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Acta Pharmaceutica (Zagreb, Croatia) Dec 2020The aim of this work is to improve the solubility and bioavailability of chlortetracycline and the function of the immune response. Chlortetracycline bisulfate and...
The aim of this work is to improve the solubility and bioavailability of chlortetracycline and the function of the immune response. Chlortetracycline bisulfate and chlortetracycline mesylate were successfully synthesized and characterized with several techniques, including spectroscopy, chromatography and mass spectrometry, which demonstrated that the C4-dimethylamino group of chlortetracycline can accept a proton from sulfuric acid and methanesulfonic acid to form the corresponding salts. In addition, chlortetracycline bisulfate and chlortetracycline mesylate were more soluble in water than chlortetracycline hydrochloride, but the antibacterial activity was not enhanced. The influences of chlortetracycline hydrochloride, chlortetracycline bisulfate and chlortetracycline mesylate on chlortetracycline and immunoglobulin concentrations in mouse serum were also investigated. These results suggested that the chlortetracycline bisulfate and chlortetracycline mesylate have good bioavailability and strong immune response and have potential applications in animal breeding and formulation technologies.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Biological Availability; Chlortetracycline; Immunity, Cellular; Immunoglobulins; Mesylates; Mice; Microbial Sensitivity Tests; Solubility; Sulfates
PubMed: 32412434
DOI: 10.2478/acph-2020-0041 -
Environmental Science and Pollution... Nov 2023In this study, the toxicity induced by the alkylating agent methyl methanesulfonate (MMS) in Allium cepa L. was investigated. For this aim, bulbs were divided into 4...
In this study, the toxicity induced by the alkylating agent methyl methanesulfonate (MMS) in Allium cepa L. was investigated. For this aim, bulbs were divided into 4 groups as control and application (100, 500 and 4000 µM MMS) and germinated for 72 h at 22-24 °C. At the end of the germination period root tips were collected and made ready for analysis by applying traditional preparation methods. Germination, root elongation, weight, mitotic index (MI) values, micronucleus (MN) and chromosomal abnormality (CAs) numbers, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities and anatomical structures of bulbs were used as indicators to determine toxicity. Moreover the extent of DNA fragmentation induced by MMS was determined by comet assay. To confirm the DNA fragmentation induced by MMS, the DNA-MMS interaction was examined with molecular docking. Correlation and principal component analyses (PCA) were performed to examine the relationship between all parameters and understand the underlying structure and relationships among these parameters. In the present study, a deep neural network (DNN) with two hidden layers implemented in Matlab has been developed for the comparison of the estimated data with the real data. The effect of MDA levels, SOD and CAT activities at 4 different endpoints resulting from administration of various concentrations of MMS, including MN, MI, CAs and DNA damage, was attempted to be estimated by DNN model. It is assumed that the predicted results are in close agreement with the actual data. The effectiveness of the model was evaluated using 4 different metrics, MAE, MAPE, RMSE and R2, which together show that the model performs commendably. As a result, the highest germination, root elongation, weight gain and MI were measured in the control group. MMS application caused a decrease in all physiological parameters and an increase in cytogenetic (except MI) and biochemical parameters. MMS application caused an increase in antioxidant enzyme levels (SOD and CAT) up to a concentration of 500 µM and a decrease at 4000 µM. MMS application induced different types of CAs and anatomical damages in root meristem cells. The results of the comet assay showed that the severity of DNA fragmentation increased with increasing MMS concentration. Molecular docking analysis showed a strong DNA-MMS interaction. The results of correlation and PCA revealed significant positive and negative interactions between the studied parameters and confirmed the interactions of these parameters with MMS. It has been shown that the DNN model developed in this study is a valuable resource for predicting genotoxicity due to oxidative stress and lipid peroxidation. In addition, this model has the potential to help evaluate the genotoxicity status of various chemical compounds. At the end of the study, it was concluded that MMS strongly supports a versatile toxicity in plant cells and the selected parameters are suitable indicators for determining this toxicity.
Topics: Methyl Methanesulfonate; Molecular Docking Simulation; Antioxidants; Plant Roots; Meristem; Superoxide Dismutase; Chromosome Aberrations; Onions; DNA; DNA Damage
PubMed: 37874518
DOI: 10.1007/s11356-023-30465-0 -
Acta Crystallographica. Section E,... Aug 2019The asymmetric unit of the title compound, CHN·CHOS, consists of three (3,5-di-methyl-adamantan-1-yl)ammonium cations, CHN, and three methane-sulfonate anions, CHOS. In...
The asymmetric unit of the title compound, CHN·CHOS, consists of three (3,5-di-methyl-adamantan-1-yl)ammonium cations, CHN, and three methane-sulfonate anions, CHOS. In the crystal, the cations and anions associate N-H⋯O hydrogen bonds into layers, parallel to the (001) plane, which include large supra-molecular hydrogen-bonded rings.
PubMed: 31417806
DOI: 10.1107/S2056989019009988 -
Biochemistry and Biophysics Reports Dec 2020The treatment of methyl methane sulfonate (MMS) increases sensitivity to the DNA damage which, further leads to the cell death followed by a cell cycle delay. Delay in...
