Th1 and Th17 cells are crucial in immune regulation and autoimmune disease development. By adding Stat6 deficiency to T-bet deficiency, and thus negating effects from elevated levels of IL-4/Stat6/GATA3 Th2 signals in T-bet-deficient cells, we investigated the signals important for Th1 and Th17 cell differentiation and their role in colitis development. The data reveal that Eomesodermin compensates T-bet deficiency for IFN-γ and Th1 development. However, without T-bet, IFN-γ production and Th1 differentiation are susceptible to inhibition by IL-6 and TGFβ. As a result, Th17 development is strongly favored, the threshold for TGFβ requirement is lowered, and IL-6 drives Th17 differentiation, elucidating a critical role for T-bet in directing T cell differentiation to Th1 vs Th17. In contrast to IL-6 plus TGFβ-driven Th17, IL-6-driven Th17 cells do not express IL-10 and they induce a more intense colitis. Naive CD4 T cells deficient in Stat6 and T-bet also induce a Th17-dominant colitis development in vivo. Our data provide new insights into the choice between Th1 and Th17 development and their roles in autoimmunity.
Comorbid diabetes, and more extensive as opposed to partial superficial parotidectomy, may be associated with transient facial palsy following operation for benign parotid disease. The incidence of permanent facial palsy may be higher when a more extensive parotidectomy is performed.
Recent studies indicate that metabolic disorders such as diabetes and obesity are a major risk factor of psychiatric diseases. This relationship opens the opportunity to develop new antidepressant drugs by repurposing antidiabetic drugs. Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In addition, the GLP-1 analog liraglutide has been shown to promote neurogenesis, which is seen to play important roles in memory formation and cognitive and emotional processing. However, whether liraglutide is an effective antidepressant remains unknown. Therefore, we tested this hypothesis in the depression model of chronic administration of corticosterone (CORT) in mice and treated the animals daily with liraglutide (5 or 20 nmol/kg ip.) to assess its therapeutic potential as an antidepressant. Behavioral studies showed that liraglutide administration attenuated depressive- and anxiety- like behaviors in this depression mouse model, and attenuated the hyperactivity induced by the stress hormone. Additionally, liraglutide treatment protected synaptic plasticity and reversed the suppression of hippocampal long-term potentiation induced by CORT administration, demonstrating synaptic protective effects of liraglutide. We also found that liraglutide treatment increased the cell density of immature neurons in the subgranular dentate gyrus region of the hippocampus. In addition, liraglutide prevented the CORT induced impairments and simultaneously increased the level of phosphorylated GSK3β in the hippocampus, which may be instrumental in the anti-depressant activity of liraglutide treatment. Taken together, liraglutide has the potential to act as a therapeutic treatment of depression.
Three new dihydroisocoumarin penicimarins G–I (1–3), together with one known dihydroisocoumarin (4) and three known meroterpenoids (5–7), were obtained from a fungus Penicillium citrinum isolated from the mangrove Bruguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of spectroscopic data. The absolute configuration of 1 was determined by the X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of 2 and 3 were determined by comparison of their circular dichroism (CD) spectra with the literature. All compounds were evaluated for their antibacterial activities and cytotoxic activities.
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