Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease.

Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis1. Amelogenesis depends on multiple ameloblast-derived proteins that function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta2. Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency3,4, and in patients diagnosed with coeliac disease5-7. However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and coeliac disease develop autoantibodies (mostly of the IgA isotype) against ameloblast-specific proteins, the expression of which is induced by AIRE in the thymus. This in turn results in a breakdown of central tolerance, and subsequent generation of corresponding autoantibodies that interfere with enamel formation. However, in coeliac disease, the generation of such autoantibodies seems to be driven by a breakdown of peripheral tolerance to intestinal antigens that are also expressed in enamel tissue. Both conditions are examples of a previously unidentified type of IgA-dependent autoimmune disorder that we collectively name autoimmune amelogenesis imperfecta.

PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype.

Cancers reprogram macrophages (MΦs) to a tumor-growth-promoting TAM (tumor-associated MΦ) phenotype that is similar to the anti-inflammatory M2 phenotype. Poly(ADP-ribose) polymerase (PARP) enzymes regulate various aspects of MΦ biology, but their role in the development of TAM phenotype has not yet been investigated. Here, we show that the multispectral PARP inhibitor (PARPi) PJ34 and the PARP14 specific inhibitor MCD113 suppress the expression of M2 marker genes in IL-4-polarized primary murine MΦs, in THP-1 monocytic human MΦs, and in primary human monocyte-derived MΦs. MΦs isolated from PARP14 knockout mice showed a limited ability to differentiate to M2 cells. In a murine model of TAM polarization (4T1 breast carcinoma cell supernatant transfer to primary MΦs) and in a human TAM model (spheroids formed from JIMT-1 breast carcinoma cells and THP-1-MΦs), both PARPis and the PARP14 KO phenotype caused weaker TAM polarization. Increased JIMT-1 cell apoptosis in co-culture spheroids treated with PARPis suggested reduced functional TAM reprogramming. Protein profiling arrays identified lipocalin-2, macrophage migration inhibitory factor, and plasminogen activator inhibitor-1 as potential (ADP-ribosyl)ation-dependent mediators of TAM differentiation. Our data suggest that PARP14 inhibition might be a viable anticancer strategy with a potential to boost anticancer immune responses by reprogramming TAMs.

The influence of immediate intraoperative loading with a splinting component on supporting tissues during a one-stage implant.

OBJECTIVE: Aim: To study the specifics of the impact of immediate intraoperative loading with a splinting component on supporting tissues during a one-stage implantation protocol. PATIENTS AND METHODS: Materials and Methods: In the course of the study, orthopedic treatment was carried out for 55 patients aged 29 to 60 years. The following were performed: cone-beam computed tomography, software planning and intraoral scanning with an optical scanner, one-stage implantation protocol, assessment of implant stability with the Osstell ISQ device, microcirculation study in the peri-implant area using laser Doppler flowmetry (LDF). RESULTS: Results: It was established that around loaded implants there is an increase in blood flow and vasomotor activity of the microcirculatory channel of the supporting tissues, an increase in the volume of bone tissue and an increase in torque, which is the optimal forecast for the acceleration of the pace of osseointegration. CONCLUSION: Conclusions: The use of a splinting component during immediate intraoperative functional masticatory load accelerates the dynamics of bone tissue remodeling processes around the implant, which is an optimal prediction of osseointegration rates in various dental implantation protocols and is consistent with high values of the implant stability coefficient.

KDM1A inhibition increases UVA toxicity and enhances photodynamic therapy efficacy.

BACKGROUND: Lysine-specific histone demethylase 1 (KDM1A/LSD1) regulates multiple cellular functions, including cellular proliferation, differentiation, and DNA repair. KDM1A is overexpressed in squamous cell carcinoma of the skin and inhibition of KDM1A can suppress cutaneous carcinogenesis. Despite the role of KDM1A in skin and DNA repair, the effect of KDM1A inhibition on cellular ultraviolet (UV) response has not been studied. METHODS: The ability of KDM1A inhibitor bizine to modify cell death after UVA and UVB exposure was tested in normal human keratinocytes and melanocytes, HaCaT, and FaDu cell lines. KDM1A was also downregulated using shRNA and inhibited by phenelzine in HaCaT and FaDu cells to confirm the role of KDM1A in UVA response. In addition, cellular reactive oxygen species (ROS) changes were assessed by a lipid-soluble fluorescent indicator of lipid oxidation, and ROS-related gene regulation using qPCR. During photodynamic therapy (PDT) studies HaCaT and FaDu cells were treated with aminolaevulinic acid (5-ALA) or HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) sodium and irradiated with 0-8 J/cm2 red LED light. RESULTS: KDM1A inhibition sensitized cells to UVA radiation-induced cell death but not to UVB. KDM1A inhibition increased ROS generation as detected by increased lipid peroxidation and the upregulation of ROS-responsive genes. The effectiveness of both ALA and HPPH PDT significantly improved in vitro in HaCaT and FaDu cells after KDM1A inhibition. CONCLUSION: KDM1A is a regulator of cellular UV response and KDM1A inhibition can improve PDT efficacy.

Large-Scale Cellular Vehicle-to-Everything Deployments Based on 5G-Critical Challenges, Solutions, and Vision towards 6G: A Survey.

The proliferation of fifth-generation (5G) networks has opened up new opportunities for the deployment of cellular vehicle-to-everything (C-V2X) systems. However, the large-scale implementation of 5G-based C-V2X poses critical challenges requiring thorough investigation and resolution for successful deployment. This paper aims to identify and analyze the key challenges associated with the large-scale deployment of 5G-based C-V2X systems. In addition, we address obstacles and possible contradictions in the C-V2X standards caused by the special requirements. Moreover, we have introduced some quite influential C-V2X projects, which have influenced the widespread adoption of C-V2X technology in recent years. As the primary goal, this survey aims to provide valuable insights and summarize the current state of the field for researchers, industry professionals, and policymakers involved in the advancement of C-V2X. Furthermore, this paper presents relevant standardization aspects and visions for advanced 5G and 6G approaches to address some of the upcoming issues in mid-term timelines.

ß-Tricalcium Phosphate-Modified Aerogel Containing PVA/Chitosan Hybrid Nanospun Scaffolds for Bone Regeneration.

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of ß-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using 18F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.

Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition.

Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol-d-mannose, 1-butanol-butyric acid, ethylene glycol-glycolic acid-oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties.

CHANGES IN THE ULTRASTRUCTURAL ELEMENTS OF PERIODONTAL NEUROTROPHY UNDER CONDITIONS OF ACUTE SIMPLE COAGULATION DYSTROPHY IN THE EXPERIMENT.

OBJECTIVE: Aim: To determine the role of damage to the ultrastructural elements of the periodontal nervous system in the pathogenesis of dystrophic periodontal disease. PATIENTS AND METHODS: Materials and Methods: The basis of the experimental part of the study was the preparation of ultrathin sections from blocks of gum tissue of white rats, which were prepared using the UMTP-3M device. The study and analysis of biopsy samples was carried out with the help of an electron microscope UEMV-100K. RESULTS: Results: With the help of transmission electron microscopy, it was found that from the first minutes after the injection of hemolysate of isogenic erythrocytes into the rats, aggregates of erythrocytes, clumps of blood plasma, clusters of fibrin monomer masses, bundles of fibrin fibers, platelet and homogeneous were present in the connective tissue of the gums, and in particular in the lumens of hemocapillaries microthrombi, which confirms damage to the ultrastructures of the periodontium, which lead to the development of a pathological process, which is described when simple coagulation dystrophy is reproduced. CONCLUSION: Conclusions: Coagulative damage to the ultrastructural elements of the periodontal nervous system is one of the important factors in the pathogenesis of dystrophic periodontal damage. Under these conditions, trophic disturbances occur, similar to those that occur when the integrity of the nerve is disturbed - neurotrophic mechanism of dystrophy.

EVALUATION OF DYNAMIC CHANGES IN THE MICROCIRCULATION OF THE MUCOSA IN THE ZONE OF DENTAL IMPLANTATION WITH IMMEDIATE INTRAOPERATIVE LOAD.

