Nanomaterials Regulate Bacterial Quorum Sensing: Applications, Mechanisms, and Optimization Strategies.

Anti-virulence therapy that interferes with bacterial communication, known as "quorum sensing (QS)", is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti-virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in-depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti-virulence therapy. This review provides reference and inspiration for further research on the anti-virulence application of nanomaterials.

Immune signature and phagocytosis of circulating DC subsets in healthy adults during aging.

Dendritic cells (DC) play a pivotal role in the onset and progression of immunosenescence-associated diseases, serving as a link between innate and adaptive immunity. Thus, there is a need to establish reference ranges for DC subset levels in healthy adults and investigate the potential impact of age on DC subset levels and phagocytic activity. Single-platform multi-color flow cytometry was performed to assess the proportions of circulating conventional type 1 DC (cDC1), conventional type 2 DC (cDC2), and plasmacytoid DC (pDC), as well as the percentages of CD80, CD86, CD83, PD-L1, and CD32 in cDC1, cDC2, and pDC. Reference ranges were established based on age and gender, and the percentage of circulating DC subsets in different age groups was compared. In addition, circulating DC were enriched using a magnetic bead sorting kit and co-cultured with polystyrene (PS) beads, categorized by age groups, followed by the evaluation of PS bead phagocytosis using light microscopy and flow cytometry. The results indicated that the percentages of circulating cDC1, cDC2, and CD32+cDC2 decreased with age (P < 0.05) and revealed age-related impairment in phagocytic percentage of cDC2 (P < 0.05). These findings provide a deeper understanding of the impact of age on the phenotype and phagocytic activity of DC subsets, shedding light on their role and function in immunosenescence.

Effect of perioperative cognitive behavioral interventions on pain, anxiety, and sleep quality in elderly patients after sinus floor elevation and immediate implantation: A randomized controlled trial.

BACKGROUND: Sinus floor elevation and immediate dental implantation are commonly performed to treat dentition defects in elderly patients. Targeted cognitive behavioral interventions (CBI) during the perioperative period can reduce pain and anxiety as well as improve sleep quality. This can lead to improvements in patient cooperation during follow-up treatment and enhance the overall efficacy of the surgery. OBJECTIVE: The study aimed to investigate the impact of a cognitive behavioral intervention method on perioperative pain, anxiety, and sleep quality in elderly patients undergoing sinus floor elevation and immediate dental implantation. METHODS: Forty patients who required the treatment at the Stomatology Clinic in our hospital between December 2018 and December 2022 were enrolled in this randomized controlled trial. The patients were randomly divided into two groups: a control group (n= 20), which received conventional treatment and care during the perioperative period, and an intervention group (n= 20), which received comprehensive behavioral intervention in addition to the conventional treatment and care during the perioperative period. The perioperative anxiety, pain, and sleep quality of the patients in both groups were evaluated. Anxiety was assessed using the Self-Rating Anxiety Scale (SAS), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and pain was measured using the visual analog scale (VAS). RESULTS: No statistically significant differences in SAS and PSQI were observed between the two groups at the initial visit; the values were significantly higher than those measured postoperatively. The SAS scores and PSQI of patients on days 0 and 7 post-surgery in the intervention group were significantly lower than those in the control group (P< 0.05). CONCLUSION: Perioperative cognitive behavioral intervention can effectively improve anxiety, postoperative pain and sleep quality in elderly patients who have undergone sinus floor elevation and immediate dental implantation, thereby reducing the incidence of complications.

The effect of motivational interviewing based on the transtheoretical model on oral cleaning behavior of patients with periodontitis who have undergone implant restoration.

BACKGROUND: Implant-restored patients with periodontitis have a higher risk of developing peri-implantitis, and helping them develop oral cleaning habits is significant. OBJECTIVE: To evaluate the effectiveness of motivational interviewing based on the transtheoretical model on the modification of oral cleaning behaviors of implant-restored patients with periodontitis. METHODS: Patients with periodontitis (n= 70) who would receive dental implant treatment were included. And they were randomly divided into two groups: experimental (n= 35) and control (n= 35). Control patients received routine oral hygiene education, and those in the experimental group received motivational interviewing based on the transtheoretical model. Oral cleaning behavior was compared between the two groups before and after intervention. In addition, periodontal health status was compared on the day of implant restoration and three months later. RESULTS: Compared to the control, the experimental group demonstrated significantly better oral hygiene behavior after intervention (P< 0.05). Three months after implant restoration, significantly better results were obtained by the experimental group in terms of mPLI and mSBI (P< 0.05). CONCLUSION: Motivational interviewing based on the transtheoretical model can effectively improve the oral cleaning behavior and periodontal health of implant-restored patients with periodontitis.

Sensitive angle-dependent magnetoelectric coupling in cluster-assembled flexible composites.

