted "3+2" cycloaddition reaction. All of them exhibit intense red light absorption with maxima between 659 and 663 nm, considerable fluorescence emission with quantum yields of 0.16-0.23, high singlet oxygen generation efficiency ranging from 0.22 to 0.34, excellent mitochondria-targeting ability, and good biocompatibility. Upon illumination, they induce significant cancer cell death through a mitochondria-related apoptosis pathway. The IC50 values of these BDP dyes against MCF-7 cells were determined to be as low as 0.046-0.113 µM under rather low dosage of light irradiation (1.5 J ⋅ cm-2 ).


Subject(s)
Photochemotherapy , Photosensitizing Agents , Boron/metabolism , Coloring Agents/metabolism , Mitochondria/metabolism , Photosensitizing Agents/pharmacology , Porphobilinogen/analogs & derivatives , Singlet Oxygen/metabolism
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 270: 120779, 2022 Apr 05.
Article in English | MEDLINE | ID: mdl-34974293

ABSTRACT

ETC (3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-ethylthiacarbocyanine triethylammonium salt), as a derivative of thiazole, is capable of forming various aggregates by the short-range noncovalent interaction forces under specific conditions, accompanying with significant absorbance and fluorescence characteristics. In this work, a label-free probe (ETC) for the detection of Cys (Cysteine) and Hg2+ was developed based on transformation between monomers and J-aggregations by AGRO100. AGRO100 can transform between single-stranded DNA and G-quadruplex to realize recognition of Cys and Hg2+ in dual-channel mode. These recognitional signals can be captured by UV-visible absorption spectra and fluorescence spectroscopy. ETC exhibits high sensitivity and selectivity with the detection limit of 0.197 nM in a wide range of 0-15 µM, which can apply of Cys and Hg2+ detection in human serum.


Subject(s)
Aptamers, Nucleotide , Mercury , Cysteine , Fluorescent Dyes , Humans , Oligodeoxyribonucleotides
9.
Mol Pharm ; 19(2): 630-641, 2022 02 07.
Article in English | MEDLINE | ID: mdl-35034440

ABSTRACT

Combination treatments are more effective than conventional monotherapy in combating cancer. Herein, a multifunctional prodrug BDP-L-CPT was rationally engineered and prepared by the conjugation of a boron dipyrromethene (BDP)-based photosensitizer (PS) to the active site of the chemotherapeutic drug camptothecin (CPT) via a phenyl benzoate group. After modification, the cytotoxicity of CPT was locked. Moreover, the fluorescence emission at 430 nm from the CPT component in the prodrug was substantially inhibited through the intramolecular fluorescence resonance energy transfer process. The phenyl benzoate linker in BDP-L-CPT could be selectively cleaved by exogenous carboxylesterase in phosphate-buffered saline solution and endogenous carboxylesterase overexpressed in cancer cells, which was followed by self-immolation to release free CPT. The drug release process could be monitored by the turn-on of CPT fluorescence in solution and cells. Owing to the combination of site-specific chemotherapy with light-driven photodynamic therapy, the IC50 values of the prodrug BDP-L-CPT against HepG2 human hepatocellular carcinoma and HeLa human cervical carcinoma cells were lower than those of the controls, BDP-COOH and CPT. The combined antitumor effects of the prodrug BDP-L-CPT were also observed in the mice bearing H22 tumors. Furthermore, BDP-L-CPT had a more prolonged blood circulation time in mice than CPT, which is beneficial to persistent therapy. This study may provide a promising strategy for a selective combination cancer treatment by conjugating a prodrug to a PS.


