Shock is a life-threatening condition characterized by inadequate tissue perfusion leading to systemic hypoxia and metabolic failure. Ischemia/reperfusion (I/R) injury exacerbates shock progression through oxidative stress and immune dysregulation, contributing to multi-organ dysfunction. This narrative review synthesizes current evidence on the interplay between I/R injury, oxidative stress, and immune modulation in shock states. We analyze the classification of shock, its progression, and the molecular pathways involved in ischemic adaptation, inflammatory responses, and oxidative injury. Shock pathophysiology is driven by systemic ischemia, triggering adaptive responses such as hypoxia-inducible factor (HIF) signaling and metabolic reprogramming. However, prolonged hypoxia leads to mitochondrial dysfunction, increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, and immune activation. The transition from systemic inflammatory response syndrome (SIRS) to compensatory anti-inflammatory response syndrome (CARS) contributes to immune imbalance, further aggravating tissue damage. Dysregulated immune checkpoint pathways, including CTLA-4 and PD-1, fail to suppress excessive inflammation, exacerbating oxidative injury and immune exhaustion. The intricate relationship between oxidative stress, ischemia/reperfusion injury, and immune dysregulation in shock states highlights potential therapeutic targets. Strategies aimed at modulating redox homeostasis, controlling immune responses, and mitigating I/R damage may improve patient outcomes. Future research should focus on novel interventions that restore immune balance while preventing excessive oxidative injury.

The circadian rhythms generated by the master biological clock located in the brain’s hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription–translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

Shock is a life-threatening condition characterized by inadequate tissue perfusion, leading to systemic hypoxia and metabolic failure. Ischemia-reperfusion (I/R) injury exacerbates shock progression through oxidative stress and immune dysregulation, contributing to multi-organ dysfunction. This narrative review synthesizes current evidence on the interplay between I/R injury, oxidative stress, and immune modulation in shock states. We analyze the classification of shock, its progression, and the molecular pathways involved in ischemic adaptation, inflammatory responses, and oxidative injury. Shock pathophysiology is driven by systemic ischemia, triggering adaptive responses such as hypoxia-inducible factor (HIF) signaling and metabolic reprogramming. However, prolonged hypoxia leads to mitochondrial dysfunction, increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, and immune activation. The transition from systemic inflammatory response syndrome (SIRS) to compensatory anti-inflammatory response syndrome (CARS) contributes to immune imbalance, further aggravating tissue damage. Dysregulated immune checkpoint pathways, including CTLA-4 and PD-1, fail to suppress excessive inflammation, exacerbating oxidative injury and immune exhaustion. The intricate relationship between oxidative stress, ischemia-reperfusion injury, and immune dysregulation in shock states highlights potential therapeutic targets. Strategies aimed at modulating redox homeostasis, controlling immune responses, and mitigating I/R damage may improve patient outcomes. Future research should focus on novel interventions that restore immune balance while preventing excessive oxidative injury.

Currently, approximately 40% of patients with dementia develop some form of sleep disorder. Benzodiazepines are widely prescribed but pose the risk of tolerance and cognitive decline; however, Z-drugs may offer safer alternatives. Therefore, this systematic review aimed to analyze the effect of benzodiazepines and Z-drugs on sleep disorders in patients with dementia. Two authors conducted a systematic search in PubMed, Scopus, Web of Science, Espistemonikos, and ACCESSSS for studies published between 2019 and 2024 using the MeSH terms “dementia”, “sleep disorders”, and “pharmacotherapy”. Randomized clinical trials comparing benzodiazepines, Z-drugs, or innovative medications with placebo or other drugs were included. Sleep and cognitive outcomes were assessed using validated instruments; the ROB-2 tool evaluated the risk of bias. The protocol was registered in “PROSPERO”. Three randomized clinical trials involving a total of 192 patients were included in the review. Zopiclone increased the main duration of nighttime sleep by 81 min, Zolpidem reduced nighttime awakenings by 21 min, and Eszopiclone improved sleep quality, benefited the progression of sleep architecture, and reduced mental symptoms such as fear and anxiety. Z-drugs show superior efficacy and safety over benzodiazepines, improving sleep and cognitive symptoms in dementia. Personalized treatment and further research across dementia subtypes are needed to optimize long-term outcomes.