Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
Add more filters










Publication year range
1.
J Org Chem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950197

ABSTRACT

Electron-rich diarylamines, exemplified by anisole-derived amines, play pivotal roles in process chemistry, pharmaceuticals, and materials. In this study, homo-diarylamines were synthesized directly from the C-H activation of electron-rich arenes by sodium nitrate/trifluoroacetic acid and the successive treatment of iron powder. Mechanistic investigations reveal that nitrosoarene serves as the reaction intermediate, and the formation of the second C-N bond between the resulting nitrosoarene and electron-rich arene is catalyzed by the nitrosonium ion (NO+). Thus, hetero-diarylamines were synthesized using preformed nitrosoarenes and various electron-rich arenes. This reaction complements a range of cross-coupling reactions catalyzed by transition metal catalysts.

2.
Phytomedicine ; 130: 155590, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38810547

ABSTRACT

BACKGROUND: Staphylococcus aureus is a versatile pathogen that can cause a wide range of infections in humans. Biofilms play a crucial role in the pathogenicity of S. aureus and contribute to its ability to cause persistent and chronic infections. Baohuoside I has garnered increasing recognition as a natural flavonol glycoside with a wide spectrum of health-related activities. PURPOSE: The antibacterial and anti-biofilm properties of Baohuoside I have not been extensively investigated. Our study aimed to assess its inhibitory effects and the underlying mechanisms on biofilm formation and hemolytic capacity in S. aureus. STUDY DESIGN/METHODS: The impact of Baohuoside I on the biofilm and virulence of S. aureus was evaluated through in vitro experiments and Galleria mellonella as an in vivo infection model. The mechanisms were explored by Drug affinity responsive target stability (DARTS) and validated in genetic knockout strain and through molecular biological experiments using DARTS, molecular docking, electrophoretic mobility shift assay (EMSA), and bio-layer interferometry (BLI). RESULTS: Baohuoside I significantly inhibits the formation of S. aureus biofilms and hemolytic activity at 6.25 µM. Proteomics analysis revealed that treatment with Baohuoside I led to a reduction in the expression of quorum-sensing system agr-regulated genes. DARTS analysis identified Staphylococcus accessory regulator factor (SarZ), a key regulator involved in the expression of virulence factors in S. aureus by acting as activator of the agr quorum-sensing system, was the direct target of Baohuoside I. Molecular docking, DARTS, BLI and EMSA assays collectively confirmed the direct binding of Baohuoside I to SarZ, inhibiting its binding to downstream promoters. Furthermore, it is found through site-directed protein mutagenesis that the Tyr27 and Phe117 residues are key for Baohuoside I binding to SarZ. Additionally, the knockout of SarZ significantly diminished the hemolytic ability of S. aureus, underscoring its crucial role as a pivotal regulator of virulence. Lastly, in vivo tests utilizing the G. mellonella infection model demonstrated the efficacy of Baohuoside I. CONCLUSION: This study provides valuable insights into the mechanism by which Baohuoside I inhibits the virulence of S. aureus through its interaction with SarZ. These findings highlight the significance of SarZ as an effective target against the virulence of S. aureus.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Biofilms , Molecular Docking Simulation , Biofilms/drug effects , Animals , Virulence/drug effects , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Moths/microbiology , Moths/drug effects , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Hemolysis/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests
3.
ACS Omega ; 9(19): 21510-21519, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38764675

ABSTRACT

Enterococcus faecalis infections pose a significant clinical challenge due to their multidrug resistance and propensity for biofilm formation. Exploring alternative treatment options, such as repurposing existing drugs, is crucial in addressing this issue. This study investigates the antibacterial activity of candesartan cilexetil against E. faecalis and elucidates its mechanism of action. Candesartan cilexetil exhibited notable antibacterial activity against both E. faecalis and Enterococcus faecium, with minimum inhibitory concentration (MIC) of ≤25 µM. Time-kill curves demonstrated concentration-dependent bactericidal effects. Candesartan cilexetil could significantly inhibited biofilm formation at the concentration of 1/4× MIC and induced alterations in biofilm structure. Permeability assays revealed compromised bacterial membranes, accompanied by the dissipation of membrane potential in E. faecalis cells after treatment with candesartan cilexetil. Checkerboard analysis showed that bacterial membrane phospholipids phosphatidylglycerol and cardiolipin could neutralize the antibacterial activity of candesartan cilexetil in a dose-dependent manner. Biolayer interferometry (BLI) assay indicated specific interactions between candesartan cilexetil and phosphatidylglycerol or cardiolipin. This study demonstrates the promising antibacterial and antibiofilm activities of candesartan cilexetil against multidrug-resistant E. faecalis. The mechanism of action involves disruption of bacterial membranes, possibly by interacting with membrane phospholipids. These findings underscore the potential utility of candesartan cilexetil as an effective therapeutic agent for combating E. faecalis infections, offering a valuable strategy in the battle against antibiotic-resistant pathogens.

