scholarly journals Probiotic Bifidobacterium breve Prevents Memory Impairment Through the Reduction of Both Amyloid-β Production and Microglia Activation in APP Knock-In Mouse

2021 ◽  
pp. 1-17
Author(s):  
Mona Abdelhamid ◽  
Chunyu Zhou ◽  
Kazuya Ohno ◽  
Tetsuya Kuhara ◽  
Ferdous Taslima ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Memory Impairment ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Synaptic Proteins ◽  
Amyloid Β Protein ◽  
Bifidobacterium Breve ◽  
Expression Levels ◽  
Mrna Expression Levels

Background: Probiotic supplementation reestablishes microbiome diversity and improves brain function in Alzheimer’s disease (AD); their molecular mechanisms, however, have not yet been fully illustrated. Objective: We investigated the effects of orally supplemented Bifidobacterium breve MCC1274 on cognitive function and AD-like pathologies in AppNL-G-F mice. Methods: Three-month-old AppNL-G-F mice were orally supplemented with B. breve MCC1274 for four months. The short-term memory function was evaluated using a novel object recognition test. Amyloid plaques, amyloid-β (Aβ) levels, Aβ fibril, amyloid-β protein precursor and its processing enzymes, its metabolic products, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated by immunohistochemistry, Aβ ELISA, western blotting, and immunofluorescence staining. The mRNA expression levels of pro- and anti-inflammatory cytokines were determined by qRT-PCR analysis. Results: We found that the oral B. breve MCC1 274 supplementation prevented memory impairment in AppNL-G-F mice and decreased hippocampal Aβ levels through the enhancement of the a-disintegrin and metalloproteinase 10 (ADAM10) level. Moreover, administration of the probiotic activated the ERK/HIF-1α signaling pathway responsible for increasing the ADAM10 level and also attenuated microglial activation, which in turn led to reduction in the mRNA expression levels of pro-inflammatory cytokines in the brain. In addition, B. breve MCC1274 supplementation increased the level of synaptic proteins in the hippocampus. Conclusion: Our findings support the possibility that oral B. breve MCC1274 supplementation might be used as a potential preventive therapy for AD progression.

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 Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruqayya Afridi ◽  
Ashraf Ullah Khan ◽  
Sidra Khalid ◽  
Bushra Shal ◽  
Hina Rasheed ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Pain ◽  
Expression Levels ◽  
Chronic Inflammatory Pain ◽  
Qrt Pcr ◽  
Pain Models ◽  
Anti Oxidant ◽  
Mrna Expression Levels

Abstract Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.

scholarly journals Probiotic Properties of Lactiplantibacillus plantarum LB5 Isolated from Kimchi Based on Nitrate Reducing Capability

Foods ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1777
Author(s):  
Hyejin Sohn ◽  
You Hyun Chang ◽  
Jong Hyeok Yune ◽  
Chang Hee Jeong ◽  
Dong Min Shin ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Pathogenic Bacteria ◽  
Probiotic Properties ◽  
Expression Levels ◽  
E Coli ◽  
Anti Inflammatory ◽  
Mrna Expression Levels

The purpose of this study was to investigate the probiotic properties of lactic acid bacteria isolated from Korean radish water kimchi (dongchimi). A total of 800 isolates of lactic acid bacteria were isolated from kimchi, and the strain having reduction and tolerance capability for nitrate and nitrite was selected and identified as Lactiplantibacillus plantarum LB5 (LPLB5) by 16S rRNA sequencing. LPLB5 showed higher tolerance to acidic pH values (pH 2.5), 0.3% bile salts, and heat treatment (40, 50, and 60 °C). Antibacterial activity showed strong inhibition against four food-borne pathogenic bacteria (E. coli O157:H7 ATCC 35150, Pseudomonas aeruginosa KCCM 12539, Listeria monocytogenes KCCM 40307, and Staphylococcus aureus ATCC 25923). The strain did not show any antibiotic resistance, β-hemolytic activity, or ability to produce β-glucuronidase. LPLB5 also exhibited a 30% auto-aggregation ability and 33–60% co-aggregation ability with four pathogenic bacteria (E. coli O157: H7 ATCC 35150, E. coli KCTC 2571, L. monocytogenes ATCC 51776, and S. aureus ATCC 25923). Moreover, the strain showed approximately 40% 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical- and 10% 2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging activity. In cell culture studies, human colon epithelial cells (Caco-2) were treated with LPLB5 (106 and 107 CFU/mL); the bacteria showed more than 70% adherence onto and a 32% invasion rate into the Caco-2 cells. LPLB5 significantly decreased the mRNA expression levels of pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) and increased the mRNA expression levels of anti-inflammatory cytokines (interleukin-4 (IL-4), interleukin-10 (IL-10), and interferon-gamma (IFN-γ)) in lipopolysaccharide-stimulated Caco-2 cells. Our data suggest that LPLB5 is safe and possesses probiotic, antioxidant, and anti-inflammatory activities.