Subject(s)
Liver Neoplasms , Photochemotherapy , Prodrugs , Animals , Binding Sites , Camptothecin/chemistry , Cell Line, Tumor , Liver Neoplasms/drug therapy , Mice , Prodrugs/chemistry
10.
Materials (Basel) ; 14(20)2021 Oct 12.
Article in English | MEDLINE | ID: mdl-34683606

ABSTRACT

TPU-coated polyester fabric was used as the substrate of a flexible temperature sensor and Ag nanoparticles were deposited on its surface as the temperature sensing layer by the magnetron sputtering method. The effects of sputtering powers and heat treatment on properties of the sensing layers, such as the temperature coefficient of resistance (TCR), linearity, hysteresis, drift, reliability, and bending resistance, were mainly studied. The results showed that the TCR (0.00234 °C-1) was the highest when sputtering power was 90 W and sputtering pressure was 0.8 Pa. The crystallinity of Ag particles would improve, as the TCR was improved to 0.00262 °C-1 under heat treatment condition at 160°. The Ag layer obtained excellent linearity, lower hysteresis and drift value, as well as good reliability and bending resistance when the sputtering power was 90 W. The flexible temperature sensor based on the coated polyester fabric improved the softness and comfortableness of sensor, which can be further applied in intelligent wearable products.

11.
ACS Appl Mater Interfaces ; 13(29): 33905-33914, 2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34278780

ABSTRACT

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.


Subject(s)
Antineoplastic Agents/therapeutic use , Drug Carriers/chemistry , Nanoparticles/chemistry , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Acrylates/chemical synthesis , Acrylates/chemistry , Animals , Antineoplastic Agents/chemistry , Boron Compounds/chemistry , Boron Compounds/therapeutic use , Cell Line, Tumor , Drug Carriers/chemical synthesis , Drug Liberation , Female , Humans , Mice , Paclitaxel/chemistry , Paclitaxel/therapeutic use , Photochemotherapy , Photosensitizing Agents/chemistry , Polyesters/chemical synthesis , Polyesters/chemistry , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/chemistry , Pyrroles/chemistry , Pyrroles/therapeutic use , Singlet Oxygen/metabolism
12.
Drug Discov Today ; 26(8): 2045-2052, 2021 08.
Article in English | MEDLINE | ID: mdl-33741495

ABSTRACT

Photothermal therapy (PTT) has emerged as a promising therapeutic approach for tumor control and ablation. Attention has focused on exploring advanced organic photothermal agents (OPTAs), with advantages of easy modification, adjustable photophysical and photochemical properties, good compatibility, and inherent biodegradability. However, few detailed studies on how to maximally channelize nonradiative heat generation from the viewpoint of the photothermal conversion mechanism have been reported. Thus, here we assimilate and elaborate on several available action mechanisms to maximize the photothermal conversion efficiency (PCE) of organic dyes. Moreover, we also propose several potential challenges that require substantial future work to address.


Subject(s)
Coloring Agents/chemistry , Neoplasms/therapy , Phototherapy/methods , Humans , Hyperthermia, Induced/methods
13.
Eur J Med Chem ; 215: 113251, 2021 Apr 05.
Article in English | MEDLINE | ID: mdl-33611187

ABSTRACT

Development of the drug with high therapeutic efficacy and low toxicity is crucial to cancer ablation. In this study, we have demonstrated a red light-responsive prodrug BDP-TK-CPT by connecting the chemotherapeutic agent camptothecin with a boron dipyrromethene (BDP)-based photosensitizer via a reactive oxygen species (ROS)-labile thioketal chain. Since camptothecin is modified by a BDP-based macrocycle at the active site, the formed prodrug displays an extremely low toxicity in dark. However, upon illumination by red light, it can efficiently generate ROS leading to cell death by photodynamic therapy. Meanwhile, the ROS generated can destroy thioketal group to release free camptothecin which further results in local cell death by chemotherapy. The combined antitumor effects of the prodrug have been verified in HepG2, EC109, and HeLa cancer cells and mice bearing H22 tumors. This study may provide an alternative strategy for stimuli-responsive combination treatment of tumors by conjugation of ROS-activatable prodrugs with photosensitizing agents.


Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Prodrugs/therapeutic use , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/radiation effects , Apoptosis/drug effects , Cell Line, Tumor , Combined Modality Therapy , Drug Therapy , Female , Humans , Light , Mice , Necrosis/chemically induced , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/radiation effects , Prodrugs/chemical synthesis , Prodrugs/radiation effects , Reactive Oxygen Species/metabolism
14.
World J Clin Cases ; 9(36): 11183-11192, 2021 Dec 26.
Article in English | MEDLINE | ID: mdl-35071549

ABSTRACT

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers among men. Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging (mp-MRI) have emerged, which may improve the accuracy of detecting clinically significant PCa in recent years. AIM: To investigate the diagnostic efficiency of a template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa. METHODS: Data from patients with an increasing prostate-specific antigen (PSA) level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed. All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area. A total of 127 patients with complete data were included in the final analysis. A multivariable logistic regression analysis was conducted, and a two-sided P < 0.05 was considered statistically significant. RESULTS: PCa was detected in 66 of 127 patients, and 56 cases presented clinically significant PCa. Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa, specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa. A randomized biopsy detected seven cases of PCa negative on targeted biopsy, and four cases had clinically significant PCa. PSA density (OR: 1.008, 95%CI: 1.003-1.012, P = 0.001; OR: 1.006, 95%CI: 1.002-1.010, P = 0.004) and Prostate Imaging-Reporting and Data System (PI-RADS) scores (both P < 0.001) were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone. CONCLUSION: This single-centered study proposed a feasible template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy. Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.

15.
World J Clin Cases ; 8(21): 5104-5115, 2020 Nov 06.
Article in English | MEDLINE | ID: mdl-33269247

ABSTRACT

BACKGROUND: The current standard surgical treatment for non-metastatic upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff excision (BCE). Typically, BCE techniques are classified in one of the following three categories: An open technique described as intrasvesical incision of the bladder cuff, a transurethral incision of the bladder cuff (TUBC), and an extravesical incision of the bladder cuff (EVBC) method. Even though each of these management techniques are widely used, there is no consensus about which surgical intervention is superior, with the best oncologic outcomes. AIM: To investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients. METHODS: We retrospectively analyzed the data of 248 primary UTUC patients, who underwent RNU with BCE between January 2004 to December 2018. Patients were analyzed according to each BCE method. Data extracted included patient demographics, perioperative parameters, and oncological outcomes. Statistical analyses were performed using chi-square and log-rank tests. The Cox proportional hazards regression model was utilized to identify independent predictors. P < 0.05 was considered statistically significant. RESULTS: Of the 248 participants, 39.9% (n = 99) underwent intrasvesical incision of the bladder cuff, 38.7% (n = 96) EVBC, and 21.4% (n = 53) TUBC. At a median follow-up of 44.2 mo, bladder recurrence developed in 17.2%, 12.5%, and 13.2% of the cases, respectively. Cancer-specific deaths occurred in 11.1%, 5.2%, and 7.5% of patients, respectively. Kaplan-Meier survival curves with a log-rank test highlighted no significant differences in intravesical recurrence-free survival, cancer-specific survival, and overall survival among these approaches with P values of 0.987, 0.825, and 0.497, respectively. Multivariate analysis showed that the lower ureter location appears to have inferior intravesical recurrence-free survival (P = 0.042). However, cancer-specific survival and overall survival were independently influenced by tumor stage (hazard ratio [HR] = 8.439; 95% confidence interval: 2.424-29.377; P = 0.001) and lymph node status (HR = 14.343; 95%CI: 5.176-39.745; P < 0.001). CONCLUSION: All three techniques had comparable outcomes; although, EVBC and TUBC are minimally invasive. While based upon rather limited data, these findings will support urologists in blending experience with evidence to inform patient choices. However, larger, rigorously designed, multicenter studies with long term outcomes are still required.

