ABSTRACT
BACKGROUND: Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies. AIM: To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism. METHODS: To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1). RESULTS: In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR. CONCLUSIONS: Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.
ABSTRACT
Perylenequinonoid natural products are a class of photosensitizers (PSs) that exhibit high reactive oxygen species (ROS) generation and excellent activity for Type I/Type II dual photodynamic therapy. However, their limited activity against gram-negative bacteria and poor water solubility significantly restrict their potential in broad-spectrum photodynamic antimicrobial therapy (PDAT). Herein, a general approach to overcome the limitations of perylenequinonoid photosensitizers (PQPSs) in PDAT by utilizing a macrocyclic supramolecular carrier is presented. Specifically, AnBox·4Cl, a water-soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host-guest complexes with high binding constants (≈107 m -1) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram-negative bacteria. As a result, the AnBox·4Cl-PQPS complexes can effectively anchor on the surfaces of gram-negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad-spectrum PDAT effect against both gram-negative and gram-positive bacteria. This work paves a new path to enhance PDAT by showcasing an efficient approach to improve PQPSs' water solubility and killing efficacy for gram-negative bacteria.
ABSTRACT
RATIONALE: This study used proteomics-based data-independent acquisition (DIA) technology with the aim of screening for differential expression proteins in type I gastric neuroendocrine neoplasm (g-NEN). METHODS: Differential expression proteins in type I g-NEN and peritumoral tissues were screened using DIA with liquid chromatography/tandem mass spectrometry (DIA-LC/MS/MS). The identified proteins were then functionally analysed using bioinformatics methods. We selected the three most highly expressed proteins, combined with patients' clinical data, for prognostic analysis. RESULTS: Compared with peritumoral tissues, 224 proteins were up-regulated, and 70 were down-regulated. The most significantly enriched biological processes and pathways were vacuolar proton-transporting V-type ATPase complex assembly and metabolism-related pathways. PCSK1, FBXO2, ACSL1, IRS2, and PTPRZ1 expression was markedly up-regulated in type I g-NENs. High IRS2 expression significantly correlated with a shorter time to recurrence. CONCLUSIONS: Our study provides a comprehensive proteomic signature based on DIA-LC/MS/MS and highlights high IRS2 expression as a potential prognostic marker for type I gNENs.
Subject(s)
Biomarkers, Tumor , Neuroendocrine Tumors , Proteomics , Stomach Neoplasms , Tandem Mass Spectrometry , Humans , Stomach Neoplasms/metabolism , Stomach Neoplasms/chemistry , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Tandem Mass Spectrometry/methods , Male , Female , Chromatography, Liquid/methods , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/chemistry , Prognosis , Proteomics/methods , Middle Aged , Adult , Aged , Proteome/analysis , Proteome/metabolism , Liquid Chromatography-Mass SpectrometryABSTRACT
We report herein a way to prepare and purify optoelectronic functional 4,9- and 4,10-substituted pyrene isomers. By tuning the size of substituents, the designed 4,9- and 4,10-isomers can be successfully isolated by recycling preparative size-exclusion chromatography (SEC) and/or repeated recrystallization. The structure and purity of the isolated compounds 1-5 have been confirmed by 1H NMR, 13C NMR, and HRMS. The photophysical and electrochemical properties of compounds 1-5 have been studied in detail both experimentally and theoretically. The lowest transitions of these pyrenes, 1-5, are allowed, with moderate to high fluorescence quantum yields and radiative decay rates around 108 s-1. The differences between the electrochemical and photophysical properties of 4,9-, 4,10-, 1,6-, and 2,7-substituted isomers are compared and concluded.
