Comparative Analysis of Differentially Expressed Genes in Chondrocytes from Rats Exposed to Low Selenium and T-2 Toxin.

The aim of this study was to construct rat models of environmental risk factors for Kashin-Beck disease (KBD) with low selenium and T-2 toxin levels and to screen the differentially expressed genes (DEGs) between the rat models exposed to environmental risk factors. The Se-deficient (SD) group and T-2 toxin exposure (T-2) group were constructed. Knee joint samples were stained with hematoxylin-eosin, and cartilage tissue damage was observed. Illumina high-throughput sequencing technology was used to detect the gene expression profiles of the rat models in each group. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed and five differential gene expression results were verified by quantitative real-time polymerase chain reaction (qRT‒PCR). A total of 124 DEGs were identified from the SD group, including 56 upregulated genes and 68 downregulated genes. A total of 135 DEGs were identified in the T-2 group, including 68 upregulated genes and 67 downregulated genes. The DEGs were significantly enriched in 4 KEGG pathways in the SD group and 9 KEGG pathways in the T-2 group. The expression levels of Dbp, Pc, Selenow, Rpl30, and Mt2A were consistent with the results of transcriptome sequencing by qRT‒PCR. The results of this study confirmed that there were some differences in DEGs between the SD group and the T-2 group and provided new evidence for further exploration of the etiology and pathogenesis of KBD.

[Analysis of diet structure of Kashin-beck disease area in Chamdo-Lhorong of Tibet in 2021].

OBJECTIVE: To investigate and compare the dietary structure between healthy people and patients in KBD area of Chamdo-Lhorong of Tibet. METHODS: A case-control study design was used, retrospectively select patients who had completed screening and registered in the national Kashin-Beck Disease surveillance system in 2021 in Luolong County, Qamdo, Tibet as the source population of the case group, and randomly selected people who had not been screened for Kashin-Beck disease in the same county as the control group. The self-made diet questionnaire was used to record the types of food consumption, frequency of food intake, basic information of the respondents, family size and other basic information in the past year by one-on-one interview. RESULTS: The staple food with the highest response among the patients(97.33%) was rice(rice/rice noodle), and the highest response among the healthy people(90%) was non-wheat products, non-fried pasta(bread/steamed bun/noodles/dumplings), except instant noodles.78.7% of patients chose not to eat local wheat(Tibetan noodles), and the number of non-patients who chose to eat non-local wheat(Tibetan noodles) 3-4 times a week was significantly higher than that of patients. The meat and meat products with the highest response in both patients(93.33%) and healthy people(90%) was yak meat(local). The control group also chose to consume beef(non-local/lamb/mutton/other non-processed meat), poultry and livestock offal, fish(all seawater and freshwater fish), shrimp and crabs or other seafood, and their consumption rate and intake frequency were significantly higher than those of the case group. The consumption rate and frequency of tomato, onion and garlic(garlic shoots/leek/onion/onion) and fresh eggs(egg/duck egg/quail egg/goose egg) in control group were significantly higher than those in case group. There was no significant difference in consumption rate and frequency of fruits, milk and dairy products between the two groups. CONCLUSION: In addition to the local highland barley(zanba), most people also chose to purchase rice and flour, which changed the situation of single staple food in the past. However, compared with the healthy population in the disease area, the consumption rate and intake frequency of fish, shrimp and crabs, poultry and livestock viscera, eggs(fresh eggs) and vegetables(tomatoes, scallions, ginger and garlic) in KBD patients were significantly lower, the selection of meat varieties is single, mainly local yak meat, and the overall dietary structure still presents the risk of single type and unbalanced diet.

A Metabolomics Study of Feces Revealed That a Disturbance of Selenium-Centered Metabolic Bioprocess Was Involved in Kashin-Beck Disease, an Osteoarthropathy Endemic to China.

Background: Kashin-Beck disease (KBD) is a distinct osteoarthropathy in China with an unclear pathogenesis. This study aims to explore whether perturbations in the intestine metabolome could be linked to KBD individuals. Methods: An investigation was conducted in KBD endemic villages and fecal samples were collected. After applying inclusion and exclusion criteria, a total of 75 subjects were enrolled for this study, including 46 KBD (including 19 Grade I KBD and 27 Grade II KBD) and 29 controls. Untargeted metabolomics analysis was performed on the platform of UHPLC-MS. PLS-DA and OPLS-DA were conducted to compare the groups and identify the differential metabolites (DMs). Pathway analysis was conducted on MPaLA platform to explore the functional implication of the DMs. Results: Metabolomics analysis showed that compared with the control group, KBD individuals have a total of 584 differential metabolites with dysregulated levels such as adrenic acid (log2FC = -1.87, VIP = 4.84, p = 7.63 × 10-7), hydrogen phosphate (log2FC = -2.57, VIP = 1.27, p = 1.02 × 10-3), taurochenodeoxycholic acid (VIP = 1.16, log2FC = -3.24, p = 0.03), prostaglandin E3 (VIP = 1.17, log2FC = 2.67, p = 5.61 × 10-4), etc. Pathway analysis revealed several significantly perturbed pathways associated with KBD such as selenium micronutrient network (Q value = 3.11 × 10-3, Wikipathways), metabolism of lipids (Q value = 8.43 × 10-4, Reactome), free fatty acid receptors (Q value = 3.99 × 10-3, Reactome), and recycling of bile acids and salts (Q value = 2.98 × 10-3, Reactome). Subgroup comparisons found a total of 267 differential metabolites were shared by KBD vs. control, KBD II vs. control, and KBD I vs. control, while little difference was found between KBD II and KBD I (only one differential metabolite detected). Conclusions: KBD individuals showed distinct metabolic features characterized by perturbations in lipid metabolism and selenium-related bioprocesses. Our findings suggest that the loss of nutrients metabolism balance in intestine was involved in KBD pathogenesis. Linking the nutrients metabolism (especially selenium and lipid) to KBD cartilage damage should be a future direction of KBD study.

Research Progress of Selenium-Enriched Foods.

Selenium is an essential micronutrient that plays a crucial role in maintaining human health. Selenium deficiency is seriously associated with various diseases such as Keshan disease, Kashin-Beck disease, cataracts, and others. Conversely, selenium supplementation has been found to have multiple effects, including antioxidant, anti-inflammatory, and anticancer functions. Compared with inorganic selenium, organic selenium exhibits higher bioactivities and a wider range of safe concentrations. Consequently, there has been a significant development of selenium-enriched foods which contain large amounts of organic selenium in order to improve human health. This review summarizes the physiological role and metabolism of selenium, the development of selenium-enriched foods, the physiological functions of selenium-enriched foods, and provides an analysis of total selenium and its species in selenium-enriched foods, with a view to laying the foundation for selenium-enriched food development.

Selenomethionine Antagonized microRNAs Involved in Apoptosis of Rat Articular Cartilage Induced by T-2 Toxin.

T-2 toxin and selenium deficiency are considered important etiologies of Kashin-Beck disease (KBD), although the exact mechanism is still unclear. To identify differentially expressed microRNAs (DE-miRNAs) in the articular cartilage of rats exposed to T-2 toxin and selenomethionine (SeMet) supplementation, thirty-six 4-week-old Sprague Dawley rats were divided into a control group (gavaged with 4% anhydrous ethanol), a T-2 group (gavaged with 100 ng/g·bw/day T-2 toxin), and a T-2 + SeMet group (gavaged with 100 ng/g·bw/day T-2 toxin and 0.5 mg/kg·bw/day SeMet), respectively. Toluidine blue staining was performed to detect the pathological changes of articular cartilage. Three rats per group were randomly selected for high-throughput sequencing of articular cartilage. Target genes of DE-miRNAs were predicted using miRanda and RNAhybrid databases, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were enriched. The network map of miRNA-target genes was constructed using Cytoscape software. The expression profiles of miRNAs associated with KBD were obtained from the Gene Expression Omnibus database. Additionally, the DE-miRNAs were selected for real-time quantitative PCR (RT-qPCR) verification. Toluidine blue staining demonstrated that T-2 toxin damaged articular cartilage and SeMet effectively alleviated articular cartilage lesions. A total of 50 DE-miRNAs (28 upregulated and 22 downregulated) in the T-2 group vs. the control group, 18 DE-miRNAs (6 upregulated and 12 downregulated) in the T-2 + SeMet group vs. the control group, and 25 DE-miRNAs (5 upregulated and 20 downregulated) in the T-2 + SeMet group vs. the T-2 group were identified. Enrichment analysis showed the target genes of DE-miRNAs were associated with apoptosis, and in the MAPK and TGF-ß signaling pathways in the T-2 group vs. the control group. However, the pathway of apoptosis was not significant in the T-2 + SeMet group vs. the control group. These results indicated that T-2 toxin induced apoptosis, whereas SeMet supplementation antagonized apoptosis. Apoptosis and autophagy occurred simultaneously in the T-2 + SeMet group vs. T-2 group, and autophagy may inhibit apoptosis to protect cartilage. Compared with the GSE186593 dataset, the evidence of miR-133a-3p involved in apoptosis was more abundant. The results of RT-qPCR validation were consistent with RNA sequencing results. Our findings suggested that apoptosis was involved in articular cartilage lesions induced by T-2 toxin, whereas SeMet supplementation antagonized apoptosis, and that miR-133a-3p most probably played a central role in the apoptosis process.

The Role of Selenium-Mediated Notch/Hes1 Signaling Pathway in Kashin-Beck Disease Patients and Cartilage Injury Models.

Kashin-Beck disease (KBD) is a nutrition-related osteoarthropathy, and selenium (Se) deficiency is an environmental risk factor for KBD. Notch/Hes1 signaling pathway plays a vital role in regulating cartilage, but its exact mechanisms in KBD remain unknown. The Se contents were determined using the hydride atomic fluorescence spectrometry assay technique, and the mRNA levels were detected via quantitative real-time PCR. The chondrocyte injury models were established by Se deficiency and tert-butyl hydroperoxide (tBHP), respectively; apoptosis and necrosis rates were detected using Hoechst 33,342/PI and Annexin V-FITC/PI. The results showed that the Se levels in the flour of KBD areas were lower than that of the non-KBD areas, and the Se levels in the plasma of KBD patients were lower than that of the controls. The expressions of Notch1, Jagged1, and Hes1 were higher in the whole blood of KBD patients than those of the controls, and Notch1 was negatively correlated with the expression of BCL2, while was positively correlated with BAX. In injury, chondrocytes induced by low Se and tBHP, the expression of Notch1, Jagged1, and Hes1 increased, apoptosis and necrosis rates increased in Se deficiency and tBHP groups, while Se supplementation reversed it. Decreased plasma Se in KBD patients may be related to low dietary Se. Se deficiency might be involved in the pathological process of KBD by activating the Notch/Hes1 signaling pathway to induce excessive apoptosis of chondrocytes, the activation of Notch/Hes1 promotes oxidative injury, and Se supplementation could reverse it. The importance of Notch/Hes1 signaling pathway in KBD development will provide a new potential target for KBD.

Dietary and drinking water intake of essential trace elements in a typical Kashin-Beck disease endemic area of Tibet, China.

BACKGROUND: Essential trace elements (ETEs), such as copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), are very important elements for human health. METHODS: In this study, 89 drinking water samples and 85 highland barleys were collected from 48 villages in 11 townships, and the average daily dose (ADD) of ETEs were calculated, in addition, health effects of ETEs to rural residents in Luolong County, a typical Kashin-Beck disease (KBD) endemic area in Tibet, were assessed. RESULTS: The mean concentrations of Cu, Fe, Mn, Mo, Se, Zn in drinking water were 0.278 ± 0.264 µg·kg-1, 0.766 ± 0.312 µg·kg-1, 0.411 ± 0.526 µg·kg-1, 0.119 ± 0.223 µg·kg-1, 0.155 ± 0.180 µg·kg-1, and 0.804 ± 1.112 µg·kg-1, respectively; and mean concentrations of Cu, Fe, Mn, Mo, Se and Zn in highland barley were 3.550 ± 0.680 mg·kg-1, 81.17 ± 38.14 mg·kg-1, 14.03 ± 1.42 mg·kg-1, 0.350 ± 0.200 mg·kg-1, 0.0028 ± 0.0056 mg·kg-1, and 23.58 ± 3.10 mg·kg-1, respectively. The ADD of Cu in the study area was appropriate; the ADD of Fe and Mn in each township were higher than the maximum oral reference dose recommended by the National Health Commission of China, indicating that Fe and Mn had non-carcinogenic health risks; the ADD of Mo and Zn in 36.36% and 54.55% of the townships exceeded the maximum oral reference dose; and 72.73% of the townships had insufficient ADD of Se. The ADD of Mo, Cu and Se in different townships was significantly correlated with the prevalence of KBD. CONCLUSIONS: Therefore, in order to prevent and control the prevalence of KBD and ensure the health of local residents, it is necessary to reduce the intake of high concentrations of Fe, Mn and Zn in diet, as well as increase the intake of Mo, Cu, especially Se.

Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

MMP-10 Deficiency Effects Differentiation and Death of Chondrocytes Associated with Endochondral Osteogenesis in an Endemic Osteoarthritis.

OBJECTIVE: The objective of this study was to determine the matrix metalloproteinase-10 (MMP-10) expression pattern and to assess how it contributes to endochondral osteogenesis in Kashin-Beck disease (KBD). DESIGN: The cartilages of KBD patients, Sprague-Dawley rats fed with selenium (Se)-deficient diet and/or T-2 toxin, and ATDC5 cells were used in this study. ATDC5 cells were induced into hypertrophic chondrocytes using a 1% insulin-transferrin-selenium (ITS) culture medium for 21 days. The expressions of MMP-10 in the cartilages were visualized by immunohistochemistry. The messenger RNA (mRNA) and protein expression levels were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting. MMP-10 short hairpin RNA (shRNA) was transfected into hypertrophic chondrocytes to knock down the gene expression of MMP-10. Meanwhile, the cell death of MMP-10-knockdown chondrocyte was detected using flow cytometry. RESULTS: The expression of MMP-10 was decreased in the growth plates of children with KBD. A decreased expression of MMP-10 also was observed in the growth plates of rats fed with an Se-deficient diet and/or T-2 toxin exposure. The mRNA and protein expression levels of MMP-10 increased during the chondrogenic differentiation of ATDC5 cells. MMP-10 knockdown in hypertrophic chondrocytes significantly decreased the gene and protein expression of collagen type II (Col II), Col X, Runx2, and MMP-13. Besides, the percentage of cell apoptosis was significantly increased after MMP-10 knockdown in hypertrophic chondrocytes. CONCLUSION: MMP-10 deficiency disrupts chondrocyte terminal differentiation and induces the chondrocyte's death, which impairs endochondral osteogenesis in the pathogenesis of KBD.

Investigation of selenium nutritional status and dietary pattern among children in Kashin-Beck disease endemic areas in Shaanxi Province, China using duplicate portion sampling method.

BACKGROUND AND OBJECTIVES: Selenium deficiency is a primary risk factor of Kashin-Beck disease (KBD). This study aimed to investigate whether children in endemic areas could maintain sufficient selenium intake after termination of selenium supplement administration, and evaluate their comprehensive nutritional status and dietary structure. METHODS: Duplicate portion sampling combined with a questionnaire was adopted to collect data on categories and quantity of all food ingested in three consecutive days. Occipital hair was also collected to detect selenium content by hydride generation atomic fluorescence spectrometry (HGAFS). CDGSS3.0 software and factor analysis were integrated to assess the children's comprehensive nutritional status and dietary structure. RESULTS: This study included 240 sex-matched (1:1) children aged 7-12 years from KBD endemic (n = 120) and non-endemic (n = 120) areas. Overall, 720 solid food, 720 liquid, and 240 hair samples were collected for selenium determination. The mean selenium level in hair of children in endemic areas (0.38 ± 0.16 mg/kg) was significantly lower than that in children in non-endemic areas (0.56 ± 0.28 mg/kg, Z = -5.249, p < 0.001). The dietary selenium intake of children in endemic areas was 40.0% lower than that in children in non-endemic areas (Z = -9.374, p < 0.001). Children in endemic areas consumed significantly less diverse dietary items leading to significantly less intake of multiple nutrients compared to children in non-endemic areas. CONCLUSIONS: The dietary selenium intake of most children in endemic areas was less than the recommended amount. The dietary structure of children was undiversified, which limited the intake of multiple nutrients. Therefore, comprehensive nutrition rather than sole selenium intake should be the primary concern in the future.

Hydrochemical characteristics of surface waters and their relationships to the Kashin-Beck Disease in Longzi County, Tibet.

Although previous studies have been reported between the Kashin-Beck Disease (KBD) epidemic and the hydrochemical characteristics of surface waters, the etiology of the disease remains unclear. In the present study, we comprehensively investigated the relationship between the KBD and the hydrochemical characteristics of surface waters in Longzi County. Results show that, the pH (mean = 7.27 ± 0.30), total hardness (TH, mean = 57.08 ± 45.74 mg L-1), total dissolved solids (TDS, mean = 67.56 ± 44.00 mg L-1) and oxidation-reduction potential (ORP, mean = 84.11 ± 23.55 mV) of surface waters in KBD endemic areas are lower than those in the non-KBD endemic areas (means of pH = 7.49 ± 0.30; TH = 262.06 ± 123.29 mg L-1; TDS = 253.25 ± 100.39 mg L-1; ORP = 215.90 ± 55.99 mV). These results suggest that long-term consumption of low TDS, essential trace elements (e.g., nickel, cobalt, iron, selenium, zinc, molybdenum, and iodine) deficient, and potential toxic elements (e.g., arsenic) enriched waters by humans likely causes the KBD. Environmental factors such as the geology and geomorphology may produce biogeochemical imbalance, geomorphic, vegetation types and local climatic conditions may have significant impact on food fungi toxin poisoning and water organic compound poisoning, and these also impact the KBD occurrence.

Growth surveillance indices and Kashin-Beck Disease in children.

Selenium, manganese, and calcium are necessary elements for maintaining normal growth and skeleton formation. Kashin-Beck disease mostly occurs in children, resulting in deformities, dwarfism, and disabilities. Selenium deficiency was considered a risk factor in China, while manganese was reportedly involved in it in Russia. Single-element regulation cannot be used in diagnosis because of unclear boundaries in patients compared to healthy individuals. In this study, new indices of elements were designed to predict the status of disease. MS (Mn/Se), CS (Ca'/Se), and MC (Mn/Ca') values were designed, and prediction formulas were generated by comparing healthy children with those with Kashin-Beck disease via multiple linear regression analysis and discriminant analysis. In the disease group, 42.86% of patients had positive MS, CS, and MC values, and 57.14% of patients had positive MS and CS values. In the treatment group, the patients presented improved indices. In the prediction group, subjects with negative clinical criteria features were predicted by new indices, and 26.67% of them presented with positive MS, CS, and MC values, whereas 40.00% had positive MS and CS values. The 3D model of MS, CS, and MC refers to the setup of elements. The MS, CS, and MC indices are helpful in disease prediction, diagnosis, prognosis, and surveillance. The distribution model of the indices could serve in the growth surveillance of children.

Abnormal Level of Manganese, Iron, Iodine, and Selenium in the Hair of Children Living in Kashin-Beck Disease Endemic Areas.

