Ischemic stroke triggers a complex cascade of cellular and molecular events leading to neuronal damage and tissue injury. This review explores the potential therapeutic avenues targeting cellular signaling pathways implicated in stroke pathophysiology. Specifically, it focuses on the articles that highlight the roles of RhoA/ROCK and mTOR signaling pathways in ischemic brain injury and their therapeutic implications. The RhoA/ROCK pathway modulates various cellular processes, including cytoskeletal dynamics and inflammation, while mTOR signaling regulates cell growth, proliferation, and autophagy. Preclinical studies have demonstrated the neuroprotective effects of targeting these pathways in stroke models, offering insights into potential treatment strategies. However, challenges such as off-target effects and the need for tissue-specific targeting remain. Furthermore, emerging evidence suggests the therapeutic potential of MSC secretome in stroke treatment, highlighting the importance of exploring alternative approaches. Future research directions include elucidating the precise mechanisms of action, optimizing treatment protocols, and translating preclinical findings into clinical practice for improved stroke outcomes.

Stroke remains a debilitating cerebrovascular condition associated with oxidative stress, while COVID-19 has emerged as a global health crisis with multifaceted systemic implications. This study investigates the hypothesis that patients experiencing acute ischemic stroke alongside COVID-19 exhibit elevated oxidative stress markers and altered antioxidant defense mechanisms compared to those with acute ischemic stroke. We conducted a single-center prospective cross-sectional study to investigate oxidative stress balance through oxidative damage markers: TBARS (thiobarbituric acid reactive substances level) and PCARB (protein carbonyls); antioxidant defense mechanisms: TAC (total antioxidant capacity), GPx (glutathione peroxidase), GSH (reduced glutathione), CAT (catalase), and SOD (superoxide dismutase); as well as inflammatory response markers: NLR (neutrophil-to-lymphocyte ratio), CRP (C-reactive protein), and ESR (erythrocyte sedimentation rate). Statistical analyses and correlation models were employed to elucidate potential associations and predictive factors. Our results revealed increased oxidative stress, predominantly indicated by elevated levels of TBARS in individuals experiencing ischemic stroke alongside a concurrent COVID-19 infection (p < 0.0001). The Stroke-COVID group displayed notably elevated levels of GSH (p = 0.0139 *), GPx (p < 0.0001 ****), SOD (p = 0.0363 *), and CAT (p = 0.0237 *) activities. Multivariate analysis found a significant association for TBARS (p < 0.0001 ****), PCARB (p = 0.0259 *), and GPx activity (p < 0.0001 ****), together with NLR (p = 0.0220 *) and CRP (p = 0.0008 ***). Notably, the interplay between stroke and COVID-19 infection appears to amplify oxidative damage, potentially contributing to exacerbated neurological deficits and poorer outcomes. This study highlights the intricate relationship between oxidative stress, inflammation, and concurrent health conditions. Understanding these interactions may open avenues for novel therapeutic strategies aimed at ameliorating oxidative damage in patients with acute ischemic stroke and COVID-19, ultimately improving their prognosis and quality of life.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71–24.47; OR 2.30, 95% CI: 1.23–4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population.

Vascular cognitive impairments are the expression of complex interactions between vascular etiology, risk factors (brain diseases, white matter lesions, etc.) and cellular changes at the brain level. Consequently, vascular cognitive impairment is highly dependent on the location, extent (volume of brain tissue affected) and number of lesions. Memory impairment is not necessarily characteristic of vascular cognitive decline, usually having an evolution with episodic exacerbations and multiple cerebrovascular attacks (cumulative effect), thus producing a gradual deterioration. In recent years, the concept of mild cognitive impairment has emerged as a potential form of predementia, but which can progress to different types of dementia, including Alzheimer's disease or vascular dementia. This review presents recent data related to the etiological and risk factors of cognitive decline after stroke, the associated neuropsychological and behavioral changes, the clinical forms/diagnosis and general principles of vascular dementia therapy. As preliminary conclusions, the Hachinski score is a very useful tool in differentiating vascular dementia from Alzheimer's dementia. A score greater than 7 points (especially when associated with imaging and anamnestic criteria) suggests a vascular etiology of dementia, whereas a score of 4 points or less excludes such an etiology. Although it is not the only factor involved, vascular etiology is still intensively studied because it is the only one that can be prevented and treated.

This cross-sectional study analyzed the lower limb (LL) behavior in terms of gait asymmetry and joints’ kinematic parameters, comparing people with multiple sclerosis (pwMS) and unaffected individuals. Methods: Data from 15 patients, EDSS ≤ 4.5, and 15 healthy control volunteers were gathered. The VICON Motion Capture System (14 infrared cameras), NEXUS software, Plug-in–Gait skeleton model and reflective markers were used to collect data for each subject during five gait cycles on a plane surface. Biomechanical analysis included evaluation of LL joints’ range of motion (ROM) bilaterally, as well as movement symmetry. Results: Comparative biomechanical analysis revealed a hierarchy of vulnerability between the groups: the ankle is the most affected joint in pwMS (p = 0.008–0.014), the knee is moderately affected (p = 0.015 in swing phase), and the hip is the least affected (p > 0.05 in all phases). The swing phase showed the most significant left–right asymmetry impairment, as reflected by root mean square error (RMSE) values: swing-phase RMSE = 9.306 ± 4.635 (higher and more variable) versus stance-phase RMSE = 6.363 ± 2.306 (lower and more consistent). Conclusions: MS does not affect the joints structurally; rather, it eliminates the ability to differentiate the fine-tuning control between them. The absence of significant left–right joint asymmetry differences during complete gait cycle indicates dysfunction in the global motor control.