Causal Association Between Tea Consumption and Gout:A Mendelian Randomization Study

Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.

Erratum to: Melatonin Alleviates Acute Gouty Inflammation In Vivo and In Vitro

The authors examined the original data of their work and noticed some mistakes.The ELISA kit was bought from IBL Co.Germany instead of Abcam Co,UK.The anti-NLRP3,anti-IL-1βand anti-caspase-1 primary antibodies were from CST Co,USA.There were 31 acute gout patients and 25 gout patients in remission who met the American Rheumatism Society(ACR)diagnostic criteria of gout in this study,and 7 normal individuals were recruited as controls.The authors sincerely apologize for the mistakes and confirm that the changes do not affect the scientific conclusion of the published work.

Melatonin Alleviates Acute Gouty Inflammation In Vivo and In Vitro

The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms.We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals.The mRNA expression of melatonin receptor 2(MT2)was also lower in gout patients than in normal individuals.To verify the in-vivo role of melatonin,a gouty arthritis model was established by intraarticular injection of monosodium urate(MSU,1 mg)crystals into the paws of C57BL/6 mice.Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw,and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin(H&E)staining.Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model,and melatonin also reduced the mRNA levels of interleukin-1 beta(IL-1β),IL-6 and NLR family pyrin domain containing 3(NLRP3)inflammasome.To mimic gouty inflammation in vitro,mouse peritoneal macrophages were stimulated with lipopolysaccharides(LPS)plus MSU.Melatonin was revealed to reduce IL-1βsecretion by stimulated macrophages.The mRNA expression levels of IL-1βand IL-6 were also inhibited by melatonin.Western blot analysis showed that the expression of NLRP3,caspase-1 and pro-IL-1βwas also inhibited by melatonin.In conclusion,our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro,and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome.

Erratum to: Melatonin Alleviates Acute Gouty Inflammation In Vivo and In Vitro

The authors examined the original data of their work and noticed some mistakes.The ELISA kit was bought from IBL Co.Germany instead of Abeam Co,UK.The anti-NLRP3,anti-IL-lp and anti-caspase-1 primary antibodies were from CST Co,USA.There were 31 acute gout patients and 25 gout patients in remission who met the American Rheumatism Society(ACR)diagnostic criteria of gout in this study,and 7 normal individuals were recruited as controls.The authors sincerely apologize for the mistakes and confirm that the changes do not affect the scientific conclusion of the published work.

Adiponectin receptor agonist AdipoRon relieves endotoxin-induced acute hepatitis in mice

Background:Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored.Methods:BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups.Results:AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01;from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced.Conclusions:These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis.