New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

Antimicrobial peptides (AMPs) have a broad spectrum of activity and unspecific mechanisms of action. Therefore, they are seen as valid alternatives to overcome clinically relevant biofilms and reduce the chance of acquired resistance. This paper reviews AMPs and anti-biofilm AMP-based strategies and discusses ongoing and future work. Recent studies report successful AMP-based prophylactic and therapeutic strategies, several databases catalogue AMP information and analysis tools, and novel bioinformatics tools are supporting AMP discovery and design. However, most AMP studies are performed with planktonic cultures, and most studies on sessile cells test AMPs on growing rather than mature biofilms. Promising preliminary synergistic studies have to be consubstantiated and the study of functionalized coatings with AMPs must be further explored. Standardized operating protocols, to enforce the repeatability and reproducibility of AMP anti-biofilm tests, and automated means of screening and processing the ever-expanding literature are still missing.     

Trace elements (copper,zinc, selenium and molybdenum) as markers in oral sub mucous fibrosis and oral squamous cell carcinoma

Oral cancer is a major cause of cancer morbidity and mortality worldwide and is prevalent in most areas where tobacco related practices are observed. Essential elements play a role in many biochemical reactions as a micro-source and there is growing evidence that their concentrations are altered on the onset and progress of malignant disease. In this study the levels of copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo) in serum of patients with oral sub mucous fibrosis (OSMF) (n = 30) and oral squamous cell carcinoma (OSCC) (n = 30); were determined and the alterations of these critical parameters were analyzed in comparison with controls (n = 30) to identify predictors amongst these parameters for disease occurrence and progression. The serum Cu and Zn were established using Flame Atomic Absorption Spectrometry. Serum estimation of Se and Mo was done by graphite furnace atomic absorption spectrometry (GFAAS). Data analysis revealed a marked, progressive and significant increase in Cu levels in precancer (OSMF) and cancer (OSCC) groups as compared to the normal group. The level of Zn in serum was slightly elevated in OSMF and OSCC though not statistically significant. Cu/Zn ratio was slightly but not significantly elevated. Serum levels of Se and Mo were significantly decreased in the precancer and cancer groups as compared to the normals.     

不同剂量丹参注射液联合泼尼松龙治疗口腔粘膜下纤维性变的临床研究

目的：探讨采用不同剂量的丹参注射液联合波尼松龙治疗口腔粘膜下纤维性病的治疗效果,为今后的治疗提供更多的依据。方法：选择从2010年1月至2013年1月期间在我院口腔科治疗的100例口腔粘膜下纤维性病患者,根据门诊号,随机将患者分为低剂量组、次低剂量组、中剂量组、高剂量组和对照组,每组各20例,低剂量组、次低剂量组、中剂量组、高剂量组,分别使用不同剂量丹参注射液联合波尼松龙治疗,对照组单纯使用波尼松龙治疗,观察治疗一个疗程后患者口腔粘膜情况及张口度。结果：中剂量组和高剂量组情况改善要明显好于低剂量、次低剂量组、对照组,差异具有显著性（P〈0．05）。结论：丹参注射液联合泼尼松龙治疗口腔粘膜下纤维性病疗效令人满意,其中低剂量丹参注射液便有效果,一定范围内剂量越高,疗效越好,值得在临床推f,     

口腔雾化药物吸入联合小儿双金清热口服液治疗疱疹性口炎的临床疗效

目的:研究口腔雾化药物吸入联合小儿双金清热口服液治疗疱疹性口炎的临床疗效。方法:选择2012年5月至2014年5月在我院接受治疗的疱疹性口炎患者122例实施研究。根据数字法随机分成观察组及对照组各61例,观察组给予口腔雾化药物吸入以及小儿双金清热口服液进行治疗,对照组单纯给予小儿双金清热口服液进行治疗,对比两组治疗后的疗效、相关康复指标以及治疗后的不良反应。结果:观察组的总有效率是98.36%,显著高于对照组的88.52%,差异有统计学意义(P0.05)。观察组的热退时间和疱疹消退时间以及康复时间均分别显著少于对照组,差异均有统计学意义(均P0.05)。观察组治疗后的总不良反应发生率与对照组相比,差异无统计学意义(P0.05)。结论:利用口腔雾化药物吸入联合小儿双金清热口服液对疱疹性口炎患儿进行治疗,效果较好,安全性更高,值得在临床上推广应用。     

Human Papillomavirus (HPV) 16 E6 seropositivity is elevated in subjects with oral HPV16 infection

IntroductionHuman Papillomavirus (HPV) 16 E6 serum antibodies are common in people with HPV-related oropharyngeal cancers (HPV-OPC), but not the general population. We explored HPV16 seroprevalence in people with and without oral HPV16 infection, the cause of HPV-OPC.MethodsOral rinse samples were collected semiannually and tested for 36 types of HPV DNA by PCR. HPV16 E6 serum antibodies were tested at the visit of first oral HPV detection in participants with prevalent (n = 54), or incident (n = 39) oral HPV16 DNA; or at baseline in matched participants with no oral HPV16 DNA (n = 155) using multiplex serology assay. Predictors of seropositivity were examined using logistic regression.ResultsHPV16 E6 seropositivity (7.5% vs 0.7%; p = 0.005) but not seropositivity to the other HPV16 antigens, was significantly more common in those with than without oral HPV16 infection. There were only 8 HPV16 E6 seropositive participants, but oral HPV16 DNA remained a strong predictor of E6 seropositivity after adjustment for other risk factors (aOR = 14.6 95%CI, 1.7–122.5). Seroprevalence was similar in those with prevalent (7.4%; 4/54), and incident (7.7%; 3/39) oral HPV16 infection (p = 1.00). E6 seroprevalence was associated with reduced oral HPV16 clearance, but was not statistically significant (HR = 0.65 95% CI, 0.16–2.70).Seropositive participants were primarily male (87.5%), HIV-positive (75.0%; median CD4 cell-count of 840) and had oral HPV16 DNA (87.5%). History of an HPV-related cancer (0/8) or HPV-related anogenital dysplasia (1/8) was rare, and 4 participants had recent screening showing no anogenital dysplasia.DiscussionHPV16 E6 seropositivity was higher among people with than without oral HPV16 infection, despite no known anogenital disease in these participants.     

Classification of Chinese herbs based on the cluster analysis of delayed luminescence

Traditional Chinese material medica are an important component of the Chinese pharmacopeia. According to the traditional Chinese medicinal concept, Chinese herbal medicines are classified into different categories based on their therapeutic effects, however, the bioactive principles cannot be solely explained by chemical analysis. The aim of this study is to classify different Chinese herbs based on their therapeutic effects by using delayed luminescence (DL). The DL of 56 Chinese herbs was measured using an ultra‐sensitive luminescence detection system. The different DL parameters were used to classify Chinese herbs according to a hierarchical cluster analysis. The samples were divided into two groups based on their DL kinetic parameters. Interestingly, the DL classification results were quite consistent with classification according to the Chinese medicinal concepts of ‘cold’ and ‘heat’ properties. In this paper, we show for the first time that by using DL technology, it is possible to classify Chinese herbs according to the Chinese medicinal concept and it may even be possible to predict their therapeutic properties. Copyright © 2015 John Wiley & Sons, Ltd.     

Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.     

环氧合酶-2/5-脂氧合酶抑制剂对酒精相关性口腔癌的抑制作用

目的:分析和比较选择性环氧合酶-2 (Cox-2)抑制剂塞来昔布、5-脂氧合酶(5-Lox)抑制剂齐留通及Cox/5-Lox双酶抑制剂利克飞龙对酒精相关性口腔癌的抑制作用。方法:选择66只C57BL/6小鼠,分为阴性对照组、模型组(4NQO组)、阳性对照组、齐留通干预组、塞来昔布干预组和利克飞龙干预组。阴性对照组不做任何处理,其余各组饮用50μg/m L四硝基喹啉-1-氧化物(4NQO)溶液16周后,阳性对照组及各干预组以8%酒精溶液代替饮用水喂养8周,同时开始分别用三蒸水和同等药量的齐留通、塞来昔布、利克飞龙(100 mg·kg-1·d-1)灌胃8周;于24周处死动物,取舌行组织病理学观察、BrdU免疫组化染色、蛋白质印迹法(Western-blot)检测舌组织中5-Lox、Cox-2蛋白的表达。结果:饮用酒精后,口腔癌发生率从16.7%增加到58.3%,5-Lox、Cox-2蛋白表达显著增加癌组织中BrdU阳性率显著升高。齐留通干预后,口腔癌发生率(41.7%)显著降低,5-Lox表达显著减少,Cox-2表达显著增加,Brd U阳性率显著降低;塞来昔布干预后,口腔癌发生率(50.0%)显著降低,Cox-2表达显著减少,5-Lox表达显著增加,BrdU阳性率显著降低;利克飞龙干预后,口腔癌发生率(25%),Brd U阳性率与阳性对照组、齐留通干预组和塞来昔布干预组相比均显著降低,5-Lox、Cox-2蛋白表达比阳性对照组显著减少(P0.05)。结论:酒精促进口腔癌变的过程可能与5-Lox和Cox-2的表达上调关系密切;齐留通和塞来昔布可以分别抑制5-Lox和Cox-2活性,使口腔癌的发生率显著降低;利克飞龙对口腔癌的抑制作用优于齐留通和塞来昔布。     

Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus

Orientia tsutsugamushi (Ott) is a causative agent of chigger‐borne zoonosis, scrub typhus which is life threatening and highly pervasive illness in humans. In this report, we have mined and classified the proteins involved in pathways unique to Ott by using high‐throughput computational techniques. The 12 metabolic pathways were found to be unique to the pathogen. Forty‐six proteins were reported to be essential for the pathogen's survival and non‐homologous to the humans. The proteins were categorized into different classes, ie, enzymes, transporters, DNA‐binding, secretory, and outer membrane proteins. Further, in silico analysis of 46 proteins showed that 25 proteins were suitable therapeutic targets with known druggable properties. The structural modeling of B3CSG3 (MurA) protein was carried out and catalytic site essential for its functioning was analyzed. Virtual screening of chemical compounds was performed against modeled structure. The docking study by AutodockVina reported compound from PubChem with CID: 16036947 as best and potential inhibitor by means of docking score and binding affinity. The reliability and stability of the MurA‐16036947 complex were confirmed with molecular dynamics simulation. The report will provide insight to understand the mechanism of pathogenesis of Ott and instigate the development of effective treatment strategies against this disease.