Effect of Comedications and Endotoxins on Mesenchymal Stem Cell Secretomes, Migratory and Immunomodulatory Capacity

Mesenchymal stem cells (MSCs) are becoming an increasingly popular therapeutic option among patients with a broad range of ailments to modulate immunity and induce regeneration. The majority of patients receiving these MSC therapies are on concurrent medication or have ongoing infection. In the present study, we examined the effect of immunosuppressive drugs and lipopolysaccharides (LPS)/endotoxins on the secretory profile, migration towards site of injury, and suppression of lymphocyte proliferation of bone marrow-derived MSCs (BMSCs). Generally, LPS coculture augmented the secretory capacity of BMSCs while exposure to immunosuppressive drugs resulted primarily in no change or attenuated secretion, with some cases of increased secretion, dependent on the cytokine assayed. Among the immunosuppressants evaluated, Hydrocortisone had the most widespread inhibitory effect, while LPS from E. coli O111:B4 had the most potent stimulatory effect. In addition, we also showed that Hydrocortisone or LPS from E. coli O111:B4 affected the migratory and immunosuppressive capacity of BMSCs. Following simulation with Hydrocortisone, BMSC migration was attenuated, and immunosuppressive capacity against T cell proliferation was enhanced, however, the opposite effects were seen with LPS from E. coli O111:B4. Our data suggests that the clinical outcomes of MSC-based therapy are affected by the use of immunosuppressive medication or the presence of endotoxemia in patients.

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A novel bis(pyrazolyl)methane compound as a potential agent against Gram-positive bacteria

Scientific Reports ◽

10.1038/s41598-021-95609-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Pedro Seguí ◽

John J. Aguilera-Correa ◽

Elena Domínguez-Jurado ◽

Christian M. Sánchez-López ◽

Ramón Pérez-Tanoira ◽

...

Keyword(s):

Antibacterial Activity ◽

Inhibitory Effect ◽

Eukaryotic Cell ◽

Liver Carcinoma ◽

Gram Positive ◽

Minimal Inhibitory Concentrations ◽

E Coli ◽

Gram Positive Bacteria ◽

Therapeutic Compounds ◽

Toxic Concentrations

AbstractThis study was designed to propose alternative therapeutic compounds to fight against bacterial pathogens. Thus, a library of nitrogen-based compounds bis(triazolyl)methane (1T–7T) and bis(pyrazolyl)methane (1P–11P) was synthesised following previously reported methodologies and their antibacterial activity was tested using the collection strains of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Moreover, the novel compound 2P was fully characterized by IR, UV–Vis and NMR spectroscopy. To evaluate antibacterial activity, minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) assays were carried out at different concentrations (2–2000 µg/mL). The MTT assay and Resazurin viability assays were performed in both human liver carcinoma HepG2 and human colorectal adenocarcinoma Caco-2 cell lines at 48 h. Of all the synthesised compounds, 2P had an inhibitory effect on Gram-positive strains, especially against S. aureus. The MIC and MBC of 2P were 62.5 and 2000 µg/mL against S. aureus, and 250 and 2000 µg/mL against E. faecalis, respectively. However, these values were > 2000 µg/mL against E. coli and P. aeruginosa. In addition, the MBICs and MBECs of 2P against S. aureus were 125 and > 2000 µg/mL, respectively, whereas these values were > 2000 µg/mL against E. faecalis, E. coli, and P. aeruginosa. On the other hand, concentrations up to 250 µg/mL of 2P were non-toxic doses for eukaryotic cell cultures. Thus, according to the obtained results, the 2P nitrogen-based compound showed a promising anti-Gram-positive effect (especially against S. aureus) both on planktonic state and biofilm, at non-toxic concentrations.

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Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Molecules ◽

10.3390/molecules26061773 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1773

Author(s):

Patchima Sithisarn ◽

Piyanuch Rojsanga ◽

Pongtip Sithisarn

Keyword(s):

Antibacterial Activities ◽

Inhibitory Effect ◽

Total Flavonoid ◽

Total Phenolic ◽

Antibacterial Effects ◽

E Coli ◽

Young Fruit ◽

Oroxylum Indicum ◽

Zoonotic Bacteria

Oroxylum indicum extracts from the seeds collected from Lampang and Pattani provinces in Thailand, and young fruits and flowers exhibited in vitro display antioxidant and antibacterial activities against clinically isolated zoonotic bacteria including Staphylococcus intermedius, Streptococcus suis, Pseudomonas aeruginosa, β-hemolytic Escherichia coli and Staphylococcus aureus. The orange crystals and yellow precipitates were obtained from the preparation processes of the seed extracts. The orange-red crystals from the seeds collected from Lampang province exhibited strong in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effects (EC50 value = 25.99 ± 3.30 μg/mL) and antibacterial effects on S. intermedius and β-hemolytic E. coli while the yellow precipitate from the same source exhibited only antioxidant activity. Quantitative analysis of phytochemicals in O. indicum samples by spectrophotometric and HPLC techniques showed that they contained different amounts of total phenolic, total flavonoid and three major flavones; baicalin, baicalein and chrysin contents. Young fruit extract, which contained low amounts of flavone contents, still promoted antibacterial effects against the tested bacteria with IC50 values lower than 1 mg/mL and MIC values between 4 to 10 mg/mL in S. intermedius, S. aureus and S suis while higher IC50 and MIC values against P. aeruginosa and β-hemolytic E. coli were found. From scanning electron microscopy, the extract of the young fruit of O. indicum promoted morphological changes in the bacterial cells by disrupting the bacterial cell walls, inducing leakage of the cellular content, and generating the abnormal accumulation of cells. The mechanism of action of the extract for this antibacterial effect may be the disruption of the cell membrane and abnormal cell aggregations. Regression analysis of the results suggests the correlation between total phenolic and total flavonoid contents and antioxidant and antibacterial effects. Baicalin was found to have a high correlation with an inhibitory effect against β-hemolytic E. coli while three unidentified peaks, which could be flavones, showed high correlations with an inhibitory effect against S. intermedius, S. suis, P. aeruginosa and S. aureus.

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The Phytochemical Analysis of Vinca L. Species Leaf Extracts Is Correlated with the Antioxidant, Antibacterial, and Antitumor Effects

Molecules ◽

10.3390/molecules26103040 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3040

Author(s):

Alexandra Ciorîță ◽

Cezara Zăgrean-Tuza ◽

Augustin C. Moț ◽

Rahela Carpa ◽

Marcel Pârvu

Keyword(s):

Bacterial Infections ◽

Inhibitory Effect ◽

Total Phenolic ◽

Phytochemical Analysis ◽

Leaf Extracts ◽

Antitumor Effects ◽

Cytotoxic Effects ◽

E Coli ◽

Lactate Dehydrogenase Release ◽

Nitric Oxide Concentration

The phytochemical analysis of Vinca minor, V. herbacea, V. major, and V. major var. variegata leaf extracts showed species-dependent antioxidant, antibacterial, and cytotoxic effects correlated with the identified phytoconstituents. Vincamine was present in V. minor, V. major, and V. major var. variegata, while V. minor had the richest alkaloid content, followed by V. herbacea. V. major var. variegata was richest in flavonoids and the highest total phenolic content was found in V. herbacea which also had elevated levels of rutin. Consequently, V. herbacea had the highest antioxidant activity followed by V. major var. variegata. Whereas, the lowest one was of V. major. The V. minor extract showed the most efficient inhibitory effect against both Staphylococcus aureus and E. coli. On the other hand, V. herbacea had a good anti-bacterial potential only against S. aureus, which was most affected at morphological levels, as indicated by scanning electron microscopy. The Vinca extracts acted in a dose-depended manner against HaCaT keratinocytes and A375 melanoma cells and moreover, with effects on the ultrastructure, nitric oxide concentration, and lactate dehydrogenase release. Therefore, the Vinca species could be exploited further for the development of alternative treatments in bacterial infections or as anticancer adjuvants.

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Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines asIn VitroCytotoxic and Antimicrobial Candidates

Journal of Chemistry ◽

10.1155/2016/2135893 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Hassan M. Faidallah ◽

Sherif A. F. Rostom ◽

Khalid A. Khan

Keyword(s):

Cell Line ◽

Colon Carcinoma ◽

Human Tumor ◽

Human Colon ◽

Pyrimidine Ring ◽

Inhibitory Effect ◽

Breast Adenocarcinoma ◽

Human Tumor Cell Lines ◽

E Coli

The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for theirin vitrocytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs33,34, and37emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione30together with its alkylthio derivatives33and34stemmed as the most active antimicrobial members being equipotent to ampicillin againstS. aureus,E. coli,andP. aeruginosa,together with a noticeable antifungal activity againstC. albicans.Compounds33and34could be considered as a promising template for possible dual antimicrobial-anticancer candidates.

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TERT Promoter Revertant Mutation Inhibits Melanoma Growth through Intrinsic Apoptosis

Biology ◽

10.3390/biology11010141 ◽

2022 ◽

Vol 11 (1) ◽

pp. 141

Author(s):

Yanbing Wang ◽

Yiwu Chen ◽

Chang Li ◽

Zhiwei Xiao ◽

Hongming Yuan ◽

...

