Heat enhances the inhibitory effect of lipopolysaccharide on duck granulosa cell proliferation and steroid biosynthesis in vitro.

Lipopolysaccharide (LPS) reduces the reproductive performance of laying ducks, especially during the hot summer months. To study the underlying mechanisms, we investigated the effects of different LPS concentrations and heat on duck granulosa cell (GC) proliferation and steroid biosynthesis in vitro. We investigated GC proliferation, secretion, and activation of the MAPK pathway. The cell cycle results showed that LPS treatment alone did not significantly affect cell proliferation, whereas the mRNA expression levels of IGF2, IGFBP2, and CyclinD1 were downregulated and p27kip1 was significantly upregulated after 2000 ng/mL LPS treatment when compared to untreated cells. In steroid hormone synthesis, although LPS increased the expression of most steroid biosynthesis genes, it inhibited the expression of CYP11A1 at high LPS concentrations. High temperatures enhanced the inhibitory effect of LPS on the expression of proliferation-promoting genes. Heat significantly reduced CYP11A1 and CYP19A1 expression. In addition, the phosphorylation of P38 was significantly upregulated by high temperatures combined with LPS, whereas the phosphorylation of ERK1/2 and JNK was downregulated. The relative protein expression of Bax/BCL-2 was upregulated at high temperatures in combination with LPS. Heat treatment enhanced the inhibitory effects of LPS on the proliferation and hormone biosynthesis of duck GCs in vitro.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

The effect of heat stress on proliferation, synthesis of steroids, and gene expression of duck granulosa cells.

Granulosa cells (GCs) play an important role in the development of follicles. In this study, we investigate the impact of heat stress at 41°C and 43°C on duck GCs' proliferation and steroids secretion. And, the transcriptomic responses to heat treatment were examined using RNA-sequencing analysis. Digital gene expression profiling was used to screen and identify differentially expressed genes (fold change ≥ 2 and Q value < 0.05). Further, the differential expression genes (DEGs) were classified into GO categories and KEGG pathways. The results show that duck GCs blocked in the G1 phase were increased on exposure to heat stress. Meanwhile, the expression of proliferative genes, which were essential for the transition from G1 to S phase, was inhibited. At the same time, heat stress inhibited the estradiol synthesis of GCs by decreasing CYP11A1 and CYP19A1 gene expression. A total of 241 DEGs including 181 upregulated and 60 downregulated ones were identified. Transcriptome result shows that heat shock protein and CXC chemokines gene were significantly activated during heat stress. While collagenases (MMP1 and MMP13) and strome lysins (MMP3) were downregulated. And, the hedgehog signaling pathway may be a prosurvival adaptive response under heat stress. These results offer a basis for better understanding the molecular mechanism underlying lay-eggs-less in ducks under heat stress.

The efficacy of group cognitive-behavioural therapy plus duloxetine for generalised anxiety disorder versus duloxetine alone.

OBJECTIVE: To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD). METHODS: Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up. RESULTS: At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen's d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36-0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32-0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02-4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27-6.16, p=0.01). CONCLUSIONS: Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.