Oxidative stress and neuronal apoptosis have been demonstrated to be key features in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have indicated that Mas receptor activation initiates an anti-oxidative and anti-apoptotic role in the brain. However, whether Mas activation can attenuate oxidative stress and neuronal apoptosis after SAH remains unknown. To investigate the beneficial effect of Mas on oxidative stress injury and neuronal apoptosis induced by SAH, a total of 196 rats were subjected to an endovascular perforation model of SAH. AVE 0991 (AVE), a selective agonist of Mas, was administered intranasally 1 h after SAH induction. A779, a selective inhibitor of Mas, and small interfering ribonucleic acid (siRNA) for UCP-2 were administered by intracerebroventricular (i.c.v) injection at 1 h and 48 h before SAH induction respectively. Neurological tests, immunofluorescence, TUNEL, Fluoro-Jade C, DHE staining, and Western blot experiments were performed. We found that Mas activation with AVE significantly improved neurobehavioral scores and reduced oxidative stress and neuronal apoptosis in SAH+AVE group compared with SAH+vehicle group. Moreover, AVE treatment significantly promoted phosphorylation of CREB and the expression UCP-2, as well as upregulated expression of Bcl-2 and downregulation of Romo-1 and Bax. The protective effects of AVE were reversed by i.c.v injection of A779 and UCP-2 siRNA in SAH+AVE+A779 and SAH+AVE+UCP-2 siRNA groups, respectively. In conclusion, our data provides evidence that Mas activation with AVE reduces oxidative stress injury and neuronal apoptosis through Mas/PKA/p-CREB/UCP-2 pathway after SAH. Furthermore, our study indicates that Mas may be a novel therapeutic treatment target in early brain injury of SAH.

Subarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high mortality and disabilities. Retinoid X receptor (RXR) has been shown to be neuroprotective against ischemia/reperfusion injury. This study aimed to investigate the effects of the selective RXR agonist bexarotene on neuroinflammation in a rat model of SAH. Two hundred male Sprague-Dawley rats were used. The endovascular perforation induced SAH. Bexarotene was administered intraperitoneally at 1 h after SAH induction. To investigate the underlying mechanism, the selective RXR antagonist UVI3003 and RXR siRNA or SIRT6 inhibitor OSS128167 was administered via intracerebroventricular 1 h before SAH induction. Post-SAH assessments including SAH grade, neurological score, brain water content, Western blot, and immunofluorescence were performed. The endogenous RXR and sirtuin 6 (SIRT6) protein levels were increased after SAH. Bexarotene treatment significantly reduced brain edema and improved the short-/long-term neurological deficit after SAH. Mechanistically, bexarotene increased the levels of PPARγ and SIRT6; decreased the expression of phosphorylated FoxO3a (p-FoxO3a), IL-6, IL-1β, and TNF-a; and inhibited the microglia activation and neutrophils infiltration at 24 h after SAH. Either UVI3003, OSS128167, or RXR siRNA abolished the neuroprotective effects of bexarotene and its regulation on protein levels of PPARγ/SIRT6/p-FoxO3a after SAH. The activation of RXR by bexarotene attenuated neuroinflammation and improved neurological deficits after SAH. The anti-neuroinflammatory effect was at least partially through regulating PPARγ/SIRT6/FoxO3a pathway. Bexarotene may be a promising therapeutic strategy in the management of SAH patients.

There is evidence that spaceflight poses acute and late risks to the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched from the Kennedy Space Center (KSC) on a 13-day mission. Within 3–5 h after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the gray and/or white matter. While there was no overlap between the white and gray matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.

Vertebrate cell surfaces exhibit intricate arrangements of glycosaminoglycan polymers, which are primarily linked to lipids and proteins. Numerous soluble secreted proteins are also decorated with either individual sugar molecules or their polymers. The carbohydrate polymers commonly possess terminal nine-carbon sugars, known as sialic acids. Due to their widespread distribution and strategic positioning, sialic acids play a crucial role in mediating and regulating a wide range of physiologic processes and pathologic conditions. Human- or animal-based investigations predominantly concentrate on the effects of sialic acids during infections, inflammations, vascular disorders, or cancers. Further investigations encompass a variety of applications, including cell–cell interactions, signaling, host–pathogen interactions, and other biological functions associated with nutrition, metabolism, or genetic disorders. Nevertheless, future mechanistic investigations are needed to clarify the specific roles of sialic acids in these varied contexts, so that more effective interventions may be developed.

N-Acetyl-D-mannosamine (ManNAc) and N-acetylneuraminic acid (Neu5Ac) are important components of glycosylation, affecting numerous physiologic processes. The effects of age, body mass index (BMI), race, or sex on serum levels of ManNAc and Neu5Ac are poorly understood. However, these associations are of substantial interest. Simultaneous quantification of ManNAc and Neu5Ac, using liquid chromatography tandem mass spectrometry (LC-MS/MS), was developed and validated for human serum samples. This method has high sensitivity, specificity, and reproducibility, with limits of detection as low as 1.02 ng/mL for ManNAc or 1.14 ng/mL for Neu5Ac. A set of 155 serum samples from the Adventist Health Study 2 (AHS-2) cohort was analyzed. Concentrations of conjugated Neu5Ac were 35.1 ± 9.4 µg/mL and 33.0 ± 9.5 µg/mL in black and white participants, respectively. Conjugated and total Neu5Ac levels were significantly higher in women, with p-values of 0.029 and 0.026, respectively. The free forms of Neu5Ac were 594 ± 421 ng/mL and 439 ± 168 ng/mL in black and white participants, respectively. Similarly, conjugated and total ManNAc levels were higher in black participants, at 1.81 ± 0.81 µg/mL and 1.90 ± 0.83 µg/mL, compared to 1.32 ± 0.52 µg/mL and 1.41 ± 0.53 µg/mL in white participants (both cases, p < 0.001). Free ManNAc was 93.1 ± 36.2 ng/mL in black and 89 ± 20.2 ng/mL in white participants. Subjects with higher BMI tend to have higher free ManNAc (p = 0.041). Furthermore, older subjects tend to have higher free (p ≤ 0.001) and total (p = 0.045) ManNAc. The improved LC-MS/MS quantification method should facilitate further investigations.

Gram-positive bacteria covalently anchor specific proteins to the peptidoglycan cell wall via sortase, a cysteine transpeptidase that targets proteins with a cell wall sorting signal. Sortase enzymes are critical for bacterial pathogenesis, and their inhibitors have become promising therapeutic targets for infection management. Filifactor alocis, a Gram-positive anaerobic bacterium, is now proposed as a diagnostic indicator of periodontal disease. Unlike other bacteria, F. alocis encodes a single putative sortase, FA1364. In this study, we functionally characterized the putative sortase FA1364 and found that it belongs to the class A family (SrtA). The SrtA-anchored surface proteins (FA1006, FA1336, FA1424, and FA1750) were identified, and MS/MS analysis confirmed that SrtA is required for their cell-surface localization. The recombinant SrtA protein could recognize and cleave the LPKTG sorting motif with cysteine 191 and arginine 200 as essential catalytic residues. F. alocis FLL101 (ΔFA1364::ermF) showed reduced ability to coaggregate and form biofilm, along with decreased collagen binding and survival in epithelial cells. Additionally, the FA1364-defective mutant exhibited increased sensitivity to air exposure. Collectively, these results suggest that the F. alocis SrtA protein is an important virulence factor and may represent a novel therapeutic target for the control of periodontal diseases.