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Background and Objectives: Bone and mineral disease (BMD) is a prevalent complication of advanced chronic kidney disease (CKD). The risk of fractures can be assessed via dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). This study aims to evaluate the effectiveness of two imaging modalities in identifying bone mineral status in individuals with pre-dialysis chronic renal disease and to assess their correlation with bone turnover markers. Materials and Methods: This controlled cross-sectional study, conducted at a single center from 2019 to 2022, assessed two groups of individuals aged 18 to 50. The patient cohort consisted of individuals with stage 4–5 chronic kidney disease, whereas the control cohort consisted of healthy participants. The participants' bone and mineral status was evaluated using both QCT and DXA methods. Diagnostic measurements of the lumbar spine and femoral neck, obtained using DXA and QCT, were compared. Z-scores were utilized to evaluate low bone mineral density, with low Z-scores identified in either lumbar spine or femoral neck measures being seen as indicative of low bone mineral density. Results: Data from 38 participants (patient group: 18; control group: 20) who underwent QCT and/or DXA were evaluated. Thirty-three subjects were assessed using both QCT and DXA (patient group: 14; control group: 19). The median age of the patient cohort was 44 (range: 22–50), whereas the median age of the control cohort was 42 (range: 27–48) (p = 0.72). Women constituted 33% of the patient cohort and 50% of the control cohort (p = 0.23). In the patient cohort, low bone mineral density was detected in four individuals (28%) through QCT, and in just two patients (14%) through DXA. Compared to DXA, QCT identified a higher number of cases of low bone mineral density in the CKD cohort; however, no statistically significant difference was observed (p = 0.06). In addition, our study found that TRACP5b had a strong negative correlation with the DXA L1–L4 Z-score. Conclusions: This study revealed that QCT may be more sensitive than DXA for detecting low bone density in pre-dialysis CKD patients. Additionally, DXA may overestimate lumbar spine BMD in this population, and the strong negative correlation between TRACP5b levels and the DXA L1–L4 Z-score highlights the potential role of biochemical markers in assessing bone status in CKD [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP), a commonly used analgesic, causes acute kidney injury (AKI) in overdose although it is rare. Mitochondrial dysfunction plays a major role in the pathophysiology of renal damage, although the exact molecular mechanism is unknown. This study aimed to evaluate the potential therapeutic effect of cyclosporin A (CsA), a mitochondrial membrane permeability transition pore (MPTP) inhibitor, with N-acetylcysteine (NAC) in APAP-induced AKI. Methods: Male BALB/c mice were divided into Control, APAP, APAP+NAC, APAP+CsA and APAP+NAC+CsA groups (n=6). A single dose of APAP (400 mg/kg) was administered intraperitoneally. All other treatments (1200 mg/kg NAC, 50 mg/kg CsA) were performed intraperitoneally 3 h after APAP administration. All animals were decapitated and blood samples and kidney tissue samples were collected for evaluation. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured. The kidney tissue 8-hydroxy-deoxyguanosine (8-OHdG), cytochrome c (Cytc) and 3-nitrotyrosine (3-NT) levels and cytochrome c (Cytc) expressions were determined. Result: Increased Cr and BUN levels, histopathological examinations and expressions of 8-OHdG, 3-NT and Cytc were detected in the APAP group. Combined NAC+CsA treatment sufficiently reversed oxidative stress, serum Cr and BUN levels and histopathological alterations induced by APAP. Moreover, cytc levels and renal tubular injury were remarkably reduced by combined drug treatment compared to the APAP+NAC group. These data suggest that the therapeutic effect of combined NAC+CsA treatment in mice with APAP-induced nephrotoxicity can be related to the combination of the antioxidant effect of NAC and the mitochondrial MPTP inhibitor effect of CsA. [ABSTRACT FROM AUTHOR]

