Disruption of Cdk5-GluN2B complex by a small interfering peptide attenuates social isolation-induced escalated intermale attack behavior and hippocampal oxidative stress in mice.

Social isolation has emerged as a significant issue during the COVID-19 pandemic that can adversely impact human mental health and potentially lead to pathological aggression. Given the lack of effective therapeutic interventions for aggressive behavior, alternative approaches are necessary. In this study, we utilized a genetic method combined with a pharmacological approach to identify and demonstrate the crucial role of Cdk5 in escalated intermale attack behavior induced by 2-week social isolation. Moreover, we developed a small peptide that effectively disrupts the interaction between Cdk5 and GluN2B, given the known involvement of this complex in various neuropsychiatric disorders. Administration of the peptide, either systemically or via intrahippocampal injection, significantly reduced oxidative stress in the hippocampus and attenuated intermale attack behavior induced by 2-week social isolation. These findings highlight the previously unknown role of the hippocampal Cdk5-GluN2B complex in social isolation-induced aggressive behavior in mice and propose the peptide as a promising therapeutic strategy for regulating attack behavior and oxidative stress.

Phosphorylation of Tyrosine 1070 at the GluN2B Subunit Is Regulated by Synaptic Activity and Critical for Surface Expression of N-Methyl-D-aspartate (NMDA) Receptors.

The number and subunit composition of synaptic N-methyl-d-aspartate receptors (NMDARs) play critical roles in synaptic plasticity, learning, and memory and are implicated in neurological disorders. Tyrosine phosphorylation provides a powerful means of regulating NMDAR function, but the underling mechanism remains elusive. In this study we identified a tyrosine site on the GluN2B subunit, Tyr-1070, which was phosphorylated by a proto-oncogene tyrosine-protein (Fyn) kinase and critical for the surface expression of GluN2B-containing NMDARs. The phosphorylation of GluN2B at Tyr-1070 was required for binding of Fyn kinase to GluN2B, which up-regulated the phosphorylation of GluN2B at Tyr-1472. Moreover, our results revealed that the phosphorylation change of GluN2B at Tyr-1070 accompanied the Tyr-1472 phosphorylation and Fyn associated with GluN2B in synaptic plasticity induced by both chemical and contextual fear learning. Taken together, our findings provide a new mechanism for regulating the surface expression of NMDARs with implications for synaptic plasticity.

[Comparing extended vertical partial laryngectomy and cricohyoidoepiglottopexy in the treatment of laryngeal carcinoma].

OBJECTIVE: To compare the results of extended vertical partial laryngectomy (similar to modified supracricoid partial laryngectomy with cricohyoidoepiglottopexy) and cricohyoidoepiglottopexy in the treatment of laryngeal carcinoma. METHODS: Retrospectively analyzed on the results and prognosis in patients underwent extended vertical partial laryngectomy and cricohyoidoepiglottopexy between 1998 and 2005. The operation was similar to extended vertical partial laryngectomy. The healthy vocal cord and ventricular band as well as about 1/3 to 2/3 laminas of thyroid cartilage were removed. The healthy cricoarytenoid joint was reserved. The vocal cord, ventricular band, fixed or limitation of motion arytenoid cartilage and 2/3 laminas of thyroid cartilage in ill side were removed. The posteroinferior border of laminas of thyroid cartilage in both sides were reserved. The cricoid was lifted and fixed with hyoid epiglottis directly. Extended vertical partial laryngectomy group consisted of 37 patients with glottic carcinoma (stage T2 16 cases, stage T3 21 cases) and cricohyoidoepiglottopexy group consisted of 34 patients with glottic carcinoma (stage T2 12 cases, stage T3 21 cases, stage T4 1 case). RESULTS: Kaplan-Meier analysis was performed to calculate the survival rates. The three-year cumulative survival rate was 91.7% in extended vertical partial laryngectomy group and 87.5% in cricohyoidoepiglottopexy group respectively. There was no significant difference between the two groups (P > 0.05). The five-year cumulative survival rate was 80.6% in extended vertical partial laryngectomy group and 81.3% in cricohyoidoepiglottopexy group respectively. There was also no significant difference between the two groups (P > 0.05). The decannulation rate was 100% (37/37) in extended vertical partial laryngectomy group and 94.1% (32/34) in cricohyoidoepiglottopexy group respectively. The decannulation time was (14.0 + or - 2.3) days in extended vertical partial laryngectomy group and (19.0 + or - 4.6) days in cricohyoidoepiglottopexy group respectively. The incidence of aspiration was 2.7% (1/37) in modified group and 23.5 (8/34) in cricohyoidoepiglottopexy group respectively evaluated at 8th weeks post-operatively. The evaluation of deglutition disorder was analyzed by Ridit analysis in both groups and the results showed that there was significant difference between the two groups (U = 7.341, P < 0.001). The symptom of aspiration in extended vertical partial laryngectomy group was significant less than in cricohyoidoepiglottopexy group. CONCLUSIONS: Although the survival rate was not different between the two groups. The preservation of laryngeal function in extended vertical partial laryngectomy group was significant better than in cricohyoidoepiglottopexy group and extended vertical partial laryngectomy.

