Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging ...modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy.
Multidrug resistance (MDR) is an issue that is not only related to cancer cells but also associated with the tumor microenvironments. MDR involves the complicated cancer cellular events and the ...crosstalk between cancer cells and their surroundings. Ideally, an effective system against MDR cancer should take dual action on both cancer cells and tumor microenvironments. The authors find that both the drug‐resistant colon cancer cells and the protumor M2 macrophages highly express two nutrient transporters, i.e., secreted protein acidic and rich in cysteine (SPARC) and mannose receptors (MR). By targeting SPARC and MR, a system can act on both cancer cells and M2 macrophages. Herein the authors develop a mannosylated albumin nanoparticles with coencapsulation of different drugs, i.e., disulfiram/copper complex (DSF/Cu) and regorafenib (Rego). The results show that combination therapy of DSF/Cu and Rego efficiently inhibits the growth of drug‐resistant colon tumor, and the combination has not been reported yet for use in anticancer treatment. The system significantly improves the treatment outcomes in the animal model bearing drug‐resistant tumors. The therapeutic mechanisms involve enhanced apoptosis, upregulation of intracellular ROS, anti‐angiogenesis, and tumor‐associated macrophage “re‐education.” This strategy is characterized by dual targeting to and the simultaneous action on cancer cells and M2 macrophages, with biomimetic codelivery of a novel drug combination.
Multidrug resistance (MDR) is a complex of various events involving not only the cancer cells but also their surroundings (tumor microenvironments). The authors develop the “one stone two birds” strategy to overcome MDR by using a mannosylated albumin nanoparticulate codelivery system to dual‐target the cancer cells and M2 macrophages, both of which overexpress mannose receptors and the albumin‐binding protein—secreted protein acidic and rich in cysteine.
We aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis.
Data of 1224 patients with NB were obtained from the Surveillance, ...Epidemiology and End Results database (2010-2018). Pearson's chi-square test, Kaplan-Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis.
The overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III-IV (OR: 26.228, P < 0 .001) and 5-10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB.
Metastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.
Hypoxia and high accumulation of lactic acid in the tumor microenvironment provide fertile soil for tumor development, maintenance and metastasis. Herein, we developed a calcium peroxide ...(CaO.sub.2)-loaded nanostructure that can play a role of "one stone kill two birds", i.e., acidic and hypoxic tumor microenvironment can be simultaneously regulated by CaO.sub.2 loaded nanostructure. Specifically, CaO.sub.2-loaded mesoporous polydopamine nanoparticles modified with sodium hyaluronate (denoted as CaO.sub.2@mPDA-SH) can gradually accumulate in a tumor site. CaO.sub.2 exposed in acidic microenvironment can succeed in consuming the lactic acid with oxygen generation simultaneously, which could remodel the acid and hypoxia tumor microenvironment. More importantly, the relief of hypoxia could further reduce lactate production from the source by down-regulating the hypoxia inducible factor-1alpha (HIF-1alpha), which further down-regulated the glycolysis associated enzymes including glycolysis-related glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). As a result, CaO.sub.2@mPDA-SH alone without the employment of other therapeutics can dually regulate the tumor hypoxia and lactic acid metabolism, which efficiently represses tumor progression in promoting immune activation, antitumor metastasis, and anti-angiogenesis.
Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a ...unique approach by combining the concepts of "antigen multi-copy display" and "calcium carbonate (CaCO.sub.3) biomineralization" to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO.sub.3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4.sup.+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO.sub.3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.
Intestinal epithelia impairment of inflammatory bowel disease (IBD) leads to the leakage of bacteria and antigens and the consequent persistent immune imbalance. Restoring the epithelial barrier is a ...promising therapeutic target but lacks effective and safe clinical interventions. By identifying the catalase (CAT) presence in the IBD pathological environment, we herein develop a CAT-catalyzed pathologically coating on the damaged epithelial barrier to inhibit intestinal leakage for IBD therapy. With the codelivery of CaO.sub.2 (a CAT substrate) and dopamine, the nanosystem can enable CAT-catalyzed oxygen (O.sub.2) production and in-situ polymerization of dopamine and then yield a thin and integrative polydopamine (PDA) coating on the intestinal barrier due to the highly adhesive property of PDA. In vivo study demonstrates that PDA coating provides not only a protective barrier by restricting intestinal leakage but also a favorable anti-inflammation effect. Beyond drug management, this work provides a physical repair strategy via catalyzed coating for IBD therapy.
Background
In the malar region, the SMAS flap can be thin and tear easily, making it difficult to securely fix it. And the surgical anatomy of the region may be unclear and confusing. The authors ...performed an anatomical study on the location of the lateral margin of the orbicularis oculi muscle (OOM) and the origin of the zygomaticus major muscle (ZMM) when using a high-SMAS facelift with finger-assisted spaces dissection technique, which included elevation of the SMAS flap with OOM.
Methods
One hundred twenty-one Asian patients underwent this facelift procedure. Of those, the distances between the posterior margin of tragus and the lateral margin of the OOM and the center of the origin of the ZMM were measured in 20 patients.
Results
The mean age of the initial 121 patients was 50.9 years. In all cases, improvement was seen in soft tissue sagging of the midface and lower face. There was no functional impairment of the OOM. In 20 patients of them, the lateral margin of the OOM and the center of the origin of the ZMM were located at mean distances of 50.6 (range 48–53 mm) and 61.0 mm (range 60–65 mm) from the posterior margin of the tragus.
Conclusions
The SMAS flap with the OOM is sufficiently strong enough so that it can maintain the pulling force and also helps to securely fix it. The authors hope that these anatomical findings would be useful when performing it and aid in the understanding of the relationship between the muscles in the malar area.
Level of Evidence IV
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In cancer immunotherapy, immune cells are the main force for tumor eradication. However, they appear to be dysfunctional due to the taming of the tumor immunosuppressive microenvironment. Recently, ...many materials-engineered strategies are proposed to enhance the anti-tumor effect of immune cells. These strategies either utilize biomimetic materials, as building blocks to construct inanimate entities whose functions are similar to natural living cells, or engineer immune cells with functional materials, to potentiate their anti-tumor effects. In this review, we will summarize these advanced strategies in different cell types, as well as discussing the prospects of this field.
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•APAP increased the comparable level of melanin biosynthesis in plasma of mice and silkworm larvae.•Liver melanization of mice induced by APAP occurred before ALF.•Melanic epidermis ...in Bombyx mori was a sensitive indicator for forecast the ALF of APAP drugs.
Acetaminophen (APAP) is an effective and widely used analgesic. However, APAP overdose is the principal cause of acute liver failure (ALF) in many countries. Here, we report the phenomenon of liver melanization which occurred before APAP-induced ALF in mice. A melanic surface induced by APAP which was time- and dose-dependent in the silkworm invertebrate model was observed. In addition, an APAP-induced acute tissue failure model (ATF) was established using a metabolic detoxification tissue fat body which simulated mouse liver. An investigation of the anabolic mechanism of melanin in experimental animals showed that dopaquinone and dopamine which were synthesized from tyrosine via dopa in silkworms were further metabolized to melanin, while in mice, epinephrine was synthesized via the dopamine branch and melanin was only synthesized via the dopaquinone branch. On this basis, it is proposed that melanin-metabolic levels in plasma could be used as an early diagnostic marker of APAP overdose and the black spots on insect epidermis could be used as a fast detection model of toxicity.
