Coadministration of epigallocatechin-3-gallate (EGCG) and caffeine in low dose ameliorates obesity and nonalcoholic fatty liver disease in obese rats.

Epigallocatechin-3-gallate (EGCG) and caffeine in tea exert anti-obesity effects and induces nonalcoholic fatty liver disease (NAFLD) amelioration. However, previous studies usually performed a high-dose EGCG administration, whereas the insecurity was arisen in recent researches. In this study, we treated obese rats with an elaborate dose-40 mg/kg EGCG, 20 mg/kg caffeine, and the coadministration of them as low dose, which were similar to the daily intake; 160 mg/kg EGCG as high dose, which was the maximum safe dose had touched the contentious edge. The results suggested that the coadministration of EGCG and caffeine exerted more remarkable function on suppressing body weight gain, reducing white adipose tissue weight and decreasing the energy intake than single use. This may be due to the variation in serum lipid profile, oxidative stress, and adipose-derived and inflammatory cytokines. The pathological micrographs showed long-term high-fat diets caused severe NAFLD, but it was ameliorated at different levels by all of the administrations. In summary, low dose of EGCG or caffeine only showed a mild effect of anti-obesity and NAFLD amelioration. The coadministration of them could exert a superior curative effect as well as high dose EGCG but no anxiety regarding safety.

Global Indigenous gender concepts, gender-based violence and resilience: A scoping review.

BACKGROUND & OBJECTIVE: The legacy of colonialism includes ongoing trauma and disruption of traditional teachings on relationality, which has contributed to Indigenous populations being disproportionately exposed to gender-based violence (GBV). GBV in Indigenous populations is explored to consider gender-specific findings and points of resilience in relational networks. PARTICIPANTS & SETTING: Included articles sampled Indigenous groups in Canada, US, Mexico, Guatemala, and Israel. All participants self-identified as Indigenous, and were either GBV survivors or service providers working in GBV contexts. METHODS: A scoping review was conducted in OVID Medline, Embase, APA Psycinfo, and Informit Indigenous Collection, using keywords for Indigenous peoples, gender concepts, and GBV. Articles were screened and extracted by two reviewers; a third reviewer resolved conflicts. RESULTS: Our search yielded one mixed-method study and seven qualitative studies, all published since 2016. North American studies identified colonial, patriarchal disruptions (e.g. residential schools) to positive pre-contact gender norms (e.g. non-hierarchical roles) that contribute to emerging GBV. Studies conducted in Guatemala and Israel also described local patriarchal cultures contributing to GBV. Lack of understanding of the Two-Spirit identity (i.e. supra-binary gender identity used by Indigenous persons) led to harmful attitudes and stigma. Interpersonal support and return to traditional matriarchal practices were identified as key resilience processes. CONCLUSIONS: There is limited literature on Indigenous gender concepts and GBV, particularly regarding GBV against males and Two-Spirit persons. Colonization-related violence and/or patriarchal gender norms were identified as precursors for GBV. Decolonization processes should be further explored to address GBV in Indigenous populations.

Harmine exerts anxiolytic effects by regulating neuroinflammation and neuronal plasticity in the basolateral amygdala.

Increasing evidence indicates that an altered immune system is closely linked to the pathophysiology of anxiety disorders, and inhibition of neuroinflammation may represent an effective therapeutic strategy to treat anxiety disorders. Harmine, a beta-carboline alkaloid in various medicinal plants, has been widely reported to display anti-inflammatory and potentially anxiolytic effects. However, the exact underlying mechanisms are not fully understood. Our recent study has demonstrated that dysregulation of neuroplasticity in the basolateral amygdala (BLA) contributes to the pathological processes of inflammation-related anxiety. In this study, using a mouse model of anxiety challenged with Escherichia coli lipopolysaccharide (LPS), we found that harmine alleviated LPS-induced anxiety-like behaviors in mice. Mechanistically, harmine significantly prevented LPS-induced neuroinflammation by suppressing the expression of pro-inflammatory cytokines including IL-1ß and TNF-α. Meanwhile, ex vivo whole-cell slice electrophysiology combined with optogenetics showed that LPS-induced increase of medial prefrontal cortex (mPFC)-driven excitatory but not inhibitory synaptic transmission onto BLA projection neurons, thereby alleviating LPS-induced shift of excitatory/inhibitory balance towards excitation. In addition, harmine attenuated the increased intrinsic neuronal excitability of BLA PNs by reducing the medium after-hyperpolarization. In conclusion, our findings provide new evidence that harmine may exert its anxiolytic effect by downregulating LPS-induced neuroinflammation and restoring the changes in neuronal plasticity in BLA PNs.