4.
Int J Mol Sci ; 24(5)2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36902305

ABSTRACT

Truffles are known worldwide for their peculiar taste, aroma, and nutritious properties, which increase their economic value. However, due to the challenges associated with the natural cultivation of truffles, including cost and time, submerged fermentation has turned out to be a potential alternative. Therefore, in the current study, the cultivation of Tuber borchii in submerged fermentation was executed to enhance the production of mycelial biomass, exopolysaccharides (EPSs), and intracellular polysaccharides (IPSs). The mycelial growth and EPS and IPS production was greatly impacted by the choice and concentration of the screened carbon and nitrogen sources. The results showed that sucrose (80 g/L) and yeast extract (20 g/L) yielded maximum mycelial biomass (5.38 ± 0.01 g/L), EPS (0.70 ± 0.02 g/L), and IPS (1.76 ± 0.01 g/L). The time course analysis of truffle growth revealed that the highest growth and EPS and IPS production was observed on the 28th day of the submerged fermentation. Molecular weight analysis performed by the gel permeation chromatography method revealed a high proportion of high-molecular-weight EPS when 20 g/L yeast extract was used as media and the NaOH extraction step was carried out. Moreover, structural analysis of the EPS using Fourier-transform infrared spectroscopy (FTIR) confirmed that the EPS was ß-(1-3)-glucan, which is known for its biomedical properties, including anti-cancer and anti-microbial activities. To the best of our knowledge, this study represents the first FTIR analysis for the structural characterization of ß-(1-3)-glucan (EPS) produced from Tuber borchii grown in submerged fermentation.


Subject(s)
Glucans , Polysaccharides , Fermentation , Molecular Weight , Polysaccharides/chemistry
5.
ACS Omega ; 8(6): 5415-5425, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36816695

ABSTRACT

As methicillin-resistant Staphylococcus aureus has become the most prevalent antibiotic-resistant pathogen in many countries, there is an urgent demand to develop novel antibacterial agents. The purpose of this study is to investigate sertindole's antibacterial and antibiofilm properties, as well as its antibacterial mechanism against S. aureus. The MIC50 and MIC90 values for sertindole against S. aureus were both determined to be 50 µM, and sertindole significantly reduced S. aureus growth at a subinhibitory concentration of 1/2× MIC. Sertindole also showed remarkable potency in inhibiting the development of biofilms. Additionally, proteomic analysis revealed that sertindole could dramatically decrease the biosynthesis of amino acids and trigger the cell wall stress response and oxidative stress response. A series of tests, including membrane permeability assays, quantitative real-time reverse transcription-PCR, and electron microscope observations, revealed that sertindole disrupts cell integrity. The two-component system VraS/VraR knockout S. epidermis strain also showed enhanced sensitivity to sertindole. Overall, our data suggested that sertindole exhibited antibacterial and biofilm-inhibiting activities against S. aureus and that its antibacterial actions may involve the destruction of cell integrity.

6.
Comput Intell Neurosci ; 2022: 3656572, 2022.
Article in English | MEDLINE | ID: mdl-36471665

ABSTRACT

This study aimed to evaluate the consistency of ultrasound TI-RADS classification used by sonographers with different ultrasound diagnosis experience in the diagnosis of thyroid nodules and the diagnostic value of using artificial intelligence ultrasound S-Detect technology in the differentiation of benign and malignant thyroid lesions. 100 patients who underwent ultrasound examination of thyroid masses in our hospital from June 2019 to June 2021 and were further punctured or operated on were included in the study. Pathological results were used as the gold standard to evaluate ultrasound S-Detect technology and the value of TI-RADS classification and the combined application of the two in diagnosing benign and malignant thyroid TI-RADS 4 types of nodules, and the consistency of judgments of doctors of different ages is assessed by a Kappa value. There were 128 nodules in 100 patients, 51 benign nodules, and 77 malignant nodules. For senior physicians, the sensitivity of diagnosis using TI-RADS classification combined with ultrasound S-Detect technology is 93.5%, specificity is 94.1%, and accuracy is 93.8%; for middle-aged physicians using TI-RADS classification combined with ultrasound S-Detect technology for diagnosis, the sensitivity is 89.6%, specificity is 92.2%, and accuracy is 90.6%; for junior doctors, the sensitivity of diagnosis using TI-RADS classification combined with ultrasound S-Detect technology is 83.1%, specificity is 88.2%, and accuracy is 85.1%. Regardless of seniority, the combined application of artificial intelligence ultrasound S-Detect technology and TI-RADS classification can improve the diagnostic ability of sonographers for thyroid nodules and at the same time improve the consistency of judgment among physicians, and this is especially important for radiologists.


