The post-antibiotic effect (PAE) is the delay in bacterial regrowth following removal of an antibiotic and has important implications for dosing regimens. Several classes of antibiotics generate PAEs including the streptogramins which are comprised of two components, type A and type B, that bind to adjacent sites on the ribosome and act synergistically to inhibit bacterial growth. In the present work, we investigated the activity of the type A and type B streptogramins virginiamycin (VM1) and virginiamycin (VS1) toward two Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus. In agreement with previous studies, we show that the combination of VM1 and VS1 resulted in synergistic antibacterial activity defined by the minimum inhibitor concentration (MIC). However, the PAE generated by VM1 was similar to that of the VM1 VS1 combination, whereas VS1 generated only a minimal PAE. These data contrast with the general expectation that the synergy resulting from the combination of streptogramins lowers both the MIC and extends the PAE compared to either component alone, and again reflecting fundamental differences in drug activity at fixed concentrations compared to time-dependent activity.

Diabetes mellitus is a much-studied disorder, characterized by hyperglycemia and numerous oral and medical complications. The latter includes (above all) decreased life-span — and these are widely discussed in the dental and medical literature. The oral complications include impaired wound healing; increased severity of periodontal disease and peri-implantitis; dry mouth (xerostomia); and dental caries. The relationship between diabetes and oral health is bi-directional: Optimal management of local oral disease can profoundly affect the systemic metabolic control of the diabetic patient, and strict management of the patient’s hyperglycemia can reduce its impact on oral disease. The only host modulation therapy (HMT), approved by the U.S. Food and Drug Administration (FDA) to treat periodontal disease, is a novel NON-antimicrobial (low-dose) formulation of doxycycline (Periostat®; 20 mg b.i.d). A publication in Scientific Reports (2017), which supported the clinical rationale of efficacy and safety of low-dose doxycycline in diabetics, stated: “doxycycline not only ameliorated insulin resistance, fasting blood glucose, and insulin levels, and lipid profiles in the circulation and liver, but also improved islet morphology and increased glucose-stimulated insulin secretion.” Additional developments include the biphenolic chemically-modified curcumins, as HMT for managing oral diseases. A lead compound, chemically-modified curcumin 2.24 (CMC2.24), has demonstrated safety and efficacy in vitro, in cell culture, and in vivo using mouse, rat, rabbit, and dog models of disease. In conclusion, novel host-modulation compounds have shown significant promise as adjuncts to traditional local therapy in the clinical management of periodontal and other oral diseases.

IntroductionPrevious studies have shown Streptococcus mutans (S. mutans) esterase is a key mediator of dental composite biodegradation, which can contribute to recurrent caries. This study is to investigate the inhibitory effects of a novel Chemically-Modified-Curcumin (CMC 2.24) on esterase activities and related dental material biodegradation.MethodsDental adhesive materials and composite resins were incubated in S. mutans suspension with CMC 2.24 and other compounds, including doxycycline, Chemically-Modified-Tetracycline (CMT-3), and curcumin for 4 weeks. The pre- and post-incubation surface roughness were evaluated by either laser diffraction pattern and/or a 3D laser scanning microscope. Esterase enzyme inhibition assays were performed with the same test groups and activities were determined spectrophotometrically.ResultsAmong all experimental groups, CMC 2.24 significantly reduced surface roughness of dental composite (p < 0.01) and adhesive (p < 0.01) materials compared to bacteria-only group. Additionally, CMC 2.24 reduced porcine esterase activity by 46.5%, while other compounds showed minimal inhibition. In the S. mutans esterase assay, CMC 2.24 showed inhibition of 70.0%, while other compounds showed inhibition ranging from 19% to 36%.ConclusionOur study demonstrated that CMC 2.24 inhibited biodegradation of dental composite material more effectively than its mother compound, curcumin. Moreover, the mechanism of this biodegradation was likely mediated through bacterial esterase activity. Doxycycline achieved similar inhibition by completely eradicating S. mutans with its antibiotic action; hence, it is not recommended for long-term use.