The treatment of methyl methane sulfonate (MMS) increases sensitivity to the DNA damage which, further leads to the cell death followed by a cell cycle delay. Delay in the cell cycle is because of the change in global transcription regulation which results into proteome change. There are several microarray studies on the transcriptome changes after MMS treatment, but very few studies are reported related to proteome change. The proteome analysis in this report identified subgroups of proteins, belonging to known cell cycle regulators, metabolic pathways and protein folding. About 53 proteins were identified by MS/MS and found that 36 of them were induced, 10 were repressed and few of them showed insignificant change. Our results indicated the change in the interactome as well as phosphorylation status of carboxy terminal domain (CTD) of RNA Polymerase II (RNAP-II) after MMS treatment. The RNAP-II complex was affinity purified and ~1640 peptides were identified using nano LC/MS corresponding to 27 interacting proteins along with the twelve RNAP-II subunit. These identified proteins participated in the repair of the damage, changes the function of the main energetic pathways and the carbon flux in various end products. The main metabolic enzymes in the glycolysis, pyruvate phosphate and amino acid biosynthesis pathways showed significant change. Our results indicate that DNA damage is somehow related to these pathways and is co-regulated simultaneously.
PubMed: 33072891
DOI: 10.1016/j.bbrep.2020.100820 -
Journal of the American Chemical Society Jun 2020While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different sulfonate...
While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different sulfonate esters is unknown. We report here a general solution to this challenge catalyzed by a combination of Ni and Pd with Zn reductant and LiBr as an additive. The reaction has broad scope, as demonstrated in 33 examples (65% ± 11% average yield). Mechanistic studies show that Pd strongly prefers the aryl triflate, the Ni catalyst has a small preference for the aryl tosylate, aryl transfer between catalysts is mediated by Zn, and Pd improves yields by consuming arylzinc intermediates.
Topics: Catalysis; Mesylates; Molecular Structure; Nickel; Palladium; Sulfonic Acids; Tosyl Compounds; Zinc
PubMed: 32486635
DOI: 10.1021/jacs.0c04670 -
Pediatrics International : Official... Jan 2023
Topics: Humans; Anemia, Diamond-Blackfan; Busulfan; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease
PubMed: 36495472
DOI: 10.1111/ped.15440 -
Bone Marrow Transplantation Apr 2022After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the recurrence of recent thymic emigrants (RTE) and self-tolerant T cells indicate normalized...
After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the recurrence of recent thymic emigrants (RTE) and self-tolerant T cells indicate normalized thymic function. From 2008 to 2019, we retrospectively analyzed the RTE-reconstitution rate and the minimal time to reach normal age-specific first percentiles for CD31CD45RACD4T cells in 199 pediatric patients after allo-HSCT for various malignant and non-malignant diseases. The impact of clinically significant graft-versus-host disease (GvHD), age at transplantation, underlying disease and cumulative area under the curve of busulfan on RTE-reemergence was assessed in multivariable longitudinal analysis. RTE-reconstitution (coefficient -0.24, 95% CI -0.33 to -0.14, p < 0.001) was slowed down by GvHD and the time to reach P1 was significantly longer (Event Time Ratio 1.49, 95% CI 1.25 to 1.78, p < 0.001). Older age at transplantation was also associated with a slower RTE-reconstitution (coefficient -0.028, 95% CI -0.04 to -0.02, p < 0.001) and time to reach P1 was significantly longer (Event Time Ratio 1.03, 95% CI 1.02 to 1.05, p < 0.001). RTE-reconstitution velocity was not influenced by underlying disease or cumulative busulfan exposure. In summary, duration until thymic reactivation was independent of both conditioning intensity and underlying disease and was negatively influenced by older age and GvHD.
Topics: Busulfan; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; T-Lymphocytes; Thymus Gland; Transplantation Conditioning; Transplantation, Homologous
PubMed: 35140350
DOI: 10.1038/s41409-022-01594-w -
Journal of Healthcare Engineering 2022To observe the therapeutic effect and the incidence of adverse reactions of total body irradiation plus cyclophosphamide (TBI/CY) and busulfan plus cyclophosphamide... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To observe the therapeutic effect and the incidence of adverse reactions of total body irradiation plus cyclophosphamide (TBI/CY) and busulfan plus cyclophosphamide (BU/CY) in the treatment of pediatric hematopoietic stem cell transplantation.
METHODS
By searching the Cochrane Library, PubMed, Web of Knowledge, Embase, Chinese Biomedical Literature Database (CBM), and screening randomized controlled trials (RCTs), quality evaluation and data extraction were performed for the included literature, and meta-analysis was performed for RCTs included at using Review Manager 5.2 software.
