scholarly journals Association of TGF-β1 and IL-10 Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 930
Author(s):  
Min-Yu Tu ◽  
Kuei-Yang Han ◽  
Ying-Wei Lan ◽  
Ku-Yi Chang ◽  
Cheng-Wei Lai ◽  
...  
Keyword(s):  
Body Height ◽  
World Population ◽  
Mineral Density ◽  
Positive Effects ◽  
Skeletal Disease ◽  
Taiwanese Women ◽  
Hip Bmd ◽  
Anti Inflammatory ◽  
The Many ◽  
Tgf Β1

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (−509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (−509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (−509 C/T) genotype in all subjects and TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (−509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.

scholarly journals Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fast Green ◽  
Expression Levels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Tgf Β1

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

scholarly journals Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1184
Author(s):  
Armin Mooranian ◽  
Thomas Foster ◽  
Corina M Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
...  
Keyword(s):  
Bile Acids ◽  
Biological Effects ◽  
Cellular Respiration ◽  
Full Potential ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
Β Cells ◽  
Positive Effects ◽  
Wide Range ◽  
Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

scholarly journals The association between bone mineral density and postoperative drainage volume following cruciate-substituting primary total knee arthroplasty: a cross-sectional study

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Yuthasak Peerakul ◽  
Jirapong Leeyaphan ◽  
Karn Rojjananukulpong
Keyword(s):  
Blood Loss ◽  
Primary Total Knee Arthroplasty ◽  
Cross Sectional Study ◽  
Postoperative Blood Loss ◽  
Mineral Density ◽  
Cross Sectional ◽  
Total Hip ◽  
Drainage Volume ◽  
Hip Bmd ◽  
Postoperative Drainage

Abstract Background The prevalence of osteoporosis in patients who undergo a primary total knee arthroplasty (TKA) is increasing. Low bone mineral density (BMD) is related to unfavorable outcomes following TKA such as migration of uncemented tibial components. Postoperative blood loss in TKA is an important complication. Non-modifying predicting factors for postoperative blood loss in patients undergoing primary TKA need further elucidation. Studies on the association between BMD and blood loss after TKA are limited. We aimed to demonstrate the relationship between BMD and postoperative drainage volume following primary TKA. Methods A cross-sectional study was conducted between January 2014 and August 2020. A total of 119 primary varus osteoarthritis knees with BMD results were included in the study. Patients with secondary causes of osteoporosis were excluded. Results The median postoperative drainage volume of participants in the normal total hip BMD group and the normal trochanter BMD group was higher than that of patients in the low total hip BMD group and the low trochanter BMD group (285.0 ml vs 230.0 ml, P = 0.003; 282.5 ml vs 240.0 ml, P = 0.013, respectively). Multivariate regression analyses showed that operative time, spinal anesthesia, and normal total hip BMD status were significant predictive factors associated with increased postoperative drainage volume (P = 0.014, 0.022, and 0.013, respectively). No association was identified between the lumbar spine BMD status and postoperative drainage volume. Conclusions The relationship between BMD and postoperative blood loss in primary TKA was identified in this study. Normal total hip BMD was found to be associated with an increased postoperative drainage volume after primary TKA compared with low BMD.

scholarly journals From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors

2020 ◽  
Vol 21 (22) ◽  
pp. 8826
Author(s):  
Elena Guillén-Gómez ◽  
Irene Silva ◽  
Núria Serra ◽  
Francisco Caballero ◽  
Jesús Leal ◽  
...  
Keyword(s):  
Deceased Donor ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
A2a Adenosine Receptor ◽  
A2a Receptors ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pka Pathway ◽  
Tgf Β1 ◽  
M2 Phenotype

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-β1 and other profibrotic markers, as well as CD163, C/EBPβ, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-β1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-β1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA–CREB axis, inducing the macrophage M2 phenotype, TGF-β1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.

scholarly journals A pilot study of possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lillemor Berntson
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Health Assessment ◽  
Short Chain Fatty Acids ◽  
Carbohydrate Diet ◽  
Positive Effects ◽  
Link Type ◽  
Parents And Children ◽  
Inflammatory Proteins ◽  
Anti Inflammatory ◽  
Specific Carbohydrate Diet