Carduus adpressus has been used for its anti-hair loss effect in traditional folk medicine. The plant species is mainly distributed in Türkiye, Bulgaria, and the Western Caucasus. The studies on this specific plant in the genus Carduus is limited which remarks the significance of the current study. This study aims to investigate the antibacterial, antioxidant, and wound-healing properties of the methanolic extract of Carduus adpressus. Extract was obtained by maceration. The broth microdilution assay was performed on Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. DPPH and ABTS radical scavenging assays were performed to detect the antioxidant capacity. Wound-healing activity was tested using alloxan-induced diabetic BALB-c mice. 4 groups, control, vehicle, CAE and Carduus adpressus groups were treated with the relative agent for 10 days. Extract demonstrated 62.5 μg/mL MIC against S. aureus and E. faecalis, and 125 μg/mL MIC against P. aeruginosa and E. coli. ABTS assay showed higher antioxidant activity compared to the DPPH assay. Carduus adpressus group demonstrated strong regeneration, epithelisation, and angiogenesis compared to the control group on day 10. Additionally, expression of PDGF, VEGF, and collagen formation was increased in the Carduus adpressus group compared to the control group on day 10. Extract demonstrated strong antibacterial, antioxidant, and wound-healing activities which indicate that it could be a source in developing wound-healing agents. [ABSTRACT FROM AUTHOR]

Disruption of the gut‐brain axis in Parkinson's disease (PD) may lead to motor symptoms and PD pathogenesis. Recently, the neuroprotective potential of different PPARδ‐agonists has been shown. We aimed to reveal the effects of erucic acid, peroxisome proliferator‐activated receptors (PPARs)‐ligand in rotenone‐induced PD model in zebrafish, focusing on the gut‐brain axis. Adult zebrafish were exposed to rotenone and erucic acid for 30 days. Liquid chromatography‐mass spectrometry and tandem mass spectrometry (LC–MS/MS) analysis was performed. Raw files were analysed by Proteome Discoverer 2.4 software; peptide lists were searched against Danio rerio proteins. STRING database was used for protein annotations or interactions. Lipid peroxidation (LPO), nitric oxide (No), alkaline phosphatase, superoxide dismutase, glutathione S‐transferase (GST), acetylcholinesterase and the expressions of PD‐related genes were determined. Immunohistochemical tyrosine hydroxylase (TH) staining was performed. LC–MS/MS analyses allowed identification of over 2000 proteins in each sample. The 2502 and 2707 proteins overlapped for intestine and brain. The 196 and 243 significantly dysregulated proteins in the brain and intestines were found in rotenone groups. Erucic acid treatment corrected the changes in the expression of proteins associated with cytoskeletal organisation, transport and localisation and improved locomotor activity, expressions of TH, PD‐related genes (lrrk2, park2, park7, pink1) and oxidant‐damage in brain and intestines in the rotenone group as evidenced by decreased LPO, No and increased GST. Our results showed beneficial effects of erucic acid as a PPARδ‐ligand in neurotoxin‐induced PD model in zebrafish. We believe that our study will shed light on the mechanism of the effects of PPARδ agonists and ω9‐fatty acids in the gut‐brain axis of PD. [ABSTRACT FROM AUTHOR]

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Acetaminophen (APAP)-induced hepatotoxicity is the most common cause of acute liver failure in worldwide. N-acetyl cysteine (NAC) is used as the APAP antidote. Cyclosporin A (CsA) is suppressed mitochondrial damage by binding cyclophilin, a mitochondrial pore transport component. The study aimed to evaluate the effects of NAC, CsA, and NAC+CsA treatments on APAP-induced hepatotoxicity in mice. Mice were randomly divided into five groups (n = 6). 400 mg/kg/ip/single dose APAP, 1200 mg/kg/i.p/single dose NAC and 50 mg/kg/i.p/single dose CsA were performed. Light and electron microscopic alterations were investigated in liver samples. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver glutathione (GSH) were analyzed. 3-nitrotyrosine and cytochrome c immunoreactivities were evaluated in liver tissue. Here, we found that APAP leads to histopathological and ultrastructural changes in mice liver. Also, APAP increased cytochrome c and 3-nitrotyrosine immunopositive staining. Besides, a significant decrease in liver GSH and an increase in serum AST and ALT levels were detected in the APAP group. Interestingly, NAC+CsA treatment improved histological alterations, cytochrome c, and 3-nitrotyrosine immunoreactivities and liver GSH, serum AST/ALT levels caused by APAP. We suggest that the combination of NAC and CsA reduces acetaminophen-induced hepatotoxicity in mice. [ABSTRACT FROM AUTHOR]

