A transcranial sonography study of brainstem and its association with depression in idiopathic generalized epilepsy with tonic-clonic seizures.

Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with depression. But, up to date, the association of BR alterations in TCS with depression in patients with epilepsy has never been reported. This study was to investigate the possible role of BR examination via TCS in patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression. Forty-six patients with IGE-TCS and 45 healthy controls were recruited. Echogenicity of the caudate nuclei (CN), lentiform nuclei (LN), substantia nigra (SN), and BR and widths of the lateral ventricle (LV) frontal horns and the third ventricle (TV) were assessed via TCS. The determination of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), and depression severity measured by Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II). The width of TV in patients with epilepsy was found significantly larger than that in healthy controls (p = 0.001), but there was no significant difference in TV width between patients with IGE-TCS with and without depression. There were no significant differences between patients with IGE-TCS and healthy controls in LV frontal horn width, as well as in SN, CN, LN, and BR echogenicity. Here, it seems that patients with IGE-TCS were detected with smaller SN echogenic area compared with controls though they had no statistical significance. Patients with IGE-TCS with hypoechogenic BR had significantly higher C-NDDI-E and BDI-II scores than those with normal BR signal, and most patients with IGE-TCS with depression exhibited hypoechogenic BR, but few patients with IGE-TCS without depression exhibited hypoechogenic BR. In conclusion, BR echogenic signal alterations in TCS can be a biomarker for depression in epilepsy, but it might not be associated with epilepsy itself. The alterations of SN echogenic area and TV width in TCS may reflect a potential role of SN and diencephalon structure in the pathogenesis of epilepsy, which needs to be further elucidated.

GGPP-Mediated Protein Geranylgeranylation in Oocyte Is Essential for the Establishment of Oocyte-Granulosa Cell Communication and Primary-Secondary Follicle Transition in Mouse Ovary.

Folliculogenesis is a progressive and highly regulated process, which is essential to provide ova for later reproductive life, requires the bidirectional communication between the oocyte and granulosa cells. This physical connection-mediated communication conveys not only the signals from the oocyte to granulosa cells that regulate their proliferation but also metabolites from the granulosa cells to the oocyte for biosynthesis. However, the underlying mechanism of establishing this communication is largely unknown. Here, we report that oocyte geranylgeranyl diphosphate (GGPP), a metabolic intermediate involved in protein geranylgeranylation, is required to establish the oocyte-granulosa cell communication. GGPP and geranylgeranyl diphosphate synthase (Ggpps) levels in oocytes increased during early follicular development. The selective depletion of GGPP in mouse oocytes impaired the proliferation of granulosa cells, primary-secondary follicle transition and female fertility. Mechanistically, GGPP depletion inhibited Rho GTPase geranylgeranylation and its GTPase activity, which was responsible for the accumulation of cell junction proteins in the oocyte cytoplasm and the failure to maintain physical connection between oocyte and granulosa cells. GGPP ablation also blocked Rab27a geranylgeranylation, which might account for the impaired secretion of oocyte materials such as Gdf9. Moreover, GGPP administration restored the defects in oocyte-granulosa cell contact, granulosa cell proliferation and primary-secondary follicle transition in Ggpps depletion mice. Our study provides the evidence that GGPP-mediated protein geranylgeranylation contributes to the establishment of oocyte-granulosa cell communication and then regulates the primary-secondary follicle transition, a key phase of folliculogenesis essential for female reproductive function.

Psycho-social and educational interventions for enhancing adherence to dialysis in adults with end-stage renal disease: A meta-analysis.

AIMS AND OBJECTIVES: To examine the influence of psycho-social and educational interventions on improving adherence to dialysis for patients with end-stage renal disease. BACKGROUND: Adherence to the complex regimen is poor, contributing to avoidable hospitalisation and morbidity. Psycho-social and educational interventions may be beneficial coping strategies. DESIGN: Systematic literature review and meta-analysis were conducted. METHODS: We conducted a systematic search of 8 databases from their inceptions to 16 January 2019 to identify relevant articles. Only randomised controlled trials (RCTs) were included in the analysis. The PRISMA checklist was used. RESULTS: A total of forty RCTs were included to evaluate the effect. The aggregated results of the studies showed that psycho-social and educational interventions elevated adherence rate in both peritoneal dialysis (PD) and haemodialysis (HD) patients. For physiological and biochemical indicators, meta-analysis revealed that significant post-treatment effects were evident for interdialytic weight gain (IDWG), IDWG/dry weight, serum potassium, phosphate, creatinine and blood urea nitrogen (BUN), except for albumin. In particular, subgroup analysis indicated that only the interventions carried out individually exerted significant combined effect for lowering IDWG. As for subjective measures, meta-analysis also revealed small but significant combined effects. CONCLUSIONS: The results of this meta-analysis suggest that psycho-social and educational interventions were associated with significant effects on adherence in patients receiving dialysis regimen. RELEVANCE TO CLINICAL PRACTICE: The analysis suggests that psycho-social and educational interventions should be considered as effective strategies for enhancing adherence to dialysis in adults with end-stage renal disease. The potential utility of these interventions should focus on how best to promote individually implementation in clinical practice.

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Hypoechogenicity of brainstem raphe correlates with depression in migraine patients.

BACKGROUND: Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with major depression (MD) and in depressed patients with different neurodegenerative diseases. But, up to date, the association of BR alterations in TCS with depression in migraineurs has never been reported. This study was to investigate the possible role of BR examination via TCS in migraineurs with depression. METHODS: Forty two migraine without aura (MwoA) patients and 40 healthy controls were recruited. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and brainstem raphe (BR) and width of the frontal horns of the lateral ventricles and the third ventricle were assessed with TCS. The diagnosis of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM -IV), and the severity of depression was measured by Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D). RESULTS: There were no significant differences between migraineurs and controls in the width of frontal horn of the lateral ventricle (p = 0.955), width of third ventricle (p = 0.129) as well as in the echogenicity of SN (p = 0.942), CN (p = 0.053), LN (p = 0.052) and BR (p = 0.677). Here, it seems that more migraineurs were detected with increased echogenecity of CN and LN compared with controls (33.3% versus 15.0% for CN, 19.0% versus 5.0% for LN) though they had no statistical significance. Patients with hypoechogenic BR had significantly higher HAM-D and HADS-D scores than those with normal BR signal (p = 0.000 for both HAM-D and HADS-D), and most (83.33%) migraineurs with depression exhibited hypoechogenic raphe but none (0.00%) of the migraineurs without depression exhibited hypoechogenic raphe (p = 0.000). CONLUSIONS: TCS signal alteration of BR can be a biomarker for depression in migraine but it is not associated with migraine headache itself. LN and CN alterations in TCS may reflect a potential role of them in the pathogenesis of migraine, which needs to be further elucidated.

[Incompatibility mechanism of Crotonis Semen Pulveratum and Glycyrrhizae Radix et Rhizoma based on diuretic effect and intestinal flora structure].

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae＿ukn. The relative abundance of Desulfovibrio and Streptococcaceae＿ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.

[Incompatible mechanism of compatibility of Chinese medicines based on Qianjinzi and Gancao effect on intestinal flora/barrier system].

The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.

Effects of non-pharmacological supportive care for hot flushes in breast cancer: a meta-analysis.

PURPOSE: To assess the efficacy of non-pharmacological therapies for hot flushes (HFs) in women with breast cancer (BC). METHODS: Nine databases (MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), China Biology Medicine (CBM), and Wan Fang Database) were searched from their inceptions to October 2016. We also hand-searched reference lists of reviews and included articles, reviewed conference proceedings, and contacted experts. Finally, randomized controlled trials (RCTs) were aggregated to evaluate the therapeutic effect of acupuncture for HFs in women with BC. RESULTS: Sixteen trials were included in the meta-analysis. Significant combined effects of non-pharmacological therapies were observed in reducing frequency and severity of HFs after treatment (d = -0.57, P < 0.001). These effects were sustained, albeit reduced in part, during follow-up (d = -0.36, P < 0.001), with the exception of frequency (P = 0.41). Meta-analysis according to therapy types showed that for hypnosis, HFs scores instead of scores of HFs-related daily interference scale (HFRDIS) were significantly lowered at the post-treatment time point (d = -13.19, P < 0.001); for acupuncture, a small but significant effect on HFRDIS was found at the post-treatment time point (d = -3.34, P < 0.001). The effect was sustained during follow-up; however, no effect was evident for HFs frequency; for cognitive behavioral therapy (CBT), at the post-treatment time point, but not during follow-up, a small but significant effect was documented for HFs score (d = -0.88, P < 0.01). No serious adverse effect was reported in the included studies. CONCLUSIONS: Various types of non-pharmacological therapies were associated with significant effects on HFs in women with BC.

Chemical Constituents from Euphorbia kansui.

In this research, a new triterpenoid, tirucalla-8,24-diene-3ß,11ß-diol-7-one (1), and eupha-8,24-diene-3ß,11ß-diol-7-one (2), which was isolated from Euphorbia kansui for the first time, together with twelve other known compounds (3-14), were isolated from the ethyl acetate extract of Euphorbia kansui. Their structures were elucidated based on High resolution electrospray ionization mass spectrometry (HR-ESI-MS), Infrared Spectroscopy (IR), 1D and 2D Nuclear Magnetic Resonance (NMR) data. Both constituents 1 and 2 exhibited moderate cytotoxicity against colon cancer HCT-116, gastric cancer MKN-45 and breast cancer MCF-7.

[Antidepressant activity of flavonoid ethanol extract of Abelmoschus manihot corolla with BDNF up-regulation in the hippocampus].

Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-ß-D-glucoside (1), gossypetin-8-O-ß-D-glucuronide (2, G-8-G), gossypetin-3'-O-ß-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg−1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg ·kg−1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).

The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes.

[Effect of Postpartum Depression on Adolescent Depression of Mice Offspring].

OBJECTIVE: To study the effect of postpartum depression (PPD) on adolescent depression of mice offspring. METHODS: Totally 48 Balb/c female mice were equally randomized into control group and stress group. Control group was not given any stress, whereas stress group were given chronic stress: constraining (6 h/d) combined with light stimulation for 24 hours (twice a week). The stress group was divided into 3 groups to measue the animals' behaviors immediately after modeling, three weeks after modeling, and three weeks after delivery to test whether the PPD models were successfully constructed. The first generation (F1) of normal mothers and PPD-born F1 were as follows: control group (CTL-F1) and PPD offspring group (PPD-F1). The 3-4-week-old male CTL-F1 and PPD-F1 mice (n=8 each) were weighed, and received sucrose preference test, forced swimming test, and novelty-supressed feeding test to measure the depression-like behaviors. RESULTS: The 3-and 4-week-old PPD-F1 had significantly lower body mass than CTL-F1 (P=0.000, P=0.002). Also, the sucrose preference significantly decreased (P=0.000), the forced swimming immobility time significantly increased (P=0.001), the latency to feed significantly increased (P=0.000), while food intake significantly decreased (P=0.005). CONCLUSION: PPD offspring may be more susceptible to depression,with a possible eary onset in adolescence.

[Effect of flavonoids from Abelmoschus manihot on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

Abelmoschus manihot was rich in flavonoids, which has been reported the activity on protecting angiocarpy and improving renal function. This study aimed to explore the action mechanism of five flavonoids from A. manihot on how to ameliorating insulin resistance through the regulation of the glucose and expression of PPARγ, C/EBPα, SREBP-1, resistin, visfatin, adiponectin in 3T3-L1 adipocytes. After the 3T3-L1 preadipocytes were differentiated into mature adipocytes, insulin resistance model was built. Insulin resistance adipocytes were treated with 5, 100 µmol•L⁻¹ quercetin, isoquercitrin, hyperoside, quercitrin-3'-O-glucoside, gossypetin-8-O-ß-glucoside. The glucose was indirectly determined by BCA kit. The mRNA expression levels of PPARγ, C/EBPα, SREBP-1, resistin, visfatin, adiponectin were detected by real-time quantitative PCR. Results showed that five flavonoids at 5 µmol•L⁻¹ could accelerate preadipocytes proliferation and inhibit that at 100 µmol•L⁻¹ Compared with the normal group, glucose uptake reduced significantly in model group (P<0.01). With the treatment of five flavonoids at 100 µmol•L⁻¹, glucose consumption increased significantly (P<0.01). The high expression of PPARγ, C/EBPα, adiponectin expression was significantly increased (P<0.01), and low expression of SREBP-1, resistin, visfatin after respective administration with five flavonoids at 100 µmol•L-1 promoted adipocyte differentiation. This study showed that, HY, JY, QT, QG, GG can control preadipocytes proliferation, promote adipocyte differentiation and regulate the expression of relative factors with lipid metabolism, such as PPARγ, C/EBPα, SREBP-1, adiponectin, resistin, visfatin, increasing glucose utilization and improving insulin resistance in 3T3-L1 adipocyte.

Psycho-oncologic interventions to reduce distress in cancer patients: a meta-analysis of controlled clinical studies published in People's Republic of China.

OBJECTIVE: This study aimed to summarize the current result of controlled clinical studies published in China and analyzed the effect of psycho-oncologic interventions on distress of cancer patients. METHODS: Electronic searches were conducted in four databases. The study inclusion criteria were established on the basis of the PICOS (population, intervention, comparator, outcomes, and study design) framework. The main outcome measures were emotional distress, anxiety, and depression. Meta-analytic techniques were applied to analyze published data from the retrieved studies. RESULTS: A total of 207 controlled studies (involving 19,607 cancer patients) were included, among which 31 studies (3007 patients) were meta-analyzed. Pooled analysis showed large effects for psycho-oncologic interventions on anxiety (d = -8.71, p < 0.001) and depression (d = -8.12, p < 0.001). Health education combined with psychological support (d = -8.17, p = 0.04) or with relaxation training (d = -12.95, p < 0.001) significantly lowered the anxiety level in cancer patients. However, health education combined with relaxation training did not lower the depression levels (p > 0.05). Nurses were the primary health professionals (69.08%) responsible for delivering interventions. Meanwhile, none of the reports followed all the items of the consolidated standards of reporting trials checklist. Most studies suffered from some flaws concerning blinding, randomization procedures, participant follow-up, attrition, and so on. CONCLUSION: The findings pointed out that psycho-oncologic interventions significantly reduced distress in cancer patients of China; however, the quality of the randomized controlled trials was low. In the future, reports on controlled clinical studies should follow the consolidated standards of reporting trials statement and supply more comprehensive information.

Determination of nucleosides and nucleobases in the pollen of Typha angustifolia by UPLC-PDA-MS.

INTRODUCTION: The pollen of Typha angustifolia L. has been used traditionally for the treatment of dysmenorrhea, stranguria and metrorrhagia in China. Recently, nucleosides and nucleobases have been proven as important bioactive compounds. Exploration of the nucleoside and nucleobase profiles from the pollen of T. angustifolia is important for improving its therapeutic value and could be convenient for its quality evaluation. OBJECTIVE: To establish an UPLC-PDA-MS method for simultaneous determination of nucleosides and nucleobases in the pollen of T. angustifolia. METHODOLOGY: The analysis was performed on an Acuity UPLCHSS T3 column with a gradient elution of 5 mM ammonium acetate and methanol solution at a flow rate of 0.3 mL/min. RESULTS: Satisfactory separation of these compounds was obtained in less than 12 min. All calibration curves showed good linear regression (r² > 0.9995). The method provided good accuracy, precision, recovery, and sensitivity for the quantification of the 10 compounds analysed. CONCLUSION: The UPLC method established is very helpful for optimising their content and could be convenient for quality evaluation of the pollen of T. angustifolia, which has not been reported as far as we are aware.

Euryale Small Auxin Up RNA62 promotes cell elongation and seed size by altering the distribution of indole-3-acetic acid under the light.

Euryale (Euryale ferox Salisb.) is an aquatic crop used as both food and drug in Asia, but its utilization is seriously limited due to low yield. Previously, we hypothesized that Euryale small auxin up RNAs (EuSAURs) regulate seed size, but the underlying biological functions and molecular mechanisms remain unclear. Here, we observed that the hybrid Euryale lines (HL) generate larger seeds with higher indole-3-acetic acid (IAA) concentrations than those in the North Gordon Euryale (WT). Histological analysis suggested that a larger ovary in HL is attributed to longer cells around. Overexpression of EuSAUR62 in rice (Oryza sativa L.) resulted in larger glumes and grains and increased the length of glume cells. Immunofluorescence and protein interaction assays revealed that EuSAUR62 modulates IAA accumulation around the rice ovary by interacting with the rice PIN-FORMED 9, an auxin efflux carrier protein. Euryale basic region/leucine zipper 55 (EubZIP55), which was highly expressed in HL, directly binds to the EuSAUR62 promoter and activated the expression of EuSAUR62. Constant light increased the expression of both EubZIP55 and EuSAUR62 with auxin-mediated hook curvature in HL seedlings. Overall, we proposed that EuSAUR62 is a molecular bridge between light and IAA and plays a crucial role in regulating the size of the Euryale seed.

