The evaluation of miR-874 antagomiR and miR-146a toxicity in cardiomyocytes

AbstractMore and more studies have shown that microRNAs (miRNAs) play key roles in the treatment of heart failure. Studies have shown that miR-874 (miR-874) inhibitors can reduce H2O2-induced cardiomyocyte necrosis and may have a therapeutic effect on heart failure in terms of cardiomyocyte necrosis. Therefore, the purpose of this experiment is to study the other effects of miR-874 and miR-146a on the key pathways in cardiomyocytes and cardiac fibroblasts. In this study, the roles of miR-874 antagomiR and miR-146a in cardiomyocytes and cardiac fibroblasts were analyzed. we investigated the level of miR-874 expression in H9C2 cardiomyocytes after miR-874 antagomiR transfection and found that the miR-874 expression in the H9C2 cells transfected with miR-874 antagomiR group was significantly lower than that in the control group. The results showed that miR-874 was successfully knocked down by the transfection of miR-874 antagomiR. Our results demonstrated that miR-874 inhibition has no effect on the activity of Caspase-3/7 in cardiomyocytes. miR-874 antagomiR has no effect on the proliferation of cardiac fibroblasts, whereas it can inhibit the activity of caspase-8 in cardiac fibroblasts. In addition, the potential effect of miR-874 antagomiR on cardiac remodeling associated genes were examined. miR-874 antagomiR had no effect on SERCA2a mRNA level in H9C2 cells. In addition, miR-874 antagomiR were able to down-regulate the mRNA level of MMP9 and had no effect on MMP2 mRNA levels in H9C2 cells. Finally, The concentration of Ca2+ was measured using Fluo-4 NW Calcium Assay Kits following transfection of miRNAs or negative control in primary cardiomyocytes. miR-874 antagomiR was found to have no effect on Ca2+ concentration in cardiomyocytes. the concentration of Ca2+ in the cardiomyocytes transfected with miR-146a mimics was significantly lower than the mimic negative control group. In summary, miR-874 antagomiR and miR-146a may have a therapeutic effect on heart failure, but may also have side effects on heart failure treatment. Therefore, miR-874 antagomiR should be further studied to provide a basis for the development of drugs for heart failure.

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Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.120.007638 ◽

2021 ◽

Author(s):

Susan X. Zhao ◽

Andres Deluna ◽

Kate Kelsey ◽

Clifford Wang ◽

Aravind Swaminathan ◽

...

Keyword(s):

Heart Failure ◽

Health Planning ◽

Statistical Significance ◽

Negative Control Group ◽

International Classification Of Diseases ◽

Negative Control ◽

Control Group ◽

Public Health Response ◽

Classification Of Diseases ◽

Age Adjusted Rates

BACKGROUND: Methamphetamine-associated cardiomyopathy/heart failure (MethHF) is an increasingly recognized disease entity in the context of a rising methamphetamine (meth) epidemic that most severely impacts the western United States. Using heart failure (HF) hospitalization data from the Office of Statewide Health Planning and Development, this study aimed to assess trend and disease burden of MethHF in California. METHODS: Adult patients (≥18 years old) with HF as primary hospitalization diagnosis between 2008 and 2018 were included in this study. The association with Meth (MethHF) and those without (non-MethHF) were determined by meth-related International Classification of Diseases -based secondary diagnoses. Statistical significance of trends in age-adjusted rates of hospitalization per 100 000 adults were evaluated using nonparametric analysis. RESULTS: Between 2008 and 2018, 1 033 076 HF hospitalizations were identified: 42 565 were MethHF (4.12%) and 990 511 (95.88%) were non-MethHF. Age-adjusted MethHF hospitalizations per 100 000 increased by 585% from 4.1 in 2008 to 28.1 in 2018, while non-MethHF hospitalizations decreased by 6.0% from 342.3 in 2008 to 321.6 in 2018. The rate of MethHF hospitalization increase more than doubled that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold versus 3.48-fold, P <0.001). Annual inflation–adjusted hospitalization charges because of MethHF increased by 840% from $41.5 million in 2008 to $390.2 million in 2018, as compared with an 82% increase for all HF hospitalization from $3.503 billion to $6.376 billion. Patients with MethHF were significantly younger (49.64±10.06 versus 72.20±14.97 years old, P <0.001), predominantly male (79.1% versus 52.4%, P <0.001), with lower Charlson Comorbidity Index, yet they had longer length of stay, more hospitalizations per patient, and more procedures performed during their stays. CONCLUSIONS: MethHF hospitalizations increased sharply during the study period and contributed significantly to the HF hospitalization burden in California. This emerging HF phenotype, which engenders considerable financial and societal costs, calls for an urgent and concerted public health response to contain its spread.