ABSTRACT
The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood-brain barrier (BBB) and the dense glioblastoma tissue. To achieve efficient BBB crossing and deep GBM penetration, this work demonstrates a strategy of active transcellular transport of a mitochondrion-disturbing nanomedicine, pGBEMA22-b-pSSPPT9 (GBEPPT), in the GBM tissue through mitocytosis. GBEPPT is computer-aided designed and prepared by self-assembling a conjugate of an amphiphilic block polymer and a drug podophyllotoxin (PPT). When GBEPPT is delivered to the tumor site, overexpressed γ-glutamyl transpeptidase (GGT) on the brain-blood endothelial cell, or the GBM cell triggered enzymatic hydrolysis of γ-glutamylamide on GBEPPT to reverse its negative charge to positive. Positively charged GBEPPT rapidly enter into the cell and target the mitochondria. These GBEPPT disturb the homeostasis of mitochondria, inducing mitocytosis-mediated extracellular transport of GBEPPT to the neighboring cells via mitosomes. This intracellular-to-intercellular delivery cycle allows GBEPPT to penetrate deeply into the GBM parenchyma, and exert sustainable action of PPT released from GBEPPT on the tumor cells along its penetration path at the tumor site, thus improving the anti-GBM effect. The process of mitocytosis mediated by the mitochondrion-disturbing nanomedicine may offer great potential in enhancing drug penetration through malignant tissues, especially poorly permeable solid tumors.
Subject(s)
Glioblastoma , Mitochondria , Polymers , Mitochondria/metabolism , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Cell Line, Tumor , Polymers/chemistry , Animals , Blood-Brain Barrier/metabolism , Podophyllotoxin/chemistry , Podophyllotoxin/pharmacology , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , gamma-Glutamyltransferase/metabolism , Drug Carriers/chemistryABSTRACT
Genetic manipulations and pharmaceutical interventions to disturb lipid metabolism homeostasis have emerged as an attractive approach for the management of cancer. However, the research on the utilization of bioactive materials to modulate lipid metabolism homeostasis remains constrained. In this study, heptakis (2,3,6-tri-O-methyl)-ß-cyclodextrin (TMCD) is utilized to fabricate homomultivalent polymeric nanotraps, and surprisingly, its unprecedented ability to perturb lipid metabolism homeostasis and induce pyroptosis in tumor cells is found. Through modulation of the density of TMCD arrayed on the polymers, one top-performing nanotrap, PTMCD4, exhibits the most powerful cholesterol-trapping and depletion capacity, thus achieving prominent cytotoxicity toward different types of tumor cells and encouraging antitumor effects in vivo. The interactions between PTMCD4 and biomembranes of tumor cells effectively enable the reduction of cellular phosphatidylcholine and cholesterol levels, thus provoking damage to the biomembrane integrity and perturbation of lipid metabolism homeostasis. Additionally, the interplays between PTMCD4 and lysosomes also induce lysosomal stress, activate the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasomes, and subsequently trigger tumor cell pyroptosis. To sum up, this study first introduces dendronized bioactive polymers to manipulate lipid metabolism and has shed light on another innovative insight for cancer therapy.
Subject(s)
Amides , Cyclopropanes , Neoplasms , Pyroptosis , Humans , Lipid Metabolism , Homeostasis , Cholesterol , Neoplasms/drug therapy , Polymers/metabolismABSTRACT
Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.
Subject(s)
Paclitaxel , Stomach Neoplasms , Humans , Angiogenesis Inhibitors , Cathepsin B , Cell Line, Tumor , Phosphatidylinositol 3-Kinases , Polymers , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-akt , Stomach Neoplasms/drug therapyABSTRACT
Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multifunctional and tunable physiochemical properties in alignment with tumor genetic profiles can achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, this work reviews the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy, and outlines novel strategies for the development of nanomedicine against drug resistance. This work focuses on engineering design, customized delivery, current challenges, and clinical translation of nanomedicine in the application of resistant lung cancer.
Subject(s)
Antineoplastic Agents , Lung Neoplasms , Neoplasms , Humans , Nanomedicine , Lung Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Drug Delivery Systems , Drug Resistance, NeoplasmABSTRACT
A novel class of multiple BâN Lewis pair-functionalized polycyclic aromatic hydrocarbons with different BR2 groups (R = Cl or Et) directly attached at positions 1, 6, and 11 of triazatruxene was synthesized. The triazatruxene backbone of 4 displays a bowl shape, and its molecular skeleton shows a highly twisted propeller-like structure with C3 symmetry. The introduction of BâN Lewis pairs not only results in a large decrease in the HOMO-LUMO gap but also lowers the LUMO to -3.00 eV. Both compounds show excellent stability with large Stokes shifts of ≤8234 cm-1 and solvatochromic emission in solvents of different polarities.
