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PloS One 2022Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer...
OBJECTIVE
Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer (EC). Our study aims to detect shared gene signatures and biological mechanism between PCOS and EC by bioinformatics analysis.
METHODS
Bioinformatics analysis based on GEO database consisted of data integration, network construction and functional enrichment analysis was applied. In addition, the pharmacological methodology and molecular docking was also performed.
RESULTS
Totally 10 hub common genes, MRPL16, MRPL22, MRPS11, RPL26L1, ESR1, JUN, UBE2I, MRPL17, RPL37A, GTF2H3, were considered as shared gene signatures for EC and PCOS. The GO and KEGG pathway analysis of these hub genes showed that "mitochondrial translational elongation", "ribosomal subunit", "structural constituent of ribosome" and "ribosome" were highly correlated. Besides, associated transcription factors (TFs) and miRNAs network were constructed. We identified candidate drug molecules including fenofibrate, cinnarizine, propanil, fenthion, clindamycin, chloramphenicol, demeclocycline, hydrochloride, azacitidine, chrysene and artenimol according to these hub genes. Molecular docking analysis verified a good binding interaction of fenofibrate against available targets (JUN, ESR1, UBE2I).
CONCLUSION
Gene signatures and regulatory biological pathways were identified through bioinformatics analysis. Moreover, the molecular mechanisms of these signatures were explored and potential drug molecules associated with PCOS and EC were screened out.
Topics: Computational Biology; Endometrial Neoplasms; Female; Fenofibrate; Gene Regulatory Networks; Humans; Molecular Docking Simulation; Polycystic Ovary Syndrome
PubMed: 35830453
DOI: 10.1371/journal.pone.0271380 -
Photodiagnosis and Photodynamic Therapy Mar 2022This study examined the effect of various root canal irrigants and medicaments on dentin fluorescence elicited by 655 nm visible red laser light. To replicate clinical...
This study examined the effect of various root canal irrigants and medicaments on dentin fluorescence elicited by 655 nm visible red laser light. To replicate clinical use, irrigants were applied onto dentin samples for 2 min, while medicaments were applied for 2 weeks. Fluorescence values tracked from baseline across the following to 24 h, starting 5 min after exposure. Sodium hypochlorite, hydrogen peroxide, and articaine local anaesthetic (4% articaine with 1:1000,000 adrenaline) all significantly quenched fluorescence (p < 0.0001), which then returned to baseline levels after 20 min. Conversely, elevated fluorescence readings were recorded after 3% mepivacaine (p < 0.05), 0.2% chlorhexidine (p < 0.01) and chloroform (p <0.05). A 2 week application of Ledermix™ paste containing 3% demeclocycline caused an irreversible increase in fluorescence (p < 0.0001). Other tested endodontic materials (15% EDTA, eucalyptus oil, calcium hydroxide, Odontopaste™ clindamycin paste, and distilled water) had no impact on dentine fluorescence. The influences of endodontic materials on dentin fluorescence need to considered when using fluorescence endpoints to guide the progress of root canal treatment.
Topics: Calcium Hydroxide; Dental Pulp Cavity; Dentin; Fluorescence; Photochemotherapy; Root Canal Irrigants; Sodium Hypochlorite
PubMed: 34838696
DOI: 10.1016/j.pdpdt.2021.102651 -
Pharmaceuticals (Basel, Switzerland) Apr 2023Type 2 diabetes mellitus is a chronic health problem that can be controlled by slowing one's carbohydrate metabolism by inhibiting α-glucosidase, an enzyme responsible...
