Bacterial biofilms are complex surface attached communities of bacteria held together by self-produced polymer matrixs mainly composed of polysaccharides, secreted proteins, and extracellular DNAs. Bacterial biofilm formation is a complex process and can be described in five main phases: (i) reversible attachment phase, where bacteria non-specifically attach to surfaces; (ii) irreversible attachment phase, which involves interaction between bacterial cells and a surface using bacterial adhesins such as fimbriae and lipopolysaccharide (LPS); (iii) production of extracellular polymeric substances (EPS) by the resident bacterial cells; (iv) biofilm maturation phase, in which bacterial cells synthesize and release signaling molecules to sense the presence of each other, conducing to the formation of microcolony and maturation of biofilms; and (v) dispersal/detachment phase, where the bacterial cells depart biofilms and comeback to independent planktonic lifestyle. Biofilm formation is detrimental in healthcare, drinking water distribution systems, food, and marine industries, etc. As a result, current studies have been focused toward control and prevention of biofilms. In an effort to get rid of harmful biofilms, various techniques and approaches have been employed that interfere with bacterial attachment, bacterial communication systems (quorum sensing, QS), and biofilm matrixs. Biofilms, however, also offer beneficial roles in a variety of fields including applications in plant protection, bioremediation, wastewater treatment, and corrosion inhibition amongst others. Development of beneficial biofilms can be promoted through manipulation of adhesion surfaces, QS and environmental conditions. This review describes the events involved in bacterial biofilm formation, lists the negative and positive aspects associated with bacterial biofilms, elaborates the main strategies currently used to regulate establishment of harmful bacterial biofilms as well as certain strategies employed to encourage formation of beneficial bacterial biofilms, and highlights the future perspectives of bacterial biofilms.

/pdf/beyond-risk-bacterial-biofilms-and-their-regulating-4xnboj91j5.pdf

Beyond Risk: Bacterial Biofilms and Their Regulating Approaches.

https://www.hal.inserm.fr/inserm-02437801/document

PML-regulated mitochondrial metabolism enhances chemosensitivity in human ovarian cancers

To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. Instead, we uncover previously unrecognized molecular and pathway events, for example, several miRNA target correlations present at protein but not at mRNA level. Notably, we identify two metabolic shifts in the citric acid cycle (TCA cycle) during prostate cancer development and progression. Our proteogenomic analysis uncovers robustness against genomic and transcriptomic aberrations during prostate cancer progression, and significantly extends understanding of prostate cancer disease mechanisms.

/pdf/integrative-proteomics-in-prostate-cancer-uncovers-sgo25m90d4.pdf

Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression.

Human oral cavity (mouth) hosts a complex microbiome consisting of bacteria, archaea, protozoa, fungi and viruses. These bacteria are responsible for two common diseases of the human mouth including periodontal (gum) and dental caries (tooth decay). Dental caries is caused by plaques, which are a community of microorganisms in biofilm format. Genetic and peripheral factors lead to variations in the oral microbiome. It has known that, in commensalism and coexistence between microorganisms and the host, homeostasis in the oral microbiome is preserved. Nonetheless, under some conditions, a parasitic relationship dominates the existing situation and the rise of cariogenic microorganisms results in dental caries. Utilizing advanced molecular biology techniques, new cariogenic microorganisms species have been discovered. The oral microbiome of each person is quite distinct. Consequently, commonly taken measures for disease prevention cannot be exactly the same for other individuals. The chance for developing tooth decay in individuals is dependent on factors such as immune system and oral microbiome which itself is affected by the environmental and genetic determinants. Early detection of dental caries, assessment of risk factors and designing personalized measure let dentists control the disease and obtain desired results. It is necessary for a dentist to consider dental caries as a result of a biological process to be targeted than treating the consequences of decay cavities. In this research, we critically review the literature and discuss the role of microbial biofilms in dental caries.

Oral microbial biofilms: an update

Effective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells. The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years. Antimicrobial dental materials based on antimicrobial agent release, contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface. Among the therapeutic approaches for managing biofilms in clinical practice, antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms, and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches. Nevertheless, more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data. The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.

/pdf/advancing-antimicrobial-strategies-for-managing-oral-biofilm-3lwqtv765w.pdf

Advancing antimicrobial strategies for managing oral biofilm infections

Effective management of biofilm-related oral infectious diseases is a global challenge. Oral biofilm presents increased resistance to antimicrobial agents and elevated virulence compared with planktonic bacteria. Antimicrobial agents, such as chlorhexidine, have proven effective in the disruption/inhibition of oral biofilm. However, the challenge of precisely and continuously eliminating the specific pathogens without disturbing the microbial ecology still exists, which is a major factor in determining the virulence of a multispecies microbial consortium and the consequent development of oral infectious diseases. Therefore, several novel approaches are being developed to inhibit biofilm virulence without necessarily inducing microbial dysbiosis of the oral cavity. Nanoparticles, such as pH-responsive enzyme-mimic nanoparticles, have been developed to specifically target the acidic niches within the oral biofilm where tooth demineralization readily occurs, in effect controlling dental caries. Quaternary ammonium salts (QAS) such as dimethylaminododecyl methacrylate (DMADDM), when incorporated into dental adhesives or resin composite, have also shown excellent and durable antimicrobial activity and thus could effectively inhibit the occurrence of secondary caries. In addition, custom-designed small molecules, natural products and their derivatives, as well as basic amino acids such as arginine, have demonstrated ecological effects by modulating the virulence of the oral biofilm without universally killing the commensal bacteria, indicating a promising approach to the management of oral infectious diseases such as dental caries and periodontal diseases. This article aims to introduce these novel approaches that have shown potential in the control of oral biofilm. These methods may be utilized in the near future to effectively promote the clinical management of oral infectious diseases and thus benefit oral health.