RESULTS
A total of 10160 patients were enrolled in 15 RCTs, including 5211 patients in the TBI/CY group and 4949 patients in the BU/CY group. Meta-analysis showed that there was a statistical difference in transplant failure rate (OR = 1.56, 95% CI (1.23, 1.97), = 0.0002, = 56%, = 3.69), transplant mortality (OR = 1.45, 95% CI (1.24, 1.68), < 0.00001, = 76%, = 4.80), transplantation long-term disease-free survival rate (OR = 1.52, 95% CI (1.09, 2.12), = 0.01, = 0%, = 2.50), and transplantation adverse reactions (OR = 1.28, 95% CI (1.08, 1.52), = 0.004, = 0%, = 2.85).
CONCLUSION
Meta-analysis showed that TBI/CY combined pretreatment regimen was more effective than BU/CY regimen alone in the treatment of pediatric hematologic transplantation, with a lower incidence of adverse reactions and significant long-term survival efficacy.
Topics: Busulfan; Child; Cyclophosphamide; Humans; Leukemia; Transplantation Conditioning; Treatment Outcome
PubMed: 35340233
DOI: 10.1155/2022/2825712 -
Drug and Chemical Toxicology Jul 2022Here, we studied the protective effect of gallic acid (GAL) as a potent anti-oxidant and anti-inflammatory agent against damage caused by busulfan (BUS) in the testes of...
Here, we studied the protective effect of gallic acid (GAL) as a potent anti-oxidant and anti-inflammatory agent against damage caused by busulfan (BUS) in the testes of adult rats. The adult Wistar rats were assigned as control, BUS: was intraperitoneally () treated with busulfan (15mg/kg, day 7 and 14), GAL + BUS: was co-treated with busulfan ( 15mg/kg, day 7 and 14) and orally treated ( with gallic acid (60days, 20mg/kg) and GAL: was treated with gallic acid (, 60days, 20mg/kg). The results showed that GAL co-treatment increased the numbers of spermatogonia (Type A and B), spermatocytes (primary and secondary) and round spermatids, along with the tubular diameter, epithelial height and gonado-somatic index. In addition, BUS-induced increase in 3β-hydroxysteroid dehydrogenase and γ-glutamyl transpeptidase activities were inhibited on GAL co-treatment. Similarly, BUS-induced decrease in gluthathione concentration, catalase and superoxide dismutase activities along with increase in myeloperoxidase activity and malondialdehyde concentration were significantly normalized to control values on GAL co-treatment. Busulfan-induced elimination of tubular germ cells was completely prevented by GAL. Overall, GAL may inhibit BUS-mediated spermatogenesis arrest via decreasing inflammatory-mediated oxidative stress in a rat experimental model.
Topics: Animals; Antioxidants; Busulfan; Gallic Acid; Male; Oxidative Stress; Rats; Rats, Wistar; Testis
PubMed: 33730944
DOI: 10.1080/01480545.2021.1892949 -
Annals of Medicine Dec 2022Previous studies have proven that Purinostat Mesylate (PM) is a new HDAC inhibitor and exhibits significant antitumor efficacy. However, the clinical application of PM...
Previous studies have proven that Purinostat Mesylate (PM) is a new HDAC inhibitor and exhibits significant antitumor efficacy. However, the clinical application of PM was greatly limited by its poor solubility in water and low bioavailability.To increase the solubility of PM through pharmaceutical research, and prepare it into an injection that meets the needs of intravenous use to promote its clinical application.The prepared PM/HP-β-CD inclusion complex was studied by computer simulation, fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (1H-NMR spectroscopy), and scanning electron microscopy (SEM). Then, the antitumor effects of PM/HP-β-CD inclusion complex were studied by in vitro cytotoxicity assay, apoptosis assay, pharmacokinetic study and in vivo antitumor assay.Phase Solubility Analysis revealed that PM and HP-β-CD were compatible and the solubility of PM increased almost 220 times, to 2.02 mg/mL. The interaction mechanism studies revealed that PM could be embedded into the cavity of HP-β-CD through the side of the aminobenzene ring. Cell viability and apoptosis assays showed that PM/HP-β-CD complex maintained the good anti-cancer activity of PM, and PM/HP-β-CD complex has a better anti-tumor effect and lower toxicity than LBH589 and Hyper-CVAD/RTX in vivo. All the results suggest that HP-β-CD can solve the problem of PM administration and provide a way for clinical application of PM. In this study, an injectable formulation of PM in HP-β-CD (10% w/v) was prepared to improve its water solubility. Our research provides a way for clinical administration of PM, which has been under phase I clinical trial for the treatment of relapsed or refractory B-cell-related hematologic malignancies in China and the USA.KEY MESSAGESWe developed a preparation of Purinostat Mesylate that can be administered intravenously, reducing the toxicity associated with oral administration.This preparation has an outstanding therapeutic effect on SU-DHL-6 xenograft tumour, indicating its clinical value, which has been under phase I clinical trial for the treatment of relapsed or refractory B-cell-related haematologic malignancies in China and the USA.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Calorimetry, Differential Scanning; Computer Simulation; Humans; Mesylates; Spectroscopy, Fourier Transform Infrared
PubMed: 35243950
DOI: 10.1080/07853890.2022.2045347