scholarly journals Caspase-1 Inhibition Impacts the Formation of Chondrogenic Nodules, and the Expression of Markers Related to Osteogenic Differentiation and Lipid Metabolism

2021 ◽  
Vol 22 (17) ◽  
pp. 9576
Author(s):  
Alice Ramesova ◽  
Barbora Vesela ◽  
Eva Svandova ◽  
Herve Lesot ◽  
Eva Matalova
Keyword(s):  
Lipid Metabolism ◽  
Treatment Strategies ◽  
Treated Group ◽  
Bone Cell ◽  
Bone Maintenance ◽  
Caspase 1 ◽  
Cd36 Expression ◽  
Inverse Effect ◽  
Bone Cell Differentiation ◽  
Abnormal Pattern

Caspase-1, as the main pro-inflammatory cysteine protease, was investigated mostly with respect to inflammation-related processes. Interestingly, caspase-1 was identified as being involved in lipid metabolism, which is extremely important for the proper differentiation of chondrocytes. Based on a screening investigation, general caspase inhibition impacts the expression of Cd36 in chondrocytes, the fatty acid translocase with a significant impact on lipid metabolism. However, the engagement of individual caspases in the effect has not yet been identified. Therefore, the hypothesis that caspase-1 might be a candidate here appears challenging. The primary aim of this study thus was to find out whether the inhibition of caspase-1 activity would affect Cd36 expression in a chondrogenic micromass model. The expression of Pparg, a regulator Cd36, was examined as well. In the caspase-1 inhibited samples, both molecules were significantly downregulated. Notably, in the treated group, the formation of the chondrogenic nodules was apparently disrupted, and the subcellular deposition of lipids and polysaccharides showed an abnormal pattern. To further investigate this observation, the samples were subjected to an osteogenic PCR array containing selected markers related to cartilage/bone cell differentiation. Among affected molecules, Bmp7 and Gdf10 showed a significantly increased expression, while Itgam, Mmp9, Vdr, and Rankl decreased. Notably, Rankl is a key marker in bone remodeling/homeostasis and thus is a target in several treatment strategies, including a variety of fatty acids, and is balanced by its decoy receptor Opg (osteoprotegerin). To evaluate the effect of Cd36 downregulation on Rankl and Opg, Cd36 silencing was performed using micromass cultures. After Cd36 silencing, the expression of Rankl was downregulated and Opg upregulated, which was an inverse effect to caspase-1 inhibition (and Cd36 upregulation). These results demonstrate new functions of caspase-1 in chondrocyte differentiation and lipid metabolism-related pathways. The effect on the Rankl/Opg ratio, critical for bone maintenance and pathology, including osteoarthritis, is particularly important here as well.

scholarly journals Comparison of the Different Treatment Strategies for Patients with Rectus Sheath Haematoma

Medicina ◽  
2018 ◽  
Vol 54 (3) ◽  
pp. 38 ◽  
Author(s):  
Audrius Gradauskas ◽  
Linas Venclauskas ◽  
Matas Pažusis ◽  
Andrius Karpavičius ◽  
Almantas Maleckas
Keyword(s):  
Hospital Stay ◽  
Hypovolemic Shock ◽  
Vital Signs ◽  
Treatment Strategies ◽  
Rectus Sheath ◽  
Treated Group ◽  
Packed Red Blood Cells ◽  
Type Iii ◽  
Physical Status Classification ◽  
American Society

