Exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) impairs 5-HT metabolism by impacting the brain-gut axis in mice.

Hexafluoropropylene oxide trimer acid (HFPO-TA) has been found to cause hepatotoxicity, lipotoxicity, and cytotoxicity. However, the effects of HFPO-TA exposure on nervous system toxicity are still unclear. Here, six-week-old male C57BL/6J mice were treated with 2, 20, and 200 µg/L HFPO-TA for six weeks. The untargeted transcriptome analysis was employed to identify differentially expressed mRNAs in the tissue of mouse hippocampi. Then, the levels of neurotransmitters were detected by ELISA analysis in hippocampal and colonic tissues. Real-time quantitative PCR and western blotting analysis were performed to detect the expression of genes associated with modulation of serotonin (5-HT) metabolism and blood-brain barrier. HFPO-TA exposure reduced the mRNA and protein expression of several tight junction protein-coded genes, including Occludin, Claudin-1, and ZO-1, in mice hippocampi, indicating that the blood-brain barrier was disrupted. Moreover, HFPO-TA exposure elevated the expression of neuroinflammatory factors, including TNF-α, IL-6, IL-1ß, TGF-α, and TGF-ß. Analysis of hippocampal transcriptomics suggested that HFPO-TA exposure would impair 5-HT generation and metabolic pathways. In keeping with this prediction, our findings confirmed that the levels of several neurotransmitters, including tryptophan (TRP), 5-HT, 5-HTP, and 5-HIAA, were all impaired by HFPO-TA exposure in the serum, colon, and hippocampus, as was the colonic and hippocampal expression of TRP and 5-HT metabolism-related genes such as SERT, MAO-A, and IDO. These results suggest that HFPO-TA nervous system toxicity in mice may be partly modulated by the brain-gut axis and that HFPO-TA exposure may negatively impact human mental health.

Anxiety, depression symptoms, and psychological resilience among hospitalized COVID-19 patients in isolation: A study from Wuhan, China.

OBJECTIVE: To investigate the status of anxiety, depression, and psychological resilience among individuals with COVID-19, and their interrelationships to provide a scientific basis for developing psychological intervention strategies for these patients. METHODS: A total of 126 patients with COVID-19 who were admitted to Wuhan Huoshenshan Hospital were recruited in this study. A comprehensive survey was conducted using a general information questionnaire, the Self-Rating Anxiety Scale, the self-rating depression scale, and the Chinese version of the psychological Connor-Davidson resilience scale; a questionnaire-based survey was conducted. RESULTS: Significant differences in anxiety scores were observed among COVID-19 patients with different education levels and the number of immediate family members. The differences in depression scores were noted among patients of different age groups, and marital statuses were also significant. The total psychological resilience score and the scores of all dimensions are negatively correlated with anxiety and depression. Furthermore, the patient's gender, the number of immediate family members, and the psychological resilience dimensions are associated with the severity anxiety of patients. Patient age and psychological resilience are associated with the depression level of patients. CONCLUSION: Patients with COVID-19 exhibit elevated levels of both anxiety and depression. Notably, psychological resilience emerges as a protective factor against the development of anxiety and depression.

Dynamic functional thalamocortical dysconnectivity in schizophrenia correlates to antipsychotics response.

Although many studies have showed abnormal thalamocortical networks in patients with schizophrenia (SCZ), the dynamic functional thalamocortical connectivity of individuals with SCZ and the effect of antipsychotics on this connectivity have not been investigated. Drug-naïve first-episode individuals with SCZ and healthy controls were recruited. Patients were treated with risperidone for 12 weeks. Resting-state functional magnetic resonance imaging was acquired at baseline and week 12. We identified six functional thalamic subdivisions. The sliding window strategy was used to determine the dynamic functional connectivity (dFC) of each functional thalamic subdivision. Individuals with SCZ displayed decreased or increased dFC variance in different thalamic subdivisions. The baseline dFC between ventral posterior-lateral (VPL) portions and right dorsolateral superior frontal gyrus (rdSFG) correlated with psychotic symptoms. The dFC variance between VPL and right medial orbital superior frontal gyrus (rmoSFG) or rdSFG decreased after 12-week risperidone treatment. The decreased dFC variance between VPL and rmoSFG correlated with the reduction of PANSS scores. Interestingly, the dFC between VPL and rmoSFG or rdSFG decreased in responders. The dFC variance change of VPL and the averaged whole brain signal correlated with the risperidone efficacy. Our study demonstrates abnormal variability in thalamocortical dFC may be implicated in psychopathological symptoms and risperidone response in individuals with schizophrenia, suggesting that thalamocortical dFC variance may be correlated to the efficacy of antipsychotic treatment.Registration: ClinicalTrials.gov Identifier: NCT00435370. https://www.clinicaltrials.gov/ct2/show/NCT00435370?term=NCT00435370&draw=2&rank=1.

Facile engineering of resveratrol nanoparticles loaded with 20(S)-protopanaxadiol for the treatment of periodontitis by regulating the macrophage phenotype.

