Effect of Bee Venom on an Experimental Cellular Model of Alzheimer’s Disease

2020 ◽  
Vol 48 (08) ◽  
pp. 1803-1819
Author(s):  
Yong Ho Ku ◽  
Jae Hui Kang ◽  
Hyun Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Bee Venom ◽  
Control Group ◽  
Cellular Model ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is a neurodegenerative disease and is characterized by the deposition of the [Formula: see text]-Amyloid peptide ([Formula: see text]A), which causes the inflammation of neurons. Bee venom (BV) elicits a strong anti-inflammatory response, and therefore we conducted an in vitro experiment to study the efficacy of BV in an AD cellular model. To mimic AD, the U87MG cell line was incubated for 168 hours with 2.5 [Formula: see text]M [Formula: see text]A. Changes were confirmed by microscopy, and peptides were measured under stain-free conditions using homo-tomography. Sulforhodamine B analysis was performed to analyze the cell viability. Real-Time quantitative polymerase chain reaction (qPCR) analysis was conducted to analyze mRNA expression levels of pro-inflammatory cytokines (NF-[Formula: see text]B, COX-2, TNF-[Formula: see text], IL-1), and Western blot was performed to measure the Caspase-3 protein levels. BV showed no cytotoxicity at concentrations below 10 [Formula: see text]g/mL. The NF-[Formula: see text]B mRNA levels were not significantly different between the BV group and the control group. The amount of [Formula: see text]A accumulation in the BV group decreased significantly. The mRNA expression levels of COX-2, TNF-[Formula: see text], and IL-1 were significantly reduced using 10 [Formula: see text]g/mL of BV compared to those in the control group. Additionally, Caspase-3 levels were also reduced compared to those of the control group when BV was used at a concentration of 10 [Formula: see text]g/mL. BV could inhibit apoptosis and inflammatory responses in an AD cellular model. In addition, it prevented cell accumulation of [Formula: see text]A, an important pathogenic mechanism in AD.

scholarly journals Protective effects of ginkgolide on a cellular model of Alzheimer’s disease via suppression of the NF-κB signaling pathway

2021 ◽  
Author(s):  
Tiantong Niu ◽  
He Yin ◽  
Baolei Xu ◽  
Tingting Yang ◽  
Huiqin Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Viability ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Hek293 Cells ◽  
Control Group ◽  
Cellular Model ◽  
Intracellular Protein ◽  
Tnf Α

Abstract NF-κB signaling has been reported to play a key regulatory role in the pathogenesis of Alzheimer’s disease (AD). The purpose of this study is to investigate the effects of ginkgolide on cell viability in an AD cellular model involving an APP/PS1 double gene-transfected HEK293 cell line (APP/PS1-HEK293) and further explored the mechanisms of action related to NF-κB signaling. The optimal time point and concentration of ginkgolide for cell proliferation were screened using a cell counting kit-8 assay. Based on the results, an in vitro study was performed by co-culture of APP/PS1-HEK293 with different dosages of ginkgolide, followed by an enzyme-linked immunosorbent assay to measure the levels of supernatant tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as western blotting and real-time polymerase chain reaction to detect intracellular protein and mRNA expression of NF-κB p65, IκBa, Bcl-2 and Bax. APP/PS1-HEK293 cells exhibited the highest cell viability at a concentration of 100 µg/ml after 48 h of treatment with ginkgolide. The supernatant levels of TNF-α, IL-1β and IL-6 in the high-dosage ginkgolide-treated groups were lower than those in the control group. Compared with the control group, there were decreased intracellular protein and mRNA expression of NF-κB p65 and Bax, but increased protein and mRNA expression of IκBa in both high-dosage and low-dosage group. Ginkgolide may enhance cell viability, indicative of its neuroprotective effects on AD, at least partially via suppression of the NF-κB signaling pathway involving anti-apoptosis and anti-inflammation mechanisms. Therefore, ginkgolide might be a promising therapeutic agent against AD.

scholarly journals Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xin-Yi Lu ◽  
Shun Huang ◽  
Qu-Bo Chen ◽  
Dapeng Zhang ◽  
Wanyan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Insulin Degrading Enzyme ◽  
Antidiabetic Drug ◽  
Degrading Enzyme ◽  
Expression Levels ◽  
The Brain ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.

