n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not: NHANES 2007-2016.

Background and aims: Gout, the most prevalent inflammatory arthritis, has undesirable effects on the quality of life. Omega-3 polyunsaturated fatty acids (n-3 PUFA) has a strong link with anti-inflammatory impacts. However, whether the harmful effects of seafood in relation to gout may vary owing to different levels of n-3 PUFA in seafood is still unclear. It was the goal of this study to examine the relationship between n-3 PUFA poor/rich seafood consumption and gout. Methods: Between 2007 and 2016, five NHANES cycles were performed, with 12,505 subjects having complete data for gout and two 24-h dietary intake interviews. The 24-h dietary recalls were utilized to evaluate dietary habits. Gout was defined based on questionnaires. Weighted logistic regression models were conducted to investigate the association between n-3 PUFA poor/rich seafood consumption and gout. Moreover, subgroup analysis was utilized to estimate the stability of results. Covariates including age, gender, race/ethnicity, income, education, body mass index, chronic kidney disease, diabetes mellitus, hypertension, smoking status, and drinking status were stratified in different models. Results: In the fully adjusted model, each unit of increase of n-3 PUFA poor seafood intake was associated with an 8.7% increased risk of gout (OR = 1.087, 95% CI: 1.039, 1.138, P < 0.001), whereas, no correlation was found between n-3 PUFA rich seafood consumption and gout. It also provided a proof-of-concept regarding the potential for n-3 PUFA rich seafood to counteract harmful effects of purines in relation to gout. A dose-response analysis showed that there was a non-linear relationship between n-3 PUFA rich seafood intake and the risk of gout in the female group. Conclusion: Findings suggest that n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not.

Relationship between diet-related inflammation and bone health under different levels of body mass index.

BACKGROUND: Osteoporosis is a major public health problem. Dietary inflammatory preference and body mass index (BMI) are emerging factors that tends to affect bone health. There is limited evidence regarding the joint influence of BMI and dietary status on the bone health. This study aimed to investigate the relationship between dietary inflammatory index (DII) and bone health among adults under different levels of BMI utilizing the National Health and Nutrition Examination Survey (NHANES). METHODS: Data were collected from 2005-2010, 2013-2014 to 2017-2018 in NHANES. In total, 10,521 participants who aged ≥ 20 years and had complete data for dietary intake interview, bone mineral density (BMD) and bone mineral content (BMC) were included. DII was performed to evaluate the dietary inflammatory potential based on dietary intake interview. We evaluated bone health by femoral neck BMD and BMC measured by dual energy X-ray absorptiometry. Weighted multivariable linear regression and BMI-stratified subgroup analysis were performed. RESULTS: The average DII score for 10,521 participants was 1.24 ± 0.04, mean femoral neck BMD was 0.82 ± 0.00 g/cm2 and mean BMC was 4.37 ± 0.01 g. In the fully adjusted model, there was a negative correlation between DII with BMD (ß = - 0.016, P < 0.001) and BMC (ß = - 0.011, P < 0.001) in the most anti-inflammatory diet. Using BMI-stratified subgroup analysis, this correlation became more evident in both the overweight (BMD: ß = - 0.024, P < 0.001; BMC: ß = - 0.058, P = 0.042) and obese groups (BMD: ß = - 0.015, P = 0.049; BMC: ß = - 0.009, P = 0.042), while this correlation was opposite in DII tertile 2 (middle DII score) in the underweight group (BMD: ß = 0.047, P = 0.038; BMC: ß = 0.274, P = 0.010). CONCLUSION: Relationship between higher consumption of pro-inflammatory and increased risk of lower BMD and BMC was only existed in overweight and obese participants.

Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats.

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats. Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman's correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO. Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

MiR-291a-3p regulates the BMSCs differentiation via targeting DKK1 in dexamethasone-induced osteoporosis.

Osteoporosis is a skeleton disease affecting 55% of people over age 60, and the number is still increasing due to an ageing population. One method to prevent osteoporosis is to increase the formation of new bone while preventing the resorption of older bone. Thus, osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of osteoporosis. On the other hand, glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders, but long-term exposure to GCs can induce osteoporosis. In present study, we treated BMSCs with dexamethasone (DEX) to simulate GC-induced osteoporosis. MTT assay, ALP activity, and Alizarin Red were used to evaluate the role miRNA-291a-3p in the DEX-induced osteogenic differentiation suppression. Further, we used qPCR and western blot to investigate the mechanisms of miRNA-291a-3p affecting BMSCs differentiation. The results showed that miRNA-291a-3p could improve the cell viability, osteogenic differentiation, and ALP activity, which are suppressed by DEX in BMSCs. Furthermore, we found that the osteogenesis genes Runx2, DMP1, and ALP were upregulated whereas the lipogenic genes C/EBPα and PPARγ were downregulated when miRNA-291a-3p mimics were transfected. Additionally, we demonstrated that miRNA-291a-3p promoted BMSCs' osteogenic differentiation by directly suppressing DKK1 mRNA and protein expression and subsequently activating Wnt/ß-catenin signaling pathway. Our study suggests that miR-291a-3p plays an important role in preventing osteoporosis and may serve as a potential miRNA osteoporosis biomarker.

Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment.

BACKGROUND: Intervertebral disc degeneration is a pathological process that involves an inflammation response. As a classical cellular feature, several studies have demonstrated that inflammation can promote nucleus pulposus (NP) cell apoptosis. Therefore, attenuation of NP cell apoptosis may be a potential way to retard disc degeneration. OBJECTIVE: The present study was aimed to investigate the protective effects of osteogenic protein-1 (OP-1) against NP cell apoptosis in an inflammation environment, and the potential signaling transduction pathway. METHODS: Rat NP cells were cultured in medium with or without inflammatory cytokine tumor necrosis factor (TNF)-α for 6 days. The exogenous TNF-α was added into the medium to investigate its protective effects. NP cell apoptosis was evaluated by cell apoptosis ratio, caspase-3 activity, gene/protein expression of apoptosis-related molecules (Bcl-2, Bax, and caspase-3). Additionally, the intracellular reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed. RESULTS: Compared with the control NP cells, TNF-α significantly increased cell apoptosis ratio, caspase-3 activity, gene/protein expression of Bcl-2, Bax and caspase-3, ROS content, and activity of the NF-κB pathway. However, OP-1 partly attenuated these effects in NP cells treated with TNF-α. CONCLUSION: OP-1 is effective in attenuating TNF-α-caused NP cell apoptosis, and the ROS/NF-κB pathway may be the potential signaling transduction pathway. The present study indicates that OP-1 may be helpful to inhibit inflammation-mediated disc degeneration.

Interleukin-1ß secreted from betanodavirus-infected microglia caused the death of neurons in giant grouper brains.

High interleukin (IL)-1ß gene expression was observed in dead giant grouper brains after nervous necrosis virus (NNV) infection. To investigate the neuronal death caused by NNV infection, primary tissue culture of giant grouper brains (pGB) was performed. In NNV-infected pGB cells, the viral capsid protein was detected in both neurons and microglia; furthermore, microglial proliferation and neuronal death were observed. The culture supernatant (CS) of NNV-infected pGB cells contained IL-1ß and tumor necrosis factor-α, which were mainly released from the microglia. A new batch of pGB cells was treated with CS, resulting in neuronal death, which could be prevented by blocking the IL-1ß in the CS by using anti-IL-1ß polyclonal antibodies. Moreover, pGB cells treated with recombinant IL-1ß showed microglial proliferation and neuronal death. Thus, NNV infection may activate microglial proliferation and stimulate microglial secretion of IL-1ß, which is a critical cytokine responsible for neuronal death in NNV-infected grouper brains.

Upregulation of a disintegrin and metalloprotease 8 influences tumor metastasis and prognosis in patients with osteosarcoma.

To investigate the clinicopathological and prognostic value of a disintegrin and metalloprotease 8 (ADAM8) in osteosarcoma. ADAM8 expression in osteosarcoma tissues was examined by immunohistochemistry in 69 patients. ADAM8 was positively expressed in 61 of 69 (88.4%) osteosarcoma specimens with cytoplasmic staining, and also increased in the specimens with recurrence (P = 0.008) and metastasis (P = 0.002). Patients with strong ADAM8 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with the patients with the weak expression of ADAM8. On multivariate analysis, ADAM8 expression was found to be an independent prognostic factor for both OS (P < 0.001) and DFS (P < 0.001). Our results suggest for the first time that ADAM8 might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with osteosarcoma.

Effect of 5/6 nephrectomized rat serum on epithelial-to-mesenchymal transition in vitro.

OBJECTIVE: To investigate whether the 5/6 nephrectomized (5/6Nx) rats' 12-week serum could lead to tubular epithelial-to-mesenchymal transition (EMT) and its molecular mechanism, so as to probe the potential stimulation from circulation in chronic progressive kidney disease. METHODS: A total of 24 Sprague Dawley (SD) rats were randomly divided into two groups: sham operation group (sham group) and 5/6Nx group. Rats were killed 12 weeks after surgery to obtain 5/6Nx rats' 12-week serum. Then we detected the expression of E-cadherin in renal tubular epithelial cells of the remaining kidney and we investigated whether the 12th week serum of 5/6Nx rats could cause HK-2 (human kidney proximal tubular cell line) cells to transdifferentiate into fibroblasts. RESULTS: Our data confirmed that E-cadherin expression decreased significantly in the remaining kidney at 12 weeks, and the 5/6Nx rats' 12-week serum could suppress E-cadherin protein and mRNA expression (p < 0.05). We also found that the 5/6Nx rats' 12-week serum could upregulate ZEB1, ß-catenin, and wnt3 protein expression (p < 0.05). CONCLUSIONS: Our results demonstrated that the 5/6Nx rats' 12-week serum could suppress the expression of E-cadherin in HK-2 cells. It was partially through modulating the increase of ZEB1. The loss of E-cadherin could lead ß-catenin to localize to the cytoplasm and nucleus, and feed into the Wnt signaling pathway. It means that the pathogenic serum in chronic kidney disease (CKD) plays an important role in the loss of renal function and turns to be a new avenue of research with potential clinical implications.