Publications by authors named "Chun-Hao Tsai"

138 Publications

Acetabular Fractures with Central Hip Dislocation: A Retrospective Consecutive 50 Case Series Study Based on AO/OTA 2018 Classification in Midterm Follow-Up.

Biomed Res Int 2021 17;2021:6659640. Epub 2021 Sep 17.

Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan.

Introduction: Management of acetabular fractures is challenging, especially when a medial acetabular fracture is complicated by central hip dislocation. We retrospectively investigated the clinical outcome and risk factors of secondary hip osteoarthritis requiring total hip arthroplasty after the surgical treatment of acetabular fractures with central hip dislocation.

Materials And Methods: The medical records of all patients who had acetabular medial wall fractures with central hip dislocation treated with open reduction and internal fixation by a single surgeon between January 2015 and June 2017 were reviewed. Surgical reduction was performed with the modified Stoppa with/without the Kocher-Langenbeck (KL) approach. Patients were followed for a minimum of three years, and the Majeed scoring system was used for functional evaluation. Multivariate logistic regression analysis was used to assess the association of patients' characteristics with the likelihood of advanced posttraumatic arthritis developing with conversion to total hip arthroplasty.

Results: Fifty patients were included in this study, with disease classified as AO/OTA 2018 62B/62C. Thirty-five patients (70%) had good or excellent Majeed pelvic scores. Eleven patients (22%) eventually received total hip arthroplasty because of end-stage posttraumatic arthritis. Three risk factors identified for total hip arthroplasty were male sex, initial marginal impaction, and sciatic nerve injury. Kaplan-Meier survivorship analysis estimated that the cumulative probability of free-from-end-stage arthritis was 78% (95% confidence interval, 73%-90%) at the 5-year follow-up.

Conclusion: Surgical fixation with the modified Stoppa and the KL approach for acetabular medial wall fractures with central hip dislocation is an effective approach with a satisfactory functional outcome. A prodromal factor was marginal impaction concomitant with articular damage. The trauma of high axial loading and the occupational distribution (males performing heavy manual labor and heavy lifting) with preoperative sciatic nerve injury increased the odds of developing end-stage arthritis.
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http://dx.doi.org/10.1155/2021/6659640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463190PMC
September 2021

Nesfatin-1 facilitates IL-1β production in osteoarthritis synovial fibroblasts by suppressing miR-204-5p synthesis through the AP-1 and NF-κB pathways.

Aging (Albany NY) 2021 Sep 24;13(18):22490-22501. Epub 2021 Sep 24.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

The progression of osteoarthritis (OA) is mediated by adipokines, one of which is nesfatin-1, which is responsible for the production of inflammatory cytokines. However, how this molecule may affect the synthesis of the proinflammatory cytokine interleukin 1 beta (IL-1β) in OA is unclear. Our analyses of records from the Gene Expression Omnibus (GEO) dataset and clinical specimens of synovial tissue revealed higher levels of nesfatin-1 and IL-1β in OA samples compared with normal healthy tissue. We found that nesfatin-1 facilitates IL-1β synthesis in human OA synovial fibroblasts (OASFs) and suppresses the generation of micro-RNA (miR)-204-5p, as the miR-204-5p levels in OA patients were lower than those in healthy controls. Nesfatin-1-induced stimulation of IL-1β in human OASFs occurred via the suppression of miR-204-5p synthesis by the PI3K, Akt, AP-1 and NF-κB pathways. We suggest that nesfatin-1 is worth targeting in OA treatment.
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http://dx.doi.org/10.18632/aging.203559DOI Listing
September 2021

CXCL13/CXCR5 axis facilitates endothelial progenitor cell homing and angiogenesis during rheumatoid arthritis progression.

Cell Death Dis 2021 09 13;12(9):846. Epub 2021 Sep 13.

School of Medicine, China Medical University, Taichung, Taiwan.

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays important roles in several cellular functions such as infiltration, migration, and motility. We report significantly higher levels of CXCL13 expression in collagen-induced arthritis (CIA) mice compared with controls and also in synovial fluid from RA patients compared with human osteoarthritis (OA) samples. RA synovial fluid increased endothelial progenitor cell (EPC) homing and angiogenesis, which was blocked by the CXCL13 antibody. By interacting with the CXCR5 receptor, CXCL13 facilitated vascular endothelial growth factor (VEGF) expression and angiogenesis in EPC through the PLC, MEK, and AP-1 signaling pathways. Importantly, infection with CXCL13 short hairpin RNA (shRNA) mitigated EPC homing and angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with CIA. CXCL13 is therefore a novel therapeutic target for RA.
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http://dx.doi.org/10.1038/s41419-021-04136-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437941PMC
September 2021

S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis.

Cells 2021 Aug 23;10(8). Epub 2021 Aug 23.

School of Medicine, China Medical University, Taichung 40402, Taiwan.

