scholarly journals Initial Harm Reduction by N-Acetylcysteine Alleviates Cartilage Degeneration after Blunt Single-Impact Cartilage Trauma in Vivo

2019 ◽  
Vol 20 (12) ◽  
pp. 2916 ◽  
Author(s):  
Jana Riegger ◽  
Frank Leucht ◽  
Hans-Georg Palm ◽  
Anita Ignatius ◽  
Rolf E. Brenner
Keyword(s):  
Harm Reduction ◽  
Ex Vivo ◽  
Cluster Formation ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Group B ◽  
Trauma Model

Joint injuries are highly associated with the development of post-traumatic osteoarthritis. Previous studies revealed cell- and matrix-protective effects of N-acetylcysteine (NAC) after ex vivo cartilage trauma, while chondroanabolic stimulation with bone morphogenetic protein 7 (BMP7) enhanced type II collagen (COL2) expression. Here, as a next step, we investigated the combined and individual efficacy of intra-articular antioxidative and chondroanabolic treatment in a rabbit in vivo cartilage trauma model. Animals were randomly divided into group A (right joint: trauma (T); left joint: T+BMP7) and group B (right joint: T+NAC; left joint: T+BMP7+NAC). Condyles were impacted with the use of a spring-loaded impact device to ensure defined, single trauma administration. After 12 weeks, histopathological analysis was performed and the presence of matrix metalloproteinase 13 (MMP-13) and COL2 was assessed. Trauma-induced hypocellularity, MMP-13 expression, and cell cluster formation were reduced in NAC-treated animals. In contrast, BMP7 further increased cluster formation. Moreover, synovial concentrations of COL2 carboxy propeptide (CPII) and proteoglycan staining intensities were enhanced in NAC- and NAC+BMP7-treated joints. For the first time, the efficacy of NAC regarding early harm reduction after blunt cartilage trauma was demonstrated in vivo. However, parallel administration of BMP7 was not significantly superior compared to NAC alone.

scholarly journals Chondro-Protective Effects of Shikimic Acid on Osteoarthritis via Restoring Impaired Autophagy and Suppressing the MAPK/NF-κB Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongbo You ◽  
Rui Zhang ◽  
Lingying Wang ◽  
Qiyong Pan ◽  
Zekai Mao ◽  
...  
Keyword(s):  
Shikimic Acid ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Mitogen Activated Protein Kinase ◽  
Blue Staining ◽  
Autophagic Flux ◽  
Protective Effects ◽  
Limited Mobility ◽  
Safranin O

Osteoarthritis (OA) is a major cause of cartilage pain and limited mobility in middle-aged and elderly individuals. The degeneration of cartilage induced by inflammation and cartilage anabolic and catabolic disorder plays a key role in OA. Shikimic acid (SA), a natural ingredient extracted from Illicium verum, has been shown to exert notable anti-inflammatory effects in previous studies, suggesting its potential effects in the treatment of OA. In this study, we revealed that the pretreatment of SW1353 human chondrocytes with SA before interleukin 1β (IL-1β) stimulation effectively decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, matrix metalloproteinases (MMPs; MMP3 and MMP13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, type X collagen, and p62; increased the expression of type II collagen, ATG7, Beclin-1, and LC3; and increased the autophagic flux. Mechanistically, we found that SA suppressed the IL-1β-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. Furthermore, the results of safranin O staining and toluidine blue staining of primary rat cartilage chondrocytes and a trauma-induced rat model of OA showed that SA alleviated progression of OA in vivo. Collectively, our research enhances understanding of the mechanism of protective effect of SA against the progression of OA, which involves amelioration of cartilage degeneration, thereby providing new evidence for the use of SA as a therapy to prevent the development of OA.

Histopathological analysis of incompetent great saphenous veins after mechanochemical ablation treatment – An ex-vivo experiment

Vascular ◽  
2021 ◽  
pp. 170853812110076
Author(s):  
Bo Yang ◽  
Qiang-Qiang Nie ◽  
Xue-Qiang Fan ◽  
Jian-Bin Zhang ◽  
Peng Liu
Keyword(s):  
Ex Vivo ◽  
Endothelial Damage ◽  
Statistical Result ◽  
Histopathological Analysis ◽  
Saphenous Veins ◽  
Mechanochemical Ablation ◽  
Group A ◽  
Endothelium Damage ◽  
Group B ◽  
Group D

Background The endovascular technique of mechanochemical ablation (MOCA) has become popular in treating patients with saphenous reflux. We reported the histopathological findings in human ex-vivo incompetent great saphenous veins following treatment with saline, polidocanol, mechanical ablation and MOCA using ClariVein device. Methods Twenty-four vein GSV specimens were obtained via traditional surgery and treated with four methods: Group A: 0.9% normal saline (NS); Group B: 3% polidocanol; Group C: mechanical ablation + 0.9% NS; Group D: mechanical ablation + 3% polidocanol (MOCA). Hematoxylin and eosin (HE), Masson’s trichrome and immunohistochemical staining were performed on each specimen and integrated optical densities were measured with vWF and a-SMA stains and statistically evaluated. vWF staining was used to assess endothelial damage and a a-SMA staining was used to assess media injury. Results HE and Masson’s trichrome staining of Groups C and D revealed severe damage to the endothelium and media compared to Groups A and B. The statistical result of vWF staining showed the damage of endothelium was significantly increased by Group D compared to Groups A, B and C. The statistical result of a-SMA staining showed the damage of media was significantly increased by Groups C and D compared to Groups A and B. Conclusions The mechanism of MOCA was caused by both endothelium damage and media tearing. The damage of endothelium was significantly increased by MOCA when compared with mechanical ablation alone.

scholarly journals EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erik H. J. G. Aarntzen ◽  
Edel Noriega-Álvarez ◽  
Vera Artiko ◽  
André H. Dias ◽  
Olivier Gheysens ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Radionuclide Imaging ◽  
Musculoskeletal Diseases ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Large Body ◽  
Therapeutic Interventions ◽  
Histopathological Analysis ◽  
Complementary Value

AbstractInflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.

Influence of estrogen on individual exercise motivation and bone protection in ovariectomized rats

2018 ◽  
Vol 52 (5) ◽  
pp. 479-489 ◽  
Author(s):  
Sebastian T Müller ◽  
Annekathrin M Keiler ◽  
Kristin Kräker ◽  
Oliver Zierau ◽  
Ricardo Bernhardt
Keyword(s):  
Bone Loss ◽  
Ex Vivo ◽  
Voluntary Exercise ◽  
Ovariectomized Rats ◽  
Protective Effects ◽  
Exercise Motivation ◽  
Running Wheel ◽  
Future Studies ◽  
Bone Protection

Bone protection and metabolism are directly linked to estrogen levels, but exercise is also considered to have bone protective effects. Reduced estrogen levels lead to a variety of disorders, for example, bone loss and reduced movement drive. The objective of this study was to investigate the effects of estrogen on individual voluntary exercise motivation and bone protection. We investigated sham operated, ovariectomized, and ovariectomized with estrogen supplemented Wistar rats (20 weeks old) either with or without access to exercise wheels. We selected an experimental approach where we could monitor the individual exercise of group-housed rats with ad libitum access to a running wheel with the help of a subcutaneous chip. In vivo and ex vivo microcomputed tomography analyses of the tibia were performed at two-week intervals from week 0 to week 6. Furthermore, tibial trabecular structure was evaluated based on histomorphometric analyses. We observed a significant bone protective effect of E2. For exercise performance, a substantially high intra-group variability was observed, especially in the E2 group. We presume that dominant behavior occurs within the group-housed rats resulting in a hierarchical access to the running wheel and a high variability of distance run. Exercise did not prevent ovariectomy-induced bone loss. However, lack of estrogen within the ovariectomized rats led to a drastically reduced activity prevented by estrogen supplementation. Our findings are important for future studies working with group-housed rats and exercise. The reason for the high intra-group variability in exercise needs to be investigated in future studies.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

scholarly journals Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression

2013 ◽  
Vol 304 (8) ◽  
pp. H1134-H1146 ◽  
Author(s):  
Patrick Y. Sips ◽  
Tomoya Irie ◽  
Lin Zou ◽  
Shohei Shinozaki ◽  
Michihiro Sakai ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ex Vivo ◽  
Myocardial Dysfunction ◽  
Endotoxic Shock ◽  
Protein S ◽  
Septic Cardiomyopathy ◽  
Protective Effects ◽  
Myocardial Depression ◽  
Lps Challenge

Myocardial depression is an important contributor to morbidity and mortality in septic patients. Nitric oxide (NO) plays an important role in the development of septic cardiomyopathy, but also has protective effects. Recent evidence has indicated that NO exerts many of its downstream effects on the cardiovascular system via protein S-nitrosylation, which is negatively regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme promoting denitrosylation. We tested the hypothesis that reducing cardiomyocyte S-nitrosylation by increasing GSNOR activity can improve myocardial dysfunction during sepsis. Therefore, we generated mice with a cardiomyocyte-specific overexpression of GSNOR (GSNOR-CMTg mice) and subjected them to endotoxic shock. Measurements of cardiac function in vivo and ex vivo showed that GSNOR-CMTg mice had a significantly improved cardiac function after lipopolysaccharide challenge (LPS, 50 mg/kg) compared with wild-type (WT) mice. Cardiomyocytes isolated from septic GSNOR-CMTg mice showed a corresponding improvement in contractility compared with WT cells. However, systolic Ca2+ release was similarly depressed in both genotypes after LPS, indicating that GSNOR-CMTg cardiomyocytes have increased Ca2+ sensitivity during sepsis. Parameters of inflammation were equally increased in LPS-treated hearts of both genotypes, and no compensatory changes in NO synthase expression levels were found in GSNOR-overexpressing hearts before or after LPS challenge. GSNOR overexpression however significantly reduced total cardiac protein S-nitrosylation during sepsis. Taken together, our results indicate that increasing the denitrosylation capacity of cardiomyocytes protects against sepsis-induced myocardial depression. Our findings suggest that specifically reducing protein S-nitrosylation during sepsis improves cardiac function by increasing cardiac myofilament sensitivity to Ca2+.

Exopolysaccharide from Bifidobacterium longum subsp. longum 35624™ modulates murine allergic airway responses

2018 ◽  
Vol 9 (5) ◽  
pp. 761-773 ◽  
Author(s):  
E. Schiavi ◽  
S. Plattner ◽  
N. Rodriguez-Perez ◽  
W. Barcik ◽  
R. Frei ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Bifidobacterium Longum ◽  
Immunological Tolerance ◽  
Respiratory Allergy ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Eosinophil Recruitment

Interactions between the host and the microbiota are thought to significantly influence immunological tolerance mechanisms at mucosal sites. We recently described that the loss of an exopolysaccharide (EPS) from Bifidobacterium longum 35624™ eliminated its protective effects in colitis and respiratory allergy murine models. Our goal was to investigate the immune response to purified EPS from B. longum 35624, determine if it has protective effects within the lung and identify the protective mechanisms. Isolated EPS from B. longum 35624 cultures was used for in vitro, ex vivo and in vivo studies. Human monocyte-derived dendritic cells (MDDCs) were used to investigate in vitro immunological responses to EPS. Cytokine secretion, expression of surface markers and signalling pathways were examined. The ovalbumin (OVA) respiratory allergy murine model was used to evaluate the in vivo immunomodulatory potential of EPS. In addition, interleukin (IL)-10 knockout (KO) mice and anti-Toll-like receptor (TLR)-2 blocking antibody were used to examine the underlying protective mechanisms of intranasal EPS administration. Stimulation of human MDDCs with EPS resulted in IL-10 secretion, but not proinflammatory cytokines. IL-10 secretion was TLR-2-dependent. Eosinophil recruitment to the lungs was significantly decreased by EPS intranasal exposure, which was associated with decreased expression of the Th2-associated markers C-C motif chemokine 11 (CCL11), C-C chemokine receptor type 3 (CCR3), IL-4 and IL-13. TLR-2-mediated IL-10 secretion was shown to be required for the reduction in eosinophils and Th2 cytokines. EPS-treatment reduced eosinophil recruitment within the lung in a respiratory inflammation mouse model, which is both TLR-2 and IL-10 mediated. EPS can be considered as a novel molecule potentially reducing the severity of chronic eosinophil-related airway disorders.

scholarly journals Rat Chondrocyte Inflammation and Osteoarthritis Are Ameliorated by Madecassoside

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Safwat Adel Abdo Moqbel ◽  
Yuzhe He ◽  
Langhai Xu ◽  
Chiyuan Ma ◽  
Jisheng Ran ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Centella Asiatica ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Treated Group ◽  
Joint Disease ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Osteoarthritic Chondrocytes

As a joint disease, osteoarthritis (OA) is caused by the breakdown of subchondral bone and cartilage damage. Inflammatory factors, such as interleukin- (IL-) 1β, mediate the progression of OA. Madecassoside (MA), a triterpenoid component derived from the gotu kola herb (Centella asiatica), exhibits various pharmacological effects, including antioxidative and anti-inflammatory properties. In the present study, the protective effects and possible mechanism of MA on the treatment of OA were investigated. MA was demonstrated to significantly suppress the IL-1β-induced overexpression of matrix metalloproteinase- (MMP-) 3, MMP-13, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and to decrease the IL-1β-induced degradation of type II collagen and sox9. Additionally, MA was able to reduce the IL-1β-induced phosphorylation of p65 in osteoarthritic chondrocytes. Furthermore, in a rat OA model, MA prevented cartilage degeneration and reduced the OARSI score in the MA-treated group compared with the OA group. The present study showed that MA suppresses the nuclear factor-κB signaling pathway, reducing IL-1β-induced chondrocyte inflammation, which indicates the therapeutic potential of MA in patients with OA.

Abstract 2559: Reflectance, Fluorescence, and Raman Spectroscopy Identify Features of Vulnerable Atherosclerotic Plaque In Vivo Including a Thin Fibrous Cap, Necrotic Core or Superficial Foam Cells, and Thrombus

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Obrad R Šćepanović ◽  
Maryann Fitzmaurice ◽  
Arnold Miller ◽  
Chae-Ryon Kong ◽  
Ramachandra R Dasari ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Early Detection ◽  
Ex Vivo ◽  
Foam Cells ◽  
Necrotic Core ◽  
Histopathological Analysis ◽  
Artery Wall ◽  
Fibrous Cap ◽  
Vulnerable Plaques

Early detection and treatment of vulnerable atherosclerotic plaques, the lesions most prone to rupture, is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy - termed multimodal spectroscopy (MMS) - provides complementary and depth-sensitive information about tissue composition. We assessed the hypothesis that MMS can detect morphological features of vulnerable plaque: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), intralesional hemorrhage (IH), and thrombus. Methods. In vivo and ex vivo MMS spectra were collected from 12 patients undergoing peripheral vascular surgeries. The data collection was facilitated by means of a novel MMS probe catheter and a portable clinical instrument developed in our laboratory. During carotid endarterectomies, MMS spectra were collected in vivo from the intimal surface of the plaque with the probe held normal to the artery wall. During femoral bypasses, MMS spectra were collected in vivo either through the proximal anastomosis site from the posterior artery wall or adjacent to the incision. A tissue specimen was excised for additional MMS spectral collection ex vivo. Histopathological analysis was performed by a blinded cardiovascular pathologist to assess the vulnerability of each spectrally evaluated tissue site using a quantitative index based on the dimension or severity of the following: TFC, NC, SFC, IH, and thrombus. Across the total set of 76 evaluated tissue locations, MMS is shown to have the ability to detect vulnerability features including a TFC, NC or SFCs, and thrombus. A TFC is detected by measuring the relative amount of collagen assessed by fluorescence, a large NC or SFCs are detected through the combination of beta-carotene absorption and the Raman spectral signature of lipids, and thrombus is detected through its Raman signature. The results indicate that rupture-prone vulnerable plaques could be detected with a sensitivity of 96% and specificity of 72%. In conclusion, these encouraging results will help bring MMS into the clinical arena as a powerful, catheter-based diagnostic technique for early detection of vulnerable plaques.

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