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Histomorphometric measurements of the wall thickness and internal diameter of the macrovessels of the chorionic villi of placentas from pregnancies complicated by preeclampsia or fetal growth restriction in comparison with normotensive pregnancy., Methods: The research included placentas from singleton pregnancies complicated by preeclampsia and/or fetal growth restriction, women delivered in medical institutions in Karaganda city (Kazakhstan). Placentas were divided into three groups: PE ( n = 59), isolated FGR ( n = 24), and PE with FGR ( n = 41). The control group consisted of normotensive pregnancies, compared by gestation period. Placental examination and selection of placental tissue fragments were carried out in accordance with the consensus recommendations of the Amsterdam Placental Workshop Group. The sections were stained with hematoxylin and eosin and Masson trichrome. Morphometric measurements were performed using ImageJ software version 1.52p., Results: Our data showed that, in the PE group, there was a significant decrease in the wall thickness of the proximal and distal vessels with an increase in internal diameter compared with the control group ( p < 0.01). In the PE + FGR group, there was a thickening of the wall of the proximal part of the vessels with a decrease in their lumen and a decrease in the wall thickness of the vessels with an increase in the lumen in the distal part compared with the control group ( p < 0.01)., Conclusions: Two histopatterns of placental macrovessels in preeclampsia were revealed: the histophenotype of diffuse (proximal and distal) ectatic macroangiopathy with a thin vascular wall with a decrease in the thickness of the muscle layer and the histophenotype of proximal fibromuscular sclerosis with vascular obliteration/spasm and distal ectatic macroangiopathy. We believe that significant structural differences in vascular remodeling may reflect the different temporal and spatial nature of the pathological factor. Future research is needed to investigate the associations between histopatterns of placental vascular remodeling in preeclampsia and long-term perinatal/maternal outcomes.

Purpose: The present study aimed to evaluate and compare the effect of nanofibrillated cellulose (NFC)-based composite with dicalcium phosphate dihydrate and an autologous blood clot (ABC) on the formation of new bone tissue in vivo by histological and histomorphometric assessment., Materials and Methods: A total of 72 rats with created femoral defects (2 mm) were used. The rats were divided into three groups: (1) with filling of the defect with an ABC, (2) NFC-1-with filling of both the cortical plate and intramedullary space in the defect area, and (3) NFC-2-with filling of only the intramedullary space in the defect area. Histological and histomorphometric analysis was performed to assess the healing of the bone defect after 14, 30 and 60 days., Results: Complete closure of the cortical plate defect was detected in the NFC-2 group on Day 30 ( p  < 0.0001). Moreover, in both NFC groups on the 30th and 60th days, ongoing osteogenesis was observed, characterized by a large volume of newly formed circular pattern bone tissue in the intramedullary space., Сonclusion: This study demonstrated that the NFC-based composite, which is located below the level of the cortical plate, tamponing only the intramedullary space (NFC-2), improves bone tissue repair at the site of a bone defect of the cortical plate and has the potential of prolonged osteoinductivity., Level of Evidence: Not applicable., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare's milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare's milk-derived exosomes as potential therapeutic carriers. Three extraction methods-immunoprecipitation, size exclusion chromatography, and total exosome isolation-were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare's milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers.