Flexible magnetoelectric (ME) device is one of the indispensable elements. However, the complicated fabrication process and low sensitivity hinder the practical applications. Here, flexible NiFe anisotropic magnetoelastic composites were prepared by cluster-supersonic expansion method assistant with polyvinylidene fluoride (PVDF) substrates. The NiFe/PVDF composites possess sensitive angle-resolution ME coupling coefficient at room temperature, and the value can reach 0.66µV deg-1. The strong anisotropic magnetoelasticity phenomenon is reminiscent of the short-range ordered cluster structure. The anisotropic magnetoelastic coefficient can be deduced by temperature- and magnetic field strength-dependent anisotropic magnetoresistance. The magnetic torque results also prove the strong anisotropic magnetoelastic trait. The coupling between piezoelectricity and anisotropic magnetostrictive effect endows great possibilities toward flexible electronic compass. These results shed light on future in non-invasive tracking of vital biological health via wearable electronic devices.

Involvement of Apelin/APJ Axis in Thrombogenesis in Valve Heart Disease Patients with Atrial Fibrillation.

The mechanism underlying thrombosis in atrial fibrillation (AF) is not yet clearly understood. The apelin/APJ axis parallel and counter-regulate with the angiotensin system. The present study hypothesizes that apelin/APJ axis exert its anti-thrombus effect in normal left atrial tissue and is disrupted by up-regulated renin-angiotensin-aldosterone system (RAAS) signaling during AF. The specimens of left atrial appendages collected from patients with rheumatic mitral stenosis who underwent valve replacement were divided into 3 groups: sinus rhythm, AF+/thrombus-, and AF+/thrombus+. The amounts of angiotensin II receptor subtype 1 (AT1), apelin/APJ and its downstream plasminogen activator inhibitor-1 (PAI-1) were detected by western blot. The expression of apelin/APJ was significantly decreased in the AF+/thrombus+ group compared with the sinus rhythm and AF+/thrombus- groups. Meanwhile the expressions of AT1 and PAI-1 were highest in the AF+/thrombus+ group compared to the other two groups. Taken together, the present study reveals apelin/APJ axis might be correlated with thrombosis in patients with AF mediated by PAI-1.

Effects of Qishen Yiqi Dripping Pills () in Reducing Myocardial Injury and Preserving Microvascular Function in Patients Undergoing Elective Percutaneous Coronary Intervention: A Pilot Randomized Study.

OBJECTIVE: To evaluate the effect of treatment with Qishen Yiqi Dripping Pills (, QSYQ) on myocardial injury and myocardial microvascular function in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: Eighty patients undergoing elective PCI were randomly assigned to QSYQ and control groups. The QSYQ group received QSYQ at a dosage of 0.5 g 3 times daily (3-7 days before PCI and then daily for 1 month) and regular medication, which comprised of aspirin, clopidogrel, statin, ß-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the absence of contradiction. The control group received only the regular medication. The index of microcirculatory resistance (IMR) was measured at maximal hyperemia after PCI. The fractional flow reserve was measured before and after the procedure. Troponin I levels were obtained at baseline and 20-24 h after the procedure. RESULTS: Pre-PCI troponin I levels between the two groups were similar (0.028±0.05 vs. 0.022±0.04 ng/mL, P=0.55). However, post- PCI troponin I levels in the QSYQ group were significantly lower than that in the control group (0.11±0.02 vs. 0.16±0.09 ng/mL, P<0.01). IMR values were significantly lower in the QSYQ group as compared to the control group (16.5±6.1 vs. 31.2±16.0, P<0.01). Multivariate analysis identified QSYQ treatment as the only independent protective factor against IMR >32 (odds ratio=0.29, 95% confidence interval: 0.11-0.74, P=0.01). CONCLUSIONS: The present study demonstrated the benefit of QSYQ in reducing myocardial injury and preserving microvascular function during elective PCI.

Mutation network-based understanding of pleiotropic and epistatic mutational behavior of Enterococcus faecalis FMN-dependent azoreductase.

We previously identified a highly active homodimeric FMN-dependent NADH-preferred azoreductase (AzoA) from Enterococcus faecalis, which cleaves the azo bonds (R-NË­N-R) of diverse azo dyes, and determined its crystal structure. The preliminary network-based mutational analysis suggested that the two residues, Arg-21 and Asn-121, have an apparent mutational potential for fine-tuning of AzoA, based on their beneficial pleiotropic feedbacks. However, epistasis between the two promising mutational spots in AzoA has not been obtained in terms of substrate binding and azoreductase activity. In this study, we further quantified, visualized, and described the pleiotropic and/or epistatic behavior of six single or double mutations at the positions, Arg-21 and Asn-121, as a further research endeavor for beneficial fine-tuning of AzoA. Based on this network-based mutational analysis, we showed that pleiotropy and epistasis are common, sensitive, and complex mutational behaviors, depending mainly on the structural and functional responsibility and the physicochemical properties of the residue(s) in AzoA.

