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

To establish the UPLC fingerprint of Zhongyi Angong Niuhuang Pills, in order to evaluate its quality by chemical pattern recognition. The method was developed on a column of Poroshell 120 EC-C_(18), with methanol-0.1% formic acid solution as the mobile phase for gradient elution at a flow rate of 0.4 mL·min~(-1). The column temperature was 30 ℃,and the detective wavelength was 254 nm. The similarity of 24 batches of Angong Niuhuang Pills was compared by using Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2004 A). Hydrophobic cluster analysis,principal components analysis and partial least squares discriminant analysis were conducted by using SIMCA 13.0 software to investigate different components among these products. The UPLC characteristic fingerprint was established in this study. And 17 common peaks were identified by standard reference and UPLC-MS. The similarity of 24 batches samples were above 0.980,which can be classified into three categories for pattern recognition. Baicalin,berberine,jatrorrhizine,wogonin and wogonoside were identified as the main markers that cause differences of various batches. The method is simple,rapid,accurate and reproducible,and can provide scientific basis for improving the quality standard of Zhongyi Angong Niuhuang Pills.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry

Ultrasonography plays an important role in liver surgery of colorectal cancer liver metastases. Recently, besides grey and doppler ultrasonography, contrast-enhanced ultrasonography, elastography and infusion-image technique has developed and attracted increasing interest. Intraoperative ultrasonography is applied for tumor detection, localization and characterization. It is also used for liver resection and planning surgical strategy, which may improve surgical effect and safety. This article discussed the application of intraoperative ultrasonography in liver resection of colorectal cancer liver metastases.

To establish the HPLC fingerprint and determine five index components (loganic acid， chlorogenic acid， loganin， sweroside and asperosaponin Ⅵ) of Zishen Yutai pills by high performance liquid chromatography, and provide a scientific basis for its quality control. The fingerprint chromatogram was analysed by the chromatographic fingerprint similarity evaluation system for tradition Chinese medicine (2012), fifteen common peaks were obtained at the wavelength of 254 nm. Different batches of Zishen Yutai pills showed a similarity of above 0.90 in HPLC fingerprint profiles. For the quantitive analysis method, The separation of five components showed good regression (>0.999 2) with linear ranges, and the mean recoveries were in the range of 97.62%-101.9%, with the RSD (=9) less than 3%. The established fingerprint and quantitative analysis methods are highly specific, simple and accurate, which can reflect the quality of Zishen Yutai pills more comprehensively, and can be used for its quality control.

Objective:To investigate the effect of MT01 on the differentiation of osteoblasts under infected condition through determining the expression level of collagen Ⅰ (Col Ⅰ )mRNA in MG63 cells treated with Porphyromonas gingivalis (Pg).Methods:The cultured MG63 cells were divided into blank control,MT01,Pg, and MT01+Pg groups.MT01 at a concentration of 1 mg·L-1 was added into the MG63 cells,and the cells were incubated for 3 h.The cells treated with PBS (1 mg·L-1 )were used as control group.Then Pg (MOI=100∶1) was added.Real-time PCR was used to detect the expression levels of ColⅠ mRNA in MG63 cells at 2,4,6,8, 12 and 24 h after incubation.Results:Compared with blank control group,the levles of ColⅠ mRNA in the MG63 cells in MT01 and MT01 + Pg groups had no significant changes at 2 and 4 h (P > 0.05);the Col Ⅰ mRNA expression levels in MT01 group at 8,12 and 24 h were increased (P < 0.05 or P < 0.01).Compared with Pg group,the expression levels of ColⅠ mRNA in MT01+ Pg at 2 and 4 h were decreased,but the expression levels of ColⅠ mRNA were increased at 6,8,12 and 24 h (P <0.05 or P <0.01).Conclusion:MT01 can up-regulate the expression level of Col Ⅰ mRNA in the infected MG63 cells; MT01 could promot the differentiation of osteoblasts under infected condition.

To improve the extraction of solanesol from tobacco waste, we developed an enzymatic cell wall-breaking process with combined cellulase and ligninase. The effects of reaction time, temperature, pH and enzyme/substrate ratio were determined. The results show that the catalytic effect was better than either single enzyme when the ratio of cellulase to ligninase was 15:1 (U/U). Under the optimized conditions of 175 U/g (enzymes/substrate), tobacco to water 1:5 (W/W), temperature 40 degrees C and pH 6.0, the concentration of solanesol in the solution could reach 0.33 g/L after 8 h. And the average leaching rate reached 96.53% which was 1.68 times of the extraction methods of chemical reflux. It provides new way for the extraction of solanesol from tobacco waste, and worthwhile to be further explored.
Cell Wall ; metabolism ; Cellulase ; metabolism ; Oxygenases ; metabolism ; Plant Leaves ; chemistry ; Terpenes ; isolation & purification ; Tobacco ; chemistry

Objective To explore the effects of alanyl-glutamine (Ala-Gln) dipeptide supplemented parenteral nutrition (PN) on the short-term outcomes in critically ill adult patients.Methods In this retrospective study,we reviewed the clinical data of critically ill adult patients who were treated by standard PN from January 2006 to December 2011.The length of stay in intensive care unit (ICU-LOS),incidences of infections and multiple organ dysfunction syndrome (MODS),and mortality were compared between the group of Ala-Gln dipeptide supplemented PN (intervention group) and the group of PN without Ala-Gln dipeptide (control group).Results Finially,617 cases were enrolled in the study,including 312 cases in the control group and 305 cases in the intervention group.The ICU-LOS was significantly shorter in the intervention group than that in the control group [(17.2 ± 6.5) d vs.(16.1 ± 5.3) d,P =0.011).Compared with the control group,the incidences of infection (42.9％ vs.33.1％,P =0.011) and MODS (46.5％ vs.38.0％,P =0.030) and the mortality (34.9％vs.25.9％,P =0.014) in the intervention group patients were significantly lower.Conclusion Ala-Gln dipeptide supplemented PN can improve the short-term outcomes of critically ill adult patients.