/pdf/novel-approaches-to-the-control-of-oral-microbial-biofilms-tg5q3qv2m7.pdf

Novel Approaches to the Control of Oral Microbial Biofilms

BACKGROUND

Resistance to chemotherapy represents a significant obstacle in prostate cancer therapeutics. Novel mechanistic understandings in cancer cell chemotherapeutic sensitivity and resistance can optimize treatment and improve patient outcome. Molecular alterations in the metabolic pathways are associated with cancer development; however, the role of these alterations in chemotherapy efficacy is largely unknown.



METHODS

In a bed-side to bench-side reverse translational approach, we used cDNA microarray and qRT-PCR to identify genes that are associated with biochemical relapse after chemotherapy. Further, we tested the function of these genes in cell proliferation, metabolism, and chemosensitivity in prostate cancer cell lines.



RESULTS

We report that the gene encoding mitochondrial malate dehydrogenase 2 (MDH2) is overexpressed in clinical prostate cancer specimens. Patients with MDH2 overexpression had a significantly shorter period of relapse-free survival (RFS) after undergoing neoadjuvant chemotherapy. To understand the molecular mechanism underlying this clinical observation, we observed that MDH2 expression was elevated in prostate cancer cell lines compared to benign prostate epithelial cells. Stable knockdown of MDH2 via shRNA in prostate cancer cell lines decreased cell proliferation and increased docetaxel sensitivity. Further, MDH2 shRNA enhanced docetaxel-induced activations of JNK signaling and induced metabolic inefficiency.



CONCLUSION

Taken together, these data suggest a novel function for MDH2 in prostate cancer development and chemotherapy resistance, in which MDH2 regulates chemotherapy-induced signal transduction and oxidative metabolism. Prostate 73: 1028–1037, 2013. © 2013 Wiley Periodicals, Inc.

/pdf/malate-dehydrogenase-2-confers-docetaxel-resistance-via-1hydcy923v.pdf

Malate dehydrogenase 2 confers docetaxel resistance via regulations of JNK signaling and oxidative metabolism.

BACKGROUND Audiovisual distraction, a non-pharmacological intervention, has been used to manage dental anxiety in prior clinical trials. AIM Synthesize the available evidences to evaluate the efficacy of audiovisual distraction techniques on the management of dental anxiety in children. DESIGN Electronic databases (PubMed, Cochrane Central Register of Controlled Trials, and Embase) were searched. We included randomized controlled trials (RCTs), and methodological quality of included trials was assessed using the Cochrane Collaboration's criteria. Information on reported anxiety, pain, behaviors, vital signs (including blood pressure, oxygen saturation, and pulse rate), and children satisfaction was analyzed. RESULTS Nine studies were included for a systematic review, and none of them had low risk of bias. Significant differences in anxiety were found. According to the study, a majority of results indicated a significant difference in pain and behavior between the audiovisual and control group. Three studies reported children in the audiovisual group preferred usage of an audiovisual device for future dental visits. No significant differences could be found regarding blood pressure. CONCLUSIONS There is some low-quality evidence suggesting that the usage of audiovisual distraction during dental treatment may relieve children's dental anxiety.

Effect of audiovisual distraction on the management of dental anxiety in children: A systematic review

The enzyme alanine racemase (Alr) has been a new target for the development of antibacterial drugs based on the involvement of D-Ala in bacterial cell wall biosynthesis. Our previous study noted that Alr is essential for the growth and interspecies competitiveness of S. mutans, the major causative organism of dental caries. However, physiological activity and cariogenicity of S. mutans affected by Alr remains unknown. The current study examined the biofilm biomass, biofilm structure, extracellular polysaccharide (EPS) synthesis, glucosyltransferase (gtf) gene expression, acid production and acid tolerance in the alr-mutant strain. We found that biofilm formation, biofilm structure, and EPS synthesis was in a D-Ala dose-dependent manner. Biofilm structure was loose in alr-mutant group and the ratio of EPS/bacteria was also elevated. Additionally, the expression levels of multiple gtfs were up-regulated, and acid tolerance was decreased. We also established in vivo models of dental caries and found that the incidence and severity of the caries were decreased in the alr-mutant group in comparison to the parental S. mutans group. Our in vivo and in vitro experiments demonstrate that Alr is essential for the cariogenicity of S. mutans and that Alr might be a potential target for the prevention and treatment of caries.

/pdf/function-of-alanine-racemase-in-the-physiological-activity-5fs5fdwiag.pdf

Vivian Chen

Papers

Novel Approaches to the Control of Oral Microbial Biofilms

Malate dehydrogenase 2 confers docetaxel resistance via regulations of JNK signaling and oxidative metabolism.

Effect of audiovisual distraction on the management of dental anxiety in children: A systematic review

Function of alanine racemase in the physiological activity and cariogenicity of Streptococcus mutans

Evaluation of right ventricular mechanics with 4d echocardiography: an in vitro validation against sonomicrometry