Descriptive epidemiology of soft tissue sarcomas and gastrointestinal stromal tumors in Thailand.

This study aimed to analyze burden of STS and GIST in population and survival rate which represented the current situation of treatment in Thailand. The data was collected from five population-based cancer registries around the country for the period 2001 through 2015. The Segi world standard population was used to calculated age-standardized incidence rates (ASR). Standardized rate ratios (SRR) were used to compare populations. Joinpoint Trend Analysis was used to assess changes in incidence. STATA was used to examine patient survival rates. During the study period, 4080 cases of STS and 457 cases of GIST were reported. The ASR of STS and GIST was 2.14/100,000 person-years and 0.22/100,000 person-years, respectively. The most common histological types of STS were unspecified sarcoma (24.8%), leiomyosarcoma (19.0%) and liposarcoma (11.4%). The overall ASR of STS in Thailand was relatively low compared to Western countries. The five-year survival rate was 62.6% for STS and 63.4% for GIST, which was comparable to the rates reported in other countries. This is the first report of STS and GIST from PBCRs in Thailand. Based on current healthcare service, an overall survival rates of STS and GIST are comparable to those reported from others.

Biochemistry of Amaranthus polyphenols and their potential benefits on gut ecosystem: A comprehensive review of the literature.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Amaranthus is phytonutrients-rich plant distributed worldwide and has been recognized as having medicinal value in traditional use against several diseases and conditions. There are a large amount of research data on the polyphenol profiles of Amaranthus plants and their links with potential benefits against gastrointestinal disorders. AIM OF THE REVIEW: This review article aims to provide a comprehensive review of Amaranthus phenolic compounds and their microbial metabolites, as well as the biological and/or pharmacological effects of those compounds/metabolites. METHODOLOGY: The relevant information about the genus Amaranthus was collected from various sources and databases, including Google Scholar, Google Books, PubMed, Web of Science, Scopus, Science Direct, and other internet sources. The World Flora Online (2021) database was used to verify the scientific names of the plants. RESULTS: Comprehensive review of identified compounds in Amaranthus plants revealed the presence of phenolic acids, flavonoids, and coumarins in each part of the plants. The biotransformation by gut microbiota enzymes prominently produces diverse bioactive metabolites that are potentially active than their precursors. Lines of the evidence support the beneficial roles of Amaranthus extracts in several gastrointestinal diseases, particularly with the polar extracts of several plant parts. Dietary fibers in Amaranthus plants also coordinate the alteration of gut microbiota-related metabolisms and may be beneficial to certain gastrointestinal disorders in particular, such as constipation. CONCLUSIONS: Amaranthus plants are rich in polyphenols and dietary fibers. Several microbial metabolites are biologically active, so alteration of gut microbiota is largely linked to the metabolic feature of the plants. Based on the evidence available to date, several Amaranthus plants containing a combination of phytonutrients, particularly polyphenols and dietary fibers, may be a promising candidate that is of interest to be further developed for use in the treatment of certain gastrointestinal conditions/disorders.

Kaempferia parviflora Extract Alleviated Rat Arthritis, Exerted Chondroprotective Properties In Vitro, and Reduced Expression of Genes Associated with Inflammatory Arthritis.

Kaempferia parviflora Wall. ex Baker (KP) has been reported to attenuate cartilage destruction in rat model of osteoarthritis. Previously, we demonstrated that KP rhizome extract and its active components effectively suppressed mechanisms associated with RA in SW982 cells. Here, we further evaluated the anti-arthritis potential of KP extract by using multi-level models, including a complete Freund's adjuvant-induced arthritis and a cartilage explant culture model, and to investigate the effects of KP extract and its major components on related gene expressions and underlying mechanisms within cells. In arthritis rats, the KP extract reduced arthritis indexes, with no significant changes in biological parameters. In the cartilage explant model, the KP extract exerted chondroprotective potential by suppressing sulfated glycosaminoglycans release while preserving high accumulation of proteoglycans. In human chondrocyte cell line, a mixture of the major components equal to their amounts in KP extract showed strong suppression the expression of genes-associated inflammatory joint disease similar to that of the extract. Additionally, KP extract significantly suppressed NF-κB and MAPK signaling pathways. The suppressing expression of necroptosis genes and promoted anti-apoptosis were also found. Collectively, these results provided supportive evidence of the anti-arthritis properties of KP extract, which are associated with its three major components.

Proinflammatory Effects of IL-1ß Combined with IL-17A Promoted Cartilage Degradation and Suppressed Genes Associated with Cartilage Matrix Synthesis In Vitro.

Combinations of IL-1ß and other proinflammatory cytokines reportedly promote the severity of arthritis. We aimed to investigate the effects of IL-1ß combined with IL-17A on cartilage degradation and synthesis in in vitro models. Cartilage explant degradation was determined using sulfated glycosaminoglycans (S-GAGs) levels, matrix metalloproteinase (MMP13) gene expression, uronic acid, and collagen contents. Cell morphology and accumulation of proteoglycans were evaluated using hematoxylin-eosin and safranin O staining, respectively. In the pellet culture model, expressions of cartilage-specific anabolic and catabolic genes were evaluated using real-time qRT-PCR. Early induction of MMP13 gene expression was found concomitantly with significant S-GAGs release. During the prolonged period, S-GAGs release was significantly elevated, while MMP-13 enzyme levels were persistently increased together with the reduction of the cartilaginous matrix molecules. The pellet culture showed anabolic gene downregulation, while expression of the proinflammatory cytokines, mediators, and MMP13 genes were elevated. After cytokine removal, these effects were restored to nearly basal levels. This study provides evidence that IL-1ß combined with IL-17A promoted chronic inflammatory arthritis by activating the catabolic processes accompanied with the suppression of cartilage anabolism. These suggest that further applications, which suppress inflammatory enhancers, especially IL-17A, should be considered as a target for arthritis research and therapy.

