scholarly journals Mitochondrial Dysfunction in EAE Mice Brains and Impact of HIF1-α Induction to Compensate Energy Loss

2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Mahboobeh Mosavimehr ◽  
Seyed Alireza Mesbah-Namin
Keyword(s):  
Energy Loss ◽  
Mitochondrial Dysfunction ◽  
Demyelinating Disease ◽  
Specific Activity ◽  
Hypoxia Inducible Factor ◽  
Neuronal Loss ◽  
Negative Control ◽  
Potential Candidate ◽  
Mice Model ◽  
Control Groups

Background: Mitochondrial dysfunction may be involved in the process of degradation and death of gray matter cells of the central nervous system (CNS) in patients with multiple sclerosis (MS). MS is known as a chronic, progressive demyelinating disease of the CNS. Objectives: Experimental autoimmune encephalomyelitis (EAE) mouse model of MS is the best method for extracting data trend for diagnosing this disorder. The aim of this study was to evaluate the specific activity of the Cytochrome oxidase (COX), ATP, and hypoxia-inducible factor 1 alpha (HIF-1α) in brain tissues of the EAE mice model. Methods: Twenty-one female mice (C57BL/6) were used, 9 for inducing the EAE model and 6 for each of both negative and sham control groups. The specific activity of the COX, ATP, and HIF-1α levels were evaluated in the whole brain of all 3 mice groups. Results: According to the findings, specific COX activity and ATP levels were decreased significantly, which could be due to the mitochondrial dysfunction and neuronal loss in MS lesions, whereas HIF-1α levels increased significantly in the EAE mice group, compared to the sham and negative control groups. The significant increase of HIF-1α levels reinforces the hypothesis that the HIF-1α induction may provide prevention of neuronal death by compensating energy loss under hypoxia-like conditions in EAE mice brains. Conclusions: The results of this study suggest that HIF-1α induction may also be a potential target for controlling the progression of MS, or the development of HIF-1α inducing compounds could be a potential candidate for the management of this disease and provide a rationale to conduct further research in this area.

Effect of HylocereusPolyrhizus Rind Extract Toward Interleukin-1β, Vascular Endothelial Growth Factor Expression, Endometriosis Implant Area

2017 ◽  
Vol 9 (08) ◽  
Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Group ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Vascular Endothelial ◽  
Mice Model ◽  
Endothelial Growth Factor ◽  
Fruit Rind

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.

Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis

2020 ◽  
Vol 19 (6) ◽  
pp. 376-385
Author(s):  
Md. A. Islam ◽  
Shoumik Kundu ◽  
Rosline Hassan
Keyword(s):  
Multiple Sclerosis ◽  
Gene Therapy ◽  
Disease Progression ◽  
Demyelinating Disease ◽  
Human Subjects ◽  
Mice Model ◽  
Focal Lesions ◽  
Protective Function ◽  
Monocytes And Macrophages ◽  
Specific Symptoms

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.

scholarly journals Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769756 ◽  
Author(s):  
Hui Shi ◽  
Jin Pu ◽  
Xiao-Li Zhou ◽  
Yun-Ye Ning ◽  
Chong Bai
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Negative Control ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Control Groups ◽  
Over Expression ◽  
Non Coding Rna ◽  
Protein Expressions ◽  
Long Non Coding Rna

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.

scholarly journals Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle

2015 ◽  
Vol 112 (37) ◽  
pp. 11642-11647 ◽  
Author(s):  
Tomohiro Suhara ◽  
Takako Hishiki ◽  
Masataka Kasahara ◽  
Noriyo Hayakawa ◽  
Tomoko Oyaizu ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Oxygen Sensor ◽  
Lethal Dose ◽  
Hypoxia Inducible Factor ◽  
Tolerance Test ◽  
Null Mouse ◽  
Mice Model ◽  
Hypoxic Response ◽  
Cori Cycle

Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.

scholarly journals Pengaruh Pemberian Ekstrak Teripang Pasir terhadap Hambatan Pertumbuhan Shigella Dysentriae Secara In Vitro

2020 ◽  
Vol 18 (1) ◽  
pp. 47
Author(s):  
FERIZAL NEGERI SAMUDRA ◽  
RETNO BUDIARTI ◽  
IRMAWATI IRMAWATI
Keyword(s):  
Sea Cucumber ◽  
Antibacterial Effect ◽  
Positive Control ◽  
Negative Control ◽  
Shigella Dysenteriae ◽  
Control Group ◽  
Control Groups ◽  
Shigella Spp ◽  
Diarrhea Disease

