Modification on phenolic profiles and enhancement of antioxidant activity of proso millets during germination.

Changes in phenolic profiles and antioxidant activity of three varieties of proso millet during germination were investigated. Total phenolic content (TPC) and total flavonoid content (TFC) increased significantly with prolongation in germination period. After germination for 6 days, TPC of the free and bound fractions increased 6.30-8.66-fold and 77.65-116.18%, respectively. The free and bound phenolic compounds identified by UPLC-MS/MS, displayed significant variations. Feruloylquinic acid and N,N'-bis-(p-coumaroyl)-putrescine biosynthesized during germination, are reported for the first time in proso millets. Other phenolics including trans- and cis-ferulic, trans-p-coumaric, vanillic acid and ferulic acid dimers (DFAs) were increased significantly along with a new DFA (8,5'-DFA) seemingly produced during germination. The germinated proso milllets displayed superior antioxidant activity than the corresponding ungerminated samples indicating that germination could be one applicable method for improving phenolic profiles and antioxidant capacity of proso millets. Thus germinated proso millet could be exploited as a functional ingredient in several products.

Solamargine Alleviates Proliferation and Metastasis of Cervical Cancer Cells by Blocking the CXCL3-Mediated Erk Signaling Pathway.

Solamargine has unique antitumor efficacy in a variety of cancers. The study is to explore the role of solamargine in cervical cancer. HeLa and SiHa cells were exposed to solamargine treatment at divergent concentrations (0, 5, 10, and 20 µM). The antitumor role of solamargine in cervical cancer cells was determined by cell counting kit 8 (CCK-8), colony formation, scratch test, transwell assay, and western blot. The expression of mRNAs regulating the extracellular regulated protein kinases (Erk) pathway in solamargine-treated cells was detected by qRT-PCR. Rescue experiments were conducted to explore the effect of C-X-C motif chemokine ligand 3 (CXCL3). Following that, we inhibited Erk1/2 by PD98059 to investigate the interplay between CXCL3 and Erk pathway in solamargine-treated cells by measuring migration, invasion, and related matrix metalloproteinase (MMP) expressions. Solamargine inhibited the viability, proliferation, migration, and invasion of cervical cancer cells in a dose-dependent manner. The expression of p-Erk1/2 was downregulated by solamargine. CXCL3 overexpression abrogated the antitumor effect of solamargine on cervical cancer cells. The inhibition of the Erk signaling pathway restored the inhibiting role of solamargine which interfered with CXCL3 overexpression, in invasion, migration, and expressions of MMP-2 and MMP-9 in cervical cancer cells. Moreover, solamargine inhibited the growth of tumor in vivo xenograft model. Solamargine alleviated proliferation and metastasis of cervical cancer cells by blocking the CXCL3-mediated Erk signaling pathway.

Downregulation of interleukin-1 beta via Jmjd3 inhibition improves post-myocardial infarction depression.

Background: Patients with myocardial infarction (MI) comorbid with the depressive disorder may have increased serum cytokine concentrations, notably, of interleukin-1 beta (IL-1ß). The histone H3 lysine-27 (H3K27) demethylase Jmjd3 is crucial in cytokine regulation, and administering an H3K27 demethylase-selective inhibitor (GSK J4) might ameliorate inflammatory symptoms. We hypothesized that Jmjd3 might regulate IL-1ß concentrations, thus affecting the development of post-MI depression (PMD). In this study, a mouse model was created to examine the connection between IL-1ß and PMD and determine the regulatory function of cytokine in controlling inflammation and depressive symptoms. Methods: MI was induced in 30 5-week-old male C57BL/6N mice via a left coronary ligation, and MI onset was confirmed by electrocardiogram (ECG). After treatment with dimethylsulfoxide (DMSO) or GSK J4 for 14 days, the mice were subjected to tail-suspension tests (TSTs) and forced swimming tests (FSTs) before being sacrificed for tissue harvest. Results: In the TSTs, the GSK J4-treated MI mice displayed a significantly shorter immobility time than did the DMSO-treated MI mice (P<0.001). In the FSTs, the DMSO-treated MI mice showed a significantly longer immobility time than did the DMSO-treated sham-operated mice (P<0.001). The GSK J4-treated MI mice had a significantly reduced immobility time compared to the DMSO-treated MI mice (P<0.001). IL-1ß expression in the myocardium, hippocampus, prefrontal cortex (PFC), and hypothalamus increased after MI onset (P=0.003, 0.015, 0.0003, and 0.013, respectively) but decreased after treatment with GSK J4 (P<0.001, P=0.005, P<0.001, P=0.018, respectively). In the myocardium and hypothalamus, Jmjd3 expression levels were lower in mice that received GSK J4 treatment than in those that received DMSO treatment (P<0.05). Conclusions: GSK J4 inhibited the cardiac expression of IL-1ß and Jmjd3, and alleviated PMD in MI mice. Therefore, IL-1ß and Jmjd3 may be critical in the pathogenesis of PMD, and Jmjd3 may potentially serve as a target for PMD treatment.