Subject(s)
Thyroid Nodule , Middle Aged , Humans , Thyroid Nodule/diagnostic imaging , Artificial Intelligence , Sensitivity and Specificity , Ultrasonography/methods , Technology , Retrospective Studies
7.
Front Genet ; 13: 900168, 2022.
Article in English | MEDLINE | ID: mdl-36386833

ABSTRACT

The purpose of this study was to evaluate the effectiveness of ultrasound techniques in the analysis of respiratory-related muscles in rats. Respiratory parameters, including diaphragm end-expiratory thickness, mean rectus abdominis (RA) thickness, and RA area, were measured by ultrasound and compared with histological findings. Spearman's correlation and Logistic regression analysis were used to detect the differences in the correlation between ultrasound results and histological examinations, and Student's t test was used to compare the differences between ultrasound results and histological examination data. The results showed that there was no significant difference between the end-expiratory thickness of the diaphragm, the average thickness of RA, and the area of RA in the right RA and histological values under ultrasound detection (p > 0.05), but there was a significant positive correlation between ultrasound, and histological values (p < 0.05).); in addition, tidal volume was significantly positively correlated with total RA area, rapid shallow breathing index (RSBI) was significantly negatively correlated with total RA area, and mean diaphragm TF was significantly positively correlated with tidal volume. In conclusion, ultrasound imaging has a high degree of accuracy and reproducibility and can be used to assess the structure and function of the rat diaphragm and RA.

8.
Opt Express ; 30(15): 26690-26700, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-36236856

ABSTRACT

In this work, a novel design for the electrodes in a near quasi-single-mode (QSM) vertical-cavity surface-emitting laser (VCSEL) array with Zn-diffusion apertures inside is demonstrated to produce an effective improvement in the high-speed data transmission performance. By separating the electrodes in a compact 2×2 coupled VCSEL array into two parts, one for pure dc current injection and the other for large ac signal modulation, a significant enhancement in the high-speed data transmission performance can be observed. Compared with the single electrode reference, which parallels 4 VCSEL units in the array, the demonstrated array with its separated electrode design exhibits greater dampening of electrical-optical (E-O) frequency response and a larger 3-dB E-O bandwidth (19 vs. 15 GHz) under the same amount of total bias current (20 mA). Moreover, this significant improvement in dynamic performance does not come at the cost of any degradation in the static performance in terms of the maximum near QSM optical output power (17 mW @ 20 mA) and the Gaussian-like optical far-field pattern which has a narrow divergence angle (full-width half maximum (FWHM): 10° at 20 mA). The advantages of the separated electrode design lead to a much better quality of 32 Gbit/sec eye-opening as compared to that of the reference device (jitter: 1.5 vs. 2.8 ps) and error-free 32 Gbit/sec transmissions over a 500 m multi-mode fiber has been achieved under a moderate total bias current of 20 mA.