Objectives: The superior properties of nickel oxide-nanoparticles (NiO-NPs) have led to their wide use in various fields. However, there is little comprehensive knowledge about their toxicity, especially after oral exposure. The toxic effect of NiO-NPs of mean size 15.0 nm was investigated in Caco-2 (human intestinal epithelial) cells as no study has been performed on their intestinal toxicity. Materials and Methods: Following identification of their particle size distribution and cellular uptake potential, the risk of exposure to NiO-NPs was evaluated by cellular morphologic changes, cyto- and genotoxic potentials, oxidative damage, and apoptotic induction. Results: NiO-NPs induced a 50% reduction in cell viability at 351.6 µg/mL and caused DNA damage and oxidative damage at 30-150 µg/mL. It appears that apoptosis might be a main cell death mechanism in NiO-NP-exposed intestinal cells. Conclusion: NiO-NPs might be hazardous to the gastrointestinal system. The results should raise concerns about using NiO-NPs in food-contact appliances and about NiO-NP-containing wastes. Further in vivo and in vitro research should be conducted to explain the specific toxicity mechanism of these particles and reduce their risk to humans. [ABSTRACT FROM AUTHOR]

The potential benefits of platelet-rich plasma in the healing of isolated defects are unclear. The purpose of this study was to evaluate the effects of PRP on bone healing in titanium bone chambers, which represented isolated defects. PRP was prepared from blood collected from six adult female albino New Zealand rabbits. Titanium bone chambers with a 4-mm inner diameter were implanted into the tibiae of each animal at baseline and 2 weeks later; chambers healed for 6 or 8 weeks, either with PRP (test) or without PRP (control). Bone chambers were harvested from each animal and processed for histologic evaluation. Bone formation in 8-week test samples was not significantly different from that of the 6-week test samples. In control samples, more bone formation was seen at 8 weeks than at 6 weeks. The fibrous tissue content in control samples was higher than that of the test group in superficial sections, revealing that the tissue differentiation rate was higher in the test chambers. Time-dependent bone tissue differentiation in bone chambers augmented with PRP is higher than in normal wound healing, and PRP seems to increase the rate of tissue differentiation in early healing. [ABSTRACT FROM AUTHOR]

Repair of cranial bone defects is an important problem in the clinical area. The use of scaffolds combined with stem cells has become a focus in the reconstruction of critical-sized bone defects. Electrospinning became a very attracting method in the preparation of tissue engineering scaffolds in the last decade, due to the unique nanofibrous structure of the electrospun matrices. However, they have a limitation for three dimensional (3D) applications, due to their two-dimensional structure and pore size which is smaller than a cellular diameter which cannot allow cell migration within the structure. In this study, electrospun poly(ε-caprolactone) (PCL) membranes were spirally wounded to prepare 3D matrices composed of nanofibers and macrochannels. Mesenchymal stromal/stem cells were injected inside the scaffolds after the constructs were implanted in the cranial bone defects in rats. New bone formation, vascularisation and intramembranous ossification of the critical size calvarial defect were accelerated by using mesenchymal stem cells combined 3D spiral-wounded electrospun matrices. [ABSTRACT FROM AUTHOR]