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Therapeutic effect of various ginsenosides on rheumatoid arthritis

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03302-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Meng Zhang ◽

Hongwei Ren ◽

Kun Li ◽

Shengsheng Xie ◽

Ru Zhang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Flow Cytometry ◽

T Cell ◽

Therapeutic Effect ◽

Negative Control Group ◽

Negative Control ◽

Control Group ◽

Potential Candidate ◽

Tnf Α ◽

Huvec Cells

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. Methods The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides. Results All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6. Conclusion Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.

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Impact effect of lycopene and tomato-based products network on cardio-protective biomarkers in vivo

Functional Foods in Health and Disease ◽

10.31989/ffhd.v2i5.92 ◽

2012 ◽

Vol 2 (5) ◽

pp. 151 ◽

Cited By ~ 2

Author(s):

Nermin N. El-Nashar ◽

Soha Hashim Abduljawad

Keyword(s):

Oxidative Stress ◽

Density Lipoprotein ◽

Negative Control Group ◽

Potential Effect ◽

Negative Control ◽

Control Group ◽

High Fat ◽

Tomato Paste ◽

Tomato Products

Background: Dietary intake plays an important role as nutritional supplements are known to provide potential health benefits in cardiovascular disease. Recent studies suggest that the dietary intake of tomatoes and tomato products containing lycopene are associated with a decreased risk of cardiovascular disease. In order to substantiate these facts, the present study was undertaken to investigate the effectiveness of lycopene from tomato products on the potential effects of oxidative stress and atherosclerosis in vivo, focusing on early atherosclerotic events.Methods: Thirty male albino rats were assigned randomly into 5 groups; group C was the negative control group fed a basal diet, group H was the positive control fed a high-fat diet (HFD), group TS (HFD) was fed a 8% lyophilized tomato paste, group TW (HFD) was fed a 24% lyophilized raw tomato, and group L (HFD) was fed 0.1% mg pure lycopene. The level of serum; total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) was measured after 8 weeks of experimental treatment. Malondialdehyde (MDH) plasma levels were measured in heart tissue homogenate. Furthermore, pathologic changes of the heart and aorta were also assessed.Results: We found that TC, TG, LDL-c and MDH, levels were significantly increased in group H (P < 0.05) compared to the negative control group. Administration of TS, TW and L demonstrated significant changes in these parameters (P < 0.05). The TW group (fed 24% of lyophilized raw tomato components) had more positive effects than the TS & L groups. Furthermore, morphologic changes of heart and aorta revealed that TW and TS had a similar preventive effect against the development of atherosclerosis.Conclusion: Our study indicated that raw tomatoes have a higher potential effect when compared to tomato paste or lycopene alone. This potential effect includes the ability to attenuate and/or reverse oxidative stress and other atherosclerosis related parameters induced by the consumption of a high-fat diet.Key words: Cardioprotective, Lipid profile, Lycopene, Oxidative stress, Tomatoes products

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Angiogenic Potential of VEGF Mimetic Peptides for the Biofunctionalization of Collagen/Hydroxyapatite Composites

Biomolecules ◽

10.3390/biom11101538 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1538

Author(s):

Suya Wang ◽

Felix Umrath ◽

Wanjing Cen ◽

Siegmar Reinert ◽

Dorothea Alexander

Keyword(s):

Negative Control Group ◽

Tube Formation ◽

Negative Control ◽

Control Group ◽

Mrna Levels ◽

Vascular Endothelial ◽

Scaffold Material ◽

Angiogenic Potential ◽

Mimetic Peptides ◽

Endothelial Growth Factor

Currently, the focus on bioinspired concepts for the development of tissue engineering constructs is increasing. For this purpose, the combination of collagen (Coll) and hydroxyapatite (HA) comes closest to the natural composition of the bone. In order to confer angiogenic properties to the scaffold material, vascular endothelial growth factor (VEGF) is frequently used. In the present study, we used a VEGF mimetic peptide (QK) and a modified QK-peptide with a poly-glutamic acid tag (E7-QK) to enhance binding to HA, and analyzed in detail binding efficiency and angiogenic properties. We detected a significantly higher binding efficiency of E7-QK peptides to hydroxyapatite particles compared to the unmodified QK-peptide. Tube formation assays revealed similar angiogenic functions of E7-QK peptide (1µM) as induced by the entire VEGF protein. Analyses of gene expression of angiogenic factors and their receptors (FLT-1, KDR, HGF, MET, IL-8, HIF-1α, MMP-1, IGFBP-1, IGFBP-2, VCAM-1, and ANGPT-1) showed higher expression levels in HUVECs cultured in the presence of 1µM E7-QK and VEGF compared to those detected in the negative control group without any angiogenic stimuli. In contrast, the expression of the anti-angiogenic gene TIMP-1 showed lower mRNA levels in HUVECs cultured with E7-QK and VEGF. Sprouting assays with HUVEC spheroids within Coll/HA/E7-QK scaffolds showed significantly longer sprouts compared to those induced within Coll/HA/QK or Coll/HA scaffolds. Our results demonstrate a significantly better functionality of the E7-QK peptide, electrostatically bound to hydroxyapatite particles compared to that of unmodified QK peptide. We conclude that the used E7-QK peptide represents an excellently suited biomolecule for the generation of collagen/hydroxyapatite composites with angiogenic properties.