Type 2 diabetes mellitus is a chronic health problem that can be controlled by slowing one's carbohydrate metabolism by inhibiting α-glucosidase, an enzyme responsible for carbohydrate degradation. Currently, drugs for type 2 diabetes have limitations in terms of safety, efficiency, and potency, while cases are rapidly increasing. For this reason, the study planned and moved towards drug repurposing by utilizing food and drug administration (FDA)-approved drugs against α-glucosidase, and investigated the molecular mechanisms. The target protein was refined and optimized by introducing missing residues, and minimized to remove clashes to find the potential inhibitor against α-glucosidase. The most active compounds were selected after the docking study to generate a pharmacophore query for the virtual screening of FDA-approved drug molecules based on shape similarity. The analysis was performed using (ADV)-based on binding affinities (-8.8 kcal/mol and -8.6 kcal/mol) and root-mean-square-deviation (RMSD) values (0.4 Å and 0.6 Å). Two of the most potent lead compounds were selected for a molecular dynamics (MD) simulation to determine the stability and specific interactions between receptor and ligand. The docking score, RMSD values, pharmacophore studies, and MD simulations revealed that two compounds, namely Trabectedin (ZINC000150338708) and Demeclocycline (ZINC000100036924), are potential inhibitors for α-glucosidase compared to standard inhibitors. These predictions showed that the FDA-approved molecules Trabectedin and Demeclocycline are potential suitable candidates for repurposing against type 2 diabetes. The in vitro studies showed that trabectedin was significantly effective with an IC of 1.263 ± 0.7 μM. Further investigation in the laboratory is needed to justify the safety of the drug to be used in vivo.
PubMed: 37111312
DOI: 10.3390/ph16040555 -
Analytical Methods : Advancing Methods... Apr 2021A dissolvable layered double hydroxide-based solid-phase extraction combined with high-performance liquid chromatography was developed for the analysis of minocycline,...
A dissolvable layered double hydroxide-based solid-phase extraction combined with high-performance liquid chromatography was developed for the analysis of minocycline, oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline and doxycycline in milk samples. In situ formation of the layered double hydroxide was achieved by the addition of MgCl-AlCl solution to alkaline deproteinized milk. The analytes were efficiently extracted by the Mg/Al layered double hydroxide. After centrifugation, the co-precipitates were dissolved in 0.1 mol L NaEDTA-McIlvaine buffer prior to HPLC analysis. Under optimized conditions, the method achieved low detection limits of 0.414-0.986 μg L and quantification limits of 1.38-3.29 μg L, and good recoveries of 93.5-100% with intra- and inter-day RSDs of 0.498-4.08% and 1.23-10.0%, respectively. This method is convenient, accurate, sensitive, rapid, cost-effective, eco-friendly, and suitable for the determination of seven tetracycline antibiotics in milk samples.
Topics: Animals; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Hydroxides; Milk; Solid Phase Extraction
PubMed: 33734258
DOI: 10.1039/d1ay00154j -
Talanta Feb 2021In this paper, for the first time, the study of voltammetric determination of tetracycline antibiotic demeclocycline was conducted. The oxidation of compound was...
In this paper, for the first time, the study of voltammetric determination of tetracycline antibiotic demeclocycline was conducted. The oxidation of compound was investigated using a commercially available boron-doped diamond electrode pretreated electrochemically (anodic and subsequent cathodic). Addition of anionic surfactant, sodium dodecylsulfate (SDS) and cationic surfactant, cetyltrimethylammonium bromide (CTAB) to the demeclocycline-containing electrolyte solution at pH 2.0 and 9.0, respectively, was found to improve the sensitivity of the stripping voltammetric measurements. Employing square-wave stripping mode (after 30 s accumulation at open-circuit condition) in Britton-Robinson buffer, the limits of detection were found to be 1.17 μg mL (2.3 × 10 M) for 4 × 10 SDS-containing buffer solution at pH 2, and 0.24 μg mL (4.8 × 10 M) for 1 × 10 CTAB-containing buffer solution at pH 9.0. The feasibility of the developed approach for the quantification of demeclocycline was tested in urine samples.
Topics: Anti-Bacterial Agents; Boron; Demeclocycline; Diamond; Electrodes; Surface-Active Agents
PubMed: 33303147
DOI: 10.1016/j.talanta.2020.121695 -
Frontiers in Cellular and Infection... 2021Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most...
Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug. Despite the success of artemisinin combination therapies, the current gold standard treatment, new alternatives are constantly needed due to the ability of malaria parasites to become resistant to almost all drugs that are in heavy clinical use. antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against and the zoonotic . In contrast to tetracyclines, boromycin rapidly killed asexual stages of both species already at low concentrations (~ 1 nM) including multidrug resistant strains (Dd2, K1, 7G8). In addition, boromycin was active against stage V gametocytes at a low nanomolar range (IC: 8.5 ± 3.6 nM). Assessment of the mode of action excluded the apicoplast as the main target. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite.
Topics: Animals; Anti-Bacterial Agents; Antimalarials; Borates; Malaria, Falciparum; Plasmodium falciparum
PubMed: 35096650
DOI: 10.3389/fcimb.2021.802294 -
ACS Chemical Neuroscience Feb 2023H,N-Heteronuclear Single Quantum Coherence (HSQC) NMR is a powerful technique that has been employed to characterize small-molecule interactions with intrinsically...
H,N-Heteronuclear Single Quantum Coherence (HSQC) NMR is a powerful technique that has been employed to characterize small-molecule interactions with intrinsically disordered monomeric α-Synuclein (aSyn). We report how solution pH can impact the interpretation of aSyn HSQC NMR spectra and demonstrate that small-molecule formulations (e.g., complexation with acidic salts) can lower sample pH and confound interpretation of drug binding and concomitant protein structural changes. Through stringent pH control, we confirm that several previously identified compounds (EGCG, Baicalin, and Dopamine (DOPA)) as well as a series of potent small-molecule inhibitors of aSyn pathology (Demeclocycline, Ro90-7501, and (±)-Bay K 8644) are capable of direct target engagement of aSyn. Previously, DOPA-aSyn interactions have been shown to elicit a dramatic chemical shift perturbation (CSP) localized to aSyn's H50 at low DOPA concentrations then expanding to aSyn's acidic C-terminal residues at increasing DOPA levels. Interestingly, this CSP profile mirrors our pH titration, where a small reduction in pH affects H50 CSP, and large pH changes induce robust C-terminal CSP. In contrast, under tightly controlled pH 5.0, DOPA induces significant CSPs observed at both ionizable and nonionizable residues. These results suggest that previous interpretations of DOPA-aSyn interactions were conflated with pH-induced CSP, highlighting the need for stringent pH control to minimize potential false-positive interpretations of ligand interactions in HSQC NMR experiments. Furthermore, DOPA's preferential interaction with aSyn under acidic pH represents a novel understanding of DOPA-aSyn interactions that may provide insight into the potential gain of toxic function of aSyn misfolding in α-synucleinopathies.
Topics: alpha-Synuclein; Dihydroxyphenylalanine; Hydrogen-Ion Concentration; Nuclear Magnetic Resonance, Biomolecular; Small Molecule Libraries
PubMed: 36749138
DOI: 10.1021/acschemneuro.2c00782 -
Analytica Chimica Acta Oct 2021A reciprocating magnetic-field-assisted on-line solid-phase extraction (RMF-SPE) method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been...
A reciprocating magnetic field assisted on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry determination of trace tetracyclines in water.
A reciprocating magnetic-field-assisted on-line solid-phase extraction (RMF-SPE) method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for continuous enrichment of trace chemicals in water samples. Under the assist of the reciprocating magnetic field, carboxyl-modified magnetic nanoparticles (CMNPs) were applied to prepare microcolumn with even dispersion by periodical motion, instead of traditional compaction as extraction sorbents. When water sample passed through the extraction region, dynamic sorbents generates an advantage of countless contacts between sorbents and targets without blocking for high efficient extraction. In this study, the on-line RMF-SPE method was established and evaluated by determination of tetracyclines (TCs) from water samples as analysis models, including oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline, and doxycycline. Experimental conditions have been investigated such as flow rate, reciprocating speed, elution time, and so on. The method showed high relative recovery (95.4-111.1%) and good repeatability with RSD from 2.9 to 11.8% for the 200 mL water sample. The linearity range, limits of detection (LODs), and limits of quantification (LOQs) were 0.5-200 μg L (chlortetracycline) and 0.1-200 μg L (other TCs), 12.0-74.1 ng L, and 40.1-247 ng L, respectively. More importantly, the high enrichment factors in a range of 204 (chlortetracycline) to 276 (demeclocycline) indicate that a small amount of dynamic sorbents (only 10 mg) give full play to extraction attributing to the reciprocating movement, especially for trace analysis and continuous extraction, which is significant for water samples from sea, river and domestic waste.