The postantibiotic effect (PAE) is the persistent suppression of microbial growth following the removal of antimicrobial therapy. In general, antibiotics that generate a PAE are dosed less frequently, and thus, the PAE has important implications for dosing regimens. PAEs can arise through several mechanisms, including the extended occupancy of the drug target following drug elimination, and the correlation between drug-target residence time and PAE provides insight into target vulnerability. To assess the vulnerability of Escherichia coli leucyl-tRNA synthetase (ecLeuRS), which is an essential enzyme in protein synthesis, the time-dependent inhibition of the enzyme was studied by the benzoxaborole class of compounds that inhibit LeuRS by forming a stable LeuRS-tRNALeu-benzoxaborole adduct. Preincubation of epetraborole with ecLeuRS resulted in a decrease in the IC50 value for enzyme inhibition from 38 to 3 nM, consistent with the slow formation of the final enzyme-inhibitor complex, and similar shifts in IC50 were observed for three other benzoxaboroles. The benzoxaboroles generated short PAEs (<1 h) in E. coli, however, the PAE values of AN3334 and epetraborole increased from 0.88 to 1.70-3 h when a sub-MIC concentration of the aminoglycoside tobramycin was included in the media. pSILAC revealed that the synthesis rate of ecLeuRS was reduced 1.6-fold in the presence of sub-MIC tobramycin, reinforcing the role that protein turnover plays in target vulnerability.

The postantibiotic effect (PAE) is the delay in bacterial regrowth following antibiotic removal. It has important implications for dosing regimens since drugs that have extended activity following their elimination can be dosed less frequently, widening the therapeutic window. While the PAE has been associated with target vulnerability and the rate of target turnover, little is known about the genetic components that modulate the PAE. Here, we developed a high-throughput assay to screen the Escherichia coli Keio collection of ∼4000 deletion strains, identifying genes that enhance the PAE for CHIR-090, an inhibitor of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). This screen revealed approximately 400 gene knockouts that enhanced the PAE of CHIR-090. The list of PAE enhancers was enriched for genes involved in transmembrane transport and outer membrane synthesis. Notably, deletion of the rfaE gene, which is involved in lipopolysaccharide (LPS) biosynthesis, increased the PAE of the LpxC inhibitors CHIR-090 and LPC-058 by 2 and 3 h, respectively. Consistent with this phenotype, cotreatment of wild-type E. coli with an RfaE inhibitor increased the PAE of CHIR-090 or LPC-058 by 1 h. To probe the mechanism of this interaction, we measured the rate of LpxC turnover and found that knocking out rfaE extended the half-life of LpxC by 2-fold, suggesting that disrupting RfaE increases the stability of LpxC, increasing target vulnerability and enhancing the PAE of LpxC inhibitors.

INTRODUCTION:Endodontic treatment failures remain a significant treatment challenge. Different bacterial combinations are implicated in posttreatment disease. Enterococcus faecalis is often detected in these biofilms. Calcium hydroxide has many limitations, including low flowability, difficult retrieval, high pH, and limited efficacy against E. faecalis. Here, we show that these difficulties can be overcome using calcium salicylate (CASA) encapsulated in a photocrosslinked thermoreversible F127-dimethacrylamide (DMA) hydrogel. METHODS:CASA was prepared by mixing calcium hydroxide and salicylic acid in a 1:6 ratio, respectively and incorporated into F127-DMA at different concentrations. The mixture was photocrosslinked using lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate. Chemical properties were analyzed using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, while injectability and retrievability were assessed using plastic root canal training blocks, bovine teeth cone beam computed tomography scans, and oscillatory rheology. In Vitro antibacterial efficacy against E. faecalis biofilm was probed by injection of the compound, following inoculation on bovine extracted teeth. Cytotoxicity of the compound was measured using dental pulp stem cells. RESULTS:Encapsulation of CASA in F127-DMA reduced the viscosity by three orders of magnitude compared to the paste form, facilitating injection and enabling retrieval. Following retrieval, F127-DMA/CASA showed significantly lower residual medicament (∼6%) compared to Vista-Cal (26%). X-ray diffraction, Raman, and Fourier transform infrared spectroscopy analyses confirmed the formation of CASA and successful integration of CASA into photocrosslinked F127-DMA. Treatment with the F127-DMA/20% CASA following 21-day inoculation with E. faecalis resulted in a 6-log reduction in CFU and complete elimination of biofilm. No significant change in the doubling time of treated dental pulp stem cell was observed. CONCLUSIONS:F127-DMA/CASA exhibits superior flowability, retrievability, near-neutral pH (∼6), biocompatibility, and anti-E. faecalis efficacy, which highlights its potential as a significant improvement over calcium hydroxide as an endodontic intracanal medicament.

