Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on ...rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles' photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal.
Chemo-photothermal nanotheranostics has the advantage of synergistic therapeutic effect, providing opportunities for optimized cancer therapy. However, current chemo-photothermal nanotheranostic ...systems generally comprise more than three components, encountering the potential issues of unstable nanostructures and unexpected conflicts in optical and biophysical properties among different components. We herein synthesize an amphiphilic semiconducting polymer (PEG-PCB) and utilize it as a multifunctional nanocarrier to simplify chemo-photothermal nanotheranostics. PEG-PCB has a semiconducting backbone that not only serves as the diagnostic component for near-infrared (NIR) fluorescence and photoacoustic (PA) imaging, but also acts as the therapeutic agent for photothermal therapy. In addition, the hydrophobic backbone of PEG-PCB provides strong hydrophobic and π-π interactions with the aromatic anticancer drug such as doxorubicin for drug encapsulation and delivery. Such a trifunctionality of PEG-PCB eventually results in a greatly simplified nanotheranostic system with only two components but multimodal imaging and therapeutic capacities, permitting effective NIR fluorescence/PA imaging guided chemo-photothermal therapy of cancer in living mice. Our study thus provides a molecular engineering approach to integrate essential properties into one polymer for multimodal nanotheranostics.
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Hypoxia plays crucial roles in many diseases and is a central target for them. Present hypoxia imaging is restricted to the covalent approach, which needs tedious synthesis. In this work, a new ...supramolecular host–guest approach, based on the complexation of a hypoxia‐responsive macrocycle with a commercial dye, is proposed. To exemplify the strategy, a carboxyl‐modified azocalix4arene (CAC4A) was designed that binds to rhodamine 123 (Rho123) and quenches its fluorescence. The azo groups of CAC4A were selectively reduced under hypoxia, leading to the release of Rho123 and recovery of its fluorescence. The noncovalent strategy was validated through hypoxia imaging in living cells treated with the CAC4A–Rho123 reporter pair.
A supramolecular strategy for fluorescent hypoxia imaging is proposed based on the host–guest complexation of azomacrocycles with commercial dyes.
The role of vaginal microecology in the cervical cancer Wei, Wei; Xie, Liang‐Zhen; Xia, Qing ...
The journal of obstetrics and gynaecology research,
September 2022, 2022-09-00, 20220901, Letnik:
48, Številka:
9
Journal Article
Recenzirano
Aim
To explore the role of vaginal microecology in cervical cancer, so as to increase the understanding of cervical cancer and lay a foundation for future large‐sample clinical trials.
Methods
We ...reviewed and summarized the literature comprehensively, and discussed the relationship between vaginal microecology and HPV infection, CIN progression and cervical cancer, as well as the potential molecular mechanism and the prospects of probiotics and prebiotics in future cancer treatments.
Results
With the popularization of high‐throughput sequencing technology and the development of bioinformatics analysis technology, many evidences show that the increase in the diversity of the bacterial community in the vaginal microecological environment and the decrease in the number of Lactobacilli are associated with the continuous infection of HPV and the further development of CIN, cervical cancer‐related.
Conclusions
Vaginal microecological imbalance has an important impact on the occurrence and development of cervical cancer. However, the pathogenesis is not completely clear, and more high‐level basic research and longitudinal clinical studies are needed to verify.
Microglia are rapidly activated after acute ischemic stroke, and the polarization of microglial is associated with the prognosis of acute ischemic stroke. Lipoxin A4 (LXA4), an anti-inflammatory ...agent, has a protective effect against ischemic stroke. However, the role of LXA4 on the polarization of microglial after acute ischemic stroke remains undetermined. We hypothesized that LXA4 may exert the neuroprotective effect though regulating the polarization of microglial. In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted protective effects on focal cerebral ischemia-reperfusion injury and reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, LXA4 inhibited the expression of Notch-1, Hes1, iNOS and CD32 all of which are associated with the differentiation into M1 microglia. By contrast, LXA4 upregulated the expression of Hes5, Arg-1 and CD206 all of which are associated with M2 phenotype in microglia. In addition, blocking the Notch signaling pathway with the inhibitor DAPT significantly mitigated the effect of LXA4 on microglia differentiation. These data suggest that LXA4 may regulate the polarization of microglia after cerebral ischemia-reperfusion injury through the Notch signaling pathway.
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•Microglia, is activated after acute ischemic stroke, which plays a dual role in promoting and alleviating inflammation.•LXA4 can inhibit the pro-inflammatory response after ischemic stroke and regulate the polarization of microglia.•Blocking Notch signaling pathway with DAPT weaken the effect of LXA4.
Semiconducting polymer nanoparticles (SPNs) emitting in the second near-infrared window (NIR-II, 1000–1700 nm) are promising materials for deep-tissue optical imaging in mammals, but the brightness ...is far from satisfactory. Herein, we developed a molecular design strategy to boost the brightness of NIR-II SPNs: structure planarization and twisting. By integration of the strong absorption coefficient inherited from planar π-conjugated units and high solid-state quantum yield (ΦPL) from twisted motifs into one polymer, a rise in brightness was obtained. The resulting pNIR-4 with both twisted and planar structure displayed improved ΦPL and absorption when compared to the planar polymer pNIR-1 and the twisted polymer pNIR-2. Given the emission tail extending into the NIR-IIa region (1300–1400 nm) of the pNIR-4 nanoparticles, NIR-IIa fluorescence imaging of blood vessels with enhanced clarity was observed. Moreover, a pH-responsive poly(β-amino ester) made pNIR-4 specifically accumulate at tumor sites, allowing NIR-IIa fluorescence image-guided cancer precision resection. This study provides a molecular design strategy for developing highly bright fluorophores.
