Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases.

Regenerative medicine harnesses the body's innate capacity for self-repair to restore malfunctioning tissues and organs. Stem cell therapies represent a key regenerative strategy, but to effectively harness their potential necessitates a nuanced understanding of the stem cell niche. This specialized microenvironment regulates critical stem cell behaviors including quiescence, activation, differentiation, and homing. Emerging research reveals that dysfunction within endogenous neural stem cell niches contributes to neurodegenerative pathologies and impedes regeneration. Strategies such as modifying signaling pathways, or epigenetic interventions to restore niche homeostasis and signaling, hold promise for revitalizing neurogenesis and neural repair in diseases like Alzheimer's and Parkinson's. Comparative studies of highly regenerative species provide evolutionary clues into niche-mediated renewal mechanisms. Leveraging endogenous bioelectric cues and crosstalk between gut, brain, and vascular niches further illuminates promising therapeutic opportunities. Emerging techniques like single-cell transcriptomics, organoids, microfluidics, artificial intelligence, in silico modeling, and transdifferentiation will continue to unravel niche complexity. By providing a comprehensive synthesis integrating diverse views on niche components, developmental transitions, and dynamics, this review unveils new layers of complexity integral to niche behavior and function, which unveil novel prospects to modulate niche function and provide revolutionary treatments for neurodegenerative diseases.

Clinical Efficacy of Extracellular Vesicle Therapy in Periodontitis: Reduced Inflammation and Enhanced Regeneration.

Periodontitis, a prevalent inflammatory condition, affects the supporting structures of teeth, leading to significant oral health challenges. Traditional treatments have primarily focused on mechanical debridement, antimicrobial therapy, and surgery, which often fail to restore lost periodontal structures. Emerging as a novel approach in regenerative medicine, extracellular vesicle (EV) therapy, including exosomes, leverages nano-sized vesicles known for facilitating intercellular communication and modulating physiological and pathological processes. This study is a proof-of-concept type that evaluates the clinical efficacy of EV therapy as a non-surgical treatment for stage I-III periodontitis, focusing on its anti-inflammatory and regenerative potential. The research involved seven patients undergoing the therapy, and seven healthy individuals. Clinical parameters, including the plaque index, bleeding on probing, probing depth, and attachment level, were assessed alongside cytokine levels in the gingival crevicular fluid. The study found significant improvements in clinical parameters, and a marked reduction in pro-inflammatory cytokines post-treatment, matching the levels of healthy subjects, underscoring the therapy's ability to not only attenuate inflammation and enhance tissue regeneration, but also highlighting its potential in restoring periodontal health. This investigation illuminates the promising role of EV therapy in periodontal treatment, advocating for a shift towards therapies that halt disease progression and promote structural and functional restoration of periodontal tissues.

Cytokine Dynamics in Autism: Analysis of BMAC Therapy Outcomes.

Autism spectrum disorder (ASD) has recently been linked to neuroinflammation and an aberrant immune response within the central nervous system. The intricate relationship between immune response and ASD remains elusive, with a gap in understanding the connection between specific immune mechanisms and neural manifestations in autism. In this study, we employed a comprehensive statistical approach, fusing both overarching and granular methods to examine the concentration of 16 cytokines in the cerebrospinal fluid (CSF) across each autologous bone marrow aspirate concentrate (BMAC) intrathecal administration in 63 male and 17 female autism patients. Following a six-month period post the third administration, patients were stratified into three categories based on clinical improvement: Group 1- no/mild (28 subjects), Group 2-moderate (16 subjects), and Group 3-major improvement (15 subjects). Our integrated analysis revealed pronounced disparities in CSF cytokine patterns and clinical outcomes in autism subjects pre- and post-BMAC transplantation. Crucially, our results suggest that these cytokine profiles hold promise as predictive markers, pinpointing ASD individuals who might not exhibit notable clinical amelioration post-BMAC therapy.

Cytokine producing ability of peripheral blood cells from COVID-19 patients after unspecific in vitro stimulation.