Ganfeborole (GSK3036656) inhibits the Mycobacterium tuberculosis leucyl-tRNA-synthetase (mtLeuRS) and is in Phase 2a clinical trials for the treatment of tuberculosis. Here we show that ganfeborole is a time-dependent inhibitor of mtLeuRS (IC50 1 nM) and generates a postantibiotic effect of 77 h at 50xMIC (MIC 0.058 μM) with M. tuberculosis H37Rv, indicating that mtLeuRS is a highly vulnerable drug target and supporting the excellent in vivo efficacy of the drug. Ganfeborole is also a potent time-dependent inhibitor of Escherichia coli LeuRS (ecLeuRS, IC50 2 nM), however no antibacterial activity is observed toward E. coli up to 1 mM ganfeborole despite the observation that less potent ganfeborole analogs have antibacterial activity. To rationalize this observation, we propose that ganfeborole forms a complex with AMP that binds to the ecLeuRS editing site but does not impact aminoacylation. In support, addition of 12.5 μM norvaline generates a ganfeborole MIC of 0.4 μM since ecLeuRS is unable to hydrolyze norvaline-tRNALeu. Additionally, mutations that reduce the affinity and residence time of ganfeborole-AMP on ecLeuRS result in antibacterial activity. We propose that the activity of ganfeborole toward M. tuberculosis is because mtLeuRS is a highly vulnerable target so that only low levels of enzyme need to be inhibited by the ganfeborole-tRNALeu complex in contrast to ecLeuRS, which we previously demonstrated is a low vulnerability target.

Introduction: Recurrent endodontic infections are primarily caused by Enterococcus faecalis and are more challenging to treat, compared with primary infection of the root canal system. Calcium hydroxide (CH) is used as an interappointment dressing in endodontics despite its inefficacy against E. faecalis and other pathogens. To improve antimicrobial properties and limit cytotoxicity of CH, we added salicylic acid to CH (CASA) to disinfect the canal. CASA overcomes the main pathogen responsible for recurrent endodontic infections. The aim of this study was to evaluate the antimicrobial activity of CASA and its cytotoxicity against dental pulp stem cells (DPSCs) and its effect on the differentiation potential of DPSCs.Methods: Mature E. faecalis biofilm cultured on dentin chips was exposed to CASA and studied using confocal laser scanning microscopy. The dose-dependency of CASA was also studied using the liquid suspension test. The cytotoxicity was tested against DPSCs, and its effect on the expression of osteocalcin and alkaline phosphatase was studied.Results: CASA produced larger zones of inhibition than CH for all species tested and demonstrated superior efficacy than CH against E. faecalis biofilm. Cytotoxicity studies indicated DPSC's high tolerance for CASA; addition of CASA to DPSCs was observed to increase the expression of biological markers related to mineralization. Conclusions: CASA was proved to have superior antibacterial efficacy against E. faecalis when compared with CH. It also increased the expression of some DPSC differentiation markers involved in mineralization. (J Endod 2023;49:205-211.)

Biomolecular condensates formed by liquid-liquid phase separation have been implicated in multiple diseases. Modulation of condensate dynamics by small molecules has therapeutic potential, but so far, few condensate modulators have been disclosed. The SARS-CoV-2 nucleocapsid (N) protein forms phase-separated condensates that are hypothesized to play critical roles in viral replication, transcription, and packaging, suggesting that N condensation modulators might have anti-coronavirus activity across multiple strains and species. Here, we show that N proteins from all seven human coronaviruses (HCoVs) vary in their tendency to undergo phase separation when expressed in human lung epithelial cells. We developed a cell-based high-content screening platform and identified small molecules that both promote and inhibit condensation of SARS-CoV-2 N. Interestingly, these host-targeted small molecules exhibited condensate-modulatory effects across all HCoV Ns. Some have also been reported to exhibit antiviral activity against SARS-CoV-2, HCoV-OC43, and HCoV-229E viral infections in cell culture. Our work reveals that the assembly dynamics of N condensates can be regulated by small molecules with therapeutic potential. Our approach allows for screening based on viral genome sequences alone and might enable rapid paths to drug discovery with value for confronting future pandemics.

UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a promising drug target in Gram-negative bacteria. Previously, we described a correlation between the residence time of inhibitors on Pseudomonas aeruginosa LpxC (paLpxC) and the post-antibiotic effect (PAE) caused by the inhibitors on the growth of P. aeruginosa. Given that drugs with prolonged activity following compound removal may have advantages in dosing regimens, we have explored the structure-kinetic relationship for paLpxC inhibition by analogues of the pyridone methylsulfone PF5081090 (1) originally developed by Pfizer. Several analogues have longer residence times on paLpxC than 1 (41 min) including PT913, which has a residence time of 124 min. PT913 also has a PAE of 4 h, extending the original correlation observed between residence time and PAE. Collectively, the studies provide a platform for the rational modulation of paLpxC inhibitor residence time and the potential development of antibacterial agents that cause prolonged suppression of bacterial growth.

The relationship between drug-target residence time and the post-antibiotic effect (PAE) provides insights into target vulnerability. To probe the vulnerability of bacterial acetyl-CoA carboxylase (ACC), a series of heterobivalent inhibitors were synthesized based on pyridopyrimidine 1 and moiramide B (3) which bind to the biotin carboxylase and carboxyltransferase ACC active sites, respectively. The heterobivalent compound 17, which has a linker of 50 Å, was a tight binding inhibitor of Escherichia coli ACC (Kiapp 0.2 nM) and could be displaced from ACC by a combination of both 1 and 3 but not just by 1. In agreement with the prolonged occupancy of ACC resulting from forced proximity binding, the heterobivalent inhibitors produced a PAE in E. coli of 1-4 h in contrast to 1 and 3 in combination or alone, indicating that ACC is a vulnerable target and highlighting the utility of kinetic, time-dependent effects in the drug mechanism of action.

A Rhizobium tropici (R. tropici) derived biopolymer has been reported as an effective, biodegradable, additive to reduce erosion. In addition to directly modifying the mechanical properties of the soil, it was postulated that indirectly it enhanced vegetation, which in turn stabilized the soil through enhanced root infrastructure. We therefore chose to study its impact directly on Green Bush Bean plants, where its effect could be measured in the early stages of plant development, starting from germination of the seeds through the initial growth of leaves and shoots. EPM derived from R. tropici bacteria ATCC (strain) grown in two laboratories were tested with similar results, indicating a high degree of reproducibility. Watering Bush Bean seeds with EPM concentrations as low as 50 and 100 mg/L produced a small increase of the germination rate, from 87% to 93% for seeds grown for ten days in a moist environment. The seeds were then transplanted into potting soil and allowed to grow for another three weeks, during which they were watered daily with tap water or the EPM solutions. Continued watering with EPM after transplantation showed enhancement in both root and stem/leaf mass three weeks after transplantation into potting soil by 45% for the two EPM biopolymers. Root density was also higher by 29% to 71% for EPM1.The mass of the leaf and shoots also showed a significant enhancement over the control, but in this case favoring EPM2, consistent with plants preferring either root or leaf production.

Background: Fogging is an efficient method when disinfection of large areas is desired.Methods: Two methods of ultrasonic fogging, pulsed and continuous, were compared on bacteria dried on either aluminum or polystyrene surfaces. We characterized commercial and home-made hypochlorous acid (HOCl) with respect to storage and means of production.Results: We found that the initial chlorine concentration of the commercial solution was approximately 550 ppm, and when stored open under ambient conditions, the chlorine content decreased at a rate of 30% every 100 days. The HOCl produced using the home synthesizers had a maximum chlorine content of 257.6 ppm which decayed by 65% after 100 days. A second synthesizer produced a liquid with high chlorine content and pH, 750ppm and pH = 8.55. The anti-bacterial efficacy was probed using Enterococcus faecalis, a persistent source of infection in public and clinical spaces. Time course studies determined that E. faecalis could survive dry on surfaces for more than 12 weeks, but was easily eliminated in half the fogging time.Conclusions: The most effective mode of application was determined to be continuous fogging where a 6.59 log reduction was established in vertical geometry. The optimal pulsed fogging protocol produced a similar reduction, but required nearly 5 times as long. The home synthesized versions yielded much lower log bacte-rial reductions. No significant differences in outcome were determined between polymer or metal surfaces.(c) 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The translation of time-dependent drug-target occupancy to extended pharmacological activity at low drug concentration depends on factors such as target vulnerability and the rate of target turnover. Previously, we demonstrated that the postantibiotic effect (PAE) caused by inhibitors of bacterial drug targets could be used to assess target vulnerability, and that high levels of target vulnerability coupled with relatively low rates of target resynthesis resulted in a strong correlation between drug-target residence time and the PAE following compound washout. Although the residence time of inhibitors on UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) in Pseudomonas aeruginosa (paLpxC) results in significant PAE, inhibitors of the equivalent enzyme in Escherichia coli (ecLpxC) do not cause a PAE. Hyperactivity of the fatty acid biosynthesis enzyme FabZ or the inclusion of sub-MIC levels of azithromycin lead to the observation of a PAE for three inhibitors of ecLpxC. FabZ hyperactivity has been shown to stabilize ecLpxC, and using mass spectrometry, we demonstrate that the appearance of a PAE can be directly linked to a 3-fold increase in the stability of ecLpxC. These studies substantiate the importance of target turnover in time-dependent drug activity.

Rare sequence variants in the microglial cell surface receptor TREM2 have been shown to increase the risk for Alzheimer’s disease (AD). Disease-linked TREM2 mutations seem to confer a partial loss of function, and increasing TREM2 cell surface expression and thereby its function(s) might have therapeutic benefit in AD. However, druggable targets that could modulate microglial TREM2 surface expression are not known. To identify such targets, we conducted a screen of small molecule compounds with known pharmacology using human myeloid cells, searching for those that enhance TREM2 protein at the cell surface. Inhibitors of the kinases MEK1/2 displayed the strongest and most consistent increases in cell surface TREM2 protein, identifying a previously unreported pathway for TREM2 regulation. Unexpectedly, inhibitors of the downstream effector ERK kinases did not have the same effect, suggesting that noncanonical MEK signaling regulates TREM2 trafficking. In addition, siRNA knockdown experiments confirmed that decreased MEK1 and MEK2 were required for this recruitment. In iPSC-derived microglia, MEK inhibition increased cell surface TREM2 only modestly, so various cytokines were used to alter iPSC microglia phenotype, making cells more sensitive to MEK inhibitor-induced TREM2 recruitment. Of those tested, only IFN-gamma priming prior to MEK inhibitor treatment resulted in greater TREM2 recruitment. These data identify the first known mechanisms for increasing surface TREM2 protein and TREM2-regulated function in human myeloid cells and are the first to show a role for MEK1/MEK2 signaling in TREM2 activity.

OBJECTIVE:Peri-implantitis has been attributed to a myriad of factors, including microleakage at the abutment-implant interface. Implant abutment access channel sealing materials (IACSM) are readily used in implant dentistry, with little evidence on their effect on microleakage. This study aims to evaluate the effect of IACSM on the microbial composition in the implant access channel and the peri-implant sulcus.METHODS:A total of n = 8 patients (64 implants) were included in this single-blinded, randomized controlled trial, whereas four different materials (cotton, polytetrafluoroethylene [PTFE], synthetic foam, or polyvinyl siloxane [PVS]) were randomly placed as an IACSM. Following 6 months, microbial analysis was completed on the IACSM and samples from the peri-implant sulci via PCR and high-throughput sequencing. Bacterial samples on the IACSM and in the peri-implant sulci were classified according to Socransky's microbial complexes.RESULTS:There was a preponderance of early colonizing bacteria within the IACSM, while the peri-implant sulci were dominated by Orange complex bacteria. The proportion of Red and Orange complex members on the IACSM was significantly less than in the peri-implant sulci. The proportion of Green, Yellow, and Blue complex members found on the IACSM was significantly greater than in the peri-implant sulci. Atopobium, a diverse species not included in the microbial complexes, was frequently detected in the peri-implant sulcus samples.CONCLUSIONS:No detectable effects of IACSM on the microbial community in the peri-implant sulcus or on the IACSM were identified. Variation of bacterial species was most dependent on the individual patient. No significant differences were found in the periodontal parameters between the different treatment groups.