Background and objective: Rectus sheath haematoma (RSH) is an uncommon condition that may vary from contained haematoma to life-threatening bleeding. Timely diagnosis and treatment is crucial in this patient population. The aim of the current study was to investigate the results of the different RSH treatment strategies among patients admitted to a surgery department. Materials and methods: A retrospective analysis of 29 patients treated for RSH in surgery departments of two medical centres from 1 January 2007 to 30 September 2017 was conducted. The patient’s age, sex, ASA (American Society of Anesthesiologists; physical status classification system), use of anticoagulants, cause of haematoma, radiological data, vital signs, blood investigations, and type of treatment were extracted. The results were analysed according to the type of treatment. Results: The patients’ mean age was 67.6 ± 14.3 years, and the mean duration of in-hospital stay was 10.7 ± 6.7 days. All patients were on anticoagulant treatment, and 82.8% of them had spontaneous haematoma. Nine patients (31%) needed transfusion of packed red blood cells with an average of 2.6 units (range: 1–4). Five patients (17.2%) presented with symptoms and signs of hypovolemic shock, and four of them underwent embolisation. Embolisation was successful in all cases. Open surgery was performed in 6 patients, 8 patients underwent percutaneous drainage, and 10 patients were treated conservatively. Two patients (6.7%) died in our series. Both of these patients had type III RSH. Patients in the conservatively treated group had the shortest hospital stay. There were no readmissions due to repeated haematoma or infection. Conclusions: Embolisation of epigastric arteries is a useful tool to stop bleeding into RSH in patients with unstable haemodynamics. Conservative treatment is comparable to ultrasound (US) drainage of RSH but results in a shorter hospital stay. Type III RSH is associated with a higher death rate.

scholarly journals Short Review On Varicose Vein And Its Management

2021 ◽  
Vol 12 (1) ◽  
pp. 832-836
Author(s):  
Pranav N ◽  
Anila K N ◽  
Riju.R.Menon
Keyword(s):  
Quality Of Life ◽  
Varicose Vein ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Treatment Strategies ◽  
Short Review ◽  
Disease Diagnosis ◽  
Treated Group ◽  
Severe Condition

A varicose vein is a condition which affects a large number of people in Western countries and India especially, the northern areas. For curing this proper disease diagnosis, sufficient care for patient and treatment strategies are required, to control the symptoms and signs of varicose vein, the flavonoid group of drugs have been widely used for many years. Under this group, Daflon is the most potent and efficient drug which can be used. This enhances the bioavailability and absorption from the gastrointestinal area. Improved quality of patient's life and efficacy makes this drug therapy more potent and significant. Some of the clinical studies have shown its better action for increased venous tone, lymphatic drainage, decreases cosmetic disfigurement, inflammatory responses occur in microcirculation, protection from free radicals and improved quality of life and efficacy. When compared with other available drugs like Polidocanol, Sotradecol, Asclera, Varithena, Sodium tetradecyl sulfate etc. .clinical benefits of Daflon is more. This drug is useful in the early stage and can be used in severe condition along with sclerotherapy, compression treatment and surgery. Increased patient’s quality of life and increased efficacy were observed in Daflon treated group. Thus it is efficacious as a standard therapy alone and also in combination with other conservative treatment.

Chlorpyrifos exposure induces lipid metabolism disorder at the physiological and transcriptomic levels in larval zebrafish

2019 ◽  
Vol 51 (9) ◽  
pp. 890-899
Author(s):  
Xiaoyu Wang ◽  
Jiajie Zhou ◽  
Manlu Shen ◽  
Jiayan Shen ◽  
Xinyue Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Acid Synthesis ◽  
Treated Group ◽  
Heart Tissue ◽  
Lipid Metabolism Disorder ◽  
Larval Zebrafish ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders ◽  
Cellular Apoptosis

Abstract Chlorpyrifos (CPF) is a widely used insecticide in pest control, and it can affect aquatic animals by contaminating the water. In this study, larval zebrafish were exposed to CPF at concentrations of 30, 100 and 300 μg/l for 7 days. In the CPF-treated group, lipid droplet accumulation was reduced in larval zebrafish. The levels of triglyceride (TG), total cholesterol (TC), and pyruvate were also decreased after CPF exposure. Cellular apoptosis were significantly increased in the heart tissue after CPF exposure compared with the control. Transcription changes in cardiovascular genes were also observed. Through transcriptome analysis, we found that the transcription of 465 genes changed significantly, with 398 upregulated and 67 downregulated in the CPF-treated group, indicating that CPF exposure altered the transcription of genes. Among these altered genes, a number of genes were closely related to the glucose and lipid metabolism pathways. Furthermore, we also confirmed that the transcription of genes related to fatty acid synthesis, TC synthesis, and lipogenesis were significantly decreased in larval zebrafish after exposure to CPF. These results indicated that CPF exposure induced lipid metabolism disorders associated with cardiovascular toxicity in larval zebrafish.

