Naproxen as a potential candidate for promoting rivastigmine anti-Alzheimer activity against aluminum chloride-prompted Alzheimer's-like disease in rats; neurogenesis and apoptosis modulation as a possible underlying mechanism

2021 ◽  
pp. 174695
Author(s):  
Raafat A. Abdel-Aal ◽  
Ola A. Hussein ◽  
Reham G. Elsaady ◽  
Lobna A. Abdelzaher
Keyword(s):  
Aluminum Chloride ◽  
Underlying Mechanism ◽  
Potential Candidate

scholarly journals Verapamil/Curcumin treatment attenuates the behavioral alterations observed in Williams Syndrome mice by regulation of MAPK pathway and Microglia overexpression

2021 ◽  
Author(s):  
Paula Ortiz-Romero ◽  
Gustavo Egea ◽  
Luis A Pérez-Jurado ◽  
Victoria Campuzano
Keyword(s):  
Mapk Pathway ◽  
Neurodevelopmental Disorder ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Mapk Signaling ◽  
Potential Candidate ◽  
Neuroprotective Effects ◽  
Behavioral Deficits ◽  
Activated Microglia ◽  
Beneficial Effects

AbstractWilliams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there currently are not any effective treatments. We investigated the progression of behavioral deficits present in CD (complete deletion) mice, a rodent model of WBS, after chronic treatment with curcumin, verapamil and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism in CD mice. Behavioral improvement correlates with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation with the control of synaptic transmission. Moreover, CD mice showed an increased activated microglia density in different brain regions, which was prevented by treatment. Therefore, results show that treatment prevented behavioral deficits by recovering altered gene expression in cortex of CD mice, reducing activated microglia and normalizing Bdnf expression levels. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice, and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.

scholarly journals Co-Treatment With Verapamil and Curcumin Attenuates the Behavioral Alterations Observed in Williams–Beuren Syndrome Mice by Regulation of MAPK Pathway and Microglia Overexpression

2021 ◽  
Vol 12 ◽  
Author(s):  
Paula Ortiz-Romero ◽  
Alejandro González-Simón ◽  
Gustavo Egea ◽  
Luis A. Pérez-Jurado ◽  
Victoria Campuzano
Keyword(s):  
Mapk Pathway ◽  
Neurodevelopmental Disorder ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Potential Candidate ◽  
Behavioral Alterations ◽  
Neuroprotective Effects ◽  
Behavioral Deficits ◽  
Activated Microglia ◽  
Beneficial Effects

Williams–Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there are currently no effective treatments. We investigated the progression of behavioral deficits present in WBS complete deletion (CD) mice, after chronic treatment with curcumin, verapamil, and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and, thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism. CD mice showed an increased density of activated microglia in the motor cortex and CA1 hippocampal region, which was prevented by co-treatment. Behavioral improvement correlated with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation to the control of synaptic transmission, and inflammation. Therefore, the results show that co-treatment prevented behavioral deficits by recovering altered gene expression in the cortex of CD mice and reducing activated microglia. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.

scholarly journals The apoptotic effect of polysaccharides with specific molecular weight extracted from Inonotus obliquus on HT-29 colon cancer cells

2020 ◽  
Author(s):  
Xue Han ◽  
Sainan Zhao ◽  
Yu Wang ◽  
Jialei Sun ◽  
Shiwei Chen
Keyword(s):  
Molecular Weight ◽  
Cancer Cells ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Nuclear Condensation ◽  
Inonotus Obliquus ◽  
Apoptotic Effect ◽  
Ht 29

Abstract Background: Recently, natural products, particularly Inonotus obliquus (I. obliquus), have attracted lots of attention due to their effective anticancer effects with relatively low toxicity. Results: I. obliquus polysaccharides (IOP) with different molecular weights were obtained by filtering the aqueous extract through fractional membrane. IOP60b (10 kDa ≤ molecular weight ≤ 30 kDa) with the highest yield and inhibition ratio of HT-29 cancer cells was chosen to evaluate the apoptotic effect on HT-29 cancer cells. After treated with different concentrations of IOP60b, morphological changes including cell shrinkage and nuclear condensation and DNA fragmentation of HT-29 cancer cells were observed. In addition, the proportions of cells in early apoptosis and late apoptosis were significantly (p<0.05) increased in a dose-dependent manner. To further explore the underlying mechanism, RT-PCR and Western blotting were employed. Results indicated that both Bcl-2 family and Caspase family were involved in the regulation process of apoptosis and IOP60b induced cellular apoptosis via upregulation of Bax/Bcl-2 ratio and activation of Caspase-3.Conclusion: These data suggested that IOP60b could be a potential candidate for the clinical prevention and treatment of colorectal cancer.

scholarly journals Streptococcus thermophilus Attenuates Inflammation in Septic Mice Mediated by Gut Microbiota

2020 ◽  
Vol 11 ◽  
Author(s):  
Fu Han ◽  
Gaofeng Wu ◽  
Yijie Zhang ◽  
Haotian Zheng ◽  
Shichao Han ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Streptococcus Thermophilus ◽  
Underlying Mechanism ◽  
Treatment Method ◽  
Inflammatory Factors ◽  
Potential Candidate ◽  
Septic Mouse ◽  
16S Rdna Sequence Analysis

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to infection and lack of effective treatment method. Supplementation of probiotics has emerged as a potential biotherapy for inflammatory diseases in recent years, but its role in protecting viscera against the damage caused by sepsis and the underlying mechanism is poorly understood. Streptococcus thermophilus 19 is one of the most well-studied probiotics, which is selected in this study among seven strains isolated from homemade yogurt due to its optimal ability of suppressing the inflammation response in vitro. It showed significant decrease in the expression of TNF-α, IL-1β, and IL-6 in the co-culture of S. thermophilus 19 and LPS-treated mouse macrophage. The effect of S. thermophilus 19 in mice and the response of mice gut microbiota were subsequently investigated. In LPS-induced septic mouse model, S. thermophilus 19 was highly resistant to LPS and exhibited significantly decreased expressions of inflammatory factors compared to LPS-treated mice. A MiSeq-based 16S rDNA sequence analysis revealed that the decrease of gut microbial diversity in mice intraperitoneally injected with 1 mg/ml LPS were mitigated by the administration of S. thermophilus 19. Fusobacterium significantly decreased during the development of sepsis and rose again after supplement strain 19, while Flavonifractor showed the opposite trend, which demonstrated these two genera were the key bacteria that may function in the mice gut microbiota for alleviation of LPS-induced inflammation reaction. To conclude, S. thermophilus 19 may be a potential candidate for novel biotherapeutic interventions against inflammation caused by sepsis.

scholarly journals The Role of TP53 in Cisplatin Resistance in Mediastinal and Testicular Germ Cell Tumors

2021 ◽  
Vol 22 (21) ◽  
pp. 11774
Author(s):  
Dennis M. Timmerman ◽  
Thomas F. Eleveld ◽  
Ad J. M. Gillis ◽  
Carlijn C. Friedrichs ◽  
Sanne Hillenius ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Line ◽  
Cisplatin Resistance ◽  
Germ Cell Tumors ◽  
Underlying Mechanism ◽  
Potential Candidate ◽  
Knock Out ◽  
Tp53 Mutations ◽  
Platinum Based Chemotherapy

Germ cell tumors (GCTs) are considered to be highly curable; however, there are major differences in the outcomes related to histology and anatomical localization. GCTs originating from the testis are, overall, sensitive to platinum-based chemotherapy, whereas GCTs originating from the mediastinum show a worse response, which remains largely unexplained. Here, we address the differences among GCTs from two different anatomical locations (testicular versus mediastinal/extragonadal), with a specific focus on the role of the P53 pathway. It was recently shown that GCTs with TP53 mutations most often localize to the mediastinum. To elucidate the underlying mechanism, TP53 knock-out lines were generated in cisplatin-sensitive and -resistant clones of the representative 2102Ep cell line (wild-type TP53 testicular GCT) and NCCIT cell line (hemizygously mutated TP53, mutant TP53 mediastinal GCT). The full knock-out of TP53 in 2102Ep and resistant NCCIT resulted in an increase in cisplatin resistance, suggesting a contributing role for P53, even in NCCIT, in which P53 had been reported to be non-functional. In conclusion, these results suggest that TP53 mutations contribute to the cisplatin-resistant phenotype of mediastinal GCTs and, therefore, are a potential candidate for targeted treatment. This knowledge provides a novel model system to elucidate the underlying mechanism of clinical behavior and possible alternative treatment of the TP53 mutant and mediastinal GCTs.

scholarly journals Quercetin Protects H9c2 Cardiomyocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Oxidative Stress and Mitochondrial Apoptosis by Regulating the ERK1/2/DRP1 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Fen Li ◽  
Dongsheng Li ◽  
Shifan Tang ◽  
Jianguang Liu ◽  
Jie Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Underlying Mechanism ◽  
Oxygen Glucose Deprivation ◽  
Potential Candidate ◽  
Low Concentrations ◽  
H9c2 Cardiomyocytes ◽  
Signaling Activation ◽  
Preventive Effects

Reperfusion of blood flow during ischemic myocardium resuscitation induces ischemia/reperfusion (I/R) injury. Oxidative stress has been identified as a major cause in this process. Quercetin (QCT) is a member of the flavonoid family that exerts antioxidant effects. The aim of this study was to investigate the preventive effects of QCT on I/R injury and its underlying mechanism. To this end, H9c2 cardiomyocytes were treated with different concentrations of QCT (10, 20, and 40 μM) and subsequently subjected to oxygen-glucose deprivation/reperfusion (OGD/R) administration. The results indicated that OGD/R-induced oxidative stress, apoptosis, and mitochondrial dysfunction in H9c2 cardiomyocytes were aggravated following 40 μM QCT treatment and alleviated following the administration of 10 and 20 μM QCT prior to OGD/R treatment. In addition, OGD/R treatment inactivated ERK1/2 signaling activation. The effect was mitigated using 10 and 20 μM QCT prior to OGD/R treatment. In conclusion, these results suggested that low concentrations of QCT might alleviate I/R injury by suppressing oxidative stress and improving mitochondrial function through the regulation of ERK1/2-DRP1 signaling, providing a potential candidate for I/R injury prevention.