Biological geochemistry is a main suggested cause of Kashin-Beck disease (KBD), due to the absence or excess of elements in the environment. Initially, Se deficiency is regarded as the most key role in the etiology of KBD, and selenium supplementation effectively helps to prevent and control KBD. However, several elements are reported to be relevant to KBD or selenium in succession, which indicated selenium deficiency is not the original etiology of KBD. The study comprehensively analyzed the characteristics of the bio-element profile of KBD and further re-examined the unique role of selenium in etiology. The study measured 14 elements, including sodium, potassium, calcium, phosphorus, magnesium, copper, iron, zinc, selenium, iodine, manganese, lead, arsenic, and mercury, which were detected from hair samples collected from 150 boys. Research participants were separated based on whether they had received any preventative treatment (with and without selenium supplementation). From endemic areas, 30 KBD and 30 healthy children without any preventative treatment were selected alongside 30 KBD and 30 healthy children with selenium supplementation. The participants from endemic areas were then compared to 30 healthy children living in non-endemic areas. Compared to the non-endemic group, the levels of iron and manganese were all significantly higher in the endemic groups and were further elevated in KBD participants (p < 0.05). In contrast, selenium and iodine levels in endemic areas were much lower than those of the control group (p < 0.05). The proportions of selenium excess (p < 0.05) and iodine deficiency (p < 0.05) in endemic groups were significantly lower than participants from non-endemic areas. Meanwhile, excess levels of iron (p < 0.05) and manganese (p < 0.05) were higher in the endemic groups. Moreover, the proportions of Zn/Fe and Se/Mn were found to be significantly lower in endemic area participants than those in the control group (p < 0.05). Three pairs of elements had a correlation coefficient value of more than 0.6: 0.7423 for manganese and calcium, 0.6446 for potassium and sodium, and 0.6272 for manganese and iron. The ratios of Se/Mn and Zn/Fe were associated with a correlation coefficient value of 0.8055. Magnesium, sodium, copper, and iodine levels were meticulously examined using binary regression analysis. This was also used to determine the ratios of Ca/Mg, Ca/P, Zn/Fe, Se/Mn, and Se/I. Thus, the study largely revealed the vital role of manganese, iron, and iodine (in conjunction with selenium) in KBD etiology and pathogenesis. High manganese and iron levels with low selenium and iodine levels were identified as characteristic features of the bio-element profile of KBD. The different element ratios reflect the interaction between several elements. The most significant of these were the proportions of Se/Mn and Zn/Fe, which may be significant in the occurrence and development of KBD.

Status and potential diagnostic roles of essential trace elements in Kashin- Beck disease patients.

BACKGROUND: This updated and comprehensive meta-analysis study sought to explore the changes of seven essential trace elements, including selenium (Se), iron (Fe), zinc (Zn), manganese (Mn), fluorine (F), iodine (I) and copper (Cu) in Kashin-Beck disease (KBD) patients compared with healthy individuals. The findings of the current study will provide a valuable reference for implementation of early clinical intervention and prevention of KBD. METHODS: All related articles included in this review were retrieved from the following databases: Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, China Biology Medicine disc (CBM disc), PubMed and Web of Science up to April 30, 2020. The following combination keywords were used as the search criteria: "(Kashin-Beck disease OR KBD) AND ((selenium OR iron OR zinc OR manganese OR fluorine OR iodine OR copper) OR (Se OR Fe OR Zn OR Mn OR F OR I OR Cu))". All statistical analyses were performed using RevMan 5.3 and Stata 16.0 software. RESULTS: A total of 55 articles were included in the current study. Meta-analysis showed that the levels of serum Se (SMD = -2.37, 95 % CI: -1.58 to -0.72, P < 0.00001), hair Se (SMD = -2.19, 95 % CI: -3.05 to -1.33, P < 0.00001), urinary Se (SMD = -2.36, 95 % CI: -3.26 to -1.46, P < 0.00001) and erythrocyte Se (SMD = -5.12, 95 % CI: -9.55 to -0.69, P = 0.02) were significantly lower in KBD patients compared with the levels in healthy controls. Then, the findings showed that the levels of serum F (SMD = -0.58, 95 % CI: -1.04 to -0.12, P = 0.01) and hair I (SMD = -0.57, 95 % CI: -1.06 to -0.08, P = 0.02) in patients were substantially lower than that in controls. Analysis showed that the levels of hair Zn (SMD = 0.26, 95 % CI: 0.04 to 0.49, P = 0.02) and hair Mn (SMD = 0.55, 95 % CI: 0.24 to 0.85, P = 0.0005) were markedly higher in patients compared with the levels in healthy controls. Notably, urinary Se (AUC = 0.7851, P = 0.0235, Sensitivity = 81.82 %, Specificity = 81.82 %) showed a good diagnostic value for KBD. CONCLUSIONS: The findings of the current study showed that the levels of Se, serum F and hair I were lower in patients with KBD compared with those in healthy controls, whereas the levels of hair Zn and hair Mn were higher in KBD patients compared with the levels in controls. This outcome would be further validated in our future studies. Of note, these results indicated that Se, F and I deficiencies were associated with the pathogenesis of KBD.

Effectiveness of Selenium on Chondrocyte Glycoprotein Glycosylation Which Play Important Roles in the Pathogenesis of an Endemic Osteoarthritis, Kashin-Beck Disease.

In this study, we aimed to explore the effectiveness of selenium on the chondrocyte glycoprotein glycosylation which plays important roles in the pathogenesis of Kashin-Beck disease (KBD). Cartilage samples were collected from KBD patients after total knee replacement surgery. Chondrocytes were cultured with sodium selenium. The group of chondrocytes which were cultured without adding sodium selenium was considered as control group. Lectin microarray was used to screen the differences in lectin levels between KBD and KBD with selenium groups. Stronger signals for Bandeiraea simplicifolia (BS-I), Hippeastrum hybrid lectin (HHL), Pisum sativum agglutinin (PSA), Psophocarpus tetragonolobus lectin I (PTL-I), Psophocarpus tetragonolobus lectin II (PTL-II), Sophora japonica agglutinin (SJA), Lotus tetragonolobus lectin (LTL), and Triticum vulgaris (WGA) were observed in the KBD group. Meanwhile, Aleuria aurantia lectin (AAL), Lens culinaris agglutinin (LCA), Lycopersicon esculentum (tomato) lectin (LEL), Peanut agglutinin (PNA), and Sambucus nigra lectin (SNA) signals were lower in the KBD group. Selenium may have the function of influence the expression levels of carbohydrate chains Galα1,3-Gal, high mannose, and GlcNAc.

Dysregulation of Transcription Profile of Selenoprotein in Patients with Kashin-Beck Disease and Its Effect on Se Deficiency-Induced Chondrocyte Apoptosis.

Kashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy related to selenium (Se) deficiency. Se participates in the synthesis of selenoprotein in the form of selenocysteine. In total, 25 selenoproteins, encoded by 25 genes, are currently found in humans; however, the effects of selenoprotein genes on chondrocyte apoptosis, particularly in apoptosis-related genes, remain poorly elucidated. Therefore, in the current study, the expression of selenoprotein genes and apoptosis-related genes were determined by RT-qPCR in patients and chondrocytes and the correlations between them were analyzed using Pearson and Spearman's rank correlation, and the chondrocyte apoptosis rate was detected by Annexin V-FITC/PI. The results showed that the mRNA levels of 17 selenoprotein genes were downregulated, whereas two genes were upregulated in patients with KBD. The BAX/BCL2 ratio and the mRNA levels of BAX and P53 were increased, but the mRNA levels of BCL2 and NF-κB p65 were decreased in patients with KBD. The mRNA levels of GPX2, GPX3, DIO1, TXNRD1, TXNRD3, and SPS2 were most closely associated with apoptosis-related genes in patients with KBD. Moreover, in the Se deficiency group, the mRNA levels of GPX3, DIO1, and TXNRD1 were downregulated and GPX activity was decreased, but the late apoptosis rate, the mRNA levels of BAX and P53, and the BAX/BCL2 ratio were increased; the opposite trend was observed in the Se supplement group. Collectively, these results indicate that selenoprotein transcription profile is dysregulated in patients with KBD. Furthermore, the expression of GPX3, DIO1, and TXNRD1 genes might be involved in the development of chondrocyte apoptosis by affecting antioxidant capacity.

Progress of Selenium Deficiency in the Pathogenesis of Arthropathies and Selenium Supplement for Their Treatment.

Selenium, an essential trace element for human health, exerts an indispensable effect in maintaining physiological homeostasis and functions in the body. Selenium deficiency is associated with arthropathies, such as Kashin-Beck disease, rheumatoid arthritis, osteoarthritis, and osteoporosis. Selenium deficiency mainly affects the normal physiological state of bone and cartilage through oxidative stress reaction and immune reaction. This review aims to explore the role of selenium deficiency and its mechanisms existed in the pathogenesis of arthropathies. Meanwhile, this review also summarized various experiments to highlight the crucial functions of selenium in maintaining the homeostasis of bone and cartilage.

Mechanism of DNA methylation-mediated downregulation of O6-methylguanine-DNA methyltransferase in cartilage injury of Kashin-Beck disease.