9.
J Med Microbiol ; 71(10)2022 Oct.
Article in English | MEDLINE | ID: mdl-36288093

ABSTRACT

Introduction. Staphylococcus aureus is a major cause of chronic diseases and biofilm formation is a contributing factor. 20S-ginsenoside Rg3 (Rg3) is a natural product extracted from the traditional Chinese medicine red ginseng.Gap statement. The effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial mechanism against S. aureus have not been reported.Aim. This study aimed to investigate the effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial action against clinical S. aureus isolates.Methodology. The effect of Rg3 on biofilm formation of clinical S. aureus isolates was studied by crystal violet staining. Haemolytic activity analysis was carried out. Furthermore, the influence of Rg3 on the proteome profile of S. aureus was studied by quantitative proteomics to clarify the mechanism underlying its antibacterial action and further verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR).Results. Rg3 significantly inhibited biofilm formation and haemolytic activity in clinical S. aureus isolates. A total of 63 with >1.5-fold changes in expression were identified, including 34 upregulated proteins and 29 downregulated proteins. Based on bioinformatics analysis, the expression of several virulence factors and biofilm-related proteins, containing CopZ, CspA, SasG, SaeR/SaeS two-component system and SaeR/SaeS-regulated proteins, including leukocidin-like protein 2, immunoglobulin-binding protein G (Sbi) and fibrinogen-binding protein, in the S. aureus of the Rg3-treated group was downregulated. RT-qPCR confirmed that Rg3 inhibited the regulation of SaeR/SaeS and decreased the transcriptional levels of the biofilm-related genes CopZ, CspA and SasG.Conclusions. Rg3 reduces the formation of biofilm by reducing cell adhesion and aggregation. Further, Rg3 can inhibit the SaeR/SaeS two-component system, which acts as a crucial signal transduction system for the anti-virulence activity of Rg3 against clinical S. aureus isolates.


Subject(s)
Biological Products , Staphylococcal Infections , Humans , Staphylococcus aureus/genetics , Leukocidins , Gentian Violet/metabolism , Proteome/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Transcription Factors/genetics , Virulence Factors/genetics , Virulence Factors/metabolism , Biofilms , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Fibrinogen/metabolism , Immunoglobulins/metabolism
10.
Front Genet ; 13: 894716, 2022.
Article in English | MEDLINE | ID: mdl-35754796

ABSTRACT

As an important means of physical examination, palpation is usually limited to the physical examination before surgery and used as an auxiliary method for disease diagnosis in the field of surgery. In practice, palpation is also used in every aspect of the surgical procedure, and its application is of great significance to surgery. The purpose of this study was to investigate the ability of ultrasound imaging to assess the ability of rotating physicians to locate musculoskeletal structures by palpation. Rotating physicians were asked to palpate and locate the long head tendon of the biceps (LHB), posterior tibialis (TPT), acromioclavicular joint (ACJ), and medial tibiofemoral joint (TFJ) spaces on two volunteer models. After positioning, a truncated steel needle was attached to the skin and parallel to the palpable structure, and the position of the steel needle relative to the designated structure was assessed by ultrasound imaging, using the Cohen kappa test to study the inter-rater agreement. The results showed that the assessor's Kappa coefficient for judging the location of all structures was 0.816, LHB was 1.00, TPT was 0.912, ACJ gap was 0.796, and TFJ medial space was 0.844, and the success rate of palpation for TPT was 62.2%, TFJ medial space was 37.8%, ACJ clearance was 24.3%, and LHB was 8.1%. In conclusion, the teaching methods of anatomy and palpation skills need further improvement, and ultrasound imaging is an effective tool for assessing palpation skills.

11.
J Glob Antimicrob Resist ; 30: 66-74, 2022 09.
Article in English | MEDLINE | ID: mdl-35508286

ABSTRACT

OBJECTIVES: This study aimed to investigate the in vitro activities of tigecycline (TGC) and the underlying molecular mechanisms of TGC stress response and resistance in clinical Enterococcus faecalis isolates from China. METHODS: Antimicrobial susceptibility and antibiofilm activities of TGC in 399 E. faecalis isolates were evaluated. Heteroresistance was evaluated by population analysis profiling. Resistance and heteroresistance mechanisms were investigated by identifying genetic mutations in tetracycline (tet) target sites and through analysis of efflux protein inhibitors (EPIs). Furthermore, quantitative proteomics was used to investigate the global proteomic response of E. faecalis to TGC stress, as well as the resistance mechanisms of TGC within in vitro induced resistant isolate. RESULTS: TGC minimum inhibitory concentrations (MICs) against clinical E. faecalis isolates were ≤0.5 mg/L. TGC displayed remarkable inhibitory activity against biofilm formation. The occurrence rate of TGC heteroresistance was 1.75% (7/399), and the increased TGC MIC values of heteroresistance-derived clones could be reversed by EPI. TGC resistance was associated with mutations in the 16S rRNA site or 30S ribosomal protein S10. A total of 105 and 356 differentially expressed proteins was identified after being exposed to 1/2× MIC concentrations of TGC, while 356 differentially expressed proteins was identified in TGC-resistant isolate. The differentially expressed proteins were enriched in the translation and DNA replication process. In addition, multiple adenosine triphosphate (ATP)-binding cassette (ABC) transporters were upregulated. CONCLUSIONS: TGC exhibited excellent activity against a substantial proportion of clinical isolates from China. However, E. faecalis exhibited a strong adaptation mechanism during TGC exposure: mutation of TGC target sites and elevated expression of efflux pumps under TGC selection, resulting in TGC resistance.


