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Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.

This study was designed to evaluate the effects of purple potato extract of the Blue Congo variety (PP) on diabetes and its antioxidant activities after two-week administration tostreptozotocin (STZ)-induced diabetic rats. The activities of PP were evaluated at a dose of 165 mg/kg body weight (b.w.) by estimating biochemical changes in blood plasma and through a histopathological study of kidney, muscles, and liver tissue. We evaluated the effect of treatment with extract on glucose level, glycated hemoglobin, activities of enzymatic antioxidants (including superoxide dismutase, glutathione peroxidase, and catalase), and lipid peroxidation. Moreover, we determined advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), and the level of oxidative modified proteins (OMPs) as markers of carbonyl-oxidative stress in rats with diabetes. Using high-performance liquid chromatography, we identified five anthocyanins and six phenolic acids in the extract from Blue Congo with the dominant acylated anthocyanin as petunidin-3-p-coumaroyl-rutinoside-5-glucoside. The administration of Blue Congo extract lowered blood glucose, improved glucose tolerance, and decreased the amount of glycated hemoglobin. Furthermore, PP demonstrated an antioxidative effect, suppressed malondialdehyde levels, and restored antioxidant enzyme activities in diabetic rats. After administration of PP, we also noticed inhibition of OMP, AGE, and AOPP formation in the rats′ blood plasma.

Macrodontia is the enlargement of tooth dimensions of different ethologies. This work aims to show a histological evaluation of macrodontic teeth in guinea pigs. The material was obtained from animals postmortem. Ninety structural changes derived from 24 guinea pigs were evaluated. All teeth used in the study showed macrodontic changes. The samples were decalcified, dehydrated and embedded in paraffin. Material was cut in the transverse and longitudinal planes in relation to the alveolar bone. Histological evaluation included apical bud cells, pulp cavity cells, periodontium, dentin, enamel, cementum and alveolar bone tissue. Individual elements were evaluated with respect to their morphology and distribution. Moreover, the arrangement of the individual hard tooth structures was assessed on the teeth. No atypia was found among the cells that make up the apical bud, pulp or periodontal cavity. Displacement of periodontal cells or odontoblasts towards the pulp cavity as well as disorganization of the cell system in the pulp cavity were observed. Changes in the dentine ligaments and the reconstruction of the alveolar bone were also observed in areas where dentine and cement systems were affected. Dental slides were observed and showed that the enamel is also involved in structural remodelling of the pulp cavity. The histological assessment revealed that structural changes in macrodontic teeth involve the rearrangement of typical tooth tissues.  

The biocompatibility of orthodontic archwires is crucial for ensuring patient safety and the long-term success of orthodontic treatment. This study evaluated the biocompatibility of stainless steel (SS) and nickel–titanium (Ni-Ti) orthodontic archwires, as well as stainless steel metal brackets, before and after the application of a graphene coating. The assessment was based on the materials’ effects on a fibroblast cell line and on the development of a foetal chicken egg embryo. Fibroblasts that had been in temporary contact with steel and NiTi archwires after CW-CVD (cold wall chemical vapour deposition) treatment exhibited changes in morphology in the presence of the material. The materials exhibited moderate cytotoxicity. For metal brackets, the treated samples caused stronger cytotoxic changes in the culture. Unlike graphene-coated implants, where cells were found to directly adhere to the surface, the embryonic tissues did not treat the non-graphene-coated implants as an adhesive material. This study suggests that depositing carbon-based coatings, including graphene, on stainless steel archwires may reduce the cytotoxicity of orthodontic components. Using graphene increases adhesion of the implant surface to membrane-derived cells and the embryonic yolk and does not inhibit the further development of the chicken egg embryo.

