Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). Methods: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. Results: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. Conclusion Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.

Objective:To explore the impact of adverse drug events (ADE) on readmission in renal transplant recipients and survival of the transplanted kidney.Methods:The hospital information system was searched and medical records of patients who underwent renal transplantation in Beijing Road Medical Area of Xinjiang Military Region General Hospital from January 2008 to December 2018 and were re-admitted at least once (as of December 2020) were collected and analyzed retrospectively. Patient information such as gender, age, weight, ethnicity, kidney transplantation status, postoperative immunosuppressive treatment plan, readmission status, and kidney transplant survival time was extracted and the ADE signals were detected through reviewing the patient re-admission medical history using a self-established global trigger tool. The correlation between ADE and readmission was evaluated by Karch and Lasagna method; patients were included in the ADE-related readmission group (ADE admission group) and the non-ADE-related readmission group (non-ADE admission group) based on the correlation results. The clinical characteristics and the cumulative survival rate of kidney transplants between the 2 groups were compared.Results:A total of 198 patients (1 426 times of readmission) were entered in the analysis, including 154 males and 44 females with an age of 14-62 years, and 118(59.6%) were Han nationality. The immunosuppressive drugs included cyclosporine, tacrolimus, sirolimus, etc. After renal transplantation, 240 times of readmission (16.8%) in 94 patients (47.5%) were associated with ADE. In the ADE readmission group, the number of diagnosed diseases and postoperative readmission times were more and the length of hospital stay was longer than those in the non-ADE readmission group [4 (3,6) vs. 3 (2,5), P=0.001; 6(3, 9) times vs. 4 (2, 8) times, P=0.022; 20(13, 33) days vs. 14 (11, 25) days, P=0.010]. Kaplan-Meier curve showed that the 1-, 3-, 5-, and 10-year cumulative survival rates of kidney transplants were 90.1%, 84.1%, 79.0%, and 57.6% in ADE-related readmission group, which were 99.0%, 94.7%, 90.8%, and 80.4% in non-ADE-related readmission, and the difference was statistically significant ( P=0.001). Conclusions:ADE can increase the readmission times, prolong the length of hospital stay, and reduce the cumulative survival rate of kidney transplants. The monitoring of ADE in renal transplant recipients should be strengthened.

Objective:To explore the impact of adverse drug events (ADE) on readmission in renal transplant recipients and survival of the transplanted kidney.Methods:The hospital information system was searched and medical records of patients who underwent renal transplantation in Beijing Road Medical Area of Xinjiang Military Region General Hospital from January 2008 to December 2018 and were re-admitted at least once (as of December 2020) were collected and analyzed retrospectively. Patient information such as gender, age, weight, ethnicity, kidney transplantation status, postoperative immunosuppressive treatment plan, readmission status, and kidney transplant survival time was extracted and the ADE signals were detected through reviewing the patient re-admission medical history using a self-established global trigger tool. The correlation between ADE and readmission was evaluated by Karch and Lasagna method; patients were included in the ADE-related readmission group (ADE admission group) and the non-ADE-related readmission group (non-ADE admission group) based on the correlation results. The clinical characteristics and the cumulative survival rate of kidney transplants between the 2 groups were compared.Results:A total of 198 patients (1 426 times of readmission) were entered in the analysis, including 154 males and 44 females with an age of 14-62 years, and 118(59.6%) were Han nationality. The immunosuppressive drugs included cyclosporine, tacrolimus, sirolimus, etc. After renal transplantation, 240 times of readmission (16.8%) in 94 patients (47.5%) were associated with ADE. In the ADE readmission group, the number of diagnosed diseases and postoperative readmission times were more and the length of hospital stay was longer than those in the non-ADE readmission group [4 (3,6) vs. 3 (2,5), P=0.001; 6(3, 9) times vs. 4 (2, 8) times, P=0.022; 20(13, 33) days vs. 14 (11, 25) days, P=0.010]. Kaplan-Meier curve showed that the 1-, 3-, 5-, and 10-year cumulative survival rates of kidney transplants were 90.1%, 84.1%, 79.0%, and 57.6% in ADE-related readmission group, which were 99.0%, 94.7%, 90.8%, and 80.4% in non-ADE-related readmission, and the difference was statistically significant ( P=0.001). Conclusions:ADE can increase the readmission times, prolong the length of hospital stay, and reduce the cumulative survival rate of kidney transplants. The monitoring of ADE in renal transplant recipients should be strengthened.

