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1.
Genes (Basel) ; 15(5)2024 04 25.
Article in English | MEDLINE | ID: mdl-38790176

ABSTRACT

Krascheninnikovia ewersmanniana is a dominant desert shrub in Xinjiang, China, with high economic and ecological value. However, molecular systematics research on K. ewersmanniana is lacking. To resolve the genetic composition of K. ewersmanniana within Amaranthaceae and its systematic relationship with related genera, we used a second-generation Illumina sequencing system to detect the chloroplast genome of K. ewersmanniana and analyze its assembly, annotation, and phylogenetics. Total length of the chloroplast genome of K. ewersmanniana reached 152,287 bp, with 84 protein-coding genes, 36 tRNAs, and eight rRNAs. Codon usage analysis showed the majority of codons ending with base A/U. Mononucleotide repeats were the most common (85.42%) of the four identified simple sequence repeats. A comparison with chloroplast genomes of six other Amaranthaceae species indicated contraction and expansion of the inverted repeat boundary region in K. ewersmanniana, with some genes (rps19, ndhF, ycf1) differing in length and distribution. Among the seven species, the variation in non-coding regions was greater. Phylogenetic analysis revealed Krascheninnikovia ceratoides, Dysphania ambrosioides, Dysphania pumilio, and Dysphania botrys to have a close monophyletic relationship. By sequencing the K. ewersmanniana chloroplast genome, this research resolves the relatedness among 35 Amaranthaceae species, providing molecular insights for germplasm utilization, and theoretical support for studying evolutionary relationships.


Subject(s)
Amaranthaceae , Genome, Chloroplast , Phylogeny , Amaranthaceae/genetics , Codon Usage , Microsatellite Repeats/genetics , Evolution, Molecular , Chloroplasts/genetics , China , Molecular Sequence Annotation
2.
World J Diabetes ; 14(7): 1103-1111, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37547593

ABSTRACT

BACKGROUND: Retinopathy is the most common microvascular disease of type 2 diabetes, and seriously threatens the life, health and quality of life of patients. It is worth noting that the development of diabetic retinopathy (DR) can be hidden, with few symptoms. Therefore, the preliminary screening of diabetic patients should identify DR as soon as possible, delay disease progression, and play a vital role in its diagnosis and treatment. AIM: To investigate the correlation between glycated hemoglobin A1c (HbA1c), urinary microalbumin (U-mALB), urinary creatinine (U-CR), mALB/U-CR ratio, ß2 microglobulin (ß2MG), retinol binding protein (RBP) and DR. METHODS: A total of 180 patients with type 2 diabetes mellitus attending the Second People's Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists. Based on whether they had combined retinopathy and its degree, 68 patients with diabetes mellitus without retinopathy (NDR) were assigned to the NDR group, 54 patients with non-proliferative DR (NPDR) to the NPDR group, and 58 patients with proliferative DR to the PDR group. General data, and HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR results were collected from the patients and compared among the groups. Pearson's correlation method was used to analyze the correlation between HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR indices, and multiple linear regression was applied to identify the risk factors for DR. Receiver operator characteristic (ROC) curves were also drawn. RESULTS: The differences in age, gender, systolic and diastolic blood pressure between the groups were not statistically significantly (P > 0.05), but the difference in disease duration was statistically significant (P < 0.05). The differences in fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglyceride between the groups were not statistically significant (P > 0.05). HbA1c in the PDR group was higher than that in the NPDR and NDR groups (P < 0.05). The levels of mALB, ß2MG, RBP, mALB/U-CR and U-CR in the PDR group were higher than those in the NPDR and NDR groups (P < 0.05). Multiple linear regression analysis showed that disease duration, HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR were risk factors for the development of DR. The ROC curve showed that the area under the curve (AUC) for the combination of indices (HbA1c + mALB + mALB/U-CR + U-CR + ß2MG + RBP) was 0.958, with a sensitivity of 94.83% and specificity of 96.72%, which was higher than the AUC for single index prediction (P < 0.05). CONCLUSION: HbA1c, mALB, mALB/U-CR, U-CR, ß2MG and RBP can reflect the development of DR and are risk factors affecting PDR, and the combination of these six indices has predictive value for PDR.