Subject(s)
Enterococcus faecalis , Proteomics , Enterococcus faecalis/genetics , Microbial Sensitivity Tests , RNA, Ribosomal, 16S , Tigecycline/pharmacology
12.
BMC Microbiol ; 22(1): 114, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35473561

ABSTRACT

BACKGROUND: The increasing emergence of multidrug-resistant Gram-positive bacterial infections necessitates new antibacterial agents with novel mechanisms of action that can be used to treat these infections. Lomitapide has been approved by FDA for years in reducing levels of low-density lipoprotein (LDL) in cases of familial hypercholesterolemia, whereas the antibacterial effect of lomitapide remains elusive. In this study, the inhibitory activities of lomitapide against Gram-positive bacteria were the first time explored. Quantitative proteomics analysis was then applied to investigate the mechanisms of action of lomitapide. RESULTS: The minimum inhibitory concentration (MIC) values of lomitapide against Gram-positive bacteria including both methicillin sensitive and resistant Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, and Streptococcus agalactiae were range 12.5-50 µM. Moreover, lomitapide also inhibited anti-biofilm activity against clinical S. aureus isolates. A total of 106 proteins with > 1.5-fold changes in expression were identified upon 1/2 × MIC lomitapide exposure, including 83 up-regulated proteins and 23 down-regulated proteins. Based on bioinformatics analysis, the expression of cell wall damage response proteins including two-component system VraS/VraR, lipoteichoic acid (LPA) D-alanylnation related proteins D-alanyl carrier protein (dltC) and carrier protein ligase (dltA), methionine sulfoxide reductases (mrsA1 and mrsB) were up-regulated. Moreover, the expression of SaeS and multiple fibrinogen-binding proteins (SAOUHSC_01110, FnBPB, SAOUHSC_02802, SdrC, SdrD) which were involved in the bacterial adhesion and biofilm formation, was inhibited by lomitapide. Furthermore, VraS/VraR deletion mutant (ΔvraSR) showed an enhanced lomitapide sensitivity phenotype. CONCLUSION: Lomitapide displayed broad antimicrobial activities against Gram-positive bacteria. The antibacterial effect of lomitapide may be caused by cell wall destruction, while the anti-biofilm activity may be related to the inhibition of surface proteins.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Benzimidazoles , Carrier Proteins , Gram-Positive Bacteria , Humans , Staphylococcal Infections/microbiology , Staphylococcus aureus
13.
J Antibiot (Tokyo) ; 75(5): 287-295, 2022 05.
Article in English | MEDLINE | ID: mdl-35288676

ABSTRACT

Triclabendazole (TBD) has been widely used in the treatment of helminthic infection. The anti-biofilm activity and antibacterial mechanism of TBD against Staphylococcus aureus were not known. Here, the anti-biofilm activity of TBD against clinical S. aureus isolates from China was systematically evaluated. Under TBD pressure, TBD-induced tolerant S. aureus with elevated TBD minimum inhibitory concentration (MIC) was selected in vitro and the genetic mutations between the parental isolates and TBD-induced tolerant derivatives were determined by whole-genome sequencing. TBD could significantly inhibit biofilm formation at sub-inhibitory concentration and disperse mature biofilm of clinical S. aureus isolates. In addition, TBD displayed bactericidal activity against the bacterial cells embedded in the biofilm and showed anti-persisters activity. Proteomic analysis showed that KEGG pathways of ABC transporters and beta-lactam resistance were significantly changed after TBD exposure. Moreover, SAUSA300_RS08395 (molecular chaperone DnaK), SAUSA300_RS11200 (sensor histidine kinase KdpD), SAUSA300_RS06325 (DNA translocase FtsK) were identified as candidate targets of TBD in S. aureus. Overexpression experiments further demonstrated that the elevated transcriptional level of DnaK resulted in S. aureus growth delay after exposure to a sub-MIC concentration of 1/2× MIC TBD. In conclusion, TBD exhibits antibacterial and anti-biofilm activity against S. aureus possibly by targeting the DnaK chaperone system.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Biofilms , Humans , Microbial Sensitivity Tests , Proteomics , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus , Triclabendazole
14.
Microbiol Spectr ; 10(1): e0099121, 2022 02 23.
Article in English | MEDLINE | ID: mdl-35019708