Objective To observe the targeting function of high affinity anti-EGFR monoclonal antibody (Cetuximab)conjugated superparamagnetic iron oxide-dopamine (anti-EGFR-PEG-SPIO) lung cancer cells via epidermal growth factor receptor (EGFR),as well as the feasibility for surveillance of tumor targeting with MRI.Methods Nanoparticles (NPs)of anti-EGFR-PEG-SPIO and PEG-SPIO were prepared,and the morphology of nanoparticles was observed with transmission electron microscope (TEM).The hydrodynamic diameter and R2 values of nanoparticles before and after conjugation with anti-EGFR were performed with dynamic light scattering (DLS) and MRI.MRI was performed in incubation with anti-EGFR-PEG-SPIO and PEG-SPIO after 2 h in vitro.The cellular uptake of anti-EGFR-PEG-SPIO and PEG-SPIO was further evaluated using Prussian blue staining and TEM.Results Anti-EGFR-PEG-SPIO and PEG-SPIO showed signal intensity of H460 cells on T2WI,decreased significantly compared with PEG-SPIO.The rate of signal intensity change was -58.2％,-82.7％,-94.4％ and-98.3％,respectively,at iron concentrations of (0,10,20,40,80 μg/ml) of antiEGFR-PEG-SPIO.Prussian blue staining and TEM showed that a lot of intracellular irons of anti-EGFR-PEG-SPIO were observed in H460 cells,but few of PEG-SPIO.Conclusion The effect of active targeting via anti-EGFR in EGFR overexpressed cells can be achieved with anti-EGFR-PEG-SPIO in H460 cells in vitro,and the targeting delivery process could be monitored with 3.0T MRI.

OBJECTIVETo study the toxic effect of toremifene (TOR) and its synergistic effect with cisplatin (DDP) on human lung adenocarcinoma cell line A549.

METHODSThe cytotoxic effects of these agents on human lung cancer cell line A549 were monitored by a tetrazolium-based colorimetric assay (MTT assay). The cell cycle and DNA content were detected by flow cytometer technic. p21 expression level was monitored by Western blot.

RESULTSToremifene inhibited the growth of A549 cell, with > or = 5 micromol/L significantly enhancing the chemosensitivity of cisplatin. TOR enhanced the antitumor activity of DDP at S, G(2) and M phases of cells. And p21 expression was increased after TOR and DDP had been given.

CONCLUSIONToremifene (> or = 5 micromol/L) combined with cisplatin shows significant synergistic anti-tumor effect on A549 cells.

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Division ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Lung Neoplasms ; pathology ; Toremifene ; pharmacology ; Tumor Cells, Cultured

Objective: To study the role of inducible nitric oxide synthase (iNOS) in activated macrophages and nitric oxide (NO) in the defence against tumors. Methods: Macrophages were obtained by alveolar lavages of mice and activated through incubation with recombinant murine INF? in vitro. P815 cells were added to the culture. Culture supernates were collected to measure the activity of iNOS and NO. Tumoricidal activity of macrophages was determined in presence and absence of the specific inhibitor of NO synthase: L NMMA. Results: NO production and activity of iNOS induced by activated macrophages were positively related with concentration of INF? in macrophage P815 coculture. The addition of L NMMA to the culture suppressed NO production, the inhibitory rate of activated macrophages against P815 cells was reduced distinctly ( P