Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury.

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood-brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Nanogels as Novel Nanocarrier Systems for Efficient Delivery of CNS Therapeutics.

Nanogels have come out as a great potential drug delivery platform due to its prominently high colloidal stability, high drug loading, core-shell structure, good permeation property and can be responsive to environmental stimuli. Such nanoscopic drug carriers have more excellent abilities over conventional nanomaterials for permeating to brain parenchyma in vitro and in vivo. Nanogel-based system can be nanoengineered to bypass physiological barriers via non-invasive treatment, rendering it a most suitable platform for the management of neurological conditions such as neurodegenerative disorders, brain tumors, epilepsy and ischemic stroke, etc. Therapeutics of central nervous system (CNS) diseases have shown marked limited site-specific delivery of CNS by the poor access of various drugs into the brain, due to the presences of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Hence, the availability of therapeutics delivery strategies is considered as one of the most major challenges facing the treatment of CNS diseases. The primary objective of this review is to elaborate the newer advances of nanogel for CNS drugs delivery, discuss the early preclinical success in the field of nanogel technology and highlight different insights on its potential neurotoxicity.

Increasing Trends in Mental Health Problems Among Urban Chinese Adolescents: Results From Repeated Cross-Sectional Data in Changsha 2016-2020.

This study performed a repeated cross-sectional analysis to explore possible trends in mental health problems among Chinese adolescents over the years of 2016-2020. A total of 2,837 different seventh-grade students were surveyed in three waves from a junior high school in Changsha city, Hunan province in China (978 in 2016, 949 in 2019, and 910 in 2020) using the Mental Health Inventory of Middle School Students (MMHI-60). The results showed that obsessive-compulsive tendencies, interpersonal sensitivity, depression, anxiety, academic stress, and emotional disturbance problems were significantly increased in surveyed adolescents from 2016 to 2020. Moreover, positive rates of most of these problems were significantly higher in females than males, and were significantly increased in only females. These results highlight the importance of focusing on mental health problems among urban Chinese adolescents, especially among girls.

Changes of psychotic-like experiences and their association with anxiety/depression among young adolescents before COVID-19 and after the lockdown in China.

OBJECTIVE: Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study. METHODS: In total, 1825 adolescents were surveyed before COVID-19 and after the lockdown in China (T0, October 20th, 2019 and T1, May 18th, 2020). PLEs, anxiety, and depression were measured with paranoia, anxiety and depression subscales of the Mental Health Inventory of Middle school students (MMHI-60). Within-subjects Wilcoxon test, Spearman correlation test, and Kruskal-Wallis test were adopted. RESULTS: Significant increase in adolescent PLEs scores was observed after the lockdown (Wilcoxon's w = 9.302, p < 0.001). We also found positive correlation between changes of PLEs and changes of anxiety/depression (Spearman's rho = 0.59/0.53, both p < 0.001). Furthermore, four PLEs trajectories were identified based on the report of PLEs at two timepoints: 60.4% with no PLEs, 9.3% remitted PLEs, 16.7% new PLEs, and 13.6% persistent PLEs. Significant difference was found in changes of anxiety/depression among four groups (p < 0.001); notably, the group with new-onset PLEs had the greatest exacerbation in anxiety/depression symptoms (both p Bonferroni <0.001). CONCLUSIONS: This work is the first to identify increases in adolescent PLEs across the COVID-19 pandemic and suggested a close longitudinal association between PLEs and anxiety/depression. Our findings have implications for adolescent mental health crisis interventions during the pandemic.

Family functioning as a moderator in the relation between perceived stress and psychotic-like experiences among adolescents during COVID-19.

BACKGROUND: The COVID-19 pandemic has increased psychological stress among adolescents, and the relation between perceived stress (PS) and psychotic-like experiences (PLEs) has been well-established. However, little is known about the role of family functioning (FF) in this relation, especially when adolescents experienced the extended lockdown period with family members. METHODS: A total of 4807 adolescents completed this retrospective paper-and-pencil survey after school reopening between May 14th and June 6th, 2020 in Hunan Province, China. We measured PS with the Perceived stress scale (PSS-10), PLEs with the eight positive items from Community Assessment of Psychic Experiences (CAPE-8), and FF with the Family APGAR scale. We conducted subgroup analysis based on three FF levels (good, moderate, and poor) determined by previous studies. Finally, correlation and moderation analysis were performed to detect the effect of FF in the relation between PS and PLEs after adjusting for demographic variables. RESULTS: Adolescents with poor FF had higher levels of PS and higher prevalence of PLEs compared to those with good FF (both p < 0.001). FF was negatively associated with both PS (r = -0.34, p < 0.001) and PLEs (r = -0.29, p < 0.001). Higher FF significantly attenuated the effect of PS on PLEs after adjusting for sex and age (effect = -0.011, bootstrap 95% CI -0.018, -0.005). CONCLUSION: Our findings indicate that well-functioned family could protect against stress-induced PLEs among adolescents during this crisis. Thus family system could be an early interventional target for distressing psychotic-like experiences in youngsters.