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Purpose To investigate the effect of gestational diabetes mellitus (GDM) on the expression and methylation of PGC-1α and PDX1 in placenta and their effects on fetal glucose metabolism. Methods 20 cases of full-term placenta without pregnancy complications and umbilical cord abnormalities and 20 cases of GDM group were collected. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery. DNA methylation was quantified at 7 CpG sites within the PGC-1α and PDX1 genes using PCR amplification of bisulfite treated DNA and subsequent DNA sequencing. PGC-1α and PDX1 mRNA levels were measured by reverse transcription-quantitative PCR (RT-qPCR). Meanwhile, the placental insulin, blood glucose and HbA1c levels were determined. Results The fetus birth weight and placental weight in GDM group were significantly higher than those in control group (P < 0.05). Insulin, HbA1c and blood glucose levels in GDM group were significantly higher than those in control group (P < 0.01). Insulin content was positively correlated with newborn birth weight and placental weight while HbA1c and blood glucose were positively correlated with insulin concentration (r = 0.92, P < 0.01, r = 0.85, P < 0.01). The levels of PGC-1α and PDX1 mRNA were lower in the GDM group compared to the control group. The methylation level of PGC-1α gene was higher in the GDM group compared to the control group (P < 0.05). Blood glucose was negatively correlated with the expression of PGC-1α and PDX1 mRNA in the placenta (r = −0.42, P < 0.01, r = −0.49, P < 0.01). Conclusion The changes of epigenetic modification of PGC-1α gene in pregnant women with gestational diabetes mellitus may be a mechanism of abnormal glucose metabolism in offspring. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) regulates endothelial injury and methylation status of key genes in cerebral ischemia. Thrombomodulin (TM) may be protective against cerebral ischemia by downregulating coagulation. However, it remains unclear whether Hcy involved in methylation and expression of TM in cerebral infarction (CI). Here, we find patients with cerebral infarction had a higher TM methylation level than controls (74.2% vs 47.5%, X 2 = 14.724, P = 0.00), which are positively correlated with plasma levels of tHcy (r = 0.701, P = 0.00) and negatively related to mRNA expression of TM (r = −0.711, P = 0.00). Plasma levels of tHcy (t = 7.566, P = 0.00) and sTM (t = 17.268, P = 0.00) are significantly higher in cases than in controls. Our data indicate hyperhomocysteine leads to hypermethylation of the TM gene and further induces TM gene silencing, which may play an important role in the occurrence and development of CI. Plasma higher concentrations of sTM in cases are not caused by TM expression and may be only a result of Hcy induced endothelial injury. [ABSTRACT FROM AUTHOR]

This paper investigates Cauchy problems for nonlinear fractional time–space generalized Keller–Segel equation D t β 0 c ρ + ( − △ ) α 2 ρ + ∇ ⋅ ( ρ B ( ρ ) ) = 0 , where Caputo derivative D t β 0 c ρ models memory effects in time, fractional Laplacian ( − △ ) α 2 ρ represents Lévy diffusion and B ( ρ ) = − s n , γ ∫ R n x − y | x − y | n − γ + 2 ρ ( y ) d y is the Riesz potential with a singular kernel which takes into account the long rang interaction. We first establish L r − L q estimates and weighted estimates of the fundamental solutions ( P ( x , t ) , Y ( x , t ) ) (or equivalently, the solution operators ( S α β ( t ) , T α β ( t ) ) ). Then, we prove the existence and uniqueness of the mild solutions when initial data are in L p spaces, or the weighted spaces. Similar to Keller–Segel equations, if the initial data are small in critical space L p c ( R n ) ( p c = n α + γ − 2 ), we construct the global existence. Furthermore, we prove the L 1 integrability and integral preservation when the initial data are in L 1 ( R n ) ∩ L p ( R n ) or L 1 ( R n ) ∩ L p c ( R n ) . Finally, some important properties of the mild solutions including the nonnegativity preservation, mass conservation and blowup behaviors are established. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an incurable and highly complex chronic inflammatory bowel disease (IBD) affecting millions of people worldwide. C-phycocyanin (C-PC) has been reported to possess outstanding anti -inflammatory activities and can effectively inhibit various inflammation-related diseases. Whether C-PC-derived bioactive peptides can inhibit intestinal inflammation is worth research and consideration. The inhibition activities of three anti -neuroinflammatory peptides were evaluated using 2-4-6-trinitrobenzen sulfonic acid (TNBS)-induced zebrafish colitis model. Subsequently, the abilities of peptides to promote gastrointestinal motility were also examined. The changes in the intestinal pathological symptoms and ultrastructure of intestinal, reactive oxygen species (ROS) levels, and antioxidant enzymes were then determined after co-treatment with peptides and TNBS. Transcriptome analysis was used to investigate the underlying ameliorating TNBS-induced colitis effects molecular mechanisms of better activity peptide. Furthermore, quantitative reverse-transcription polymerase chain reaction and molecular docking techniques verified the mRNA sequencing results. Three peptides, MHLWAAK, MAQAAEYYR and MDYYFEER, which significantly inhibit macrophage migration, were synthesized. The results showed that these peptides could effectively alleviate the inflammatory responses in the TNBS-induced zebrafish model of colitis. In addition, co-treatment with TNBS and C-PC peptides could decrease ROS production and increase antioxidant enzyme activities in zebrafish larvae. Moreover, MHLWAAK had the most significantly therapeutic effects on colitis in zebrafish. The transcriptome analysis suggests that the effect of MHLWAAK on TNBS-induced colitis may be associated with the modulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinase (MAPK) signaling pathway associated genes. In addition, molecular docking was conducted to study the prospective interaction between peptides and the key proteins that streamline the Nrf2 and MAPK signaling pathways. IL-6, JNK3, TNF-α, KEAP1-NRF2 complex and MAPK may be the core targets of MHLWAAK in treating colitis. The results suggested that the three C-PC-derived peptides could ameliorate TNBS-induced colitis in zebrafish, and these peptides might be a promising therapeutic candidate for UC treatment. • C-phycocyanin peptides could improve the intestinal histopathological damage. • C-phycocyanin peptides could decrease oxidative stress and repair immune capacity of gut. • It could change the expression levels of genes in MAPK/Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Ce-UiO-66 was firstly used as a supercapacitor electrode material and exhibited a high capacitance of 6.9 Fcm−2 in a redox electrolyte. A novel self-supported structure of Ce-UiO-66/TNF was firstly synthesized by growing Ce-UiO-66 on a TNF substrate. This novel Ce-UiO-66/TNF material was proved to possess a high supercapacitive performance in the redox electrolyte of Fe(CN) 6 3−/4−, and it was also the first study for Ce-UiO-66 material on the supercapacitor application. High specific capacitances of 6.9 and 2.5 Fcm−2 can be achieved at large current densities of 20 and 80 mAcm−2, respectively. After 10,000 charge-discharge cycles, the capacitance retention can be kept at 95% and the coulomb efficiency can be maintained over 98%. Such outstanding electrochemical performance may be related to the redox property of the electrolyte, high specific surface area of the Ce-UiO-66 material, porous characteristic of the TNF substrate and self-supported structure of the whole electrode. [ABSTRACT FROM AUTHOR]

Crocetin is a major active constituent of Gardenia jasminoides J. Ellis, and can aid in the prevention of cardiovascular disease. The effect and possible mechanism of crocetin on the migration of vascular smooth muscle cells (VSMCs) induced by advanced glycosylation end products (AGEs) were investigated. VSMCs were pre-incubated with or without crocetin and exposed to AGEs subsequently. The invasion of the cells was investigated using a 24-well Cell Invasion Chamber. The anti-proliferative activity of crocetin was evaluated by MTT assay and VSMCs cell-cycle distribution was examined by flow cytometry. Cytokine TNF-α and IL-6 secreted by VSMCs and the amount of matrix metalloproteinase MMP-2 and MMP-9 in the culture supernatant were detected by ELISA. The expression level of RAGE (AGEs receptor), in cells was analyzed by western blot. The results demonstrated that AGEs increased about two-fold migration of VSMCs compared with control (OD = 0.778 ± 