16.
Eur J Med Chem ; 193: 112203, 2020 May 01.
Article in English | MEDLINE | ID: mdl-32197150

ABSTRACT

Here, we have synthesized and characterized a novel activatable photosensitizer (PS) 8a in which two well-designed boron dipyrromethene (BODIPY) derivatives are utilized as the photosensitizing fluorophore and quencher respectively, which are connected by a disulfide linker via two successive Cu (І) catalyzed click reactions. The fluorescence emission and singlet oxygen production of 8a are suppressed via intramolecular fluorescence resonance energy transfer (FRET) from the excited BODIPY-based PS part to quencher unit, but both of them can be simultaneously switched on by cancer-related biothiol glutathione (GSH) in phosphate buffered saline (PBS) solution with 0.05% Tween 80 as a result of cleavage of disulfide. Also, 8a exhibits a bright fluorescence image and a substantial ROS production in A549 human lung adenocarcinoma, HeLa human cervical carcinoma and H22 mouse hepatoma cells having a relatively high concentration of GSH, thereby leading to a significant photocytotoxicity, with IC50 values as low as 0.44 µM, 0.67 µM and 0.48 µM, respectively. In addition, the photosensitizer can be effectively activated and imaged in H22 transplanted hepatoma tumors of mice and shows a strong inhibition on tumor growth. All these results suggest that such a GSH-responsive photosensitizer based on FRET mechanism may provide a new strategy for tumor-targeted and fluorescence imaging-guided cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Fluorescence Resonance Energy Transfer , Glutathione/chemistry , Optical Imaging , Photochemotherapy , Photosensitizing Agents/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Boron Compounds/chemical synthesis , Boron Compounds/chemistry , Boron Compounds/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Mice , Mice, Inbred Strains , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Porphobilinogen/analogs & derivatives , Porphobilinogen/chemical synthesis , Porphobilinogen/chemistry , Porphobilinogen/pharmacology , Structure-Activity Relationship
17.
Chem Asian J ; 14(7): 1059-1065, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30776197

ABSTRACT

By using a copper-promoted alkyne-azide cycloaddition reaction, two boron dipyrromethene (BODIPY) derivatives bearing a bis(1,2,3-triazole)amino receptor at the meso position were prepared and characterized. For the analogue with two terminal triethylene glycol chains, the fluorescence emission at 509 nm responded selectively toward Hg2+ ions, which greatly increased the fluorescence quantum yield from 0.003 to 0.25 as a result of inhibition of the photoinduced electron transfer (PET) process. By introducing two additional rhodamine moieties at the termini, the resulting conjugate could also detect Hg2+ ions in a highly selective manner. Upon excitation at the BODIPY core, the fluorescence emission of rhodamine at 580 nm was observed and the intensity increased substantially upon addition of Hg2+ ions due to inhibition of the PET process followed by highly efficient fluorescence resonance energy transfer (FRET) from the BODIPY core to the rhodamine moieties. The Hg2+ -responsive fluorescence change of these two probes could be easily seen with the naked eye. The binding stoichiometry between the probes and Hg2+ ions in CH3 CN was determined to be 1:2 by Job's plot analysis and 1 H NMR titration, and the binding constants were found to be (1.2±0.1)×1011 m-2 and (1.3±0.3)×1010 m-2 , respectively. The overall results suggest that these two BODIPY derivatives can serve as highly selective fluorescent probes for Hg2+ ions. The rhodamine derivative makes use of a combined PET-FRET sensing mechanism which can greatly increase the sensitivity of detection.


Subject(s)
Boron Compounds/chemistry , Fluorescent Dyes/chemistry , Mercury/analysis , Pyrroles/chemistry , Triazoles/chemistry , Boron Compounds/chemical synthesis , Fluorescence , Fluorescence Resonance Energy Transfer , Fluorescent Dyes/chemical synthesis , Limit of Detection , Pyrroles/chemical synthesis , Rhodamines/chemical synthesis , Rhodamines/chemistry , Spectrometry, Fluorescence/methods , Triazoles/chemical synthesis
18.
Asian-Australas J Anim Sci ; 32(8): 1145-1152, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30744357

