羟基磷灰石复合支架负载抗菌性药物:药物与支架的相互作用机制

背景:骨修复材料植入后引起的局部感染是最严重的手术并发症之一,提高植入部位的抗菌药物的作用效果是非常必要的。目的:综述基于羟基磷灰石支架载抗菌性药物的方式、抗菌性药物的种类以及药物与支架之间的相互作用,总结该载药体系的发展趋势。方法:检索CNKI数据库、PubMed数据库及Web of Science数据库中收录的相关文献,中文检索词为“羟基磷灰石,骨组织工程,骨修复,骨感染,药物递送,抗菌”,英文检索词为“hydroxyapatite,bone tissue engineering,bone repair,bone infection,drug delivery,antibacterial”,查阅1997年1月至2021年1月期间基于羟基磷灰石复合支架载抗菌性药物的相关文章,包括综述、基础研究及临床研究。结果与结论:在羟基磷灰石复合支架材料上负载抗菌性药物能有效提高局部药物浓度,同时避免引发全身毒性,更好地促进骨组织再生。羟基磷灰石复合支架负载抗菌性药物具有良好的药物缓释效果和抗感染功效。但是药物的掺入会潜在地影响磷酸钙类支架材料的力学性能,目前制备抗菌性药物递送体系的挑战在于:在不影响载体机械性能的同时负载足够量的药物分子,同时也要考虑该浓度对细胞和组织的毒性大小。组织工程支架的制备工艺还有待进一步的提高,药物与支架之间的相互作用机制还有待进一步的探究。

Genetic Study on JS399-19 Resistance in Hyphal Fusion of Fusarium graminearum by Using Nitrate Nonutilizing Mutants as Genetic Markers

Twenty-two nitrate nonutilizing （nit） mutants were recovered from five wild-type isolates of Fusarium graminearum and fifty nit mutants were recovered from three JS399-19-resistant mutants of F. graminearum cultured on MMC medium. Some biological properties were compared between nit mutants and their parental isolates. The results showed that there were no significant differences in growth rate, cultural characters or pathogenicity between JS399-19-resistant nit mutants and their parental isolates. But the conidial production and the sexual reproduction ability changed to some extent. There was no cross resistance toward chlorate and JS399-19 in F. graminearum and the resistance could be stable through 20-time subcultures. Therefore, the nit could be used as a genetic marker for studying the genetics of JS399-19 resistance in E graminearum, which was used to study JS399-19 resistance transferability in hyphal fusion. Resistance in JS399-19 could not be transferred by hyphal fusion or could be transferred with low chance between two compatible isolates, which would delay the development of JS399-19 resistance in the field.

Synthesis and Antibacterial Effect of New Alkylenedibiguanides

Seven new alkylenedibiguanides were synthesized and comfirmed by 1H NMR, MS and elemental analyses. The preliminary test in vitro showed that some of them had potential antibacterial activities.

盆腔炎汤联合穴位敷贴治疗慢性盆腔炎的临床研究

目的:探究盆腔炎汤与穴位敷贴对慢性盆腔炎的治疗效果。方法:选取2019年10月至2021年10月中医科收治的94例慢性盆腔炎患者作为研究对象,采用随机数字表法分成观察组与对照组,其中观察组45例,对照组49例。对照组患者接受常规抗菌性药物治疗,在此基础上,观察组患者加服盆腔炎汤、外用中药穴位敷贴进行联合治疗。对两组患者治疗前后的症状积分(白带增多、下腹坠痛、腰骶不适、月经不调)、炎症介质水平[肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)]、血浆黏度、全血低切黏度、全血高切黏度以及治疗后临床疗效等进行比较。结果:两组患者经过连续4周治疗后,其炎症介质水平、血浆黏度、全血低切黏度以及全血高切黏度较治疗前均有所改善,且差异具有统计学意义(P<0.05);且相较于对照组,观察组指标改善情况更为明显,两组之间差异具有统计学意义(P<0.05);治疗后,观察组临床疗效较对照组更优,两组之间差异具有统计学意义(P<0.05)。结论:较单一使用抗菌性药物治疗慢性盆腔炎,联合口服盆腔炎汤与外用中药穴位敷贴,其治疗效果更佳。

A Bioactive Diterpene from the Chinese Herb Aster souliei

Aster souliei Franch, (Compositae) is a. herbaceous plant distributed innorth China. It has been used in folk medicine as antipyretic, detoxicant, expectorant andantitussive. In an effort to find biologically active components from Chinese medicinal plants ' ,we have examined the aerial parts of this herb, leading to the isolation of a clerodane-typediterpene, 18, 19-dihydroxy-5α, 10β-neo-cleroda-3, 13 (l4)-dien-16, 15-butenolide (1). In thispaper we report the structural elucidation, and the antitumor and antibacterial activities of thiscompound. It was found that 1 possesses moderate cytotoxicity against human leukemia cells (HL-60)and activity against microorganisms.

