Background: Rheumatoid arthritis is characterized by chronic polyarticular synovitis and presents systemic changes that impact quality of life, such as impaired muscle function, seen in up to 66% of the patients. This can progress to severely debilitating state known as rheumatoid cachexia—without loss of fat mass and body weight—for which there is little consensus in terms of diagnosis or treatment. This study aims to evaluate whether the collagen‐induced arthritis (CIA) animal model also develops clinical and functional features characteristic of rheumatoid cachexia.Methods: Male DBA1/J mice were randomly divided into 2 groups: healthy animals (CO, n = 11) and CIA animals (n = 13). The clinical score and edema size, animal weight and food intake, free exploratory locomotion, grip strength, and endurance exercise performance were tested 0, 18, 35, 45, 55, and 65 days after disease induction. After euthanasia, several organs, visceral and brown fat, and muscles were dissected and weighed. Muscles were used to assess myofiber diameter. Ankle joint was used to assess arthritis severity by histological score. Statistical analysis were performed using one‐way and two‐way analyses of variance followed by Tukey's and Bonferroni's test or t‐test of Pearson and statistical difference were assumed for a P value under 0.05.Results: The CIA had significantly higher arthritis scores and larger hind paw edema volumes than CO. The CIA had decreased endurance exercise performance total time (fatigue; 23, 22, 24, and 21% at 35, 45, 55, and 65 days, respectively), grip strength (27, 55, 63, 60, and 66% at 25, 35, 45, 55, and 65 days, respectively), free locomotion (43, 57, 59, and 66% at 35, 45, 55, and 65 days, respectively), and tibialis anterior and gastrocnemius muscle weight (25 and 24%, respectively) compared with CO. Sarcoplasmic ratios were also reduced in CIA (TA: 23 and GA: 22% less sarcoplasmic ratio), confirming the atrophy of skeletal muscle mass in these animals than in CO. Myofiber diameter was also reduced 45% in TA and 41% in GA in CIA when compared with the CO. Visceral and brown fat were lighter in CIA (54 and 39%, respectively) than CO group.Conclusions: The CIA model is a valid experimental model for rheumatoid cachexia given that the clinical changes observed were similar to those described in patients with rheumatoid arthritis.

Although advanced age, male sex, and some comorbidities impact the clinical course of COVID-19, these factors only partially explain the inter-individual variability in disease severity. Some studies have shown that genetic polymorphisms contribute to COVID-19 severity; however, the results are inconclusive. Thus, we investigated the association between polymorphisms in ACE1, ACE2, DPP9, IFIH1, IFNAR2, IFNL4, TLR3, TMPRSS2, and TYK2 and the clinical course of COVID-19. A total of 694 patients with COVID-19 were categorized as: (1) ward inpatients (moderate symptoms) or patients admitted at the intensive care unit (ICU; severe symptoms); and (2) survivors or non-survivors. In females, the rs1990760/IFIH1 T/T genotype was associated with risk of ICU admission and death. Moreover, the rs1799752/ACE1 Ins and rs12329760/TMPRSS2 T alleles were associated with risk of ICU admission. In non-white patients, the rs2236757/IFNAR2 A/A genotype was associated with risk of ICU admission, while the rs1799752/ACE1 Ins/Ins genotype, rs2236757/IFNAR2 A/A genotype, and rs12329760/TMPRSS2 T allele were associated with risk of death. Moreover, some of the analyzed polymorphisms interact in the risk of worse COVID-19 outcomes. In conclusion, this study shows an association of rs1799752/ACE1, rs1990760/IFIH1, rs2236757/IFNAR2, rs12329760/TMPRSS2, and rs2304256/TYK2 polymorphisms with worse COVID-19 outcomes, especially among female and non-white patients.