scholarly journals Caspase-1 as a regulatory molecule of lipid metabolism

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Meseret Derbew Molla ◽  
Birhanu Ayelign ◽  
Gashaw Dessie ◽  
Zeleke Geto ◽  
Tesfahun Dessale Admasu
Keyword(s):  
Lipid Metabolism ◽  
Caspase 1 ◽  
Regulatory Molecule

scholarly journals Origins of Alterations to Rankl Null Mutant Mouse Dental Root Development

2020 ◽  
Vol 21 (6) ◽  
pp. 2201
Author(s):  
Andrea Gama ◽  
Jorge William Vargas-Franco ◽  
Diana Carolina Sánchez Mesa ◽  
Elizabeth Restrepo Bedoya ◽  
Jérome Amiaud ◽  
...  
Keyword(s):  
Root Development ◽  
Alveolar Bone ◽  
Bone Cells ◽  
Cell Communication ◽  
Neutralizing Antibody ◽  
Bone Cell ◽  
Experimental Models ◽  
Nuclear Antigen ◽  
Bone Cell Differentiation ◽  
Proliferating Cell

The purpose of the present study was to assess the early stages of development of mouse first molar roots in the osteopetrotic context of RANKL invalidation in order to demonstrate that the radicular phenotype observed resulted not only from defective osteoclasts, but also from loss of cell-to-cell communication among dental, periodontium and alveolar bone cells involving RANKL signaling. Two experimental models were used in this study: Rankl mutants with permanent RANKL invalidation, and C57BL/6J mice injected during the first postnatal week with a RANKL neutralizing antibody corresponding to a transient RANKL invalidation. The dento-alveolar complex was systematically analyzed using micro-CT, and histological and immunohistochemical approaches. These experiments showed that the root elongation alterations observed in the Rankl-/- mice were associated with reduced proliferation of the RANK-expressing HERS cells with a significant decrease in proliferating cell nuclear antigen (PCNA) expression and a significant increase in P21 expression. The phenotypic comparison of the adult first molar root at 35 days between permanent and transitory invalidations of RANKL made it possible to demonstrate that alterations in dental root development have at least two origins, one intrinsic and linked to proliferation/differentiation perturbations in dental-root-forming cells, the other extrinsic and corresponding to disturbances of bone cell differentiation/function.

scholarly journals Supplementing Genistein for Breeder Hens Alters the Fatty Acid Metabolism and Growth Performance of Offsprings by Epigenetic Modification

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Zengpeng Lv ◽  
Hao Fan ◽  
Bochen Song ◽  
Guang Li ◽  
Dan Liu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Growth Performance ◽  
Fatty Acid Biosynthesis ◽  
Cholesterol Metabolism ◽  
Epigenetic Modification ◽  
Treated Group ◽  
Control Group ◽  
Histone H4 ◽  
Acyl Coenzyme A

