The SMXL8-AGL9 module mediates crosstalk between strigolactone and gibberellin to regulate strigolactone-induced anthocyanin biosynthesis in apple.

Although the strigolactone (SL) signaling pathway and SL-mediated anthocyanin biosynthesis have been reported, the molecular association between SL signaling and anthocyanin biosynthesis remains unclear. In this study, we identified the SL signal transduction pathway associated with anthocyanin biosynthesis and the crosstalk between gibberellin (GA) and SL signaling in apple (Malus × domestica). ELONGATED HYPOCOTYL5 (HY5) acts as a key node integrating SL signaling and anthocyanin biosynthesis, and the SL-response factor AGAMOUS-LIKE MADS-BOX9 (AGL9) promotes anthocyanin biosynthesis by activating HY5 transcription.

DNA vaccines targeting amyloid-β oligomer ameliorate cognitive deficits of aged APP/PS1/tau triple-transgenic mouse models of Alzheimer's disease.

The amyloid-β (Aβ) oligomer, rather than the Aβ monomer, is considered to be the primary initiator of Alzheimer's disease. It was hypothesized that p(Aβ3-10)10-MT, the recombinant Aβ3-10 gene vaccine of the Aβ oligomer has the potential to treat Alzheimer's disease. In this study, we intramuscularly injected the p(Aβ3-10)10-MT vaccine into the left hindlimb of APP/PS1/tau triple-transgenic mice, which are a model for Alzheimer's disease.

Immunization with Aβ3-10-KLH vaccine improves cognitive function and ameliorates mitochondrial dysfunction and reduces Alzheimer's disease-like pathology in Tg-APPswe/PSEN1dE9 mice.

Alzheimer's disease is a common cause of dementia, for which no disease-modifying therapy is yet available. Aβ3-10-KLH, a vaccine for active immunization, has been shown to prevent pathological changes in young transgenic models of AD, but the effects of treatment with it and its effects on mitochondrial dysfunction remain unclear. We immunized 6-month-old Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH to analyze whether it is capable of eliminating amyloid-β after its appearance.

Early active immunization with Aβ-KLH vaccine reduces tau phosphorylation in the hippocampus and protects cognition of mice.

Active and passive anti-Aβ immunotherapies have successfully been used for the prevention and treatment of Alzheimer's disease animal models. However, clinical use of these immunotherapies is not effective, because the vaccination is administered too late. At 1 month of age, 100 μL of Aβ-KLH peptide (vaccine, 2 μg/μL) was subcutaneously injected into the neck of an amyloid precursor protein/presenilin-1/tau transgenic (3×Tg-AD) mouse model.

Reduction of amyloid beta by Aβ3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-β (Aβ) accumulation, neurofibrillary tangles (NFTs) formation and synaptic alterations. Active immunotherapy is regarded as one of the most promising strategies for AD prevention and treatment. In this research, we used APPswe/PS1M146 V/TauP301 L triple transgenic (3×Tg-AD) mice, in which the pathological changes are the most similar to those in AD patients.

An Aβ3-10-KLH vaccine reduced Alzheimer's disease-like pathology and had a sustained effect in Tg-APPswe/PSEN1dE9 mice.

Alzheimer's disease is a neurodegenerative disease that affects many patients worldwide. The amyloid cascade hypothesis has been adopted by most researchers as the mechanism underlying Alzheimer's disease. Aβ plaques have been considered the core factor in the neurotoxic effect in Alzheimer's disease, though some controversy remains.

Immunization of Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH vaccine prevents synaptic deficits of Alzheimer's disease.

The amyloid cascade hypothesis is widely accepted by researchers as the mechanism of Alzheimer's disease. Active immunization to eliminate Aβ depositions has been used in preclinical and clinical studies. Aβ3-10-KLH is a vaccine of the Aβ3-10 peptide combined with keyhole limpet hemocyanin (KLH).

Prophylactic active immunization with a novel epitope vaccine improves cognitive ability by decreasing amyloid plaques and neuroinflammation in APP/PS1 transgenic mice.

Both amyloid-β peptide (Aβ) deposition and neuroinflammation are considered to be early events that play pivotal roles in Alzheimer's disease (AD) pathogenesis and its associated cognitive impairment. Prophylactic anti-Aβ active immunotherapy is a promising therapeutic strategy for AD, if the Aβ-specific autoimmune responses to self T cell epitopes of Aβ can be avoided. This can be achieved by the use of antigen, which contains the B cell epitope of Aβ and excludes the Aβ-specific T cell epitope.

Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-Aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice.

Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aβ3-10-KLH and 5Aβ3-10, prepared respectively by coupling Aβ3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aβ3-10 epitopes linearly in tandem.

[Genome-wide identification and analyses of 4CL gene families in Pyrus bretschneideri Rehd].

4-coumaric acid: coenzyme A ligase (4CL) gene is one of the key genes involved in the regulation of lignin metabolism and the synthesis of flavonoid and other secondary metabolites in plant, while the synthesized and polymerized lignin is deposited in cell walls and leads to thickening of secondary walls in some parenchyma cells and formation of stone cells. To better understand the variety and quantity of 4CL genes in Pyrus bretschneideri Rehd., we used the amino acid and cDNA databases of Pyrus bretschneideri Rehd.

Nicorandil inhibits oxidative stress and amyloid-β precursor protein processing in SH-SY5Y cells overexpressing APPsw.

It has been demonstrated that ATP-sensitive potassium (KATP) channel activation has neuroprotective effects against neuronal damage induced by hypoxia, ischemia or metabolism stress. This study investigated the multiply protective effects of KATP channel opener nicorandil against neurotoxicity in SH-SY5Y cells transiently transfected with Swedish mutant APP (APPsw) and also the potential involvement of PI3K/Akt/GSK-3β pathway. Cells were treated with nicorandil (1 mM) for 24 h with and without glibenclamide (10 μM), a KATP channel inhibitor.

Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation.

The aggregation of amyloid β-peptide (Aβ) is thought to play a pivotal role in the disease progression of Alzheimer's disease (AD). Amyloid β directed immunotherapy has been considered an alternative AD treatment. In this study, we constructed a DNA vaccine, p(Aβ3-10)10-mIL-4, encoding ten tandem repeats of Aβ3-10 fused with mouse IL-4.

Esophageal sarcomatoid carcinoma presenting as a Fever with elevated serum leukocytes.

The study presented a case of esophageal cancer presenting as intermittent fever with markedly elevated serum leukocyte and C-reactive protein. The patient's symptoms had not improved with antibiotic treatment. However, after thoracic esophagectomy, the fever faded and leukocyte serum levels rapidly normalized.

Common Polymorphisms in the GSK3β Gene May Contribute to the Pathogenesis of Alzheimer Disease: A Meta-Analysis.

Objective: Although it is well known that GSK3β participates in the proliferation and survival of various tumor cells, its role in diseases of the central nervous system has been sparsely documented. In the past few years, studies regarding the relationship between GSK3β rs334558 T>C and rs6438552 C>T polymorphisms and Alzheimer disease (AD) risk have yielded contradictory results. As such, this meta-analysis seeks to satisfy the need to further investigate this relationship.

Active immunotherapy facilitates Aβ plaque removal following through microglial activation without obvious T cells infiltrating the CNS.

Immunization of AD mouse models with Aβ reduced Aβ deposits and improved memory and learning deficits, but some clinical trials of immunization with Aβ were halted due to brain inflammation which was presumably induced by a T cell-mediated autoimmune response. We have developed a "possibly safer" vaccine. Our results demonstrate that pcDNA3.

Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation.

Tyrosine phosphatase STEP61 negatively regulates amyloid β-mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors.

Striatal-enriched phosphatase 61 (STEP61 ) plays an essential role in synaptic plasticity and has recently been implicated in neurodegenerative disease. Here we characterized a possible role of STEP61 in Alzheimer's disease (AD) pathology using a mouse model of AD (Tg-APPswe/PSEN1dE9, APP/PS1 mice) and an in vitro model of AD [cortical neurons treated with amyloid β (Aβ)1-42 peptides]. Our data indicate age-related elevation of STEP61 levels and the proportion of dephosphorylated STEP61 (active STEP61 ) in wild-type mice, which was enhanced in APP/PS1 mice.

CXCL1 contributes to β-amyloid-induced transendothelial migration of monocytes in Alzheimer's disease.

Background: Bone marrow-derived microglia that originates in part from hematopoietic cells, and more particularly from monocytes preferentially attach to amyloid deposition in brains of Alzheimer's disease (AD). However, the mechanism of monocytes recruited into the amyloid plaques with an accelerated process in AD is unclear.