Low-grade inflammation and oxidative stress are key mechanisms involved in obesity and related disorders. Polyphenols from blueberry (BB) and bilberries (BiB) might protect against oxidative damage and inflammation. To summarize the effects of BiB or BB consumption in parameters related to obesity and its comorbidities, a search of the literature was performed in PubMed, Embase, and Cochrane Library repositories to identify all studies that evaluated associations of whole BB or BiB with obesity and associated disorders. Thirty-one studies were eligible for inclusion in this review: eight clinical trials and 23 animal studies. In humans, BB consumption only consistently decreased oxidative stress and improved endothelial function. In rodents, BB or BiB consumption caused positive effects on glucose tolerance, nuclear factor-kappa B (Nf-κb) activity, oxidative stress, and triglyceride (TG) content in the liver and hepatic steatosis. The high content of anthocyanins present in BB and BiB seems to attenuate oxidative stress. The decrease in oxidative stress may have a positive impact on glucose tolerance and endothelial function. Moreover, in rodents, these berries seem to protect against hepatic steatosis, through the decreased accumulation of hepatic TGs. BB and BiB might also attenuate inflammation by decreasing Nf-κb activity and immune cell recruitment into the adipose tissue.

There is no consensus for diagnosis or treatment of RA muscle loss. We aimed to investigate metabolites in arthritic mice urine as biomarkers of muscle loss. DBA1/J mice comprised collagen-induced arthritis (CIA) and control (CO) groups. Urine samples were collected at 0, 18, 35, 45, 55, and 65 days of disease and subjected to nuclear magnetic resonance spectroscopy. Metabolites were identified using Chenomx and Birmingham Metabolite libraries. The statistical model used principal component analysis, partial least-squares discriminant analysis, and partial least-squares regression analysis. Linear regression and Fisher’s exact test via the MetaboAnalyst website were performed (VIP-score). Nearly 100 identified metabolites had CIA vs. CO and disease time-dependent differences (p < 0.05). Twenty-eight metabolites were muscle-associated: carnosine (VIPs 2.8 × 10²) and succinyl acetone (VIPs 1.0 × 10) showed high importance in CIA vs. CO models at day 65; CIA pair analysis showed histidine (VIPs 1.2 × 10²) days 55 vs. 65, histamine (VIPs 1.1 × 10²) days 55 vs. 65, and L-methionine (VIPs 1.1 × 10²) days 0 vs. 18. Carnosine was fatigue- (0.039) related, creatine was food intake- (−0.177) and body weight- (−0.039) related, and both metabolites were clinical score- (0.093; 0.050) and paw edema- (0.125; 0.026) related. Therefore, muscle metabolic alterations were detected in arthritic mice urine, enabling further validation in RA patient’s urine, targeting prognosis, diagnosis, and monitoring of RA-mediated muscle loss.

Single nucleotide polymorphisms (SNPs) in the HLA DR/DQ region have the greatest impact on susceptibility to type 1 diabetes mellitus (T1DM). Non-HLA SNPs interact with the HLA, influencing the risk for T1DM. The aim of this study was to develop a genetic risk score (GRS) based on HLA DR/DQ and non-HLA SNPs to discriminate patients with T1DM. The sample comprised 466 patients with T1DM and 469 controls. The rs689/INS, rs2476601/PTPN22, rs231775/CTLA-4, rs2304256/TYK2, rs2292239/ERBB3, and HLA DR/DQ SNPs were genotyped using real-time PCR. The unweighted GRS (uGRS) was calculated by summing the risk alleles of each SNP and the weighted GRS (wGRS) by multiplying the risk alleles by their odds ratios. The uGRS was higher in T1DM patients than in non-diabetic controls (0.34 ± 0.14 vs. 0.26 ± 0.13, P <0.0001), being positively correlated with HbA1c levels (P <0.0001). wGRSs exhibited higher AUCs than uGRSs. The wGRS containing only HLA DR/DQ SNPs showed an AUC of 0.75 (95% CI 0.72 - 0.78). The wGRS containing both HLA DR/DQ and non-HLA SNPs, adjusted for race, demonstrated the best discriminative power [AUC 0.91 (95% CI 0.89 - 0.93)]. The race adjusted-wGRS, including all SNPs, seems to be a useful genetic tool for assessing individual’s predisposition to T1DM.