D5 receptor is a subtype of dopamine D1-like receptor, and it plays a functional role in many neurological disorders. Some natural compounds from Chinese herbs, which were shown to have the property as that of receptor agonist, might provide a rich source in search of new candidates for therapeutic use. For exploring this possibility, we developed a cell-based high throughput (HTS) D5 receptor assay to screen the herb-based natural compound library established in our centre. The D5 receptor plasmid (hD5R/pcDNA3.1) and reporter gene plasmid (4 x CRE/TK/Luci/pGL3) were co-transfected into HEK293 cell line. After G418 being selected, the monoclonal cell lines bearing hD5R and the reporter gene were established and used for agonist screening. To optimize the assay condition, the effects of some factors such as cell number per well, incubation time, and the doses of SKF38393 (a potent selective partial D1-like agonist) were examined by using forskolin, a positive compound for cAMP response element. The best condition for this HTS assay included: the cell number at 5 x 10(4)/mL, the dose of forskolin at 5-20 micromol/L, the dose of SKF38393 at 100 nmol/L-100 micromol/L, and the agonist incubation time at 6 -8 h. Thereafter, water extracts from more than 200 Chinese herbs in our library were screened and three of these water extracts showed positive activity, with higher or similar activity as SKF38393. In conclusion, we have established a cell-based HTS assay for D5 receptor agonist screening, and by use of this HTS assay, 3 Chinese herbs maybe contain components exhibiting D5 receptor agonist property. This work provides an alternative vision of how to use herb medicines and a way to develop potential drugs for treatment of neurological disorders.
Cell Line ; Dopamine Agonists ; isolation & purification ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; High-Throughput Screening Assays ; methods ; Humans ; Plants, Medicinal ; chemistry ; Receptors, Dopamine D5 ; agonists

OBJECTIVETo investigate the effect of the total flavonoids of orange peel (TFO) against adjuvant arthritis (AA) and the underlying mechanism.

METHODAA model was induced in male Wistar (correction of SD) rats by immunization with Freund's complete adjuvant Pad thickness was assayed by caliper. Pathological impairment of ankle joint was analysised by hematoxylin and eosin (H&E) staining. Levels of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and prostaglandin (PG) E2 in serum was detected by radioimmunoassay method. Cyclooxygenase (COX)-2 expression in synovium tissues was measured by Western blot assay.

RESULTThe 75 mg x kg(-1) and 150 mg x kg(-1) TFO treatment obviously decreased the pad thickness and improve the pathological impairment of ankle joint of AA rats. In addition, abnormal elevation of TNF-alpha, IL-1beta and PGE2 in serum and COX-2 expression in synovium tissues of AA rats were markedly repressed by TFO treatment.

CONCLUSIONTFO can inhibit the development of AA in rats, and the mechanism were likely due to depressing inflammatory mediators production.

Animals ; Arthritis, Experimental ; chemically induced ; drug therapy ; immunology ; Citrus sinensis ; chemistry ; Disease Models, Animal ; Flavonoids ; administration & dosage ; Freund's Adjuvant ; adverse effects ; Humans ; Interleukin-1 ; immunology ; Male ; Plant Extracts ; administration & dosage ; Random Allocation ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; immunology

Objective To explore the impacts of different nutrition support methods on short-term outcome in critically ill adult patients. Methods We retrospectively reviewed the clinical data of 1503 critically ill adult patients who needed nutrition support in an mixed intensive care unit (ICU) of a tertiary care university hospital from January 1994 to December 2009. The complication of nutrition support, length of stay (LOS) in ICU, morbidity of infection and multiple organ dysfunction syndrome (MODS), and mortality among different nutrition support methods were compared. Results The Nutritional Risk Screening (NRS) scores of the enrolled patients were no less than 3. LOS in early enteral nutrition (EN) patients were significantly shorter than those in not-early EN patients (P ＜ 0. 001) and parenteral nutrition (PN) patients (both P ＜ 0. 001). Infection rate (P ＜ 0. 001),morbidity of MODS (P ＜ 0. 001) and mortality (P ＜ 0. 001) were significantly lower than those in not-early EN and PN patients. LOS of patients receiving PN rich in glutamine (Gln) was significantly shorter than that in conventional formula (P = 0. 0000). Morbidity of infection (P= 0. 0252) and MODS (P = 0. 0030), mortality (P =0. 0305) were significantly lower than that of conventional patients. LOS of patients receiving intensive insulin therapy (IIT) was significantly shorter than that of controlled group (P = 0. 0000). Morbidity of infection (P =0. 0001) and MODS (P = 0. 0237) and mortality (P =0. 0427) were significandy lower than those of controlled group. Conclusions Nutritional risk is prevalent among critically ill adult patients. Early EN, PN of rich in Gln,and receiving IIT can shorten LOS, decrease morbidity of infection and MODS, and improve prognosis among these patients.