OBJECTIVE AND DESIGN: Perturbations of peripheral T cell homeostasis and dysregulation of the immune response to SARS-CoV-2, especially in severely ill patients, were observed. The aim of this study was to analyze the cytokine producing ability of peripheral blood cells from severely ill COVID-19 patients upon non-specific in vitro stimulation with phytohemagglutinin (PHA). Possible associations of cytokine levels with patients' age and gender, glucocorticosteroid therapy, as well as the trend of the inflammatory process at the time of sampling (increased or decreased) were also analyzed. SUBJECTS AND METHODS: The study included 23 COVID-19 patients and 17 healthy control subjects. The concentrations of selected Th1/Th2/Th9/Th17/Th22 cytokines were determined using a multi-analyte flow assay kit. RESULTS: Our results showed that peripheral blood cells from severely ill COVID-19 patients had a much reduced ability to produce cytokines in comparison to healthy controls. When inflammation was raised, blood cells produced more IL-6 and IL-17, which led to increases of some Th17/Th1 and Th17/Th2 ratios, skewing towards the Th17 type of response. The methylprednisolone used in the treatment of patients with COVID-19 influences the production of several cytokines in dose dependent manner. CONCLUSION: Our results indicate that the stage of the inflammatory process at the time of sampling and the dose of the applied glucocorticosteroid therapy might influence cytokine producing ability upon non-specific stimulation of T cells in vitro.

Analysis of the concentrations of some haematological parameters, C-reactive protein and anti-Müllerian hormone in bitches affected by pyometra.

The work was aimed to research into the vital signs, haematological and biochemical parameters, acute-phase protein concentrations (CRP, albumin), progesterone (PG) and anti-Müllerian hormone (AMH) concentrations in bitches with pyometra and their comparison with those in healthy bitches. In addition, the goal of this work was to assess if some of the tested parameters may be used as a biomarker in the diagnostics of pyometra and the monitoring of the postoperative recovery. Forty 3-6-year-old bitches of various breeds were included in the research and allotted to two groups: the control (C, n = 20) and the diseased - bitches diagnosed with pyometra (P, n = 20). Blood samples for the analyses were taken immediately before surgery (0 h), and 12 h, 24 h, 48 h and 72 h after, excepting for AMH and PG concentrations, which were determined only at 0 h. Clinical examination detected significantly higher respiration rates in bitches with pyometra in comparison to healthy ones at all time points, higher heart rates before and 12 h after surgery, and higher body temperature before and 12 h, 48 h and 72 h post operation (p < .01). Significantly higher concentrations of CRP (p < .01) and lower concentrations of albumin were detected in bitches with pyometra in comparison to their healthy counterparts at all time points. Progesterone and AMH concentration analysis immediately before surgery detected significantly higher levels of the hormone in bitches with pyometra than in the control (p < .01). The inflammatory reaction of the endometrium resulted in a significant AMH concentration increase, whilst increased CRP concentrations and lower albumin concentrations throughout the research may be used as biomarkers of proinflammatory activities, that is of the acute-phase response.

Stem Cell Homing in Intrathecal Applications and Inspirations for Improvement Paths.

A transplanted stem cell homing is a directed migration from the application site to the targeted tissue. Intrathecal application of stem cells is their direct delivery to cerebrospinal fluid, which defines the homing path from the point of injection to the brain. In the case of neurodegenerative diseases, this application method has the advantage of no blood-brain barrier restriction. However, the homing efficiency still needs improvement and homing mechanisms elucidation. Analysis of current research results on homing mechanisms in the light of intrathecal administration revealed a discrepancy between in vivo and in vitro results and a gap between preclinical and clinical research. Combining the existing research with novel insights from cutting-edge biochips, nano, and other technologies and computational models may bridge this gap faster.

Is otitis media with effusion associated with Samter's triad a new nosological entity? A preliminary report on inflammatory mediator production.

PURPOSE: Otitis media with effusion (OME) associated with Samter's triad (ST) is a difficult entity to treat. The aim of study was an investigation of the middle ear and nasal production of inflammatory mediators (IM) in patients with ST and analysing differences between them and controls. METHODS: Prospective case-control study. Nineteen patients with OME (five had allergic rhinitis, four had nasopharyngeal lymphoid hyperplasia, five had no evident sino-nasopharyngeal disease and five had confirmed ST) and 15 healthy participants were included. The concentrations of IM interleukin-1 beta (IL-1ß), interferon-alpha 2 (IFN-α2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23 and IL-33 were measured in nasal and middle ear secretions. RESULTS: There was a difference that was close to a level of statistical significance only for IL-1ß levels in middle ear fluid (p = 0.052) between the ST subgroup and the other patients with OME. Also, we found a significant difference for IL-23 in nasal secretions between these subgroups (p = 0.040), whereas the difference in nasal fluid IL-33 was close to a level of statistical significance (p = 0.052). There was a significant difference in nasal concentrations of IL-1ß, IFN-α2, MCP-1, IL-8, IL-18 and IL-33 (p < 0.001, p = 0.005, p = 0.008, p = 0.011, p = 0.011 and p = 0.011, respectively) between the OME group and the healthy subjects. There were significant positive correlations between concentrations of IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-17A, IL-18 and IL-33 (p < 0.001, p < 0.001, p = 0.002, p = 0.028, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively) in nasal and middle ear secretions. CONCLUSION: This preliminary report showed some differences in IM production between the patients with OME associated with ST and those without it. Our results suggest a uniformity of the production of nasal and middle ear IM and supported the concept of a united airway respiratory disease.

