Depression is a common mental disorder, the effective treatment of which remains a challenging issue worldwide. The clinical pathogenesis of depression has been deeply explored, leading to the formulation of various pathogenic hypotheses. Among these, the monoamine neurotransmitter hypothesis holds a prominent position, yet it has significant limitations as more than one-third of patients do not respond to conventional treatments targeting monoamine transmission disturbances. Over the past few decades, a growing body of research has highlighted the link between inflammation and depression as a potential key factor in the pathophysiology of depression. In this review, we first summarize the relationship between inflammation and depression, with a focus on the pathophysiological changes mediated by inflammation in depression. The mechanisms linking inflammation to depression as well as multiple anti-inflammatory strategies are also discussed, and their efficacy and safety are assessed. This review broadens the perspective on specific aspects of using anti-inflammatory strategies for treating depression, laying the groundwork for advancing precision medicine for individuals suffering from "inflamed" depression.

High mortality rates due to cardiovascular diseases (CVDs) have attracted worldwide attention. It has been reported that mitochondrial dysfunction is one of the most important mechanisms affecting the pathogenesis of CVDs. Mitochondrial DNA (mtDNA) mutations may result in impaired oxidative phosphorylation (OXPHOS), abnormal respiratory chains, and ATP production. In dysfunctional mitochondria, the electron transport chain (ETC) is uncoupled and the energy supply is reduced, while reactive oxygen species (ROS) production is increased. Here, we discussed and analyzed the relationship between mtDNA mutations, impaired mitophagy, decreased OXPHOS, elevated ROS, and CVDs from the perspective of mitochondrial dysfunction. Furthermore, we explored current potential therapeutic strategies for CVDs by eliminating mtDNA mutations (e.g., mtDNA editing and mitochondrial replacement), enhancing mitophagy, improving OXPHOS capacity (e.g., supplement with NAD⁺, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nano-drug delivery), and reducing ROS (e.g., supplement with Coenzyme Q10 and other antioxidants), and dissected their respective advantages and limitations. In fact, some therapeutic strategies are still a long way from achieving safe and effective clinical treatment. Although establishing effective and safe therapeutic strategies for CVDs remains challenging, starting from a mitochondrial perspective holds bright prospects.

The environment on the space station is quite unique compared to Earth, which is a composite of multiple stressors, such as microgravity, isolation, confinement, noise, circadian rhythm disturbance, and so on. During prolonged space missions, astronauts have to stay in such extreme environments for long periods, which could induce adverse effects on both their physical and mental health. In some circumstances, this kind of long-term spaceflight composite stress (LSCS) could also induce depression and cognitive impairment in various ways, including dysregulating the neuroplasticity of the brains of astronauts, which should be attached to great importance. Here, we have comprehensively reviewed the impact of individual and combined stressors on depression and cognitive function during long-term spaceflight, explained the underlying mechanisms of those effects from the perspective of neuroplasticity, and current countermeasures for mitigating these challenges. This review provides insights into LSCS and potential neuroplasticity mechanisms, current with potentially great impact for understanding and mitigating the mental health risks and traumas of career astronauts and space tourists.

Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.

The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. C_max and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t_1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, β-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90β (HSP90β), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be effective through the blood–brain barrier in the future.