OBJECTIVE: The aim: Study of the dynamics of changes in the average values of the index of mucosal microcirculation after dental implantation with immediate intraoperative prosthetics. PATIENTS AND METHODS: Materials and methods: In clinical conditions, 55 patients aged from 29 to 60 years with a diagnosis of partial absence of teeth requiring orthopedic treatment using implants on the lower jaw were treated and examined. In the course of the latest achievements, the following methods were used: clinical protocol of immediate implantation with Solidum and Simplex implants of the «ART IMPLANT¼ system on the lower jaw by the one-stage implantation method, with immediate intraoperative loading and the manufacture of a temporary non-removable dental prosthesis, determination of the microcirculation index in dynamics using the laser Doppler method flowmetry, statistical analysis. RESULTS: Results: The obtained results indicate a pronounced reaction of microcirculation up to the 3rd day after surgery, an increase in blood perfusion of the mucous membrane by 2.7 times while maintaining vasomotor activity, which indicates adaptation to the injury and immediate loading of the denture in the postoperative period. 3 months after dental surgery and immediate intraoperative prosthetics, all indicators of microcirculation approach the initial values before surgery. CONCLUSION: Conclusions: With the help of laser Doppler flowmetry, the fact of a sharp restoration of microcirculation after dental implantation surgery with immediate intraoperative prosthetics is confirmed.

The multitargeted receptor tyrosine kinase inhibitor sunitinib induces resistance of HER2 positive breast cancer cells to trastuzumab-mediated ADCC.

Despite recent advances in the development of novel personalized therapies, breast cancer continues to challenge physicians with resistance to various advanced therapies. The anticancer action of the anti-HER2 antibody, trastuzumab, involves antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells. Here, we report a repurposing screen of 774 clinically used compounds on NK-cell + trastuzumab-induced killing of JIMT-1 breast cancer cells. Using a calcein-based high-content screening (HCS) assay for the image-based quantitation of ADCC that we have developed and optimized for this purpose, we have found that the multitargeted tyrosine kinase inhibitor sunitinib inhibits ADCC in this model. The cytoprotective effect of sunitinib was also confirmed with two other assays (lactate dehydrogenase release, and electric cell substrate impedance sensing, ECIS). The drug suppressed NK cell activation as indicated by reduced granzyme B deposition on to the target cells and inhibition of interferon-γ production by the NK cells. Moreover, sunitinib induced downregulation of HER2 on the target cells' surface, changed the morphology and increased adherence of the target cells. Moreover, sunitinib also triggered the autophagy pathway (speckled LC3b) as an additional potential underlying mechanism of the cytoprotective effect of the drug. Sunitinib-induced ADCC resistance has been confirmed in a 3D tumor model revealing the prevention of apoptotic cell death (Annexin V staining) in JIMT-1 spheroids co-incubated with NK cells and trastuzumab. In summary, our HCS assay may be suitable for the facile identification of ADCC boosting compounds. Our data urge caution concerning potential combinations of ADCC-based immunotherapies and sunitinib.

Novel Polyurethane Scaffolds Containing Sucrose Crosslinker for Dental Application.

In this paper, the synthesis, characterization, and properties of crosslinked poly(ε-caprolactone)-based polyurethanes as potential tissue replacement materials are reported. The polyurethane prepolymers were prepared from poly(ε-caprolactone)diol (PCD), polyethylene glycol (PEG)/polylactic acid diol (PLAD), and 1,6-hexamethylene diisocyanate (HDI). In these segmented polyurethanes, the role of PEG/PLAD was to tune the hydrophobic/hydrophilic character of the resulting polymer while sucrose served as a crosslinking agent. PLAD was synthesized by the polycondensation reaction of D,L-lactic acid and investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance spectroscopy (NMR). The crosslinked polyurethane samples (SUPURs) obtained were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (AT-FT-IR), swelling, and mechanical (uniaxial tensile tests) experiments. The thermo and thermomechanical behavior were studied by differential scanning calorimetry (DSC) and dynamical mechanical analysis (DMA). The viability of dental pulp stem cells was investigated in the case of polyurethanes composed of fully biocompatible elements. In our studies, none of our polymers showed toxicity to stem cells (DPSCs).

COMPARATIVE EVALUATION OF CLINICAL APPLICATION OF MONOLITHIC AND FOLDING IMPLANTS IN REHABILITATION OF ELDERLY PATIENTS WITH VARIOUS DEGREES OF ATROPHY OF ALVEOLAR PROCESSES.