A Roadmap towards Precision Periodontics.

Periodontitis is among the most common health conditions and represents a major public health issue related to increasing prevalence and seriously negative socioeconomic impacts. Periodontitis-associated low-grade systemic inflammation and its pathological interplay with systemic conditions additionally raises awareness on the necessity for highly performant strategies for the prevention and management of periodontitis. Periodontal diagnosis is the backbone of a successful periodontal strategy, since prevention and treatment plans depend on the accuracy and precision of the respective diagnostics. Periodontal diagnostics is still founded on clinical and radiological parameters that provide limited therapeutic guidance due to the multifactorial complexity of periodontal pathology, which is why biomarkers have been introduced for the first time in the new classification of periodontal and peri-implant conditions as a first step towards precision periodontics. Since the driving forces of precision medicine are represented by biomarkers and machine learning algorithms, with the lack of periodontal markers validated for diagnostic use, the implementation of a precision medicine approach in periodontology remains in the very initial stage. This narrative review elaborates the unmet diagnostic needs in periodontal diagnostics, the concept of precision periodontics, periodontal biomarkers, and a roadmap toward the implementation of a precision medicine approach in periodontal practice.

Interleukin-33 pretreatment promotes metastatic growth of murine melanoma by reducing the cytotoxic capacity of CD8+ T cells and enhancing regulatory T cells.

Interleukin-33 (IL-33) regulates innate and acquired immune response to pathogens, self-antigens and tumors. IL-33 effects on tumors depend on the dose and mode of administration along with the type of malignancy. We studied the effects of IL-33 on the development of primary and metastatic melanoma induced by B16-F1 cell line in C57BL/6 mice. Intraperitoneally applied IL-33 restricts primary tumor growth. When administered intranasally 3 days prior to the intravenous injection of the tumor cells, IL-33 promoted growth of B16-F1 melanoma metastases, while B16-F10 gave massive metastases independently of IL-33. To mimic natural dissemination, we next used a limited number (5 × 104) of B16-F1 cells intravenously followed by application of IL-33 intraperitoneally. IL-33 increased the size of metastases (10.96 ± 3.96 mm2) when compared to the control group (0.86 ± 0.39 mm2), without changing incidence and number of metastases. IL-33 increased expression of ST2 on both tumor and immune cells in metastases. Also, IL-33 enhanced eosinophils and anti-tumor NK cells in the lung. The striking finding was reduced cytotoxicity of CD8+ T cells derived from metastatic lung of IL-33 injected mice. IL-33 reduced the percentage of TNF-α+ and IFN-γ+ CD8+ T cells while increasing the frequency of CD8+ T cells that express inhibitory molecules (PD-1, KLRG-1 and CTLA-4). There was a significant accumulation of CD11b+Gr-1+ myeloid suppressor cells and FoxP3+, IL-10+ and CTLA-4+ regulatory T cells in the metastatic lung of IL-33 injected mice. The relevance of IL-33 for melanoma metastases was also documented in a significantly increased level of serum IL-33 in stage III melanoma patients.

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma.

BACKGROUND AND OBJECTIVES: The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. METHODS: Concentrations of galectin-3, TNF-α, TGF-ß, IL-10, and IL-1ß were analyzed in samples of blood and stool of 60 patients with CRC. RESULTS: Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-ß and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. CONCLUSIONS: Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. METHODS: A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. RESULTS: NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. CONCLUSIONS: NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma.

Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR(-/low), CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI) < 12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI.

Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium.

Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O2·-) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.

Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children.

UNLABELLED: In order to assess the association between gene polymorphisms and otitis media (OM) proneness, tumor necrosis factor alpha (TNFA) -308, interleukin (IL) 10-1082 and -3575, IL6 -597, IL2 -330, and CD14 -159 genotyping was performed in 58 OM-prone children and 85 controls who were exposed to similar number and frequency of environmental and host risk factors. The frequencies of genotypes (wild type vs. genotypes containing at least one polymorphic allele) were not significantly different between groups, except for IL10 -1082. Polymorphic genotypes IL10 -1082 GA and GG were more frequent in OM-prone children than in control group (RR 1.145, 95 % CI 1.011-1.298; p = 0.047). However, logistic regression did not confirm IL10 -1082 polymorphic genotypes as an independent risk factor for OM proneness. CONCLUSION: The present study indicates that high-producing IL10 -1082 GA/GG genotypes may increase the risk for OM proneness in its carriers when exposed to other environmental/host risk factors (day care attendance, passive smoking, male sex, respiratory infections, and atopic manifestations). This study revealed no significant independent genetic association, but the lack of breastfeeding in infancy was found to be the only independent risk factor for development of OM-prone phenotype, implying that breastfeeding had a protective role in development of susceptibility to OM. WHAT IS KNOWN: • The pathogenesis of OM is of multifactorial nature, dependent on infection, environmental factors, and immune response of the child. • Cytokines and CD14 play an important role in the presentation and clinical course of otitis media, but a clear link with otitis media proneness was not established. What is new: • This is the first clinical and genetic study on Montenegrin children with the otitis media-prone phenotype. • The study revealed that high-producing IL10 -1082 genotypes may influence otitis media proneness in children exposed to other environmental/host risk factors.

Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma.

PURPOSE: Advanced lung carcinoma is charasterized with fast disease progression. Interleukin (IL)10 and transforming growth factor (TGF)b1 are immunosuppressive mediators and their role in lung carcinoma pathogenesis and in the antitumor response has not yet been elucidated. The purpose of this study was to correlate IL10 and TGFb1 levels in the serum and lung tumor microcirculation with clinical stage, disease extent, histological features and TNM stage. METHODS: The study included 41 lung cancer patients in clinical stage III and IV. Histological type was determined immunohistochemically, while tumor size, localization and dissemination were determined radiologically by multislice computerized tomography (MSCT). IL10 and TGFb1 levels were quantified with commercial flow cytometric test in serum and lung tumor microcirculation samples. RESULTS: Non small cell lung cancer (NSCLC) patients had significantly elevated TGFb1 while small cell lung cancer (SCLC) patients had significantly increased IL10 in tumor microcirculation. IL10 was significantly elevated in patients with the largest tumors, as well as in patients with III clinical stage and without metastases, both in the serum and tumor microcirculation. TGFb1 was significantly increased in serum and tumor microcirculation in patients with larger tumors. We found significant correlation between these two immunosuppressive cytokines, IL10 and TGFb1, in tumor microcirculation but not in patient serum samples. CONCLUSION: IL10 and TGFb1 in systemic and tumor microcirculation are significantly associated with particular histological type of lung cancer, tumor size and degree of disease extent.

CD14 and TNFα single nucleotide polymorphisms are candidates for genetic biomarkers of peri-implantitis.

OBJECTIVES: This study aims to investigate whether CD14-159 C/T and TNFα -308 A/G single nucleotide polymorphisms are associated with peri-implantitis and to evaluate their effects on bone resorption by correlating with local levels of receptor activator nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). MATERIAL AND METHODS: Study population included 369 Southeastern Europe Caucasians (180 with peri-implantitis and 189 with healthy peri-implant tissues). Genotyping was performed using polymerase chain reaction from the periphery blood samples, while RANKL and OPG were evaluated in peri-implant crevicular fluid specimens using enzyme-linked immunosorbent assay. RESULTS: Analysis of CD14-159 C/T polymorphism showed that genotype of CC nucleic acid combination was associated with peri-implantitis demonstrating a fivefold increased risk in these carriers. Furthermore, for TNFα -308 A/G polymorphisms, it was evidenced that AG genotype was associated with peri-implantitis and a fivefold increased risk in these carriers. Peri-implantitis patients with CC genotype at CD14-159 exhibited significantly higher concentrations of RANKL and relative ratio RANKL/OPG when compared to patients with CT genotype, while concentration of biomarkers between different genotypes at TNFα -308 remained insignificant. CONCLUSION: Within the limitations of the study, we can conclude that CD14-159 C/T and TNFα -308 A/G polymorphisms are associated with peri-implantitis and may present biomarkers for peri-implantitis. CLINICAL RELEVANCE: Investigated genetic markers might serve as precious parameters in clinical practice in course of treatment planning and prognosis, since preventive and treatment approach could be positively shifted and adjusted depending on present genotype.

Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study.

OBJECTIVES: VEGF is prototypic marker of neovascularization, repeatedly proposed as intrinsic characteristic of peri-implantitis. This study aimed to assess pattern of VEGF in peri-implantitis, its correlation with titanium particles (TPs) and capacity as respective biomarker. MATERIAL AND METHODS: Pathological specificity of VEGF was assessed in peri-implant granulations using immunohistochemistry, periodontal granulations represented Ti-free positive controls. VEGF was correlated to TPs, identified using scanning electron microscopy coupled with dispersive x-ray spectrometry. Diagnostic accuracy, sensitivity and specificity of VEGF were estimated in PICF specimens from peri-implantitis, peri-implant mucositis (PIM) and healthy peri-implant tissues (HI) using machine learning algorithms. RESULTS: Peri-implantitis exhibited rich neovascular network with expressed density in contact zones toward neutrophil infiltrates without specific pattern variations around TPs, identified in all peri-implantitis specimens (mean particle size 8.9 ± 24.8 µm2; Ti-mass (%) 0.380 ± 0.163). VEGF was significantly more expressed in peri-implantitis (47,065 ± 24.2) compared to periodontitis (31,14 ± 9.15), and positively correlated with its soluble concentrations in PICF (p = 0.01). VEGF was positively correlated to all clinical endpoints and significantly increased in peri-implantitis compared to both PIM and HI, but despite high specificity (96%), its overall diagnostic capacity was average. Two patient clusters were identified in peri-implantitis, one with 8-fold higher VEGF values compared to HI, and second with lower values comparable to PIM. SIGNIFICANCE: VEGF accurately reflects neovascularization in peri-implantitis that was expressed in contact zones toward implant surface without specific histopathological patter variation around TPs. VEGF answered requests for biomarker of peri-implantitis but further research is necessary to decrypt its exact underlying cause.

The effect of nasal douching by hypertonic 2.3 per cent sea water with algae extracts on the concentration of epidermal growth factor, transforming growth factor-α and interleukin-8 in nasal secretions of patients with nasal polyposis following endoscopic surgical treatment.

OBJECTIVE: To investigate epidermal growth factor, transforming growth factor-α and interleukin-8 production in nasal mucosa irrigated with hypertonic 2.3 per cent solution with algae extracts, in comparison to 0.9 per cent NaCl during the first two weeks after surgery for nasal polyposis, in relation to symptoms and local findings. METHODS: This prospective study included 20 nasal polyposis patients postoperatively irrigated with hypertonic solution and 20 nasal polyposis patients postoperatively irrigated with isotonic solution. We evaluated nasal symptom score, endoscopic score and mediator levels in nasal secretions before and after irrigation. RESULTS: Following treatment, nasal symptom score and endoscopic score were significantly lower in the hypertonic solution group (p = 0.023; p < 0.001, respectively). The increase in the epidermal growth factor and the decrease in the transforming growth factor-α and interleukin-8 concentration were higher in the hypertonic group (p < 0.001 for all mediators). CONCLUSION: Irrigation with a hypertonic solution was found to be more effective than an isotonic solution in nasal mucosa reparation.

Bone loss biomarkers associated with peri-implantitis. A cross-sectional study.

AIM: To investigate the levels of biomarkers associated with osteoclastogenesis in patients suffering peri-implantitis and to compare them with levels in healthy peri-implant sites and severe chronic periodontitis. MATERIAL AND METHODS: Peri-implant/gingival crevicular fluid samples and clinical parameters including: bleeding on probing, modified Plaque Index (PlI), pocket depth and clinical attachment level were collected from 70 patients (23 with peri-implantitis, 25 with healthy peri-implant tissues and 22 with severe chronic periodontitis). The concentrations of sRANKL, RANK and OPG were evaluated using enzyme-linked immunosorbent assays; they were compared between the groups and correlated with the clinical findings. RESULTS: sRANKL (P = 0.01), RANK (P = 0.01) and OPG (P = 0.03) concentrations were significantly higher in peri-implantitis sites when compared to those in healthy implant sites, although differences in the sRANKL/OPG ratio were not statistically significant. In these sites all three markers were significantly correlated with the clinical parameters, with exception of OPG/PI correlation that remained insignificant (P = 0.121). When comparing peri-implantitis and periodontitis findings, RANK was significantly higher in peri-implantitis sites whereas, sRANKL (P = 0.03) and sRANKL/OPG ratio (P = 0.004) were significantly higher in periodontitis sites. Among periodontitis and healthy implant sites the same differences have been observed for both sRANKL (P = 0.000) and sRANKL/OPG ratio (P = 0.000), furthermore RANK was higher in periodontitis sites as well (P = 0.010). CONCLUSION: The findings of this preliminary study on a relatively small sample size suggest that the PICF levels of biomarkers sRANKL, RANK, and OPG are associated with peri-implant tissue destruction and the pattern of these biomarkers differed when compared to periodontitis.