scholarly journals Multi-Omics Profiling in Marfan Syndrome: Further Insights into the Molecular Mechanisms Involved in Aortic Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 438
Author(s):  
Judith M. A. Verhagen ◽  
Joyce Burger ◽  
Jos A. Bekkers ◽  
Alexander T. den Dekker ◽  
Jan H. von der Thüsen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Marfan Syndrome ◽  
Molecular Mechanisms ◽  
Aortic Wall ◽  
Aortic Disease ◽  
Cellular Respiration ◽  
Expression Levels ◽  
Aneurysm Formation ◽  
Gene And Protein Expression ◽  
Mrna Expression Levels

Thoracic aortic aneurysm is a potentially life-threatening disease with a strong genetic contribution. Despite identification of multiple genes involved in aneurysm formation, little is known about the specific underlying mechanisms that drive the pathological changes in the aortic wall. The aim of our study was to unravel the molecular mechanisms underlying aneurysm formation in Marfan syndrome (MFS). We collected aortic wall samples from FBN1 variant-positive MFS patients (n = 6) and healthy donor hearts (n = 5). Messenger RNA (mRNA) expression levels were measured by RNA sequencing and compared between MFS patients and controls, and between haploinsufficient (HI) and dominant negative (DN) FBN1 variants. Immunohistochemical staining, proteomics and cellular respiration experiments were used to confirm our findings. FBN1 mRNA expression levels were highly variable in MFS patients and did not significantly differ from controls. Moreover, we did not identify a distinctive TGF-β gene expression signature in MFS patients. On the contrary, differential gene and protein expression analysis, as well as vascular smooth muscle cell respiration measurements, pointed toward inflammation and mitochondrial dysfunction. Our findings confirm that inflammatory and mitochondrial pathways play important roles in the pathophysiological processes underlying MFS-related aortic disease, providing new therapeutic options.

scholarly journals Sinisan Protects Primary Hippocampal Neurons Against Corticosterone by Inhibiting Autophagy via the PI3K/Akt/mTOR Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingjia Zhang ◽  
Yi Zhang ◽  
Haitao Sun ◽  
Hui Ni ◽  
Jialing Sun ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Mtor Pathway ◽  
Therapeutic Effects ◽  
Protein Ratio ◽  
Expression Levels ◽  
Primary Hippocampal Neurons ◽  
Mrna Expression Levels

Objective: Corticosterone causes significant neurotoxicity in primary hippocampal neurons which is associated with depression. Dysfunctional autophagy is implicated in cognitive impairment and depressive-like behavior. The traditional Chinese medicine Sinisan (SNS) is highly effective in clinical treatment of depression. However, the molecular mechanisms underlying therapeutic effects of SNS are unknown.Purpose: The aim of this study was to elucidate the protective effect of SNS and the underlying mechanisms against corticosterone-induced neuronal damage.Study Design: The effects of serum derived from rats containing SNS (or untreated controls) on the expression of autophagy-related molecules in primary rat hippocampal neurons exposed to different concentrations of corticosterone for different intervals were explored.Methods: CCK-8 assay, LDH assay were used to analyze cell viability and LDH activity. Western blot, qRT-PCR, and immunofluorescence assays were used to determine protein and mRNA expression levels of molecules such as LC3, p62, Beclin1, ULK1, PI3K, p-PI3K, Akt p-Akt, mTOR, p-mTOR, p70S6, p-p70S6, 4ebp1 and p-4ebp1.Results: Corticosterone induced a dose- and time-dependent reduction in cellular viability. Moreover, corticosterone (100–400 μM) treatment for 24 h increased LC3-II/LC3-I protein ratio, increased Beclin1 and ULK1 protein expression levels, and decreased p62, PI3K, p-PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein expression levels. Notably, SNS-containing serum reversed corticosterone-induced reduction of neuronal viability, and increased p62, PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein and mRNA expression levels. In addition, SNS-containing serum decreased LC3-II/LC3-I protein ratio, and downregulated Beclin1, and ULK1 protein and mRNA expression in primary hippocampal neurons.Conclusion: SNS protects primary hippocampal neurons against corticosterone-induced neurotoxicity by preventing excessive autophagy through activation of PI3K/AKT/mTOR pathway.