OBJECTIVE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, in which excessive apoptosis of chondrocytes occurs. O6-methylguanine-DNA methyltransferase (MGMT), a DNA damage repair gene, plays an important role in apoptosis, but the mechanism is unclear in KBD cartilage injury. This study was to investigate the expression and promoter methylation of MGMT in KBD patients and its role in DNA damage and apoptosis of chondrocytes. METHODS: MGMT mRNA and protein level were detected by quantitative real-time PCR and immunohistochemistry. Demethylation of MGMT was carried out using 5-Aza-2'-deoxycytidine, and the methylation level of MGMT promoter was measured by quantitative methylation specific PCR. Next, small hairpin RNA was used to knockdown the expression of MGMT. Cell viability, apoptosis and DNA damage were determined by MTT assay, flow cytometry, Hoechst 33342 staining and alkaline comet assay following T-2 toxin and selenium treatment. RESULTS: MGMT protein expression and mRNA levels were decreased (P = 0.02, P = 0.007) and promoter methylation was increased (P = 0.008) in KBD patients. Meanwhile, MGMT level was upregulated by 5-Aza-2'-deoxycytidine in chondrocytes (P = 0.0002). DNA damage and apoptosis rates were increased in MGMT-silenced chondrocytes (all P < 0.0001). Furthermore, DNA damage and apoptosis were increased in chondrocytes treated with T-2 toxin (all P < 0.0001), but were decreased after selenium treatment (P < 0.0001, P = 0.01). Decreased mRNA level and increased methylation of MGMT were found in the T-2 toxin group (P = 0.005, P = 0.002), while selenium reversed it (P = 0.02, P = 0.004). CONCLUSIONS: MGMT might play a crucial part in the pathogenesis of KBD cartilage injury, which could provide a therapeutic target for KBD.

Differences of selenium and other trace elements abundances between the Kaschin-Beck disease area and nearby non-Kaschin-Beck disease area, Shaanxi Province, China.

In order to find out the environmental geochemical characteristics of KBD affected area, KBD and non-KBD villages in KBD Counties, Weibei KBD area, Shaanxi Province, China were studied. Contents of Se and other elements in soil, wheat, maize and drinking water were analyzed. The results show that soil of Weibei KBD area is deficient in trace elements comparing with BSC and non-KBD area. Wheat of Weibei KBD area is deficient both in major elements and trace elements comparing with REC. Wheat of KBD village is especially deficient in Cr, Co, Se, Mo and Mg. Contents of Sr, Li and Mo in wheat of KBD village are significantly lower than nearby non-KBD village, but the average Se content is slightly higher. The deficiency of trace elements, especially Se, Sr, Li and Mo in staple food and trace elements in soil, is the main characteristic for the environment of KBD area.

[Evaluation of dietary diversity of rural residents in Arun Banner, a typical area of low selenium belt in China].

OBJECTIVE: To understand the dietary diversity and food sources of different groups in Arun Banner. Comparing and analyzing the changes of dietary diversity of local residents in different periods. METHODS: In October 2019, according to the differences of Kashin-Beck disease conditions and land use patterns of Arun Banner, Hulun Buir, 78 rural residents were randomly selected from four villages to investigate the frequency of daily food consumption by using self-made food frequency questionnaire. Dietary diversity score(DDS) was used to evaluate the dietary diversity of different populations. RESULTS: The average DDS of the investigated residents was 9. 76±2. 32. DDS of the residents of Minzu and Tieshan villages(10. 14±2. 66) in the West was higher than that of Longtoushan and Hongqi villages(9. 42±1. 95) in the East. However, the difference was not statistically significant(Z=-1. 875, P& gt; 0. 05). DDS in males(10. 37±2. 47) was significantly higher than that in females(9. 36±2. 14)(P& lt; 0. 05). There was no significant difference in DDS(9. 52±2. 29) between Kashin-Beck disease affected patients and healthy residents(9. 85±2. 34)(Z=-0. 601, P& gt; 0. 05). There was no significant difference in DDS among different age groups. The average of DDS was higher in those younger than 60 years old(9. 90±2. 35). Residents mainly eat rice and flour, and the proportion of purchasing food from other places reaches 96% and 95%, respectively. CONCLUSION: The staple food in Arun Banner was mainly rice and flour purchased from other places. The dietary structure of residents tends to be diversified. Residents reduced dependence on low selenium natural environment is an important factor for local selenium-susceptible endemic diseases to be stable and gradually controlled.