Notes

Mitochondrial genome regarding Geomydoecus aurei, any pocket-gopher louse.
As STING is localized to the ER, we analyzed the relation between STING activation and ER stress. In HRVECs, STING pathway was shown to be activated under chemical-induced ER stress, but attenuated when IRE1α was abolished by genetic deletion or pharmacological inhibition. Taken together, our findings revealed that STING signaling plays an important role in mediating lipotoxicity-induced endothelial inflammatory and injury, and IRE1α-XBP1 signaling potentiated STING signaling. Thus, targeting the IRE1α or STING pathways to alleviate endothelial inflammation provides candidate therapeutic target for treating DR as well as other microvascular complications.Sulforaphane is a bioactive metabolite with anti-inflammatory activity and is derived from the glucosinolate glucoraphanin, which is highly abundant in broccoli sprouts. However, due to its inherent instability its use as a therapeutic against inflammatory diseases has been limited. There are few studies to investigate a whole food approach to increase sulforaphane levels with therapeutic effect and reduce inflammation. In the current study, using a mouse model of inflammatory bowel disease, we investigated the ability of steamed broccoli sprouts to ameliorate colitis and the role of the gut microbiota in mediating any effects. We observed that despite inactivation of the plant myrosinase enzyme responsible for the generation of sulforaphane via steaming, measurable levels of sulforaphane were detectable in the colon tissue and feces of mice after ingestion of steamed broccoli sprouts. In addition, this preparation of broccoli sprouts was also capable of reducing chemically-induced colitis. This protective effect was dependent on the presence of an intact microbiota, highlighting an important role for the gut microbiota in the metabolism of cruciferous vegetables to generate bioactive metabolites and promote their anti-inflammatory effects.Mitochondrial reactive oxygen species (ROS)generation plays an essential role in the process of adipocyte differentiation and is involved in the development of obesity and associated metabolic diseases. Various dietary flavonoids possess the substantial anti-adipogenic activity. However, it is unclear whether these flavonoids inhibit adipocyte differentiation by reducing ROS generation. In this study, the effects of six common dietary flavonoids on adipocyte differentiation were assessed in 3T3-L1 cells. The flavonoids with the same backbone of 5,7-dihydroxylflavone, including flavones apigenin, chrysin, luteolin and flavonols kaempferol, myricetin, quercetin, dose-dependently inhibited 3T3-L1 adipocyte differentiation, suggesting an associated hierarchy of inhibitory capability luteolin > quercetin > myricetin > apigenin/kaempferol > chrysin. Meanwhile, six flavonoids were found to inhibit adipogenic gene expression and the early stage of adipocyte differentiation. Among the tested flavonoids, luteolin significantly reduced both intracellular and mitochondrial ROS generation during adipocyte differentiation. p38 MAPK activation Further, luteolin treatment depressed the elevation of H2O2 concentration in the early stage of 3T3-L1 differentiation and reversed the facilitated effects of exogenous H2O2 on 3T3-L1 adipocyte differentiation and ROS generation. Altogether, the activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation, elucidating a new mechanism underlying the anti-adipogenic actions of flavonoids.Observational study indicated that folic acid (FA) supplementation may protect against tuberculosis-drug-induced liver injury (TBLI). The aim is to investigate the effect and mechanism of FA on TBLI in rats. Liver injury was induced by a daily gavage of isoniazid (INH) and rifampicin (RIF) in the model and FA groups. Rats in the FA group were also treated with 2.5 mg/kg body weight FA. Rats in the control group were not treated. Eight rats were used in each group. The severity of liver injury was measured by the serum levels of hepatic enzymes and histological score. The metabolites in serum and liver tissues were analyzed by HPLC-Q-TOF-MS/MS. FA treatment significantly reduced alanine aminotransferase and liver necrosis. Seventy-nine differential metabolites in the serum and liver tissues were identified among the three groups. N-acylethanolamines, INH and RIF metabolites, phosphatidylcholines, lysophosphatidylcholines, monoglycerides, diglycerides and bile acids were regulated by FA treatment, involving key metabolic pathways, such as N-acylethanolamine metabolism, INH and RIF metabolism, liver regeneration, inflammation alleviation and bile acid metabolism. RT-PCR and western blotting results confirmed the altered N-acylethanolamine metabolism and improved drug metabolism by FA. In conclusion, FA was protective against TBLI, which may be related to the regulation of N-acylethanolamine metabolism and drug detoxification by FA.Folic acid, a water-soluble B-vitamin, has been demonstrated to decrease the risk of first stroke and improve its poor prognosis. However, the molecular mechanisms responsible for the beneficial effect of folic acid on recovery from ischemic insult remain largely unknown. Excessive activation of the N-methyl-d-aspartate receptors (NMDARs) has been shown to trigger synaptic dysfunction and excitotoxic neuronal death in ischemic brains. Here, we hypothesized that the effects of folic acid on cognitive impairment may involve the changes in synapse loss and NMDAR expression and function following cerebral ischemia/reperfusion injury. The ischemic stroke models were established by middle cerebral artery occlusion/reperfusion (MCAO/R) and by oxygen-glucose