Topics: Chromatography, Liquid; Magnetic Fields; Solid Phase Extraction; Tandem Mass Spectrometry; Tetracyclines; Water
PubMed: 34602203
DOI: 10.1016/j.aca.2021.338957 -
Drug Testing and Analysis Jul 2022Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and...
Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and wound infections in cattle and swine. The present work proposes a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for oxytetracycline quantification in bull plasma, seminal plasma and urine, requiring limited sample treatment before analysis. Extraction with trichloroacetic acid followed by dilution of the supernatant in mobile phase proved to be effective in all three matrices, allowing to rapidly process large batches of samples. Sharp and symmetrical peak shape was obtained using a BEH C18 reversed-phase column in a chromatographic run of just 3.5 min. The mass spectrometer operated in positive electrospray ionization mode and monitored specific transitions for oxytetracycline (461.1 → 425.8) and the internal standard demeclocycline (465.0 → 447.6). The method was validated over concentration ranges suitable for field concentrations of oxytetracycline found in each matrix, showing good linearity during each day of testing (R always >0.99), as also confirmed by analysis of variance (ANOVA) and lack-of-fit tests. Excellent accuracy and precision were demonstrated by calculated bias always within ±15% and CV% below 10% at all quality control (QC) levels in the three matrices. Matrix effect and recovery were investigated for both analytes, which showed consistent and comparable behaviour in each matrix. To our knowledge, this is the first validated approach for mass spectrometric determination of oxytetracycline in seminal plasma and urine. The method was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to assess the oxytetracycline concentration-time profile in plasma, seminal plasma and urine.
Topics: Animals; Anti-Bacterial Agents; Cattle; Chromatography, High Pressure Liquid; Chromatography, Liquid; Male; Oxytetracycline; Reproducibility of Results; Semen; Spectrometry, Mass, Electrospray Ionization; Swine; Tandem Mass Spectrometry
PubMed: 35195370
DOI: 10.1002/dta.3246 -
Journal of Bone and Joint Infection 2020is gaining recognition as a leading pathogen after orthopaedic shoulder procedures. Photodynamic therapy, a combination of light and a photosensitizer, has...
is gaining recognition as a leading pathogen after orthopaedic shoulder procedures. Photodynamic therapy, a combination of light and a photosensitizer, has demonstrated antimicrobial activity against in the treatment of acne vulgaris. We sought to evaluate the effect of photodynamic therapy using blue light and photosensitizers on isolates from shoulder prosthetic joint infections. strains isolated from 19 patients with shoulder PJI were exposed to blue light alone (415 nm) or in combination with photosensitizers (fluorescein, riboflavin and demeclocycline). strains were divided into 4 categories: , to blue light. 13 of 19 strains (68% were or to blue light alone. Of these 19 strains tested, 11 were tested with blue light and fluorescein or blue light plus riboflavin. Fluorescein (1 µg/mL) enhanced the effect of blue light in 6 of 11 strains (55%). Blue light plus riboflavin (10 µg/mL) resulted enhanced killing in 3 of 11 strains (27%), but produced a paradoxical photoprotective effect in 4 of 11 strains (36%), resulting in a net decrease compared to blue light alone. Demeclocycline, however, enhanced the effect of blue light in 16 of 17 strains (94 %). Blue light with the addition of photosensitizers killed from periprosthetic shoulder infections , with demeclocycline having the most pronounced effect.
PubMed: 32670773
DOI: 10.7150/jbji.46199