OBJECTIVE: The aim: Comparative evaluation of long-term results of clinical application of one- and two-stage surgical protocols of dental implantation with the use of monolithic and collapsible implants in the rehabilitation of elderly patients. PATIENTS AND METHODS: Materials and methods: Under clinical observation were 46 patients with various clinical diagnoses of dentition defects aged 60 to 70 years. The following methods were used in the study: one - stage surgical protocol of dental implantation operation with non - detachable implants of ART IMPLANT system with subsequent temporary splint fixed prosthesis and immediate occlusive functional load, mechanical oscillatory - resonance method, questionnaire and statistical analysis. RESULTS: Results: The duration of surgical stages of treatment and complete rehabilitation showed statistically significant differences (p <0.05) and was significantly less when using a single-stage protocol of dental implant surgery and non-detachable implants and averaged 3.9 ± 0.8, p <0.05 months against 7.3 ± 1.2, p <0.05 months in implants according to the two-stage protocol. Assessment of patient satisfaction with the treatment was directly correlated with his timing. CONCLUSION: Conclusions: Thus, it should be noted that the clinical use of one-stage surgical protocol of implantation and non-detachable (monolithic) dental implants of the system «ART IMPLANT¼ in the rehabilitation of elderly patients with varying degrees of atrophy of the alveolar processes of the jaws is clinically justified.

Effect of Inducible BMP-7 Expression on the Osteogenic Differentiation of Human Dental Pulp Stem Cells.

BMP-7 has shown inductive potential for in vitro osteogenic differentiation of mesenchymal stem cells, which are an ideal resource for regenerative medicine. Externally applied, recombinant BMP-7 was able to induce the osteogenic differentiation of DPSCs but based on our previous results with BMP-2, we aimed to study the effect of the tetracyclin-inducible BMP-7 expression on these cells. DPSC, mock, and DPSC-BMP-7 cell lines were cultured in the presence or absence of doxycycline, then alkaline phosphatase (ALP) activity, mineralization, and mRNA levels of different osteogenic marker genes were measured. In the DPSC-BMP-7 cell line, the level of BMP-7 mRNA significantly increased in the media supplemented with doxycycline, however, the expression of Runx2 and noggin genes was upregulated only after 21 days of incubation in the osteogenic medium with doxycycline. Moreover, while the examination of ALP activity showed reduced activity in the control medium containing doxycycline, the accumulation of minerals remained unchanged in the cultures. We have found that the induced BMP-7 expression failed to induce osteogenic differentiation of DPSCs. We propose three different mechanisms that may worth investigating for the engineering of expression systems that can be used for the induction of differentiation of mesenchymal stem cells.

NMNAT1 Is a Survival Factor in Actinomycin D-Induced Osteosarcoma Cell Death.

Osteosarcoma is a frequent and extremely aggressive type of pediatric cancer. New therapeutic approaches are needed to improve the overall survival of osteosarcoma patients. Our previous results suggest that NMNAT1, a key enzyme in nuclear NAD+ synthesis, facilitates the survival of cisplatin-treated osteosarcoma cells. A high-throughput cytotoxicity screening was performed to identify novel pathways or compounds linked to the cancer-promoting role of NMNAT1. Nine compounds caused higher toxicity in the NMNAT1 KO U2OS cells compared to their wild type counterparts, and actinomycin D (ActD) was the most potent. ActD-treatment of NMNAT1 KO cells increased caspase activity and secondary necrosis. The reduced NAD+ content in NMNAT1 KO cells was further decreased by ActD, which partially inhibited NAD+-dependent enzymes, including the DNA nick sensor enzyme PARP1 and the NAD+-dependent deacetylase SIRT1. Impaired PARP1 activity increased DNA damage in ActD-treated NMNAT1 knockout cells, while SIRT1 impairment increased acetylation of the p53 protein, causing the upregulation of pro-apoptotic proteins (NOXA, BAX). Proliferation was decreased through both PARP- and SIRT-dependent pathways. On the one hand, PARP inhibitors sensitized wild type but not NMNAT1 KO cells to ActD-induced anti-clonogenic effects; on the other hand, over-acetylated p53 induced the expression of the anti-proliferative p21 protein leading to cell cycle arrest. Based on our results, NMNAT1 acts as a survival factor in ActD-treated osteosarcoma cells. By inhibiting both PARP1- and SIRT1-dependent cellular pathways, NMNAT1 inhibition can be a promising new tool in osteosarcoma chemotherapy.