LL-37 alone and in combination with IL17A enhances proinflammatory cytokine expression in parallel with hyaluronan metabolism in human synovial sarcoma cell line SW982-A step toward understanding the development of inflammatory arthritis.

LL-37 is the only human cathelicidin-family host defense peptide and has been reported to interact with invading pathogens causing inflammation at various body sites. Recent studies showed high levels of LL-37 in the synovial-lining membrane of patients with rheumatoid arthritis, a common type of inflammatory arthritis. The present study aims to investigate the role of LL-37 on mechanisms associated with pathogenesis of inflammatory arthritis. The effects of LL-37 on the expression of proinflammatory cytokines, hyaluronan (HA) metabolism-related genes, cell death-related pathways, and cell invasion were investigated in SW982, a human synovial sarcoma cell line. Time-course measurements of proinflammatory cytokines and mediators showed that LL-37 significantly induced IL6 and IL17A mRNA levels at early time points (3-6 hr). HA-metabolism-related genes (i.e., HA synthase 2 (HAS2), HAS3, hyaluronidase 1 (HYAL1), HYAL2, and CD44) were co-expressed in parallel. In combination, LL-37 and IL17A significantly enhanced PTGS2, TNF, and HAS3 gene expression concomitantly with the elevation of their respective products, PGE2, TNF, and HA. Cell invasion rates and FN1 gene expression were also significantly enhanced. However, LL-37 alone or combined with IL17A did not affect cell mortality or cell cycle. Treatment of SW982 cells with both LL-37 and IL17A significantly enhanced IKK and p65 phosphorylation. These findings suggest that the chronic production of a high level of LL-37 may synchronize with its downstream proinflammatory cytokines, especially IL17A, contributing to the co-operative enhancement of pathogenesis mechanisms of inflammatory arthritis, such as high production of proinflammatory cytokines and mediators together with the activation of HA-metabolism-associated genes and cell invasion.

Ethanolic extract of Kaempferia parviflora interrupts the mechanisms-associated rheumatoid arthritis in SW982 culture model via p38/STAT1 and STAT3 pathways.

BACKGROUND: Kaempferia parviflora Wall. ex Baker (KP) has long been used in traditional medicine to treat various diseases because active compounds in rhizome extracts are important anti-inflammatory agents. PURPOSE: This study aims to investigate the effects of an ethanolic extract of KP on the molecular mechanisms associated with rheumatoid arthritis (RA), which was induced by a combination of proinflammatory cytokines (IL-1ß or TNF-α with IL-17A) in a human synovial sarcoma cell line (SW982) culture model. METHODS: SW982 cells pretreated with cytokines were incubated with KP extract at 3-30 µg/ml, or three major compounds of KP (5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, and 3,5,7,3',4'-pentamethoxyflavone) for up to 72 h. Dexamethasone was used as positive control. RA-associated genes and inflammatory products were measured in parallel with cell death genes. Apoptosis by flow cytometry and migration assay were also analyzed. Western blotting was used to examine the effects on intracellular signaling mechanisms. RESULTS: KP extract markedly reduced the expression of genes and levels of proinflammatory cytokines, inflammatory mediators, and matrix-degraded enzymes, but neither induced apoptosis nor altered the cell cycle. Its major constituents differently exerted suppressive effects on inflammatory genes. The KP extract downregulated the expression of genes associated with autophagosome and necroptosome formations. The extract also inhibited cell migration, reduced the mRNA expression of cadherin-11, and selectively reduced the phosphorylation of p38 MAPK, STAT1, and STAT3 signaling molecules, but did not interfere with the NF-κB pathway. CONCLUSION: These results suggest that the anti-arthritic potential of KP extract results from anti-inflammation and anti-migration via the suppression of the cytokines-induced p38/STAT1 and STAT3 pathways.

Suppression of Cartilage Degradation by Zingerone Involving the p38 and JNK MAPK Signaling Pathway.

Zingerone, an active compound that is present in cooked ginger, has been claimed to be a bioactive ingredient that holds the potential of preventing and/or treating diseases involving inflammation. In this study, zingerone was used to discover its properties against joint inflammation using interleukin-1ß-induced osteoarthritis in cartilage explant and cell culture models. Zingerone was supplemented into the cartilage explant and cell culture media at different concentrations along with the presence of interleukin-1ß, an inducer of osteoarthritis. Markers indicating cartilage degradation, inflammation, and the signaling molecules involved in the inflammatory induction were investigated. Diacerien, an anti-osteoarthritic drug, was used as a positive control. Zingerone at a concentration of 40 µM reduced the level of matrix metalloproteinase-13 to about 31.95 ± 4.33 % compared with the interleukin-1ß-treated group and halted cartilage explant degradation as indicated by reducing the accumulative release of sulfated glycosaminoglycans by falling to the control concomitantly with an elevation of the remaining contents of uronic acid and collagen in the explant tissues when zingerone was added. In the SW1353 cell line model, zingerone efficiently suppressed the expression of TNF-α, interleukin-6, and interleukin-8 mRNA levels and tended to reduce the levels of both p38 and c-Jun N-terminal kinase phosphorylation. From the results of this study, it can be concluded that zingerone potentially reduced cartilage degradation, which is partially involved in p38 and c-Jun N-terminal kinases of the mitogen activator protein kinase signaling pathway leading to the reduction of proinflammatory cytokine amplification effects and cartilage-degrading enzyme syntheses. This finding supports the contention that ginger holds positive pharmaceutical effects against osteoarthritis.