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 (SphK1) produces sphingosine-1-phosphate (S1P), which increases inflammatory cytokine production, although the role of S1P in RA angiogenesis is unclear. In this study, we evaluated the impact of S1P treatment on VEGF-dependent angiogenesis in osteoblast-like cells (MG-63 cells) and the significance of SphK1 short hairpin RNA (shRNA) on S1P production in an in vivo model. We found significantly higher levels of S1P and VEGF expression in synovial fluid from RA patients compared with those with osteoarthritis by ELISA analysis. Treating MG-63 cells with S1P increased VEGF production, while focal adhesion kinase (FAK) and Src siRNAs and inhibitors decreased VEGF production in S1P-treated MG-63 cells. Conditioned medium from S1P-treated osteoblasts significantly increased EPC tube formation and migration by inhibiting miR-16-5p synthesis via proto-oncogene tyrosine-protein kinase src (c-Src) and FAK signaling in chick chorioallantoic membrane (CAM) and Matrigel plug assays. Infection with SphK1 shRNA reduced angiogenesis, articular swelling and cartilage erosion in the ankle joints of mice with collagen-induced arthritis (CIA). S1P appears to have therapeutic potential in RA treatment.
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http://dx.doi.org/10.3390/cells10082168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393529PMC
August 2021

Cruciate-Retaining vs Posterior-Stabilized Antibiotic Cement Articulating Spacers for Two-Stage Revision of Prosthetic Knee Infection: A Retrospective Cohort Study.

J Arthroplasty 2021 Jun 25. Epub 2021 Jun 25.

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; X-Dimension Center for Medical Research and Translation, China Medical University Hospital, Taichung, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.

Background: Antibiotic cement articulating spacers are recommended during 2-stage revision for prosthetic knee infection because of increased range of motion (ROM) and improved function; however, spacer mechanical complications have been reported. We aimed to determine the association between different constraints of articulating spacers and the rate of complications and infection eradication, functional outcomes, and ROM.

Methods: A retrospective study of prosthetic knee infection using cruciate-retaining (CR) or posterior-stabilized (PS) spacers was conducted between 2011 and 2018. The rate of spacer mechanical complications, infection eradication after reimplantation and reoperation, Hospital of Special Surgery (HSS) knee score, and ROM during the interim stage were analyzed. All patients were regularly followed up for 2 years.

Results: One hundred forty-one patients were included, with 66 CR and 75 PS spacers. Overall mechanical complication rate was lower in PS (9.3%) than in CR spacers (45.5%) (P < .001), especially in joint dislocation (1.3% vs 30.3%, respectively, P < .001). Overall reoperation rate was lower in PS (16.0%) than in CR spacers (36.4%) (P < .001), especially for mechanical complications (1.3% vs 24.2%, respectively, P < .001). HSS knee score was higher in PS (72.3) than in CR spacers (63.8) (P < .001). ROM was greater in PS (90.3°) than in CR spacers (80.6°) (P = .005), especially at maximum flexion (102.4° vs 89.6°, respectively, P = .003). Infection eradication was comparable between the spacers.

Conclusion: Both spacers can control infection; however, PS spacers had a lower rate of mechanical complications and reoperation, better HSS knee scores, and greater ROM than CR spacers.
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http://dx.doi.org/10.1016/j.arth.2021.06.023DOI Listing
June 2021

Digital Light Processing Bioprinted Human Chondrocyte-Laden Poly (γ-Glutamic Acid)/Hyaluronic Acid Bio-Ink towards Cartilage Tissue Engineering.

Biomedicines 2021 Jun 23;9(7). Epub 2021 Jun 23.

x-Dimension Center for Medical Research and Translation, China Medical University Hospital, Taichung 40447, Taiwan.

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.
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http://dx.doi.org/10.3390/biomedicines9070714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301387PMC
June 2021

miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts.

Aging (Albany NY) 2021 07 1;13(13):17227-17236. Epub 2021 Jul 1.

School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.
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http://dx.doi.org/10.18632/aging.203201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312412PMC
July 2021

DPP4 reduces proinflammatory cytokine production in human rheumatoid arthritis synovial fibroblasts.

J Cell Physiol 2021 Jun 30. Epub 2021 Jun 30.

Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan.

Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by increasing levels of proinflammatory cytokines. The ubiquitous enzyme dipeptidyl peptidase-4 (DPP4, also known as CD26) regulates different immune disorders, although the effects of DPP4 in RA are uncertain. Here, we found lower levels of DPP4 in RA synovial tissues compared with normal tissues. DPP4 levels were also lower in a rat collagen-induced arthritis model than in control (healthy) rats. Overexpression of DPP4 or exogenous treatment of RA synovial fibroblasts with DPP4 reduced levels of proinflammatory interleukin (IL)-1β, IL-6, and IL-13, and increased anti-inflammatory IL-10 synthesis, while DPP4 inhibitors sitagliptin and vildagliptin increased proinflammatory cytokine production, indicating an enhanced risk of RA development. The evidence suggests that increasing DPP4 expression is a novel strategy for RA disease.
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http://dx.doi.org/10.1002/jcp.30494DOI Listing
June 2021

Safety and efficacy of single CHAP Hyaluronan injection versus three injections of linear Hyaluronan in pain relief for knee osteoarthritis: a prospective, 52-week follow-up, randomized, evaluator-blinded study.

BMC Musculoskelet Disord 2021 Jun 23;22(1):572. Epub 2021 Jun 23.

Department of Orthopedics, China Medical University Hospital, No.91 Hsueh-Shih Road, Taichung, 404, Taiwan.