Periodontitis is an inflammatory disease, mainly caused by the formation of a subgingival plaque biofilm. In recent years, growing attention has been paid to immunotherapy in the treatment of periodontitis, and the importance of communal intervention associated with macrophage polarization was emphasized. Herein, resveratrol (RES) and 20(S)-protopanaxadiol (PPD) were successfully self-assembled into RES@PPD nanoparticles (NPs) by the phenolic resin reaction. RES@PPD NPs have good stability and biocompatibility. The combined application of PPD and RES enhances the anti-inflammatory and antioxidant properties of nanocomposites, remarkably reduces the level of reactive oxygen species, and finally realizes the coordinated regulation of host immunity in periodontitis. The detailed mechanism is as follows: RES@PPD NPs inhibit M1 polarization of macrophages, promote M2 polarization by scavenging ROS, and then inhibit the NF-κB signalling pathway to regulate host immunity. In the animal model of periodontitis, RES@PPD NPs can remarkably decrease the level of pro-inflammatory cytokines, up-regulate the anti-inflammatory cytokines, and exhibit a profound therapeutic effect on local inflammation. Therefore, RES@PPD NPs are effective in antioxidation and anti-inflammation, thus providing a promising candidate drug for the treatment of periodontitis.

Growth and elongation of axons through mechanical tension mediated by fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@PDA superparticles.

BACKGROUND: The primary strategy to repair peripheral nerve injuries is to bridge the lesions by promoting axon regeneration. Thus, the ability to direct and manipulate neuronal cell axon regeneration has been one of the top priorities in the field of neuroscience. A recent innovative approach for remotely guiding neuronal regeneration is to incorporate magnetic nanoparticles (MNPs) into cells and transfer the resulting MNP-loaded cells into a magnetically sensitive environment to respond to an external magnetic field. To realize this intention, the synthesis and preparation of ideal MNPs is an important challenge to overcome. RESULTS: In this study, we designed and prepared novel fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@polydopamine superparticles (FMSPs) as neural regeneration therapeutics. With the help of their excellent biocompatibility and ability to interact with neural cells, our in-house fabricated FMSPs can be endocytosed into cells, transported along the axons, and then aggregated in the growth cones. As a result, the mechanical forces generated by FMSPs can promote the growth and elongation of axons and stimulate gene expression associated with neuron growth under external magnetic fields. CONCLUSIONS: Our work demonstrates that FMSPs can be used as a novel stimulator to promote noninvasive neural regeneration through cell magnetic actuation.

Schwann Cell Migration through Magnetic Actuation Mediated by Fluorescent-Magnetic Bifunctional Fe3O4·Rhodamine 6G@Polydopamine Superparticles.

Peripheral nerve injuries always cause dysfunction but without ideal strategies to assist the treatment and recovery successfully. The primary way to repair the peripheral nerve injuries is to bridge the lesions by promoting axon regeneration. Schwann cells acting as neuroglial cells play a pivotal role during axonal regeneration. The orderly and organized migration of Schwann cells is beneficial for the extracellular matrix connection and Büngner bands formation, which greatly promote the regeneration of axons by offering mechanical support and growth factors. Thus, the use of Schwann cells as therapeutic cells offers us an attractive method for neurorepair therapies, and the ability to direct and manipulate Schwann cell migration and distribution is of great significance in the field of cell therapy in regards to the repair and regeneration of the peripheral nerve. Herein, we design and characterize a type of novel fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G (R6G)@polydopamine (PDA) superparticles (SPs) and systematically study the biological behaviors of Fe3O4·R6G@PDA SP uptake by Schwann cells. The results demonstrate that our tailor-made Fe3O4·R6G@PDA SPs can be endocytosed by Schwann cells and then highly magnetize Schwann cells by virtue of their excellent biocompatibility. Furthermore, remote-controlling and noninvasive magnetic targeting migration of Schwann cells can be achieved on the basis of the high magnetic responsiveness of Fe3O4·R6G@PDA SPs. At the end, gene expression profile analysis is performed to explore the mechanism of Schwann cells' magnetic targeting migration. The results indicate that cells can sense external magnetic mechanical forces and transduce into intracellular biochemical signaling, which stimulate gene expression associated with Schwann cell migration.

Targeting mitochondria with Au-Ag@Polydopamine nanoparticles for papillary thyroid cancer therapy.

The incidence of papillary thyroid cancer has rapidly increased in the past decade because of the progress in modern diagnostic technology. Novel therapeutic strategies for papillary thyroid cancer (which has low malignancy) based on organelle-targeted nanomaterials are greatly welcome in order to avoid over-treatment by conventional surgery. Herein, we demonstrate the mitochondria-targeted and exocytosis inhibition strategy of polydopamine (PDA)-coated inorganic nanoparticles (NPs) for enhanced papillary thyroid cancer therapy. PDA-coated gold-silver alloy NPs (Au-Ag@PDA NPs) were employed as the model of composite NPs. TPC-1 cells were chosen as the model of human papillary thyroid cancer cells. To better understand the effect of composite NPs on papillary thyroid cancer cells, the intracellular fate and corresponding cellular responses of Au-Ag@PDA NPs in TPC-1 cells were studied. The results indicate that Au-Ag@PDA NPs are internalized through a caveolae-mediated and macropinocytosis pathway and they are difficult to excrete by the TPC-1 cells. Au-Ag@PDA NPs mainly accumulate in mitochondria, resulting in the mitochondrial dysfunction and the decreased expression of dihydroorotate dehydrogenase. This leads to up-regulation of the p53 levels and therefore the S-phase cell cycle arrest and cell proliferation inhibition. In addition, despite cancer cells being able to survive by an autophagy-mediated pathway to escape apoptosis or necrosis, targeting mitochondria by Au-Ag@PDA NPs enables the destructive thermal ablation of TPC-1 cells by combination with photothermal therapy.