0.191 vs OD = 0.413 ± 0.214, P < 0.01), and the proliferation increased by about 20% (OD = 0.335 ± 0.043 vs OD = 0.281 ± 0.037, P < 0.01). Pre-treatment with crocetin (1.0 μM) or RAGE antibody (10 μg/ml) could inhibit the AGEs triggered migration of VSMCs obviously. Furthermore, both crocetin and RAGE antibody inhibited the increase of RAGE protein in VSMCs stimulated by AGEs. The levels of TNF-α and IL-6 decreased in the crocetin (1.0 μM) pre-treated group compared to the AGEs (without pre-treated) group (37.60 ± 3.08 pg/ml vs 46.59 ± 1.92 pg/ml, 32.11 ± 4.69 pg/ml vs 49.99 ± 8.84 pg/ml, respectively). Crocetin (1.0 μM) also reduced the value of MMP-2 and MMP-9 compared with the AGEs group (2.81 ± 0.35 ng/ml vs 6.40 ± 0.85 ng/ml, 2.69 ± 0.25 ng/ml vs 4.32 ± 0.57 ng/ml, respectively). In summary, crocetin inhibits the migration of VSMCs induced by AGEs through RAGE-dependent signaling pathway. And it is meaningful to diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Purpose Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, 18 F-Al labeled exendin-4 analog, 18 F-Al-NOTA-MAL-Cys 39 -exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. Methods The targeting of 18 F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with 18 F-Al-NOTA-MAL-Cys 39 -exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. Results The pancreas of healthy rats was readily visualized after administration of 18 F-Al-NOTA-MAL-Cys 39 -exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. Conclusion The favorable preclinical data indicated that 18 F-Al-NOTA-MAL-Cys 39 -exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells. [ABSTRACT FROM AUTHOR]

Necroptosis, an alternative mode of programmed cell death, has crucial pathophysiological roles in many diseases, but its effect on chronic kidney disease (CKD) is poorly understood. Therefore, we assessed necroptosis and its pathophysiological effects in a widely used remnant-kidney rat model. We found that necroptotic cell death and the highest level of receptor interaction protein kinase 1 (RIP1) and receptor interaction protein kinase 3 (RIP3), critical signalling molecules for necroptosis, appeared 8 weeks after subtotal nephrectomy (SNX) surgery. After treatment with Necrostatin-1 (Nec-1), renal function and renal pathologic changes were significantly improved; the overexpression of RIP1, RIP3, mixed lineage kinase domain-like (MLKL) and dynamin-related protein 1 (Drp1) was reduced; and necroptosis was inhibited. These results indicated that necroptosis mediated by RIP1 and RIP3 participates in the loss of renal cells of subtotal nephrectomised rats and might be one of main causes of the excessive loss of renal cells during the sustained progression of renal fibrosis. [ABSTRACT FROM AUTHOR]

• A fluorescently labeled berberine was used for subcellular localization study. • The mitochondria pathway might be involved in berberine-induced apoptosis. • A strategy for studying the molecular mechanisms of natural product was developed. Berberine is a naturally occurred isoquinoline alkaloid that shows great potential for developing anticancer drugs. However, the problem stays of poor understanding of the mechanisms of anticancer action of berberine. It depends on evaluation of berberine's pharmacokinetics, namely monitoring of its uptake and distribution in cells, tissues and organs. In order to address these problems, we have designed and synthesized a novel berberine derivative BBR-BODIPY bearing a fluorescent tag that allows screening its interaction with the targeted cells. It was shown that the synthesized fluorescent derivative could penetrate into human breast carcinoma MCF7 cells, and then induced apoptosis detected by the Western Blot analysis as changed expression of apoptosis-related proteins, including Bax, Bcl2, and Cyto C released from mitochondria, Cleaved Caspase 9, Cleaved PARP, Pro-Caspase 3, and Cleaved Caspase 3. The results of MitoTracker analysis followed by the confocal microscopy of sub-cellular localization of BBR-BODIPY in the MCF7 cells demonstrated excellent cell-penetrating ability of this compound even at low concentrations, and mitochondria was the main site of its accumulation. Together with the results of Western Blot analysis, these data indicated that the mitochondria pathway might be involved in berberine-induced apoptosis. [ABSTRACT FROM AUTHOR]