[Identification of differentially expressed genes in recurrent nasopharyngeal carcinoma and analysis of their chromosomal location].

OBJECTIVE: To identify differentially expressed genes in recurrent nasopharyngeal carcinoma (rNPC) by DNA microarrays, and analyze chromosomal localizations and molecular function by bioinformatics. METHODS: The primary nasopharyngeal carcinoma (pNPC) tissue samples and rNPC tissue samples were selected, and Affymetrix Gene1.0 ST gene chips were used to identify differential expressed genes in rNPC, and the bioinformatics was used to analyze their chromosomal localizations as well as molecular functions. RESULTS: A total of 44 genes were identified to be differential expressed in rNPC. Thirty-six genes were down regulated, 8 genes were up regulated. Functional classification of down-regulation genes showed that most genes (10 genes, 27.8%) belonged to the enzyme activity genes, followed by calcium ion binding genes (7 genes, 19.4%), protein binding genes (5 genes, 13.9%), receptor activity genes (4 genes, 11.1%), ATP binding genes (2 genes, 5.6%), transcription factor genes (2 genes, 5.6%), extracellular matrix binding and growth factor binding have 1 gene respectively (each accounted for 2.8%). In addition, the functions of 4 genes (11.1%) were unknown. Functional classification of up-regulation genes showed most genes (3 genes, 37.5%) were unknown, followed enzyme activity genes (2 genes, 25.0%), receptor activity, calcium ion binding and voltage-gated ion channel activity genes have 1 genes respectively (each accounted for 12.5%). These genes were localized randomly on the most the chromosomes, with a majority of them localized on chromosomes 1, 17. Chromosome 1 contained the most differentially expressed genes (10, 22.7%), followed by chromosomes 17 (5, 11.3%). CONCLUSIONS: The differential expressed genes in rNPC were supposed to be randomly distributed on most chromosomes, but the majorities were found on chromosomes 1, 17. Abnormality in three groups of genes, including in enzyme activity, calcium ion binding and protein binding associate genes, might play important roles in rNPC. Those genes need to be further studied.

[Quality of life, personality, coping style in the patients with advanced laryngeal cancer].

OBJECTIVE: To evaluate the relationship between the life quality of advanced laryngeal squamous cell cancer patients and their personality, coping style and other psychological factors. METHODS: The life quality were measured for 2 sub-groups of advanced laryngeal cancer patients and the normal control group. The Eysenck personality questionnaire (EPQ), coping style questionnaires (CSQ) and University of Washington-quality of life (UW-QOL) were used for life quality evaluation. The 2 sub-groups of the patients on the worse speech, job and ability (group I), the better speech, job and ability (group II), and normal control. RESULTS: (1) UW-QOL score: the total, activity, recreation, job and speech scores of group II were significantly higher than those of group I (P < 0.01). Group II was better than group I in appearance (P < 0.05). (2) EPQ score: the P and N scores in group II were lower than that in group I (P < 0.05). The E scores in group II were significantly higher than that in group I (P < 0.01). (3) CSQ score: the problem-saving factor and help-seeking factor in group II were more significantly lower than that in group I (P < 0.01). The self-blaming factor in group II were higher than that in group I (P < 0.05). (4) There was positive correlation between total scores of QOL and the problem-saving factor, help-seeking factor of CSQ, the E scores of EPQ (P < 0.05), there was negative correlation between total scores of QOL and the P scores, the N scores of EPQ (P < 0.05). CONCLUSIONS: The advanced laryngeal cancer patients of group II have better life quality, and their personalities showed more extroversive, stable feeling, adaptable, mature coping styles. The above characteristics may have good effects on the prognosis of advanced laryngeal cancer.