<p><strong>ABSTRACT</strong></p><p><strong>Background</strong>; In Indonesia, most diarrhea disease in 1995 to 2001 are caused by Shigella spp. Shigella spp infection can cause various symptom dan complication. Generally, the treatment by using antibiotic can cause antibiotic resistance. Sea cucumber (Holoturia scabra) is an herb that known, available, and easy to consume by society and has an antibacterial effect. Therefore, further research to study the effect of Holoturia Scabra on <em>Shigella Dysentriae</em> growth in vitro is needed.</p><p><strong>Objectives</strong>: The goal of this research is demonstrate the effect of sea cucumber (Holoturia scabra) to the growth of the <em>Shigella dysentriae</em> bacteria in vitro.</p><p><strong>Method</strong>: The method in this research is Posttest Only Control Group. There are 6 groups, 4 types of and 2 control groups. The concentration of the treatment group is 100%,50%, 25%, and, 12.5% while for positive control tests using chloramphenicol and aquadest as a negative control.</p><p><strong>Result</strong>: The result showed there is an influence on the intake of sand cucumber to the growth of the Shigella dysenteriae.</p><p><strong>Conclusion</strong>: Sea cucumber (<em>Holoturia scabra</em>) inhibit the growth of <em>Shigella dysenteriae</em>.</p><p><strong>Key words</strong>: <em>Shigella dysenteriae</em>, sea cucumber (<em>Holoturia scabra</em>), antibacterial</p>

scholarly journals Antiproliferation Effects of Nanophytosome-Loaded Phenolic Compounds From Fruit of Juniperus Polycarpos Against Breast Cancer in Mice Model: Synthesis, Characterization and Therapeutic Effects

2021 ◽  
Author(s):  
Soheila Moeini ◽  
Ehsan Karimi ◽  
Ehsan Oskoueian
Keyword(s):  
Breast Cancer ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Fruit Extract ◽  
Phenolic Fraction ◽  
Juniperus Polycarpos

Abstract Background: This research was performed to synthesize nanophytosomes-loaded high phenolic fraction (HPF) from Juniperus polycarpos fruit extract and investigate its antiproliferation effects against breast cancer in mice model. Results: The nanophytosomes-loaded HPF from Juniperus polycarpos fruit extract was synthesized. The mice trial was conducted to determine the possible toxic effects of the synthesized nanophytosomes. The anticancer, pro-apoptotic, and antioxidative activities of the nanophytosomes were determined. The nanophytosomes-loaded HPF had a spherical structure with a size of 176 nm and a polydispersity index coefficient of 0.24. The in-vivo study manifested that nanophytosomes-loaded HPF significantly improved weight gain and food intake compared to the negative control group (p<0.05). The nanophytosomes-loaded HPF significantly enhanced the expression of bax (3.4-fold) and caspase-3 (2.7-fold) genes but reduced bcl2 (3.6-fold) gene expression in tumor cells. The average tumor size was significantly decreased in mice treated with nanophytosomes-loaded HPF (p<0.05). The expression of GPX (2.3-fold) and SOD (2.7-fold) antioxidants in the liver of mice supplemented with nanophytosomes-loaded HPF was significantly developed compared to the negative control (p<0.05). The nanophytosomes-loaded HPF did not show toxicity on normal cells. Conclusion: Our results indicated that nanophytosomes-loaded HPF might be a potential anticancer agent for the breast cancer treatment.

scholarly journals Dermal application of lactic acid based cream of a non pathogenic Kocuria marina (BMKO1) strain against Epidermophyton floccosum (MTCC 613) symptomatic excision mice model

2019 ◽  
Vol 9 (1-s) ◽  
pp. 113-120
Author(s):  
Soumya S Dash ◽  
Smaranika Pattnaik
Keyword(s):  
Lactic Acid ◽  
Mouse Models ◽  
Drug Application ◽  
Clinical Signs ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Weight Changes ◽  
Mice Model ◽  
Epidermophyton Floccosum

The aim of this study was to evaluate the antifungal efficacy of Kocuria marina (BMKo1) derived Lactic acid against Epidermophyton floccosum (MTCC-613) infections induced on male Swiss Albino mice model (Mus musculus).  For this purpose, the isolated strain was subjected to ‘flask fermentation’ and the Lactic acid produced as fermentation product, was quantified and analysed. Prior to preclinical test, healthy mice models of approximately 8 weeks old and 25-30 gm (weight) were subjected to intra-dermal administration for a period of 15 days to test for toxicity. Mortality, clinical signs, body weight changes were continually monitored. Then the mouse models were inoculated with 100 µl/ml (V/V) of E. floccosum (MTCC-613) spore suspensions following ‘Excision model’. After induction of the infection, the symptomatic mice groups were subjected to topical application of Kocuria lactic acid cream based formulation at a concentration of 1µl/ml (V/V). The naked eye observations were made on the infected lesions till the absolute deduction of infection of excised skin surfaces. The degrees of deduction of infection were converted into scores and the percentages (%) of deduction of infection were calculated and the average value was derived. There were inclusion of positive control (Fluconazole) and negative control (group with infection induced excision, but without any drug application) mice groups for the sake of comparison. Further, with absolute deduction of infection score observed in mice group, applied with Kocuria derived Lactic acid was akin to Fluconazole activity. However, the infection induced mice group was found to be with substantial increase of degree of infection. This study have curtain raised about the anti Epidermophyton infection activity of a cream based  Cell free Lactic acid derived from a non pathogenic strain of Kocuria marina on mouse models. Keywords: Kocuria marina, Epidermophyton floccosum, Lactic acid

scholarly journals Hyperbaric Oxygen (HBO) Reduce Expression of Hypoxia Inducible Factor-1 Alpha (HIF-1 alpha) and Endometriotic Tissue Size in Mice Model of Endometriosis

