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Cytokines as biochemical markers for knee osteoarthritis

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World Journal of Orthopedics 2015年第1期6卷 95-105页

作者： Thomas Mabey sittisak honsawek Department of Biochemistry Faculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial HospitalThai Red Cross Society

Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.

关键词： Biomarker Cytokines Interleukin Knee osteoarthritis

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

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World Journal of Gastroenterology 2010年第43期16卷 5467-5473页

作者： sittisak honsawek Maneerat Chayanupatkul Voranush Chongsrisawat Paisarn Vejchapipat Yong Poovorawan Department of Biochemistry Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Department of Physiology Faculty of Medicine Chulalongkorn University Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University Department of Surgery Faculty of Medicine Chulalongkorn University

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

关键词： Biliary atresia Fibroscan Jaundice Liver stiffness Osteopontin

Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

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World Journal of Hepatology 2016年第33期8卷 1471-1477页

作者： Wanvisa Udomsinprasert sittisak honsawek Napaphat Jirathanathornnukul Voranush Chongsrisawat Yong Poovorawan Department of Biochemistry Faculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial HospitalThai Red Cross Society Center of Excellence in Clinical Virology Department of PediatricsFaculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial HospitalThai Red Cross Society

AIMTo investigate serum urokinase-type plasminogen activator receptor (uPAR) and liver stiffness in biliary atresia (BA) and examine the correlation of circulating uPAR, liver stiffness, and clinical outcomes in postoperative BA children. METHODSEighty-five postKasai BA children and 24 control subjects were registered. Circulating uPAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography. RESULTSBA children had significantly greater circulating uPAR and liver stiffness scores than control subjects (P P r = 0.507, P r = 0.364, P r = 0.559, P r = 0.325, P r = 0.508, P CONCLUSIONCirculating uPAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating uPAR was associated with liver dysfunction in BA. As a consequence, serum uPAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in postKasai BA.

关键词： Biliary atresia Jaundice Liver stiffness Severity Urokinase plasminogen activator receptor

Glomus tumors of the fingers:Expression of vascular endothelial growth factor

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World Journal of Orthopedics 2016年第12期7卷 843-846页

作者： sittisak honsawek Pravit Kitidumrongsook Pobe Luangjarmekorn Kawee Pataradool Voranuch Thanakit Adisorn Patradul Vinai Parkpian Orthopaedic Research Center Department of OrthopaedicsFaculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial Hospital Department of Biochemistry Faculty of MedicineChulalongkorn University Department of Pathology Faculty of MedicineChulalongkorn University

Glomus tumors are uncommon,benign,small neuro-vascular neoplasms derived from glomus bodies in the reticular dermis. Glomus bodies are found throughout the body to regulate body temperature and skin circulation; however,they are concentrated in the fingers and the sole of the foot. The typical presentation is a solitary nodule in the subungual or periungual area of the distal phalanx. The primary treatment of choice is surgical removal. We investigated expression of vascular endothelial growth factor(VEGF) using immunohistochemistry in glomus tumors of the fingers. All five glomus tumor samples were positive for VEGF expression. VEGF immunoreactivity was largely localized to the cytoplasm of tumor cells,suggesting a contribution of VEGF to the vascularization of glomus tumors.

关键词： Glomus tumors Fingers Vascular endotheligrowth factor

Low bone mineral density and the severity of cholestasis in biliary atresia

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World Journal of Hepatology 2017年第16期9卷 746-751页

作者： Krittapak Homchan Tawatchai Chaiwatanarat Wanvisa Udomsinprasert Voranush Chongsrisawat Yong Poovorawan sittisak honsawek Center of Excellence in Clinical Virology Department of PediatricsFaculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial HospitalThai Red Cross Society Department of Radiology Faculty of MedicineChulalongkorn University Department of Biochemistry Faculty of MedicineChulalongkorn University

AIM To investigate the prevalence of osteopenia and osteoporosis in postoperative biliary atresia(BA) children and the association of bone mineral density(BMD) and biochemical parameters in post Kasai BA subjects. METHODS A total of 70 patients with post Kasai BA were enrolled in this prospective study. The patients were classified into two groups according to their jaundice status. BMD of the lumbar spine was analyzed using dual energyX-ray *** The prevalence of low bone mass(osteopenia and osteoporosis) in BA patients were 51.4%(36 out of 70). Ten patients(35.7%) in the jaundice group and 8 patients(19.0%) in the non-jaundice group had osteopenia. Sixteen patients(57.1%) in the jaundice group and 2 patients(4.8%) in the no jaundice group had osteoporosis. In addition, lumbar spine BMD Z-score was substantially lower in the jaundice BA patients compared with non-jaundice patients. BA subjects with persistent jaundice had significantly lower serum 25-hydroxyvitamin D than those without jaundice. Further analysis revealed that lumbar spine BMD was correlated with age(r = 0.774, P < 0.001), serum albumin(r = 0.333, P = 0.005), total bilirubin(r =-0.476, P < 0.001), aspartate aminotransferase(r =-0.583, P < 0.001), alanine aminotransferase(r =-0.428, P < 0.001), and alkaline phosphatase(r =-0.456, P < 0.001).CONCLUSION Low BMD was associated with biochemical parameters reflecting the severity of cholestasis in post Kasai BA patients.