ABSTRACT

With the increasing reports of community-acquired and nosocomial infection caused by multidrug-resistant Gram-positive pathogens, there is an urgent need to develop new antimicrobial agents with novel antibacterial mechanisms. Here, we investigated the antibacterial activity of the natural product ginkgolic acid (GA) (15:1), derived from Ginkgo biloba, and its potential mode of action against the Gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus. The MIC values of GA (15:1) against clinical E. faecalis and S. aureus isolates from China were ≤4 and ≤8 µg/mL, respectively, from our test results. Moreover, GA (15:1) displayed high efficiency in biofilm formation inhibition and bactericidal activity against E. faecalis and S. aureus. During its inhibition of the planktonic bacteria, the antibacterial activity of GA (15:1) was significantly improved under the condition of abolishing iron homeostasis. When iron homeostasis was abolished, inhibition of planktonic bacteria by GA (15:1) was significantly improved. This phenomenon can be interpreted as showing that iron homeostasis disruption facilitated the disruption of the functions of ribosome and protein synthesis by GA (15:1), resulting in inhibition of bacterial growth and cell death. Genetic mutation of ferric uptake regulator (Fur) led to GA (15:1) tolerance in in vitro-induced resistant derivatives, while overexpression of Fur led to increased GA (15:1) susceptibility. Additionally, GA (15:1) significantly decreased the bacterial loads of S. aureus strain USA300 in the lung tissues of mice in a pneumonic murine model. Conclusively, this study revealed an antimicrobial mechanism of GA (15:1) involving cross talk with iron homeostasis against Gram-positive pathogens. In the future, the natural product GA (15:1) might be applied to combat infections caused by Gram-positive pathogens. IMPORTANCE The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity. However, its antibacterial mechanisms remain unclear. Our current study found that the function of ferric uptake regulator (Fur) was highly correlated with the antimicrobial activity of GA (15:1) against E. faecalis and that the antibacterial activity of GA (15:1) could be strengthened by the disruption of iron homeostasis. This study provided important insight into the mode of action of GA (15:1) against Gram-positive bacteria and suggested that GA (15:1) holds the potential to be an antimicrobial treatment option for infection caused by multidrug-resistant Gram-positive pathogens.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Enterococcus faecalis/drug effects , Gram-Positive Bacterial Infections/drug therapy , Iron/metabolism , Plant Extracts/administration & dosage , Salicylates/administration & dosage , Staphylococcus aureus/drug effects , Animals , Enterococcus faecalis/metabolism , Female , Ginkgo biloba , Gram-Positive Bacterial Infections/microbiology , Homeostasis/drug effects , Humans , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Staphylococcus aureus/metabolism
15.
Org Biomol Chem ; 19(47): 10390-10402, 2021 12 08.
Article in English | MEDLINE | ID: mdl-34825694

ABSTRACT

Bromotrimethylsilane (TMSBr)-promoted intramolecular cyclization of (o-arylethynyl)benzyl ethers to form 1H-isochromenes at room temperature is reported. Further studies indicated that vinyl carbocations are the reaction intermediates which are stabilized by the conjugated aryl groups. Thus, O-addition of benzyl ethers/tetrahydropyrans to alkynes was achieved under metal-free, acidic conditions. These reaction conditions were compatible with an alkynyl Prins reaction; therefore, 1H-isochromenes were produced directly from alkynyl benzaldehydes and alkynyl alcohols using a one-pot procedure.

16.
Dev Comp Immunol ; 106: 103638, 2020 05.
Article in English | MEDLINE | ID: mdl-32017956

ABSTRACT

Small heat shock proteins (shsps) are conserved across invertebrate species. They are implicated in the modulation of various biological processes, such as immune responses, abiotic stress tolerance metamorphosis, and embryonic development. Herein, we identified a heat shock protein 20 from the red swamp crayfish, Procambarus clarkii (named as Pc-Hsp20), and performed in vivo studies to elucidate its physiological functions in the innate immunity. The open reading frame of Pc-Hsp20 was 609 base pair, encoding a protein of 202 amino acid residues with a hsp20/alpha crystallin family domain. Pc-Hsp20 was ubiquitously expressed in various tissues; however, it was highest in the hepatopancreas. The challenge with immune elicitors remarkably enhanced the transcript level of Pc-Hsp20 in the hepatopancreas when compared with the control. Administration of double-stranded RNA could significantly reduce expression of the Pc-Hsp20 mRNAs, and most of the immune-related genes expression enhanced with a variable concentration in the hepatopancreas. Altogether, these results suggest that Pc-Hsp20 may participate in innate immunity against microbial pathogens.


