Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway.

Scope: Individuals deficient in vitamin D are more likely to have higher circulating cholesterol levels and cardiovascular diseases. However, the underlying mechanisms are still unclear.

Methods And Results: A cross-sectional survey, animal study, and in vitro experiments were conducted to investigate the effect and mechanisms of vitamin D deficiency on endogenous cholesterol metabolism.

Over-expression of X-linked inhibitor of apoptosis protein modulates multiple aspects of neuronal Ca2+ signaling.

X-linked inhibitor of apoptosis (XIAP) protects and preserves the function of neurons in both in vitro and in vivo models of excitotoxicity. Since calcium (Ca(2+)) overload is a pivotal event in excitotoxic neuronal cell death, we have determined whether XIAP over-expression influences Ca(2+)-signaling in primary cultures of mouse cortical neurons. Using cortical neuron cultures derived from wild-type (Wt) mice transiently transfected with XIAP or from transgenic mice that over-express XIAP, we show that XIAP opposes the rise in intracellular Ca(2+) concentration by a variety of triggers.

Appetite regulation and weight control: the role of gut hormones.

The overwhelming increase in the prevalence of overweight and obesity in recent years represents one of the greatest threats to the health of the developed world. Among current treatments, however, gastrointestinal (GI) surgery remains the only approach capable of achieving significant weight loss results with long-term sustainability. As the obesity prevalence approaches epidemic proportions, the necessity to unravel the mechanisms regulating appetite control has garnered significant attention.

ω-3 fatty acid eicosapentaenoic acid attenuates MPP+-induced neurodegeneration in fully differentiated human SH-SY5Y and primary mesencephalic cells.

Eicosapentaenoic acid (EPA), a neuroactive omega-3 fatty acid, has been demonstrated to exert neuroprotective effects in experimental models of Parkinson's disease (PD), but the cellular mechanisms of protection are unknown. Here, we studied the effects of EPA in fully differentiated human SH-SY5Y cells and primary mesencephalic neurons treated with MPP(+) . In both in-vitro models of PD, EPA attenuated an MPP(+) -induced reduction in cell viability.

Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance.

The present study was carried out to determine the effect of berberine on glucose homeostasis and several biomarkers associated with insulin sensitivity in male Wistar rats with intraperitoneal injection of streptozotocin (STZ)-induced diabetes. Rats with fasting blood glucose 16.7 mmol/L after 2 weeks of STZ injection were divided into two groups.

Ethyl-eicosapentaenoate (E-EPA) attenuates motor impairments and inflammation in the MPTP-probenecid mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by hypokinesia, but also mood and cognitive disorders. Neuropathologically, PD involves loss of nigrostriatal dopamine (DA) and secondary non-dopaminergic abnormalities. Inflammation may contribute to PD pathogenesis, evident by increased production of pro-inflammatory cytokines.

Liuwei dihuang lowers body weight and improves insulin and leptin sensitivity in obese rats.

The present study was aimed at investigating the efficacy and mechanism(s) of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH), as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD) rats were divided into 4 groups (n = 12 each). One group served as a positive control for obesity (OP), while the other 3 were challenged twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg BW LWDH, respectively, for 10 weeks.

Chemical structures and bioactivities of sulfated polysaccharides from marine algae.

Sulfated polysaccharides and their lower molecular weight oligosaccharide derivatives from marine macroalgae have been shown to possess a variety of biological activities. The present paper will review the recent progress in research on the structural chemistry and the bioactivities of these marine algal biomaterials. In particular, it will provide an update on the structural chemistry of the major sulfated polysaccharides synthesized by seaweeds including the galactans (e.

The mechanism of memory impairment induced by Aβ chronic administration involves imbalance between cytokines and neurotrophins in the rat hippocampus.

It has been demonstrated that the onset and progression of Alzheimer's disease (AD) are associated with inflammatory disorders in the brain. Although the interactions of inflammatory cytokines with neurotrophins have been reported in vitro, the balance change between inflammatory cytokines and neurotrophic factors (NTFs), such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF), due to amyloid β (Aβ) chronic administration in vivo is still unclear. The hypothesis of the present study was that the accumulation of Aβ activated glial cells to produce inflammatory mediators and NTFs to maintain the neurons survival, however the failure of crosstalk between NTFs and inflammatory cytokines might occur in the brain and the NTFs expressions would decrease after Aβ chronic treatment, which, therefore, would contribute to the neuronal death and memory impairments.

Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices.

Evidence suggests a link between Parkinson's disease and the dietary intake of omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs). Presently, we investigated whether an acute dose of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) affects brain n-3 and n-6 PUFA content and expression of fatty acid metabolic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in brain slices from C57Bl/6 mice. Furthermore, we investigated whether feeding a diet of n-3 PUFA ethyl-eicosapentaenoate (E-EPA) to these mice can attenuate the MPP(+) induced changes in brain PUFA content and expression of cPLA2 and COX-2, and attenuate MPP(+) induced changes in neurotransmitters and metabolites and apoptotic markers, bax, bcl-2 and caspase-3.

Isolation of tissue mast cells.

Located primarily in tissues, mast cells are one of the principal effector cells in allergic inflammation. Mast cells derive from mononuclear precursor cells which undergo their final phase of differentiation in the tissues. Mast cells express a unique set of proteases and display functional diversity depending on the tissue in which they differentiate--a phenomenon often referred to as mast cell heterogeneity.

The role of G protein-coupled receptors in mast cell activation by antimicrobial peptides: is there a connection?

Antimicrobial peptides (AMPs) are ancient and essential elements of the host defense system, which are found in a wide variety of species. They show antimicrobial activity against a wide range of pathogenic microorganisms. In addition, AMPs are expressed by different immune cells and have a important function in host innate immune response against pathogens by mechanisms that are different from those involved in direct microbial cytolysis.

Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats.

Hypoglycemic effects of berberine (BBR) have been reported in several studies in cell and animal models. However, the mechanisms of action are not fully understood. The present study was therefore aimed at determining the effect and underlying mechanisms of action of BBR on diabetes in a high-fat diet- and streptozotocin-induced diabetic rat model.

The potential of natural products as effective treatments for allergic inflammation: implications for allergic rhinitis.

The impact of natural products on human health has been enormous, and the study of natural products continues to influence research in the fields of chemistry, biology, and ecology. Historically, the majority of our medicines originate from natural products and their synthetic derivatives, many of which have taught us valuable lessons about biology. While advances in synthetic and combinatorial chemistry have given rise to notable successes in the development of new drugs, the perceived value of natural products in the treatment of allergic disease has yet to be fully explored.

Berberine and plant stanols synergistically inhibit cholesterol absorption in hamsters.

The present study was conducted to determine the efficacy and underlying mechanism of berberine (BBR), plant stanols (PS) and their combination on plasma lipids. Male Golden Syrian hamsters were randomly divided into 4 groups (n=15/group) and fed a cornstarch-casein-sucrose-based diet containing 0.15% cholesterol and 5% fat.

Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats.

The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague-Dawley rats. Four groups of animals were fed a cornstarch-casein-sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet.

Strategies that modulate inflammasomes: insights from host-pathogen interactions.

The innate immune system is a dynamic and complex network for recognizing and responding to cellular insult or tissue damage after infection or injury. The primary effector mechanism of innate immunity is the generation of acute and chronic inflammatory responses through regulation of the processing and activation of proinflammatory caspases, particularly caspase 1, and cytokines, most notably IL-1beta and IL-18. Inflammasomes, cytosolic multi-protein complexes that function as molecular scaffolds for caspase activation, have recently emerged as the pivotal mechanism by which host innate immune and inflammatory responses are regulated.

Amyloid-beta-(1-42) increases ryanodine receptor-3 expression and function in neurons of TgCRND8 mice.

Disruption of intracellular calcium homeostasis precedes the neurodegeneration that occurs in Alzheimer disease (AD). Of the many neuronal calcium-regulating proteins, we focused on endoplasmic reticulum (ER)-resident ryanodine receptors (RyRs) because they are increased in the hippocampus of mice expressing mutant presenilin-1 and are associated with neurotoxicity. Others have observed that ryanodine binding is elevated in human postmortem hippocampal regions suggesting that RyR(s) are involved in AD pathogenesis.

Effects of chenodeoxycholic acid and deoxycholic acid on cholesterol absorption and metabolism in humans.

Quantitative and qualitative differences in intralumenal bile acids may affect cholesterol absorption and metabolism. To test this hypothesis, 2 cross-over outpatient studies were conducted in adults with apo-A IV 1/1 or apo-E 3/3 genotypes. Study 1 included 11 subjects 24 to 37 years of age, taking 15 mg/kg/day chenodeoxycholic acid (CDCA) or no bile acid for 20 days while being fed a controlled diet.