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INTRODUCTION: Periodontitis-related oral microbial dysbiosis is thought to contribute to Alzheimer's disease (AD) neuroinflammation and brain amyloid production. Since probiotics can modulate periodontitis/oral dysbiosis, this study examined the effects of a probiotic/lantibiotic, nisin, in modulating brain pathology triggered by periodontitis. METHODS: A polymicrobial mouse model of periodontal disease was used to evaluate the effects of this disease on brain microbiome dysbiosis, neuroinflammation, Alzheimer's-related changes, and nisin's therapeutic potential in this context. RESULTS: 16S sequencing and real-time PCR data revealed that Nisin treatment mitigated the changes in the brain microbiome composition, diversity, and community structure, and reduced the levels of periodontal pathogen DNA in the brain induced by periodontal disease. Nisin treatment significantly decreased the mRNA expression of pro-inflammatory cytokines (Interleukin-1ß/IL-1 ß, Interleukin 6/IL-6, and Tumor Necrosis Factor α/TNF-α) in the brain that were elevated by periodontal infection. In addition, the concentrations of amyloid-ß 42 (Aß42), total Tau, and Tau (pS199) (445.69 ± 120.03, 1420.85 ± 331.40, 137.20 ± 36.01) were significantly higher in the infection group compared to the control group (193.01 ± 31.82, 384.27 ± 363.93, 6.09 ± 10.85), respectively. Nisin treatment markedly reduced the Aß42 (261.80 ± 52.50), total Tau (865.37 ± 304.93), and phosphorylated Tau (82.53 ± 15.77) deposition in the brain of the infection group. DISCUSSION: Nisin abrogation of brain microbiome dysbiosis induces beneficial effects on AD-like pathogenic changes and neuroinflammation, and thereby may serve as a potential therapeutic for periodontal-dysbiosis-related AD.
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Enfermedad de Alzheimer , Bacteriocinas , Microbiota , Nisina , Periodontitis , Probióticos , Ratones , Animales , Enfermedad de Alzheimer/patología , Nisina/metabolismo , Bacteriocinas/metabolismo , Enfermedades Neuroinflamatorias , Disbiosis/tratamiento farmacológico , Disbiosis/metabolismo , Periodontitis/metabolismo , Encéfalo/metabolismo , Péptidos beta-Amiloides/metabolismo , Interleucina-6/metabolismo , Probióticos/uso terapéuticoRESUMEN
Periodontal disease is driven by dysbiosis in the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola, is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed significant upregulation of genes associated with extracellular matrix organization and degradation including potentially tissue-specific inducible MMPs that may play novel roles in modulating host immune responses that have yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of expression of either abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs while a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 lead to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data suggest that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.
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Proteínas Bacterianas/metabolismo , Péptido Hidrolasas/metabolismo , Enfermedades Periodontales , Infecciones por Treponema/metabolismo , Factores de Virulencia/metabolismo , Células Cultivadas , Humanos , Metaloproteinasas de la Matriz/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Enfermedades Periodontales/metabolismo , Enfermedades Periodontales/microbiología , Enfermedades Periodontales/patología , Ligamento Periodontal , Factor de Transcripción Sp1/metabolismo , Receptor Toll-Like 2/metabolismo , Treponema denticola , Infecciones por Treponema/patología , Regulación hacia ArribaRESUMEN
The oral squamous cell carcinoma (OSCC) 5 year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per year from 2005 to 2017, with higher survival rates when detected at early stages. Based on histopathological grading of oral dysplasia, it is estimated that severe dysplasia has a malignant transformation rate of 7%-50%. Despite these numbers, oral dysplasia grading does not reliably predict its clinical behavior. Thus, more accurate markers predicting oral dysplasia progression to cancer would enable better targeting of these lesions for closer follow-up, especially in the early stages of the disease. In this context, molecular biomarkers derived from genetics, proteins, and metabolites play key roles in clinical oncology. These molecular signatures can help predict the likelihood of OSCC development and/or progression and have the potential to detect the disease at an early stage and, support treatment decision-making and predict treatment responsiveness. Also, identifying reliable biomarkers for OSCC detection that can be obtained non-invasively would enhance management of OSCC. This review will discuss biomarkers for OSCC that have emerged from different biological areas, including genomics, transcriptomics, proteomics, metabolomics, immunomics, and microbiomics.