2020 ◽  
Vol 151 ◽  
pp. 01003
Author(s):  
Dedy Syahrizal ◽  
Cut Mustika ◽  
Teuku Renaldi ◽  
Mohammad G. Suryokusumo ◽  
Hendy Hendarto
Keyword(s):  
Hyperbaric Oxygen ◽  
Hypoxia Inducible Factor ◽  
Control Group ◽  
Mice Model ◽  
Control Group Design ◽  
Hypoxia Inducible Factor 1 ◽  
Peritoneal Tissue ◽  
Implant Size ◽  
Experimental Laboratory ◽  
Tissue Size

Hypoxia in endometriosis will increase the expression of Hypoxia Inducible Factor-1alpha (HIF1alpha) and its expression could be decreased by Hyperbaric Oxygen (HBO). This study aimed to analyze the effect of HBO 2.4 ATA for 3x30 minutes per day for 10 days on the expression of HIF-1 alpha and endometriotic tissue size on mice model of endometriosis. This study was an experimental laboratory study with a separate pretest-posttest control group design. The mice were divided into three groups, the first was a pretest control group (which describes the condition after endometrium transplantation), the second was the endometriotic group that received hyperbaric oxygen, and the third was the endometriotic group that did not receive hyperbaric oxygen therapy. The endometriosis implant size in the peritoneal tissue was assessed and the immunohistochemistry examination was conducted to determine the expression of HIF-1 alpha. The endometriosis tissue size was reduced in the HBO group compared to the control and nonHBO group. The lowest expression of HIF-1 alpha was significantly found in HBO over the other group. The decrease of HIF1 alpha expression mediates the reduction of size endometriotic tissue due to the therapy of HBO.

scholarly journals Solanum incanum extract enhances wound healing and tissue regeneration in burn mice model

2019 ◽  
Vol 14 (2) ◽  
pp. 101-106
Author(s):  
Zainab Qureshi ◽  
Taous Khan ◽  
Abdul Jabbar Shah ◽  
Fazli Wahid
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Histological Analysis ◽  
Negative Control ◽  
Wound Contraction ◽  
Mice Model ◽  
Wound Area ◽  
Solanum Incanum ◽  
Partial Thickness ◽  
Partial Thickness Burn

This study was conducted to evaluate the topical efficacy of Solanum incanum for the treatment of partial-thickness burn in mice model. Mice were treated with topical ointment of S. incanum three times daily for 14 days. The wound healing was observed through wound contraction and histological parameters. The group treated with S. incanum ointment showed 81% reduction in wound area as compared to negative control where wound area reduced to 22%. The histological analysis further confirmed that ointment favors the tissue regeneration and reepithelization thus heal wound rapidly as com-pared to other groups. In conclusion, S. incanum extract enhances wound healing and tissue regeneration.

scholarly journals [18F]Amylovis as a Potential PET Probe for β-Amyloid Plaque: Synthesis, In Silico, In vitro and In vivo Evaluations

2019 ◽  
Vol 12 (1) ◽  
pp. 58-71 ◽  
Author(s):  
Suchitil Rivera-Marrero ◽  
Laura Fernández-Maza ◽  
Samila León-Chaviano ◽  
Marquiza Sablón-Carrazana ◽  
Alberto Bencomo-Martínez ◽  
...  
Keyword(s):  
In Silico ◽  
Specific Activity ◽  
Senile Plaques ◽  
Coupling Reaction ◽  
In Vitro Assays ◽  
Mice Model ◽  
Wild Mice ◽  
In Silico Studies

Background: Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart ([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice. </p><p> Methods: Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were carried out to obtain 5 and 18F-Amylovis. Protein/A&#223; plaques binding, biodistribution, PET/CT Imaging and immunohistochemical studies were conducted in healthy/transgenic mice. </p><p> Results: The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5 should have affinity to the A&#946;-peptide, mainly through &#960;-&#960; interactions. According to a dynamic simulation study the ligand-A&#946; peptide complexes are stable in simulation-time (&#916;G = -5.31 kcal/mol). [18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The [18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB). According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to A&#946; plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with rapid uptake (7 %ID/g at 5 min) and good washout (0.11&#177;0.03 %ID/g at 60 min). Comparative PET dynamic studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant high uptake in the mice model. </p><p> Conclusion: The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a promissory PET imaging agent to detect the presence of A&#946; senile plaques.

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