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis.

Jujube (Ziziphus jujuba Mill.) fruit (JF) is widely consumed as food in Asian countries due to its potential effects for human health. As a traditional Chinese medicine, JF is often used to treat anorexia, fatigue and loose stools caused by spleen deficiency syndromes in China, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, a rat model of spleen deficiency syndromes was adopted to investigate the therapeutic effect of JF extract and its possible mechanism by metabolomics analyses of plasma and urine as well as the intestinal flora analysis. The results showed that the changes in plasma and urine metabolites caused by spleen deficiency were reversed after administration of JF, and these changed endogenous metabolites were mainly involved in retinol metabolism, pentose and glucuronate interconversions, nicotinate and niacinamide metabolism pathways. The 16S rDNA sequencing results showed that JF could regulate intestinal flora imbalance caused by spleen deficiency. The covariance analysis of intestinal flora structure and metabolome indicated that Aerococcus may be a candidate strain for predicting and treating the metabolic pathways of spleen deficiency and related disorders. In summary, it can be revealed that spleen deficiency, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by JF extract.

Morinda officinalis oligosaccharides mitigate chronic mild stress-induced inflammation and depression-like behaviour by deactivating the MyD88/PI3K pathway via E2F2.

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.

Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou Seed Ameliorates Insomnia in Rats by Regulating Metabolomics and Intestinal Flora Composition.

The seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou (ZSS) is often used as a traditional Chinese medicine for insomnia due to its sedative and hypnotic effects, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, an insomnia model induced by intraperitoneal injection of DL-4-chlorophenylalanine suspension in Sprague-Dawley rats was adopted to investigate the therapeutic effect of ZSS extract. Metabolomics analyses of plasma and urine as well as 16S rRNA gene sequencing of the intestinal flora were performed. The relationships between the plasma and urine metabolites and the intestinal flora in insomnia rats were also analyzed. The results showed that changes in plasma and urine metabolites caused by insomnia were reversed after administration of ZSS, and these changes were mainly related to amino acid metabolism, especially phenylalanine metabolism. The results of 16S rRNA gene sequencing and short-chain fatty acid determination showed that the ZSS extract could reverse the imbalance of intestinal flora caused by insomnia and increase the contents of SCFAs in feces. All of these improvements are mainly related to the regulation of inflammation. Therefore, it is concluded that insomnia, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by ZSS extract.

A novel P38α MAPK activator Bruceine A exhibits potent anti-pancreatic cancer activity.

Pancreatic cancer remains one of the cancers with the poorest prognosis bearing an overall 5-year survival rate of about 5%. Efficient new chemotherapic drugs are still highly desired. Here, bruceine A, a quassinoid identified from the dried fruits of Brucea javanica (L.) Merr., displayed the most potent anti-proliferation activity against pancreatic cancer in vitro and in vivo. Phosphoproteomic analysis revealed p38α MAPK phosphorylation was involved in bruceine A's action in MIA PaCa-2 cells. Utilizing fortebio octet system and microscale thermophoresis, we found p38α MAPK had high affinity for bruceine A. Molecular docking and molecular dynamic simulations showed that bruceine A widely bound to residues (Leu171, Ala172, Met179, Thr180, Val183) in P-loop of p38α MAPK. Key determinants of bruceine A binding with P-loop of p38α MAPK were 19-C[bond, double bond]O, 22-CH3, 32-CH3, and 34-CH3. Taken together, our findings demonstrate that bruceine A binds directly to p38α MAPK, which can be used to probe the role of p38α MAPK phosphorylation in pancreatic cancer progression, and as a novel lead compound for pancreatic cancer therapy.