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Cureus Jan 2024Periodontitis is a dramatic inflammatory disease, representing vigorous interactions between specific causative pathogens and host immune responses resulting in the...
INTRODUCTION
Periodontitis is a dramatic inflammatory disease, representing vigorous interactions between specific causative pathogens and host immune responses resulting in the activation of the destructive inflammatory cascade with the subsequent irreversible destruction of the teeth-supporting apparatus.
AIM
This study aims to evaluate the effect of using erythropoietin (EPO) injectable hydrogel, as an additional therapeutic option to scaling and root planing (SRP) in the treatment of stage II periodontitis patients, and to assess its effect on the level of osteocalcin and interleukin (IL)-1β in the gingival crevicular fluid (GCF).
METHODOLOGY
A total number of 40 patients clinically diagnosed with stage II periodontitis were included. The participants were allocated into two equal groups: study and control groups. Patients in the control group received SRP, while those in the study group received SRP followed by injectable hydrogel containing EPO. Clinical parameters such as plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and two months post treatment. GCF samples were collected at baseline and two months post treatment from both groups to analyze GCF IL-1β and osteocalcin levels using enzyme-linked immunosorbent assay (ELISA).
RESULTS
Significant reductions in all tested clinical parameters were revealed in both groups in comparison to baseline values. A marked significant reduction in GCF IL-1β level was detected in the study group. However, two months post treatment, the osteocalcin level was decreased significantly in both groups.
CONCLUSION
This preliminary study shows great promise for the local application of EPO hydrogel as an adjunct to SRP for the management of stage II periodontitis.
PubMed: 38406126
DOI: 10.7759/cureus.52825 -
Indian Journal of Pathology &... Feb 2024Indistinct and analogous histopathological features of various fibro-osseous lesions make establishing a definitive diagnosis a challenge. There is a need for additional...
BACKGROUND
Indistinct and analogous histopathological features of various fibro-osseous lesions make establishing a definitive diagnosis a challenge. There is a need for additional molecular and histochemical tools to support and differentiate these lesions in order to establish a concrete diagnosis.
MATERIALS AND METHODS
A retrospective analysis of biopsied lesions in formalin-fixed paraffin-embedded sections (10 cases each of fibrous dysplasia, ossifying fibroma, and cement-osseous dysplasia) retrieved from the archives was studied for immunoexpression of osteocalcin (quantitative analysis in osteocytes), collagen characterization using Azan, Picrosirus, and Toluidine blue stain for evaluating intensity and localization of collagen fibers, and morphometric analysis of vasculature (for evaluating mean vessel density as square microns).
RESULTS
Positive immunostaining of osteocalcin suggested mutations of the GNAS-1 gene found in fibrous dysplasia indirectly, as it is a negative regulator of bone formation. Osteocalcin immunopositivity was quantitatively measured in the fibro-osseous lesions, with fibrous dysplasia measuring 14.47 ± 3.628 as compared to ossifying fibroma measuring 5.23 ± 1.33, followed by cemento-osseous dysplasia measuring 2.30 ± 1.409. Toluidine blue suggests the presence of oxytalan fibers (resistant to acid hydrolysis) in ossifying fibroma and cemento-osseous dysplasia, pointing toward the pathogenesis of the lesion. Azan stain and Picrosirus (under a polarizing microscope) helped in distinguishing hard tissue characteristics (70% of cases of fibrous dysplasia showed only a magenta component followed by intermixed magenta with a blue component in 20% of cases and only 10% of cases showed magenta with blue borders whereas for ossifying fibroma, 40% of cases depicted magenta with blue borders along with the other 40% with intermixed magenta with blue component). The mean vessel density was also highest in fibrous dysplasia measuring 7.90 ± 1.079 (in Sq. micron area), followed by ossifying fibroma and cemento-osseous dysplasia.
CONCLUSION
The diagnosis of fibro-osseous lesions by hematoxylin and eosin alone is confusing and thus should be supported by relatively simple histomorphometric analysis for better treatment outcomes. At the diagnostic stage of fibro-osseous lesions, evaluation of intralesional vessel size, reliable molecular marker, and histochemical nature can aid in differentiating fibrous dysplasia from central ossifying fibroma and cemento-osseous dysplasia alongside, other clinical, radiographic and pathological criteria. These parameters help in the diagnostic decision-making of fibro-osseous lesions.