Keyword(s):

Therapeutic Option ◽

B Cell Lymphoma ◽

Inhibitory Effect ◽

Migration And Invasion ◽

Catalytic Core ◽

Tert Promoter ◽

Human Telomerase ◽

Mutant Cells

Human telomerase is a specialized DNA polymerase whose catalytic core includes both TERT and human telomerase RNA (hTR). Telomerase in humans, which is silent in most somatic cells, is activated to maintain the telomere length (TEL) in various types of cancer cells, including melanoma. In the vast majority of tumor cells, the TERT promoter is mutated to promote proliferation and inhibit apoptosis. Here, we exploited NG-ABEmax to revert TERT -146 T to -146 C in melanoma, and successfully obtained TERT promoter revertant mutant cells. These TERT revertant mutant cells exhibited significant growth inhibition both in vitro and in vivo. Moreover, A375−146C/C cells exhibited telomere shortening and the downregulation of TERT at both the transcription and protein levels, and migration and invasion were inhibited. In addition, TERT promoter revertant mutation abrogated the inhibitory effect of mutant TERT on apoptosis via B-cell lymphoma 2 (Blc-2), ultimately leading to cell death. Collectively, the results of our work demonstrate that reverting mutations in the TERT promoter is a potential therapeutic option for melanoma.

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Antibacterial Potentials of some Toothpaste Products against some Oral Bacterial Isolates

Brazilian Dental Science ◽

10.14295/bds.2021.v24i2.2361 ◽

2021 ◽

Vol 24 (2) ◽

Author(s):

Bernard Oluwapelumi Oluboyo ◽

Maihankali J Charles ◽

Richard Akele ◽

Funmilayo Akinseye ◽

Adeola Oluboyo

Keyword(s):

Benzyl Alcohol ◽

Sodium Fluoride ◽

Zinc Sulphate ◽

Potassium Nitrate ◽

Inhibitory Effect ◽

Oral Microbiome ◽

Diffusion Method ◽

E Coli ◽

Test Microorganism ◽

Bactericidal Effects

Objetive: Manufacturers of toothpastes claim that their products are active against oral microbiome capable of causing tooth decay. The objective of this study was to investigate the manufacturers’ claim using some of the toothpaste products sold in Ado-Ekiti, Nigeria. Material and methods: The antibacterial potentials of five commercialized toothpaste products (designated sodium fluoride-zinc sulphate, benzyl alcohol-sodium fluorophosphate, sodium fluoride-eugenol, sodium fluoridesodium laurylsulfate and sodium fluoridepotassium nitrate) were tested against six oral isolates of dental caries and periodontal origin – Staphylococcus aureus, Streptococcus mitis, Streptococcus salivarius, Streptococcus pyogenes and Pseudomonas aeruginosa. The antimicrobial potentials were evaluated using modified agar well diffusion method. Various dilutions of the toothpaste products from 1:1 to 1:16 were tested against each test microorganism. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the toothpastes were determined. Results: sodium fluoride-zinc sulphate, benzyl alcoholsodium fluorophosphate and sodium fluorideeugenol toothpastes showed inhibitory effects on S. aureus, S. mitis and S. salivarius. Sodium fluoride-sodium laurylsulfate and sodium fluoride-potassium nitrate toothpastes showed no inhibitory effect on the organisms except S. pyogenes. Only sodium fluoride-potassium nitrate toothpaste inhibited E. coli while none of the toothpastes inhibited P. aeruginosa. The MIC and MBC of sodium fluoride-zinc sulphate, benzyl alcohol-sodium fluorophosphate, and sodium fluoride-eugenol toothpastes showed bacteriostatic and bactericidal effects on the organisms. Sodium fluoride-zinc sulphate, benzyl alcohol-sodium fluorophosphate, and sodium fluoride-eugenol toothpastes showed comparable effects on S. aureus, S. mitis and S. salivarius. Sodium fluoride-eugenol toothpaste was strongest against S. mitis, benzyl alcoholsodium fluorophosphates toothpaste was strongest against S. pyogenes, sodium fluoridezinc sulphate toothpaste was strongest against S. salivarius and only sodium fluoride-potassium nitrate toothpaste inhibited E. coli. Conclusion: The manufacturer’s claim is upheld by this study for sodium fluoride-zinc sulphate, benzyl alcohol-sodium fluorophosphate and sodium fluoride-eugenol toothpastes. However, sodium fluoride-sodium laurylsulfate and sodium fluoride-potassium nitrate toothpastes showed limited inhibitory potentials. Keywords Antibacterial; Caries; Oral isolates; Periodontitis; Toothpastes.