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The potential of ethanolic extract of Moringa oleifera leaves on HSF1 expression in oral cancer induced by benzo[a]pyrene

Dental Journal (Majalah Kedokteran Gigi) ◽

10.20473/j.djmkg.v53.i2.p107-110 ◽

2020 ◽

Vol 53 (2) ◽

pp. 107

Author(s):

Vania Syahputri ◽

Theresia Indah Budhy ◽

Bambang Sumaryono

Keyword(s):

Heat Shock ◽

Oral Cancer ◽

Moringa Oleifera ◽

Ethanolic Extract ◽

Negative Control Group ◽

Potential Effect ◽

Negative Control ◽

Control Group ◽

Heat Shock Factor 1 ◽

Moringa Oleifera Leaves

Background: Oral cancer is the sixth most common malignancy that occurs in the world, with more than 330,000 deaths a year. In cancer, mutations occur in proteins, accompanied by unfolding proteins, caused by the unstable micro-environment in cells. To stabilise this condition, protein protectors called heat shock proteins (HSPs) are needed. HSPs are activated by a group of transcription factors known as heat shock factor 1 (HSF1). HSF1 is a considered target in cancer therapy. Moringa oleifera leaves are known to have anti-cancer properties because of bioactive compounds called flavonoid and isothiocyanate and are used as herbal therapy for cancer. Purpose: To investigate the potential effect of ethanolic extract of Moringa oleifera on HSF1 expression in oral cancer induced by benzo[a]pyrene. Methods: This study used 25 male Wistar rats divided into five groups consisting of the negative control group (K-), which was only given aquadest; the positive control group (K+), which was induced with benzo[a]pyrene and given aquadest; and treatment groups that were induced with benzo[a]pyrene and given Moringa oleifera leaf extract at concentrations of 3.125% (P1), 6.25% (P2), and 9.375% (P3). Examination of HSF1 expression was carried out by immunohistochemistry staining. Data were analysed using the Kruskal–Wallis test and post-hoc Tukey HSD. Results: HSF1 expression in the P1, P2, and P3 groups decreased significantly compared to the K+ group. There were no significant differences between the P1, P2, and P3 groups (p > 0.005). Conclusion: Ethanolic extract of Moringa oleifera leaves in three concentrations can decrease expression of HSF1 in oral cancer induced by benzo[a]pyrene.

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Effect of Atractylodes macrocephala extract on chronic heart failure in rats

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i10.11 ◽

2021 ◽

Vol 18 (10) ◽

pp. 2075-2079

Author(s):

Huang Kang ◽

Lu Shi-juan ◽

Zhong Jiang-hua ◽

Wu Miao ◽

Zhang Wei ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Diastolic Pressure ◽

Negative Control Group ◽

Negative Control ◽

Left Ventricular ◽

Heart Weight ◽

Control Group ◽

Chronic Congestive Heart Failure ◽

Whole Heart

Purpose: To investigate the effect of Atractylodes macrocephala extract (AME) on oxidative stress and hemodynamics in chronic congestive heart failure (CHF) rats. Methods: After Sprague Dawley (SD) rats were successfully establised into CHF, they were randomly divided into normal control group, negative control group, captopril group, as well as 1.4, 2.8 and 5.6 g/kg of AME groups, and treated with drugs for 4 weeks. Hemodynamic function, whole heart weight index, blood creatinine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS) were measured. Results: Compared with the normal control group, arterial systolic pressure (SBP)(83.12 ± 16.21 mmHg), diastolic pressure (DBP, (75.16 ± 20.18 mmHg), mean arterial pressure (MAP 76.32 ± 13.43 mmHg), heart rate (HR 353.25 ± 36.34 beats/min), left ventricular systolic peak (LVSP 101.24 ± 16.13 mmHg), and left ventricular pressure change rate (dp/dt max) significantly decreased (p < 0.05), while left ventricular end diastolic pressure (LVEDP (22.13 ± 1.57 mmHg), whole heart weight index (2.74 ± 0.16 mg/g), blood CK (0.93 ± 0.14 U/mL), MDA (19.13 ± 2.26 nmol/mL), NO (34.21 ± 3.16 umol/L), and NOS (42.13 ± 3.24 U/mL) increased significantly increased in the negative control group (p < 0.05). High dose AME significantly improved hemodynamic function, lowered MDA (8.75 ± 2.09 nmol/mL) and NO (22.14 ± 3.27 umol/L) levels (p < 0.05), and also decreased CK (0.57 ± 0.31 U/mL) and NOS (24.24 ± 3.38 U/mL) in CHF rats (p < 0.05). Conclusion: AME significantly improve adriamycin-induced chronic congestive heart failure in rats, which could be used for the therapeutic management of chronic congestive heart failure in future.