PubMed: 38391368
DOI: 10.4103/ijpm.ijpm_918_22 -
Advances in Pharmacological and... 2024Ticagrelor (TICA) and clopidogrel (CLP) are extensively used antiplatelet drugs that act by antagonizing the P2Y12 receptors that are found on platelets in addition to...
Ticagrelor (TICA) and clopidogrel (CLP) are extensively used antiplatelet drugs that act by antagonizing the P2Y12 receptors that are found on platelets in addition to bone cells. . The purpose of this study was to investigate the effect of clopidogrel and ticagrelor on stem cells osteogenic differentiation . . Human adipose-derived mesenchymal stem cells (hAd-MSCs) were divided into (1) control group, (2) osteogenic group (osteo group), (3) clopidogrel group (CLP group), and (4) ticagrelor group (TICA group). The osteogenic differentiation potential was determined by mineralization nodule formation using Alizarin Red S staining, measuring ALP enzyme activity by alkaline phosphatase assay. Quantitative determination for osteogenic markers included osteocalcin (OC); runt-related transcription factor 2 (RUNX2) performed using western blot; osteoprotegerin (OPG) using enzyme-linked immunosorbent assay (ELISA) and inflammatory markers; and tumor necrosis factor (TNF-) and interleukin-6 (IL-6) measured using real-time polymerase chain reaction quantitative (RT-PCR) and ELISA. . In comparison to all study groups, the TICA group showed significant increase in the mineralized extracellular matrix, ALP enzyme activity, and bone markers expression as RUNX2 ( < 0.0001), OC, and OPG ( < 0.05). The expression of IL-6 and TNF- was determined by RT-qPCR and ELISA techniques. TICA and CLP significantly decreased both markers compared to the control group. The TICA group showed statistically significant lower levels of both markers ( < 0.0001) than the CLP and control groups via the ELISA technique. . TICA may possess a positive effect on hAd-MSCs osteogenic differentiation compared to CLP.
PubMed: 38390313
DOI: 10.1155/2024/2990670 -
Biochemistry and Biophysics Reports Jul 2024Stem cell therapy for regenerative medicine has been sincerely investigated, but not still popular although some clinical trials show hopeful results. This therapy is...
INTRODUCTION & OBJECTIVES
Stem cell therapy for regenerative medicine has been sincerely investigated, but not still popular although some clinical trials show hopeful results. This therapy is suggested to be a representative candidate such as bone defect due to the accident, iatrogenic resection oncological tumor, congenital disease, and severe periodontitis in oral region. Recently, the Bio-3D printer "Regenova®" has been introduced as an innovative three-dimensional culture system, equipped scaffold-free bio-assembling techniques without any biomaterials. Therefore, we expected a mount of bone defect could be repaired by the structure established from this Bio-3D printer using osteogenic potential stem cells.
MATERIAL & METHODS
The gingival tissue (1x1 mm) was removed from the distal part of the lower wisdom tooth of the patients who agreed our study. Human Gingival Mesenchymal Stem Cells (hGMSCs) were isolated from this tissue and cultured, since we confirmed the characteristics such as facile isolation and accelerated proliferation, further, strong potential of osteogenic-differentiation. Spheroids were formed using hGMSC in 96-well plates designed for low cell adhesion. The size of the spheroids was measured, and fluorescent immunostaining was employed to verify the expression of stem cell and apoptosis marker, and extracellular matrix. Following four weeks of bone differentiation, μCT imaging was performed. Calcification was confirmed by alizarin red and von Kossa staining. Fluorescent immunostaining was utilized to assess the expression of markers indicative of advanced bone differentiation.
RESULTS
We have established and confirmed the spheroids (∼600 μm in diameter) constructed from human GMSCs (hGMSCs) still maintain stem cell potentials and osteogenic differentiation abilities from the results that CD73 and not CD34 were expressed as stem cell positive and negative marker, respectively. These spheroids were pilled up like cylindal shape to the "Kenzan" platform of Bio-3D printer and cultured for 7days. The cylindal structure originated from compound spheroids were tried to differentiate into bone four weeks with osteogenic induction medium. The calcification of bio-3D printed bone-like structures was confirmed by alizarin red and Von Kossa staining. In addition, μCT analysis revealed that the HU (Hounsfield Unit) of the calcified structures was almost identical to that of trabecular bone. Immunofluorescent staining detected osteocalcin expression, a late-stage bone differentiation marker.
CONCLUSION
For the first time, we have achieved the construction of a scaffold-free, bone-like luminal structure through the assembly of spheroids comprised of this hGMSCs. This success is sure to be close to the induction of clinical application against regenerative medicine especially for bone defect disease.
PubMed: 38379857
DOI: 10.1016/j.bbrep.2024.101656 -
Frontiers in Cardiovascular Medicine 2023Coronary heart disease (CHD) is an abbreviation of coronary atherosclerotic heart disease, which remains challenging for diagnosis and treatment. Current study aims to...
Coronary heart disease (CHD) is an abbreviation of coronary atherosclerotic heart disease, which remains challenging for diagnosis and treatment. Current study aims to explore the correlation between geriatric nutritional risk index (GNRI) and osteoporosis, sarcopenia, cognitive dysfunction in elderly patients with CHD, and to analyze the clinical diagnostic value of GNRI in the above complications. A total of 92 elderly patients with CHD treated in Suzhou Ninth People's Hospital from January 2020 to October 2023 were retrospectively collected as the experimental group, and 68 non-CHD subjects matched for sex and age in the same period of physical examination were randomly selected as the control group. Osteoporosis, sarcopenia and cognitive dysfunction were analyzed in all patients, and the correlation between GNRI and these indices in different populations was analyzed by Spearman's rank correlation. The diagnostic efficacy of GNRI in osteoporosis, sarcopenia, and cognitive impairment was analyzed by ROC curves. There was no significant difference in age, sex distribution, body mass index (BMI) and serum biological indexes between the elderly patients with CHD and the control group (all > 0.05). Correlation analysis showed that GNRI level was positively correlated with bone mineral content (BMC), bone mineral density (BMD) T value and osteocalcin (OCN) (All > 0, < 0.05). In addition, GNRI levels were positively correlated with skeletal muscle mass (ASMI), grip strength and calf circumference (CC) (All > 0, < 0.05). However, there was no significant correlation between GNRI levels and cognitive dysfunction-related indicators (> 0.05). In the elderly and elderly with CHD, the diagnostic AUC of GNRI was 0.875 and 0.862 in osteoporosis, and 0.912 and 0.932 in sarcopenia, respectively. The level of GNRI is significantly correlated with osteoporosis and sarcopenia. GNRI level, as an auxiliary diagnostic tool in elderly patients with CHD, exerts important clinical significance for early detection of the risk of complications, such as osteoporosis and sarcopenia.
PubMed: 38371735
DOI: 10.3389/fcvm.2023.1335572 -
Journal of Materials Science. Materials... Feb 2024Intracanal medications are used in endodontic treatment due to their antibacterial activity and ability to induce the periapical repair. Among the intracanal...
Intracanal medications are used in endodontic treatment due to their antibacterial activity and ability to induce the periapical repair. Among the intracanal medications, the Calen (CAL; SS. White, Brazil) is a calcium hydroxide-based medication that provides an alkaline pH and releases calcium, exerting an antimicrobial activity. Bio-C Temp (BIO; Angelus, Brazil), a ready-to-use bioceramic intracanal medication, was designed to stimulate the mineralized tissues formation. Here, we investigated the bioactive potential of BIO in comparison to the CAL in the rat subcutaneous. Polyethylene tubes filled with medications, and empty tubes (control group, CG) were implanted in the subcutaneous tissue of rats. After 7, 15, 30 and 60 days, the blood was collected for calcium (Ca) and alkaline phosphatase (ALP) measurement, and the capsules around the implants were processed for morphological analyses. The data were submitted to two-way ANOVA and Tukey test (p < 0.05). At 7, 15 and 30 days, the ALP level was grater in BIO and CAL than in CG (p < 0.0001). At 7 and 15 days, greater Ca level was seen in the serum of CAL samples. From 7 to 60 days, an increase in the number of fibroblasts, osteocalcin- and osteopontin-immunolabelled cells was observed in BIO and CAL groups (p < 0.0001). In all periods, BIO and CAL specimens showed von Kossa-positive structures. Moreover, ultrastructural analysis revealed globules of mineralization in the capsules around the BIO and CAL specimens. Thus Bio-C Temp caused an increase in the ALP, osteocalcin and osteopontin, which may have allowed the formation of calcite, suggesting bioactive potential.
Topics: Animals; Rats; Osteopontin; Osteocalcin; Calcium; Subcutaneous Tissue; Anti-Bacterial Agents; Calcinosis
PubMed: 38353838
DOI: 10.1007/s10856-024-06781-3 -
EClinicalMedicine Mar 2024Childhood obesity is a pressing health crisis of epidemic proportions. Bariatric surgery (BS) is an effective weight loss solution however its role in the paediatric...
BACKGROUND
Childhood obesity is a pressing health crisis of epidemic proportions. Bariatric surgery (BS) is an effective weight loss solution however its role in the paediatric population is contentious owing to the paucity of weight specific and generalised health outcomes. This systematic review and meta-analysis aimed to assess the impact of paediatric BS on bone health.
METHODS
This prospectively registered systematic review (PROSPERO ID: CRD42023432035) was performed in accordance with PRISMA guidelines. We searched MEDLINE (1946-1928 September 2023), EMBASE (1947-1928 September 2023) via the Ovid platform, and the Cochrane Review Library to identify scientific publications reporting bone outcome measures in patients under the age of 18 years who underwent BS. Meta-analysis was undertaken on post-operative weight and bone parameters in paediatric patients following BS. Outcomes were reported as weighted or standardized mean difference with 95 percent confidence intervals. Subgroup analysis by intervention, quality scoring and risk of bias were assessed.
FINDINGS
Twelve studies with 681 patients across 5 countries (mean age 17 ± 0.57 years) were included. The quality of included studies was rated as high and there was substantial between-study heterogeneity for most factors included in the meta-analysis ( from 0% to 99.1%). Patients underwent Roux-en-Y gastric bypass (RYGB, n = 216), sleeve gastrectomy (SG, n = 257), gastric band (n = 184) or intragastric balloon placement (n = 24). BS was associated with significant weight reduction, body mass index (BMI) -12.7 kg/m (95% CI -14.5 to -10.9, p < 0.001), with RYGB being most effective, BMI -16.58 kg/m (95% CI -19.6 to -13.6, p < 0.001). Patients who underwent SG or RYGB had significantly lower lumbar bone mineral density, -0.96 g/cm (95% CI -0.1 to -0.03, p < 0.001), Z score, -1.132 (95% CI -1.8 to -0.45, p < 0.001) and subtotal body bone mineral density, -0.7 g/cm (95% CI -1.2 to -0.2, p < 0.001) following surgery. This was accompanied with higher markers of bone resorption, C-terminal telopeptide of type 1 collagen 0.22 ng/ml (95% CI 0.12-0.32, p < 0.001) and osteocalcin, 10.83 ng/ml (95% CI 6.01-15.67, p < 0.001). There was a significant reduction in calcium levels following BS, -3.78 mg/dl (95% CI -6.1 to -1.5, p < 0.001) but no difference in 25-hydroxyvitamin D, phosphate, bone alkaline phosphatase, procollagen type 1 N propeptide or parathyroid hormone.
INTERPRETATION
BS effectively reduces weight in paediatric patients, but RYGB and SG may have adverse effects on bone health in the medium term. It is crucial to monitor and support bone health through appropriate nutritional supplementation and judicious follow-up. Long-term data is needed to fully understand the clinical implications of these findings on bone outcomes.
FUNDING
Medical Research Council (MRC), United Kingdom.
PubMed: 38333369
DOI: 10.1016/j.eclinm.2024.102462 -
Biomedicine & Pharmacotherapy =... Mar 2024Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid)...
BACKGROUND
Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD).
METHODS
PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated.
RESULTS
The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds.
CONCLUSION
Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.
Topics: Animals; Rabbits; Humans; Durapatite; Tissue Scaffolds; Polylactic Acid-Polyglycolic Acid Copolymer; Linezolid; Phosphatidylinositol 3-Kinases; Printing, Three-Dimensional
PubMed: 38320333
DOI: 10.1016/j.biopha.2024.116228 -
Journal of Dental Sciences Jan 2024The modification in 3D hydrogels, tissue engineering, and biomaterials science has enabled us to fabricate novel substitutes for bone regeneration. This study aimed to...
BACKGROUND/PURPOSE
The modification in 3D hydrogels, tissue engineering, and biomaterials science has enabled us to fabricate novel substitutes for bone regeneration. This study aimed to combine different biomaterials by 3D technique to fabricate a promising all-rounded hydrogel for bone regeneration.
MATERIALS AND METHODS
In this study, glycidyl methacrylate (GMA)-modified poly γ-glutamic acid (γ-PGA-GMA) hydrogels with calcium silicate (CS) hydrogel of different concentrations were fabricated by a 3D printing technique, and their biocompatibility and capability in bone regeneration were also evaluated.
RESULTS
The results showed that CS γ-PGA-GMA could be successfully fabricated, and the presence of CS enhanced the rheological and mechanical properties of γ-PGA-GMA hydrogels, thus making them more adept at 3D printing and implantations. SEM images of the surface structure showed that higher CS concentrations (5% and 10%) contributed to denser surface architectures, thus achieving improved cellular adhesion and stem cell proliferation. Furthermore, higher concentrations of CS resulted in elevated expressions of osteogenic-related markers such as alkaline phosphatase (ALP) and osteocalcin (OC), as well as enhanced calcium deposition represented by the increased Alizarin Red S staining. In vivo studies referring to critical defects of rabbit femur further showed that the existence of hydrogels alone was able to induce partial bone regeneration, demonstrated by the results from quantitative and qualitative analysis of micro-CT scans. However, CS alterations caused significant increases in bone regeneration, as indicated by micro-CT and histological staining.
CONCLUSION
These results robustly suggest combining different biomaterials is crucial to producing a well-rounded hydrogel for tissue regeneration. We hope this study could be applied as a platform for others to brainstorm potential out-of-the-box solutions, contributing to developing high-potential biomaterials for bone regeneration.
PubMed: 38303841
DOI: 10.1016/j.jds.2023.09.008 -
Journal of Animal Science Jan 2024Diets that provide a negative dietary anion cation difference (DCAD) and supplement with a vitamin D metabolite 25-OH-D3 (calcidiol) may increase calcium availability at...
Diets that provide a negative dietary anion cation difference (DCAD) and supplement with a vitamin D metabolite 25-OH-D3 (calcidiol) may increase calcium availability at parturition, and enhance piglet survival and performance. This factorial study assessed the effects of DCAD, calcidiol (50 µg/kg), and parity (parity 1 or >1) and their interactions. Large White and Landrace sows (n = 328), parity 1 to 8 were randomly allocated in blocks to treatment diets from day 103 of gestation until day 3 postfarrow: 1) negative DCAD without calcidiol (negative DCAD + no CA), n = 84, 2) negative DCAD with calcidiol (negative DCAD + CA) n = 84, 3) positive DCAD without calcidiol (negative DCAD + no CA), n = 81, and 4) positive DCAD with calcidiol (positive DCAD + CA), n = 79. Negative DCAD diets were acidified with an anionic feed (2 kg/t) and magnesium sulfate (2 kg/t). All treatment diets contained cholecalciferol at 1,000 IU/kg. Dry sow diets contained 14.8% crude protein (CP), 5.4% crude fiber (CF), 0.8% Ca, and 83 mEq/kg DCAD. Treatment diets 1 and 2 contained 17.5% CP, 7.3% CF, 0.8% Ca, and -2 mEq/kg DCAD. Treatment diets 3 and 4 contained 17.4% CP, 7.4% CF, 0.8% Ca, and 68 mEq/kg DCAD. Before farrowing, all negative DCAD sows had lower urine pH than all sows fed a positive DCAD (5.66 ± 0.05 and 6.29 ± 0.05, respectively; P < 0.01); urinary pH was acidified for both DCAD treatments indicating metabolic acidification. The percentage of sows with stillborn piglets was not affected by DCAD, calcidiol, or parity alone but sows fed the negative DCAD + CA diet had a 28% reduction in odds of stillbirth compared to the negative DCAD + no CA diet and even lesser odds to the positive DCAD + CA diet. At day 1 after farrowing, blood gas, and mineral and metabolite concentrations were consistent with feeding a negative DCAD diet and that negative DCAD diets influence energy metabolism, as indicated by increased glucose, cholesterol, and osteocalcin concentrations and reduced nonesterified free fatty acids and 3-hydroxybutyrate concentrations. In the subsequent litter, total piglets born and born alive (14.7 ± 0.3 and 13.8 ± 0.3 piglets, respectively; P = 0.029) was greater for positive DCAD diets compared to negative DCAD diets; and there was an interaction between DCAD, calcidiol, and parity (P = 0.002). Feeding a negative DCAD diet influenced stillbirth, subsequent litter size, and metabolic responses at farrowing. More studies are needed to define optimal diets prefarrowing for sows.
Topics: Pregnancy; Female; Animals; Swine; Calcifediol; Stillbirth; Lactation; Diet; Dietary Supplements; Anions; Cations; Animal Feed; Swine Diseases
PubMed: 38285624
DOI: 10.1093/jas/skae027