Background: The hyaluronic acid (HA) injections are widely used in knee osteoarthritis (OA) patients. We conducted the study comparing the efficacy and safety of single injection of Crosslinked Hyaluronic Acid Platform Hyaluronan (CHAP-HA) with 3-injection of linear hyaluronan in knee OA patients.

Methods: This was a randomized two-arms, evaluator-blinded, controlled, single-center study. Participants with knee OA received single CHAP-HA or three-injection of linear-HA. The 140 patients aged 35-85 years with radiographically confirmed knee OA were enrolled. At week 4, 12, 26, 39, and 52, visual analog scale (VAS) pain score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, timed up and go (TUG) and subject's adverse events (AE) of these 2 groups were recorded. Primary outcome of the differences of VAS pain score at week 26 between groups was analyzed with analysis of covariance (ANCOVA). At week 52, those who met the inclusion criteria could receive a CHAP-HA injection and being followed-up for the adverse events for 4 weeks.

Results: The trial was conducted from September 2015 to April 2017. A total 140 subjects were available for analysis (71 in the CHAP-HA group and 69 in the linear-HA group). At 26th week, there were significant more improvements in VAS pain scores in CHAP-HA compared with linear-HA. Both CHAP-HA and linear-HA showed significant improvements in the VAS pain score at week 26 compared with the baseline, and the occurrence of adverse events during the study period showed no between-group difference. In subjects with KL = 2, both groups showed significant improvements in VAS pain scores within 26 weeks. In patients with KL = 3, only CHAP-HA group showed significant improvement in VAS pain from 4 to 39 weeks. No unexpected or severe AEs were reported.

Conclusions: A single injection of CHAP-HA may be safe and more effective for 26 weeks in patients with knee OA by comparing to linear-HA; moreover, the pain relief effect of CHAP-HA may remain until 52 weeks. For patients with more severe OA, CHAP-HA was demonstrated to be more preferable to relieve OA pain. Furthermore, repeat treatment of CHAP-HA or using CHAP-HA after a three-injection HA was proved to be safe.

Trial Registration: ClinicalTrials.gov : NCT03643588 . Date: August 23, 2018 (retrospectively registered).

Level Of Evidence: Therapeutic Level I.
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http://dx.doi.org/10.1186/s12891-021-04467-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223367PMC
June 2021

A cross-sectional analysis of the association between sleep duration and osteoporosis risk in adults using 2005-2010 NHANES.

Sci Rep 2021 04 27;11(1):9090. Epub 2021 Apr 27.

Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan.

Controversy remains regarding the relationship between bone health and sleep. In the literature, the effect of sleep on bone density in the clinical setting varies depending on the definition of normal sleep duration, sleep quality, selected population, and diagnostic tools for bone density. The aim of this study was to examine the association between bone mineral density (BMD)assessed by dual-energy X-ray absorptiometry and sleep duration/quality in the defined adult population from the National Health and Nutrition Examination Survey (NHANES) (a national household survey) within a 6-year period (2005-2010) and explore age differences. The basic variables, metabolic diseases, and bone density in the femoral neck as determined through dual-energy X-ray absorptiometry, were segregated, and analyzed according to different sleep durations (1-4, 5-6,7-8, and > 9 h/day) and sleep quality using multinomial regression models. A total of 12,793 subjects were analyzed. Our results reveal that women aged > 50 years with sleep duration < 5 h/day had a 7.35 (CI 3.438-15.715) odds of osteoporosis than those in other groups. This analysis is based on a nationally representative sample using survey and inspection data and clarifies the relationship between bone density and the effect of the combination of sleep quality and duration.
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http://dx.doi.org/10.1038/s41598-021-88739-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079413PMC
April 2021

Bidirectional relationship between temporomandibular disorder and ankylosing spondylitis: a population-based cohort study.

Clin Oral Investig 2021 Apr 14. Epub 2021 Apr 14.

Program for Aging, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402, Taiwan.

Objectives: This study aimed to determine the relation between temporomandibular disorder (TMD) and ankylosing spondylitis (AS) bidirectionally and ascertain the important comorbidities for AS occurrence in TMD patients.

Materials And Methods: We conducted this population-based cohort study through Longitudinal Health Insurance Database, Taiwan. Study 1 investigated the risk of TMD in AS patients. Study 2 assessed the risk of AS in TMD patients.

Results: In total, 3204 AS patients and 12,816 age-matched and gender-matched comparisons were enrolled in study 1. The TMD incidence in the AS cohort was 2.88-fold higher when compared with the comparisons (1.54 vs. 0.53 per 10,000 person-years). After adjusting for age, gender, and comorbidity, the AS cohort had a 2.66-fold (95% CI = 1.79-3.97) increased risk of TMD occurrence (P < 0.0001). The second study recruited 4998 TMD patients and 19,991 age-matched and gender-matched comparisons. Both TMD and comparison cohorts showed similar AS risk (HR = 1.49, 95% CI = 0.91-2.43, P = 0.1108) in the adjusted model. Study 2 identified a 3.66-fold increased risk of AS occurrence in TMD patients with comorbidity, including parapsoriasis, rheumatoid arthritis, osteoporosis, Cushing's syndrome, and climacteric arthritis (P < 0.012).

Conclusions: AS appears to significantly impact the occurrence of TMD. TMD might play a synergic role in AS development.

