Fused in sarcoma regulates glutamate signaling and oxidative stress response.

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor GLR-1. We found that fust-1 ALS mutations act as loss-of-function in SOD-1 and VGLUT/EAT-4 phenotypes, whereas the fust-1 ALS mutations act as gain-of-function in redox homeostasis and the microbe-induced oxidative stress response. We hypothesized that FUST-1 is a link between glutamate signaling and SOD-1. Our results may provide new insights into the human ALS alleles and their roles in pathological mechanisms that lead to ALS.

The mediating effect of depression on the relationship between osteoarthritis and cardiovascular disease mortality: A cohort study.

BACKGROUND: To explore the mediator role of depression in the association of osteoarthritis (OA) and cardiovascular disease (CVD) mortality based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: Totally 19,605 adults from NHANES 2009-2018 were included in this cohort study ultimately. The outcome was considered as the CVD related mortality in this study. The follow-up duration was 81.09 ± 1.05 months. Weighted univariate and multivariate linear regressions were used to explore the association between OA and depression. Weighted univariate and multivariate COX regressions were performed to assess the relationship of OA and CVD related mortality. Also, we analyzed the mediating role of depression on the association between OA and CVD mortality through the Sobel Test. RESULTS: The CVD related mortality in this study was 2.57 %. After adjusting age, gender, physical activity, history of CVD, history of hypertension and eGFR, OA was positively correlated with depression [ß = 0.78, 95 % confidence interval (CI) = 0.54-1.02], and OA was associated the death risk of CVD [hazard ratio (HR): 1.35, 95%CI, 1.09-1.68]. Additionally, depression slightly mediated the association between OA and CVD related mortality in this study, with this mediating variable accounting for 5.61 % of the association. CONCLUSION: OA was associated with depression and CVD related mortality, respectively. Additionally, the increased risk of CVD related mortality in OA patients may be slightly mediated by depression. These results serve as a reminder that giving careful attention to and effectively managing mental health may be beneficial to prevent CVD related mortality, especially for those with OA.

Neutrophil-Lymphocyte Ratio as a Predictor of Cerebral Small Vessel Disease in a Geriatric Community: The I-Lan Longitudinal Aging Study.

Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.

Superoxide dismutase SOD-3 regulates redox homeostasis in the intestine.

There are four cellular superoxide dismutase paralogs in C. elegans . The role of these superoxide dismutases in redox homeostasis remains largely unknown. Here, we generated the integrated redox reporter rxRFP to detect changes in redox homeostasis using live fluorescence imaging. We found that sod-3 deletion contributes to oxidative stress elevation. Deletions in additional paralogs ameliorate the oxidative stress of sod-3 . Complete elimination of all four paralogs elicits the same increase in rxRFP fluorescence as in the sod-3 single mutation, suggesting a compensatory role of other sod s. Our results suggest that SOD-3 plays a key role in regulating gut redox homeostasis.

Report of a Patient With Anti-Jo-1 Syndrome With Loss of Consciousness.

A 51-year-old febrile woman presented to the emergency department because of loss of consciousness while worshipping at a temple. She experienced muscle weakness and blurred vision before fainting. She also felt pain in her left shoulder and suffered from dry cough and shortness of breath during the previous week. The chest radiograph (CXR) showed bilateral reticular infiltration, indicating interstitial lung disease (ILD), and chest computed tomography revealed reticular, nodular, and reticulonodular patterns of infiltration that were compatible with ILD. Blood tests showed a creatinine kinase level of 3,307 IU/L and an Anti-Jo-1 autoantibody level of 586 AU/mL. It was found via right thigh biopsy results 8 days later that she had polymyositis with perivascular inflammation and degenerative muscle fiber change. Pulse therapy with methylprednisolone (1 gm/day for 3 days) was administered. After 4 days, she felt better and was discharged. Around 25.0%-34.1% of myositis patients have anti-Jo-1 autoantibodies, and ILD was noted in 65%-68% of anti-Jo-1-positive patients. A ground glass pattern may be observed in the CXRs of anti-Jo-1 ILD patients, and some articles described multiple pulmonary nodules mimicking lung metastasis or concomitant with pleural effusion. The conditions of approximately 42%-66% of ILD patients are controlled or are not worsened after treatment with corticosteroid and immunosuppressive drug treatment. However, some rapidly progressive cases are not sensitive to corticosteroid therapy alone.

Outcome of pregnancy in patients with systemic lupus erythematosus.

OBJECTIVE: To study the maternal and fetal outcomes in women with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Over a period of 10 years, 24 pregnancies in 17 females with SLE in a single center were enrolled. Fetal and maternal outcomes were studied retrospectively. RESULTS: The mean patient age was 27.7 years. Twenty-one of the 24 pregnancies occurred in the period of disease remission at the time of conception. Proteinuria presented in 12 pregnancies; however, no patient developed acute renal failure or deterioration of renal function. There were three cases of preeclampsia in this study. Two patients had their disease flare up and delivered stillborns. One woman with secondary antiphospholipid syndrome (APS) had a fetal loss. There was no maternal mortality. The mean gestation age was 34.3 weeks (range, 17-41 weeks), and the mean birth weight was 2,179 g. The mean APGAR scores were 8 and 9 at 1 and 5 minutes, respectively. One baby with congenital atrioventricular block was born to a mother with positive anti-SSA antibody. There were five cases (20.8%) of intrauterine growth retardation and 10 preterm deliveries (41.6%) in this study. CONCLUSION: Pregnancy is relatively safe in women with SLE in remission but should be considered as a high-risk pregnancy. APS is associated with poor pregnancy outcome. The patient needs to cooperate with obstetricians and physicians for optimal disease control and detailed monitoring throughout the gestation.