scholarly journals Assessment of the therapeutic potential of anti-miR 24 and anti-miR 34 in cardiac diseases

2020 ◽  
Vol 19 (7) ◽  
pp. 1435-1440
Author(s):  
Chunli Li ◽  
Jue Li ◽  
Xiaojun Sun ◽  
Jin Huang ◽  
Chunyan Yao
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Negative Control ◽  
Therapeutic Drug ◽  
Control Group ◽  
Therapeutic Effects ◽  
Cardiac Diseases ◽  
Transfected Cells ◽  
Synthetic Oligonucleotides ◽  
Tgf Β1

Purpose: To study the therapeutic effects of anti-miR-24 and anti-miR-34 in cardiac diseasesMethods: H9c2 rat cardiomyocyte cell lines were transfected with the synthetic oligonucleotides antimiR-24 and anti-miR-34 which reduced the expressions of miR-24 and miR-34. Proliferation assay, real time-polymerase chain reaction (RT-PCR) and immunoblotting were carried out to determine the effect of the transfections on cardiomyocyte proliferation, expressions of miR-24 and miR-34, as well as expressions of the target genes, TGF-β1 and E2F3.Results: The proliferation ability of the transfected cells was decreased significantly, relative to negative control. In contrast, percentage apoptosis was higher in the negative control group than in transfected cells. The expression profiles of anti-miR-24 and anti-miR-34 were significantly reduced, when compared to negative control. These results were further confirmed using immunoblot which revealed that the expression of the target genes, TGF-β1 and E2F3, were upregulated in the transfected cells.Conclusion: These results suggest that the synthetic oligonucleotides (anti-miR-24 and anti-miR-34) might be useful in developing therapeutic drug targets for cardiac diseases by suppressing the expressions of miR-24 and miR-34. Keywords: H9c2rat cardiomyocyte miRNA, Anti-miR-24, Anti-miR-34, Cardiac diseases

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 Role of the Hippo signaling pathway in safflower yellow pigment treatment of paraquat-induced pulmonary fibrosis

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052090542
Author(s):  
Hai Li ◽  
Baotian Kan ◽  
Lingli Song ◽  
Yufa Liu ◽  
Xiangdong Jian
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Tissue Growth ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hippo Signaling ◽  
Exposure Group ◽  
Tgf Β1

Objective To elucidate the molecular mechanisms by which safflower yellow (SY) mediates therapeutic effects in rats with paraquat intoxication-induced pulmonary fibrosis. Methods Rats received combinations of paraquat, SY, and SB431542, a transforming growth factor (TGF)-β1 receptor antagonist. Survival over 28 days was assessed by Kaplan–Meier analysis. Rat tissue and serum samples were assessed by hematoxylin and eosin staining, Masson’s Trichrome staining, immunoblotting, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and transmission electron microscopy. Results Survival rates were higher in SY and SB431542 groups (treatment and paraquat) than in the exposure group (paraquat alone). In the exposure group, serum TGF-β1 levels increased between days 3 and 14; mammalian STE20-like (MST) levels increased between days 3 and 7; TGF-β1 and Smad3 levels increased between days 3 and 14; and Yap and connective tissue growth factor levels increased between days 3 and 28. TGF-β1 levels were lower in SY and SB431542 groups than in the exposure group. Pathology scores were higher in exposure, SY, and SB431542 groups than in the control group throughout the experiment. Conclusions In rats with paraquat intoxication-induced pulmonary fibrosis, Hippo signaling could be activated by the MST-Yap pathway; SY and SB431542 could alleviate pulmonary fibrosis via Hippo signaling.

scholarly journals Doping β-TCP as a Strategy for Enhancing the Regenerative Potential of Composite β-TCP—Alkali-Free Bioactive Glass Bone Grafts. Experimental Study in Rats

Materials ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 4 ◽  
Author(s):  
Manuel Ferreira ◽  
Ana Brito ◽  
Daniela Brazete ◽  
Inês Pereira ◽  
Eunice Carrilho ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Biomedical Applications ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
New Bone Formation ◽  
Autologous Bone ◽  
Bone Filling

The present work aims at evaluating the potential gains derived from partially replacing calcium in resorbable β-tricalcium phosphate (β-TCP) by two different molar percentages of strontium (5, 10) and zinc (1, 2), concomitantly with a fixed molar percentage (0.5) of manganese. Synthetic granular composite bone filling grafts consisting of doped β-TCP and an alkali-free bioactive glass were prepared and implanted in ~4 mm diameter bone defects drilled in the calvaria of Wistar rats used as animal models. The animals were sacrificed after 9 weeks of implantation and the calvaria was excised. Non-manipulated bone was used as positive control, while empty defects were used as a negative control group. The von Kossa staining revealed an enhanced new bone formation with increasing doping levels, supporting the therapeutic effects exerted by the doping elements. The percentage of newly formed bone was similar when the defects were filled with autologous bone, BG (previous results) or 3TCP2/7BG, which indicates that the latter two are excellent candidates for replacement of autologous bone as bone regeneration material. This finding confirms that doping with suitable doses of therapeutic ions is a good strategy towards transposing the bone graft materials to biomedical applications in humans.