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OBJECTIVES: The objective of this study was to examine the association between the oral microbiome and pregnancy outcomes, specifically healthy or preterm low birth weight (PLBW) in individuals with and without periodontal disease (PD). MATERIAL AND METHODS: In this prospective clinical trial, we recruited 186 pregnant women, 17 of whom exhibited PD and delivered PLBW infants (PD-PLBW group). Of the remaining women, 155 presented PD and delivered healthy infants; 18 of these subjects with similar periodontal condition and age matched to the PD-PLBW group, and they became the PD-HD group. From the total group, 11 women exhibited healthy gingiva and had a healthy delivery (HD) and healthy infants (H-HD group), and 3 exhibited healthy gingiva and delivered PLBW infants (H-PLBW group). Periodontal parameters were recorded, and subgingival plaque and serum were collected during 26-28 gestational weeks. For the plaque samples, microbial abundance and diversity were accessed by 16S rRNA sequencing. RESULTS: Women with PD showed an enrichment in the genus Porphyromonas, Treponema, and Filifactor, whereas women with healthy gingiva showed an enrichment in Streptococcus, Actinomyces, and Corynebacterium, independently of the birth status. Although no significant difference was found in the beta diversity between the 4 groups, women that had PLBW infants presented a significantly lower abundance of the genus Neisseria, independently of PD status. CONCLUSION: Lower levels of Neisseria align with preterm low birth weight in pregnant women, whereas a higher abundance of Treponema, Porphyromonas, Fretibacterium, and Filifactor and a lower abundance of Streptococcus may contribute to periodontal disease during pregnancy. CLINICAL RELEVANCE: The oral commensal Neisseria have potential in the prediction of PLBW.
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Microbiota , Nacimiento Prematuro , Femenino , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Neisseria , Embarazo , Resultado del Embarazo , ARN Ribosómico 16SRESUMEN
The oral microbiome is a community of microorganisms, comprised of bacteria, fungi, viruses, archaea, and protozoa, that form a complex ecosystem within the oral cavity. Although minor perturbations in the environment are frequent and compensable, major shifts in the oral microbiome can promote an unbalanced state, known as dysbiosis. Dysbiosis can promote oral diseases, including periodontitis. In addition, oral dysbiosis has been associated with other systemic diseases, including cancer. The objective of this review is to evaluate the epidemiologic evidence linking periodontitis to oral, gastrointestinal, lung, breast, prostate, and uterine cancers, as well as describe new evidence and insights into the role of oral dysbiosis in the etiology and pathogenesis of the cancer types discussed. Finally, we discuss how antimicrobials, antimicrobial peptides, and probiotics may be promising tools to prevent and treat these cancers, targeting both the microbes and associated carcinogenesis processes. These findings represent a novel paradigm in the pathogenesis and treatment of cancer focused on the oral microbiome and antimicrobial-based therapies.
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Antiinfecciosos , Microbiota , Neoplasias de la Boca , Antiinfecciosos/uso terapéutico , Disbiosis , Humanos , Masculino , Neoplasias de la Boca/tratamiento farmacológicoRESUMEN
The effects of probiotic supplementation on systemic health and gastrointestinal diseases have been investigated in numerous studies. The aim of this review is to provide an overview of probiotics and their effects on periodontal health. Probiotics show beneficial effects as adjunctive therapeutics and as stand-alone agents in the treatment and prevention of gingivitis as well as specific clinical parameters of periodontitis. This review focuses on the clinical and microbiological aspects of probiotics in the context of health, gingivitis, and periodontitis. In addition, a special focus on nisin-producing probiotics and nisin itself showcase their significant potential for oral and systemic use.
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Gingivitis , Nisina , Periodontitis , Probióticos , HumanosRESUMEN
Schizophrenia is one of the top 25 causes of global diseases burdens in terms of years lived with the disease and the emotional and economical strains it imposes on the society. Several strategies have been used to treat the patients, specially using typical and atypical psychoactives. However, due to its multifactorial characteristic and patient resistance, schizophrenia is still a difficult disease to diagnose and treat. Thus, new strategies for diagnostics and treatment must be researched to optimize the efficacy and reduce the side effects of the actual therapy. Nanomedicine tries to improve low-weight molecular agents for treatment of diseases through the use of nanoscaled carriers. Among nanomedicine, nanopsychiatry specifically deals with the potential role of nanotechnology in solving psychiatry diseases problems. Therefore, the objective of this work is to provide an overview of the state of the art of nanopsychiatry in the sense of treating schizophrenia.
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Nanomedicina/métodos , Nanotecnología/métodos , Psiquiatría/métodos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , HumanosRESUMEN
Several scientific hurdles still have to be overcome before gene therapy becomes a reality. One of them is the development of safe and efficient gene delivery system. Here, we have employed factorial design to optimize the production of solid lipid nanoparticles (SLN) for gene delivery. A 2 x 3 full-factorial experimental design was used for the optimization of SLNs formulations. The variables were defined by the components of the formulation: concentration of stearic acid, DOTAP, and Pluronic F68 at two levels (-1, 1) and 3 central points (0). Different SNL formulations were prepared by varying the amount of components and several properties were tested, including their capacity to accommodate DNA and protection against DNase degradation, colloidal stability, in vitro cytotoxicity, and transfection efficiency in prostate cancer cells. Finally, response Surface Methodology was used to select the most effective formulation for gene delivery to prostate cancer cells in vitro. In conclusion, this study revealed that stearic acid and Pluronic F68 were determinant to SLN size and stability, respectively, while small amounts of DOTAP are essential for a successful transfection.
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ADN/genética , Terapia Genética/métodos , Lípidos/química , Liposomas/química , Neoplasias de la Próstata/genética , Transfección/métodos , Animales , Línea Celular Tumoral , Simulación por Computador , ADN/administración & dosificación , ADN/química , Diseño de Fármacos , Análisis Factorial , Liposomas/administración & dosificación , Masculino , Ratones , Modelos EstadísticosRESUMEN
Periodontal disease is characterized by the destruction of the hard and soft tissues comprising the periodontium. This destruction translates to a degradation of the extracellular matrices (ECM), mediated by bacterial proteases, host-derived matrix metalloproteinases (MMPs), and other proteases released by host tissues and immune cells. Bacterial pathogens interact with host tissue, triggering adverse cellular functions, including a heightened immune response, tissue destruction, and tissue migration. The oral spirochete Treponema denticola is highly associated with periodontal disease. Dentilisin, a T. denticola outer membrane protein complex, contributes to the chronic activation of pro-MMP-2 in periodontal ligament (PDL) cells and triggers increased expression levels of activators and effectors of active MMP-2 in PDL cells. Despite these advances, no mechanism for dentilisin-induced MMP-2 activation or PDL cytopathic behaviors leading to disease is known. Here, we describe a method for purification of large amounts of the dentilisin protease complex from T. denticola and demonstrate its ability to activate MMP-2, a key regulator of periodontal tissue homeostasis. The T. denticola dentilisin and MMP-2 activation model presented here may provide new insights into the dentilisin protein and identify potential therapeutic targets for further research. Key features ⢠This protocol builds upon a method described by Cunningham et al. [1] for selective release of Treponema outer membrane proteins. ⢠We adapted the protocol for the purification of biologically active, detergent-stable outer membrane protein complexes from large batch cultures of T. denticola. ⢠The protocol involves large-scale preparative electrophoresis using a Model 491 Prep Cell. ⢠We then use gelatin zymography to demonstrate the activity of the purified dentilisin complex by its ability to activate matrix metalloproteinase 2 (MMP-2).