Objective(s): Comparative clinical and morphological characterization of lesions of the vascular and nervous system in cases of maternal death associated with COVID-19., Study Design: The study included autopsy in 12 cases of maternal death with a positive intravital result for SARS-CoV-2 by reverse transcription polymerase chain reaction. For histopathology, tissue samples were taken from the internal organs of each patient. Pieces of organs were fixed and stained according to the standard protocol. The relative number of microvessels with vasculitis and fibers of the peripheral nervous system with infiltration by immune cells was studied. All morphological changes were classified depending on the severity of the damage., Results: The average age of patients with a fatal outcome was 35 ± 4.4 years. Time to death after onset of symptoms averaged 16 ± 4.4 days. Dystrophic lesions (necrosis and apoptosis) of the villous and extravillous trophoblast and decidual tissue were observed in the studied placentas. Histopathological signs of mild and severe lesions of the peripheral nervous system in the organs of the gastrointestinal tract were detected in 2 (16.7%) and 10 (83.3%) cases, respectively, in the myocardium in 4 (33.3%) and 8 (66.7%) cases. Histopathological signs of severe damage to the microvascular bed in the organs of the gastrointestinal tract were registered in 9 (75%) cases., Conclusion(s): The main clinical feature of this cohort was that death occurred in a long-term period, in most cases with a negative PCR. The histopathological pattern was a non-acute injury with an immune component of the microvascular bed and the autonomic nervous system with predominant damage to the myocardium and intestines., What Does This Study Add to the Clinical Work: This study makes it possible to even better study the immunopathological profile in organs and tissues in pregnant women with a fatal outcome when affected by a viral infection, in particular Covid-19. This knowledge can be used when humanity encounters other viral pandemics in the future., (© 2024. The Author(s).)

This study aimed to compare the new bone formation, the process of remodeling, and the viability of bone grafts, using a combination of platelet-rich plasma (PRP) and Marburg bone graft versus bone grafts without any additional elements. For this study, 48 rabbits (with 24 rabbits in each group) were used. Bone defects were made in the femur, and the bone graft used was the human femoral head prepared according to the Marburg Bone Bank. Rabbits were divided into the following groups: heat-treated bone graft (HTBG group) and HTBG with PRP (HTBG + PRP group). After 14, 30, and 60 days post-surgery, the assessment of the results involved X-ray, histopathological, and histomorphometric analyses. The greater new bone formation was detected in the HTBG + PRP group on the 14 and 30 day ( p < 0.001). Furthermore, the group using bone grafts with PRP demonstrated notably enhanced remodeling, characterized by stronger bone integration, more significant graft remineralization, and a circular pattern of newly formed bone. The PRP-bone graft complex improves bone tissue repair in the bone defect in the initial stages of bone regeneration. PRP has been identified to enhance the remodeling process and amplify the osteoconductive and osteoinductive capabilities of HTBGs., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

This research aimed to assess the effect of bone allograft combined with platelet-rich plasma (PRP), recombinant human bone morphogenetic protein-2 (rhBMP-2), and zoledronic acid (Zol) on bone formation. A total of 96 rabbits were used, and femoral bone defects (5 mm) were created. The rabbits were divided into four groups: (1) bone allograft with PRP (AG + PRP), (2) bone allograft with rhBMP-2 5 μg (AG + BMP-2), (3) bone allograft with Zol 5 μg (AG + Zol), and (4) bone allograft (AG). A histopathological examination was performed to evaluate bone defect healing after 14, 30, and 60 days. The new bone formation and neovascularization inside the bone allograft was significantly greater in the AG + PRP group compared to AG and AG + Zol groups after 14 and 30 days ( p < 0.001). The use of bone allograft with rhBMP-2 induced higher bone formation compared to AG and AG + Zol groups on days 14 and 30 ( p < 0.001), but excessive osteoclast activity was observed on day 60. The local co-administration of Zol with a heat-treated allograft inhibits allograft resorption as well as new bone formation at all periods. In conclusion, this study demonstrated that PRP and rhBMP-2, combined with a Marburg bone allograft, can significantly promote bone formation in the early stage of bone defect healing.

Determining the most appropriate cannula diameter for lipoaspirate harvesting is important, both in terms of the quality and composition of the material obtained, and the ease of practical use of the cannula. The size of the cannula is one of the main factors affecting the qualitative characteristics of the obtained lipoaspirate sample for further use of adipose tissue. The purpose of the investigation was to clinically and histomorphometrically determine the optimal cannula diameter for lipoaspirate samples collection from rabbit inguinal fat pad in an experimental study. The methods of Animal models, Surgical procedures, Macroscopic examination, Histological examination, and Morphometric study were applied. There is a direct correlation between the percentage of connective tissue fibres in the lipoaspirate and the diameter of the cannula. The lack of clear criteria for selecting a lipoaspiration cannula is one of the limitations to obtaining generally accepted lipoaspiration protocols with subsequent use of adipose tissue. In this study, the animal experiment determined the most ideal cannula diameter suitable for collecting the largest amount of lipoaspirate for subsequent use., Competing Interests: The authors report no conflicts of interest in this work.

