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Renalase, a novel flavoprotein that is mainly expressed in the kidney and heart, plays a crucial role in hypertension. Recent studies have shown that renalase is expressed at low levels in the serum of patients with heart failure, while the role of renalase and its mechanism in cardiac failure is unclear. Adult Sprague-Dawley (SD) rats were used to investigate the role and function of renalase in the pathological process of transverse aortic constriction (TAC)-induced heart failure. Renalase-human protein chip analysis showed that renalase was directly associated with P38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling. We further used lentivirus-mediated RNA interference to study the role of renalase in the progression of pathological ventricular hypertrophy and found that renalase inhibition attenuated the noradrenaline-induced hypertrophic response in vitro or the pressure overload-induced hypertrophic response in vivo. Recombinant renalase protein significantly alleviated pressure overload-induced cardiac failure and was associated with P38 and ERK1/2 signaling. These findings demonstrate that renalase is a potential biomarker of hypertrophy and that exogenous recombinant renalase is a potential and novel drug for heart failure.

Objectives Postoperative cognitive dysfunction (POCD) is a common clinical complication, with an underlying pathophysiology linked to heightened levels of neuroinflammation. However, it requires clarification as to whether the depth of anesthesia modulates postoperative cognitive dysfunction. This study investigated the association between depth of anesthesia and POCD in elderly patients undergoing abdominal surgery. Methods A total of 120 patients aged 60 years or older who were planned for abdominal surgery under total intravenous anesthesia were included in this study. The depth of anesthesia was guided by monitoring Bispectral Index (BIS) data. All study participants completed a battery of nine neuropsychological tests before surgery and at 7 days and 3 months after surgery. POCD was calculated by using the reliable change index. Plasma concentration of C‐reactive protein (CRP), interleukin (IL)‐1β, IL‐10, S‐100β, and norepinephrine (NE) were measured. Results The incidence of POCD at 7 days after surgery in the deep anesthesia group was 19.2% (10/52), which was significantly lower (p = 0.032) than the light anesthesia group 39.6% (21/53). The depth of anesthesia had no effect on POCD at 3 months after surgery (10.3% vs 14.6%, respectively, p = 0.558). Similarly, plasma levels of CRP and IL‐1β in deep anesthesia group were lower than that in light anesthesia group at 7 days after surgery (p < 0.05), but not at 3 months after surgery (p > 0.05). There were no significant differences in the plasma concentration of IL‐10, S‐100β, and NE between the groups (p > 0.05). Conclusions Deep anesthesia under total intravenous anesthesia could decrease the occurrence of short‐term POCD and inhibit postoperative peripheral inflammation in elderly patients undergoing abdominal surgery, compared with light anesthesia. Deep anesthesia under total intravenous anesthesia could decrease the occurrence of short‐term POCD and inhibit postoperative peripheral inflammation in elderly patients undergoing abdominal surgery, compared with light anesthesia.

Members of the aging population who undergo surgery are at risk of postoperative cognitive dysfunction (POCD). Exploring an effective and reliable early predictor of POCD is essential to the identification of high-risk patients and to making prospective decisions. The purpose of this study was to examine whether preoperative insulin resistance is an independent predictor of POCD. A total of 124 patients aged 60 years and older and who were scheduled for gastrointestinal surgery were enrolled in a prospective observational clinical study. All participants completed a battery of neuropsychological tests before surgery and 7 days later. POCD was defined as a decline of at least 1.5 SD on two or more of neuropsychological tests. Plasma concentration of the tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and S-100β protein were measured. The status of insulin resistance was assessed by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The relationship between HOMA-IR and POCD was assessed by Multivariable logistic regression models and the receiver operating characteristic (ROC) curve. Fifty one patients (41.1%) were diagnosed with POCD at 7 days after surgery. Preoperative HOMA-IR values of the POCD group were significantly higher than the non-POCD group. Furthermore, CRP and TNF-α levels of the POCD group were significantly higher at each postoperative time point ( < 0.05). The preoperative HOMA-IR value was an independent predictor of POCD (adjusted OR 1.88, 95% CI, 1.18-2.99) even after adjust for confounding variables, and when dichotomized, individuals above the HOMA-IR threshold (HOMA-IR > 2.6) had a three-times higher risk of POCD (OR 3.26; 95% CI, 1.07-9.91) compared to individuals below the threshold. The areas under the ROC curve of HOMA-IR was 0.804 (95% CI, 0.725-0.883; < 0.001). The optimal cut-off value was found to be 0.583, with a sensitivity of 84.3% and specificity of 74%. The HOMA-IR value was positively associated with the TNF-α concentration at baseline ( = 0.43, < 0.01) and 1 day after surgery ( = 0.3861, < 0.01). Preoperative insulin resistance is an effective predictor for the occurrence of POCD. Targeted prevention and treatment strategies of insulin resistance may be effective interventions of patients at risk for POCD.

Neuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h prior to anesthesia and surgery. Cognitive function and movement were tested 24 h after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues were collected to detect the following: neuroinflammation (Iba-1, IL-1α, IL-1β, TNF-α), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription factor kappa B (NF-κB) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, GluA2). We found that anesthesia and surgery induced a significant deficit in spatial memory acquisition and impairment of executive function and memory to simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for prevention of POCD in elderly patients.

Mounting evidence shows that chronic stress can affect both the structure and function of the brain resulting in decreased synaptic plasticity and cognitive dysfunction. Although several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown how to prevent stress-induced memory deficits in aged animals. Neuroinflammation plays an important role in the pathogenesis of chronic stress-related brain dysfunction. Receptor-interacting protein 1 (RIP1) is a key molecule that can modulate inflammation, apoptosis, and necroptosis. Here, we investigated whether inhibiting RIP1 using necrostatin-1 during chronic stress could improve chronic stress-related brain dysfunction in D-galactose-induced aging mice. The stressed mice underwent restraint stress for 14 days. Necrostatin-1 (6.25 mg/kg) or vehicle was administered intraperitoneally once every 3 days during the stress period. Locomotor activity was tested using the open field test and cognitive function was assessed using the novel object recognition and Barnes maze tests. The hippocampus was collected to assess neuroinflammation (Iba1, IL-1α, IL-1β, TNF-α, and C1q), necroptosis [RIP1, RIP3, mixed lineage kinase domain-like (MLKL), and NF-κB], neuroplasticity (doublecortin, NR1, NR2A, NR2B, GluA1, and GluA2), and the expression of glucocorticoid and mineralocorticoid receptors. Blood samples were collected to quantify the levels of corticosterone. We found that chronic stress induced obvious memory impairment and neuroinflammation, decreased neurogenesis and GluA2 expression, and increased the expression of RIP1 and NF-κB. Inhibiting RIP1 by necrostatin-1 during chronic stress rescued the memory impairment and alleviated the pathological changes induced by stress. These suggest that inhibiting RIP1 using necrostatin-1 improves chronic stress-related brain dysfunction in D-galactose-induced aging mice. The potential mechanisms include limitation of neuroinflammation and the rescue of neurogenesis and GluA2 expression.

Objectives A growing body of data indicates that the kynurenine pathway may play a role in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenic aminotransferase (KAT) is an important kynurenine pathway enzyme, catalyzing kynurenine (KYN) into kynurenic acid (KYNA). This study investigated as to whether genetic variations in KAT are associated with PDS. Methods A cohort of 360 Chinese women scheduled to undergo cesarean delivery was enrolled into this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13. A total of eight KAT single nucleotide polymorphisms (SNPs) were genotyped and their association with PDS investigated. Serum concentrations of KYN, KYNA, and quinolinic acid (QUIN) in women with or without PDS were also measured. This allowed the determination of the KYNA/KYN ratio, which is reflective of KAT activity. Results Postpartum depressive symptoms incidence was 7.2%. Advanced maternal age, lower education, antenatal depression, and postpartum blues were risk factors for PDS (p < .05). Women with PDS, versus non‐PDS, had heightened KYN levels one day prior to surgery (ante‐d1) (p < .05), as well as having significantly lower KYNA and higher QUIN levels at postnatal day three (post‐d3) (p < .05). Women with, versus without, PDS also had a significantly higher QUIN/KYNA ratio at post‐d3 (p < .05). KAT activity was significantly lower in women with, versus without, PDS at ante‐d3 (p < .05). No significant association was evident between the KAT SNPs and PDS. Conclusion Our data support a role for alterations in the kynurenine pathway in the pathogenesis of PDS, although no significant association was found for the eight tested KAT SNPs with PDS. Our data support a role for alterations in the kynurenine pathway in the pathogenesis of PDS, although no significant association was found for the eight tested KAT SNPs and PDS.

Dinoflagellates are important components of marine ecosystems and essential coral symbionts, yet little is known about their genomes. We report here on the analysis of a high-quality assembly from the 1180-megabase genome of Symbiodinium kawagutii. We annotated protein-coding genes and identified Symbiodinium-specific gene families. No whole-genome duplication was observed, but instead we found active (retro) transposition and gene family expansion, especially in processes important for successful symbiosis with corals. We also documented genes potentially governing sexual reproduction and cyst formation, novel promoter elements, and a microRNA system potentially regulating gene expression in both symbiont and coral. We found biochemical complementarity between genomes of S. kawagutii and the anthozoan Acropora, indicative of host-symbiont coevolution, providing a resource for studying the molecular basis and evolution of coral symbiosis.