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

International Journal of Pharmaceutical and Clinical Research ◽

10.25258/ijpcr.v9i08.9588 ◽

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.

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The Comparison of Ostecyte in the Pressure area and Tension area on Tooth Movement Because of Hyperbaric Oxygen Therapy

DENTA ◽

10.30649/denta.v12i1.162 ◽

2018 ◽

Vol 12 (1) ◽

pp. 34

Author(s):

Arya Barahmanta ◽

Muhammad Faizal Winaris ◽

Pambudi Raharjo

Keyword(s):

Hyperbaric Oxygen ◽

Oxygen Therapy ◽

Tooth Movement ◽

Bone Remodelling ◽

Orthodontic Tooth Movement ◽

Negative Control Group ◽

Positive Control ◽

Negative Control ◽

Control Group ◽

Pressure Area

Background: Orthodontic tooth movement is a interaction prosess of resorption and deposition of bone remodeling. Orthodontic tooth movement by mechanical strength causes changes in alveolar bone. Osteocyte is an essential cell to respond bone remodelling. Hyperbaric Oxygen Therapy affects production of osteocyte because it can release Reactive Oxygen Species (ROS) and Nitrid Oxide (NO). Purpose: To determine the difference number of osteocyte in pressure and tension area during tooth movement by adjuvant of Hyperbaric Oxygen 2,4 ATA during 7 days starting on day 8 to day 14. Materials and Methods: This research used Completery Randomized Control Group Post Test Only Design. 36 cavia cobaya (male) were divided into 3 groups randomly : the negative control groups, positive control group, and treatment group. Preparat staining used Hematoxylin Eosin (HE) and calculated on microscop 1000x with 20 field of view. Data analyses used one way ANOVA and LSD test then compared each area by using paired T test. Result: The data showed that the treatment group (P=10,67) tension area has the highest number of osteocyte than negative control group (K-=3,67), positive control (K+=7,42). In the pressure area showed that negative control group (K-=5,00) has the highest than positive control group (K+=3,83) and treatment (P=3,25). Conclusion: Therapy HBO 2,4 ATA 7 days starting on day 8 to day 14 is could increase osteocyte in the tissue to stimulate process of bone remodelling.<pre> </pre>Keywords: Hyperbaric Oxygen, Tooth movement, Bone remodeling, Osteocyte Correspondence: Arya Brahmanta, Department of Orthodonty, Faculty of Dentistry, Hang Tuah University, Arif Rahman Hakim 150, Surabaya, Phone 031-5945864, Email: <a href="mailto:[email protected]">arya.brahmanta@hangtuah.ac.id</a>

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Antiurolithiatic effect of Cymbopogon Proximus, Alhagi Maurorum, on Sulfadimidine induced urolithiasis in male New Zealand rabbits

Mansoura Veterinary Medical Journal ◽

10.35943/mvmj.2019.01.107 ◽

2019 ◽

Vol 20 (1) ◽

pp. 12-18

Author(s):

Sameh El-Nabtity

Keyword(s):

New Zealand ◽

Intramuscular Injection ◽

Negative Control Group ◽

Negative Control ◽

Control Group ◽

Aqueous Extracts ◽

Blood And Urine Samples ◽

Group 2 ◽

New Zealand Rabbits ◽

Group 1

The present study aimed to investigate the prophylactic effect of Cymbopogon proximus and Alhagi maurorum on Sulfadimidine induced urolithiasis in rabbits . Thirty New Zealand male rabbits were allocated into six equal groups (each of five): Group (1) was used as a negative control. Group(2) were administered sulfadimidine (200mg/kg) by intramuscular injection.Groups(3) and (4) were administered sulfadimidine(200mg/kg) by intramuscular injection and 330mg/kg of Cymbopogon proximus alcoholic and aqueous extracts respectively orally.Groups(5) and (6) were administered sulfadimidine(200mg/kg) by intramuscular injection and 400mg/kg of Alhagi maurorum alcoholic and aqueous extracts respectively orally. The period of experiment was 10 days. Blood and urine samples were collected from rabbits on the 10th day. The results recorded a significant decrease in serum creatinine, urea, uric acid and crystalluria in Cymbopogon proximus and Alhagi maurorum groups compared to sulfadimidine treated group.We conclude that Cymbopogon proximus and Alhagi maurorum have a nephroprotective and antiurolithiatic effects against sulfadimidine induced crystalluria.

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