3.
Chem Commun (Camb) ; 59(65): 9832-9835, 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37505224

ABSTRACT

Unlike traditional methods of modifying phthalocyanines (Pcs), we herein report a smart and visible way to switch the aromaticity of silicon(IV) phthalocyanines via a reversible nucleophilic addition reaction of the Pc skeleton induced by alkalis and acids, leading to an interesting allochroism phenomenon and the switching of photosensitive activities.

4.
Food Res Int ; 164: 112344, 2023 02.
Article in English | MEDLINE | ID: mdl-36737936

ABSTRACT

Hypertrophy of adipose tissues and dysbiosis are hallmarks of obesity. Although drugs are applied for obesity treatment, side effects limit their use. The anti-obesity capacity of rosmarinic acid (RA) has been documented. Trichodesma khasianum Clarke is an edible RA-rich plant grown in Taiwan. Our previous study found that an 80 % ethanol extract of T. khasianum Clarke leaves (80EETC) ameliorates gastric mucosal damage through its anti-inflammatory, antioxidant, and microbiota modulation abilities. However, the anti-obesity effect of 80EETC remains unclear. Therefore, the objective of this study was to explore the protective effects of low-dose 80EETC (125 mg/kg b.w., 80EETCL) or high-dose 80EETC (250 mg/kg b.w., 80EETCH) on obesity development through gut microbiota modulation in high-fat diet (HFD)-induced C57BL/6 mice. The results showed a high RA content (89.2 ± 7.4 mg/g) in 80EETC. 80EETC administration significantly decreased body weight, body fat ratio, serum lipid levels (TC, TG, and LDL-C), adipose tissue accumulation, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in HFD-fed mice. Furthermore, supplementation with 80EETC reduced the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of gut microbiota (p_Bacteroidetes, f_Lactobacillus, f_Muribaculaceae, f_Prevotellaceae, g_Lactobacillus, g_Prevotellaceae_NK3B31_group, g_Ruminococcaceae_UCG-013, and g_Ruminococcaceae_UCG-014), which negatively correlated with obesity-related factors such as body weight, energy intake, fat accumulation in adipose tissue, TC, TG, LDL, and MDA. In conclusion, RA-rich 80EETC had a protective effect against obesity development and it has potential in healthy food applications.


Subject(s)
Diet, High-Fat , Microbiota , Mice , Animals , Mice, Obese , Diet, High-Fat/adverse effects , Dysbiosis/drug therapy , Mice, Inbred C57BL , Obesity/drug therapy , Body Weight , Bacteroidetes , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rosmarinic Acid
5.
Chempluschem ; 87(10): e202200113, 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36220346

ABSTRACT

This work reports the development of a multifunctional thermosensitive liposomal nanoplatform (PcS4 @Lip-FA) based on a metal-free phthalocyanine modified with tetra-sulfonates (PcPS4 ), which exhibited photodynamic and photothermal activities simultaneously. Upon irradiation with a near infrared laser, thermosensitive PcS4 @Lip-FA could release PcS4 as a result of the local hyperthermia of PcS4 . Interestingly, PcS4 could easily chelate with Cu2+ , leading to the enhancement of photothermal activity and decrease of photodynamic activity. In addition, in vivo fluorescence imaging revealed that PcS4 @Lip-FA could selectively accumulate in tumor tissue of H22 tumor-bearing mice after tail vein injection, and exhibited a significant anticancer phototherapeutic effect, with a tumor inhibition rate of 83.5 %. Therefore, PcPS4 @Lip-FA has realized fluorescence imaging-guided combined cancer treatment, providing a promising multifunctional nanoplatform for cancer diagnostics and therapy.

