High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.

Self-Reported Neurological Symptoms Two Years After Hospital Discharge Among COVID-19 Survivors.

Background: The acute stage of COVID-19 often presents with neurological manifestations. Objective: This study aims to investigate the long-term neurological effects on survivors. Methods: This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19. Results: Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms. Conclusion: Neurological symptoms are common among COVID-19 survivors, especially in severe cases.

Combined chemo and photo therapy of programmable prodrug carriers to overcome delivery barriers against nasopharyngeal carcinoma.

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.

sFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma.

BACKGROUND: The current methods used for diagnosing hepatocellular carcinoma (HCC) are unsatisfactory. Here, we assessed the serum levels of secreted frizzled related protein 4 (sFRP-4) for diagnosing HCC in patients infected with chronic hepatitis B (CHB). METHODS: In 272 patients with CHB enrolled, 142 were patients with HCC. Thirty-three healthy subjects were recruited as healthy controls. The CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients (8 CHB-related HCC patients, 7 CHB patients) for serum markers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. RESULTS: Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients (P<0.05). Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group (79.7 vs 41.3 ng/mL; P<0.001) and validation group (89.0 vs 39.0 ng/mL; P<0.001). Areas under the Receiver Operating Characteristic curves (AUCs) for alpha-fetoprotein (AFP) and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 (a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL) and AFP (a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL) showed better performance for diagnosing HCC (a sensitivity of 79.2% and a specificity of 95.3%). The AUC for combined sFRP-4 and AFP increased to 0.941 (95% CI: 0.908-0.975), and similar results were seen in the validation group. CONCLUSION: sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.