Abstract Background To explore possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis. This diet has shown anti-inflammatory effect in children with inflammatory bowel disease. Methods Twenty-two patients with juvenile idiopathic arthritis (age 6.3–17.3 years), with ≤2 inflamed joints and an erythrocyte sedimentation rate < 30 mm/h, were included in this explorative study. Fifteen children completing four weeks on the diet were evaluated. A dietician introduced parents and children to the diet, and two follow-ups were performed during the intervention. Conventional laboratory tests and multiplex analyses of 92 inflammatory proteins were used. Short-chain fatty acids in faecal samples were examined. Results The diet significantly decreased morning stiffness (p = 0.003) and pain (p = 0.048). Physical function, assessed through the child health assessment questionnaire, improved (p = 0.022). Arthritis improved in five of the seven children with arthritis; in those seven, multiplex analyses showed a significant decrease in nine inflammatory proteins, including TNF-alpha (p = 0.028), after four weeks. Faecal butyrate, analysed in all 15 participants, increased significantly (p = 0.020). Conclusion The specific carbohydrate diet may have significant positive effects on arthritis in children with juvenile idiopathic arthritis, but further studies are needed. Clinical trials identifier NCT04205500, 2019/12/17, retrospectively registered. URL: https://register.clinicaltrials.gov

Circulating Biomarkers Related to Osteocyte and Calcium Homeostasis between Postmenopausal Women with and without Osteoporosis

2021 ◽  
Vol 21 ◽  
Author(s):  
Chin Yi Chan ◽  
Shaanthana Subramaniam ◽  
Norazlina Mohamed ◽  
Norliza Muhammad ◽  
Fitri Fareez Ramli ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Postmenopausal Women ◽  
Calcium Homeostasis ◽  
Bone Cells ◽  
Control Group ◽  
Protein Markers ◽  
Mineral Density ◽  
Hydroxyvitamin D ◽  
Hip Bmd ◽  
Turnover Markers

Background: The currently available bone turnover markers are mostly derived from osteoblasts or osteoclasts. Protein markers derived from osteocytes, the most abundant bone cells that can regulate bone turnover activities by other cells, are less explored. Objective: This study aimed to compare the circulating markers of osteocytes and calcium homeostasis between Malaysian postmenopausal women with and without osteoporosis. Method: Postmenopausal women with (n=20) or without osteoporosis (n=20) as determined by dual-energy X-ray absorptiometry were randomly drawn from a bone health cohort. Their fasting blood was collected and assayed by a multiplex immunoassay panel. Results: The results showed that osteoprotegerin and sclerostin levels were significantly lower among postmenopausal women with osteoporosis than the normal control. No significant differences in other markers were observed between the two groups. Sclerostin level correlated positively with spine bone mineral density (BMD), while 25-hydroxyvitamin D correlated negatively with hip BMD in the control group. No significant correlation was observed between other markers with spine or hip BMD. Conclusion: These data provide an insight into the possible roles of osteocyte markers, especially osteoprotegerin and sclerostin in classifying subjects with osteoporosis. However, the lack of association between these markers and BMD indicates that osteoporosis is a complex and multifactorial condition.

scholarly journals A Comparison of the Effects of Raloxifene and Estrogen on Bone in Postmenopausal Women1

2000 ◽  
Vol 85 (6) ◽  
pp. 2197-2202
Author(s):  
Karen M. Prestwood ◽  
Michele Gunness ◽  
Douglas B. Muchmore ◽  
Yili Lu ◽  
Mayme Wong ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Biochemical Markers ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Markers Of Bone Turnover ◽  
Bone Biopsies ◽  
Hip Bmd ◽  
Total Body

Raloxifene HCl, a selective estrogen receptor modulator, has been shown to increase bone mineral density (BMD) and decrease biochemical markers of bone turnover in postmenopausal women without stimulatory effects on the breast and uterus. However, it is not known whether the changes in BMD and bone turnover are associated with changes at the tissue level, nor how changes with raloxifene compare with estrogen. In this randomized, double blind study, we evaluated the effects of raloxifene (Evista, 60 mg/day) or conjugated equine estrogens (CEE; Premarin, 0.625 mg/day) on bone architecture, bone turnover, and BMD. Iliac crest bone biopsies were obtained at baseline and at the end of the study after double tetracycline labeling and were analyzed for standard histomorphometric indexes. Serum and urinary biochemical markers of bone turnover were measured at baseline and at 4, 10, 18, and 24 weeks of treatment. Total body, lumbar spine, and hip BMD were measured at baseline and at the end of the study by dual energy x-ray absorptiometry. Activation frequency and bone formation rate/bone volume were significantly decreased from baseline in the CEE, but not in the raloxifene, group. Bone mineralization did not change in either group. Most markers of bone resorption and formation decreased in both groups, but to a greater degree in the CEE group (P &lt; .05). Total body and lumbar spine BMD increased from baseline in both groups, with a greater increase in the CEE group (P&lt; 0.05). Hip BMD significantly increased from baseline in the raloxifene group, but the change was not different from that in the CEE group. These results suggest that raloxifene reduces bone turnover and increases bone density, although to a lesser extent than CEE. Thus, raloxifene is an alternative to CEE for the prevention and treatment of osteoporosis in postmenopausal women.

Diphenyl diselenide subcutaneous supplementation of dairy sheep: effects on oxidant and antioxidant status, inflammatory response and milk composition

2019 ◽  
Vol 59 (3) ◽  
pp. 461 ◽  
Author(s):  
Angelisa H. Biazus ◽  
Chrystian J. Cazarotto ◽  
Gustavo Machado ◽  
Nathieli B. Bottari ◽  
Mariana S. Alves ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Interleukin 10 ◽  
Milk Composition ◽  
Fat Content ◽  
Control Group ◽  
Lactation Period ◽  
Diphenyl Diselenide ◽  
Dairy Sheep ◽  
Positive Effects ◽  
Anti Inflammatory

Diphenyl diselenide ((PhSe)2) is a organoselenium compound with potent antioxidant properties. Therefore, the aim of the present study was to evaluate whether subcutaneous supplementation of (PhSe)2 in dairy sheep has positive effects on milk composition, as well as on the prevention of oxidative stress and exacerbated inflammatory response. For this, 16 primiparous recently calved sheep were divided into the following two groups, with eight animals in each: Group A, the control group; and Group B, the group subcutaneously supplemented with five doses of (PhSe)2 of 3.0µmol/kg each every 7 days. Blood samples from supplemented animals showed increased concentration of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase), and reduced reactive oxygen species and lipid peroxidation, which prevented oxidative damage in the lactation period, as well as increased seric interleukin-10, an anti-inflammatory cytokine. In the sera, supplemented animals showed increased total antioxidant capacity and ferric-reducing ability of plasma compared with the control group. As a consequence, supplemented animals showed increased antioxidant variables, as well as reduced protein oxidation in milk samples. Moreover, milk from supplemented sheep showed a higher fat content, and lower total protein and lactose contents in some periods in the study, than did not-supplemented ewes. Seric concentrations of interleukin-1 were lower on Days 30 and 45 in supplemented animals, as well as the concentrations of tumour necrosis factor α in all periods, than were those in the control group, whereas the interleukin-10 concentrations were higher. Thus, dairy sheep supplementation of (PhSe)2 activated antioxidant and anti-inflammatory responses, and increased milk fat content. Moreover, this protocol increased the antioxidant and, consequently, reduced the oxidant concentration in milk, which is desirable for product quality.

scholarly journals Role of Harmaline as Adiponectin Modulator in Defeating Liver Cirrhosis Induced By Thioacetamide in Mice

2021 ◽  
Vol 14 (1) ◽  
pp. 123-131
Author(s):  
Doha M. Beltagy ◽  
Khloud Gamal Abdelsalam ◽  
Tarek M Mohamed ◽  
Mai M. El-Keey
Keyword(s):  
Oxidative Stress ◽  
Liver Cirrhosis ◽  
Transforming Growth Factor Beta ◽  
Liver Tissue ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Matrix Deposition ◽  
Anti Inflammatory ◽  
Tgf Β1

Liver cirrhosis is currently the 11th most common cause of death which includes inflammatory, oxidative damage, and immune response. Harmaline has antioxidant and anti-inflammatory mechanisms which can defeat against hepatic cirrhosis pathways. The present work aimed to evaluate the ameliorating effect of harmaline against liver cirrhosis induced by thioacetamide in mice. The study was carried out on sixty male mice divided into three main groups. Control and harmaline groups (GIa and GIb), thioacetamide-group (GII) and harmaline co-treated and treated groups (GIIIa and GIIIb). By the end of the experiment, adiponectin concentrations were measured in serum and liver tissue. Gene expression of adiponectin, transforming growth factor beta-1 (TGF-β1), tissue inhibitor metalloprotease-1(TIMP-1) and peroxisome proliferator activated receptor-gamma (PPAR-γ) were assessed. Some oxidative stress biomarkers as malondialdehyde, reduced glutathione, catalase, superoxide dismutase and nitric oxide were determined. The results indicated that harmaline administration cause significant suppression of oxidative stress and inflammatory response.Inhibition of hepatic stellate cell activation and extracellular matrix deposition were also noticed with a significant decrease in the expression of the profibrotic markers(TGF-β1 and TIMP-1) which have direct effects on adiponectin activation. These results were confirmed by the histological studies in liver tissue. In Conclusion,Harmaline has excellent protective role against liver cirrhosis induced by thioacetamide in mice via its antioxidant and anti-inflammatory properties.It can be therapeutically used as a safe liver support by a dose of 10 mg/kg after furtherin vivo studies.

scholarly journals Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

2021 ◽  
Vol 18 (16) ◽  
pp. 8538
Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Control Group ◽  
Study Group ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

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