Objective: We compared electron microscopic histologic changes of the radial artery grafts in non-diabetic and diabetic patients.Methods: Thirty-six patients were divided into three groups according to their diabetic status (Group I had no diabetes mellitus [DM], Group II had type two DM and HbA1c levels were <7.5%, and Group III had type 2 DM but HbA1c levels were >7.5%). Distal parts of radial artery grafts were evaluated with scanning electron microscopy in a blind fashion by two histologists. Electron microscopic scores were compared among the groups.Results: Radial artery electron microscopic scores were significantly different between group 1, 2 and 1, 3 and 2, 3 (p = 0.028, p < 0.001, and p < 0.001). In linear regression analysis, duration of DM (p = 0.027) and fasting plasma glucose (p = 0.001) were found as independent risk factors for histologic changes of radial artery grafts.Conclusion: Duration of DM and poor glycemic control were found to be associated with radial artery electron microscopic changes. doi: 10.1111/jocs.12761 (J Card Surg 2016;31:410-415). [ABSTRACT FROM AUTHOR]

HEMA-Lactate-Dextran cryogel scaffolds were produced by cryogelation. Mesencyhmal stem cells (MSC) were isolated from rat bone marrow. Critical sized cranial bone defects were created in rat cranium. Stem cells were injected inside the macropores of the cryogel scaffolds prepared from HEMA-Lactate-Dextran possessing the same dimensions with the defect and placed in the cranial bone. The cryogels placed in the defect without stem cells served as control. After selected time intervals the experimental sites were removed from the animals and new bone formation and tissue integration were investigated by histological analysis. The in vivo results exhibited osseous tissue integration within the implant and mineralized functionally stable bone restoration of the cranial defects. Tissue formation started in the macrospores of the scaffold starting from periphery to the center. A significant ingrowth of connective tissue cells and new blood vessels allowed new bone formation. Histological data demonstrated that new bone per total defect area ratio, were not significantly different in 'scaffold-stem cells' group compared to that of 'scaffold only' group on all time points. However, the blood vessel density was significantly higher in 'scaffold-stem cells' group comparing to that of the 'scaffold only' group on day 30. 'Scaffold-stem cells' given group gave better tissue response score when compared to 'scaffold only' group on day 180. [ABSTRACT FROM AUTHOR]

Two biodegradable polymers, poly(L-lactide) and poly(ε-caprolactone) were blended (50/50) and used to produce polymeric scaffolds by the dual porogen approach using a salt leaching technique to create pores within the matrix, while supercritical-CO 2 treatment was used to enhance the interconnectivity and to remove impurities from synthesis steps. The scaffolds were highly porous (porosity >90%) with interconnected pore morphologies. These biodegradable scaffolds were evaluated in Sprague Dawley rats for osteoconductive properties over a 6-month period. Bone specimens were analyzed after 1, 3, and 6 months, for bone healing and tissue response. The cortical bone remodeling by controlled osteoblastic and osteoclastic activities as well as the bone marrow elements recovery were semi-quantitatively examined for each group. Excellent integration and biocompatibility behavior was observed in all groups. No adverse tissue responses were observed. [ABSTRACT FROM PUBLISHER]

Reconstruction of large bone defects is still a major problem. Tissue-engineering approaches have become a focus in regeneration of bone. In particular, critical- sized defects do not ossify spontaneously. The use of electrospinning is attracting increasing attention in the preparation of tissue-engineering scaffolds. Recently, acellular scaffolds carrying bioactive agents have been used as scaffolds in ''in situ'' tissue engineering for soft and hard tissue repair. Poly(ε-caprolactone) (PCL) with two different molecular weights were synthesized, and the blends of these two were electrospun into nonwoven membranes composed of nanofibers/micropores. To stimulate bone formation, an active drug, ''simvastatin'' was loaded either after the membranes were formed or during electrospinning. The matrices were then spiral-wound to produce scaffolds with 3D-structures having both macro- and microchannels. Eight-millimeter diameter critical size cranial defects were created in rats. Scaffolds with or without simvastatin were then implanted into these defects. Samples from the implant sites were removed after 1, 3, and 6 months postimplantation. Bone regeneration and tissue response were followed by X-ray microcomputed tomography and histological analysis. These in vivo results exhibited osseous tissue integration within the implant and mineralized bone restoration of the calvarium. Both microCT and histological data clearly demonstrated that the more successful results were observed with the ''simvastatincontaining PCL scaffolds,'' in which simvastatin was incorporated into the PCL scaffolds during electrospinning. For these samples, bone mineralization was quite significant when compared with the other groups. [ABSTRACT FROM AUTHOR]