We have previously shown that exposure to TiO2 nanoparticles (NPs) reduces the resistance of HeLa cells to bacterial infection. Here we demonstrate that the increased infectivity is associated with enhanced asymmetry in the cholesterol distribution. We applied a live cell imaging method which uses tunable orthogonal cholesterol sensors to visualize and quantify in-situ cholesterol distribution between the two leaflets of the plasma membrane (PM). In the control culture, we found marked transbilayer asymmetry of cholesterol, with the concentration in the outer plasma membrane (OPM) being 13 +/- 2-fold higher than that in the inner plasma membrane (IPM). Exposure of the culture to 0.1 mg/mL of rutile TiO2 NPs increased the asymmetry such that the concentration in the OPM was 51 +/- 10 times higher, while the total cholesterol content increased only 21 +/- 2%. This change in cholesterol gradient may explain the increase in bacterial infectivity in HeLa cells exposed to TiO2 NPs since many pathogens, including Staphylococcus aureus used in the present study, require cholesterol for proper membrane attachment and virulence. RT-PCR indicated that exposure to TiO2 was responsible for upregulation of the ABCA1 and ABCG1 mRNAs, which are responsible for the production of the cholesterol transporter proteins that facilitate cholesterol transport across cellular membranes. This was confirmed by the observation of an overall decrease in bacterial infection in ABCA1 knockout or methyl-beta-cyclodextrin-treated HeLa cells, as regardless of TiO2 NP exposure. Hence rather than preventing bacterial infection, TiO2 nanoparticles upregulate genes associated with membrane cholesterol production and distribution, hence increasing infectivity. Statement of significance A great deal of work has been done regarding the toxicology of the particles, especially focusing on detrimental outcomes associated with reactive oxygen species (ROS) production. In this paper we show unambiguously a very surprising result, namely the ability of these particles to enhance bacterial infection even at very small exposure levels, where none of the deleterious effects of ROS products can yet be detected. Using a new imaging technique, we are able to demonstrate, in operando, the effect of the particles on cholesterol generation and distribution in live HeLa cells. This paper also represents the first in a series where we explore other consequences of increased membrane cholesterol, due to particle exposure, which are known to have multiple other consequences on human tissue function and development. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

We have previously shown that exposure to TiO2 nanoparticles (NPs) reduces the resistance of HeLa cells to bacterial infection. Here we demonstrate that the increased infectivity is associated with enhanced asymmetry in the cholesterol distribution. We applied a new live cell imaging method which uses tunable orthogonal cholesterol sensors to visualize and quantify in-situ cholesterol distribution between the two leaflets of the plasma membrane (PM). In the control culture, we found marked transbilayer asymmetry of cholesterol, with the concentration in the outer plasma membrane (OPM) being 12.5(2.2)-fold higher than that in the inner plasma membrane (IPM). Exposure of the culture to 0.1 mg/mL of rutile TiO2 NPs increased the asymmetry such that the concentration in the OPM was 50.8(9.5) times higher, while the total cholesterol content increased only 20.5(2.4)%. This change in cholesterol gradient may explain the increase in bacterial infectivity in HeLa cells exposed to TiO2 NPs since many pathogens, including Staphylococcus aureus used in the present study, require cholesterol for proper membrane attachment and virulence. RT-PCR indicated that exposure to TiO2 was responsible for upregulation of the ABCA1 and ABCG1 mRNAs, which are responsible for the production of the cholesterol transporter proteins that facilitate cholesterol transport across cellular membranes. This was confirmed by the observation of an overall decrease in bacterial infection in ABCA1 knockout or methyl-β-cyclodextrin-treated HeLa cells, as regardless of TiO2 NP exposure. Hence rather than preventing bacterial infection, TiO2 nanoparticles upregulate genes associated with membrane cholesterol production and distribution, hence increasing infectivity.

Of particular interest to the readers of this journal, “Physical Medicine and Rehabilitation”, recent studies (and experience) in the field of “Oral and Dental Rehabilitation”, indicate that Host-Modulation Therapy (HMT), originally developed as adjunctive treatment for the management of microbial-induced inflammatory periodontal disease (periodontitis) around natural teeth, is also likely applicable to promote the health of soft tissues, and jaw bone (mandible/maxilla) supporting dental implants