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Complex metal nanostructures represent an exceptional category of materials characterized by distinct morphologies and physicochemical properties. Nanostructures with shape anisotropies, such as nanorods, nanostars, nanocages, and nanoprisms, are particularly appealing due to their tunable surface plasmon resonances, controllable surface chemistries, and effective targeting capabilities. These complex nanostructures can absorb light in the near-infrared, enabling noteworthy applications in nanomedicine, molecular imaging, and biology. The engineering of targeting abilities through surface modifications involving ligands, antibodies, peptides, and other agents potentiates their effects. Recent years have witnessed the development of innovative structures with diverse compositions, expanding their applications in biomedicine. These applications encompass targeted imaging, surface-enhanced Raman spectroscopy, near-infrared II imaging, catalytic therapy, photothermal therapy, and cancer treatment. This review seeks to provide the nanomedicine community with a thorough and informative overview of the evolving landscape of complex metal nanoparticle research, with a specific emphasis on their roles in imaging, cancer therapy, infectious diseases, and biofilm treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Diagnostic Nanodevices.
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Nanopartículas del Metal , Nanomedicina , Neoplasias , Humanos , Animales , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Nanoestructuras/química , RatonesRESUMEN
Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.
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Bacteriocinas , Nisina , Enfermedad del Hígado Graso no Alcohólico , Enfermedades Periodontales , Ratones , Humanos , Animales , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Nisina/farmacología , Nisina/metabolismo , Disbiosis , Enfermedades Periodontales/microbiología , Porphyromonas gingivalis/metabolismo , Inflamación/complicaciones , Estrés OxidativoRESUMEN
Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. Recent studies indicate that periodontal disease-associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Yet, the microbial signatures associated with the transition from healthy mucosa to dysplasia have not been established. To characterize oral microbial signatures at these different sites, we performed a 16S sequencing analysis of both oral swab and formalin-fixed, paraffin-embedded tissue (FFPE) samples. We collected oral swabs from healthy mucosa (from healthy patients), histologically normal mucosa adjacent to dysplasia, and low-grade oral dysplasia. Additionally, FFPE samples from histologically normal mucosa adjacent to OSCC, plus low grade and high-grade oral dysplasia samples were also collected. The collected data demonstrate significant differences in the alpha and beta microbial diversities of different sites in oral mucosa, dysplasia, and OSCC, as well as increased dissimilarities within these sites. We found that the Proteobacteria phyla abundance increased, concurrent with a progressive decrease in the Firmicutes phyla abundance, as well as altered levels of Enterococcus cecorum, Fusobacterium periodonticum, Prevotella melaninogenica, and Fusobacterium canifelinum when moving from healthy to diseased sites. Moreover, the swab sample analysis indicates that the oral microbiome may be altered in areas that are histologically normal, including in mucosa adjacent to dysplasia. Furthermore, trends in specific microbiome changes in oral swab samples preceded those in the tissues, signifying early detection opportunities for clinical diagnosis. In addition, we evaluated the gene expression profile of OSCC cells (HSC-3) infected with either P. gingivalis, T. denticola, F. nucelatum, or S. sanguinis and found that the three periodontopathogens enrich genetic processes related to cancer progression, including skin keratinization/cornification, while the commensal enriched processes related to RNA processing and adhesion. Finally, we reviewed the dysplasia microbiome literature and found a significant decrease in commensal bacteria, such as the Streptococci genus, and a simultaneous increase in pathogenic bacteria, mainly Bacteroidetes phyla and Fusobacterium genus. These findings suggest that features of the oral microbiome can serve as novel biomarkers for dysplasia and OSCC disease progression.