Epilepsy is a neurological disease of the central nervous system. The prevalence of epilepsy is about 2- 3% in the population. The epilepsy is characterized by the seizures. The symptoms of epilepsy include several symptoms such as confusion, uncontrollable jerking movements of the arms and legs, and loss of consciousness or awareness. There are different types of epilepsy. In the etiology of epilepsy, several factors were proposed by the researchers. The excessive Ca2+ influx has a main role in the seizure of epilepsy. There are several drugs for the treatment of epilepsy, but they have limited action in the treatment of some types of epilepsy. TRPV1 channel is a member of the TRP superfamily. TRPV1 is a Ca2+ permeable ion channel within the TRP superfamily. The TRPV1 are activated in neuronal cells by several stimuli such as hot chili pepper component (capsaicin), acidic pH (≤ 5.5), and heat (≥ 43 °C). The involvements of the calcium channels such as chemical and voltage gated were deeply indicated in the studies of cell culture, experimental animals, and human. However, the recent data indicated involvement of TRPV1 in the etiology of epilepsy. In addition, the administration of TRPV1 agonist (capsaicin) accelerated the seizures of epilepsy, although the pretreatments of TRPV1 antagonists (capsazepine and AMG9810) inhibited the formation of epileptic seizures in the rodents (Nazıroğlu 2015; Mohandass et al. 2020; Gladkikh et al. 2021). However, there are conflicting results on the subject, and the modulator role of TRPV1 in the formation of epileptic seizures in the pentylenetetrazolinduced kindling model in mice (Suemaru et al. 2018). In conclusion, it seems that TRPV1 has an essential role in the etiology of epilepsy. The inhibition of TRPV1 may be a new strategy for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a broad spectrum chemotherapeutic, has toxic effects on healthy tissues. Mitochondrial processes and oxidative stress act in the DOX-induced toxicity, therefore antioxidant therapies are widely used. The study was aimed to evaluate the therapeutic potential of Pleurotus eryngii extract (PEE), an extract of a fungus with antioxidant properties, against DOX-induced lung damage. Rats were divided into Control, DOX, DOX + PEE, and PEE groups (n = 6). DOX was administered intraperitoneally in a single dose (10 mg/kg BW) and PE (200 mg/kg BW) was administered by oral gavage every other day for 21 days. Histopathological evaluations, immunohistochemical analyses, total oxidant status (TOS)/total antioxidant status (TAS) method, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed. DOX led to severe histopathological disruptions in rat lungs. Also, DOX remarkably increased the expression of dynamin 1 like (DRP1) and decreased the expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) genes, which are related to mitochondrial dynamics. Moreover, DOX caused an increase in TOS/ TAS and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. On the other hand, PEE treatment remarkably normalized the histopathological findings, mitochondrial dynamics-related gene expressions, markers of oxidative stress, and DNA damage. The present study signs out that PEE can ameliorate the DOX-mediated lung toxicity and the antioxidant mechanism associated with mitochondrial dynamics can have a role in this potent therapeutic effect.