Tooth Loss Induces Memory Impairment and Gliosis in App Knock-In Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 80 (4) ◽  
pp. 1687-1704
Author(s):  
Ferdous Taslima ◽  
Cha-Gyun Jung ◽  
Chunyu Zhou ◽  
Mona Abdelhamid ◽  
Mohammad Abdullah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mrna Expression ◽  
Neuronal Activity ◽  
Memory Impairment ◽  
Tooth Loss ◽  
Amyloid Β ◽  
Glial Activation ◽  
Expression Levels ◽  
Mrna Expression Levels

Background: Epidemiological studies have shown that tooth loss is associated with Alzheimer’s disease (AD) and dementia. However, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear. Objective: We investigated the effects of tooth loss on memory impairment and AD pathogenesis in AppNL-G-F mice. Methods: Maxillary molar teeth on both sides were extracted from 2-month-old AppNL-G-F mice, and the mice were reared for 2 months. The short- and long-term memory functions were evaluated using a novel object recognition test and a passive avoidance test. Amyloid plaques, amyloid-β (Aβ) levels, glial activity, and neuronal activity were evaluated by immunohistochemistry, Aβ ELISA, immunofluorescence staining, and western blotting. The mRNA expression levels of neuroinflammatory cytokines were determined by qRT-PCR analysis. Results: Tooth loss induced memory impairment via an amyloid-cascade-independent pathway, and decreased the neuronal activity, presynaptic and postsynaptic protein levels in both the cortex and hippocampus. Interestingly, we found that tooth loss induced glial activation, which in turn leads to the upregulation of the mRNA expression levels of the neuroinflammation cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in the hippocampus. We also found that tooth loss activated a stress-activated protein kinase, c-Jun N-terminal kinase (JNK), and increased heat shock protein 90 (HSP90) levels in the hippocampus, which may lead to a glial activation. Conclusion: Our findings suggest that taking care of teeth is very important to preserve a healthy oral environment, which may reduce the risk of cognitive dysfunction.

scholarly journals A novel kit for early diagnosis of Alzheimer’s disease using a fluorescent nanoparticle imaging

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jun Sung Park ◽  
Sang Tae Kim ◽  
Sang Yun Kim ◽  
Min Gi Jo ◽  
Myeong Jun Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Control Group ◽  
Fluorescent Nanoparticles ◽  
Ht22 Cells ◽  
Expression Levels ◽  
Nanoparticle Imaging ◽  
Fluorescent Nanoparticle ◽  
Primary Focus

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease and chronic illness with long preclinical phases and a long clinical duration. Until recently, a lack of potential therapeutic agents against AD was the primary focus of research, which resulted in less effort directed towards developing useful diagnostic approaches. In this study, we developed a WO2002/088706 kit that is composed of fluorescent nanoparticles for the early detection of AD. We provided a fluorescent nanoparticle for detecting markers and a kit for the early diagnosis of AD. The kit consists of a probe molecule comprising an oligonucleotide capable of detecting one or more AD-specific microRNAs (miRNAs) and biomarkers related to AD. Through screening, we selected miR-106b, miR-146b, miR-181a, miR-200a, miR-34a, miR-124b, miR-153, miR-155, Aβ1-42 monomer (mAβ), Aβ1–42 oligomer (oAβ), UCHL1, NLRP3, Tau, STAT3, SORL1, Clusterin, APOE3, APOE4, Nogo-A, IL-13, and Visfatin to serve as AD- and inflammation-related markers. For detection of kit-binding properties, we checked the expression levels of amyloid beta (Aβ), tau protein, and inflammatory mediators in APP/PS/ApoE knockdown (KD) mice and a control group using co-localisation analysis conducted with a confocal microscope. Using a similar approach, we checked the expression levels of miRNAs in HT22 cells. Finally, we used the plasma from AD patients to confirm that our fluorescent nanoparticles and the WO2002/088706 kit will provide a possible early diagnosis to serve as an AD detector that can be further improved for future studies on targeting AD.

