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Biodegradable Magnesium (Mg) implants are promising alternatives to permanent metallic prosthesis. To improve the biocompatibility and with the aim of degradation control, we provided Plasma Electrolytic Oxidation (PEO) of pure Mg implant in silicate-based solution with NaOH (S1 250 V) and Ca(OH)2 (S2 300 V). Despite the well-structured surface, S1 250 V implants induced enormous innate immunity reaction with the prevalence of neutrophils (MPO+) and M1-macrophages (CD68+), causing secondary alteration and massive necrosis in the peri-implant area in a week. This reaction was also accompanied by systemic changes in visceral organs affecting animals' survival after seven days of the experiment. In contrast, S2 300 V implantation was associated with focal lymphohistiocytic infiltration and granulation tissue formation, defining a more favorable outcome. This reaction was associated with the prevalence of M2-macrophages (CD163+) and high density of αSMA+ myofibroblasts, implying a resolution of inflammation and effective tissue repair at the site of the implantation. At 30 days, no remnants of S2 300 V implants were found, suggesting complete resorption with minor histological changes in peri-implant tissues. In conclusion, Ca(OH)2-contained silicate-based solution allows generating biocompatible coating reducing toxicity and immunogenicity with appropriate degradation properties that make it a promising candidate for medical applications. [ABSTRACT FROM AUTHOR]

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/β-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 β-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. [ABSTRACT FROM AUTHOR]

Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel's therapeutic effect was manifested by slowing weight gain by 17% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders. [ABSTRACT FROM AUTHOR]

In this study, we investigated the relationship between the tumor immune microenvironment (TIME), histological differentiation and hypoxia in patients with muscular-invasive urothelial carcinomas (MIUC) after radical cystectomy. Forty-two cases of pT2-3N0M0 MIUCs underwent clinical, histological and immunohistochemical evaluation by counting CD8+, FOXP3+, CD68+, CD163+ cells and polymorphonuclear leukocytes (PMN) in intra-tumoral and peritumoral areas, assessing PD-L1 and GLUT1 expression for defining the impact of tumor immune contexture on patients' outcomes. Five-year survival rates and overall survival were calculated. Most of the MIUCs demonstrated the immune-desert or immune-excluded TIME, reflecting altered mechanisms of T-cells' activation or traffic into tumors. Tumor immune contexture was closely related to histological differentiation. CD8+ cells were scant in MIUCs with papillary and squamous differentiation, while basal-like or mesenchymal-like histological differentiation was associated with increased density of CD8+ cells. A high rate of PD-L1 expression (47.6%) was not related to immune cell infiltration. M2-macrophages predominated under CD8+ lymphocytes. The abundance of PMN and CD163+ macrophages in MIUCs was associated with high GLUT1 expression. CD8+, CD68+, FOXP3+ cells and PD-L1 status did not affect patients' outcomes, while high CD163+ density and PMN infiltration were associated with the unfavorable outcome of patients with MIUC. These data drive the hypothesis that in MIUC, immune escape mechanisms are shifted towards the role of the innate immunity cells rather than CD8+ lymphocytes' functioning. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the relation between the level of thyroid stimulating hormone (TSH) and progression of papillary thyroid carcinoma (PTC) with or without BRAFV600E mutation. The medical records and laboratory data of 547 patients with PTC and 94 patients with follicular adenoma (FA) were collected. The relationship between hormones levels and such end-points as extrathyroid extension (ETE), lymphovascular invasion (LVI) and lymph node metastasis (LNM) was assessed. In addition, age, gender, BRAFV600E mutation status, histological type and Hashimoto's thyroiditis (HT) were considered. Most of the patients with PTC had hormones levels within the normal range, however, serum TSH concentration was significantly higher in PTC comparing with FA (P = 0.022). High levels of TSH in PTC were more frequent among women rather than men (P = 0.03) due to the gender differences in coexisting HT rate (P = 0.003). In contrast, LNM rate was higher in men (P = 0.0014). Coexisting HT significantly decreased the risk of ETE (OR = 0.67; 95%CI 0.44–1.00; P = 0.05) and LNM (OR = 0.59; 95%CI 0.37−0.94; P = 0.028) among males with PTC. However, there was no significant relationship between HT and PTC-related ETE and LNM in females. BRAF V600E mutation was associated with presence of lymphocytic infiltration (P < 0.001) but not with HT (P = 0.08) and violation of thyroid function. The present study showed the lack of significant relationship between TSH levels and PTC aggressiveness (LNM, TNM stage, BRAF V600E mutation). Higher TSH levels were found in patients with coexisting HT that was associated with female sex and multifocality of PTC. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to assess the impact of leukocytes reaction on rebleeding development among patients with peptic ulcers. Methods This was a single-center cohort study enrolling 232 patients with a diagnosis of gastroduodenal ulcer bleeding. The end point was the in-hospital rebleeding rate during the three days after admission. The impact of clinical, demographic, endoscopic and laboratory data at the time of admission, as well as macrophages (CD68) and neutrophils count in ulcer margin, on bleeding outcome was assessed. In addition, impact of the leukocytes on the platelets aggregation induced with ADP (5 μM) and collagen (1 μM) was measured in vitro. Results Acute ulcer bleeding was accompanied with an acute inflammatory response to damage and hemorrhage. Despite the increase of neutrophil count ( P = 0.031) in peripheral blood of bleeders, there were not significant influence of this parameter on the outcome. It was shown that the most significant predicting factors were an increased neutrophils (OR 1.4; 95% CI 1.1–1.8) and macrophages count in the ulcer margin (OR 3.5; 95% CI 1.9–4.87); an endoscopically diagnosed active bleeding (OR 3.0; 95% CI 1.4–6.3); an enhanced level of plasma fibrinogen (OR 1.04; 95% CI 1.0–1.08). Co-incubation of platelets with leukocytes significantly decreased the collagen induced aggregation ( P = 0.008) that could indicate either alteration of mechanisms of platelets adhesion, or inhibition of stabilization phase of thrombogenesis. Conclusion The severity of the local acute inflammatory reaction promotes progressive tissue damage of ulcer margin, and increases the risk of rebleeding. [ABSTRACT FROM AUTHOR]