Background Mesenchymal stem cells (MSCs) secrete a cocktail of growth factors and cytokines, which could promote tissue regeneration and wound healing. Therefore, in clinical practice, post-culture MSC supernatant treatment could be a more attractive alternative to autologous stem cell transplantation. In this study, we compared the regenerative properties of supernatants harvested from four newly established human adipose tissue mesenchymal stem cell lines (HATMSCs) derived from chronic wound patients or healthy donors. Methods HATMSC supernatants were produced in a serum-free medium under hypoxia and their content was analyzed by a human angiogenesis antibody array. The regenerative effect of HATMSCs supernatants was investigated in an in vitro model of chronic wound, where cells originating from human skin, such as microvascular endothelial cells (HSkMEC.2), keratinocytes (HaCaT), and fibroblasts (MSU-1.1), were cultured in serum-free and oxygen-reduced conditions. The effect of supernatant treatment was evaluated using an MTT assay and light microscopy. In addition, fibroblasts and HATMSCs were labeled with PKH67 and PKH26 dye, respectively, and the effect of supernatant treatment was compared to that obtained when fibroblasts and HATMSCs were co-cultured, using flow cytometry and fluorescent microscopy. Results A wide panel of angiogenesis-associated cytokines such as angiogenin, growth-regulated oncogene (GRO), interleukin-6 and 8 (IL-6, IL-8), vascular endothelial growth factor (VEGF), insulin growth factor 1 (IGF-1), and matrix metalloproteinase (MMP) were found in all tested HATMSCs supernatants . Moreover, supernatant treatment significantly enhanced the survival of fibroblasts, endothelial cells, and keratinocytes in our chronic wound model in vitro. Importantly, we have shown that in in vitro settings, HATMSC supernatant treatment results in superior fibroblast proliferation than in the case of co-culture with HATMSCs. Conclusions Our results suggest that therapy based on bioactive factors released by the immortalized atMSC into supernatant has important effect on skin-derived cell proliferation and might preclude the need for a more expensive and difficult cell therapy approach to improve chronic wound healing.

The jaw bones can manifest various cysts and tumors of different origins and etiologies. Any bone lesions lacking any potential odontogenic origin might require more accurate diagnostics, adequate investigation, and careful patient anamnesis. In cases of sharply demarcated radiolucency or mixed radiolucent–radiopaque radiological appearance lesions, they can sometimes extend between the displaced tooth roots or cause their resorption. The scope of cortical bone in radiographic studies might have a different status, and lesions can spread outside of the bone. If no odontogenic feature is present, an additional blood examination for bone markers and calcium–phosphate markers is useful to establish any endocrine-related pathologies. In the primary hyperparathyroidism (PHP), bone blood markers and bone scintigraphy are very useful to establish the possible occurrence of brown tumor. On the other hand, in central giant cell granuloma (CGCG), only a direct tumor lesion biopsy might confirm the diagnosis, where in microscopic evaluation, mostly fibroblasts and secondary cells have multinucleated giant cells along with some accessory cells like macrophages, dendrocytes, and other endothelial cells. Because both lesions can have similar clinical and radiological appearances and unclear borders, with different shapes, sizes, and symptoms, it is quite important to compare both clinical and radiological patient characteristics. The authors aim to present how radiological studies alone can easily lead to lesion misdiagnosis. They also aim to emphasize how local treatment methods without advanced microsurgical reconstruction can, in some cases, improve patient outcomes.

In the lateral neck area (LNA), the parotid glands and submandibular glands can be diagnosed with various lesions, especially cysts and tumors of different etiology. In the submandibular area, many lesions are related to salivary stones and some inflammations, causing a secondary gland enlargement. When no sialolithiasis is present, a close relation to other local inflammation causes, IgG4, or related chronic sclerosing disease should be estimated. Ultrasound evaluation seems to be sufficient to indicate any occurrence of salivary retention, inflammation, dilatation of ducts, and gland swelling, and to confirm the initial diagnosis of sialolithiasis or sialadenitis. Any possible tumor formation or tumor-like solid mass evaluation requires adequate computed tomography or magnetic resonance imaging. A very important question should be raised if clinical symptoms like neck asymmetry, submandibular swelling, and solid-mass formation always correspond with radiological as well as some worrisome oncological symptoms. On the other hand, when radiological imaging is insufficient or lacking, a fine needle biopsy would be useful. Problems arise when any signs of potential disease or other tumor-like lesions are inconclusive or indicate inflammation, and possible treatment options are limited. Secondly, when patient anamnesis and blood examination are normal, but a worrisome tumor-like appearance progresses in time, a serious question about improved diagnostics and scheduling for surgery should be raised. Not all cases of elevated serum IgG4 levels correspond with IgG4 lesions and the typical spectrum of those diseases, and therefore histopathological examination of excised lesion provides the scope of the following disease intensity. In the following interesting images, it is worth noticing that radiological, clinical, needle biopsy, and cytological examinations do not always correlate with each other, and in some cases, an open surgery should be considered to improve the diagnosis.