ABSTRACT
BACKGROUND: By investigating the knowledge, medication, occurrence of complications, and risks among elderly non-valvular atrial fibrillation (NVAF) patients in Shanghai communities, and providing standardized comprehensive management and follow-up, we aim to explore the impact of standardized community management on improving disease awareness, standardizing atrial fibrillation (AF) treatment, reducing the risk of complications occurrence, and addressing risk factors for AF patients. METHODS: This research selected elderly atrial fibrillation patients from Zhuanqiao Community Health Service Center, Minhang District, Shanghai from July 2020 to October 2022. Their personal health records and examination results were reviewed, and the incidence of AF, awareness, medication, and complications were investigated. Age-adjusted Charlson Comorbidity Index (aCCI), CHA2DS2-VASc score, and HAS-BLED score were used to evaluate disease burden, thromboembolic risk, and bleeding risk, respectively. The patients were subjected to standardized community management, and the compliance rate of disease awareness, treatment, resting heart rate, blood pressure, fasting blood glucose, and body mass index (BMI) were assessed at the baseline, 6 months and 1 year after management. RESULTS: A total of 243 NVAF patients were included, with an average aCCI score of (4.5 ± 1.1). Among them, 28% of the patients were aware of their AF, and 18.1% of the patients were aware of the hazards of AF. Of the patients, 11.9% used anticoagulant drugs, including 6.6% and 5.3% for warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), respectively. 7% of patients used antiplatelet drugs. 26.7% of the patients used heart rate control drugs. 10.3% of the patients experienced thromboembolic events, and 0.8% of the patients experienced bleeding events. 93.0% of the patients were at high risk of thromboembolism, and 24.7% of the patients were at high risk of bleeding. Compared with the baseline, there were significant statistical differences (P < 0.001) in disease awareness, awareness of the hazards of AF, use of anticoagulant drugs and heart rate control drugs, and control of risk factors among NVAF patients after standardized community management. Moreover, with the extension of management time, there was a linear increase in the awareness of NVAF, awareness of the hazards of AF, utilization rate of anticoagulant drugs, utilization rate of heart rate control drugs, blood pressure, blood glucose, and BMI compliance rate (P < 0.001). CONCLUSION: Currently, the awareness, treatment, and control of risk factors for AF in elderly NVAF patients in Shanghai community are not satisfactory. Standardized community management helps to improve the diagnosis, treatment, and control of risk factors in AF.
Subject(s)
Atrial Fibrillation , Stroke , Thromboembolism , Humans , Aged , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Anticoagulants/adverse effects , Administration, Oral , Stroke/drug therapy , Stroke/epidemiology , Stroke/etiology , China/epidemiology , Risk Factors , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Hemorrhage/epidemiology , Thromboembolism/epidemiology , Thromboembolism/etiology , Thromboembolism/prevention & controlABSTRACT
Developing nanoplatforms integrating superior fluorescence imaging ability in second near-infrared (NIR-II) window and tumor microenvironment responsive multi-modal therapy holds great potential for real-time feedback of therapeutic efficacy and optimizing tumor inhibition. Herein, we developed a pH-sensitive pyrrolopyrrole aza-BODIPY-based amphiphilic molecule (PTG), which has a balanced NIR-II fluorescence brightness and photothermal effect. PTG is further co-assembled with a vascular disrupting agent (known as DMXAA) to prepare PTDG nanoparticles for combined anti-vascular/photothermal therapy and real-time monitoring of the tumor vascular disruption. Each PTG molecule has an active PT-3 core which is linked to two PEG chains via pH-sensitive ester bonds. The cleavage of ester bonds in the acidic tumor environment would tricker releases of DMXAA for anti-vascular therapy and further assemble PT-3 cores into micrometer particles for long term monitoring of the tumor progression. Furthermore, benefiting from the high brightness in the NIR-II region (119.61 M-1 cm-1) and long blood circulation time (t1/2 = 235.6 min) of PTDG nanoparticles, the tumor vascular disrupting process can be in situ visualized in real time during treatment. Overall, this study demonstrates a self-assembly strategy to build a pH-responsive NIR-II nanoplatform for real-time monitoring of tumor vascular disruption, long-term tracking tumor progression and combined anti-vascular/photothermal therapy.