6.
World J Gastroenterol ; 28(33): 4861-4874, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36156921

ABSTRACT

BACKGROUND: The Rome IV criteria eliminated abdominal discomfort for irritable bowel syndrome (IBS), which was previously included in Rome III. There are questions as to whether IBS patients with abdominal discomfort (seen in Rome III but not Rome IV) are different from those with abdominal pain (Rome IV). AIM: To compare bowel symptoms and psychosocial features in IBS patients diagnosed with Rome III criteria with abdominal discomfort, abdominal pain, and pain & discomfort. METHODS: We studied IBS patients meeting Rome III criteria. We administered the IBS symptom questionnaire, psychological status, and IBS quality of life. Patients were classified according to the predominant abdominal symptom associated with defecation into an only pain group, only discomfort group, and pain & discomfort group. We compared bowel symptoms, extraintestinal symptoms, IBS quality of life, psychological status and healthcare-seeking behaviors, and efficacy among the three groups. Finally, we tested risk factors for symptom reporting in IBS patients. RESULTS: Of the 367 Rome III IBS patients enrolled, 33.8% (124 cases) failed to meet Rome IV criteria for an IBS diagnosis. There were no meaningful differences between the pain group (n = 233) and the discomfort group (n = 83) for the following: (1) Frequency of defecatory abdominal pain or discomfort; (2) Bowel habits; (3) Coexisting extragastrointestinal pain; (4) Comorbid anxiety and depression; and (5) IBS quality of life scores except more patients in the discomfort group reported mild symptom than the pain group (22.9% vs 9.0%). There is a significant tendency for patients to report their defecatory and non-defecatory abdominal symptom as pain alone, or discomfort alone, or pain & discomfort (all P < 0.001). CONCLUSION: IBS patients with abdominal discomfort have similar bowel symptoms and psychosocial features to those with abdominal pain. IBS symptoms manifesting abdominal pain or discomfort may primarily be due to different sensation and reporting experience.


Subject(s)
Irritable Bowel Syndrome , Abdominal Pain/complications , Abdominal Pain/etiology , Humans , Intestines , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/diagnosis , Quality of Life , Surveys and Questionnaires
7.
ACS Appl Mater Interfaces ; 14(25): 28581-28590, 2022 Jun 29.
Article in English | MEDLINE | ID: mdl-35709499

ABSTRACT

Phototherapy for non-invasive cancer treatment has been extensively studied. An urgent challenge in phototherapy application is to fabricate appropriate targeted agents to achieve efficient therapeutic effect. Herein, a molecular and supramolecular approach for targeting phototherapy was reasonably designed and realized through the axial sulfonate modification of silicon(IV) phthalocyanines (Pcs), followed by supramolecular interaction with albumin. This approach can not only improve the photoactivities (e.g., fluorescence emission and reactive oxygen species production) of the Pcs but also enhance their tumor targeting. Most importantly, one of the deigned Pcs (4) can target HepG2 cells through dual cell pathways, leading to an extremely high phototoxicity with an EC50 (i.e., concentration of Pcs to kill 50% of cells under light irradiation) value of 2.0 nM. This finding presents a feasible strategy to realize efficient targeting phototherapy.


Subject(s)
Antineoplastic Agents , Photochemotherapy , Albumins , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Indoles/metabolism , Indoles/pharmacology , Photosensitizing Agents/therapeutic use , Phototherapy
8.
Angew Chem Int Ed Engl ; 61(5): e202113506, 2022 01 26.
Article in English | MEDLINE | ID: mdl-34761489

ABSTRACT

The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4 A showed about 60-fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.


Subject(s)
Isoindoles
9.
J Mater Chem B ; 9(12): 2845-2853, 2021 03 28.
Article in English | MEDLINE | ID: mdl-33704321

ABSTRACT

Photothermal therapy (PTT) is a promising strategy for cancer treatment. However, the development of highly efficient photothermal agents with excellent biosafety, particularly with low liver retention, is very meaningful for clinical applications, but it is also challenging. We herein prepared a pH-sensitive nanoagent (NanoPc3) by the self-assembly of a zinc(ii) phthalocyanine substituted with hexadeca-sulphonates linked by hydrazone bonds for photoacoustic imaging and PTT. Due to the highly negative surface potential (-30.80 mV in water), NanoPc3 could effectively escape the phagocytosis of the reticuloendothelial system and be rapidly cleared from normal tissues, leading to little accumulation in the liver and excellent biosafety. The highly negatively-charged NanoPc3 changed into nearly neutral nanoparticles (NanoPc3H) under slightly acidic conditions, resulting in enhanced cellular uptake and retention time in tumor tissues. Moreover, the tumor of H22 tumor-bearing mice treated with NanoPc3 almost disappeared, suggesting an outstanding photothermal antitumor effect. NanoPc3 also hardly showed skin phototoxicity under irradiation. Its excellent antitumor effect and biosafety make NanoPc3 highly promising in clinical applications. This work will provide a new strategy for the design of tumor-targeted photothermal nanoagents with high biosafety.


Subject(s)
Antineoplastic Agents/pharmacology , Indoles/pharmacology , Nanoparticles/chemistry , Photothermal Therapy , Zinc/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , Hydrogen-Ion Concentration , Indoles/chemistry , Isoindoles , Liver Neoplasms, Experimental/drug therapy , Liver Neoplasms, Experimental/pathology , Mice , Molecular Structure , Zinc/chemistry
10.
Gastroenterol Nurs ; 44(2): 92-97, 2021.
Article in English | MEDLINE | ID: mdl-33675596

ABSTRACT

Bowel preparation is the basis of colonoscopy, and adequate bowel preparation is essential to the success of colonoscopy. Studies have been reported that telephone intervention can improve the quality of bowel preparation, while it remains unclear regarding effectiveness with the elderly. The purpose of this study was to evaluate the effect of telephone intervention on the quality of bowel preparation for colonoscopy in elderly outpatients. In total, 162 outpatients older than 65 years were enrolled and randomly divided into a control group and a study group. Patients in the study group were re-educated through telephone by a specific nurse 2 days before colonoscopy, whereas participants in the control group received education only on the day of appointment. The Ottawa score was used to evaluate the quality of bowel preparation between the two groups. In this study, no significant differences were observed in age, gender, body mass index, educational level, smoking and/or alcohol drinking, waiting time to colonoscopy, reasons for colonoscopy, and colonoscopic findings between the control group and the study group. Participants in the study group had higher adequate bowel preparation and compliance than the control group (83.1% vs. 59.5%, p = .03; 96.4% vs. 74.7%, p < .001). Univariate analysis showed that only noncompliance with start time was significantly associated with satisfactory bowel preparation in elderly patients. In conclusion, telephone intervention 2 days before colonoscopy can improve the quality of bowel preparation in the elderly.


Subject(s)
Cathartics , Colonoscopy , Aged , Aged, 80 and over , Female , Humans , Male , Prospective Studies , Single-Blind Method , Telephone
11.
J Inorg Biochem ; 217: 111371, 2021 04.
Article in English | MEDLINE | ID: mdl-33588279

ABSTRACT

To develop highly efficient photosensitizers for photodynamic therapy, herein a zinc(II) phthalocyanine-folate conjugate (PcN-FA) used to construct an activatable nanophotosensitizer (NanoPcN-FA) through a facile self-assembly. The self-assembled nanophotosensitizer (NanoPcN) without folate-modification was used as a negative control. After self-assembly, the photoactivities of NanoPcN-FA was quenched. The in vitro studies showed that NanoPcN-FA could be taken in by folate-receptor (FR)-positive SKOV3 cells and activated in the cells. It also exhibited slightly higher photocytotoxicity against SKOV3 cells than NanoPcN. Moreover, the competitive assay confirmed that the cellular uptake of NanoPcN-FA was through a FR-mediated process. Finally, the in vivo results indicated that NanoPcN-FA could target tumor tissue of S180 rat ascitic tumor-bearing mice due to the folic acid (FA) ligand, leading to a highly efficient antitumor photodynamic efficacy with the tumor inhibition rate of 95%.


Subject(s)
Antineoplastic Agents/therapeutic use , Indoles/therapeutic use , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/radiation effects , Cell Line, Tumor , Humans , Indoles/chemical synthesis , Indoles/radiation effects , Light , Mice , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/radiation effects , Rats
12.
Environ Sci Process Impacts ; 23(2): 357-366, 2021 Mar 04.
Article in English | MEDLINE | ID: mdl-33511973

ABSTRACT

Indoor dust ingestion is one of the main pathways for human exposure to organophosphate flame retardants (PFRs). The urinary concentrations of diesters (DAPs) are usually used as biomarkers to assess human exposure to PFRs. In this study, the PFR and DAP levels were measured in morning and evening urine samples of 30 workers from an e-waste dismantling site in southern China. The indoor dust samples were also collected from workshops and houses for analyzing associations between PFR and DAP levels in urine and dust. Tris(1-chloro-2-propyl) phosphate (TCIPP) and triphenyl phosphate (TPHP) were the dominant PFRs in dust, while bis(2-chloroethyl) phosphate (BCEP) and diphenyl phosphate (DPHP) were the major DAPs in dust. A significant positive correlation was observed between TPHP and DPHP concentrations in dust (p < 0.001), suggesting their potentially same source and the degradation of TPHP to form DPHP. TCIPP and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were the predominant PFRs, and BCEP, bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and DPHP were the main DAPs in both the morning and evening urine samples. The DPHP levels in evening urine samples were significantly correlated with TPHP and DPHP levels (p < 0.01) in dust. A similar correlation was found for the BCEP levels in the evening urine samples and the TCEP and BCEP levels (p < 0.01) in dust. These results indicated that in addition to being biotransformed from their respective parent PFRs, direct ingestion from indoor dust could also be the potential source for urinary DPHP and BCEP. Since relatively low detection frequencies were observed for bis(1-chloro-2-propyl) phosphate (BCIPP) and bis(butoxyethyl) phosphate (BBOEP) in urine, they may not be the major metabolites of TCIPP and tris(2-butoxyethyl) phosphate (TBOEP), respectively, in the human body. However, BDCIPP can be considered a useful biomarker because it is a unique metabolite of TDCIPP and has high detection frequencies in urine samples. The results of this study indicated the limitations of solely using urinary DAPs as biomarkers for the evaluation of human exposure to PFRs, and certain PFRs as well as hydroxylated PFRs (OH-PFRs) should also be considered for urinary biomonitoring in future studies.


Subject(s)
Electronic Waste , Flame Retardants , Biological Monitoring , China , Dust/analysis , Flame Retardants/analysis , Humans , Organophosphates/analysis
13.
J Photochem Photobiol B ; 213: 112086, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33232881

ABSTRACT

With a view to developing highly efficient photosensitizers for both antitumor and antimicrobial photodynamic therapies, herein, we reported a super cationic zinc(II) phthalocyanine (Pc4), which was prepared through the quaternization of the N, N-dimethyl-3-aminophenoxyl-hexadeca-substituted precursor Pc3. Meanwhile, two disubstituted analogues (Pc1 and Pc2) were also prepared as controls. The cationic Pc2 and Pc4 had higher photoactivities including fluorescence and singlet oxygen than the neutral counterparts Pc1 and Pc3, probably because of the inhibition of intramolecular charge transfer (ICT) effect of the amino groups. With the bulky steric effect and high hydrophilicity, Pc4 presented non-aggregated behavior in aqueous solutions. Therefore, it exhibited the highest in vitro photodynamic activity toward HepG2 cancer cells with an IC50 value as low as 0.04 µM. Furthermore, Pc4 showed a highly efficient in vivo PDT effect on H22 tumor-bearing mice with 98.7% tumor growth inhibition. In addition, Pc4 also exhibited an excellent in vitro and in vivo photodynamic inactivation against S. aureus. The results indicate that the non-aggregated hexadeca-cationic Pc4 could serve as a promising photosensitizer for both antitumor and antimicrobial photodynamic therapies.


Subject(s)
Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemical synthesis , Indoles/chemical synthesis , Organometallic Compounds/chemical synthesis , Photochemotherapy/methods , Photosensitizing Agents/chemical synthesis , Animals , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Cations/chemistry , Cell Membrane Permeability , Electron Transport , Female , Hep G2 Cells , Humans , Indoles/pharmacology , Isoindoles , Mice , Molecular Conformation , Neoplasms, Experimental , Organometallic Compounds/pharmacology , Photosensitizing Agents/pharmacology , Singlet Oxygen/chemistry , Spectrometry, Fluorescence , Staphylococcus aureus/radiation effects , Structure-Activity Relationship , Zinc Compounds
14.
Emerg Microbes Infect ; 9(1): 1628-1637, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32619386

ABSTRACT

Antimicrobial photodynamic therapy (aPDT) is an innovative approach to combat multi-drug resistant bacteria. It is known that cationic Zn(II) phthalocyanines (ZnPc) are effective in mediating aPDT against methicillin-resistant Staphylococcus aureus (MRSA). Here we used ZnPc-based photosensitizer named ZnPcE previously reported by our research group to evaluate its aPDT efficacy against broad spectrum of clinically relevant MRSAs. Remarkably, in vitro anti-MRSA activity was achieved using near-infrared (NIR, >610 nm) light with minimal bactericidal concentrations ranging <0.019-0.156 µM against the panel of MRSAs. ZnPcE was not only significantly (p < .05) more potent than methylene blue, which is a clinically approved photosensitizer but also demonstrated low cytotoxicity against human fibroblasts cell line (Hs-27) and human immortalized keratinocytes cell line (HaCaT). The toxicity was further evaluated on human 3-D skin constructs and found ZnPcE did not manifest in vivo skin irritation at ≤7.8 µM concentration. In the murine MRSA wound model, ZnPcE with PDT group demonstrated > 4 log10 CFU reduction and the value is significantly higher (p < .05) than all test groups except positive control. To conclude, results of present study provide a scientific basis for future clinical evaluation of ZnPcE-PDT on MRSA wound infection.


Subject(s)
Indoles/administration & dosage , Methicillin-Resistant Staphylococcus aureus/drug effects , Organometallic Compounds/administration & dosage , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Staphylococcal Infections/drug therapy , Administration, Topical , Animals , Cell Line , Disease Models, Animal , Humans , Indoles/chemistry , Indoles/pharmacology , Isoindoles , Male , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Mice , Microbial Sensitivity Tests , Molecular Structure , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Zinc Compounds
15.
Bioorg Med Chem Lett ; 30(12): 127164, 2020 06 15.
Article in English | MEDLINE | ID: mdl-32291134

ABSTRACT

To develop a highly efficient photosensitizer for photodynamic therapy (PDT), we have designed and synthesized a phthalocyanine-lactose conjugate (Pc-Lac) through axial modification of silicon(IV) phthalocyanine with lactose moieties. With the lactose substituents, Pc-Lac is highly hydrophilic and non-aggregated with efficient reactive oxygen species (ROS) generation in aqueous media. With these desirable properties, Pc-Lac shows high photocytotoxicity and cellular uptake toward HepG2 cells. In addition, in vivo fluorescence imaging shows that Pc-Lac could selectively remain at tumor site, leading to its enhanced photodynamic efficacy against H22 tumor-bearing mice. Therefore, Pc-Lac shows a great potential as a highly efficient molecular photosensitizer for PDT.


Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , Indoles/pharmacology , Lactose/pharmacology , Photochemotherapy , Photosensitizing Agents/pharmacology , Silicon/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , Indoles/chemistry , Isoindoles , Lactose/chemistry , Liver Neoplasms, Experimental/diagnostic imaging , Liver Neoplasms, Experimental/drug therapy , Mice , Molecular Structure , Optical Imaging , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Silicon/chemistry , Structure-Activity Relationship
16.
Bioconjug Chem ; 31(5): 1438-1448, 2020 05 20.
Article in English | MEDLINE | ID: mdl-32255337

ABSTRACT

Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application. In this work, C-phycocyanin (CPC) as a tumor-associated macrophages (TAMs) targeted vehicle was used to fabricate noncovalent ICG conjugate of CPC (ICG@CPC) via self-assembly in aqueous media. Compared to free ICG, ICG@CPC displays improved stabilities in aqueous solutions and under light irradiation and threefold increase in photothermal conversion efficiency. The in vitro results indicated that ICG@CPC could be selectively internalized into J774A.1 cells via SR-A-mediated endocytosis and lead to enhanced photocytotoxicity against J774A.1 cells. In vivo results showed that ICG@CPC had significantly improved drug accumulation in the tumor and photothermal therapeutic efficacy relative to ICG alone. This study for the first time utilizes CPC as a TAMs-targeted nanocarrier for ICG and may promote further rational design of ICG-based photothermal nanodrugs for precise and efficient cancer theranosis.


Subject(s)
Indocyanine Green/chemistry , Indocyanine Green/metabolism , Macrophages/metabolism , Phototherapy/methods , Phycocyanin/chemistry , Cell Line, Tumor , Endocytosis , Humans , Molecular Targeted Therapy , Water/chemistry
17.
ACS Appl Bio Mater ; 3(11): 7876-7885, 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-35019528

ABSTRACT

Thermodynamic therapy (TDT), one that uses heat to activate thermosensitizers and produce reactive oxygen species (ROS), has recently emerged as an attractive approach for cancer therapy. However, the development of safe and efficient thermosensitizers for TDT remains a big challenge. Here, we have found that artesunate (ARS) could produce ROS upon heating. Based on this interesting result, we have designed and prepared a pH-sensitive liposomal nanoplatform (ICG-ARS@NPs) composed of indocyanine green (ICG) and ARS for photoinduced TDT as well as photothermal therapy (PTT). Under the slightly acidic conditions in tumor tissues, the pH-sensitive liposomal ICG-ARS@NPs were able to release their drug cargos. Upon near-infrared irradiation, the photothermal agent ICG generated in situ hyperthermia and triggered the thermal sensitizing activity of ARS to produce ROS, resulting in damage to cancer cells and tumor tissues. The heat-induced ROS generation of ARS was also confirmed both in vitro and in vivo. In addition, because of their specific tumor targeting and synergistic photothermal and thermodynamic effects, ICG-ARS@NPs exhibited highly efficient anticancer therapeutic efficacy in H22 tumor-bearing mice. We believe that this work will promote the exploration of TDT for cancer therapy as well as the application of the old drug, artemisinin.

18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 615-621, 2019 Oct 30.
Article in Chinese | MEDLINE | ID: mdl-31699191

ABSTRACT

Objective To validate the Union Physio-Psycho-Social Assessment Questionnaire(UPPSAQ-70)and test its validity and reliability.Methods From April,2013 to July,2018,patients were asked to finish the computer evaluation of UPPSAQ-70 and Symptom Checklist 90(SCL-90)in Peking Union Medical College Hospital(PUMCH).Confirmatory factor analysis(CFA)was conducted on the SPSS 17.0,and the number of fixed factors was 8 factors and 3 factors.Amos 23.0 was used to verify the original 8-factor model,8-factor revision model,3-factor model,3-factor revision model,and single-factor model.Each factor of SCL-90 was used as the calibration standard to calculate the correlation coefficient between factors.The retest reliability was tested by the outpatients in PUMCH in July,2018.Results Exploratory factor analysis indicated that the 8-factor revised model included:depression,anxiety and fatigue,sleep,physical discomfort,sexual function,happiness and satisfaction,hypochondria,and social anxiety.The 3 factors revised model included that:psychological,physiological and social dimension.Confirmatory factor analysis indicated that the 8-factor modified model was superior to the 3-factor model and the single-factor model: χ 2=10 410.4,df=1862,RMSEA=0.07,CFI=0.753,and NFI=0.715.With SCL-90 as the standard criteria,except the low correlation coefficient between emotional scale and depression(r=0.600)and anxiety(r=0.520),the correlation coefficients of other symptoms were below 0.5.The chronbach's α between each factor and total score of UPPSAQ-70 was between 0.823 and 0.904,and the Chronbach's α coefficient of the whole scale was between 0.954 and 0.956 after each item was deleted.The retest reliability of the scale of 32 participants Chronbach's α was 0.847.Each item of the scale measured between one week was significantly correlated(P<0.05). Conclusion UPPSAQ-70 is a good scale for evaluating overall health status and is especially feasible in general hospitals.