scholarly journals Antiviral Effect of Hyunggaeyungyo-tang on A549 Cells Infected with Human Coronavirus

2021 ◽  
Author(s):  
Seo young Won ◽  
In-Chan Seol ◽  
Ho-Ryong Yoo ◽  
Yoon-Sik Kim
Keyword(s):  
Herbal Medicine ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Control Group ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Expression Levels ◽  
Coronavirus Infection ◽  
Mrna Expression Levels ◽  
Pro Inflammatory Cytokines

Background. Herbal medicine is widely recommended to treat viral infectious diseases. Over 123,000,000 individuals have been infected with the coronavirus since a worldwide pandemic was declared in March 2020. We conducted this research to confirm the potential of herbal medicine as a treatment for coronavirus. Methods. We infected the A549 cell line with beta coronavirus OC43 then treated with 100 μg/mL Hyunggaeyungyo-tang (HGYGT) or distilled water with a control of HGYGT. We measured the mRNA expression levels of pro-inflammatory cytokines and interferon stimulated genes (ISGs) to confirm the effectiveness of HGYGT upon coronavirus infection. Results. We found the effects of HYGYT decrease the expression level of pPKR, peIF2α, IFI6, IFI44, IFI44L, IFI27, IRF7, OASL and ISG15 when administered to cells with coronavirus infection. The expressions of IL-1, TNF-α, COX-2, NF-κB, iNOS and IKK mRNA were also significantly decreased in the HGYGT group than in the control group. Conclusion. Through the reduction of the amount of coronavirus RNA, our research indicates that HGYGT has antiviral effects. The reduction of IKK and iNOS mRNA levels indicate that HGYGT reduces coronavirus RNA expression and may inhibits the replication of coronavirus by acting on NF-kB/Rel pathways to protect oxidative injury. In addition, decreases in mRNA expression levels of pro-inflammatory cytokines indicate that the HGYGT may relieve the symptoms of coronavirus infections.

Low Miki Expression in Myelodysplastic Syndromes Results in Polynuclear Cell Formation through Decondensation of Chromosomes in Prolonged Prometaphase

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2845-2845
Author(s):  
Akiko Nagamachi ◽  
Yuko Ozaki ◽  
Hirotaka Matsui ◽  
Akinori Kanai ◽  
Toshiya Inaba
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Cell Lines ◽  
Negative Correlation ◽  
Hela Cells ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Strong Positive Correlation ◽  
Expression Levels ◽  
Mrna Expression Levels