deprivation and reperfusion (OGD/R)-treated primary neurons. The results showed that folic acid supplemented diets (8.0 mg/kg for 28 days) improved cognitive performances of rats after MCAO/R. Folic acid also caused a reduction in the number of neuronal death, an increase in the number of synapses and the expressions of synapse-related proteins including SNAP25, Syn, GAP-43 and PSD95, and a decrease in p-CAMKII expression in ischemic brains. Similar changes in synaptic functions were observed in folic acid (32 µM)-treated OGD/R neurons. Furthermore, NMDA treatment reduced folic acid-induced upregulations of synapse-associated proteins and Ca2+ influx, whereas downregulations of NMDARs by NR1 or both NR2A and NR2B siRNA further enhanced the expressions of synapse-related proteins raised by folic acid in OGD/R neurons. Our findings suggest that folic acid improves cognitive dysfunctions and ameliorates ischemic brain injury by strengthening synaptic functions via the NMDARs.Dietary restriction through low-calorie intake or intermittent fasting benefits many organs, including the brain. This study investigated the neuroprotective effects of fasting in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. We found that fasting every other day rather than weekly increased the levels of brain-derived neurotrophic factor and glial-derived neurotrophic factor in the nigrostriatal pathway. Therefore, we maintained the animals on alternate-day fasting for 2 weeks and injected MPTP (30 mg/kg/day, intraperitoneally [i.p.]) for five days. We observed that alternate-day fasting attenuated MPTP-induced dopaminergic neuronal loss and astroglial activation in the substantia nigra and the striatum. Moreover, neurochemical analysis using high-performance liquid chromatography showed that alternate-day fasting reduced MPTP-induced depletion of striatal dopamine. Consistent with these results, behavioral tests showed that fasting suppressed the motor impairment caused by MPTP. Furthermore, fasting increased the phosphorylation of phosphatidylinositol-3-kinase and protein kinase B, which are downstream signaling molecules of neurotrophic factors. Fasting also increased the phosphorylation of extracellular signal-regulated protein kinase and cAMP response element-binding protein, further supporting the involvement of neurotrophic factors in the observed neuroprotective effects. Hence, our results demonstrated the dopaminergic neuroprotection of intermittent fasting in an MPTP mouse model of Parkinson's disease, supporting the idea that fasting could be an instrumental tool for preventing neurodegeneration in the brain.Citrus peel is rich in bioactive components, especially polyphenols, which are considered to have great potential in the prevention of intestinal diseases. The intestinal mucus barrier is the first defense against the invasion of foreign substances. In this study, we aimed to explore the possibility and mechanism of citrus peel in alleviating the mucus barrier damage in high-fat-diet (HFD) mice. We found that citrus peel powder (CPP) supplementation effectively reduced body weight, fat weight, intestinal permeability, hyperlipidemia, and systemic inflammation in HFD-fed mice. In particular, CPP increased the number of goblet cells, the protein expression of Mucin-2 (Muc2), and the thickness of the mucus layer, thereby strengthening the colonic mucus barrier function. Moreover, CPP supplementation also reduced the expression of endoplasmic reticulum stress (ERS) proteins (GRP78 and CHOP) and increased the expression of T-synthase (O-glycosylation rate-limiting enzyme) and its chaperone protein (Cosmc) in the colon of HFD-fed mice, which suggested that CPP could improve the abnormal protein folding and O-glycosylation of Muc2 during processing and modification. In summary, our study indicates that CPP plays an effective role in relieving mucus barrier damage by improving the production and properties of Muc2, providing new perspectives on the development of CPP as a dietary supplement for strengthening the intestinal barrier.Increasing evidence indicate that cancer stem cells (CSCs) are the key driver of tumor initiation and recurrence. The cellular and soluble components of the tumor microenvironment (TME) impact on cancer initiation and progression, such as cytokines and chemokines. Thus, targeting CSCs and TME is a novel anti-cancer approach. Resveratrol (RES), a bioactive phytochemical extracted from various plants, exhibits tumor-suppressing activities in lung cancer, yet the mechanism remains poorly understood. Our data showed that the expression level of IL-6 was positively correlated with the presence of lung cancer stem-like cells (LCSCs) in human lung cancer tissues. In vitro results showed that IL-6 was highly elevated in lung cancer sphere-forming cells and could enhance the stemness of LCSCs, including tumor sphere formation ability, the percentage of CD133 positive cells, and the expression of LCSC specific markers (CD133, ALDH1A1 and Nanog). Simultaneously, our results confirmed that RES effectively inhibited LCSC properties, downregulated Wnt/β-catenin signaling and reduced IL-6 level in vitro and in vivo. Furthermore, we found RES treatment attenuated the activation of Wnt/β-catenin signaling by LiCl (GSK3β agonist). IL-6-promoted LCSC properties and Wnt/β-catenin signaling was also reversed by RES. Taken together, these data illustrated that RES inhibited lung cancer by targeting LCSCs and IL-6 in TME. The novel findings from this study provided evidence that RES exhibited multi-target effects on suppression of lung cancer and could be a novel potent cancer-preventive compound.
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