Iuliu Hațieganu University of Medicine and Pharmacy (Romanian: Universitatea de Medicină și Farmacie "Iuliu Hațieganu", or UMF Cluj) in Cluj-Napoca, Romania, is the oldest medical education institution in Transylvania, a continuation of the Faculty of Medicine which was founded in 1919, as a part of the Superior Dacia University. The university has over 6,000 national and international students, 2,400 resident physicians, as well as over 1,100 teachers and researchers. It was named in honor of the scientist Iuliu Hațieganu. The university is classified as an "advanced research and education university" by the Ministry of Education.
Cirrhosis represents the end stage of chronic liver injury, characterized by progressive fibrosis and architectural distortion that precipitate portal hypertension and systemic complications. Recent evidence positions gut microbiota dysbiosis and nitric oxide (NO) dysregulation as central, interacting pathophysiological mechanisms in cirrhosis progression. Intestinal barrier dysfunction facilitates bacterial translocation and thereby exposes the liver to lipopolysaccharides and pathogen-associated molecular patterns that trigger hepatic inflammation via Toll-like receptor signalling, a phenomenon aggravated by dysbiosis. This immune activation stimulates inducible NO synthase in Kupffer cells and systemic endothelium, generating excess NO that drives splanchnic vasodilation and worsens portal hypertension. Paradoxically, intrahepatic endothelial NO synthase activity becomes impaired, reducing sinusoidal NO availability and increasing intrahepatic vascular resistance. These interconnected disturbances perpetuate inflammation and fibrogenesis, contributing to cirrhosis decompensation and spontaneous bacterial peritonitis. Despite substantial mechanistic insight into these pathways, therapeutic translation remains limited. Statins show promise by restoring intrahepatic eNOS function and reducing portal pressure, while microbiota-targeted interventions (antibiotics, probiotics, fecal transplantation) address gut-derived inflammation. This review synthesizes our current understanding of the gut-liver-NO axis in cirrhosis, highlighting how dysbiosis and aberrant NO signalling reinforce each other through inflammatory feedback loops, and identifies critical gaps between mechanistic knowledge and clinical application that warrant further investigation. Dysbiosis-driven bacterial translocation sustains hepatic inflammation and fibrogenesis. Opposing intrahepatic eNOS loss and systemic iNOS excess worsen portal hypertension. Dysbiosis and nitric oxide overproduction form a self-reinforcing pathological loop. Statins and microbiota therapies show promise but lack robust clinical evidence.
Intestinal ischemia-reperfusion injury (IRI) represents a major cause of morbidity and mortality in abdominal surgery, trauma, and intestinal transplantation. The pathophysiological process involves a biphasic cascade that begins with ischemic hypoxia and progresses to amplified cellular and molecular injury upon reperfusion. This review synthesizes recent mechanistic insights regarding endothelial and microvascular dysfunction, epithelial barrier breakdown, microbiota-driven systemic propagation, and the involvement of oxidative/nitrosative stress and inflammatory signaling. The novelty of our review's approach is the focus on experimental and translational studies and correlation of the data with future directions for mechanistic research and clinical implementation. Despite promising preclinical results, heterogeneity in study protocols or/and model limitations make clinical translation challenging. Recent studies have demonstrated that mitochondria, tight junction proteins, adhesion molecules and innate immune receptors are critical determinants of lesion evolution. Based on these, the current therapeutic strategies include antioxidants, adenosine pathway modulators, dexmedetomidine, ischemic conditioning, hyperbaric oxygen therapy, and microbiota-targeted interventions. Since each mechanism is acting on distinct molecular pathways, a multimodal therapy that integrates redox modulation, endothelial protection, microbiome regulation, and the identification and employment of precision biomarkers is likely to improve outcomes. Beyond summarizing established molecular mechanisms, this review critically reassesses why decades of promising experimental strategies for intestinal ischemia-reperfusion injury has largely failed to translate into effective clinical therapies. By distinguishing context-dependent mechanisms from pathways with consistent translational relevance, we highlight key methodological and biological barriers limiting clinical applicability. Furthermore, we propose a temporally structured, multimodal therapeutic framework that integrates phase-specific pathophysiology with targeted interventions, aiming to inform future experimental design and improve translational success.