Therapeutic efficacy of synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) is limited by complex conjugation chemistry, absorption wavelength mismatch, and inadequate ...biodegradability of the PDT–PTT agents. Herein, we designed biocompatible copper sulfide nanodot anchored folic acid-modified black phosphorus nanosheets (BP-CuS-FA) to overcome these limitations, consequently enhancing the therapeutic efficiency of PDT–PTT. In vitro and in vivo assays reveal good biocompatibility and commendable tumor inhibition efficacy of the BP-CuS-FA nanoconjugate because of the synergistic PTT–PDT mediated by near-infrared laser irradiation. Importantly, folic acid unit could target folate receptor overexpressed cancer cells, leading to enhanced cellular uptake of BP-CuS-FA. BP-CuS-FA also exhibits significant contrast effect for photoacoustic imaging, permitting its in vivo tracking. The photodegradable character of BP-CuS-FA is associated with better renal clearance after the antitumor therapy in vivo. The present research may facilitate further development on straightforward approaches for targeted and imaging-guided synergistic PDT–PTT of cancer.
Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although it displays efficacy in the construction of activatable photosensitizers (PSs), direct ...covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes, and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host–guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state). When nanocarriers were accumulated into tumor tissues via the enhanced permeability and retention effect, the overexpressed biomarker adenosine triphosphates displaced PSs, accompanied by their fluorescence and photoactivity recovered (ON state). These reinstallations are unattainable in normal tissues, allowing us to concurrently achieve selective tumor imaging and targeted therapy in vivo. Compared with widely used covalent approach, the present BDA strategy provides the following advantages: (1) employment of approved PSs without custom covalent decoration; (2) traceless release of PSs with high fidelity by biomarker displacement; (3) adaptability to different PSs for establishing a universal platform and promised facile combination of diverse PSs to enhance photon utility in light window. Such a host–guest BDA strategy is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.
To investigate the association of miR-106b-5p with neuroinflammation and microglial activation in a status epilepticus (SE) mouse model. We examined changes in the expression of microRNA-106b-5p ...(miRNA-106b-5p), repulsive guidance molecule A (RGMa), triggering receptor expressed on myeloid cells 2 (TREM2), and the microglia-related markers interleukin (IL)-1β, IL-4, IL-6, IL-10, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1) in the mouse hippocampus of the lithium–pilocarpine-induced SE mouse model. Eighty-four female C57BL/6 mice were randomly divided into a normal control group (
n
= 12), and six SE groups (
n
= 12/group), which were monitored at 6 h and at 1, 3, 7, 14, and 21 days (d) post-SE induction. Unlike in the dentate gyrus, immunohistochemical staining revealed prominent neuronal swelling at 6 h, significant neuronal loss and apoptosis on day 3, and recovery by day 14 in the hippocampal
cornu ammonis
(CA)1 and CA3 pyramidal cells in SE mice. We noted elevated levels of miRNA-106b-5p and all microglia-related markers, which peaked at 3 days post-SE, except IL-4, which peaked at 7 days post-SE, indicating inflammation and microglial activation. RGMa and TREM2 levels decreased at 6 h post-SE. All markers but miRNA-106b-5p, RGMa, and TREM2 returned to baseline levels at 21 days post-SE. Dual luciferase reporter gene assay showed that microRNA-106b-5p can interact with RGMa. We observed that miR-106b-5p level increased while both RGMa and TREM2 levels decreased post-SE and showed associations with microglial activation and inflammation in the mouse hippocampus, suggesting their potential as SE therapeutic targets.
Mitochondria are critical in determining a cell’s energy homeostasis and fate, and mitochondrial dysfunction has been implicated in the pathogenesis of chronic kidney disease (CKD). We sought to ...identify causative mitochondrial microRNAs. A microarray screen of kidney tissue from healthy mice identified 97 microRNAs that were enriched in the mitochondrial fraction. We focused on microRNA-214-3p (miR-214) because of a very high ratio of mitochondrial to cytoplasmic expression in the kidney compared to other organs. Tubular expression of miR-214 was more abundant in kidney tissue from patients with CKD than from healthy controls, and was positively correlated with the degree of proteinuria and kidney fibrosis. Expression of miR-214 was also increased in the kidney of mouse models of CKD induced by obstruction, ischemia/reperfusion, and albumin overload. Proximal tubule–specific deletion of miR-214 attenuated apoptosis, inflammation, fibrosis, and mitochondrial damage in these CKD models. Pharmacologic inhibition of miR-214 had a similar effect in the albumin overload model of CKD. In vitro, overexpressing miR-214 in proximal tubular cell lines induced apoptosis and disrupted mitochondrial oxidative phosphorylation, while miR-214 expression was upregulated in response to a variety of insults. The mitochondrial genes mt-Nd6 and mt-Nd4l were identified as the specific targets of miR-214 in the kidney. Together, these results demonstrate a pathogenic role of miR-214 in CKD through the disruption of mitochondrial oxidative phosphorylation, and suggest the potential for miR-214 to serve as a therapeutic target and diagnostic biomarker for CKD.
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