An ischemic stroke (IS) is caused due to the lack of blood flow to cerebral tissue. Most of the studies have focused on how stroke affects the localized tissue, but it has been observed that a stroke can cause secondary complications in distant organs, such as Bone Marrow (BM). Our study focused on the effect of ischemic strokes on the bone marrow microenvironment. Bone marrow (BM) is a vital organ that maintains inflammatory homeostasis and aids in the repair of damaged tissue after injury/IS. We used the middle cerebral artery occlusion (MCAO) model of ischemic stroke on adult mice (6 months) and investigated the changes in the BM environment. BM cells were used for western blot and RT-PCR, and the BM supernatant was used for cytokine analysis and extracellular vesicle (EVs) isolation. We observed a significant increase in the total cell number within the BM and an increase in TNF-alpha and MCP-1, which are known for inducing a pro-inflammatory environment. Western blots analysis on the whole BM cell lysate demonstrated elevated levels of inflammatory factors (IL-6, TNF-alpha, and TLR-4) and senescence markers (p21 p16). EVs isolated from the BM supernatant showed no change in size or concentration; however, we found that the EVs carried increased miRNA-141-3p and miRNA-34a. Proteomic analysis on BM-derived EVs showed an alteration in the protein cargo of IS. We observed an increase in FgB, C3, Fn1, and Tra2b levels. The signaling pathway analysis showed mitochondrial function is most affected within the bone marrow. Our study demonstrated that IS induces changes in the BM environment and EVs secreted in the BM. 

The impact of ischemic stroke on bone marrow microenvironment and extracellular vesicles: A study on inflammatory and molecular changes

Presenilin proteins, the catalytic components of the γ-secretase enzyme, play a key role in the pathogenesis of Alzheimer's disease primarily by generating amyloid-β peptides. Although often grouped together, Presenilin-1 (PS1) and Presenilin-2 (PS2) are distinct proteins that contribute differently to γ-secretase activity. This study examines the differential expression of PS1 and PS2 in various neuroblastoma and microglial cell lines, along with compensatory responses following the ablation of one presenilin homologue. Using quantitative immunoblotting, we show that PS1 and PS2 expression levels vary significantly across cell types. Notably, the ablation of PS2 results in increased PS1 expression, particularly in microglial cells, highlighting the importance of PS2. Additionally, neuronal differentiation of two neuroblastoma lines, caused changes in protein expression levels resulting in similar expression profiles of PS1 and PS2, with PS2 levels being higher than PS1. Understanding PS expression profiles is crucial for distinguishing between PS1- and PS2-mediated γ-secretase activity and for developing γ-secretase-targeted therapeutics with improved selectivity. 

Differential expression and modulation of presenilin-1 and presenilin-2 in neural cell lines

The aim of the present systematic review was to determine whether prophylactic use of cerebrospinal fluid drainage (CSFD) contributes to a lower rate of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD).PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched to identify all relevant studies reported before May 7, 2023. A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42023441392). The primary outcome was permanent SCI. Secondary outcomes were temporary SCI and 30-day/in-hospital mortality. The data were presented as the pooled event rates (ERs) and 95% confidence intervals (CIs).A total of 1008 studies were screened, of which 34 studies with 2749 patients were included in the present analysis. The mean Downs and Black quality assessment score was 8.71 (range, 5-12). The pooled rate of permanent SCI with prophylactic CSFD was identical to that without prophylactic CSFD (2.0%; 95% CI, 1.0-3.0; P = 0.445). No statistically significant difference was found between the rates of permanent SCI with routine vs. selective prophylactic CSFD (P = 0.596). The pooled rate of temporary SCI was 1.0% (95% CI, 0.00-1.0%). The pooled rate for 30-day or in-hospital mortality was not significantly different (P = 0.525) in patients with prophylactic CSFD (4.0, 95% CI 2.0-6.0) or without prophylactic CSFD (5.0, 95% CI 2.0-7.0).The systematic review has shown that prophylactic CSFD was not associated with a lower rate of permanent SCI and 30-day or in-hospital mortality after TEVAR for TBAD. 

Systematic review of the effect of cerebrospinal fluid drainage on outcomes after endovascular type B aortic dissection repair

Spinal Hematoma Following Fluoroscopic Placement of a Spinal Drain for Thoracic Endovascular Aortic Repair: Advantages of Paramedian versus Midline Approach

Additional file 5 of Systematic review of the effect of cerebrospinal fluid drainage on outcomes after endovascular type B aortic dissection repair

Osteoarthritis (OA) is a highly prevalent degenerative joint condition that disproportionately affects females. The pathophysiology of the disease is not well understood, which makes diagnosis and treatment difficult. Given the physical connection of synovial fluid (SF) with articular tissues, the SF’s composition can reflect relevant biological modifications, and has therefore been a focus of research. Previously, we demonstrated that extracellular vesicles isolated from the synovial fluid of OA patients carry different cargo (protein and miRNA) in a sex-specific manner. Given the increased prevalence and severity of OA in females, this study aims to identify differential protein content within the synovial fluid of female OA and non-osteoarthritic (non-OA) patients. We found that several proteins were differentially expressed in osteoarthritic females compared with age-matched controls. Presenilin, Coagulation Factor X, Lysine-Specific Demethylase 2B, Tenascin C, Leucine-Rich Repeat-Containing Protein 17 fragments, and T-Complex Protein 1 were negatively regulated in the OA group, with PGD Synthase, Tubulointerstitial Nephritis Antigen, and Nuclear Receptor Binding SET Domain Protein 1 positively regulated in the OA group. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analyses established these proteins as significantly involved in many biological, cellular, and molecular processes. In conclusion, the protein content of female synovial fluid is altered in OA patients, which is likely to provide insights into gender-specific pathophysiology.

/pdf/proteomic-analysis-of-female-synovial-fluid-to-identify-18wiy8m6.pdf

Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis

A well-placed and functioning lumbar spinal drain, for spinal cord protection, is an important aspect of the perioperative care of patients undergoing thoracic endovascular aortic repair (TEVAR) procedures. Spinal cord injury (SCI) is a devastating complication of TEVAR procedures and is most often associated with Crawford type 2 repairs. Current evidence-based guidelines for the surgical management of patients with thoracic aortic disease include the role of lumbar spine catheter placement and drainage of cerebrospinal fluid (CSF) intraoperatively as part of a strategy to prevent spinal cord ischemia. More often than not, the procedure of lumbar spinal drain placement, using a standard blind technique, and subsequent drain management is the responsibility of the anesthesiologist. However, institutional protocols are inconsistent, and, failure to successfully place the lumbar spinal drain pre-operatively in the operating room, in clinical situations such as patients with poor anatomical landmarks or prior back surgery, presents a clinical dilemma and impacts spinal cord protection during TEVAR. Although a relatively safe procedure, potential complications of lumbar spine catheter placement range from a self-limiting headache to hemorrhage and permanent neurological injury. Spinal drain placement with image-guided fluoroscopy by interventional radiology should be considered in the preoperative assessment and planning and is an alternative to conventional, blind lumbar drain insertion.

Protecting the spinal cord during thoracic endovascular aortic repair—who should place the spinal drain?

Abstract Purpose SERine Protease INhibitor clade A member 3 (SERPINA3), a protease inhibitor involved in the acute phase response, is regulated by interleukin 6 trans-signaling, a pro-inflammatory pathway associated with diabetic retinopathy (DR) pathogenesis. We hypothesized that SERPINA3 may serve as a biomarker to distinguish DR patients from diabetic patients without retinopathy. Methods We measured serum SERPINA3 levels in DR patients and demographically matched diabetic patients without retinopathy to assess the biomarker potential of SERPINA3. History of COVID-19 infection was included as a demographic variable. Results Our results showed that SERPINA3 levels did not vary between cases and controls, nor was there any correlation with disease severity as measured by hemoglobin A1c and diabetic retinopathy stage. We found that excluding patients with a history of COVID-19 infection increased the predictive value of SERPINA3, and that SERPINA3 levels were significantly increased in those subjects hospitalized due to COVID-19. The predictive value of SERPINA3 for hospitalization was similar to age, duration of diabetes, and HbA1c in our cohort. Conclusions Overall, SERPINA3 had poor sensitivity and specificity for identifying DR patients, and COVID-19 infection history significantly increased variance in SERPINA3 levels. Further investigation into the potential of SERPINA3 as DR biomarker should be sufficiently powered to account for the potentially confounding effects of COVID-19 infection.

SERPINA3 in Diabetic Retinopathy: A Pilot Study Assessing the Impact of Prior COVID-19 Infection on Patients.

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Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis

Protecting the spinal cord during thoracic endovascular aortic repair—who should place the spinal drain?

SERPINA3 in Diabetic Retinopathy: A Pilot Study Assessing the Impact of Prior COVID-19 Infection on Patients.