Clinical Relevance: Clinicians have to be vigilant about the increased risk of TMD in AS patients and take care of AS disease activity and prognosis. The symptoms and signs of TMD could be a predictor of AS in patients with the aforementioned comorbidities.
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http://dx.doi.org/10.1007/s00784-021-03938-0DOI Listing
April 2021

The Effects of Tgfb1 and Csf3 on Chondrogenic Differentiation of iPS Cells in 2D and 3D Culture Environment.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Ph.D. Program for Aging, College of Medicine, China Medical University, Taichung 406040, Taiwan.

Mesenchymal stem (MS) cells, embryonic stem (ES) cells, and induced pluripotent stem (iPS) cells are known for their ability to differentiate into different lineages, including chondrocytes in culture. However, the existing protocol for chondrocyte differentiation is time consuming and labor intensive. To improve and simplify the differentiation strategy, we have explored the effects of interactions between growth factors (transforming growth factor β1 (Tgfb1) and colony stimulating factor 3 (Csf3), and culture environments (2D monolayer and 3D nanofiber scaffold) on chondrogenic differentiation. For this, we have examined cell morphologies, proliferation rates, viability, and gene expression profiles, and characterized the cartilaginous matrix formed in the chondrogenic cultures under different treatment regimens. Our data show that 3D cultures support higher proliferation rate than the 2D cultures. Tgfb1 promotes cell proliferation and viability in both types of culture, whereas Csf3 shows positive effects only in 3D cultures. Interestingly, our results indicate that the combined treatments of Tgfb1 and Csf3 do not affect cell proliferation and viability. The expression of cartilaginous matrix in different treatment groups indicates the presence of chondrocytes. We found that, at the end of differentiation stage 1, pluripotent markers were downregulated, while the mesodermal marker was upregulated. However, the expression of chondrogenic markers (col2a1 and aggrecan) was upregulated only in the 3D cultures. Here, we report an efficient, scalable, and convenient protocol for chondrogenic differentiation of iPS cells, and our data suggest that a 3D culture environment, combined with tgfb1 and csf3 treatment, promotes the chondrogenic differentiation.
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http://dx.doi.org/10.3390/ijms22062978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000805PMC
March 2021

miR-144-3p ameliorates the progression of osteoarthritis by targeting IL-1β: Potential therapeutic implications.

J Cell Physiol 2021 Oct 27;236(10):6988-7000. Epub 2021 Mar 27.

Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.

The pro-inflammatory cytokine interleukin 1 beta (IL-1β) plays a critical role in osteoarthritis (OA) disease pathogenesis. MicroRNA (miRNA) activity is related to inflammation in OA and some miRNAs specifically regulate IL-mediated degradation of cartilage type II collagen. Previous studies have indicated that miR-144-3p is a useful target in the regulation of pro-inflammatory cytokines in different diseases. However, the role of miR-144-3p in OA is unclear. In this study, we observed a negative correlation between miR-144-3p and IL-1β expression in OA. miR-144-3p mimic transfection of OA synovial fibroblasts downregulated levels of IL-1β expression, while blocking the MAPK, PI3K/Akt, and NF-κB signaling pathways relating to IL-1β production, and effectively increased miR-144-3p expression in OASFs. Findings from an anterior cruciate ligament transection rat model revealed that administration of miR-144-3p mimic effectively ameliorated OA progression and reduced the numbers of IL-1β-positive cells in synovial tissue. This study suggests that miR-144-3p is a useful therapeutic target in OA disease.
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http://dx.doi.org/10.1002/jcp.30361DOI Listing
October 2021

Melatonin interrupts osteoclast functioning and suppresses tumor-secreted RANKL expression: implications for bone metastases.

Oncogene 2021 02 15;40(8):1503-1515. Epub 2021 Jan 15.

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is capable of regulating bone homeostasis, we explored its therapeutic potential in bone metastasis. We found that melatonin directly reduces osteoclast differentiation, bone resorption activity and promotes apoptosis of mature osteoclasts. We also observed that melatonin inhibits RANKL production in lung and prostate cancer cells by downregulating the p38 MAPK pathway, which in turn prevents cancer-associated osteoclast differentiation. In lung and prostate bone metastasis models, twice-weekly melatonin treatment markedly reduced tumor volumes and numbers of osteolytic lesions. Melatonin also substantially lowered the numbers of TRAP-positive osteoclasts in tibia bone marrow and RANKL expression in tumor tissue. These findings show promise for melatonin in the treatment of bone metastases.
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http://dx.doi.org/10.1038/s41388-020-01613-4DOI Listing
February 2021

The impact of timing and modalities of dental prophylaxis on the risk of 5-fluorouracil-related oral mucositis in patients with head and neck cancer: a nationwide population-based cohort study.

Support Care Cancer 2021 Jun 19;29(6):3163-3171. Epub 2020 Oct 19.

School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, 11031, Taiwan.

Purpose: This study investigated the impact of dental prophylaxis on 5-fluorouracil (5-FU)-related oral mucositis (OM) according to the head and neck cancer (HNC) locations and treatment times.

Methods: A total of 13,969 HNC participants, including 482 5-FU-related OM subjects and 13,487 comparisons were enrolled from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2008. All subjects were stratified into subgroups based on the times to perform chlorhexidine use, scaling, and fluoride application before 5-FU administration. The dental prophylaxis related to 5-FU-related OM was estimated by multiple logistic regression and represented with odds ratio (OR) and 95% confidence interval (CI).

Results: Fluoride gel application and scaling significantly impacted on OM development (p < 0.001), and the joint effect of fluoride gel and scaling induced 5-FU-related OM (OR = 3.46, 95% CI = 2.39-5.01). The risk of OM was raised 2.25-fold as scaling within 3 weeks before 5-FU-related chemotherapy (95% CI = 1.81-2.81), and a 3.22-fold increased risk of OM while fluoride gel was applied during 5-FU-related treatment (95% CI = 1.46-7.13).

Conclusion: Dental prophylaxis significantly affected 5-FU-related OM in the HNC population. A short interval between dental scaling or fluoride application and 5-FU administration may be associated with higher prevalence of OM. Scaling simultaneously combined with chlorohexidine promoted 5-FU-related OM in specific HNC patients excluding the oral cancer and nasopharyngeal cancer population. Proper timing of the prophylactic dental treatments prior to 5-FU therapy could reduce the risk to develop 5-FU-related OM.
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http://dx.doi.org/10.1007/s00520-020-05825-yDOI Listing
June 2021

Visfatin increases ICAM-1 expression and monocyte adhesion in human osteoarthritis synovial fibroblasts by reducing miR-320a expression.

Aging (Albany NY) 2020 Sep 29;12(18):18635-18648. Epub 2020 Sep 29.

School of Nutrition, Chung Shan Medical University, Taichung, Taiwan.

Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include monocyte adhesion and infiltration, and synovial inflammation. In particular, the adhesion protein intercellular adhesion molecule type 1 (ICAM-1) promotes monocyte recruitment into the synovial tissue. Visfatin is an adipocyte hormone that promotes the release of inflammatory cytokines during OA progression. We report that visfatin enhances ICAM-1 expression in human OA synovial fibroblasts (OASFs) and facilitates the adhesion of monocytes with OASFs. AMPK and p38 inhibitors, as well as their respective siRNAs, attenuated the effects of visfatin upon ICAM-1 synthesis and monocyte adhesion. We also describe how miR-320a negatively regulates visfatin-induced promotion of ICAM-1 expression and monocyte adhesion. We detail how visfatin affects ICAM-1 expression and monocyte adhesion with OASFs by inhibiting miR-320a synthesis via the AMPK and p38 signaling pathways.
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http://dx.doi.org/10.18632/aging.103889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585076PMC
September 2020

Preliminary clinical and radiographic outcomes of proximal humeral fractures: comparison of ALPS and PHILOS plating in Asian patients in Taiwan.

J Orthop Surg Res 2020 Aug 28;15(1):364. Epub 2020 Aug 28.

Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan.

Background: Up to 20% of proximal humeral fractures need to be treated operatively. However, numerus complications were reported by using fixed angled locking plates. The ALPS Proximal Humerus Plating System is a new design implant with novel design features. The aim of this study was to compare the preliminary clinical outcomes and complications of proximal humeral fractures treated with either ALPS or the proximal humeral internal locking system (PHILOS) in Asian patients in Taiwan.

Methods: Between January 2016 and December 2018, 66 patients with displaced proximal humeral fractures were analyzed retrospectively, of whom 31 underwent ALPS implant treatment and 35 underwent PHILOS implant treatment. Intraoperative blood loss and operation time, postoperative Constant-Murley Shoulder Outcome (Constant-Murley) score, and complications variables were recorded for the comparison. All cases were regularly followed up for at least 1 year.

Results: The mean follow-up period was 400.8 days (range, 367-446 days). Union was achieved in 98.5% of patients (65/66). The ALPS group yielded similar radiologic and clinical outcomes to the PHILOS plating group for treating displaced proximal humeral fractures, including operation time, intraoperative blood loss, the Constant-Murley score, and varus malunion (P > 0.05, respectively). However, the incidence of total postoperative complications in the ALPS group was significantly lower than in the PHILOS group (P < 0.05). There was a trend of a lower complication rate of screws/pegs protrusion, avascular necrosis, subacromial impingement, postoperative infection, and reoperation in the ALPS group, although it was not statistically significant (P > 0.05, respectively).

Conclusion: The ALPS group yielded similar radiologic and clinical outcomes to the PHILOS plating group for displaced proximal humeral fractures, but the ALPS group had a significantly lower total rate of complications. Therefore, ALPS may be a better option for treating proximal humeral fractures. Further larger clinical studies are needed to confirm the findings presented here.

Trial Registration: Retrospective study.
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http://dx.doi.org/10.1186/s13018-020-01846-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456013PMC
August 2020

Resistin enhances IL-1β and TNF-α expression in human osteoarthritis synovial fibroblasts by inhibiting miR-149 expression via the MEK and ERK pathways.

FASEB J 2020 10 13;34(10):13671-13684. Epub 2020 Aug 13.

School of Medicine, China Medical University, Taichung, Taiwan.

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1β, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1β and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1β in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA.
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http://dx.doi.org/10.1096/fj.202001071RDOI Listing
October 2020

S1P promotes IL-6 expression in osteoblasts through the PI3K, MEK/ERK and NF-κB signaling pathways.

Int J Med Sci 2020 18;17(9):1207-1214. Epub 2020 May 18.