Synthesis and Antifungal Activity of 1-(1H-1,2,4-Triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols

Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols were designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14α-sterol demethylase(CYP51) and the docking results of inhibitors to the active site of the enzyme. All title compounds were first by reported. Results of preliminary biological tests showed that most of title compounds exhibited activity against the seven common pathogenic fungi. Compound 11 showed best antifungal activity with broad antifungal spectrum and proved to be more active against Cryptococcus neoformans, Candida albicans, Microsporum lanosum and Trichophyton rubrum than ketoconazole. Compounds 3, 10 and 4 also had high activities.

Research Progress in Phage

With excessive utilization of antibiotics in recent years,bacterial drug resistance problem is serious increasingly,and it is more and more difficult to develop anti-infective drug,while it does not have these problems to use phage controlling disease.Phage is a kind of prokaryotic virus,widely exists in the nature and includes bacteriophage,cyanophage and actinophage.Due to its potential of replacing antibiotics to treat disease,phage receives more and more attention.In this paper,based on development status of phage research at home and abroad,discovery process,naming method and classification basis of phage are introduced comprehensively,and advantages and limitations of phage applying in prevention and control of bacterial diseases are analyzed.We introduce application status of phage in human medicine,prevention and control of diseases for terrestrial animals and aquaculture,and the effects of phage in sewage treatment,prevention and control of microbial contamination of food and detection technology,and point out the shortages of phage in the above application.Meanwhile,we also discuss application prospects of phage in disease prevention and control,environmental protection and food safety.

Antibacterial activity of panipenem/betamipron in vitro and its pharmacokinetics and therapeutic efficacy in patients with pulmonary infection

Objective: To investigate the in vitro antimicrobial activity of panipenem/betamipron to common clinical isolates, determine its pharmacokinetics in patients with pulmonary infection and evaluate its effectiveness and safety in treatment of pulmonary infection. Methods: (1) The minimal inhibition concentrations of panipenem/betamipron were determined in 247 clinical isolates by agar dilution method. The minimal bactericidal concentrations of panipenem/betamipron for some clinical isolates were also determined. (2) Twenty cases of pulmonary infection were treated with intravenous dripping of panipenem/betamipron at 500/500 mg every 12 h for 3-7 d. Panipenem/betamipron concentration in the plasma was consecutively measured, and bacterial culture was conducted and the efficacy was evaluated. Results: (1) The in vitro antimicrobial activity of panipenem/betamipron was almost the same as that of panipenem, indicating that panipenem played the major role in antimicrobial reaction. Panipenem/betamipron had a strong antimicrobial activity against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, β-Streptococcus hemolytic, Streptococcus pneumonia, micrococcus, Escherichia coli and Klebsiea pneumonia. The drug also showed a potent effect against Haemophilus influenzae,Enterobacter cloacae, Proteus and Pseudomonas aeruginosa (2) The peak value of panipenem/betamipron in plasma was (30.25±5.43) mg/L and the level decreased to (0.66±0.34) mg/L 6 h later. The half-life of distribution and elimination of panipenem in the plasma was (0.34±0.18) h and (1.42±0.31) h, respectively. (3) The eradication rate of bacteria was 77.8% and the effective healing rate was 75%. No adverse drug reaction was found. Conclusion: Panipenem/betamipron has a strong antimicrobial activity against clinical isolates and is effective and safe for treatment of pulmonary infection.

Characterization of β-lactamase from Escherichia coli with drug-resistance to ceftazidine

The antimicrobial susceptibility testing was performed with Kirby-Bauer disc diffusion and agar diffusion methods, and the crude β-lactamase was extracted by sonication with its isoelectric point （pI） determined with isoelectric focusing, and purified by two steps of chromatography. The genome DNA fragments of bacterial strains were amplified with PCR and subjected to sequencing. The kinetic parameters for β-lactamase were detected by spectrophoto metric method. It was found that the bacterial strains isolated from clinical specimens were resistant to penicillin, ceftazidine, cefotaxime and azitreonam, but sensitive to imipenem and cefoxitin, in which two resistant strains to ceftazidine were found to produce a single extended spectrum β-lactamase（ESBL） with pI value of 8.7. Results of cloning and sequencing of the β-lactamase encoding gene showed that this gene was similar to blactx-m-l with 6 point mutations including 3 silent mutations. The amino acid sequence derived from the nucleic acid data indicated that this enzyme was distinct from β-lactamse CTX-M-1 by 3 amino acids, i.e. Val-80→Ala, Asp-117→Asn and Ser-143→Ala（CTX-M-Ⅳ）. Molecular weight of this enzyjne was 29 kDa. Kinetic analysis of the partially purified β-lactamase confirmed that this enzyine was ＇able to hydrolyze cefotaxime and aztreonanl, but not to imipenem. In addition, the the β-lactamase was well inhibited by sulbactam（IC50 94 nM） and tazobactam（IC50 5 nM）. It is concluded that CTX-M-Ⅳ is a CTX-M-type extended spectrum β-lactamase.