Surgical site infection (SSI) substantially contributes each year to patients' morbidity and mortality, accounting for about 15% of all nosocomial infections. SSI drastically increases the rehab stint and expenses while jeopardizing health outcomes. Besides prevention, the treatment regime relies on an adequate antibiotic therapy. On the other hand, resistant bacterial strains have currently reached up to 34.3% of the total infections, and this percentage grows annually, reducing the efficacy of the common treatment schemes. Thus, new antibacterial strategies are urgently demanded. Here, we demonstrated in rats the effectiveness of non-persistent silver nano-architectures (AgNAs) in infected wound healing together with their synergistic action in combination with chlorhexidine. Besides the in vivo efficacy evaluation, we performed analysis of the bacteriological profile of purulent wound, histological evaluations, and macrophages polarization quantifications to further validate our findings and elucidate the possible mechanisms of AgNAs action on wound healing. These findings open the way for the composition of robust multifunctional nanoplatforms for the translation of safe and efficient topical treatments of SSI. [ABSTRACT FROM AUTHOR]

The application of chitosan (Ch) as a promising biopolymer with hemostatic properties and high biocompatibility is limited due to its prolonged degradation time, which, in turn, slows the repair process. In the present research, we aimed to develop new technologies to reduce the biodegradation time of Ch-based materials for hemostatic application. This study was undertaken to assess the biocompatibility and hemostatic and tissue-regeneration performance of Ch-PEO-copolymer prepared by electrospinning technique. Chitosan electrospinning membranes (ChEsM) were made from Ch and polyethylene oxide (PEO) powders for rich high-porous material with sufficient hemostatic parameters. The structure, porosity, density, antibacterial properties, in vitro degradation and biocompatibility of ChEsM were evaluated and compared to the conventional Ch sponge (ChSp). In addition, the hemostatic and bioactive performance of both materials were examined in vivo, using the liver-bleeding model in rats. A penetrating punch biopsy of the left liver lobe was performed to simulate bleeding from a non-compressible irregular wound. Appropriately shaped ChSp or ChEsM were applied to tissue lesions. Electrospinning allows us to produce high-porous membranes with relevant ChSp degradation and swelling properties. Both materials demonstrated high biocompatibility and hemostatic effectiveness in vitro. However, the antibacterial properties of ChEsM were not as good when compared to the ChSp. In vivo studies confirmed superior ChEsM biocompatibility and sufficient hemostatic performance, with tight interplay with host cells and tissues. The in vivo model showed a higher biodegradation rate of ChEsM and advanced liver repair. [ABSTRACT FROM AUTHOR]