Cardiac repair in a mouse model of acute myocardial infarction with trophoblast stem cells.

Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo. In addition, a significantly high proliferation level of both transplanted stem cells and resident cardiomyocytes was observed in the TSCs group. These findings primary revealed the therapeutic potential of TSCs in transplantation therapy for MI.

Advanced Glycation Endproducts Impair Endothelial Progenitor Cell Migration and Homing via Syndecan 4 Shedding.

Endothelial progenitor cells (EPCs) are a subtype of bone marrow-derived progenitor cells. Stromal cell-derived factor 1 (SDF-1)-mediated EPC mobilization from bone marrow to areas of ischemia plays an important role in angiogenesis. Previous studies have reported that advanced glycation endproducts (AGEs), which are important mediators of diabetes-related vascular pathology, may impair EPC migration and homing, but the mechanism is unclear. Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan receptor on the cell surface, involved in SDF-1-dependent cell migration. The extracellular domain of synd4 (ext-synd4) is shed in the context of acute inflammation, but the shedding of ext-synd4 in response to AGEs is undefined. Here we investigated changes in ext-synd4 on EPCs in response to AGEs, focusing on the influence of impaired synd4 signaling on EPC migration and homing. We found decreased full length and increased residue of synd4 in cells incubated with AGEs, with concomitant increase in the soluble fragment of ext-synd4 in the cell medium. EPCs from patients with type 2 diabetes expressed less ext-synd4 as assessed by Western blotting. Flow cytometry analysis showed less ext-synd4 on circulating CD34+ peripheral blood mononuclear cells, of which EPCs form a subgroup. We then explored the role of synd4 in EPC migration and homing. Impaired migration of synd4-deficient EPCs was observed by a 2D-chemotaxis slide. Furthermore, poor homing of synd4-/- EPCs was observed in a mouse model of lower limb ischemia. This study demonstrates that the shedding of synd4 from EPCs plays a key role in AGE-mediated dysfunction of EPC migration and homing. Stem Cells 2017;35:522-531.

Bacterial Multidrug Efflux Pumps of the Major Facilitator Superfamily as Targets for Modulation.

Causative agents of infectious disease that are multidrug resistant bacterial pathogens represent a serious public health concern due to the increasingly difficult nature of achieving efficacious clinical treatments. Of the various acquired and intrinsic antimicrobial agent resistance determinants, integral-membrane multidrug efflux pumps of the major facilitator superfamily constitute a major mechanism of bacterial resistance. The major facilitator superfamily (MFS) encompasses thousands of known related secondary active and passive solute transporters, including multidrug efflux pumps, from bacteria to humans. This review article addresses recent developments involving the targeting by various modulators of bacterial multidrug efflux pumps from the major facilitator superfamily. It is currently of tremendous interest to modulate bacterial multidrug efflux pumps in order to eventually restore the clinical efficacy of therapeutic agents against recalcitrant bacterial infections. Such MFS multidrug efflux pumps are good targets for modulation.

Increased M1 Macrophages Infiltration Is Associated with Thrombogenesis in Rheumatic Mitral Stenosis Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia. In patients with AF, the role of macrophage subsets in thrombogenesis is unclear. In the present study, we analyzed the role of M1 and M2 macrophages and related cytokines in thrombogenesis of AF. Immunohistochemistry, Western blot, and TUNEL assay were used to detect M1/M2 macrophage infiltration, the expression pattern of IL-1ß and inflammasome components, and apoptosis of cardiomyocytes in 71 specimens obtained from the left atrial appendage of patients with rheumatic mitral stenosis (MS) with or without thrombosis. We demonstrated that proinflammatory M1 macrophages were predominant in the atrium of MS patients with AF and thrombus. NLRP3 inflammasomes and IL-1ß, which are primarily functional in macrophages, were activated in those patients. We also showed that increased cell death was associated with thrombogenesis in MS patients. These data indicate that infiltration of M1 macrophages and over-activation of NLRP3 inflammasomes may play a role in progressive atrial inflammation and thrombogenesis in rheumatic mitral stenosis patients with AF.

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy.

Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4-/-) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4-/- compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy.

Differential gene expression in Staphylococcus aureus exposed to Orange II and Sudan III azo dyes.