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Increased age is associated with an increased prevalence of chronic inflammatory diseases and conditions. The term inflammaging has been used to describe the age-related changes to the immune response that results in a chronic and elevated inflammatory state that contributes, in part, to the increased prevalence of disease in older adults. Periodontal disease is a chronic inflammatory condition that affects the periodontium and increases in prevalence with age. To better understand the mechanisms that drive inflammaging, a broad body of research has focused on the pathological age-related changes to key cellular regulators of the immune response. This review will focus on our current understanding of how certain immune cells (neutrophils, macrophages, T cells) change with age and how such changes contribute to inflammaging and more specifically to periodontal disease.
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Bacteriocins are peptides produced by bacteria to inhibit the growth of other prokaryotes. Nisin is a bacteriocin widely used in the food industry and for biomedical applications. However, bacteriocins have some limitations, as they experience mechanisms of resistance, degradation by proteases, and suboptimal intracellular delivery. Combining bacteriocins with nanoscale drug delivery systems (nano-DDS) is an approach that can help overcome these limitations. Among the nano-DDS, solid lipid nanoparticles (SLN) have been described as promising candidates, because of their potential for industrial scale-up and lower toxicity. The objective of this proof-of-concept study was to investigate the use of nisin-loaded SLN (SLN-Nisin) as an antimicrobial and anticancer therapeutic. We show that SLN-Nisin can significantly inhibit the growth of the oral pathogen, Treponema denticola, disrupt oral biofilms, and decrease oral squamous cell carcinoma cell (OSCC) viability compared to free nisin. Further, analysis with scanning electron microscopy (SEM) revealed significant morphological changes in OSCC cells challenged with SLN-Nisin, compared to the empty-nanoparticle or free nisin, indicating that SLN-Nisin likely decreases cell viability by increasing pore formation. This data reveals that nano-DDS are robust tools that can enhance bacteriocin properties.
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Antineoplásicos , Bacteriocinas , Carcinoma de Células Escamosas , Neoplasias de la Boca , Nanopartículas , Nisina , Antibacterianos/química , Antineoplásicos/farmacología , Bacteriocinas/química , Bacteriocinas/metabolismo , Bacteriocinas/farmacología , Biopelículas , Humanos , Liposomas , Nisina/química , Nisina/metabolismo , Nisina/farmacologíaRESUMEN
Peri-implantitis is characterized by chronic inflammation of the peri-implant supporting tissues that progressively and irreversibly leads to bone loss and, consequently, implant loss. Similar to periodontal disease, oral dysbiosis is thought to be a driver of peri-implantitis. However, managing peri-implantitis with traditional treatment methods, such as nonsurgical debridement or surgery, is not always successful. Thus, novel strategies have been proposed to address these shortcomings. One strategy is the use of probiotics as antimicrobial agents since they are considered safe for humans and the environment. Specifically, the probiotic Lactococcus lactis produces nisin, which has been used worldwide for food preservation. The objective of this study was to determine whether nisin and the wild-type (WT) nisin-producing L. lactis probiotic can disrupt oral pathogenic biofilms and promote a healthier oral microbiome within these oral biofilms on titanium discs. Using confocal imaging and 16S rRNA sequencing, this study revealed that nisin and WT L. lactis probiotic disrupt oral pathogenic biofilms in a peri-implantitis setting in vitro. More specifically, nisin decreased the viability of the pathogen-spiked biofilms dose-dependently from 62.53 ± 3.69% to 54.26 ± 3.35% and 44.88 ± 2.98%, respectively. Similarly, 105 CFU/mL of WT L. lactis significantly decreased biofilm viability to 52.45 ± 3.41%. Further, both treatments shift the composition, relative abundance, and diversity levels of these biofilms towards healthy control levels. A total of 1 µg/mL of nisin and 103 CFU/mL of WT L. lactis were able to revert the pathogen-mediated changes in the Proteobacteria (from 80.5 ± 2.9% to 75.6 ± 2.0%, 78.0 ± 2.8%, and 75.1 ± 5.3%, respectively) and Firmicutes (from 11.6 ± 1.6% to 15.4 ± 1.3%, 13.8 ± 1.8%, and 13.7 ± 2.6%, respectively) phyla back towards control levels. Thus, nisin and its nisin-producing L. lactis probiotic may be useful in treating peri-implantitis by promoting healthier oral biofilms, which may be useful for improving patient oral health.