Inhibitors of Nucleotide Excision Repair Decrease UVB-Induced Mutagenesis-An In Vitro Study.

The high incidence of skin cancers in the Caucasian population is primarily due to the accumulation of DNA damage in epidermal cells induced by chronic ultraviolet B (UVB) exposure. UVB-induced DNA photolesions, including cyclobutane-pyrimidine dimers (CPDs), promote mutations in skin cancer driver genes. In humans, CPDs are repaired by nucleotide excision repair (NER). Several commonly used and investigational medications negatively influence NER in experimental systems. Despite these molecules' ability to decrease NER activity in vitro, the role of these drugs in enhancing skin cancer risk is unclear. In this study, we investigated four molecules (veliparib, resveratrol, spironolactone, and arsenic trioxide) with well-known NER-inhibitory potential in vitro, using UVB-irradiated CHO epithelial and HaCaT immortalized keratinocyte cell lines. Relative CPD levels, hypoxanthine phosphoribosyltransferase gene mutation frequency, cell viability, cell cycle progression, and protein expression were assessed. All four molecules significantly elevated CPD levels in the genome 24 h after UVB irradiation. However, veliparib, spironolactone, and arsenic trioxide reduced the mutagenic potential of UVB, while resveratrol did not alter UVB-induced mutation formation. UVB-induced apoptosis was enhanced by spironolactone and arsenic-trioxide treatment, while veliparib caused significantly prolonged cell cycle arrest and increased autophagy. Spironolactone also enhanced the phosphorylation level of mammalian target of rapamycin (mTOR), while arsenic trioxide modified UVB-driven mitochondrial fission. Resveratrol induced only mild changes in the cellular UVB response. Our results show that chemically inhibited NER does not result in increased mutagenic effects. Furthermore, the UVB-induced mutagenic potential can be paradoxically mitigated by NER-inhibitor molecules. We identified molecular changes in the cellular UVB response after NER-inhibitor treatment, which may compensate for the mitigated DNA repair. Our findings show that metabolic cellular response pathways are essential to consider in evaluating the skin cancer risk-modifying effects of pharmacological compounds.

Poly(ADP-Ribose) Polymerase 1 Promotes Inflammation and Fibrosis in a Mouse Model of Chronic Pancreatitis.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by ductal obstructions, tissue fibrosis, atrophy and exocrine and endocrine pancreatic insufficiency. However, our understanding is very limited concerning the disease's progression from a single acute inflammation, via recurrent acute pancreatitis (AP) and early CP, to the late stage CP. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor enzyme activated mostly by oxidative DNA damage. As a co-activator of inflammatory transcription factors, PARP1 is a central mediator of the inflammatory response and it has also been implicated in acute pancreatitis. Here, we set out to investigate whether PARP1 contributed to the pathogenesis of CP. We found that the clinically used PARP inhibitor olaparib (OLA) had protective effects in a murine model of CP induced by multiple cerulein injections. OLA reduced pancreas atrophy and expression of the inflammatory mediators TNFα and interleukin-6 (IL-6), both in the pancreas and in the lungs. Moreover, there was significantly less fibrosis (Masson's trichrome staining) in the pancreatic sections of OLA-treated mice compared to the cerulein-only group. mRNA expression of the fibrosis markers TGFß, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA. CP was also induced in PARP1 knockout (KO) mice and their wild-type (WT) counterparts. Inflammation and fibrosis markers showed lower expression in the KO compared to the WT mice. Moreover, reduced granulocyte infiltration (tissue myeloperoxidase activity) and a lower elevation of serum amylase and lipase activity could also be detected in the KO mice. Furthermore, primary acinar cells isolated from KO mice were also protected from cerulein-induced toxicity compared to WT cells. In summary, our data suggest that PARP inhibitors may be promising candidates for repurposing to treat not only acute but chronic pancreatitis as well.

IMMEDIATE IMPLANTATION AND AESTHETIC COMPONENT AS A RESULT OF SUCCESSFUL FORECAST TREATMENT.