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Reducing Pathogens by Using Zinc Oxide Nanoparticles and Acetic Acid in Sheep Meat

Journal of Food Protection ◽

10.4315/0362-028x.jfp-13-210 ◽

2014 ◽

Vol 77 (9) ◽

pp. 1599-1604 ◽

Cited By ~ 8

Author(s):

MAHBOUBEH MIRHOSSEINI ◽

VAHID ARJMAND

Keyword(s):

Zinc Oxide ◽

Antibacterial Activity ◽

Acetic Acid ◽

Zno Nanoparticles ◽

Pathogenic Bacteria ◽

Inhibitory Effect ◽

Initial Growth ◽

Practical Applications ◽

E Coli ◽

Sheep Meat

Practical applications of different concentrations (0, 1, 2, 4, 6, and 8 mM) of zinc oxide (ZnO) suspensions containing 1% acetic acid were investigated against the pathogenic bacteria Listeria monocytogenes, Escherichia coli, Staphylococcus aureus, and Bacillus cereus. ZnO suspensions (0, 1, 3, 6, and 8 mM) containing acetic acid had a significant inhibitory effect on the growth of L. monocytogenes, E. coli, and S. aureus during 12 h of incubation, and the 8 mM suspensions of ZnO were the most effective against all the strains. These data suggested that the antibacterial activity of ZnO was concentration dependent. Thus, 6 and 8 mM ZnO were selected for further studies in meat. ZnO nanoparticles reduced initial growth of all inoculated strains in meat. To our knowledge, this is the first report describing the antibacterial activity of ZnO nanoparticles in meat and indicates the potential of these nanoparticles as an antibacterial agent in the food industry.

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Subcellular location and properties of bactericidal factors from human neutrophils.

Journal of Experimental Medicine ◽

10.1084/jem.164.5.1407 ◽

1986 ◽

Vol 164 (5) ◽

pp. 1407-1421 ◽

Cited By ~ 32

Author(s):

J E Gabay ◽

J M Heiple ◽

Z A Cohn ◽

C F Nathan

Keyword(s):

Protein S ◽

Subcellular Location ◽

Inhibitory Effect ◽

Human Neutrophils ◽

E Coli ◽

Fractionation Scheme ◽

Percoll Gradients ◽

Nonionic Detergent ◽

Almost All ◽

Triton X

We examined the subcellular location of bactericidal factors (BF) in human neutrophils, using an efficient fractionation scheme. Nitrogen bomb cavitates of DIFP-treated PMN were centrifuged through discontinuous Percoll gradients, each fraction extracted with 0.05 M glycine, pH 2.0, and tested for the killing of Escherichia coli. greater than 90% of BF coisolated with the azurophil granules. After lysis of azurophils, 98% of azurophil-derived BF (ADBF) sedimented with the membrane. ADBF activity was solubilized from azurophil membrane with either acid or nonionic detergent (Triton X-100, Triton X-114). Bactericidal activity was linear with respect to protein concentration over the range 0.3-30 micrograms/ml. 0.1-0.3 microgram/ml ADBF killed 10(5) E. coli within 30 min at 37 degrees C. At 1.4 micrograms/ml, 50% of 2 X 10(5) bacteria were killed within 5 min. ADBF was effective between pH 5-8, with peak activity at pH 5.5. Glucose (20 mM), EDTA (1-25 mM), and physiologic concentrations of NaCl or KCl had little or no inhibitory effect on ADBF. ADBF killed both Gram-positive and Gram-negative virulent clinical isolates, including listeria, staphylococci, beta-hemolytic streptococci, and Pseudomonas aeruginosa. Thus, under these conditions of cell disruption, fractionation, extraction, and assay, almost all BF in human PMN appeared to be localized to the membrane of azurophilic granules as a highly potent, broad-spectrum, rapidly acting protein(s) effective in physiologic medium. Some of these properties appear to distinguish ADBF from previously described PMN bactericidal proteins.

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Immunosuppressive Compounds Affect the Fungal Growth and Viability of Defined Aspergillus Species

Pathogens ◽

10.3390/pathogens8040273 ◽

2019 ◽

Vol 8 (4) ◽

pp. 273 ◽

Cited By ~ 2

Author(s):

Stanislaw Schmidt ◽

Michael Hogardt ◽

Asuman Demir ◽

Frauke Röger ◽

Thomas Lehrnbecher

Keyword(s):

Fungal Growth ◽

Invasive Fungal Disease ◽

Inhibitory Effect ◽

Immunosuppressive Drugs ◽

Aspergillus Species ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Number Of Patients ◽

Species Specific ◽

The Impact

Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.

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Naturally Occurring PCSK9 Inhibitors

Nutrients ◽

10.3390/nu12051440 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1440

Author(s):

Maria Pia Adorni ◽

Francesca Zimetti ◽

Maria Giovanna Lupo ◽

Massimiliano Ruscica ◽

Nicola Ferri

Keyword(s):

Ldl Cholesterol ◽

Current Knowledge ◽

Therapeutic Option ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Inhibitory Effect ◽

Pcsk9 Inhibitors ◽

Beneficial Effects ◽

Naturally Occurring ◽

Starting Point

Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.

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