Subject(s)
Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/pathology , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Esters , Cell Line, Tumor , Phototherapy/methods , Tumor MicroenvironmentABSTRACT
Lipid droplets (LDs) are crucial organelles used to store lipids and participate in lipid metabolism in cells. The abnormal aggregation and polarity change of LDs are associated with the occurrence of diseases, such as steatosis. Herein, the polarity-sensitive probe TBPCPP with a donor-acceptor-π-acceptor (D-A-π-A) structure was designed and synthesized. The TBPCPP has a large Stokes shift (â¼220 nm), excellent photostability, high LD targeting, and considerable two-photon absorption (TPA) cross-section (â¼226 GM), enabling deep two-photon imaging (â¼360 µm). In addition, the fluorescence lifetime of TBPCPP decreases linearly with increasing solvent polarity. Therefore, with the assistance of two-photon fluorescence lifetime imaging microscopy (TP-FLIM), TBPCPP has successfully achieved not only the visualization of polarity changes caused by LD accumulation in HepG-2 cells but also lipid-specific imaging and visualization of different polarities in lipid-rich regions in zebrafish for the first time. Furthermore, TP-FLIM revealed that the polarity gradually decreases during steatosis in HepG-2 cells, which provided new insights into the diagnosis of steatosis.
Subject(s)
Lipid Droplets , Zebrafish , Animals , Lipid Droplets/chemistry , Microscopy, Fluorescence/methods , Photons , Lipids/analysis , Fluorescent Dyes/chemistryABSTRACT
As a class of highly dynamic organelles, lipid droplets (LDs) are involved in numerous physiological functions, and the changes in polarity of LDs are closely related to a variety of diseases. In this work, we developed two polarity-sensitive fluorescent probes (CC-CH and CC-Cl) based on curcumin analogs. CC-CH and CC-Cl with a donor-acceptor-donor (D-A-D) structure exhibited the property of intramolecular charge transfer (ICT); thus, their fluorescence emissions were significantly attenuated with increasing ambient polarity. Cell experiments indicated that CC-CH and CC-Cl showed excellent photostability, a low cytotoxicity, and a superior targeting ability regarding LDs. After treatment with oleic acid (OA) and methyl-ß-cyclodextrin (M-ß-CD), the polarity changes of LDs in living cells could be visualized by using CC-CH and CC-Cl. In addition, CC-CH and CC-Cl could monitor polarity changes of LDs in different pathological processes, including inflammatory responses, nutrient deprivation, and H2O2-induced oxidative stress. Therefore, CC-CH and CC-Cl are promising potential fluorescent probes for tracking intracellular LD polarity changes.
ABSTRACT
Cancer stem cells (CSCs) have been demonstrated to be involved in tumor initiation and relapse, and the presence of CSCs in the tumor tissue often leads to therapeutic failure. BBI608 has been identified to eliminate CSCs by inhibiting signal transducer and activator of transcription 3 (STAT3). In this study, we confirm that BBI608 can efficiently suppress the proliferation and migration of non-small cell lung cancer (NSCLC) cells, and specifically kill the stemness-high population in chemoresistant NSCLC cells. To improve its bioavailability and tumor accumulation, BBI608 is successfully encapsulated into redox-responsive PEGylated branched N-(2-hydroxypropyl) methacrylamide (HPMA)-deoxy cholic acid (DA) polymeric nanoparticles (BBI608-SS-NPs). The BBI608-SS-NPs can release the drug in response to high concentrations of intracellular glutathione, and exhibit cytotoxicity against lung cancer cells and CSCs comparable to the free drug BBI608. Furthermore, the BBI608-SS-NPs preferentially accumulate in tumor sites, resulting in a superior anti-tumor efficacy in both cisplatin-resistant cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of NSCLC. Mechanistic studies demonstrate that BBI608-SS-NPs not only directly inhibit the downstream genes of the STAT3 pathway, but also indirectly inhibit the Wnt pathway. Overall, this stimuli-responsive polymeric nanoformulation of BBI608 shows great potential in the treatment of chemoresistant NSCLC by targeting CSCs.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , STAT3 Transcription Factor/metabolism , Oxidation-Reduction , Cell Proliferation , Cell Line, Tumor , Neoplastic Stem Cells/metabolismABSTRACT
Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug-tolerant state without genetic variations. These drug-tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy-resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC-targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.