Abstract Polynuclear cells (PNCs) are routinely observed in the bone marrow of MDS patients. They are binuclear, trinuclear or even multinuclear cells with or without micronuclei, the underlying molecular mechanisms for the production of which are largely unknown. Because loss of the long arm of chromosome 7 (7q-) was reported to be associated with the presence of a higher frequency of PNCs, gene(s) preventing bone marrow cells from carrying such nuclear abnormalities may be located at 7q. We previously identified three candidate anti-myeloid tumor suppressor genes, namely Samd9, Samd9L and Miki, from the microdeletion in the 7q21 band frequently detected in JMML patients. SAMD9L-deficient mice develop MDS resembling human diseases associated with 7q-, most likely through enhancement of cytokine signals (Nagamachi et al., Cancer Cell 2013). Miki (mitotic kinetics regulator) translocates from the Golgi apparatus to mitotic centrosomes coincident with the disappearance of the Golgi body after poly-ADP-ribosylation (PARsylation). Miki is indispensable for centrosome maturation [the rapid increase of pericentriolar materials (PCM) during prophase and prometaphase], which is required for the production of robust mitotic spindles to move chromosomes promptly (Ozaki et al., Mol. Cell 2012). Consequently, as observed by time-lapse imaging of HeLa cells expressing histone H2A-GFP, downregulation of Miki by siRNA markedly prolonged the duration of prometaphase to more than several hours (normally around 15 minutes). Chromosomes were scarcely able to align and cells exited from prometaphase either by cell death or by decondensation of each chromosome. In the latter, cells with decondensed chromosomes then fused with one another within 30 minutes to form cells with relatively large nuclei, resulting in PNCs containing various sizes of nuclei including micronuclei. Indeed, reduction of Miki in HeLa cells by siRNA increased the frequency of PNCs from less than 0.5% to 4.5%. To test whether the chaotic chromosome decondensation in prometaphase causes the accumulation of PNCs observed in MDS, we initially used five cell lines derived from MDS associated with 7q-. PARsylated Miki was barely detectable in these cell lines and we found more cells at prometaphase than at metaphase (the ratio of prometa:meta in the lines ranged from 1.7:1 to 5.7:1). In contrast, in seven cell lines expressing PARsylated Miki at high levels, mitotic cells in prometaphase were found less frequently or at roughly the same frequency as those in metaphase (prometa:meta ratio 0.6:1 to 1.3:1). PNCs in five cell lines harboring 7q-were also more frequent (5.9 - 10.2%) than in the seven cell lines expressing high PARsylated Miki (0.8 - 2.4%). In addition, when we reduced Miki expression levels by shRNA in K562 cells, which express PARsylated Miki at high levels, the prometa:meta ratio increased from 1.1:1 to 3.8:1 and PNCs increased from 0.8% to 8.5%. This suggests that, as in HeLa cells, low expression levels of Miki cause prolongation of prometaphase and increase PNCs in blood cells. Fresh bone marrow preparations from 37 patients with MDS were examined to determine whether Miki mRNA-expression levels influence the prometaphase:metaphase ratio and the frequency of PNCs. We found a strong negative correlation (R=-0.59, p<0.01) between Miki mRNA expression levels in mononuclear cells of bone marrow samples and the prometa:meta ratio. We also found a moderate negative correlation (R=-0.4, p<0.05) between PNC frequencies and Miki mRNA expression levels. In addition, there was a strong positive correlation between prometa:meta ratios and PNC frequencies (R=-0.56, P<0.01). In conclusion, lack of one allele of the Miki gene due to 7q-reduces PARsylated Miki, resulting in the increase of PNCs through decondensation of chromosomes in prolonged prometaphase. This may contribute to poor outcome of MDS associated with 7q-through increased chromosome instability. Disclosures No relevant conflicts of interest to declare.

Effects of Molybdenum or/and Cadmium on mRNA Expression Levels of Inflammatory Cytokines and HSPs in Duck Spleens

2015 ◽  
Vol 170 (1) ◽  
pp. 237-244 ◽  
Author(s):  
Huabin Cao ◽  
Mengmeng Zhang ◽  
Bing Xia ◽  
Jin Xiong ◽  
Yibo Zong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Expression Levels ◽  
Mrna Expression Levels

scholarly journals Cellular Stress Pathways Are Linked to Acetamiprid-Induced Apoptosis in SH-SY5Y Neural Cells

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 820
Author(s):  
Ezgi Öztaş ◽  
Mehtap Kara ◽  
Tuğçe Boran ◽  
Enes Bişirir ◽  
Ecem Fatma Karaman ◽  
...  
Keyword(s):  
Er Stress ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Cellular Stress ◽  
Mitogen Activated Protein Kinase ◽  
Neural Cells ◽  
Human Neuroblastoma ◽  
Expression Levels ◽  
Mrna Expression Levels

Acetamiprid (ACE), a commonly used neonicotinoid insecticide, is correlated with neurological symptoms, immunotoxicity and hepatotoxicity. Cellular stress and damage could play an important role in ACE-induced neurotoxicity; however, its mechanism has not been fully understood. We evaluated the effects of ACE on oxidative stress, endoplasmic reticulum (ER) stress, cellular death, mRNA expression levels of related genes and protein expressions of related molecular mechanisms in SH-SY5Y human neuroblastoma cells. The half maximal inhibition of enzyme activity (IC50) value of ACE was determined as 4.26 mM after 24 h of treatment by MTT assay. We revealed an increase in reactive oxygen species (ROS) production and calcium release. Significant increases were measured in inositol-requiring enzyme 1-alpha (IRE1-α) and binding immunoglobulin protein 90 (GRP90) levels as well as mRNA expression levels of caspase 3, 4 and 9 genes indicating enhanced ER stress. Apoptosis and ER stress-related genes were significantly upregulated at ≥2 mM. Indeed, ACE caused apoptosis and necroptosis while necrosis was not observed. There was a significant increase in the protein level of mitogen-activated protein kinase-8 (MAPK8) at 4 mM of ACE while no change was seen for nuclear factor kappa-B (NF-κB) and tumor necrosis factor-alpha (TNF-α). In conclusion, increased cellular stress markers could be proposed as an underlying mechanism of ACE-induced cell death in neural cells.

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