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Highlights This study is a community-based RCT. This study provides scientific-based evidence on the effects and safety of herbal medicines during COVID-19 Pandemic.

Various clinical studies have determined that aspirin shows anticancer effects in many human malignant cancers, including human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. However, the anti-tumor mechanism of aspirin has not been fully defined. The aim of this study was to determine the role of Compound C in enhancing the anticancer effect of aspirin. HER-2-positive breast cancer cell lines were treated with aspirin with or without Compound C pre-treatment; their phenotypes and mechanisms were then analyzed in vitro and in vivo. Aspirin exhibited anticancer effects in HER-2-positive breast cancer by inhibiting cell growth and inducing apoptosis through the activation of AMP-activated protein kinase (AMPK). Unexpectedly, pre-treatment with Compound C, a widely used AMPK inhibitor, induced robust anticancer effects in cells compared to aspirin monotherapy. This anticancer effect was not distinct in HER-2 negative breast cancer MDA-MB-231 cells and may be due to the inhibition of lipid metabolism mediated by c-myc. Besides, c-myc re-expression or palmitic acid supply could partially restored cell proliferation. Aspirin exhibits anticancer effects in HER-2-positive breast cancer by regulating lipid metabolism mediated by c-myc, and Compound C strengthens these effects in an AMPK-independent manner. Our results potentially provide a novel therapeutic strategy exploiting combined aspirin and Compound C therapy for HER-2-positive breast cancer, which acts by reducing de novo lipid synthesis.

BackgroundPrimary insomnia (PI) is one of the most common complaints among the general population. Both non-pharmacological and pharmacological therapies have proven effective in treating primary insomnia. However, the underlying mechanism of treatment remains unclear, and no studies have compared the underlying mechanisms of different treatments.MethodsIn this study, we investigated gray matter volume (GMV) and resting-state functional connectivity (rsFC) changes following both pharmacological and non-pharmacological treatments in patients with PI. A total of 67 PI patients were randomized into benzodiazepine treatment, cupping treatment, or a wait-list control group for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI), gray matter volume (GMV), and resting-state functional connectivity (rsFC) of the hippocampus were measured at the beginning and end of the experiment.ResultsWe found 1) significantly decreased PSQI scores in the cupping and benzodiazepine treatment groups compared to the control group with no significant differences between the two treatment groups; 2) significant GMV increases in the cupping group compared to the control group at the right hippocampus after 4 weeks of treatment; 3) significantly increased rsFC between the right hippocampus and left rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC) in the two treatment groups, which was significantly associated with PSQI score decreases.DiscussionOur findings suggest that benzodiazepine and cupping may share a common mechanism to relieve the symptoms of patients with PI.

Background: Depression is a common and potentially life-threatening mental illness, and currently, there is a lack of effective treatment. It has been reported that dehydrocorydaline (DHC) can inhibit monoamine transporter uptake in depressed CUMS mice, but more possible mechanisms of action remain to be further studied.Methods: C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for five consecutive weeks. The mice were administrated with dehydrocorydaline or fluoxetine (FLU) for four consecutive weeks. Behavioral tests including sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST) were applied. In parallel, hematoxylin and eosin (H&E) staining and Nissl staining were used to explore the effect of DHC on pathological changes in the hippocampus. The concentrations of depression-related factors (5-HT and DA) and inflammatory factors (TNF-α, IL-6, and IL-1β) in the hippocampus and serum were assessed by ELISA assay. NLRP3 inflammasome pathway-related proteins (NLRP3, IL-18, IL-1 IL-1α, and caspase-1) were detected by western blot. The activation of microglia and astrocytes was subjected to immunofluorescent staining. Additionally, microglia were treated with DHC (100 mg/L) for 24 h following incubation with 100 ng/ml LPS for 12 h. ov-NC or ov-NLRP3 plasmid was transfected into microglia 6 h before LPS induction for exploring the effect of NLRP3 overexpression on DHC-inhibited microglia activation. Then, conditioned media of microglia were collected from each group, followed by intervention of astrocytes for 24 h to explore the effect of NLRP3 overexpression of microglia on astrocyte activation.Results:In vivo administration of DHC was found to ameliorate depressive-like behaviors and attenuate neuron damage of CUMS mice. DHC increased neurotransmitter concentration, reduced the proinflammatory factor levels, attenuated NLRP3 inflammasome activation, and decreased A1 astrocyte and microglia activation in the hippocampus of CUMS mice. Furthermore, in vivo results showed that activated microglia induced activation of A1 astrocytes but not A2 astrocytes.Conclusion: Taken together, we provided evidence that DHC exhibited antidepressive effects on CUMS mice possibly via NLRP3 inflammasome-mediated astrocyte activation.

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