scholarly journals Identification of immune-infiltrated hub genes as potential biomarkers of Moyamoya disease by bioinformatics analysis

2021 ◽  
Author(s):  
Fa Jin ◽  
Chuanzhi Duan
Keyword(s):  
Moyamoya Disease ◽  
Expression Profiles ◽  
Molecular Transport ◽  
Neutrophil Infiltration ◽  
Negative Control Group ◽  
Negative Control ◽  
Functional Enrichment ◽  
Control Group ◽  
Hub Genes ◽  
Immune Infiltration

Abstract Background Moyamoya disease (MMD) is a unique chronic progressive cerebrovascular disease. The molecular mechanism behind pathophysiology is still elusive. This study aims to determine the key genes and their roles in the immune infiltration of MMD.Methods We download raw gene expression profiles (GSE157628, GSE141024) of cerebrovascular tissue from GEO database. Identify differentially expressed genes (DEGs) and perform functional enrichment analysis. The CIBERSORT deconvolution algorithm was used to analyze the proportion of immune cell infiltration between MMD and negative control group. We screened for neutrophil-associated DEGs, constructed a protein-protein interaction network (PPI) using STRING, and clarified hub genes using the Cytoscape plugin MCODE analysis. The receiver operating characteristic (ROC) curve is applied to test and filter the best gene signature.Results A total of 570 DEGs were detected, including 212 downregulated and 358 up-regulated genes. Reactome and KEGG enrichment revealed that DEGs are involved in the cell cycle, molecular transport, and metabolic pathways. The immune infiltration profile demonstrates that MMD cerebrovascular tissues contained a higher proportion of neutrophils, monocytes, and NK cells than negative control group. PPI network and MCODE cluster identified 9 DEGs (UNC13D, AZU1, PYCARD, ELANE, SDCBP, CCL11, CCL15, CCL20, and CXCL5) associated with neutrophil infiltration. ROC results showed that UNC13D has good specificity and sensitivity (AUC = 0.7846).Conclusions The characteristics of immune infiltration in the cerebrovascular tissues of MMD patients and abnormal expression of hub genes provide new insights for understanding MMD progression. UNC13D is promising to be one of the candidate molecules to determine neutrophil infiltration characteristics in MMD.

scholarly journals Genome-Wide Expression Difference of MicroRNAs in Basal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hai-Peng Wei ◽  
Song Zhan ◽  
Qing-An Zhu ◽  
Zhen-Juan Chen ◽  
Xian Feng ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Target Genes ◽  
Expression Profiles ◽  
Taqman Probe ◽  
Control Group ◽  
Small Rna Sequencing ◽  
Mirna Regulation ◽  
Genome Wide

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin ( n = 15 ; control group) and tissues at tumor centers from patients with cheek BCC ( n = 15 ; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the “basal cell carcinoma pathways” were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.

scholarly journals Genes of the GadX-GadW Regulon in Escherichia coli

2003 ◽  
Vol 185 (10) ◽  
pp. 3190-3201 ◽  
Author(s):  
Don L. Tucker ◽  
Nancy Tucker ◽  
Zhuo Ma ◽  
John W. Foster ◽  
Regina L. Miranda ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Target Genes ◽  
Expression Profiles ◽  
Bacterial Colonization ◽  
Gene Expression Profiles ◽  
Acid Resistance ◽  
Principal Component ◽  
Growth Conditions ◽  
Negative Control ◽  
Wild Type

ABSTRACT Acid in the stomach is thought to be a barrier to bacterial colonization of the intestine. Escherichia coli, however, has three systems for acid resistance, which overcome this barrier. The most effective of these systems is dependent on transport and decarboxylation of glutamate. GadX regulates two genes that encode isoforms of glutamate decarboxylase critical to this system, but additional genes associated with the glutamate-dependent acid resistance system remained to be identified. The gadX gene and a second downstream araC-like transcription factor gene, gadW, were mutated separately and in combination, and the gene expression profiles of the mutants were compared to those of the wild-type strain grown in neutral and acidified media under conditions favoring induction of glutamate-dependent acid resistance. Cluster and principal-component analyses identified 15 GadX-regulated, acid-inducible genes. Reverse transcriptase mapping demonstrated that these genes are organized in 10 operons. Analysis of the strain lacking GadX but possessing GadW confirmed that GadX is a transcriptional activator under acidic growth conditions. Analysis of the strain lacking GadW but possessing GadX indicated that GadW exerts negative control over three GadX target genes. The strain lacking both GadX and GadW was defective in acid induction of most but not all GadX target genes, consistent with the roles of GadW as an inhibitor of GadX-dependent activation of some genes and an activator of other genes. Resistance to acid was decreased under certain conditions in a gadX mutant and even more so by combined mutation of gadX and gadW. However, there was no defect in colonization of the streptomycin-treated mouse model by the gadX mutant in competition with the wild type, and the gadX gadW mutant was a better colonizer than the wild type. Thus, E. coli colonization of the mouse does not appear to require glutamate-dependent acid resistance.

Amelioration of Extra-articular Effects Associated with Rheumatoid Arthritis Using Anti-arthritic Herbal Formulations

2020 ◽  
pp. 11-20
Author(s):  
Kemzi N. Elechi-Amadi ◽  
Ojoye N. Briggs ◽  
Boma H. Opusunju ◽  
Ebirien-Agana S. Bartimaeus ◽  
Edna O. Nwachuku
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Day Treatment ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
Herbal Drug ◽  
Standard Drug ◽  
Herbal Formulations

Aim: This study investigated the ability of some herbal formulations to ameliorate extra-articular effects of some herbal formulations used in the management of rheumatoid arthritis in Nigeria. Methodology: Forty-nine (49) female albino Wistar rats were used for this study. They were divided into seven groups: A, B, C, D, E, F and G of seven rats each, with Group A serving as negative control while Group B was a positive control. Groups B, C, D, E, F and G were induced with rheumatoid arthritis by injecting 0.1 ml of Complete Freund's Adjuvant into the right hind paw of each rat. The rats were treated with the standard drug and herbal formulations respectively for 28 days as follows: Group C (treated with a standard drug, Celebrex), Group D (treated with the herbal drug, Jointeez), Group E (treated with a herbal drug, Arthropower), Group F (treated with combination therapy of Jointeez and Celebrex) and Group G (treated with combination therapy of Arthropower and Celebrex). At the end of the 28-day treatment period, the rats were anaesthetized with chloroform and sacrificed through puncture of the jugular vein. Five millilitres (5 ml) of blood samples were put into plain bottles for the analysis of biochemical parameters and 3 ml into K3EDTA bottles for haematological analysis. The lipid parameters were analysed using Mindray autoanalyzer while haematological parameters were determined using Sysmex haematology auto analyzer. Results: Total cholesterol (p<0.001), HDL (p=0.005) and LDL (p=0.004) were significantly reduced in the treated rats compared to the positive control group. Conversely, Packed Cell Volume (p<0.001) and Haemoglobin levels (p<0.001) were significantly reduced in the positive control rats compared to the treated rats. However, Total WBC count was significantly higher in the positive control rats than in the treated rats (p=0.001). The combination therapies used in this study did not offer a significantly different therapeutic advantage over the monotherapies used. The herbal formulations gave therapeutic effects on the extra-articular effects similar to that obtained from the orthodox drug used in this study.  Conclusion: The herbal formulations can be used as alternative regimens for rheumatoid arthritis. It is recommended that herbal formulations be considered for integration into our healthcare system for the management of rheumatoid arthritis.

scholarly journals Therapeutic Effects of Ethanolic Extract of Polygonum limbatum meism Against Reproductive Toxicity Induced by Cadmium in Male Guinea Pigs (Cavia porcellus)

2021 ◽  
Vol 8 ◽  
Author(s):  
Brice Menkem ◽  
Bertin Narcisse Vemo ◽  
Megnimeza Martine Astride Tsambou ◽  
Tadiesse Lavoisier Fonou ◽  
Nguedia Arius Baulland Dongmo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Guinea Pigs ◽  
Cadmium Chloride ◽  
Sperm Count ◽  
Antioxidant Properties ◽  
Ethanolic Extract ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects

This study aimed at evaluating the therapeutic effects of ethanolic extract of Polygonum limbatum meism (EEPLM) on the reproductive parameters of male Guinea pigs exposed to cadmium chloride. Thirty-six male guinea pigs were randomly assigned to six treatment groups (with six animals per group). Group 1 (DW) received distilled water orally; group 2 (Cd), negative control, was treated with cadmium chloride at a dose of 26.25 mg/kg body weight (bw); while group 3 (VitC), positive control, was given 26.25 mg of cadmium chloride/kg bw and 100 mg of vitamin C, and groups 4, 5, and 6 were treated, respectively, with EEPLM at doses of 50, 100, and 200 mg/kg bw in addition to cadmium chloride (26.25 mg/kg bw). After 90 days, all animals were sacrificed, and data related to reproduction, toxicity, and oxidative stress were collected. Results revealed a significant decrease (p &lt; 0.05) of serum levels of creatinine, urea, alanine, and aspartate amino transferases in guinea pigs treated with cadmium chloride and EEPLM compared to the negative control group (Cd). The weight of the bulbo-urethral gland was significantly (p &lt; 0.05) decreased in animals exposed to cadmium chloride and treated with vitamin C or EEPLM compared to the negative control (Cd). Guinea pigs orally receiving cadmium chloride and EEPLM showed significantly (p &lt; 0.05) increased motility, sperm count, spermatozoa with entire plasma membrane, and percentage of normal spermatozoa with reference to the negative control (Cd). The serum level of testosterone increased insignificantly (p &gt; 0.05) in animals given cadmium and EEPLM compared to the negative control (Cd). Animals co-administered cadmium chloride and EEPLM recorded a significantly (p &lt; 0.05) reduced level of MDA, activities of SOD, and total peroxidases compared to the group that received cadmium chloride (Cd) only. In conclusion, cadmium chloride induced reproductive impairments by generating oxidative stress. However, the administration of EEPLM can mitigate these adverse effects due to its antioxidant properties.

scholarly journals Integrative Analysis of miRNA and mRNA Expression Profiles in Calcium Oxalate Nephrolithiasis Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Chuangxin Lan ◽  
Dong Chen ◽  
Xiongfa Liang ◽  
Jian Huang ◽  
Tao Zeng ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Mrna Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Critical Role ◽  
Group Versus ◽  
Receptor Interaction ◽  
Control Group ◽  
Calcium Oxalate Stone ◽  
Qrt Pcr

The microRNA (miRNA) expression profiles and their biological functions in calcium oxalate nephrolithiasis remain unclear. In this study, we investigate the miRNA and mRNA expression profiles of kidney tissues in calcium oxalate stone rats. 16 Sprague Dawley rats were divided into control group and stone-forming group. 24-hour urine samples and kidney tissues were collected for biochemical and histological determination after 4 weeks. MiRNA and mRNA microarray were applied to evaluate the miRNA and mRNA expression profiles. To validate the microarray results, the quantitative real-time PCR (qRT-PCR) was performed. A total of 38 miRNAs and 2728 mRNAs were significantly and differentially expressed in kidney tissues of stone-forming group versus control group. Gene Ontology (GO) analysis revealed that most of the target genes were enriched in terms of oxidation reduction, ion transport, inflammatory response, and response to wounding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these targets highlights their critical role in cytokine-cytokine receptor interaction, gap junction, and chemokine signaling pathway. Furthermore, the reliability of the microarray-based results was confirmed by using qRT-PCR determination. The miRNA and mRNA expressions in calcium oxalate stone rat kidneys might provide a basis for further research on urolithiasis mechanism.

Effects of a new chlorhexidine varnish on Streptococcus mutans biofilm formation in vitro

2018 ◽  
Vol 29 (5) ◽  
pp. 573-579
Author(s):  
Ali Hayati ◽  
Farhud Najafi ◽  
Fahimeh Sadat Tabatabaei
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
Weight Changes ◽  
Oral Environment ◽  
Phosphate Buffered Saline

Abstract Background Local sustained-release drug delivery systems increase the substantivity of drugs in the oral environment and subsequently enhance their therapeutic effects. This study sought to compare the effects of two commercially available varnishes and one experimental chlorhexidine (CHX) varnish on formation of Streptococcus mutans biofilm. The solubility rates of the varnishes were evaluated as well. Methods Standard acrylic discs were fabricated and divided into groups based on the varnish applied to the disc surfaces, namely, V-varnish, Pascal, and experimental CHX varnish. The effects of the varnishes on S. mutans biofilm were assessed after 48 h. Bacterial growth on the discs was evaluated by colony count and scanning electron microscopy (SEM). Solubility was assessed by immersing the samples in phosphate buffered saline and recording their weight changes at different times. The data were analyzed using one-way ANOVA. Results In the Pascal and experimental varnish groups, the total number of bacteria did not differ from that in the negative control group. The SEM findings confirmed the aforementioned results. Solubility varied significantly among the materials. V-varnish was detached from the surfaces after 2 days. No significant weight change was noted in the experimental varnish group at 14 days, while Pascal varnish showed gradual weight loss from the 5th day to the 10th day and had a plateau thereafter. Conclusions Biofilm formation was inhibited by the Pascal and experimental varnishes but not by the V-varnish. The highest acceptable rate of solubility was observed in the Pascal samples.

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