The experiment was designed to clarify the effect and molecular mechanism of maternal genistein (GEN) on the lipid metabolism and developmental growth of offspring chicks. Laying broiler breeder (LBB) hens were supplemented with 40 mg/kg genistein (GEN), while the control group was fed with the low-soybean meal diet. The offspring chicks were grouped according to the mother generation with 8 replicates each. Hepatic transcriptome data revealed 3915 differentially expressed genes (DEGs, P adjusted < 0.05, fold change>1.5 or fold change<0.67) between chicks in the two groups. Maternal GEN activated the GH-IGF1-PI3K/Akt signaling pathway, which promoted the developmental processes and cellular amino acid metabolic processes, as well as inhibited the apoptotic process. GEN treatment significantly increased the weight gain, breast muscle percentage, and liver index in chicks. PANTHER clustering analysis suggested that maternal GEN enhanced the antioxidant activity of chicks by the upregulation of gene (SOD3, MT1, and MT4) expression. Accordingly, the activities of T-AOC and T-SOD in the liver were increased after GEN treatment. The overrepresentation tests revealed that maternal GEN influenced the glycolysis, unsaturated fatty acid biosynthesis, acyl-coenzyme A metabolism, lipid transport, and cholesterol metabolism in the chick livers. Hepatic cholesterol and long-chain fatty acid were significantly decreased after GEN treatment. However, the level of arachidonic acid was higher in the livers of the GEN-treated group compared with the CON group. Moreover, GEN treatment enhanced fatty acid β-oxidation and upregulated PPARδ expression in the chick liver. ChIP-qPCR analysis indicated that maternal GEN might induce histone H3-K36 trimethylation in the promoter region of PPARδ gene (PPARD) through Iws1, methyltransferases. It also induced histone H4-K12 acetylation at the PPARD promoter through MYST2, which activated the PPAR signaling pathways in the chick livers. In summary, supplementing LBB hens with GEN can alter lipid metabolism in the offspring chicks through epigenetic modification and improve the antioxidative capability as well as growth performance.

scholarly journals Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation

2019 ◽  
Vol 20 (13) ◽  
pp. 3147 ◽  
Author(s):  
Sun-Ju Yi ◽  
Hyerim Lee ◽  
Jisu Lee ◽  
Kyubin Lee ◽  
Junil Kim ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Bone Cells ◽  
Bone Development ◽  
Bone Cell ◽  
Gene Expressions ◽  
Chromatin Dynamics ◽  
Multinucleated Cells ◽  
Bone Cell Differentiation ◽  
Fate Determinants ◽  
The Impact

The bone tissue is a dynamic complex that constitutes of several interdependent systems and is continuously remodeled through the concerted actions of bone cells. Osteoblasts are mononucleated cells, derived from mesenchymal stem cells, responsible for bone formation. Osteoclasts are large multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage and are responsible for bone resorption. The lineage-specific differentiation of bone cells requires an epigenetic regulation of gene expressions involving chromatin dynamics. The key step for understanding gene regulatory networks during bone cell development lies in characterizing the chromatin modifying enzymes responsible for reorganizing and potentiating particular chromatin structure. This review covers the histone-modifying enzymes involved in bone development, discusses the impact of enzymes on gene expression, and provides future directions and clinical significance in this area.

Mechanisms of bone metastasis (BM) growth in patients with metastatic breast cancer (MBC): An exploratory study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1102-1102 ◽  
Author(s):  
W. S. Ooi ◽  
S. Popovic ◽  
M. Kalina ◽  
K. Harriette ◽  
G. Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Strategies ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Treated Group ◽  
Normal Breast ◽  
Primary Cancer ◽  
Comparison Results ◽  
Skeletal Related Events ◽  
Novel Treatment Strategies

1102 Background: The benefits of bisphosphonates (BPs) in reducing or delaying skeletal related events (SREs) in patients with BM have been attributed to their potent osteoclast (OC) inhibiting effect. However, despite the use of modern systemic anti-cancer therapy including potent BPs, many patients with BM continue to suffer from the consequences of their bone disease. An improved understanding of the basic mechanisms of bone destruction would allow further appropriate targeted treatment strategies to be developed. Methods: Archival paraffin embedded BM specimens from patients with MBC were examined for expression of OCs, receptor activator of nuclear factor kappa B (RANK), RANK Ligand (RANKL) and Osteoprotegerin (OPG). Histological specimens were also available for primary breast cancer, lymph node (LN) metastasis, normal breast and bone tissues for comparison. Results: BM specimens were available for 20 BP naïve pts and 2 pts treated with BP. OCs were significantly increased in the BM of the BP naive group compared to controls. There were no OCs seen in the BP treated group. RANK was expressed on tumor cells (TCs) in the both bone and nodal metastases but not on the primary cancer cells. It is also expressed on the OCs which were present in both BM and normal bone. While RANKL was absent in TCs, it was strongly expressed in all stromal cells (SCs) in all specimens and in osteoblasts. The OPG, while present in TCs of the BM and LN metastases, is not detected in the primary cancer. Conclusion: The mechanism of bone destruction in MBC are not fully understood and are clearly multifactorial. OCs may not be the singular obligatory factor for osteolysis in BM. Further investigation of various inhibitors of the RANK/RANKL/OPG pathways, may allow novel treatment strategies to be developed. No significant financial relationships to disclose.