关键词： Bone mineral density Jaundice Biliary atresia Cholestasis Severity

Association of adiponectin gene polymorphisms with knee osteoarthritis

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World Journal of Orthopedics 2017年第9期8卷 719-725页

作者： Dong Zhan Suthimon Thumtecho Aree Tanavalee Pongsak Yuktanandana Wilai Anomasiri sittisak honsawek Department of Biochemistry Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Thai Red Cross Society Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Thai Red Cross Society Vinai Parkpian Orthopaedic Research Center Department of Orthopaedics Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Thai Red Cross Society

AIM To investigate the possible relationship of adiponectin(ADIPOQ) gene polymorphisms, plasma adiponectin, and the risk of knee osteoarthritis(OA).METHODS A total of 398 subjects, 202 knee OA patients and 196 healthy individuals, were enrolled in the case-control study. Genotyping at +45T/G(rs2241766) and +276G/T(rs1501299) loci was performed using polymerase chain reaction-restriction fragment length polymorphism. Plasma adiponectin levels were assessed using enzymelinked immunosorbent assay. OA severity was determined using the Kellgren-Lawrence(KL) grading *** No significant associations were observed in the genotype distributions and allele frequencies at two loci of +45T/G and +276G/T polymorphisms in the ADIPOQ betweenknee OA patients and control subjects. There was a significant association between genotype distribution of +276G/T polymorphism and KL grade 2, 3 or 4(P = 0.037, P = 0.046, P = 0.016, respectively). At +45T/G locus, the percentage of GG genotype was notably greater in control subjects(13.40%) compared with OA subjects(1.70%)(P = 0.023). Plasma adiponectin was markedly decreased in OA subjects compared with control subjects(P = 0.03). Likewise, circulating adiponectin in OA subjects was notably lesser than that in control subjects in GG genotype of +45T/G(P = 0.029) and +276G/T polymorphisms(P = 0.012).CONCLUSION Polymorphisms +45T/G and +276G/T of the ADIPOQ gene might not be responsible for OA susceptibility among Thais.

关键词： Adiponectin ADIPOQ Polymorphism Knee osteoarthritis Plasma

Adiponectin as a novel biomarker for liver fibrosis

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World Journal of Hepatology 2018年第10期10卷 708-718页

作者： Wanvisa Udomsinprasert sittisak honsawek Yong Poovorawan Department of Biochemistry Faculty of Pharmacy Mahidol University Department of Biochemistry Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Center of Excellence in Clinical Virology Department of Pediatrics Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital

Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cellmediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptoralpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases(CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin onliver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.

关键词： Adiponectin Hyperadiponectinemia Liver fibrosis Chronic liver disease Biomarker

Mesenchymal stem cells for cartilage regeneration in osteoarthritis

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World Journal of Orthopedics 2017年第9期8卷 674-680页

作者： Baldur Kristjánsson sittisak honsawek Department of Biochemistry Faculty of Medicine Chulalongkorn University King Chulalongkorn Memorial Hospital Thai Red Cross Society Department of Orthopaedics Vinai Parkpian Orthopaedic Research Center Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Thai Red Cross Society

Osteoarthritis(OA) is a slowly progressive disease where cartilage of the synovial joint degenerates. It is most common in the elderly where patients experience pain and reduce physical activity. In combination with lack of conventional treatment, patients are often left with no other choices than arthroplasty. Over the last years, multipotent stromal cells have been used in efforts to treat OA. Mesenchymal stem/progenitor cells(MSCs) are stromal cells that can differentiate into bone, fat, and cartilage cells. They reside within bone marrow and fat. MSCs can also be found in synovial joints where they affect the progression of OA. They can be isolated and proliferated in an incubator before being applied in clinical trials. When it comes to treatment, emphasis has hitherto been on autologous MSCs, but allogenic cells from healthy donors are emerging as another source of the cells. The first adaptations of MSCs revolved in the use of cellrich matrix, delivered as invasive surgical procedure, which resulted in production of hyaline cartilage and fibrocartilage. However, the demand for less invasive delivery of cells has prompted the use of direct intraarticular injections, wherein a large amount of suspended cells are implanted in the cartilage defect.

关键词： Intra-articular injection Mesenchymal stem cells Osteoarthritis Regeneration Cartilage

Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2020年第1期21卷 42-52页

作者： Dong ZHAN Aree TANAVALEE Saran TANTAVISUT Srihatach NGARMUKOS Steven WEDWARDS sittisak honsawek Joint PhD Program in Biomedical Sciences and Biotechnology Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Department of Biochemistry Osteoarthritis and Musculoskeleton Research UnitFaculty of MedicineKing Chulalongkorn Memorial HospitalThai Red Cross SocietyChulalongkorn UniversityBangkok 10330Thailand Department of Orthopaedics Vinai Parkpian Orthopaedic Research CenterFaculty of MedicineKing Chulalongkorn Memorial HospitalThai Red Cross SocietyChulalongkorn UniversityBangkok 10330Thailand Institute of Integrative Biology University of LiverpoolLiverpool L697ZBUK

Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the *** purpose of this study was to investigate mitochondrial DNA copy number(mtDNACN)and inflammatory cytokines in primary knee OA patients and healthy volunteers.A total of 204 knee OA patients and 169 age-matched healthy volunteers were *** relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction(qRT-PCR),and ten inflammatory cytokines in their plasma were detected by multiplex *** leukocyte mtDNACN in the OA group was significantly lower than that in the control *** mtDNACN in the control group was negatively correlated with their age(r=−0.380,P<0.0001),whereas mtDNACN in the OA group was positively correlated with their age(r=0.198,P<0.001).Plasma interleukin-4(IL-4)and IL-6 were significantly higher in the knee OA group than in the control *** plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group(r=0.547,P=0.0014).IL-5 showed as a major factor(coefficient 0.69)in the second dimension of principle components analysis(PCA)-transformed data and was significantly higher in the OA group(P<0.001)as well as negatively correlated with mtDNACN(r=−0.577,P<0.001).These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee ***-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.

关键词： Inflammatory cytokine Blood leukocyte Knee Mitochondrial DNA copy number Osteoarthritis