We previously demonstrated the effects of azo dyes and their reduction metabolites on bacterial cell growth and cell viability. In this report, the effects of Orange II and Sudan III on gene expression profiling in Staphylococcus aureus ATCC BAA 1556 were analyzed using microarray and quantitative RT-PCR technology. Upon exposure to 6 µg/ml Orange II for 18 h, 21 genes were found to be differently expressed. Among them, 8 and 13 genes were up- and down-regulated, respectively. Most proteins encoded by these differentially expressed genes involve stress response caused by drug metabolism, oxidation, and alkaline shock indicating that S. aureus could adapt to Orange II exposure through a balance between up and down regulated gene expression. Whereas, after exposure to 6 µg/ml Sudan III for 18 h, 57 genes were differentially expressed. In which, 51 genes were up-regulated and 6 were down-regulated. Most proteins encoded by these differentially expressed genes involve in cell wall/membrane biogenesis and biosynthesis, nutrient uptake, transport and metabolite, and stress response, suggesting that Sudan III damages the bacterial cell wall or/and membrane due to binding of the dye. Further analysis indicated that all differentially expressed genes encoded membrane proteins were up-regulated and most of them serve as transporters. The result suggested that these genes might contribute to survival, persistence and growth in the presence of Sudan III. Only one gene msrA, which plays an important role in oxidative stress resistance, was found to be down-regulated after exposure to both Orange II and Sudan III. The present results suggested that both these two azo dyes can cause stress in S. aureus and the response of the bacterium to the stress is mainly related to characteristics of the azo dyes.

Multidrug efflux pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus bacterial food pathogens.

Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations.

[Effect of anxin granules combined with tirofiba on patients with acute myocardial infarction after elective percutaneous coronary intervention].

To investigate the influence of Anxin granules combined with tirofiban on acute myocardial infarction (AMI) Patients after elective percutaneous coronary intervention (PCI). One hundred and twenty AMI patients were randomly divided into treatment group and control group. The patients in the two groups were all given Tirofiban 30mins before PCI . The treatment group was added Anxin granules 30 mins before and after PCI. Tissue factor (TF) and von willebrand factor (vWF) were tested at 6 hours after operation. Syndromatology alteration of traditional Chinese medicine (TCM) and bleeding complications were observed at 4 weeks after operation. Both TF and vWF at 6 hours after operation of the treatment group was lower than the control group significantly (P < 0.01), while the condition of myocardial ischemia at 90 mins after operation of the treatment group was better than control group with significance. The syndromatology alteration of TCM especially spontaneous perspiration and hypodynamia of the treatment group were improved significantly compared to control group 4 weeks after operation. All patients in both groups had no bleeding complications and thrombopenia. The study suggests that Anxin granules combined with tirofiba can improve the clinical efficacy and the endothelial function of AMI patients after PCI with no increase in bleeding events.

A comparison of conventional methods for the quantification of bacterial cells after exposure to metal oxide nanoparticles.

BACKGROUND: Due to potential interference of nanoparticles on bacterial quantification, there is a challenge to develop a fast, accurate and reproducible method for bacterial quantification. Currently various bacterial quantification methods are used by researchers performing nanoparticles study, but there has been no efficacy evaluation of these methods. Here we study interference of nanoparticles on three most commonly used conventional bacterial quantification methods, including colony counting to determine the colony-forming units (CFU), spectrophotometer method of optical density (OD) measurement, and flow cytometry (FCM). RESULTS: Three oxide nanoparticles including ZnO, TiO2, and SiO2 and four bacterial species including Salmonella enterica serovar Newport, Staphylococcus epidermidis, Enterococcus faecalis, and Escherichia coli were included in the test. Results showed that there is no apparent interference of the oxide nanoparticles on quantifications of all four bacterial species by FCM measurement; CFU counting is time consuming, less accurate and not suitable for automation; and the spectrophotometer method using OD measurement was the most unreliable method to quantify and detect the bacteria in the presence of the nanoparticles. CONCLUSION: In summary, FCM measurement proved to be the best method, which is suitable for rapid, accurate and automatic detection of bacteria in the presence of the nanoparticles.

Detection of benzalkonium chloride resistance in community environmental isolates of staphylococci.

We isolated a total of 653 strains from 64 community environmental samples in Massachusetts, USA. Among these isolates, 9.65 % (63 strains) were benzalkonium chloride (BC)-resistant staphylococci. All BC-resistant strains were collected from surfaces upon which antibacterial wipes or antibacterial sprays containing 0.02-0.12 % BC had frequently been used in the fitness centres. However, isolates from surfaces upon which antibacterial wipes or antibacterial sprays had not been used were all sensitive to BC. All BC-resistant strains were also resistant to erythromycin, penicillin and ampicillin. In addition, 51 strains showed resistance to cetyltrimethylammonium bromide (CTAB), 15 strains showed resistance to chloramphenicol, 12 strains showed resistance to ciprofloxacin and four strains showed resistance to meticillin. Resistance gene analysis demonstrated that 41 strains contained qacA/B, 30 strains had qacC, 25 strains contained qacG, 16 strains had qacH and eight strains contained qacJ. These data indicate that application of BC is associated with environmental staphylococcal antimicrobial resistance.

Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae.

Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae. Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence-related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations.