Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Microsc Microanal ; 30(2): 392-400, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38502789

RESUMO

Biomineralization of brain tissues occurs both in normal and pathological conditions. Dura mater biomineralization is widespread and occurs in 1-72% of cases, depending on the patient's age and research method. The amount of biomineral deposits under the conditions of tumor growth in the meninges only increases, reaching 100% in the case of psammomatous meningiomas. Since calcifications are often found in the meninges, the problem of differential diagnosis with calcified meningiomas arises. A total of 30 samples of meningiomas with signs of biomineralization-dense structure, characteristic crunch, psammoma bodies (group I) and 30 samples of meningiomas without any signs of biomineralization were examined as controls (group II). To detect pathological biomineralization, the meningioma tissue was studied using the methods of macroscopic description, histology, histochemistry, and immunohistochemistry, scanning electron microscopy with microanalysis, and transmission electron microscopy. A significantly higher level of caspase3 and features of the expression of osteoblastic markers (a lower level of OPG expression and a higher level of the presence of RANKL in group I, the absence of fluctuations in the expression of SPARC) may indicate a dystrophic type of development of biomineral deposits in meningiomas.


Assuntos
Biomineralização , Imuno-Histoquímica , Meningioma , Meningioma/patologia , Meningioma/metabolismo , Humanos , Imuno-Histoquímica/métodos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Idoso , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Histocitoquímica/métodos , Calcinose/patologia
2.
Polymers (Basel) ; 15(18)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37765676

RESUMO

Synthetic bone grafting materials play a significant role in various medical applications involving bone regeneration and repair. Their ability to mimic the properties of natural bone and promote the healing process has contributed to their growing relevance. While calcium-phosphates and their composites with various polymers and biopolymers are widely used in clinical and experimental research, the diverse range of available polymer-based materials poses challenges in selecting the most suitable grafts for successful bone repair. This review aims to address the fundamental issues of bone biology and regeneration while providing a clear perspective on the principles guiding the development of synthetic materials. In this study, we delve into the basic principles underlying the creation of synthetic bone composites and explore the mechanisms of formation for biologically important complexes and structures associated with the various constituent parts of these materials. Additionally, we offer comprehensive information on the application of biologically active substances to enhance the properties and bioactivity of synthetic bone grafting materials. By presenting these insights, our review enables a deeper understanding of the regeneration processes facilitated by the application of synthetic bone composites.

3.
bioRxiv ; 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37461695

RESUMO

Most cases of gastric cancer are caused by chronic Helicobacter pylori infection, but the lack of early onco-diagnostics and a high risk for antibiotic resistance hampers early intervention through eradication of H. pylori infection by antibiotics. We reported on a protective mechanism where H. pylori gastric mucosal attachment can be reduced by natural antibodies that block the binding of its attachment protein BabA. Here we show that challenge infection with H. pylori induced response of such blocking antibodies in both human volunteers and in rhesus macaques, that mucosal vaccination with BabA protein antigen induced blocking antibodies in rhesus macaques, and that vaccination in a mouse model induced blocking antibodies that reduced gastric mucosal inflammation, preserved the gastric juice acidity, and fully protected the mice from gastric cancer caused by H. pylori.

4.
Pathol Res Pract ; 248: 154594, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37301085

RESUMO

Merkel cell carcinoma is a rare primary neuroendocrine malignant neoplasm of the skin, which recurs in about 40 % of cases. The main factors are Merkel cell polyomavirus (MCPyV) and mutations caused by ultraviolet radiation [Paulson, 2018]. In this study, we report a case of Merkel cell carcinoma with metastasis to the small intestine. In a 52-year-old woman, a subcutaneous formation of a nodule up to 2.0 cm in diameter was detected during the examination. This neoplasm was removed and sent for histological analysis. Dot-like expression of CK pan, CK 20, chromogranin A, and Synaptophysin was observed in tumor cells, and Ki-67 in 40 % of tumor cells. There is no reaction in tumor cells to CD 45, CK 7, TTF 1, and S100. The morphological picture corresponded to Merkel cell carcinoma. A year later, the patient underwent surgery for intestinal obstruction. The pathohistological changes and immunophenotype of the small bowel tumor were consistent with Merkel cell carcinoma metastasis.


Assuntos
Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/patologia , Raios Ultravioleta , Recidiva Local de Neoplasia , Intestino Delgado/metabolismo , Intestino Delgado/patologia
5.
Nanomaterials (Basel) ; 13(12)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37368306

RESUMO

Maxillary sinus augmentation is a commonly used procedure for the placement of dental implants. However, the use of natural and synthetic materials in this procedure has resulted in postoperative complications ranging from 12% to 38%. To address this issue, we developed a novel calcium deficient HA/ß-TCP bone grafting nanomaterial using a two-step synthesis method with appropriate structural and chemical parameters for sinus lifting applications. We demonstrated that our nanomaterial exhibits high biocompatibility, enhances cell proliferation, and stimulates collagen expression. Furthermore, the degradation of ß-TCP in our nanomaterial promotes blood clot formation, which supports cell aggregation and new bone growth. In a clinical trial involving eight cases, we observed the formation of compact bone tissue 8 months after the operation, allowing for the successful installation of dental implants without any early postoperative complications. Our results suggest that our novel bone grafting nanomaterial has the potential to improve the success rate of maxillary sinus augmentation procedures.

6.
Ann Med Surg (Lond) ; 85(5): 2216-2220, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37228960

RESUMO

Peutz-Jeghers syndrome (PJS), an uncommon inherited autosomal dominant disorder, is distinguished by mucocutaneous pigmentations, many gastrointestinal hamartomatous polyps, and a higher incidence of gastrointestinal tract, genitourinary, and extracolonic malignancies. Recurrent acute intestinal obstruction, in particular intussusception in the young, is a serious sequalae of PJS. Case presentation: A clinical observation of a 5-year-old patient with a complicated course of PJS is presented. Emphasis on recurring episodes of acute abdomen, clinical diagnosis including polyp histopathology, and surgical management is emphasised. Clinical findings and investigations: While an inpatient, bloodwork demonstrated severe iron deficiency anaemia (haemoglobin 72 g/l, red blood cell 3.1×1012/l) and multiple melanin pigmentations measuring 2-4 mm in size on the lip mucosa during a physical examination. Erosive duodenopathy and polyposis of the stomach were discovered via fibroesophagogastroduodenoscopy (multiple gastric polyps 5-10 mm in size). Acute intussusception of the intestine was discovered by ultrasonography. Interventions and outcome: A mid-median laparotomy was performed alongside manual disinvagination with gut viability intact. Histopathology of excised polyps revealed smooth muscle hyperplasia and Ki67 protein (MIB-1) positivity with small intestinal hamartomatous polyps seen macroscopically. Conservative management was initiated for standard postoperative care and intestinal motility. Patient was discharged 9 days postoperatively. Relevance and impact: Based on literature data, modern ideas concerning aetiology, diagnosis, and management of patients with PJS are considered. Attention is focused on the high risk of developing cancer of various localisation in PJS, recommendations are given for cancer screening and clinical observation of patients with hereditary gastrointestinal syndromes in childhood.

7.
ACS Appl Mater Interfaces ; 15(16): 19863-19876, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37041124

RESUMO

Dental implants have become a routine, affordable, and highly reliable technology to replace tooth loss. In this regard, titanium and its alloys are the metals of choice for the manufacture of dental implants because they are chemically inert and biocompatible. However, for special cohorts of patients, there is still a need for improvements, specifically to increase the ability of implants to integrate into the bone and gum tissues and to prevent bacterial infections that can subsequently lead to peri-implantitis and implant failures. Therefore, titanium implants require sophisticated approaches to improve their postoperative healing and long-term stability. Such treatments range from sandblasting to calcium phosphate coating, fluoride application, ultraviolet irradiation, and anodization to increase the bioactivity of the surface. Plasma electrolytic oxidation (PEO) has gained popularity as a method for modifying metal surfaces and delivering the desired mechanical and chemical properties. The outcome of PEO treatment depends on the electrochemical parameters and composition of the bath electrolyte. In this study, we investigated how complexing agents affect the PEO surfaces and found that nitrilotriacetic acid (NTA) can be used to develop efficient PEO protocols. The PEO surfaces generated with NTA in combination with sources of calcium and phosphorus were shown to increase the corrosion resistance of the titanium substrate. They also support cell proliferation and reduce bacterial colonization and, hence, lead to a reduction in failed implants and repeated surgeries. Moreover, NTA is an ecologically favorable chelating agent. These features are necessary for the biomedical industry to be able to contribute to the sustainability of the public healthcare system. Therefore, NTA is proposed to be used as a component of the PEO bath electrolyte to obtain bioactive surface layers with properties desired for next-generation dental implants.


Assuntos
Implantes Dentários , Titânio , Humanos , Titânio/química , Ácido Nitrilotriacético , Propriedades de Superfície , Oxirredução , Metais , Ligas , Eletrólitos , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
8.
J Pathol Inform ; 14: 100193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873571

RESUMO

The aim of the study is to increase the functional efficiency of machine learning decision support system (DSS) for the diagnosis of oncopathology on the basis of tissue morphology. The method of hierarchical information-extreme machine learning of diagnostic DSS is offered. The method is developed within the framework of the functional approach to modeling of natural intelligence cognitive processes at formation and acceptance of classification decisions. This approach, in contrast to neuronal structures, allows diagnostic DSS to adapt to arbitrary conditions of histological imaging and flexibility in retraining the system by expanding the recognition classes alphabet that characterize different structures of tissue morphology. In addition, the decisive rules built within the geometric approach are practically invariant to the multidimensionality of the diagnostic features space. The developed method allows to create information, algorithmic, and software of the automated workplace of the histologist for diagnosing oncopathologies of different genesis. The machine learning method is implemented on the example of diagnosing breast cancer.

9.
Diagnostics (Basel) ; 13(4)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36832224

RESUMO

The detection of microcalcifications in the breast by mammography is of great importance for the early diagnostics of breast cancer. This study aimed to establish the basic morphological and crystal-chemical properties of microscopic calcifications and their impact on breast cancer tissue. During the retrospective study, 55 out of 469 breast cancer samples had microcalcifications. The expression of the estrogen and progesterone receptors and Her2-neu showed no significant difference from the non-calcified samples. An in-depth study of 60 tumor samples revealed a higher expression of osteopontin in the calcified breast cancer samples (p ˂ 0.01). The mineral deposits had a hydroxyapatite composition. Within the group of calcified breast cancer samples, we detected six cases of colocalization of oxalate microcalcifications together with biominerals of the usual "hydroxyapatite" phase composition. The simultaneous presence of calcium oxalate and hydroxyapatite was accompanied by a different spatial localization of microcalcifications. Thus, the phase compositions of microcalcifications could not be used as criteria for the differential diagnostics of breast tumors.

10.
Contemp Oncol (Pozn) ; 26(3): 239-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36381667

RESUMO

Introduction: Patients with lung cancer receive treatment according to National Cancer Comprehensive Network (NCCN) standards. However, disease recurrence is reported in about 30% of patients during the first five years. Our study aimed to establish independent predictors of lung cancer recurrence. Material and methods: 104 patients with definitive treatment for non-small-cell lung carcinoma receiving standard adjuvant chemotherapy in the period 2014-2018 in our cancer center were retrospectively reviewed. The prognostic significance of five routine immunohistochemical (IHC) markers was examined. Results: During the follow-up period disease recurrence occurred in 42 (40.4%) of the 104 enrolled patients. The median recurrence-free survival was 56.3 months, range 4-84.0 months (95% CI = 46.866-65.683). The recurrence-free survival rate was 58.8%. The frequencies of locoregional recurrence, lung recurrence, kidney, bone, lymph nodes of the neck, liver, and brain recurrence were 23.8%, 21.5%, 16.7%, 9.5%, 9.5%, 9.5% and 9.5%, respectively. Conclusions: Using the Cox regression model, category T, histological differentiation, and smoking status were identified as independent predictors of disease recurrence. The studied biological markers (PD-L1, Ki67, p53, epidermal growth factor receptor, and ALK) did not help the model predict disease recurrence. For statistical reliability, it is necessary to conduct a study on a larger cohort of patients and compare the mutual influence of several biomarkers.

11.
Contemp Oncol (Pozn) ; 26(4): 259-267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36816393

RESUMO

Introduction: Thyroid cancer (TC) demonstrates steady growth in incidence worldwide and remains an urgent problem in oncology. The detection of sentinel lymph nodes (SLN) with a selective dye and further histological examination in selecting the proper (personalized) surgical strategy and the volume of surgical intervention for clinically undetermined regional lymph nodes. The purpose of the study is to evaluate the effectiveness and safety of intraoperative detection of SLN with a 1% toluidine blue aqueous solution. Material and methods: The significant tasks are to identify the pattern of TC metastases to cervical lymph nodes, to establish the prevalence of "skip" metastases, to compare the frequency of complications after total thyroidectomy and central neck dissection and lateral neck dissection with total thyroidectomy and central neck dissection, and to determine the feasibility of the application of lateral neck dissections in patients with papillary and follicular TC without metastases to regional lymph nodes (according to physical examination and ultrasound). Results: According to our data the SLN identification rate was 97.6%. Sensitivity, specificity, positive predictive value, negative predictive value, and frequency of false negative and false positive results was 89.2, 94.6, 88.03, 95.16, 10.8, and 5.4%, respectively. The most common metastasis was in the central neck compartment (83.7%). Skip metastases were determined in 4.9% of patients. Conclusions: The low prevalence of "skip" metastases and a significant risk of postoperative complications (wound exudation, lymphorrhagia, inflammation, hypoparathyroidism, paresis of the vocal cords) support the idea that lateral neck dissection is appropriate only in cases of confirmed metastases by physical examination and/or ultrasound at the preoperative stage.

12.
J Clin Med ; 10(24)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34945164

RESUMO

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL.

13.
Diagnostics (Basel) ; 11(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34679439

RESUMO

Calcification is one of the clinical and morphological manifestations of ovarian tumors and it begins at the initial stages of carcinogenesis. Thus, this process can be used for the early diagnostics of some malignant ovarian tumors. We compared the results of ultrasound and histology and found that calcifications of a size less than 200 µm are not detected by ultrasound. These calcified structures are round fragile particles of different sizes. In the EDX (Energy-dispersive X-ray spectroscopy) spectra, the main lines were from Ca and P, and the ratio of these elements corresponds to hydroxyapatite. Thus, we established that hydroxyapatite is the main mineral component of ovarian psammoma bodies and could be used for early diagnostics of ovarian malignant neoplasia.

14.
Mater Sci Eng C Mater Biol Appl ; 121: 111870, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579496

RESUMO

Triply periodic minimal surfaces (TPMS) are known for their advanced mechanical properties and are wrinkle-free with a smooth local topology. These surfaces provide suitable conditions for cell attachment and proliferation. In this study, the in vitro osteoinductive and antibacterial properties of scaffolds with different minimal pore diameters and architectures were investigated. For the first time, scaffolds with TPMS architecture were treated electrochemically by plasma electrolytic oxidation (PEO) with and without silver nanoparticles (AgNPs) to enhance the surface bioactivity. It was found that the scaffold architecture had a greater impact on the osteoblast cell activity than the pore size. Through control of the architecture type, the collagen production by osteoblast cells increased by 18.9% and by 43.0% in the case of additional surface PEO bioactivation. The manufactured scaffolds demonstrated an extremely low quasi-elastic modulus (comparable with trabecular and cortical bone), which was 5-10 times lower than that of bulk titanium (6.4-11.4 GPa vs 100-105 GPa). The AgNPs provided antibacterial properties against both gram-positive and gram-negative bacteria and had no significant impact on the osteoblast cell growth. Complex experimental results show the in vitro effectiveness of the PEO-modified TPMS architecture, which could positively impact the clinical applications of porous bioactive implants.


Assuntos
Nanopartículas Metálicas , Titânio , Ligas , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Porosidade , Prata/farmacologia , Alicerces Teciduais , Titânio/farmacologia
15.
Iran J Pathol ; 14(3): 212-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582998

RESUMO

BACKGROUND & OBJECTIVE: To study the immunophenotype of prostate cancer (PC) with the presence and absence of intraluminal inclusions (IIn), depending on the grade score. METHODS: A total of 30 PC samples with IIn (group E) and 30 PC samples without them (group C) were studied. These groups were divided into 2 subgroups, depending on the grade of malignancy, which was determined according to the Gleason score as moderate and high-grade tumors. Macroscopic analysis, hematoxylin-eosin staining, immunohistochemistry (androgen receptors, p53 and Bax proteins, Hsp70 and Hsp90, CD68, VEGF, OSN, MMP-1) were used. RESULTS: The expression level of VEGF was higher in the more differentiated tumors of the control group (P<0.01). Increased expression of prognostic-adverse markers p53 (in the presence of IIn, P<0.01) and MMP-1 (P<0.05) was observed. Also, a higher level of OSN expression was found in PC tissue with IIn (P<0.01) due to its participation in the processes of biomineralization. The expression level of CD68 and Bax protein was higher in the PC group with IIn (both P<0.01). Furthermore, Hsp90 had a significantly lower expression level in the PC of group E (P<0.05). CONCLUSION: the presence of IIn in the PC samples of group E promotes tissue remodeling with mechanical trauma, chronic inflammation, and fibrosis development. The presence of IIn in PC leads to the increase of OSN, CD68 and Bax expression and decrease of Hsp90 and VEGF expression. High expression of p53 and MMP-1 and low expression of OSN and VEGF was identified as a characteristic of high-grade tumors.