Human umbilical cord mesenchymal stem cells ameliorate depression by regulating Jmjd3 and microglia polarization in myocardial infarction mice.

RATIONALE: Microglia regulate the inflammation of the central nervous system and play a crucial role in the pathogenesis of depression. Moreover, Jmjd3 is involved in microglia polarization. Mounting studies reported the beneficial effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on myocardial infarction (MI), Unfortunately, its effects on MI-induced depression and its underlying mechanisms remain unclear. OBJECTIVES: We aimed to investigate the antidepressant effects of HUC-MSCs and their impacts on microglia polarization. METHODS: In the current study, the MI model was established by ligating the left anterior descending coronary artery. Mice were injected with HUC-MSCs or PBS through the tail vein 1week after the surgery. The sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were performed to evaluate depression-like behavior. Cardiac function and myocardial fibrosis were evaluated at the end of the experiments. Immunofluorescence, Western blot, ELISA, and qRT-PCR were used to detect the levels of Jmjd3 and microglia-related markers and inflammatory factors. RESULTS: HUC-MSC treatment significantly improved cardiac function, reduced the area of myocardial fibrosis, and alleviated depression-like behaviors induced by MI. HUC-MSCs inhibited the expression of Jmjd3 and promoted the switch of microglia in the prefrontal cortex, hypothalamus, and hippocampus from M1 to M2, thereby decreased the level of pro-inflammatory factors. CONCLUSION: HUC-MSCs have cardioprotective and potential anti-depressive effects induced by MI related to the inflammation improved by regulating Jmjd3 and microglial polarization.

The impact of the Type D Personality pattern on prehospital delay in patients suffering from acute myocardial infarction.

BACKGROUND: The Type D Personality (TDP) has been specifically linked to acute myocardial infarction (AMI). However, the impact on prehospital delay of AMI patients is unclear. The aim of this study was to assess the relationship between TDP and pre-hospital delay time (PHT) in a Chinese population. METHODS: A total of 256 AMI patients (47 women and 209 men) were taken from the Multicenter Delay in Patients Experiencing AMI in Shanghai (MEDEA FAR-EAST) study. Sociodemographic and psycho-behavioral characteristics were assessed by bedside interviews and questionnaires. TDP was evaluated according to the Type D Personality Scale (DS14) subdivided in social inhibition (SI) and negative affectivity (NA). Based on a significant interaction analysis of TDP and sex on PHT, all analyses were stratified by sex. RESULTS: PHT of female patients with TDP were substantially shorter compared to non-TDP female patients (108 vs. 281 min, P=0.029). In male patients, no effect of TDT on PHT was found. Spearman correlation analysis suggests that NA was negatively correlated with PHT (r=-0.358, P=0.014). Further age-adjusted logistic regression analyses showed that female patients with TDP were generally less likely to prehospital delay compared with non-TDP patients (OR =0.28; 95% CI, 0.08-0.98) and had a lower risk of PHT >360 minutes (OR =0.10; 95% CI, 0.01-0.91). However, statistical significance disappeared after adjustment for psychological factors (anxiety, depression, suboptimal wellbeing, cardiac denial and stress event). CONCLUSIONS: TDP is associated with less prehospital delay in female patients during AMI-an effect which may be particularly mediated by NA.

Microangiopathy is associated with bone loss in female type 2 diabetes mellitus patients.

OBJECTIVE: Type 2 diabetes mellitus complicated with microvascular diseases can be used as a model to study the relationship between bone health and the microvascular situation. METHODS: A total of 2,170 patients with type 2 diabetes mellitus (1,188 postmenopausal females and 982 males aged ⩾50 years) were included in our cross-sectional study. These patients were grouped according to 24-hour urine protein level: Group I (<30 mg), Group II (30-299 mg) and Group III (≥300 mg). Bone mineral density of the lumbar spine, hip and femoral neck was evaluated by dual-energy X-ray absorptiometry. Fundus oculi photography for diabetic retinopathy and 24-h urine protein for diabetic nephropathy were used as markers of microangiopathy in type 2 diabetes mellitus. Characteristics of the patients and bone mineral density were compared. Multivariate analysis was used to study the association between bone mineral density and microangiopathy. Statistical analysis was performed using SPSS 20.0. p < 0.05 was considered statistically significant. RESULTS: Group III had the lowest bone mineral density level in both genders. Multivariate analysis revealed that microangiopathy was negatively correlated with bone mineral density in females (lumbar: r = -0.522, p < 0.001; hip: r = -0.301, p = 0.010; femoral neck: r = -0.314, p = 0.009), but not in males, after adjustment for age, body mass index, hypertension, hyperlipidemia, diabetic status, hepatic function, kidney function, sex hormones and 25(OH) vitamin D. CONCLUSION: These results demonstrate an independent negative correlation between microangiopathy and bone mineral density in postmenopausal female type 2 diabetes mellitus patients.