The current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-α and IFN-γ levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4-induced hepatotoxicity in rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

The aim of this experimental study was to evaluate the effect of zolendronic acid (ZOL) combined with bone allograft prepared using the Marburg Bone Bank System on bone formation in the implant remodeling zone. Femoral bone defects with a diameter of 5 mm and a depth of 10 mm were created in 32 rabbits. Animals were divided into 2 similar groups: Group 1 (control), where defects were filled with bone allograft, and Group 2, where allograft was combined with ZOL. Eight animals from each group were sacrificed at 14- and 60-days post-surgery and bone defect healing was assessed using histopathological and histomorphometric analyses after 14 and 60 days. The results showed that new bone formation within the bone allograft was significantly greater in the control group than in the ZOL-treated group after 14 and 60 days (p<0.05). In conclusion, local co-administration of ZOL on heat-treated allograft inhibits allograft resorption and new bone formation in the bone defect., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Introduction: Fetal hypoxic events with unclear predictive value are a common indication for placenta examination. We evaluated whether the use of CD15 immunostaining can improve the assessment of severity and duration of fetal hypoxia., Methods: We compared placentas (37-42 gestational weeks) from stillborns/newborns with birth asphyxia (BA) and non-hypoxic newborns. Placental findings were studied in following groups: (1) acute BA (n = 11) due to placental abruption, (2) non-acute BA (n = 121) due to non-acute conditions, (3) non-BA (n = 46) in pregnancies with preeclampsia and gestational diabetes, and (4) controls (n = 30)., Results: A high expression of CD15 in feto-placental resistance vessels (FRVs) was present in non-acute BA (95.9%), but absent in acute BA, non-BA and controls (p < 0.0001). Furthermore, we found no causal relationship of high expression of CD15 in FRVs to coexisting placental conditions, including severity and mechanisms/patterns of placental injury, fetal erythroblastosis, and maternal conditions. According to a multivariate analysis, only a high expression of CD15 in FRVs was independently associated with severe non-acute fetal hypoxia ([OR] = 15.52; 95% [CI] = 5.92-40.67)., Discussion: We have defined a characteristic pattern of CD15 expression in FRVs that allows to interpret various clinical/placental conditions with respect to fetal hypoxia, with an improved predictability compared to conventional analyses. This approach represents a novel diagnostic strategy for placenta examination, which could indirectly assess severity and duration of intrauterine hypoxia in a heterogeneous population of newborns., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Doxorubicin is a chemotherapeutic agent known to cause cardiotoxicity that is thought to be associated with oxidative stress. The aim of the current study is to investigate the role of grape polyphenols' antioxidant property as cardioprotective against doxorubicin-induced cardiotoxicity. Adult Wistar rats weighing 200 ± 20 g were divided into 3 different groups: a doxorubicin group that received a single intraperitoneal administration of doxorubicin (8.0 mg/kg body weight), an experimental group that received doxorubicin and grape polyphenol concentrate (25 mg/kg) via intragastric route, and the third group was a negative control group that received water only. On day 8, blood samples and tissues were harvested for analyses. The results indicated that grape polyphenol concentrate was able to reduce the signs of cardiotoxicity of doxorubicin through the reduction of aspartate aminotransferase activation, increasing the plasma antioxidant levels and decreasing the level of free radicals. The results also showed that grape polyphenol concentrate was able to reverse doxorubicin-induced microscopic myocardial damage. The myocardial protective effect of grape polyphenol might likely be due to the increase in the level and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, grape polyphenol concentrate displayed cardioprotective effect and was able to reverse doxorubicin-induced-cardiomyopathy in experimental rats.