Subject(s)
Arthropod Proteins/genetics , Astacoidea/immunology , HSP20 Heat-Shock Proteins/genetics , Hepatopancreas/physiology , Infections/immunology , Animals , Arthropod Proteins/metabolism , Cloning, Molecular , HSP20 Heat-Shock Proteins/metabolism , Immunity, Innate , Phylogeny , Protein Domains/genetics , RNA, Double-Stranded/immunology , Sequence Alignment , Stress, Physiological , Transcriptome , alpha-Crystallins/genetics
17.
Int J Syst Evol Microbiol ; 70(3): 1672-1677, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31935174

ABSTRACT

Strain XY-J91T, a Gram-stain-negative, reddish orange, non-spore-forming and short-rod-shaped marine bacterium, was isolated from rhizosphere soil of the mangrove plant Kandelia candel (L.) Druce in Mai Po Nature Reserve, Hong Kong. The strain showed growth at 15-50 °C (optimum 40 °C), at pH 5.5-9.5 (optimum 7.0-8.0) and with 0-8 % (w/v) NaCl (optimum 1-2 %). The only respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified phospholipid. The G+C content of strain XY-J91T was 40.4 mol%. Strain XY-J91T exhibited highest 16S rRNA gene sequence similarities to the type strains of Algoriphagus marincola SW-2T (96.66 %), Algoriphagus taiwanensis CC-PR-82T (96.21%), Algoriphagus ornithinivorans JC2052T (96.16%), Algoriphagus confluentis HJM-2T (95.73%) and Algoriphagus zhangzhouensis 12C11T (95.52 %). Based on the phylogenetic, phenotypic and chemotaxonomic evidence presented, strain XY-J91T represents a novel species of the genus Algoriphagus, for which the name Algoriphagus kandeliae sp. nov. is proposed. The type strain is XY-J91T (=MCCC 1K03612T=KCTC 72216T).


Subject(s)
Bacteroidetes/classification , Phylogeny , Rhizophoraceae/microbiology , Rhizosphere , Soil Microbiology , Bacterial Typing Techniques , Bacteroidetes/isolation & purification , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Hong Kong , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistry
18.
Front Hum Neurosci ; 12: 279, 2018.
Article in English | MEDLINE | ID: mdl-30050420

ABSTRACT

Objective: Genetic variation, especially polymorphism of the dopamine D4 receptor gene (DRD4), has been linked to deficits in self-regulation and executive functions and to attention deficit hyperactivity disorder (ADHD), and is related to the structural and functional integrity of the default mode network (DMN), the executive control network (ECN) and the sensorimotor network (SMN). The aim of this study was to explore the effects of the 2-repeat allele of the DRD4 gene on brain network connectivity and behaviors in children with ADHD. Methods: Using independent component analysis (ICA) and dimension analyses, we examined resting-state functional magnetic resonance imaging (fMRI) data obtained from 52 Asian medicine-naive children with ADHD (33 2-repeat absent and 19 2-repeat present). Results: We found that individuals with 2-repeat absent demonstrated increased within-network connectivity in the right precuneus of the DMN, the right middle frontal gyrus (MFG) of the SMN compared with individuals with 2-repeat present. Within the ECN, 2-repeat absent showed decreased within-network connectivity in the left inferior frontal gyrus (IFG) and the left anterior cingulate cortex. A deeper study found that connectivity strength of the left IFG was directly proportional to the Stroop reaction time in 2-repeat absent group, and as well as the right MFG in 2-repeat present group. Conclusion: Polymorphisms of the DRD4 gene, specifically 2-repeat allele, had effects on the ECN, the SMN and the DMN, especially in the prefrontal cortex (PFC) circles. ADHD children with DRD4 2-repeat allele have aberrant resting-state within-network connectivity patterns in the left IFG and the right MFG related to dysfunction in inattention symptom. This study provided novel insights into the neural mechanisms underlying the effects of DRD4 2-repeat allele on ADHD.

19.
PLoS One ; 11(10): e0164221, 2016.
Article in English | MEDLINE | ID: mdl-27716782

ABSTRACT

BACKGROUND AND PURPOSE: Understanding the anatomy of the anterior septal vein (ASV) is critical for minimally invasive procedures to the third ventricle and for assessing lesion size and venous drainage in the anterior cranial fossa. Accordingly, this study evaluated topographic anatomy and anatomic variation of the ASV using susceptibility-weighted imaging (SWI). METHODS: Sixty volunteers were examined using a 3.0T MR system. The diameter of the ASV and distance between bilateral septal points were measured. ASVs were divided into types 1 (only drains frontal lobe) and 2 (drains both frontal lobe and head of the caudate nucleus). We evaluated the ASV-internal cerebral vein (ICV) junction based on its positional relationship with the appearance of a venous angle or a false venous angle and the foramen of Monro. Fused SW and T1-weighted images were used to observe positional relationships between the course of the ASV and the surrounding brain structures. RESULTS: The ASV and its small tributaries were clearly visualized in 120 hemispheres (100%). The average diameter of ASVs was 1.05±0.17 mm (range 0.9-1.6 mm). The average distance between bilateral septal points was 2.23±1.03 mm (range 1.3-6.6 mm). The ASV types 1 and 2 were in 77 (64.2%) and 43 (35.8%) hemispheres, respectively. In 83 (69.2%) hemispheres, the ASV-ICV junction was situated at the venous angle and the posterior margin of the foramen of Monro. In 37 (30.8%) hemispheres, the ASV-ICV junction was situated beyond the posterior margin of the foramen of Monro. The average distance between the posteriorly located ASV-ICV junction and the posterior margin of the foramen of Monro was 6.41±3.95 mm (range 2.4-15.9 mm). CONCLUSION: Using SWI, the topographic anatomy and anatomic variation of the ASV were clearly demonstrated. Preoperative assessment of anatomic variation of the ASV may be advantageous for minimally invasive neurosurgical procedures.


Subject(s)
Anatomic Variation/physiology , Cerebral Veins/anatomy & histology , Cerebral Veins/physiology , Adult , Caudate Nucleus/physiology , Female , Frontal Lobe/physiology , Humans , Male , Neurosurgical Procedures/methods , Third Ventricle/blood supply , Third Ventricle/physiology
20.
PLoS One ; 10(10): e0141513, 2015.
Article in English | MEDLINE | ID: mdl-26506095

ABSTRACT

BACKGROUND AND PURPOSE: Thalamostriate vein (TSV) is an important tributary of the internal cerebral vein, which mainly drains the basal ganglia and deep medulla. The purpose of this study was to explore the anatomic variation and quality of TSV and its smaller tributaries using susceptibility-weighted imaging (SWI). METHODS: We acquired SWI images in 40 volunteers on a 3.0T MR system using an 8-channel high-resolution phased array coil. The frequencies of the TSV and its tributaries were evaluated. We classified TSV into types I (forming a venous angle) and II (forming a false venous angle). We classified anterior caudate vein (ACV)into types 1 (1 trunk) and 2 (2 trunks) as well as into types A (joiningTSV), B (joining anterior septal vein), and C (joining the angle of both veins). RESULTS: The TSV drains the areas of caudate nucleus, internal capsule,lentiform nucleus, external capsule, claustrum, extreme capsule and the white matter of the frontoparietal lobes,except thalamus. The frequencies of the TSV, ACV and transverse caudate vein (ACV) were 92.5%, 87.5% and 63.8%, respectively. We found TSV types I and II in 79.7%, and 20.3% with significantly different constitution ratios (P< 0.05). The most common types of ACV were type 1 (90.0%) and type A (64.3%). CONCLUSION: The complex three-dimensional (3D) venous architecture of TSV and its small tributaries manifests great variation, with significant and practical implications for neurosurgery.


Subject(s)
Anatomic Variation , Cerebral Veins/anatomy & histology , Diagnostic Imaging , Magnetic Resonance Imaging , Adult , Caudate Nucleus/anatomy & histology , Caudate Nucleus/diagnostic imaging , Cerebral Cortex/blood supply , Cerebral Veins/diagnostic imaging , Female , Humans , Jugular Veins/anatomy & histology , Jugular Veins/diagnostic imaging , Male , Radiography , Thalamus/blood supply
SELECTION OF CITATIONS
SEARCH DETAIL
...