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OBJECTIVES: Leishmaniasis is a zoonotic disease and several drugs have been used in the treatment, including meglumine antimoniate (AME). The chemotherapy reaches clinical cure but does not eliminate parasites, contributing to drug resistance. To improve AME efficacy we incorporated it in anionic liposomes. The antiparasitic activity and intracellular localization were investigated in canine macrophages infected with Leishmania infantum. METHODS: Liposomes (L-AME) is composed of egg phosphatidylcholine, cholesterol, palmitoyl oleoyl phosphatidyl serine and α-tocopherol (4 : 3 : 0.4 : 0.07 mol%) plus AME. L-AME size, polydispersity, zeta potential and morphology were analysed as well as antileishmanial activity and intracellular localization in DH82 macrophages. KEY FINDINGS: Liposomes (360 nm) zeta potential range from -40 to -65 mV, had 23% encapsulation efficiency and were stable for 180 days at 4°C. Free AME was cytotoxic towards L. infantum infected macrophages (ID50 = 0.012 M) while L-AME did not reduce cell viability. L-AME colocalized with parasites inside macrophages in a time-dependent manner, and reduced the percentage of infected cells and the number of intracellular parasites, decreasing the infection index (75-80%) twice as compared with AME treatment. CONCLUSIONS: Liposomal AME is a promising delivery system for treating visceral leishmaniasis, improving meglumine efficacy against L. infantum and minimizing its cytotoxicity towards canine macrophages.
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Leishmania infantum , Compuestos Organometálicos , Animales , Perros , Liposomas , Macrófagos , Antimoniato de Meglumina/farmacología , Ratones , Ratones Endogámicos BALB C , Compuestos Organometálicos/farmacología , Compuestos Organometálicos/uso terapéuticoRESUMEN
Dysbiosis of the oral microbiome mediates chronic periodontal disease. Realignment of microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. Antibacterial peptides or bacteriocins, such as nisin, and a nisin-producing probiotic, Lactococcus lactis, have not been examined in this context, yet warrant examination because of their biomedical benefits in eradicating biofilms and pathogenic bacteria, modulating immune mechanisms, and their safety profile in humans. This study's goal was to examine the potential for nisin and a nisin-producing probiotic to abrogate periodontal bone loss, the host inflammatory response, and changes in oral microbiome composition in a polymicrobial mouse model of periodontal disease. Nisin and a nisin-producing Lactococcus lactis probiotic significantly decreased the levels of several periodontal pathogens, alveolar bone loss, and the oral and systemic inflammatory host response. Surprisingly, nisin and/or the nisin-producing L. lactis probiotic enhanced the population of fibroblasts and osteoblasts despite the polymicrobial infection. Nisin mediated human periodontal ligament cell proliferation dose-dependently by increasing the proliferation marker, Ki-67. Nisin and probiotic treatment significantly shifted the oral microbiome towards the healthy control state; health was associated with Proteobacteria, whereas 3 retroviruses were associated with disease. Disease-associated microbial species were correlated with IL-6 levels. Nisin or nisin-producing probiotic's ability to shift the oral microbiome towards health, mitigate periodontal destruction and the host immune response, and promote a novel proliferative phenotype in reparative connective tissue cells, addresses key aspects of the pathogenesis of periodontal disease and reveals a new biomedical application for nisin in treatment of periodontitis and reparative medicine.