Endophytes from medicinal plants and their potential for producing indole acetic acid, improving seed germination and mitigating oxidative stress

Medicinal plants have been used by marginal communities to treat various ailments. However, the potential of endophytes within these bio-prospective medicinal plants remains unknown. The present study elucidates the endophytic diversity of medicinal plants（Caralluma acutangula, Rhazya stricta, and Moringa peregrina） and the endophyte role in seed growth and oxidative stress. Various organs of medicinal plants yielded ten endophytes, which were identified as Phoma sp.（6 isolates）, Alternaria sp.（2）, Bipolaris sp.（1）, and Cladosporium sp.（1） based on 18 S rD NA sequencing and phylogenetic analysis. The culture filtrates（CFs; 25%, 50%, and 100% concentrations） from these endophytes were tested against the growth of normal and dwarf mutant rice lines. Endophytic CF exhibited dose-dependent growth stimulation and suppression effects. CF（100%） of Phoma sp. significantly increased rice seed germination and growth compared to controls and other endophytes. This growth-promoting effect was due to the presence of indole acetic acid in endophytic CF. The gas chromatography/mass spectrometry（GC/MS） analysis showed the highest indole acetic acid content（（54.31±0.21） μmol/L） in Bipolaris sp. In addition, the isolate of Bipolaris sp. exhibited significantly higher radical scavenging and anti-lipid peroxidation activity than the other isolates. Bipolaris sp. and Phoma sp. also exhibited significantly higher flavonoid and phenolic contents. The medicinal plants exhibited the presence of bio-prospective endophytic strains, which could be used for the improvement of crop growth and the mitigation of oxidative stresses.

A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents

A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-l,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher ef- ficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed.

Morphological and physiological comparison of taxa comprising the Sporothrix schenckii complex

Based on recent molecular data, it has been suggested that Sporothrix globosa is the main causal agent of sporotrichosis in China. The objective of this study was to compare the morphology, growth characteristics, patterns of carbon source usage, and susceptibility to antifungal agents among Sporothrix strains. A total of 15 clinical strains confirmed to be S. globosa, from three different regions of China, and 11 ex-type strains from the CBS-KNAW biodiversity center were obtained. The elongated conidia of S. pal/ida, S. variecibatus, S. schenckii, and S. schenckii luriei were clearly different from the subglobose and globose conidia of S. globosa strains. S. schenckii is able to assimilate sucrose, raffinose, and ribitol. Susceptibility profiles of these Sporothrix species were evaluated by measuring minimum inhibitory concentrations （MICs）. Fluconazole, itraconazole, terbinafine, and amphotericin B showed good activity against most S. globosa clinical isolates from China. Potassium iodide also showed a low MIC against S. pal/ida, while fluconazole showed a high MIC for S. mexicana, S. humicola, S. g/obosa, S. schenckii, and S. inflata; these strains might be considered tolerant. The species showed differences in susceptibility to antifungal drugs and should therefore be properly identified during diagnosis prior to designing therapeutic strategies.

New strategy for reversing biofilm-associated antibiotic resistance through ferrocene-substituted carborane ruthenium(Ⅱ)-arene complex

Bacterial biofilms are inherently resistant to antimicrobial agents and are difficult to eradicate with conventional antimicrobial agents, resulting in many persistent and chronic bacterial infections. In this contribution, a new strategy for reversing the biofilm-associated antibiotic resistance has been explored by induction of a carborane ruthenium(II)-arene complex (FcRuSB). Our results demonstrate that the FcRuSB could be utilized as an inducer to efficiently reverse the biofilm-associated antibiotic resistance of multidrug-resistant (MDR) clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa. The induced effect of FcRuSB is correlated with a considerable decrease in the expression of extracellular matrix proteins (EMP) of the two strains. The considerable decrease of the EMP of induced cells, resulting in the reduction of adherence and biofilm formation ability of the two types of MDR pathogens, and then can cause significantly enhanced sensitivity of them to antibiotics.