16.
Interv Med Appl Sci ; 10(2): 110-119, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30363347

RESUMO

Thermal behavior of biological apatite is the object of several studies. Crystal size, carbonate content, phase composition, and other parameters change during annealing up to 900 °C in biological minerals with apatite structure. The way these parameters change reflects the specific properties of the initial bioapatite. This work presents data on thermal transformations of pathological bioapatite from the human cardiovascular system, namely aortic wall deposits. Some minor elements, foreign to calcium hydroxyapatite (e.g., Na and Mg), can be both incorporated in the apatite structure and localized in the surface layers of crystals, modifying functions of the mineral. A new approach was proposed to determine the predominant location of minor elements, such as Mg, Na, and K, in the mineral of pathological deposits. Mg and Na in pathological apatite can be in both structurally bound (substituting calcium in lattice) and labile (localized on the crystal surface) states, while K is not able to join the apatite structure in significant amount or be chemically bound to it. This approach, based on atomic spectrometry, can be used effectively in combination with a set of traditional techniques, such as like EDS, IRS, and XRD.

17.
Sci Rep ; 8(1): 12836, 2018 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-30150640

RESUMO

Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimer's disease (AD) pathology. Traumatic brain injury (TBI) is viewed as a precursor state for AD. Here we have shown that S100A9-driven amyloid-neuroinflammatory cascade was initiated in TBI and may serve as a mechanistic link between TBI and AD. By analyzing the TBI and AD human brain tissues, we demonstrated that in post-TBI tissues S100A9, produced by neurons and microglia, becomes drastically abundant compared to Aß and contributes to both precursor-plaque formation and intracellular amyloid oligomerization. Conditions implicated in TBI, such as elevated S100A9 concentration, acidification and fever, provide strong positive feedback for S100A9 nucleation-dependent amyloid formation and delay in its proteinase clearance. Consequently, both intracellular and extracellular S100A9 oligomerization correlated with TBI secondary neuronal loss. Common morphology of TBI and AD plaques indicated their similar initiation around multiple aggregation centers. Importantly, in AD and TBI we found S100A9 plaques without Aß. S100A9 and Aß plaque pathology was significantly advanced in AD cases with TBI history at earlier age, signifying TBI as a risk factor. These new findings highlight the detrimental consequences of prolonged post-TBI neuroinflammation, which can sustain S100A9-driven amyloid-neurodegenerative cascade as a specific mechanism leading to AD development.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Lesões Encefálicas/complicações , Lesões Encefálicas/metabolismo , Calgranulina B/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Apoptose , Modelos Animais de Doenças , Suscetibilidade a Doenças , Imunofluorescência , Humanos , Imuno-Histoquímica , Espaço Intracelular , Camundongos , Modelos Biológicos , Neurônios/metabolismo , Placa Amiloide/metabolismo , Placa Amiloide/patologia
18.
J Neuroinflammation ; 15(1): 172, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866153

RESUMO

BACKGROUND: Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of α-synuclein (α-syn) and S100A9 both in vitro and ex vivo in PD brain. METHODS: Single and sequential immunohistochemistry, immunofluorescence, scanning electron and atomic force (AFM) microscopies were used to analyze the ex vivo PD brain tissues for S100A9 and α-syn location and aggregation. In vitro studies revealing S100A9 and α-syn interaction and co-aggregation were conducted by NMR, circular dichroism, Thioflavin-T fluorescence, AFM, and surface plasmon resonance methods. RESULTS: Co-localized and co-aggregated S100A9 and α-syn were found in 20% Lewy bodies and 77% neuronal cells in the substantia nigra; both proteins were also observed in Lewy bodies in PD frontal lobe (Braak stages 4-6). Lewy bodies were characterized by ca. 10-23 µm outer diameter, with S100A9 and α-syn being co-localized in the same lamellar structures. S100A9 was also detected in neurons and blood vessels of the aged patients without PD, but in much lesser extent. In vitro S100A9 and α-syn were shown to interact with each other via the α-syn C-terminus with an apparent dissociation constant of ca. 5 µM. Their co-aggregation occurred significantly faster and led to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers were more toxic than those of α-syn, while co-aggregation of both proteins mitigated the cytotoxicity of S100A9 oligomers. CONCLUSIONS: We suggest that sustained neuroinflammation promoting the spread of amyloidogenic S100A9 in the brain tissues may trigger the amyloid cascade involving α-syn and S100A9 and leading to PD, similar to the effect of S100A9 and Aß co-aggregation in Alzheimer's disease. The finding of S100A9 involvement in PD may open a new avenue for therapeutic interventions targeting S100A9 and preventing its amyloid self-assembly in affected brain tissues.


