Physalin B Reduces Tau Phosphorylation and Cell Apoptosis in HEK293 Cells by Activating FoxO1.

Background: Physalin B (PB) is one of the main active compounds of Solanaceae plants, with a wide range of biological activities. PB reportedly has the potential to treat Alzheimer's disease (AD).

Objective: In this study, we investigated the effect of PB on Tau phosphorylation and cell apoptosis using Tau-expressing HEK293 cells (HEK293/Tau) as a cellular model.

In silico and in vitro analyses of a novel FoxO1 agonist reducing Aβ levels via downregulation of BACE1.

Aims: FoxO1 is an important target in the treatment of Alzheimer's disease (AD). However, FoxO1-specific agonists and their effects on AD have not yet been reported. This study aimed to identify small molecules that upregulate the activity of FoxO1 to attenuate the symptoms of AD.

Physalin B reduces Aβ secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation.

Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated β-amyloid (Aβ) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood.

Alterations of fatty acid composition and metabolism in APP/PS1 transgenic mice.

Accumulating evidence suggests that abnormal fatty acid composition is related to the development of Alzheimer's disease (AD). However, there is no consistency in the fatty acid profile and metabolism associated with AD pathogenesis. This study aims to define the characteristics of fatty acid composition and metabolism in AD.

FoxO1 overexpression reduces Aβ production and tau phosphorylation in vitro.

Forkhead box O1 (FoxO1), a key molecule in the regulation of cell growth, differentiation and metabolism, is an important transcription factor. However, the effect of FoxO1 on Alzheimer's disease (AD) needs further investigation. In this study, we aimed to explore the function and mechanism of FoxO1 in amyloid-β (Aβ) production and tau phosphorylation in AD.

Effects of chain length of saturated fatty acids on Aβ generation in SH-SY5Y cells.

Many studies have shown that saturated fat diet increases the risk of AD. Recently saturated very long chain fatty acids (VLCFAs) have been found be accumulated in AD patients. The variety of saturated fatty acids are found in the diets and human bodies.

Effect of TCDD on the fate of epithelial cells isolated from human fetal palatal shelves (hFPECs).

Cleft palate is caused by the failure of palatal midline epithelial cells to disintegrate, which is necessary for palatal mesenchymal confluence. Although 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure is linked to cleft palate at a high rate, the mechanism remains to be elucidated. The present study was designed to determine the effects of TCDD on the fate of epithelial cell isolated from human fetal palatal shelves (hFPECs).

TCDD promoted EMT of hFPECs via AhR, which involved the activation of EGFR/ERK signaling.

One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin and cytokeratin14) and enhanced the mesenchymal markers (vimentin and fibronectin), but had no effect on cell migration and apoptosis.

Decreased liver peroxisomal β-oxidation accompanied by changes in brain fatty acid composition in aged rats.

Peroxisomal β-oxidation is primarily responsible for the degradation of very long chain fatty acids (VLCFAs), dicarboxylic acids, unsaturated fatty acids and branched fatty acids. The genes encoding β-oxidation enzymes are transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPARα). Age-related decreases in acyl-CoA oxidase 1 (ACOX1) activity, a key enzyme involved in peroxisomal β-oxidation, have been found in aged rodents.

[Mechanism of MBL inhibiting the LPS-induced DC maturation].

The study was aimed to investigate the mechanism of mannan-binding lectin (MBL) on bacterial lipopolysaccharide (LPS)-induced human peripheral blood monocyte-derived dendritic cell (DC) maturation. The monocytes were prepared from the peripheral blood of healthy adult volunteers. The immature dendritic cells (imDC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4.

Progesterone inhibits the expression of cycloxygenase-2 and interleukin-1β in neonatal rats with hypoxic ischemic brain damage.

Recent studies found that progesterone (PROG) has a noticeable preventive effect on brain injuries. However, the underlying mechanisms of these effects, particularly on hypoxic ischemic brain damage (HIBD), remain unclear. This study observed the influence of PROG on the expression of cycloxygenase-2 (COX-2) and interleukin-1β (IL-1β) in HIBD neonatal rats, and explored the corresponding molecular mechanisms underlying the neuroprotective effect of PROG.

[Effect of recombinant human growth hormone on the secretion of TNF-α and IL-6 by THP-1 cells and its correlation with the NF-κB pathway].

Objective: To investigate the effect of recombinant human growth hormone (rhGH) on the secretion of TNF-α and IL-6 in THP-1 cells and analyze the correlation between the secretion and NF-κB signaling pathway.

Methods: The concentrations of TNF-α and IL-6 in the supernatants of THP-1 induced by rhGH were measured with ELISA. The effects of LPS and an NF-κB inhibitor, BAY11-7082 on the secretion of TNF-α and IL-6 were also observed.

Inhibition of peroxisomal β-oxidation by thioridazine increases the amount of VLCFAs and Aβ generation in the rat brain.

Alzheimer's disease (AD) is characterized by the accumulation of the β-amyloid peptide (Aβ), which is generated from sequential cleavages of the amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. Fatty acid alterations in AD brains have recently received substantial attention. Because increased very long chain fatty acid (VLCFA) levels in AD brains imply that peroxisomal β-oxidation dysfunction may be associated with AD pathogenesis, we investigated the effects of impaired peroxisomal β-oxidation on Aβ generation in vivo and in vitro using thioridazine, a selective peroxisomal β-oxidation inhibitor.

[Effects of activation of liver X receptor and peroxisome proliferator-activated receptor alpha on bile acid synthesis in rats].

Objective: To explore the effects of the simultaneous activation of liver X receptor (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha) on bile acid biosynthesis in rats.

Methods: Totally 36 male SD rats were divided into three groups with 12 rats in each group: control group, high cholesterol (HC) group, and high cholesterol + fenofibrate (HC + FENO) group. Total bile acids (serum bile acids plus fecal bile acids) level was assayed.

[Relationship between the increase of hepatic D-bifunctional protein activity and bile acid biosynthesis in rats].

Objective: To determine the physiological role of D-bifunctional protein (DBP) in bile acid biosynthesis through investigating the effect of increasing activity of DBP on bile acid biosynthesis.

Methods: Twenty male Wistar rats were divided into two groups: diethylhexyl phthalate (DEHP) group (n = 10) and control group (n = 10). Serum triglyceride, total cholesterol, hepatic DBP activity, and fecal bile acids were assayed.