School of Medicine, China Medical University, Taichung, Taiwan.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks joint tissue. Interleukin (IL)-6 is a key proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we examined the effects of S1P on IL-6 expression in osteoblasts. Our results and records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-6 in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P increased mRNA and protein expression of IL-6. PI3K, MEK, ERK and NF-κB inhibitors and their small interfering RNAs (siRNAs) reduced S1P-promoted IL-6 expression. S1P also facilitated PI3K, MEK/ERK and NF-κB signaling cascades. Our results indicate that S1P promotes the expression of IL-6 in osteoblasts via the PI3K, MEK/ERK and NF-κB signaling pathways.
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http://dx.doi.org/10.7150/ijms.44612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294913PMC
March 2021

Visfatin Increases VEGF-dependent Angiogenesis of Endothelial Progenitor Cells during Osteoarthritis Progression.

Cells 2020 05 25;9(5). Epub 2020 May 25.

Department of Pharmacology, School of Medicine, China Medical University, Taichung 404, Taiwan.

Osteoarthritis (OA) pannus contains a network of neovascularization that is formed and maintained by angiogenesis, which is promoted by vascular endothelial growth factor (VEGF). Bone marrow-derived endothelial progenitor cells (EPCs) are involved in VEGF-induced vessel formation in OA. The adipokine visfatin stimulates the release of inflammatory cytokines during OA progression. In this study, we found significantly higher visfatin and VEGF serum concentrations in patients with OA compared with healthy controls. We describe how visfatin enhanced VEGF expression in human OA synovial fibroblasts (OASFs) and facilitated EPC migration and tube formation. Treatment of OASFs with PI3K and Akt inhibitors or siRNAs attenuated the effects of visfatin on VEGF synthesis and EPC angiogenesis. We also describe how miR-485-5p negatively regulated visfatin-induced promotion of VEGF expression and EPC angiogenesis. In our OA rat model, visfatin shRNA was capable of inhibiting visfatin and rescuing EPC angiogenesis and pathologic changes. We detail how visfatin affected VEGF expression and EPC angiogenesis in OASFs by inhibiting miR-485-5p synthesis through the PI3K and Akt signaling pathways.
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http://dx.doi.org/10.3390/cells9051315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291153PMC
May 2020

Apelin enhances IL-1β expression in human synovial fibroblasts by inhibiting miR-144-3p through the PI3K and ERK pathways.

Aging (Albany NY) 2020 05 18;12(10):9224-9239. Epub 2020 May 18.

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

Much data suggests intersecting activities between the adipokine apelin (APLN) and the pathologic processes of obesity and osteoarthritis (OA), with APLN modulating cartilage, synovium, bone, and various immune cell activities. The synovium plays an important role in the pathogenesis of OA. We investigated the crosstalk between APLN, a major OA-related adipokine, and interleukin 1 beta (IL-1β), a major proinflammatory cytokine, in human OA synovial fibroblasts (OASFs). We showed that APLN stimulated the synthesis of IL-1β in a concentration- and time-dependent manner, which was mitigated by blockade of the PI3K and ERK pathway. We also showed that APLN inhibited the expression of miRNA-144-3p, which blocks IL-1β transcription; this suppression activity was reversed via blockade of the PI3K and ERK pathway. Moreover, pathologic changes in OA cartilage were rescued when APLN was silenced by shAPLN transfection both and . Our evidence is the first to show that APLN stimulates the expression of IL-1β by activating the PI3K and ERK pathway and suppressing downstream expression of miRNA-144-3p in OASFs. We also demonstrate that knockdown of APLN expression by shAPLN transfection ameliorated changes in OA cartilage severity. These results shed light on OA pathogenesis and suggest a novel treatment pathway.
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http://dx.doi.org/10.18632/aging.103195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288923PMC
May 2020

S1P facilitates IL-1β production in osteoblasts via the JAK and STAT3 signaling pathways.

Environ Toxicol 2020 Sep 13;35(9):991-997. Epub 2020 May 13.

School of Medicine, China Medical University, Taichung, Taiwan.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)-1β is a critical proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL-1β expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-1β in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL-1β. Elevations in IL-1β mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P-promoted IL-1β expression. Our results indicate that S1P promotes the expression of IL-1β in osteoblasts via the S1P receptor and the JAK and STAT3 signaling pathways.
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http://dx.doi.org/10.1002/tox.22935DOI Listing
September 2020

Noggin Inhibits IL-1β and BMP-2 Expression, and Attenuates Cartilage Degeneration and Subchondral Bone Destruction in Experimental Osteoarthritis.

Cells 2020 04 10;9(4). Epub 2020 Apr 10.

School of Medicine, China Medical University, Taichung 404022, Taiwan.

Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1β) is abundantly expressed in OA and plays a crucial role in cartilage remodeling, although its role in the activity of chondrocytes in cartilage and subchondral remodeling remains unclear. In this study, stimulating chondrogenic ATDC5 cells with IL-1β increased the levels of bone morphogenetic protein 2 (BMP-2), promoted articular cartilage degradation, and enhanced structural remodeling. Immunohistochemistry staining and microcomputed tomography imaging of the subchondral trabecular bone region in the experimental OA rat model revealed that the OA disease promotes levels of IL-1β, BMP-2, and matrix metalloproteinase 13 (MMP-13) expression in the articular cartilage and enhances subchondral bone remodeling. The intra-articular injection of Noggin protein (a BMP-2 inhibitor) attenuated subchondral bone remodeling and disease progression in OA rats. We also found that IL-1β increased BMP-2 expression by activating the mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and specificity protein 1 (Sp1) signaling pathways. We conclude that IL-1β promotes BMP-2 expression in chondrocytes via the MEK/ERK/Sp1 signaling pathways. The administration of Noggin protein reduces the expression of IL-1β and BMP-2, which prevents cartilage degeneration and OA development.
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http://dx.doi.org/10.3390/cells9040927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226847PMC
April 2020

Seizure After Percutaneous Endoscopic Surgery-Incidence, Risk Factors, Prevention, and Management.

World Neurosurg 2020 06 3;138:411-417. Epub 2020 Apr 3.

Department of Orthopaedic Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan, Republic of China; Spine Center, China Medical University Hospital, China Medical University, Taichung, Taiwan, Republic of China; Department of Sport Medicine, College of Health Care, China Medical University, Taichung, Taiwan, Republic of China. Electronic address:

Background: Percutaneous endoscopic surgery is a popular surgery to treat lumbar spinal disorders. However, seizure after percutaneous endoscopic surgery is an unpredictable complication. The only prodromal sign for seizure currently known is neck pain. We reviewed the incidence of, and risk factors for, seizure during percutaneous endoscopic surgery and present the cases of 3 patients with seizure and our management.

Case Description: From October 2006 to March 2019, 3 of 816 patients (0.34%) with thoracic lumbar disorders who had undergone percutaneous endoscopic surgery experienced a seizure episode. The cases of those 3 patients were carefully reviewed. Studies of the risk factors for seizure after spinal procedures reported before June 13, 2019 were identified through a PubMed search. We found that infusion fluid containing cefazolin, the infusion rate, a prolonged operative time, the occurrence of a dural tear, and sevoflurane anesthesia might be associated with seizure, both described in the reported data and found in our experience. Three patients who experienced a seizure episode had had general anesthesia with sevoflurane, and the surgical approach used was interlaminar for a herniated disc in L5-S1. We noted a "red flag sign," namely an uncontrollable hypertension episode combined with a decreasing pulse rate, in all 3 patients who had experienced a seizure, which was not observed in the other patients. All 3 patients had received antihypertensive medication (labetalol) ≥3 times without response.

Conclusion: Seizure after percutaneous endoscopic surgery is rare, but lethal. Although its cause remains unknown, all risk factors for seizure should be checked and corrected immediately when a red flag sign, uncontrolled hypertension, appears.
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http://dx.doi.org/10.1016/j.wneu.2020.03.121DOI Listing
June 2020

Apelin Affects the Progression of Osteoarthritis by Regulating VEGF-Dependent Angiogenesis and miR-150-5p Expression in Human Synovial Fibroblasts.

Cells 2020 03 2;9(3). Epub 2020 Mar 2.

Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan.

Synovium-induced angiogenesis is central to osteoarthritis (OA) pathogenesis and thus a promising therapeutic target. The adipokine apelin (APLN) is involved in both OA pathogenesis and angiogenesis. We examined the role of APLN in synovium-induced angiogenesis by investigating the crosstalk between APLN and vascular endothelial growth factor (VEGF) expression in human OA synovial fibroblasts (OASFs). We found higher levels of APLN and VEGF expression in OA samples compared with normal samples. APLN-induced stimulation of VEGF expression and VEGF-dependent angiogenesis in OASFs was mitigated by FAK/Src/Akt signaling. APLN also inhibited levels of microRNA-150-5p (miR-150-5p), which represses VEGF production and angiogenesis. Analyses of an OA animal model showed that shAPLN transfection of OASFs rescued pathologic changes in OA cartilage and histology. Here, we found APLN enhances VEGF expression and angiogenesis via FAK/Src/Akt cascade and via downstream suppression of miR-150-5p expression. These findings help to clarify the pathogenesis of adipokine-induced angiogenesis in OA synovium.
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http://dx.doi.org/10.3390/cells9030594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140420PMC
March 2020

Trends and predictors of mortality in unstable pelvic ring fracture: a 10-year experience with a multidisciplinary institutional protocol.

World J Emerg Surg 2019 27;14:61. Epub 2019 Dec 27.

1Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.

Background: Pelvic ring fracture is often combined with other injuries and such patients are considered at high risk of mortality and complications. There is controversy regarding the gold standard protocol for the initial treatment of pelvic fracture. The aim of this study was to assess which risk factors could affect the outcome and to analyze survival using our multidisciplinary institutional protocol for traumatic pelvic ring fracture.

Material And Methods: This retrospective study reviewed patients who sustained an unstable pelvic ring fracture with Injury Severity Score (ISS) ≥ 5. All patients were admitted to the emergency department and registered in the Trauma Registry System of a level I trauma center from January 1, 2008, to December 31, 2017. The annular mortality rate after the application of our institutional protocol was analyzed. Patients with different systems of injury and treatments were compared, and regression analysis was performed to adjust for factors that could affect the rate of mortality and complications.