Migraine is a highly prevalent and disabling neurovascular disorder that represents a major global health burden due to its significant impact on quality of life and socioeconomic costs. Increasing evidence suggests that migraine pathophysiology involves complex interactions between neuronal hyperexcitability, vascular dysregulation, oxidative stress, and neuroinflammatory processes. Oxidative and nitrosative stress are increasingly recognized as key contributors to migraine mechanisms, influencing mitochondrial dysfunction, cortical spreading depression, and trigeminovascular activation. Nitric oxide plays a central role in these processes by regulating vascular tone, nociceptive signaling, and neurogenic inflammation through downstream pathways such as the soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling cascade. Dysregulation of nitric oxide signaling and increased oxidative stress may contribute to endothelial dysfunction and impaired cerebrovascular regulation observed in migraine patients. In addition, accumulating evidence highlights the role of neuroinflammatory mechanisms, including microglial activation and cytokine-mediated signaling, which may amplify nociceptive transmission within trigeminal pathways. Migraine is increasingly recognized as a systemic disorder associated with several comorbid conditions, including Parkinson's disease, fibromyalgia, and autoimmune diseases such as Sjögren's syndrome. This review summarizes recent advances regarding the interactions between oxidative stress, nitric oxide signaling, endothelial dysfunction, and neuroinflammation in migraine and discusses their potential therapeutic implications.
N-acetylcysteine (NAC) is a glutathione precursor with established antioxidant and anti-inflammatory properties that has been investigated as a neuroprotective agent across multiple neurological conditions. This systematic review systematically mapped the clinical evidence for NAC across seven neurological disorders. PubMed and Cochrane Library were searched for studies published between 1 January 1995 and 31 December 2025. Twenty-three studies were included: traumatic brain injury (TBI, n = 6), Alzheimer's disease (AD, n = 5), Parkinson's disease (PD, n = 5), multiple sclerosis (n = 4), amyotrophic lateral sclerosis (n = 2), and migraine (n = 1); no eligible epilepsy studies were identified. The strongest evidence emerged for acute mild TBI, where early NAC administration significantly improved symptom resolution, and for PD, where combined intravenous/oral NAC improved dopamine transporter binding. In AD, nutraceutical formulations including NAC and other active compounds showed trends toward cognitive stabilization. Most included studies had a high or serious risk of bias, and only eight of 23 assessed oxidative stress biomarkers. NAC demonstrated a favorable safety profile across all conditions. Despite fragmented and heterogeneous evidence, the encouraging signals identified warrant large-scale randomized controlled trials with a standardized biomarker assessment.
Microvascular procedures demand exceptional precision and are prone to technical errors that compromise outcomes. Performance improves fastest when errors are identified, measured, and corrected early during training. Error-based learning has become an essential part of microsurgical training, highlighting the importance of identifying and learning from mistakes to improve performance. This review aimed to systematically search the literature on all microsurgical errors and categorize them by operative phases. A structured literature search was conducted across Medline, Embase, and Web of Science databases, following PRISMA guidelines. Two reviewers independently screened records and extracted data in duplicate. Articles were included if they evaluated microvascular anastomoses with vessels less than 2 mm in diameter, and if microsurgical errors were detailed along with their impact on outcomes, in particular on anastomotic patency. Given the heterogeneity of the data, a SWiM-style (Synthesis Without Meta-analysis) narrative synthesis was used. A total of 34 studies met the inclusion criteria. Errors were categorized as pre-operative, intra-operative, and post-operative. Intra-operative errors were the most frequently reported. Back-wall stitches, uneven lumens, and excessive suture tension were consistently associated with reduced patency. Several validated scoring tools (e.g., ALI, MARS10, OSATS) were identified as effective in quantifying errors and guiding feedback in training settings. Microvascular anastomosis errors span all phases of the microsurgical procedure and significantly affect anastomotic success. This review offers a structured taxonomy of errors and underscores the importance of error-based learning and assessment in microsurgical training. Standardized error classification may enhance training programs, accelerating the acquisition of microsurgical skills along the learning curve and improving clinical outcomes.