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Pérdida de Hueso Alveolar , Lactococcus lactis , Microbiota , Nisina , Enfermedades Periodontales , Probióticos , Pérdida de Hueso Alveolar/prevención & control , Animales , Antibacterianos , Proliferación Celular , Disbiosis , Lactococcus lactis/genética , Ratones , Enfermedades Periodontales/microbiologíaRESUMEN
The oralome is the summary of the dynamic interactions orchestrated between the ecological community of oral microorganisms (comprised of up to approximately 1000 species of bacteria, fungi, viruses, archaea and protozoa - the oral microbiome) that live in the oral cavity and the host. These microorganisms form a complex ecosystem that thrive in the dynamic oral environment in a symbiotic relationship with the human host. However, the microbial composition is significantly affected by interspecies and host-microbial interactions, which in turn, can impact the health and disease status of the host. In this review, we discuss the composition of the oralome and inter-species and host-microbial interactions that take place in the oral cavity and examine how these interactions change from healthy (eubiotic) to disease (dysbiotic) states. We further discuss the dysbiotic signatures associated with periodontitis and caries and their sequalae, (e.g., tooth/bone loss and pulpitis), and the systemic diseases associated with these oral diseases, such as infective endocarditis, atherosclerosis, diabetes, Alzheimer's disease and head and neck/oral cancer. We then discuss current computational techniques to assess dysbiotic oral microbiome changes. Lastly, we discuss current and novel techniques for modulation of the dysbiotic oral microbiome that may help in disease prevention and treatment, including standard hygiene methods, prebiotics, probiotics, use of nano-sized drug delivery systems (nano-DDS), extracellular polymeric matrix (EPM) disruption, and host response modulators.
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Prostate and breast cancer are the current leading causes of new cancer cases in males and females, respectively. Phosphatidylserine (PS) is an essential lipid that mediates macrophage efferocytosis and is dysregulated in tumors. Therefore, developing therapies that selectively restore PS may be a potential therapeutic approach for carcinogenesis. Among the nanomedicine strategies for delivering PS, biocompatible gold nanoparticles (AuNPs) have an extensive track record in biomedical applications. In this study, we synthesized biomimetic phosphatidylserine-caped gold nanoparticles (PS-AuNPs) and tested their anticancer potential in breast and prostate cancer cells in vitro. We found that both cell lines exhibited changes in cell morphology indicative of apoptosis. After evaluating for histone-associated DNA fragments, a hallmark of apoptosis, we found significant increases in DNA fragmentation upon PS-AuNP treatment compared to the control treatment. These findings demonstrate the use of phosphatidylserine coupled with gold nanoparticles as a potential treatment for prostate and breast cancer. To the best of our knowledge, this is the first time that a phosphatidylserine-capped AuNP has been examined for its therapeutic potential in cancer therapy.
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Gingival crevicular fluid (GCF) is a physiological fluid and an inflammatory serum exudate derived from the gingival plexus of blood vessels and mixed with host tissues and subgingival plaque flows. In addition to proteins, GCF contains a diverse population of cells, including desquamated epithelial cells, cytokines, electrolytes, and bacteria from adjacent plaques. Recently, matrix metalloproteinases(MMPs), which are endopeptidases that are active against extracellular macromolecules, in GCF have been revealed as potential utility biomarkers for the diagnosis and follow-up of oral and systemic diseases, thereby facilitating the early evaluation of malignancy risk and the monitoring of disease progression and treatment response. Tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of matrixins that participate in the regulation of local activities of MMPs in tissues. This review provides an overview of the latest findings on the diagnostic and prognostic values of MMPs and TIMPs in GCF of oral and systemic diseases, including periodontal disease, pulpitis, peri-implantitis and cardiovascular disease as well as the extraction, detection and analytical methods for GCF.