ABSTRACT
BACKGROUND: There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. METHODS: This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. RESULTS: The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors < 8 and ≥ 8 was statistically significant (p = 0.002). CONCLUSIONS: The incidence of rectal multiple neuroendocrine neoplasms accounted for 3.8% of all rectal neuroendocrine neoplasms. For rectal multiple neuroendocrine neoplasms, the lymph node metastasis rate was higher when the number of tumors was ≥ 8. The influence of the number of tumors on lymph node metastasis should be considered in the selection of treatment.
Subject(s)
Neuroendocrine Tumors , Rectal Neoplasms , Humans , Prognosis , Lymphatic Metastasis , Retrospective Studies , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/pathology , Rectal Neoplasms/diagnosis , Rectal Neoplasms/epidemiology , Rectal Neoplasms/pathologyABSTRACT
Real-time monitoring vascular responses is crucial for evaluating the therapeutic effects of vascular-targeted photodynamic therapy (V-PDT). Herein, we developed a highly-stable and bright aggregation induced emission (AIE) fluorophore (PTPE3 NP) for dynamic fluorescence (FL) imaging of vascular dysfunction beyond 1300 nm window during V-PDT. The superior brightness (ϵmaxΦf>1000 nm ≈ 180.05 M-1 cm-1) and high resolution of PTPE3 NP affords not only high-clarity images of whole-body and local vasculature (hindlimbs, mesentery, and tumor) but also high-speed video imaging for tracking blood circulation process. By virtue of the NPs' prolonged blood circulation time (t1/2 ≈ 86.5 min) and excellent photo/chemical (pH, RONS) stability, mesenteric and tumor vascular dysfunction (thrombosis formation, vessel occlusion, and hemorrhage) can be successfully visualized during V-PDT by FL imaging for the first time. Furthermore, the reduction of blood flow velocity (BFV) can be monitored in real time for precisely evaluating efficacy of V-PDT. These provide a powerful approach for assessing vascular responses during V-PDT and promote the development of advanced fluorophores for biological imaging.
Subject(s)
Neoplasms , Photochemotherapy , Animals , Humans , Photochemotherapy/methods , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/blood supply , Optical Imaging/methodsABSTRACT
The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 107 level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HBâAnBox4+ and HBâExAnBox4+) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HBâAnBox4+ and HBâExAnBox4+ have different delivery effects at the cellular level.
ABSTRACT
Few studies have explored the association between organizational justice and mental health, particularly in collectivist countries. Hence, the aim of the present study was to evaluate the impact of organizational justice on psychological distress and to discuss the findings in collectivist culture. A cross-sectional survey was conducted among nurses from public hospitals in western of China, July 2022, which followed the STROBE guidelines. This study used Chinese versions of the Organizational Justice Scale and Kesseler Psychological Distress Scale to assess the perceptions of organizational justice and mental health levels, respectively. A total of 663 nurses completed the questionnaires. The psychological distress of university-educated and low-income nurses was poor. There was a moderately positive relationship between organizational justice and psychological distress (Râ =â 0.508, Pâ <â .01), indicating that the greater level of organizational injustice, the poorer mental health. Hierarchical regression analysis showed that organizational justice was an strong predictor of psychological distress, accounting for approximately 20.5% of the psychological distress. The findings of this study highlight the importance of interpersonal injustice and distributive injustice on psychological distress specific in Chinese culture, suggesting that nursing management or leaders should notice that the most being taken seriously by nurses is their recognition and respect for subordinate, meanwhile, alerting nurses, in some sense, a negative relationship with leaders as a kind of workplace bullying could harm their mental health. The promulgation of organizational justice policy to protect employees from the government and the real role of employee labor union organizations are urgently needed.
Subject(s)
Nurses , Organizational Culture , Humans , Cross-Sectional Studies , Social Justice/psychology , Surveys and Questionnaires , Hospitals, Public , Workplace/psychologyABSTRACT
Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used to construct long-wavelength NIR-II emitters as their optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, their wide applications in the NIR-II fluorescence imaging are impeded by the limited varieties of J-type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) with anti-quenching effect is reported for highly efficient NIR-II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation-induced emission (AIE) property for conquering the self-quenching issue of the J-type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR-II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole-body blood vessel and imaging-guided phototherapy results verify that BT6 NPs are excellent agent for NIR-II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR-II J-aggregates with precisely manipulated anti-quenching properties for highly efficient biomedical applications.