OBJECTIVE: The aim: Improving the method of immediate implantation in the aesthetic zone in case of bone deficiency to obtain the highest aesthetic and predictable treatment result. PATIENTS AND METHODS: Materials and methods: Under clinical observation were 32 patients with different clinical diagnoses in the anterior part of the upper jaw aged 30 to 55 years. In the course of recent advances, the following methods have been used: clinical protocol of immediate implantation with passive exceptional loads by temporary orthopedic constructions, X-ray method using cone-beam computed tomography, statistical analysis. RESULTS: Results: After surgical treatment of patients 1 year after surgery, the distribution of biotypes was as follows: in group 1 - thick biotype 12.87%, medium - 87.13%; in group 2 - thick biotype 27.04%, medium - 72.96%, with p <0.05. According to the results of CT, the distance between the implant and the vestibular in the first group was after 6 months - 1.67 ± 0.04 mm (p <0.05); in the second group of the study we obtained the following results after 6 months - 1.59 ± 0.06 mm (p <0.05). CONCLUSION: Conclusions: The advanced method of immediate implantation in the anterior part of the upper jaw allows to change the biotype of soft tissues, improve the color spectrum of the gums, increase the thickness of soft tissues with connective tissue autograft, and increase gum density and fixation of osteoplastic material in the presence of defect ), as well as reduce the risk of recession.

Poly(ADP-ribose) polymerase-1 depletion enhances the severity of inflammation in an imiquimod-induced model of psoriasis.

Poly(ADP-ribose) polymerase-1 (PARP1) is a pro-inflammatory protein, whose pro-inflammatory properties were demonstrated in human. The pro-inflammatory properties of PARP1 were shown in Th1- and Th2-mediated inflammatory pathologies, but not Th17-mediated inflammation. Thus, we studied the role of PARP1 in the imiquimod-induced model of psoriasis. To our surprise, in imiquimod-induced psoriasis, PARP1 acted as an anti-inflammatory factor and its genetic deletion exacerbated symptoms. We showed that in the absence of PARP1, the epidermis thickened and the number of TUNEL-positive cells decreased in the epidermis. These data indicate programmed cell death is decreased in keratinocytes. Changes in involucrin expression suggest that keratinocyte differentiation is hampered. Furthermore, epidermal expression of IL6 increased in the psoriasiform lesions of PARP1 knockout mice, suggesting that the inflammatory response is also derailed in the absence of PARP1. Finally, we showed that PARP1 expression is reduced in human psoriatic lesions compared with control skin samples. In imiquimod-treated HPV-KER keratinocytes, PARP inhibition recapitulated the in vivo findings, namely keratinocyte hyperproliferation; furthermore, the mRNA expression of psoriasis-associated cytokines (IL6, IL1ß, IL8, IL17 and IL23A) was also induced. The inhibition of TRPV1 abrogated the effects of the combined imiquimod + PARP inhibitor treatment.

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone.

High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements-like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results-electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.

SIRT1 Activation by Equisetum Arvense L. (Horsetail) Modulates Insulin Sensitivity in Streptozotocin Induced Diabetic Rats.

BACKGROUND: Equisetum arvense L., commonly known as field horsetail is a perennial fern of which extracts are rich sources of phenolic compounds, flavonoids, and phenolic acids. Activation of SIRT1 that was shown to be involved in well-known signal pathways of diabetic cardiomyopathy has a protective effect against oxidative stress, inflammatory processes, and apoptosis that are the basis of diseases such as obesity, diabetes mellitus, or cardiovascular diseases. The aim of our study was to evaluate the antidiabetic and cardioprotective effects of horsetail extract in streptozotocin induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of 45 mg/kg streptozotocin. In the control groups (healthy and diabetic), rats were administered with vehicle, whilst in the treated groups, animals were administered with 50, 100, or 200 mg/kg horsetail extract, respectively, for six weeks. Blood glucose levels, glucose tolerance, and insulin sensitivity were determined, and SIRT1 levels were measured from the cardiac muscle. RESULTS: The horsetail extract showed moderate beneficial changes in blood glucose levels and exhibited a tendency to elevate SIRT1 levels in cardiomyocytes, furthermore a 100 mg/kg dose also improved insulin sensitivity. CONCLUSIONS: Altogether our results suggest that horsetail extract might have potential in ameliorating manifested cardiomyopathy acting on SIRT1.