Optogenetically engineered calcium oscillations promote autophagy-mediated cell death via AMPK activation.

Autophagy is a double-edged sword for cells; it can lead to both cell survival and death. Calcium (Ca2+) signalling plays a crucial role in regulating various cellular behaviours, including cell migration, proliferation and death. In this study, we investigated the effects of modulating cytosolic Ca2+ levels on autophagy using chemical and optogenetic methods. Our findings revealed that ionomycin and thapsigargin induce Ca2+ influx to promote autophagy, whereas the Ca2+ chelator BAPTA-AM induces Ca2+ depletion and inhibits autophagy. Furthermore, the optogenetic platform allows the manipulation of illumination parameters, including density, frequency, duty cycle and duration, to create different patterns of Ca2+ oscillations. We used the optogenetic tool Ca2+-translocating channelrhodopsin, which is activated and opened by 470 nm blue light to induce Ca2+ influx. These results demonstrated that high-frequency Ca2+ oscillations induce autophagy. In addition, autophagy induction may involve Ca2+-activated adenosine monophosphate (AMP)-activated protein kinases. In conclusion, high-frequency optogenetic Ca2+ oscillations led to cell death mediated by AMP-activated protein kinase-induced autophagy.

Clinical and serological factors associated with lupus pericarditis: a case-control study.

OBJECTIVE: Lupus pericarditis, a common manifestation of systemic lupus erythematosus (SLE), can be fatal. We examined the prevalence of lupus pericarditis and its associated factors in a Taiwanese SLE cohort. METHODS: Patients with SLE treated at Change Gung Memorial Hospital between January 2005 and December 2012 were included, and their age, sex, SLE disease duration, SLE disease activity index (SLEDAI) score, laboratory test results, comorbidities, and treatment regimen were noted. Factors related to lupus pericarditis were examined using univariate and multivariate logistic regression analyses. RESULTS: Of the 689 patients, 88.7% were women; age at diagnosis (± standard deviation (SD)) was 40.78 ± 15.59 years, and disease duration at study entry was 11.93 ± 8.21 years. The prevalence of lupus pericarditis was 16.4% (n = 113). Notably, older age at diagnosis (p = 0.0165), longer disease duration (p = 0.009), higher SLEDAI score (p < 0.0001), renal disorder (p = 0.003), lymphocytopenia (p < 0.0001), thrombocytopenia (p = 0.004), and anti-phospholipid antibody (aPL) seropositivity (p = 0.002) were significantly associated with lupus pericarditis. In multivariate analysis, adjusted for sex, SLE disease duration, age, and SLEDAI score, patients with lymphocytopenia and aPL seropositivity were related to a twofold (odds ratio (OR) 2.015, 95% confidence interval (CI) 1.091-3.858) and 1.5-fold (OR 1.569, 95% CI 1.017-2.421) greater prevalence of lupus pericarditis, respectively. CONCLUSIONS: Lupus pericarditis occurred in approximately one fifth of patients in this cohort. Patients with SLE with lymphocytopenia or anti-phospholipid antibody seropositivity were associated with a higher rate of lupus pericarditis. Key Points • Lupus pericarditis is a common manifestation of SLE that occurred in one-fifth patients in this study. • Lymphocytopenia and aPL antibody seropositivity are associated with a higher likelihood of developing lupus pericarditis. • Patients with lupus pericarditis should be identify early and treated with caution to prevent further morbidity and mortality.

Exploring the Risk Factors for Poor Survival in Lupus Pericarditis Patients: A Retrospective Cohort Study.

Patients with systemic lupus erythematosus (SLE) have a higher risk of pericarditis, which could be fatal. The goal of this study was to identify the prognostic factors for mortality in patients with lupus pericarditis. Patients with lupus pericarditis treated at Chang Gung Memorial Hospital were included in this observational cohort study. This study conducted univariate and multivariate COX regression, as well as Kaplan−Meier survival curve analysis, to investigate mortality risk in SLE patients. The average age at admission was 40.78 ± 15.92 years. A total of 113 (16.4%) of the 689 patients had lupus pericarditis. Patients with lupus pericarditis exhibited older age, shorter follow-up, higher disease activities, and higher incidence rates of comorbidities than patients without pericarditis. Cox regression adjusted analysis indicated that lupus pericarditis (hazard ratio = 1.963, 95% CI = 1.315, 2.963, p = 0.001), old age at admission (HR = 1.053, 95% CI = 1.040, 1.065, p < 0.001), high SLEDAI score (HR = 1.079, 95% CI = 1.043, 1.116, p < 0.001), and end-stage kidney disease (ESKD) (HR = 2.533, 95% CI = 1.620, 3.961, p < 0.001) were all linked to increased mortality. Moreover, the Kaplan−Meier survival curve analysis revealed that patients with pericarditis compared to those without pericarditis had a higher mortality rate (log-rank test, p < 0.001). A high proportion of SLE patients have manifestations of lupus pericarditis. Moreover, patients with lupus pericarditis have a greater risk of mortality even if they have no pericardial tamponade. Therefore, these patients need prompt diagnosis and treatment.