Assuntos
Encéfalo/metabolismo , Calgranulina B/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Agregados Proteicos/fisiologia , alfa-Sinucleína/metabolismo , Idoso , Idoso de 80 Anos ou mais , Amiloide/metabolismo , Amiloide/ultraestrutura , Autopsia , Encéfalo/diagnóstico por imagem , Encéfalo/ultraestrutura , Calgranulina B/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular/métodos , Feminino , Humanos , Corpos de Lewy/patologia , Corpos de Lewy/ultraestrutura , Espectroscopia de Ressonância Magnética , Masculino , Microscopia Eletrônica de Varredura , Neuroblastoma/patologia , Doença de Parkinson/diagnóstico por imagem , Estatísticas não Paramétricas , Ressonância de Plasmônio de Superfície , alfa-Sinucleína/farmacologia
19.
ACS Chem Neurosci ; 9(6): 1338-1348, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29618200

RESUMO

Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroinflammatory cascades in Alzheimer's disease, leading together with Aß to plaque formation, neuronal loss and memory impairment. In order to examine if S100A9 alone in its native and amyloid states can induce neuronal stress and memory impairment, we have administered S100A9 species intranasally to aged mice. Single and sequential immunohistochemistry and passive avoidance behavioral test were conducted to evaluate the consequences. Administered S100A9 species induced widespread cellular stress responses in cerebral structures, including frontal lobe, hippocampus and cerebellum. These were manifested by increased levels of S100A9, Bax, and to a lesser extent activated caspase-3 immunopositive cells. Upon administration of S100A9 fibrils, the amyloid oligomerization was observed in the brain tissues, which can further exacerbate cellular stress. The cellular stress responses correlated with significantly increased training and decreased retention latencies measured in the passive avoidance test for the S100A9 treated animal groups. Remarkably, the effect size in the behavioral tests was moderate already in the group treated with native S100A9, while the effect sizes were large in the groups administered S100A9 amyloid oligomers or fibrils. The findings demonstrate the brain susceptibility to neurotoxic damage of S100A9 species leading to behavioral and memory impairments. Intranasal administration of S100A9 species proved to be an effective method to study amyloid induced brain dysfunctions, and S100A9 itself may be postulated as a target to allay early stage neurodegenerative and neuroinflammatory processes.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Calgranulina B/farmacologia , Administração Intranasal/métodos , Amiloide/efeitos dos fármacos , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/metabolismo , Amiloidose/patologia , Animais , Calgranulina B/administração & dosagem , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Camundongos Endogâmicos C57BL
20.
Wiad Lek ; 71(1 pt 2): 237-241, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29602940

RESUMO

OBJECTIVE: Introduction: Information on chemical and phase composition of pancreoliths is limited and discrepant. There are reports, that pancreoliths are composed by calcium, phosphate, calcium carbonate or combination of calcium with fatty acids The aim of the work is studying of structural characteristics of pancreatoliths in 5 clinical cases. PATIENTS AND METHODS: Materials and methods: Morphological and crystal-chemical study of five cases of pathological biomineralization in the pancreas were conducted in the work. RESULTS: Results: Two stones were located in the pancreatic duct, in other cases - in the ductal system of pancreas. Concretion sizes ranged from 0.5 to 1.5 cm in diameter. Pancreatic lithiasis' form depended on the location: in the duct of Wirsung single concretions were found (they were relatively large, oval stones with smooth, regular edges); multiple, small concretions with irregular edges, coral-like stones dominated in the ductal system of pancreas. Histological study of pancreas showed the signs of chronic pancreatitis, tissue fibrosis, atrophy and edema of glandular component, system distension of ducts, nidal mix-cell inflammatory infiltrates, vessels' plethora. Structural phase and chemical analysis of pathological biominerals responded calcite in all studied cases. CONCLUSION: Conclusion: The presence of pancreatic lithiasis was found to be accompanied by significant morphological changes of the pancreas. The pancreatolith crystal phase was established to be calcium carbonate in the form of calcite.


Assuntos
Litíase/patologia , Ductos Pancreáticos/patologia , Adulto , Humanos , Litíase/diagnóstico , Litíase/cirurgia , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Pâncreas/cirurgia , Ductos Pancreáticos/cirurgia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...