scholarly journals Selenium-containing compound ameliorates lipopolysaccharide-induced acute lung injury via regulating MAPKs/AP-1 pathway

2021 ◽  
Author(s):  
Wenjing Jia ◽  
Wenting Ding ◽  
Xinmiao Chen ◽  
Zhengwei Xu ◽  
Yeilin Tang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokine ◽  
Underlying Mechanism ◽  
Potential Candidate ◽  
Protective Effects ◽  
Cytokine Release ◽  
Inflammatory Reactions ◽  
Great Progress ◽  
Made In

Abstract Acute lung injury (ALI) characterized by a series of inflammatory reactions and served as the main cause of mortality in intensive care unit patients. Although great progress have been made in understanding the pathophysiology of ALI, there are no effective treatment in clinic. Recently, we have synthesized a selenium-containing compounds, which possess obvious anti-inflammatory activity. The aim of the present study is to evaluate the protective effects of the selenium-containing compound 34# in LPS-induced ALI in mice as well as its underlying mechanism. Compound 34# was found to inhibit LPS-induced macrophage inflammatory cytokine release. These effects were observed to be produced via suppression of the MAPKs/AP-1 pathway. Compound 34# was also noted to attenuate the LPS-induced lung inflammation in mice with ALI. The corresponding results suggested that compound 34# possesses remarkable protective effects on LPS-induced ALI. Furthermore, the MAPKs/AP-1 pathway may prove to be its the underlying mechanism. Accordingly, compound 34# may serve as a potential candidate for the prevention of ALI.

scholarly journals SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

2018 ◽  
Vol 48 (6) ◽  
pp. 2429-2440 ◽  
Author(s):  
Yang Xu ◽  
Jie  Xu ◽  
Yanfang Yang ◽  
Lei Zhu ◽  
Xubin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Potential Candidate ◽  
Metastatic Progression ◽  
Downstream Target ◽  
Underlying Mechanisms

Background/Aims: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues. Methods: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC. Results: Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region. Conclusions: In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.

Conditions for atomic imaging of mullite

1989 ◽  
Vol 47 ◽  
pp. 418-419
Author(s):  
T. A. Epicier ◽  
G. Thomas
Keyword(s):  
Oxygen Vacancies ◽  
High Resolution Electron Microscopy ◽  
Ceramic Materials ◽  
Work Conditions ◽  
Real Space ◽  
Potential Candidate ◽  
Silicate Mineral ◽  
Resolution Electron ◽  
The Subject ◽  
Aluminium Silicate

Mullite is an aluminium-silicate mineral of current interest since it is a potential candidate for high temperature applications in the ceramic materials field.In the present work, conditions under which the structure of mullite can be optimally imaged by means of High Resolution Electron Microscopy (HREM) have been investigated. Special reference is made to the Atomic Resolution Microscope at Berkeley which allows real space information up to ≈ 0.17 nm to be directly transferred; numerous multislice calculations (conducted with the CEMPAS programs) as well as extensive experimental through-focus series taken from a commercial “3:2” mullite at 800 kV clearly show that a resolution of at least 0.19 nm is required if one wants to get a straightforward confirmation of atomic models of mullite, which is known to undergo non-stoichiometry associated with the presence of oxygen vacancies.Indeed the composition of mullite ranges from approximatively 3Al2O3-2SiO2 (referred here as 3:2-mullite) to 2Al2O3-1SiO2, and its structure is still the subject of refinements (see, for example, refs. 4, 5, 6).

Face Inversion Effect Emerges Under Critical Configural Discrepancy

2010 ◽  
Vol 69 (3) ◽  
pp. 161-167 ◽  
Author(s):  
Jisien Yang ◽  
Adrian Schwaninger
Keyword(s):  
Face Recognition ◽  
Face Processing ◽  
Underlying Mechanism ◽  
Inversion Effect ◽  
Configural Processing ◽  
Major Contributor ◽  
Face Inversion Effect ◽  
Configural Information ◽  
Face Inversion ◽  
The Face

Configural processing has been considered the major contributor to the face inversion effect (FIE) in face recognition. However, most researchers have only obtained the FIE with one specific ratio of configural alteration. It remains unclear whether the ratio of configural alteration itself can mediate the occurrence of the FIE. We aimed to clarify this issue by manipulating the configural information parametrically using six different ratios, ranging from 4% to 24%. Participants were asked to judge whether a pair of faces were entirely identical or different. The paired faces that were to be compared were presented either simultaneously (Experiment 1) or sequentially (Experiment 2). Both experiments revealed that the FIE was observed only when the ratio of configural alteration was in the intermediate range. These results indicate that even though the FIE has been frequently adopted as an index to examine the underlying mechanism of face processing, the emergence of the FIE is not robust with any configural alteration but dependent on the ratio of configural alteration.

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