Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and ...traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co‐stimulatory molecules for robust immunotherapy. FMs share the tumor's self‐targeting character with the parent cancer cells. In bilateral tumor‐bearing mouse models, the FM‐coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post‐nanophotosensitizer‐induced photodynamic therapy (PDT). The FM‐induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy‐caused regression of the irradiation‐free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor‐specific immunotherapy‐based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.
Using the cytomembranes of fused cells derived from tumor and dendritic cells, a tumor‐specific immunotherapeutic platform is engineered, which is capable of easy cooperation with other therapy means. The hybrid‐cytomembrane‐coated nanophotosensitizer demonstrates durable immunotherapy against primary tumors post‐photodynamic‐therapy (PDT) and PDT‐enhanced immunity toward irradiation‐free distant tumors.
Objective
To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA).
Methods
In this multicenter, randomized, sham‐controlled ...trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent‐to‐treat population, which included all randomized participants who had ≥1 post‐baseline measurement.
Results
Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between‐group differences were 13.0% (97.5% confidence interval 97.5% CI 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI −1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26.
Conclusion
Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow‐up.
Photothermal therapy (PTT) has drawn extensive research attention as a promising approach for tumor treatment. In this study, a bacteria‐assisted strategy relying on the selective reduction of ...perylene diimide derivative based supramolecular complex (CPPDI) to radical anions (RAs) by Escherichia coli in hypoxic tumors is developed to realize highly precise PTT of tumors. Noninvasive E. coli are first injected intravenously for selectively accumulating and replicating in the tumor due to the hypoxia tropism. Then, CPPDI is loaded in a peptide‐hybrid matrix metalloproteinase‐2 (MMP‐2) responsive liposome (MRL) and injected intravenously. After accumulated and released from MRL in the tumor where MMP‐2 is overexpressed, CPPDI is reduced by E. coli in the hypoxic tumor environment to produce CPPDI RAs (CRAs), which serve as effective photothermal agents for tumor cells thermal ablation under near‐infrared light irradiation. Since E. coli accumulate and grow in tumor sites selectively, this strategy accurately limits the production of CRAs in tumors for highly selective PTT, which will find great potential for precise tumor inhibition.
A bacteria‐assisted photothermal therapy is reported, to realize highly precise tumor treatment. The therapy relies on the selective reduction of perylene diimide derivative based supramolecular complex to radical anions by Escherichia coli in hypoxic tumors.
Doxorubicin (DOX) is a wide spectrum antitumor drug. However, its clinical application is limited due to the cardiotoxicity. Carvedilol (CAR) is a β-blocker used to treat high blood pressure and ...heart failure. Accordingly, supplementation with natural antioxidants or plant extracts exerts protective effects against various injury in vivo. Carnosic acid (CAA), the principal constituent of rosemary, has various biological activities, including antioxidant, antitumor, and anti-inflammatory. Here, heart injury mouse model was established using DOX (20 mg/kg) in vivo. And cardiac muscle cell line of H9C2 was subjected to 0.5 μM of DOX for 24 h in vitro. Then, the protective effects of CAA and CAR alone, or the two in combination on DOX-induced cardiotoxicity in vivo and in vitro were explored. The results indicated that both CAA and CAR, when used alone, were moderately effective in attenuating DOX-induced cardiotoxicity. The combination of two drugs functioned synergistically to ameliorate cardiac injury caused by DOX, as evidenced by the significantly reduced collagen accumulation and improved dysfunction of heart. CAA and CAR exhibited stronger anti-oxidative role in DOX-treated mice partly by augmenting the expression and activities of the anti-oxidative enzymes. In addition, inflammatory response was significantly suppressed by the two in combination, proved by the decreased pro-inflammatory cytokines (COX2, TNF-α, IL-6, IL-1β and IL-18), which was associated with the inactivation of nuclear factor κB (NF-κB). Furthermore, DOX-stirred apoptosis and autophagy were dramatically attenuated by the co-treatments of CAA and CAR through down-regulating cleaved Caspase-3 and LC3B signaling pathways. The effects of CAA and CAR combination against cardiotoxicity were observed in H9C2 cells with DOX stimulation. Our findings above suggested that the use of CAR and CAA in combination could be expected to have synergistic efficacy and significant potential against cardiotoxicity induced by DOX.
Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed ...cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.
Cancer cells, with unique their metabolism, frequently exhibit a high level of redox homeostasis, which could be a feasible target for cancer treatment. Here, liquid metal (LM) nanoparticles are used ...as a template to guide the growth of yolk‐shell structured LM@MnO2 (LMN). With yolk‐shell structures, LMNs is applied to load with cinnamaldehyde (CA) (CLMN) and further coated with hyaluronic acid (HA) to construct the CA&LM@MnO2‐HA nanoflowers (CLMNF) for cancer targeted treatment. Owing to the urchin‐like structured shell, it is found that the obtained CLMNF particles rapidly deplete glutathione (GSH) and produce manganese ions, which further facilitate hydrogen peroxide converting into hydroxyl radical (·OH) for cancer cell killing. Accompanying the depletion of GSH, the balance of intracellular redox homeostasis tilts towards oxidation, resulting in amplified oxidative damage caused by CA, eventually, leading to the apoptosis of cancer cells. Combined with the remarkable near infrared (NIR) photothermal conversion properties, the novel structured CLMNF exhibits favorable inhibition of tumors in vivo, indicating that using nanoflowers to induce intracellular oxidative/thermal stress damage could be a promising strategy for anticancer treatment.
Yolk‐shell structured nanoflowers induce intracellular oxidative/thermal stress damage for cancer treatment. By using liquid metal as a template, the yolk‐shell structured manganese dioxide nanoflowers are rapidly constructed through an in situ surface reduction process. Benefiting from the guidance of multimode imaging, the nanoparticles exhibit satisfactory inhibition of tumor growth in vivo.
Non-noble metal oxides consisting of CuO and TiO2 (CuO/TiO2 catalyst) for CO2 reduction were fabricated using a simple hydrothermal method. The designed catalysts of CuO could be in situ reduced to a ...metallic Cu-forming Cu/TiO2 catalyst, which could efficiently catalyze CO2 reduction to multi-carbon oxygenates (ethanol, acetone, and n-propanol) with a maximum overall faradaic efficiency of 47.4% at a potential of −0.85 V vs. reversible hydrogen electrode (RHE) in 0.5 M KHCO3 solution. The catalytic activity for CO2 electroreduction strongly depends on the CuO contents of the catalysts as-prepared, resulting in different electrochemistry surface areas. The significantly improved CO2 catalytic activity of CuO/TiO2 might be due to the strong CO2 adsorption ability.
•Phosphoryl functionalized mesoporous silica (TBP-SBA-15) is synthesized.•The amino and phosphoryl groups are successfully grafted on SBA-15.•TBP-SBA-15 has high and rapid uranium adsorption capacity ...in broad pH range.•The U(VI) adsorption of TBP-SBA-15 is spontaneous and belongs to chemical adsorption.
Phosphoryl functionalized mesoporous silica (TBP-SBA-15) was synthesized by modified mesoporous silica with γ-amino propyl triethoxy silane and tributyl phosphate. The obtained samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), small angle X-ray diffraction (SAXRD), thermo-gravimetric/differential thermalanalyzer (TG/DTA), N2 adsorption–desorption (BET) and Fourier transform infrared spectroscopy (FT-IR) techniques. Results showed that TBP-SBA-15 had large surface areas with ordered channel structure. Moreover, the effects of adsorption time, sorbent dose, solution pH, initial uranium concentration and temperature on the uranium adsorption behaviors were investigated. TBP-SBA-15 showed a high uranium adsorption capacity in a broad range of pH values. The U(VI) adsorption rate of TBP-SBA-15 was fast and nearly achieved completion in 10min with the sorbent dose of 1g/L. The U(VI) adsorption of TBP-SBA-15 followed the pseudo-second-order kinetic model and Freundlich isotherm model, indicating that the process was belonged to chemical adsorption. Furthermore, the thermodynamic parameters (ΔG0, ΔH0 and ΔS0) confirmed that the adsorption process was endothermic and spontaneous.
Background
Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in ...several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT‐determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)‐determined skeletal muscle mass and quality at L1 are associated with mortality in initial‐dialysis patients.
Methods
This 3‐year multicentric retrospective study included initial‐dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass by skeletal muscle index, (SMI), cm2/m2 and quality by skeletal muscle density (SMD), HU. Skeletal muscle measures at L1 were compared with those at L3. The sex‐specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all‐cause mortality. The outcomes were all‐cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death.
Results
A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P < 0.001), and that between L1 and L3 SMD was 0.90 (P < 0.001). No significant association between L1 SMI and mortality was observed (P > 0.05). Low L1 SMD (n = 280, 57.73%) was diagnosed based on the optimal cutoff value (<39.56 HU for males and <33.06 HU for females). Multivariate regression analysis revealed that the low L1 SMD group had higher risks of all‐cause death (hazard ratio 1.80; 95% confidence interval 1.05–3.11, P = 0.034) and cardiac death (hazard ratio 3.74; 95% confidence interval 1.43–9.79, P = 0.007).
Conclusions
In initial‐dialysis patients, there is high agreement between the L1 and L3 measures for SMI and SMD. Low SMD measured at L1, but not low SMI, is an independent predictor of both all‐cause death and cardiac death.
Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. Oxidative stress is one of key contributors to PD. Nuclear factor erythroid‐2‐related factor 2 ...(Nrf2) is considered to be a master regulator of many genes involved in anti‐oxidant stress to attenuate cell death. Therefore, activation of Nrf2 signalling provides an effective avenue to treat PD. Ellagic acid (EA), a natural polyphenolic contained in fruits and nuts, possesses amounts of pharmacological activities, such as anti‐oxidant stress and anti‐inflammation. Recent studies have confirmed EA could be used as a neuroprotective agent in neurodegenerative diseases. Here, mice subcutaneous injection of rotenone (ROT)‐induced DA neuronal damage was performed to investigate EA‐mediated neuroprotection. In addition, adult Nrf2 knockout mice and different cell cultures including MN9D‐enciched, MN9D‐BV‐2 and MN9D‐C6 cell co‐cultures were applied to explore the underlying mechanisms. Results demonstrated EA conferred neuroprotection against ROT‐induced DA neurotoxicity. Activation of Nrf2 signalling was involved in EA‐mediated DA neuroprotection, as evidenced by the following observations. First, EA activated Nrf2 signalling in ROT‐induced DA neuronal damage. Second, EA generated neuroprotection with the presence of astroglia and silence of Nrf2 in astroglia abolished EA‐mediated neuroprotection. Third, EA failed to produce DA neuroprotection in Nrf2 knockout mice. In conclusion, this study identified EA protected against DA neuronal loss via an Nrf2‐dependent manner.
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