Purpose: This study was performed to evaluate the influence of local application of thymoquinone (TQ) on bone healing in experimental bone defects infected with Porphyromonas gingivalis (PG)., Methods: Forty-two female rats were randomly divided into 6 groups. A bone defect was created on the right tibia of all animals. The PG, PG/collagen membrane (COL) and PG/TQ/COL groups were infected with PG. In the COL and PG/COL groups, the defects were covered with a COL; in the TQ/COL and PG/TQ/COL groups, the defects were covered with a TQ-containing COL. After 28 days, all animals were sacrificed. Quantitative measurements of new bone formation and osteoblast lining, as well as semiquantitative measurements of capillary density and tissue response, were analyzed. Furthermore, the presence of bacterial infections in defect areas was evaluated., Results: The new bone formation, osteoblast number, and capillary density were significantly higher in the TQ groups than in the control groups ( P <0.001, P <0.001, and P <0.01, respectively). In a comparison between the TQ/COL group, with a TQ-containing COL (TQ/COL), and the PG - infected TQ-containing COL (PG/TQ/COL) group, the newly formed bone and capillary density were higher in the TQ/COL group ( P <0.01). When the control group was compared to the PG, PG/COL, and PG/TQ/COL groups in terms of tissue response, the differences were statistically significant ( P <0.001, P =0.02, and P =0.041, respectively). The intensity of the inflammatory cell reaction was higher in the PG, PG/COL, and PG/TQ/COL groups ( P <0.05)., Conclusions: Within the limitations of this study, the local application of a TQ-containing COL positively affected bone healing even if the bone defects were infected. The results suggest that TQ increased angiogenesis and showed promise for accelerating bone defect healing. Further research is warranted to support these findings and reach more definitive conclusions., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2022. Korean Academy of Periodontology.)

Background: The aim of this study is to determine whether glucosamine-sulfate has any effects on bone-healing., Methods: A unilateral fracture was created in the tibia of sixty-one female rats. Rats were given no drug or 230 mg/kg glucosamine-sulfate daily. Fractures were analyzed during the first, second and fourth weeks after creation of fracture. Quantitative measurement for new bone formation and osteoblast lining were determined histologically. Semiquantitative score for fracture healing was used for histomorphometric analyses. Bridging bone formation was assessed radiographically., Results: New bone formation and osteoblast lining were significantly higher in glucosamine-treated group at week 1. Surrounding connective tissue was more cellular and vascular, and the newly formed bone trabecules were present in greater amounts in glucosamine-treated group, compared to control group at week 1 and 4. But radiologically, the control group had better scores than that of the glucosamine-treated group at week 4., Conclusion: These data demonstrate that daily glucosamine-sulfate administration accelerates early phase of fracture repair in the rat tibia, with increased new bone formation and osteoblast lining histologically, but radiologic bone union is not favored on radiographs.

Biodegradable macroporous cryogels with highly open and interconnected pore structures were produced from dextran modified with oligo L-lactide bearing hydroxyethylmethacrylate (HEMA) end groups in moderately frozen solutions. Tissue responses to these novel scaffolds were evaluated in rats after dorsal subcutaneous implantation, iliac submuscular implantation, auricular implantation, or in calvarial defect model. In no case, either necrosis or foreign body reaction was observed during histological studies. The cryogel scaffolds integrated with the surrounding tissue and the formation of a new tissue were accompanied with significant ingrowth of connective tissue cells and new blood vessels into the cryogel. The tissue responses were significantly lower in auricular and calvarial implantations when compared with the subcutanous and the submuscular implantations. The degradation of the scaffold was slower in bone comparing to soft tissues. The biodegradable cryogels are highly biocompatible and combine extraordinary properties including having soft and elastic nature, open porous structure, and very rapid and controllable swelling. Therefore, the cryogels could be promising candidates for further clinical applications in tissue regeneration.

Three-dimensional cell ingrowth within biodegradable cryogel scaffolds made of cross-linked 2-hydroxyethyl methacrylate (HEMA)-lactate-dextran with interconnected macropores was studied in bioreactors at different regimes (static, perfusion, and compression-perfusion). An osteoblast-like cell line (MG63) was used in these studies. The samples taken after selected times from the bioreactors were examined by microscopy techniques (light, SEM, TEM, and laser scanning confocal). The cell culture conditions were found to have a significant impact not only on the cell morphology, such as the extent of cell attachment and ingrowth, but also on cellular activities. Dynamic conditions (perfusion and/or compression) greatly improved cell ingrowth and extracellular matrix (ECM) synthesis. Alkaline phosphatase activity results confirmed the positive effect of dynamic conditions on bone cells.