ABSTRACT

OBJECTIVE: Mulberry (Morus alba L.) is a cultivated shrub grown widely in the sub-tropical and tropical areas. It has been shown that mulberry leaf contains high levels of protein while having polyphenols as phytonutrients. Therefore, it is important to conduct an experiment to assess potential toxic level from mulberry on behavior, blood hematological and coagulation parameter using Sprague-Dawley (SD) rats. METHODS: Both male and female SD rats were given an intragastric administration of respective treatments of mulberry leaf intakes (control, low and high levels). Parameters of feed intake, hematological and coagulation of blood parameters, as well as liveweight changes were taken during the 7 d of adaptation, 28 d of treatment exposure, and 14 d of recovery periods, respectively. All treatment data were statistically analyzed using analysis of variance of SPSS17.0 for Windows Statistical Software following the Randomized complete block design with sex as a block. RESULTS: Most of the parameters of the physical symptoms of the SD rats, were not significantly different (p>0.05) when compared with that of the control group. Those which remain unchanged in each dose group were, body weight (BW) gain, feed intake, the hematology and coagulation indexes. Although, there were a few individual indicators that were abnormal, but the overall physiological appearance of the rats were normal. CONCLUSION: Results under this experiment revealed that most hematological and coagulation parameters of the SD rats in both male and female were normal, although the weight gain of female rats in high-dose group was significantly reduced than those of the male rats. Under this study, the use of mulberry leaf up to 2 g/kg BW did not result in abnormal phenomenon in the SD rats. These findings would offer useful information for further in vivo feeding trials in animals to extensively use of mulberry leaf to improve animal production, particularly in P.R. China.

19.
Molecules ; 24(1)2018 Dec 21.
Article in English | MEDLINE | ID: mdl-30577688

ABSTRACT

In this study, we demonstrate a novel H2O2 activatable photosensitizer (compound 7) which contains a diiodo distyryl boron dipyrromethene (BODIPY) core and an arylboronate group that quenches the excited state of the BODIPY dye by photoinduced electron transfer (PET). The BODIPY-based photosensitizer is highly soluble and remains nonaggregated in dimethyl sulfoxide (DMSO) as shown by the intense and sharp Q-band absorption (707 nm). As expected, compound 7 exhibits negligible fluorescence emission and singlet oxygen generation efficiency. However, upon interaction with H2O2, both the fluorescence emission and singlet oxygen production of the photosensitizer can be restored in phosphate buffered saline (PBS) solution and PBS buffer solution containing 20% DMSO as a result of the cleavage of the arylboronate group. Due to the higher concentration of H2O2 in cancer cells, compound 7 even with low concentration is particularly sensitive to human cervical carcinoma (HeLa) cells (IC50 = 0.95 µM) but hardly damage human embryonic lung fibroblast (HELF) cells. The results above suggest that this novel BODIPY derivative is a promising candidate for fluorescence imaging-guided photodynamic cancer therapy.


Subject(s)
Boron/chemistry , Hydrogen Peroxide/chemistry , Photochemotherapy , Photosensitizing Agents/chemistry , Porphobilinogen/analogs & derivatives , Biological Transport , Cell Line , Humans , Molecular Structure , Photochemistry , Photochemotherapy/methods , Photosensitizing Agents/chemical synthesis , Porphobilinogen/chemical synthesis , Porphobilinogen/chemistry , Reactive Oxygen Species/metabolism , Spectrometry, Fluorescence
20.
Materials (Basel) ; 11(10)2018 Oct 12.
Article in English | MEDLINE | ID: mdl-30322000

ABSTRACT

The applications of magnetron sputtering technology on the surface coating of fabrics have attracted more and more attention from researchers. Over the past 15 years, researches on magnetron sputtering coated fabrics have been mainly focused on electromagnetic shielding, bacterial resistance, hydrophilic and hydrophobic properties and structural color etc. In this review, recent progress of the technology is discussed in detail, and the common target materials, technologies and functions and characterization of coated fabrics are summarized and analyzed. Finally, the existing problems and future prospects of this developing field are briefly proposed and discussed.

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