Bibliometric Analysis of the Role of Occludin in the Pathogenesis of Stroke.

Over the past decade, there has been a notable surge in research dedicated to unraveling the intricate role of tight junction proteins in blood-brain barrier (BBB) damage associated with ischemic stroke. This bibliometric analysis explores the expansive landscape of occludin research, a key tight junction protein, during the years 2000-2023, shedding light on the global scientific contributions, collaborations, and emerging trends in this critical area of stroke pathogenesis. China and the United States emerge as significant contributors, underscoring their prominence in advancing our understanding of tight junction proteins. Occludin, identified as a linchpin in regulating BBB integrity, proves to be a pivotal player, with implications extending to the diagnosis of hemorrhagic transformation in ischemic stroke. This study identifies occludin as a potential biomarker, offering promise for early diagnosis and paving the way for novel diagnostic strategies. The analysis highlights the necessity for a more comprehensive exploration of tight junction proteins, including occludin and claudin-5, particularly in the context of acute cerebral ischemia. The unique healthcare landscape in Kazakhstan adds urgency to the call for further scientific research in this region, emphasizing the need for tailored investigations to address specific regional challenges. This comprehensive overview not only delineates the current state of occludin research but also signals the direction for future investigations. The identified knowledge gaps and emerging trends provide a roadmap for researchers and policymakers alike, with implications for both scientific discourse and clinical practice. Moving forward, a deeper understanding of tight junction proteins, informed by the insights gleaned from this study, holds the potential to shape targeted therapeutic interventions and diagnostic strategies, ultimately contributing to advancements in global stroke care.

Establishing prognostic significance of hypoxia predictors in patients with acute cerebral pathology.

OBJECTIVES: This research aims to study the prognostic role of serum S100 as a predictor of mortality in vascular and traumatic brain injuries. METHODS: This prospective cohort study involved 219 patients. In the blood serum, neuron-specific markers (S100, NSE) and glucose, acid-base state and gas composition of arterial blood were obtained at admission, on the 3rd, 5th and 7th days of patients' stay in the intensive care unit. RESULTS: The most significant risk factor for an unfavorable outcome is the marker S100 with a cut-off point of 0.2 mcg/l. The analysis results indicate a statistically significant direct relationship between S100 > 0.2 mcg/l and NSE ≥ 18.9 ng/ml compared to other variables, while the chance ratio (OR) is 11.9 (95%CI:3.2927-1.6693;). With blood sugar increase above 7.4 mmol/l, the OR is 3.82 (95% CI: 2.1289-0.5539;); with a Glasgow scale below 13 points, the OR is 3.69 (95% CI: 2.1316-0.4819;); with an increase in pCO2 < 43.5 mm Hg, the OR was 3.15 (95% CI: 1.8916- 0.4062;). The obtained model certainty measure according to pseudo R2 Nagelkerke criterion is 263.5, showing the excellent quality of the mathematical model's predictive ability. The developed prognostic model, including the dependent variable S100 and independent variables as predictors of a poor outcome of NSE, pCO2, GCS and Hb, reached a cut-off point of 84.51%, AUC - 0.88 with high levels of sensitivity and specificity: 91.89% and 64.14%, respectively. NOVELTY: This model can be used to predict the outcome in patients with acute cerebral pathology.

A long-term follow-up study on biochemical and clinical biomarkers of response to interferon beta-1b treatment in relapsing-remitting multiple sclerosis.

BACKGROUND: While interferon beta-1b (IFN-ß-1b) is still a commonly used disease-modifying drug in the treatment of multiple sclerosis (MS), therapeutic possibilities are expanding, and treatment failure should be identified early. Markers to predict response to IFN-ß-1b, either clinical or biochemical, are therefore urgently needed. Interferon-induced proteins, including viperin, suppressor of cytokine signaling 3 (SOCS3), ubiquitin specific peptidase-18 (USP18), and myxovirus resistance protein A (MxA), are possible markers of IFN-ß-1b bioavailability and treatment response. OBJECTIVES: To evaluate viperin, SOCS3, USP18 and MxA as markers of treatment response in Polish IFN-ß-1btreated patients with MS. MATERIAL AND METHODS: In 45 IFN-ß-1b-treated Polish patients with MS, serum concentrations of viperin, SOCS3, USP18, and MxA were assessed before and after 24 months of IFN-ß-1b treatment. The patients were followed clinically and with magnetic resonance imaging (MRI) for a median of 6.8 years. RESULTS: Low viperin, USP18 and MxA at baseline and 24 months and high SOCS3 at 24 months correlated with higher disease activity up to the 6th year of observation, but only baseline MxA and USP18 were independently related to outcome, with higher concentrations predicting less disease activity in the first 3 years and after the 1st year, respectively. CONCLUSIONS: We confirm the predictive value of MxA and propose USP18 as a possible new prognostic biomarker in IFN-ß-1btreated MS patients.

Anti-interferon-beta antibodies in Polish multiple sclerosis patients: prevalence and clinical significance in a long-term prospective study.

AIM OF THE STUDY: To determine the prevalence of anti-interferon-ß binding (BAb) and neutralising antibodies (NAb), and to investigate whether NAb measured by luciferase-based cell assay can predict treatment response in multiple sclerosis (MS) patients treated with interferon-ß-1b (IFNß-1b). CLINICAL RATIONALE FOR THE STUDY: A subgroup of IFNß-treated MS patients develop NAb directed against the drug. The clinical significance remains controversial, which could be explained to some extent by technical difficulties in NAb detection and quantification. A simple, specific and reproducible test for NAb might help elucidate these uncertainties. MATERIALS AND METHODS: Sera from 101 consecutive MS patients initiating treatment with IFNß-1b were collected at baseline and during the first two years, and assessed for BAbNAb with a novel luciferase-based cell assay. Median clinical follow-up lasted 5.1 years. RESULTS: BAb were present in 97% and NAb in 88% of the study cohort. Unexpectedly, 92% of patients tested positive for Bab and 12.5% for NAb at baseline, before drug exposure. Patients with baseline NAb positivity were more likely to remain free of disease activity in the first three years of treatment. When baseline-positive cases were grouped together with those who remained NAb-negative, and the resulting group was compared to those who became positive after drug exposure, NAb positivity was associated with a higher risk of disease activity during the entire follow-up. Direct comparison of BAb/Nab-positive and BAb/Nab-negative patients only revealed an association of BAb positivity with more active disease after four years of treatment, while NAb failed to predict the outcome. CONCLUSIONS AND CLINICAL IMPLICATIONS: Antibodies developed after treatment initiation are associated with a worse outcome. Naturally- occurring antibodies appear to predict more benign disease. Their prevalence and specificity require further investigation.