Emerging Roles of NPQ/Spexin in Physiology and Pathology

Spexin (SPX), also called neuropeptide Q (NPQ), is a novel endogenous neuropeptide. Spexin gene and protein are widely expressed in central nervous system and peripheral tissues in humans, rodents, goldfish, etc. A few of physiological and pathological roles of spexin are gradually emerged recently. This article summarized the roles of spexin in feeding behavior, gastrointestinal motility, obesity, diabetes, energy metabolism, endocrine, mental diseases, and cardiovascular function. Given the broad roles of spexin, this neuropeptide has attracted much interest from investigators and will be as a promising future target for novel therapeutic research and drug design

Prolonged dual antiplatelet therapy in patients with non-ST-segment elevation myocardial infarction: 2-year findings from EPICOR Asia.

BACKGROUND: Patients with non-ST-segment elevation myocardial infarction (NSTEMI) have a generally poor prognosis and antithrombotic management patterns (AMPs) used post-acute coronary syndrome (ACS) remain unclear. Duration of dual antiplatelet therapy (DAPT) and patient characteristics was evaluated in NSTEMI patients enrolled in EPICOR Asia. HYPOTHESIS: Patients stopping DAPT early may benefit from more intensive monitoring. METHODS: EPICOR Asia was a prospective, real-world, primary data collection, cohort study in adults with an ACS, conducted in eight countries/regions in Asia, with 2 year follow-up. Eligible patients were hospitalized within 48 hours of symptom onset and survived to discharge. We describe AMPs and baseline characteristics in NSTEMI patients surviving ≥12 months with DAPT duration ≤12 and > 12 months post-discharge. Clinical outcomes (composite of death, myocardial infarction, and stroke; and bleeding) were also explored. RESULTS: At discharge, 90.8% of patients were on DAPT (including clopidogrel, 99%). At 1- and 2-year follow-up, this was 79.2% and 60.0%. Patients who stopped DAPT ≤12 months post-discharge tended to be older, female, less obese, have prior cardiovascular disease, and have renal dysfunction. While causality cannot be inferred, the incidence of the composite endpoint over the subsequent 12 months was 10.6% and 3.1% with shorter vs longer use of DAPT, and mortality risk over the same period was 8.4% and 1.6%. CONCLUSIONS: Over 90% of NSTEMI patients were discharged on DAPT, with 60% on DAPT at 2 years. Patients stopping DAPT early were more likely to have higher baseline risk and may therefore benefit from more intensive monitoring during long-term follow-up

Potential benefits of vitamin D for sepsis prophylaxis in critical ill patients

BackgroundVitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection.MethodsThis retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups.ResultsThe results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35–0.60; P < 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92; P = 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77–1.35; P = 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort.ConclusionVitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection

A Conscious Resting State fMRI Study in SLE Patients Without Major Neuropsychiatric Manifestations

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the main causes of death in patients with systemic lupus erythematosus (SLE). Signs and symptoms of NPSLE are heterogeneous, and it is hard to diagnose, and treat NPSLE patients in the early stage. We conducted this study to explore the possible brain activity changes using resting state functional magnetic resonance imaging (rs-fMRI) in SLE patients without major neuropsychiatric manifestations (non-NPSLE patients). We also tried to investigate the possible associations among brain activity, disease activity, depression, and anxiety. In our study, 118 non-NPSLE patients and 81 healthy controls (HC) were recruited. Rs-fMRI data were used to calculate the regional homogeneity (ReHo) in all participants. We found decreased ReHo values in the fusiform gyrus and thalamus and increased ReHo values in the parahippocampal gyrus and uncus. The disease activity was positively correlated with ReHo values of the cerebellum and negatively correlated with values in the frontal gyrus. Several brain areas showed correlations with depressive and anxiety statuses. These results suggested that abnormal brain activities might occur before NPSLE and might be the foundation of anxiety and depression symptoms. Early detection and proper treatment of brain dysfunction might prevent the progression to NPSLE. More studies are needed to understand the complicated underlying mechanisms

Risk analysis of depression among adult patients with epilepsy of different sex: a retrospective single-center study from China

ObjectiveTo determine sex differences in the prevalence of depression and assess the risk factors for depression among adult patients with epilepsy from the Dali area of China.MethodsWe retrospectively analyzed the clinical data of adult patients with epilepsy who visited the First Affiliated Hospital of Dali University from January 2017 to January 2022. Patient Health Questionnaire-9 was used to assess depressive symptoms in patients with epilepsy. The risk factors of depression were analyzed by binary logistic regression among different sex in patients with epilepsy.ResultsThere were significant sex differences in depression in patients with epilepsy (p < 0.001), and females were 4.27 times more likely to suffer from depression than males (95% confidence interval: 3.70–4.92). The risk factors for depression among female patients with epilepsy included occupation (p < 0.001), years with epilepsy (p < 0.001), seizure frequency (p < 0.001), seizure type (p < 0.001), etiology (p < 0.001), number of antiseizure medications used (p < 0.001), antiseizure medications (p < 0.001), and electroencephalogram findings (p < 0.001). The risk factors for depression among male patients with epilepsy included age (p < 0.001), ethnicity (p < 0.001), occupation (p < 0.001), years with epilepsy (p < 0.001), seizure frequency (p < 0.001), seizure type (p < 0.001), etiology (p < 0.001), number of antiseizure medications used (p < 0.001), antiseizure medications (p < 0.001), and electroencephalogram findings (p < 0.001).ConclusionAdult female patients with epilepsy had a higher risk of depression than adult male patients with epilepsy. There were sex differences in the risk factors associated with depression among patients with epilepsy

Necrostatin-1 Attenuates Trauma-Induced Mouse Osteoarthritis and IL-1β Induced Apoptosis via HMGB1/TLR4/SDF-1 in Primary Mouse Chondrocytes

Necrostatin-1 (Nec-1) is a specific small molecule inhibitor of receptor-interacting protein kinase 1 (RIPK1) that specifically inhibits phosphorylation of RIPK1. RIPK1 regulates inflammation and cell death by interacting with receptor-interacting serine/threonine protein kinases 3(RIPK3). We hypothesized that Nec-1 may have anti-inflammatory efficacy in patients with osteoarthritis (OA), as the pathophysiology of OA involves the activation of inflammation-related signaling pathways and apoptosis. In this study, we explored the effects of Nec-1 on interleukin (IL)-1β-induced inflammation in mouse chondrocytes and the destabilised medial meniscus (DMM) mouse model. Inhibiting RIPK1 with Nec-1 dramatically suppressed catabolism both in vivo and in vitro, but did not inhibit changes in subchondral bone. Nec-1 abolished the in vitro increases in matrix metalloproteinase (MMP) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTs5) expression induced by IL-1β. However, adding high-mobility group box 1 (HMGB1) partially abrogated this effect, indicating the essential role of HMGB1 and Nec-1 in the protection of primary chondrocytes. Furthermore, Nec-1 decreased the expression of Toll-like receptor 4 (TLR4) and stromal cell-derived factor-1 (SDF-1), and attenuated the interaction between TLR4 and HMGB1. Western blot results suggested that Nec-1 significantly suppressed IL-1β-induced NF-κB transcriptional activity, but not MAPK pathway. Micro-computed tomography, immunohistochemical staining, and Safranin O/Fast Green staining were used in vivo to assess the degree of destruction of OA cartilage. The results show that NEC-1 can significantly reduce the degree of destruction of OA cartilage. Therefore, Nec-1 may be a novel therapeutic candidate to treat OA

Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): A single-center, single-blinded, randomized, controlled clinical trial

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis.Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome.Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49–1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups.Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration