Background: Neuroinflammation is an important pathological mechanism of depression that leads to an increase in indoleamine-2,3-dioxygenase (IDO) activity and NMDAR activation. This study aimed to observe the effects of electroacupuncture on depression-like behaviour in lipopolysaccharide (LPS)-treated rats and the underlying mechanism. Methods: Wistar rats were intraperitoneally administered LPS (0.5 mg/kg) for 7 consecutive days to establish a depression model. Electroacupuncture treatment was administered 1 hour after daily LPS injection. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to evaluate the depressive-like behaviours. IL-1β, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA); Trp, 5-hydroxytryptamine (5-HT), kynurenine (Kyn) and quinolinic acid (Quin) were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry; and N-methyl-D-aspartate receptor (NMDAR) protein and mRNA were assessed by Western blot and real-time qPCR. Results: The results showed that electroacupuncture treatment successfully corrected LPS-induced depressive-like behaviour, reduced the inflammatory factor (IL-1β, IL-6 and TNF-α) levels in the blood and hippocampus, prevented IDO over-activation and recovered NR2B expression after challenge by LPS. Conclusion: Electroacupuncture treatment provided protection against LPS-induced depressive-like behaviour, and the associated mechanisms may be related to inhibiting the inflammatory response, regulating the IDO-mediated tryptophan-degrading pathway, and inhibiting NR2B activation.

Background: Poststroke depression (PSD) is the most frequent psychological sequela after stroke. Electroacupuncture (EA) treatment is effective for PSD. The study aimed at clarifying the mechanisms of EA’s antidepressant effects in a PSD rat model. Methods: We used middle cerebral artery occlusion to establish the rat model of PSD. Tests of sucrose preference and locomotor activity were performed to examine depressive-like behaviors. We measured malondialdehyde, GSH, SOD, IL6, IL1β, TNFα, and 5HT with ELISA. The hippocampal Shh-signaling pathway was assessed by Western blot. Results: EA significantly decreased sucrose preference and locomotor activities of PSD rats, reduced IL6, TNFα, increased GSH, and upregulated 5HT, and also slightly reduced IL1β and malondialdehyde, all of which were measured with ELISA. The Shh-signaling pathway assessed by Western blotting was activated by EA. Those changes were inhibited by the Shh-pathway inhibitor cyclopamine. Conclusion: EA effectively alleviated depressive-like behaviors in PSD by suppressing inflammation and oxidative stress through activation of the Shh-signaling pathway.

Glutathione (GSH)‑degrading enzymes are essential for starting the first stages of GSH degradation. These enzymes include extracellular γ‑glutamyl transpeptidase (GGT) and intracellular GSH‑specific γ‑glutamylcyclotransferase 1 (ChaC1) and 2. These enzymes are essential for cellular activities, such as immune response, differentiation, proliferation, homeostasis regulation and programmed cell death. Tumor tissue frequently exhibits abnormal expression of GSH‑degrading enzymes, which has a key impact on the development and spread of malignancies. The present review summarizes gene and protein structure, catalytic activity and regulation of GSH‑degrading enzymes, their vital roles in tumor development (including regulation of oxidative and endoplasmic reticulum stress, control of programmed cell death, promotion of inflammation and tumorigenesis and modulation of drug resistance in tumor cells) and potential role as diagnostic biomarkers and therapeutic targets.

Introduction A number of observational studies have indicated that poststroke depression could increase the risk of stroke outcomes. There is a meta-analysis indicating that poststroke depression is a risk factor of all-cause mortality. This paper reports the protocol for a systematic review and meta-analysis to clarify the associations of poststroke depression with stroke recurrence and mortality in order to determine whether poststroke depression is a predictor of stroke outcomes according to data extracted from relevant observational studies. Methods and analysis MEDLINE, Web of Science databases, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews will be used to conduct the search. Published studies written in English will be included. The risk of bias for the studies included in the systematic review or meta-analysis will be assessed by the Newcastle–Ottawa Quality Assessment Scale. HRs for stroke recurrence and mortality with 95% CIs will be included as primary outcomes. Subgroup analyses and meta-regression will be performed. Ethics and dissemination Ethics approval will not be needed because the data used in this systematic review will be extracted from published studies. The results of the systematic review focusing on whether depression after stroke is a predictor for stroke recurrence and mortality will be disseminated by publication in a peer-reviewed journal. PROSPERO registration number CRD42018107944.