COMPARISON BETWEEN PRIMARY ANGIOPLASTY AND STENT PLACEMENT FOR SYMPTOMATIC INTRACRANIAL ATHEROSCLEROTIC DISEASE

Neurosurgery ◽  
2009 ◽  
Vol 65 (6) ◽  
pp. 1024-1034 ◽  
Author(s):  
Farhan Siddiq ◽  
Muhammad Zeeshan Memon ◽  
Gabriela Vazquez ◽  
Adnan Safdar ◽  
Adnan I. Qureshi
Keyword(s):  
Stent Placement ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Treated Group ◽  
Primary Angioplasty ◽  
Atherosclerotic Disease ◽  
Angiographic Restenosis ◽  
Intracranial Atherosclerotic Disease ◽  
Best Medical Treatment ◽  
Short And Long Term

Abstract OBJECTIVE To compare the short- and long-term rates of stroke-and/or-death associated with primary angioplasty alone and angioplasty with stent placement using a meta-analysis of published studies. Both primary angioplasty alone and angioplasty with stent placement have been proposed as treatment strategies for symptomatic intracranial atherosclerotic disease to reduce the risk of stroke-and/or-death with best medical treatment alone. However, it remains unclear which of these endovascular techniques offers the best risk reduction. METHODS We identified pertinent studies published between January 1980 and May 2008 using a search on PubMed and Cochrane libraries, supplemented by a review of bibliographies of selected publications. The incidences of stroke-and/or-death were estimated for each report and pooled for both angioplasty alone and angioplasty with stent placement at 1 month and 1 year postintervention and then compared using a random-effects model. The association of year of publication and 1-year incidence of stroke-and/or-death was analyzed with meta-regression. RESULTS After applying our selection criteria, we included 69 studies (33 primary angioplasty-alone studies [1027 patients] and 36 studies of angioplasty with stent placement [1291 patients]) in the analysis. There were a total of 91 stroke-and/or-deaths reported in the angioplasty-alone–treated group (8.9%; 95% confidence interval [CI], 7.1%–10.6%), compared with 104 stroke-and/or-deaths in the angioplasty-with-stent–treated group (8.1%; 95% CI, 6.6%–9.5%) during a 1-month period (relative risk [RR], 1.1; P = 0.48). The pooled incidence of 1-year stroke-and/or-death in patients treated with angioplasty alone was 19.7% (95% CI, 16.6%–23.5%), compared with 14.2% (95% CI, 11.9%–16.9%) in the angioplasty-with-stent–treated patients (RR, 1.39; P = 0.009). The incidence of technical success was 79.8% (95% CI, 74.7%–84.8%) in the angioplasty-alone group and 95% (95% CI, 93.4%–96.6%) in the angioplasty-with-stent–treated group (RR, 0.84; P &lt; 0.0001). The pooled restenosis rate was 14.2% (95% CI, 11.8–16.6%) in the angioplasty-alone group, as compared with 11.1% (95% CI, 9.2%–13.0%) in the angioplasty-with-stent–treated group (RR, 1.28; P = 0.04). There was no effect of the publication year of the studies on the risk of stroke-and/or-death. CONCLUSION Risk of 1-year stroke-and/or-death and rate of angiographic restenosis may be lower in symptomatic intracranial atherosclerosis patients treated by angioplasty with stent placement compared with patients treated by angioplasty alone.

Sign in / Sign up

Export Citation Format

Share Document