scholarly journals Clinical Usefulness of Monitoring Expression Levels ofCCL24(Eotaxin-2) mRNA on the Ocular Surface in Patients with Vernal Keratoconjunctivitis and Atopic Keratoconjunctivitis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Yukiko Shiraki ◽  
Jun Shoji ◽  
Noriko Inada
Keyword(s):  
Mrna Expression ◽  
Ocular Surface ◽  
Clinical Score ◽  
Clinical Severity ◽  
Vernal Keratoconjunctivitis ◽  
Control Group ◽  
Expression Levels ◽  
Atopic Keratoconjunctivitis ◽  
Clinical Scores ◽  
Mrna Expression Levels

Purpose. This study aimed to evaluate the clinical efficacy of using expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface as a biomarker in patients with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).Methods. Eighteen patients with VKC or AKC (VKC/AKC group) and 12 control subjects (control group) were enrolled in this study. The VKC/AKC clinical score was determined by objective findings in patients by using the 5-5-5 exacerbation grading scale. All subjects underwent modified impression cytology and specimens were obtained from the upper tarsal conjunctiva. Expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface were determined using real-time reverse transcription polymerase chain reaction.Results. The VKC group was divided into two subgroups, depending on the clinical score: the active stage subgroup with 100 points or more of clinical scores and the stable stage subgroup with 100 points or less.CCL24(eotaxin-2) mRNA expression levels in the active VKC/AKC stage subgroup were significantly higher than those in the stable VKC/AKC subgroup and the control group. Clinical scores correlated significantly withCCL24(eotaxin-2) mRNA expression levels in the VKC group.Conclusions.CCL24(eotaxin-2) mRNA expression levels on the ocular surface are a useful biomarker for clinical severity of VKC/AKC.

Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li
Keyword(s):  
Plasma Concentration ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Control Group ◽  
Gene Expressions ◽  
Expression Levels ◽  
Tnf Α ◽  
Healthy Control ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

Cytokine Gene Expression and IgA Production in the Spleen of Chickens Infected with Eimeria tenella

2020 ◽  
Author(s):  
Liushu Jia ◽  
Bianhua Zhou ◽  
Hongwei Wang ◽  
Fan Yang ◽  
Guoyong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Morphological Characteristics ◽  
Eimeria Tenella ◽  
Cytokine Gene Expression ◽  
Control Group ◽  
Expression Levels ◽  
New Strategy ◽  
Iga Production ◽  
Mrna Expression Levels

To explore the effect of Eimeria tenella infection on the cytokines gene expression and IgA production in the spleen of chickens, the morphological characteristics of the spleen were observed through optical and transmission electron microscopy. The IgA production was determined through immunohistochemistry. The mRNA expression levels of splenic cytokines were detected through real-time PCR. Compared to the control group, along with the infection of E. tenella, the splenic lymphocytes exhibited irregular and cracked membranes, mitochondria swelled even vacuolization, the IgA expression in spleen tissue was decreased by 55.57% (p lessthan 0.01). Likewise, the mRNA expression levels of IL-2 and IL-1â decreased by 40% (plessthan 0.01) and 43% p lessthan 0.05), respectively. By contrast, the IL-6, IFN-g and IL-10 levels increased by 158% (p lessthan 0.01), 464% (p lessthan 0.05) and 379% p lessthan 0.01), respectively. These results indicated that the spleen implement an important function in the antagonism of E. tenella, which suggest a new strategy to control coccidiosis by improving the peripheral immunity of chickens.

scholarly journals Cyclooxygenase-2 (COX-2) mRNA Expression Levels in Normal Lung Tissues and Non-small Cell Lung Cancers

1999 ◽  
Vol 90 (12) ◽  
pp. 1338-1373 ◽  
Author(s):  
Mari Ochiai ◽  
Tetsuya Oguri ◽  
Takeshi Isobe ◽  
Shinichi Ishioka ◽  
Michio Yamakido
Keyword(s):  
Mrna Expression ◽  
Small Cell ◽  
Cyclooxygenase 2 ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels
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