Early life stress induces anxiety-like behavior during adulthood through dysregulation of neuronal plasticity in the basolateral amygdala.

AIMS: Early life stress (ELS) increases the risk of psychiatric diseases such as anxiety disorders and depression in later life. Hyperactivation of the basolateral amygdala (BLA) neurons plays a pivotal role in the pathogenesis of stress-related diseases. However, the functional roles of BLA neurons in ELS-induced anxiety disorders are not completely understood. MAIN METHODS: Mice were subjected to maternal separation (MS) during postnatal days 3 to 21 to mimic ELS. Anxiety-like behavior was tested by open field test (OFT), elevated plus maze (EPM), and novelty suppressed feeding (NSF). Then, c-fos expression, a proxy for neuronal activity, was evaluated by immunofluorescence. Finally, synaptic transmission and intrinsic excitability were measured by whole-cell patch-clamp recordings. KEY FINDINGS: MS significantly increased anxiety-like behavior in adulthood, as indicated by less time spent in the center area of the OFT, less time spent in and fewer entries to the open arms of the EPM, and increased latency to feed in NSF. Mechanistically, MS increased the expression of c-fos in BLA. MS enhanced the excitatory, but not inhibitory, synaptic transmission onto BLA projection neurons (PNs), which was caused by enhanced presynaptic glutamate release. Moreover, MS also markedly increased the intrinsic neuronal excitability of BLA PNs, probably due to the reduced medium afterhyperpolarization (mAHP) in BLA PNs. SIGNIFICANCE: Our results suggest that the changes of neuronal activity and synaptic transmission in the BLA PNs may play a crucial role in ELS-induced anxiety-like behavior, and these findings provide new insights into the pathological mechanisms of stress-related anxiety disorders.

[Clinical application of extracorporeal membrane oxygenation for severe heart failure during peri-operative period of end-stage cardiopathy].

OBJECTIVE: To summarize the clinical effect and experience of extracorporeal membrane oxygenation (ECMO) support for severe heart failure during peri-operative period of end-stage cardiopathy. METHODS: From June 2007 to July 2010, 6 patients with severe heart failure during peri-operative period of end-stage cardiopathy received ECMO support. The changes in the hemodynamics and outcome of the patients during the use of ECMO were investigated. RESULTS: The duration of ECMO assistance ranged from 23 to 168 hours with a mean of 78 hours. The hemodynamics after using ECMO was much improved than before ECMO [mean arterial pressure (mm Hg, 1 mm Hg=0.133 kPa): 78.13±8.01 vs. 47.75±5.21, central venous pressure ( mm Hg ): 11.03±3.21 vs. 19.36±4.51, cardiac output (L/min): 4.93±1.01 vs. 3.50±0.81, cardiac index (L×min(-1)×m(-2)): 2.71±0.51 vs. 1.91±0.40, pulmonary artery wedge pressure ( mm Hg ): 12.72±6.52 vs. 20.22±6.91, venous oxygen saturation: 0.66±0.13 vs. 0.54±0.07], and the amount of using inotropic drug was significantly reduced compared with that before ECMO [dopamine (µg×kg(-1)×min(-1)): 5.05±0.85 vs. 14.20±5.05, epinephrine (µg×kg(-1) ×min(-1)): 0.05±0.01 vs. 0.24±0.04, all P<0.05]. All patients were successfully weaned from ECMO. After weaning, 3 patients recovered and discharged, and the hospital discharge rate was 50%, while 3 patients died of multiple organ failure (MOF). Major complication was bleeding, disseminated intravascular coagulation, infection, embolism. CONCLUSION: ECMO is an important extracorporeal method to support life. ECMO is an effective measure of treatment for end-stage cardiopathy patients with peri-operative severe heart failure. It is important to properly select patients for ECMO.