Methodology/principal Findings: Here we reported that monocytes from AD patients express significantly higher chemokine (C-X-C motif) ligand 1 (CXCL1) compared to age-matched controls.

(-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus.

Alzheimer's disease (AD) fundamentally represents a metabolic disease associated with brain insulin resistance. TNF-α/c-Jun N-terminal kinase (JNK) signaling plays a central role in serine phosphorylation of insulin receptor substrate-1 (IRS-1). (-)-Epigallocatechin-3-gallate (EGCG), a potent antioxidant, has been verified to attenuate peripheral insulin resistance by reducing IRS-1 signaling blockage.

Intranasal inoculation with an adenovirus vaccine encoding ten repeats of Aβ3-10 reduces AD-like pathology and cognitive impairment in Tg-APPswe/PSEN1dE9 mice.

To develop a safe and efficient vaccine for AD treatment, we constructed an adenovirus vector vaccine encoding ten repeats of Aβ3-10 and CpG motif as a molecular adjuvant. We demonstrated that therapeutic immunization with Ad-10×Aβ3-10-CpG elicits Aβ3-10 specific Th2-polarized immune response with high titers of anti-Aβ antibodies in APPswe/PSEN1dE9 mice, which in turn reduced Aβ deposits in brains and cognitive impairment. In addition, Ad-10×Aβ3-10-CpG reduced astrocytosis without increasing the incidence of microhemorrhage.

In vivo electroporation of a new gene vaccine encoding ten repeats of Aβ3-10 prevents brain Aβ deposition and delays cognitive impairment in young Tg-APPswe/PSEN1dE9 mice.

Active immunization holds great promise for the treatment of Alzheimer's disease but the infiltration of T-lymphocytes and associated meningoencephalitis observed in clinical trials needs to be overcome. To avoid this toxicity, previous studies have used synthetic truncated derivatives of Aβ to promote humoral immunity. In this study, we developed a novel vaccine [p(Aβ3-10)10-MT] that expresses ten repeats of Aβ3-10 with melatonin (MT) as an adjuvant, and administered it intramuscularly in three-month-old Tg-APPswe/PSEN1dE9 (Tg) mice by in vivo electroporation.

Amyloid β 3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice.

Background: Amyloid β(1-42) (Aβ(42)) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models. But the phase II trial of Aβ(42) peptide vaccine was halted because of T cell-mediated meningoencephalitis. In this study, a DNA vaccine, p(Aβ(3-10))(10)-CpG, was constructed to test whether it would induce predominant T(H)2 immune response upon immunization of BALB/c mice.

Intranasal inoculation with an adenovirus vaccine encoding ten repeats of Aβ3-10 induces Th2 immune response against amyloid-β in wild-type mouse.

To develop a safe and efficient vaccine for the treatment of Alzheimer's disease, we constructed a novel adenovirus vaccine encoding ten repeats of Aβ3-10 and CpG motif as an adjuvant and investigated the immune response in BALB/c mouse after intranasal inoculation with this vaccine. The Ad-10×Aβ3-10-CpG induces an IgG1 predominant humoral response and production of IL-4 and IL-10 in splenocytes in vitro, indicating a Th2-polarized immune response. Stimulation of splenocytes with Aβ3-10 peptide induces robust proliferation but not with full-length Aβ42 peptide, demonstrating that Ad-10×Aβ3-10-CpG does not induces Aβ42 specific T cell immune response.

Improving memory and decreasing cognitive impairment in Tg-APPswe/PSEN1dE9 mice with Aβ3-10 repeat fragment plasmid by reducing Aβ deposition and inflammatory response.

The present study aimed to investigate the effects of Aβ3-10 repeat fragment plasmid for the treatment of Tg-APPswe/PSEN1dE9 (Tg) mice. The plasmid pcDNA3.1-(Aβ3-10)10-CpG was constructed and intramuscularly injected into 12-month-old Tg mice.

Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease.

This study is to examine if hydrogen-rich saline reduced amyloid-beta (Aβ) induced neural inflammation and oxidative stress in a rat model by attenuation of activation of JNK and NF-κB. Sprague-Dawley male rats (n=18, 280-330 g) were divided into three groups, sham operated, Aβ1-42 injected and Aβ1-42 plus hydrogen-rich saline treated animals. Hydrogen-rich saline (5 ml/kg, i.