Background/Aim: Olfactory ensheathing cells (OECs) are widely studied for neural repair, yet OB- and OM-derived primary cultures differ in accessibility and cellular composition. This study aimed to establish donor-matched canine OB- and OM-derived primary cultures using harmonized isolation conditions and to quantify source-dependent differences in culture composition and proliferative activity. Materials and Methods: Olfactory bulbs (OBs) and olfactory mucosa (OM) were collected post-mortem from client-owned dogs (n = 10). Primary cultures were established under identical enzymatic dissociation and culture conditions. Culture composition was quantified by immunocytochemistry using p75^NTR (OEC marker) and fibronectin (fibroblast-associated marker), with an epithelial fraction assessed morphologically in OM. Proliferation was assessed by Ki-67 labeling using the Muse® Ki-67 kit (n = 5 donors/group). Results: Both tissues yielded viable primary cultures. OB-derived cultures had a higher OEC fraction than OM-derived cultures (60.7 ± 6.4% vs. 39.0 ± 6.2%), whereas OM cultures consistently included an epithelial component (27.0 ± 6.6%). Ki-67 labeling was higher in OB-derived cultures than OM-derived cultures (30.2 ± 6.2% vs. 13.0 ± 2.5%; Welch’s t-test p = 0.0018). Conclusions: Canine OB and OM generate source-distinct primary cultures under standardized conditions: OB-derived cultures are OEC-enriched and more proliferative in vitro, while OM-derived cultures are more heterogeneous. These findings inform future optimization of OM-based protocols and motivate functional assays to test regenerative efficacy.

Brown tumors (BTs) are rare osteolytic lesions that typically occur in association with primary or secondary hyperparathyroidism (PHP and SHP). Excessive secretion of parathyroid hormone induces increased bone resorption, resulting in lesions characterized by fibrosis, vascularization, and hemosiderin deposition. The most common sites include the jaws, ribs, pelvis, and long bones. Clinical manifestations may involve pain, swelling, or pathological fractures. We present the case of a mandibular BT in a 48-year-old female with chronic renal failure and secondary hyperparathyroidism. The patient exhibited progressive mandibular swelling with radiological features resembling an aggressive odontogenic or malignant lesion. Laboratory analysis confirmed markedly elevated parathyroid hormone levels, while scintigraphy demonstrated increased focal uptake in the mandible and ribs. Histopathological evaluation revealed multinucleated giant cells within a fibrous stroma, consistent with BT. Despite initiation of systemic endocrine therapy, the lesion continued to enlarge, necessitating complete surgical excision of the mandibular mass. This case underscores the diagnostic dilemmas of mandibular BT, which may closely mimic aggressive jaw pathologies. Importantly, while many BTs regress after systemic management of hyperparathyroidism, this case illustrates that surgical excision may be unavoidable in patients with unstable systemic status or progressive local disease. Comprehensive clinical, radiological, laboratory, and histopathological evaluation remains essential to ensure timely diagnosis and appropriate treatment.

In our research we used the extract from dietary supplement of elderberry (EE) and its dominant anthocyanin—cyanidin 3-O-glucoside (Cy 3-gluc). By interacting with a model membrane that reflects the main lipid composition of tumor membranes, the extract components, including Cy 3-gluc, caused an increase in packing order, mainly in the hydrophilic region of the membrane. It can thus be stated that EE caused a rigidifying effect, which is fundamental for understanding its anticancer and antioxidant activity. This study represents the first attempt to unravel the mechanism of interaction of elderberry extract with membranes. The results of the interaction with human serum albumin (HSA) proved that the studied substance quenches the fluorescence of HSA through a static mechanism in which the main interaction forces are Van der Waals and hydrogen bonding. The antioxidant activity of EE and Cy 3-gluc on liposomal membranes, antiradical properties and ability to inhibited the activity of the enzymes cyclooxygenase-1 and cyclooxygenase-2 were also demonstrated. Moreover, the anticancer activity of EE and Cy 3-gluc on human breast adenocarcinoma cell line were investigated. In addition, EE also exhibited the ability to form lipid aggregates in the form of liposomal capsules that can be applied as carriers of active biological substances, and the highest efficacy of EE encapsulation was obtained for multilayered liposome formulations.