Results: During the 10-year study period, there were 825 unstable pelvic ring injuries, with a mean ISS higher than that of other non-pelvic trauma cases. The annual mortality rate declined from 7.8 to 2.4% and the mean length of stay was 18.1 days. A multivariable analysis showed that unstable initial vital signs, such as systolic blood pressure < 90 mmHg (odds ratio [OR] 2.53; confidence interval [CI] 1.11-5.73), Glasgow Coma Scale < 9 (OR 3.87; CI 1.57-9.58), 24 > ISS > 15 (OR 4.84; CI 0.85-27.65), pulse rate < 50 (OR 11.54; CI 1.21-109.6), and diabetes mellitus (OR 3.18; CI 1.10-9.21) were associated with higher mortality. No other specific system in the high Abbreviated Injury Scale increased the rates of mortality or complications.

Conclusion: Poor initial vital signs and Glasgow Coma Scale score, higher ISS score, and comorbidity of diabetes mellitus affect the mortality rate of patients with unstable pelvic ring fractures. No single system of injury was found to increase mortality in these patients. The mortality rate was reduced through institutional efforts toward the application of guidelines for the initial management of pelvic fracture.
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http://dx.doi.org/10.1186/s13017-019-0282-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935111PMC
July 2020

The Accuracy of 3D Printing Assistance in the Spinal Deformity Surgery.

Biomed Res Int 2019 11;2019:7196528. Epub 2019 Nov 11.

Department of Orthopaedic Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan.

Background: The pedicle screw is one of the main tools used in spinal deformity correction surgery. Robotic and navigated surgeries are usually used, and they provide superior accuracy in pedicle screw placement than free-hand and fluoroscopy-guided techniques. However, their high cost and space limitation are problematic. We provide a new solution using 3D printing technology to facilitate spinal deformity surgery.

Methods: A workflow was developed to assist spinal deformity surgery using 3D printing technology. The trajectory and profile of pedicle screws were determined on the image system by the surgical team. The engineering team designed drill templates based on the bony surface anatomy and the trajectory of pedicle screws. Their effectiveness and safety were evaluated during a preoperative simulation surgery. The surgery consisted in making a pilot hole through the drill template on a computed tomography- (CT-) based, full-scale 3D spine model for every planned segment. Somatosensory evoke potential (SSEP) and motor evoke potential (MEP) were used for intraoperative neurophysiological monitoring. Postoperative CT was obtained 6 months after the correction surgery to confirm the screw accuracy.

Results: From July 2015 to November 2016, we performed 10 spinal deformity surgeries with 3D printing technology assistance. In total, 173 pedicle screws were implanted using drill templates. No notable change in SSEP and MEP or neurologic deficit was noted. Based on postoperative CT scans, the acceptable rate was 97.1% (168/173). We recorded twelve pedicle screws with medial breach, six with lateral breach, and five with inferior breach. Medial breach (12/23) was the main type of penetration. Lateral breach occurred mostly in the concave side (5/6). Most penetrations occurred above the T8 level (69.6%, 16/23).

Conclusion: 3D printing technology provides an effective alternative for spinal deformity surgery when expensive medical equipment, such as intraoperative navigation and robotic systems, is unavailable.
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http://dx.doi.org/10.1155/2019/7196528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885147PMC
April 2020

Association of Matrix Metalloproteinase-9 rs3918242 Promoter Genotypes With Colorectal Cancer Risk.

Anticancer Res 2019 Dec;39(12):6523-6529

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.

Background/aim: Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk.

Materials And Methods: A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology.

Results: The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location.

Conclusion: MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.
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http://dx.doi.org/10.21873/anticanres.13867DOI Listing
December 2019

Increased risk of eczema after joint replacement: A population-based retrospective cohort study.

Medicine (Baltimore) 2019 Nov;98(45):e17914

School of Medicine, China Medical University.

There are very few reports of eczema and other prosthetic-related allergic skin complications following arthroplasty. We aimed to assess the risk of eczema after joint replacement.We performed a retrospective population-based cohort study in 2024 joint replacement patients using the Longitudinal Health Insurance Database. For comparison, 8096 controls were selected, with 4 control subjects for each joint replacement patient matched for age, sex, and index year, to assess eczema risk. We examined 14-year cumulative eczema incidence associated with age, sex, immunity, disease history, and joint replacement location.Eczema rates in the joint replacement patients were 38% higher than in the control group (57.90 vs 41.84 per 1000 person-years, respectively). Compared with the control group, joint replacement patients showed a 1.35-fold increased risk of eczema according to the multivariable Cox model (95% Confidence interval [CI] = 1.23-1.49). Knee replacement patients had higher eczema risk compared with the control group (Hazard ratio [HR] = 1.45, 95% CI = 1.33-1.70). Stratified by study period, the joint replacement cohort had a higher eczema risk after the 3-month follow-up.Our study revealed that joint arthroplasty increased risk of eczema in this 14-year follow-up study, and this was not related to personal atopic history or gender.
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http://dx.doi.org/10.1097/MD.0000000000017914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855572PMC
November 2019

Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis.

Int J Med Sci 2019 20;16(10):1397-1403. Epub 2019 Sep 20.

School of Medicine, China Medical University, Taichung, Taiwan.

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; = 0.01). Our findings suggest that gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the gene may be promising for RA treatment.
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http://dx.doi.org/10.7150/ijms.34659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818187PMC
April 2020
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