Subject(s)
Psychological Tests/standards , Psychometrics , Surveys and Questionnaires , Factor Analysis, Statistical , Humans , Reproducibility of Results
19.
ACS Appl Mater Interfaces ; 11(40): 36435-36443, 2019 Oct 09.
Article in English | MEDLINE | ID: mdl-31525892

ABSTRACT

Self-assembled phototheranostic nanomaterials used for photodynamic therapy (PDT) have attracted increasing attention owing to their several advantages. Herein, we developed a novel strategy for size-tunable self-assembled nanophotosensitizers for PDT through a simple method. A series of switchable self-assembled nanophotosensitizers (NanoPc90, NanoPc40, NanoPc20, and NanoPc10) of different particle sizes were readily prepared based on an amphiphilic silicon(IV) phthalocyanine (SiPc)-biotin conjugate by regulating the amount of the Cremophor EL surfactant used. The photoactivities, including fluorescence and reactive oxygen species (ROS), of the self-assemblies could be regulated by the particle size. The self-assemblies could be specifically disassembled by tumor-overexpressing biotin receptors, leading to the recovery of quenched photoactivities. Demonstrated by the competitive assay, the self-assemblies were able to enter HepG2 cells through a biotin-receptor-mediated pathway, followed by biotin-receptor-triggered fluorescence recovery at the cellular level. Moreover, the particle size could also affect the in vitro and in vivo PDT effects and tumor targeting. The photocytotoxicity of NanoPc20 against HepG2 cells was more potent compared to that of NanoPc90 because of its strong intracellular fluorescence, higher intracellular ROS generation, and different subcellular localization. In addition, NanoPc20 showed higher in vivo tumor targeting and photodynamic therapeutic efficacy than NanoPc90. This work would provide a valuable reference for the development of self-assembled nanophotosensitizers for cancer diagnosis and therapy.


Subject(s)
Biotin/chemistry , Indoles/chemistry , Nanostructures/chemistry , Photochemotherapy , Photosensitizing Agents/pharmacology , Animals , Avidin/chemistry , Cell Proliferation/drug effects , Fluorescence , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Isoindoles , Mice , Nanostructures/ultrastructure , Particle Size , Reactive Oxygen Species/metabolism
20.
Biomater Sci ; 7(1): 211-219, 2018 Dec 18.
Article in English | MEDLINE | ID: mdl-30426113

ABSTRACT

Development of a photosensitizer that can achieve tumor specificity, improve therapeutic efficacy, and reduce side effects remains a challenge for photodynamic therapy (PDT). In this work, a pH-sensitive activatable nanophotosensitizer (SMSN-ZnPc1) has been elaborately designed, which could be readily prepared by using a functionalized zinc(ii) phthalocyanine (ZnPc) to conjugate with stellate mesoporous silica nanoparticles (SMSNs) through an acid-sensitive hydrazone bond. Meanwhile, a non-activatable analogue SMSN-ZnPc2 has also been prepared as a negative control. The fluorescence emission and singlet oxygen generation of the photosensitizer are essentially quenched in the intact nanophotosensitizer. However, these properties of SMSN-ZnPc1 can be restored greatly both in acidic solutions and at the cellular level. More importantly, after intravenous administration, SMSN-ZnPc1 can also be selectively activated at the tumor site and exhibit efficient tumor growth inhibition in S180 rat ascitic tumor-bearing KM mice with negligible systemic toxicity. It thus may serve as a promising nanoplatform for cancer diagnosis and targeted PDT.


Subject(s)
Delayed-Action Preparations/chemistry , Indoles/therapeutic use , Nanoconjugates/therapeutic use , Neoplasms/diagnosis , Neoplasms/drug therapy , Organometallic Compounds/therapeutic use , Photosensitizing Agents/therapeutic use , Silicon Dioxide/chemistry , Animals , Delayed-Action Preparations/administration & dosage , Female , HeLa Cells , Humans , Hydrogen-Ion Concentration , Indoles/administration & dosage , Indoles/chemistry , Isoindoles , Mice , Nanoconjugates/administration & dosage , Nanoconjugates/chemistry , Neoplasms/pathology , Optical Imaging/methods , Organometallic Compounds/administration & dosage , Organometallic Compounds/chemistry , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemistry , Porosity , Rats , Silicon Dioxide/administration & dosage , Zinc Compounds
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