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Melatonin administration has been associated with different benefits in animals and patients suffering from liver diseases. However, there is no published data about circulating melatonin levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Thus, the objective of this observational and retrospective study was to determine whether patients with HCC with lower serum melatonin levels prior to LT have a higher risk of one-year mortality after LT. We measured serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity (to assess antioxidant state) before LT. One-year surviving LT patients (n = 129) showed higher serum levels of melatonin (p = 0.001) and total antioxidant capacity (p = 0.001) and lower serum levels of malondialheyde (p = 0.01) than non-surviving LT patients (n = 16). Logistic regression analysis showed that high serum melatonin levels prior to LT were associated with lower one-year LT mortality (odds ratio = 0.525; 95% confidence interval (CI) = 0.331–0.834; p = 0.006). We found an association between serum levels of melatonin with serum levels of malondialheyde (rho = −0.22; p = 0.01) and total antioxidant capacity (rho = 0.21; p = 0.01). Thus, the novel findings of our study were the association between high serum melatonin levels prior to LT and survival at first year after LT and the association between serum levels of melatonin with malondialheyde and total antioxidant capacity.

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301–73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%–84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.

Brain remodeling after an ischemic stroke represents a promising avenue for exploring the cellular mechanisms of endogenous brain repair. A deeper understanding of these mechanisms is crucial for optimizing the safety and efficacy of neuroprotective treatments for stroke patients. Here, we interrogated the role of extracellular vesicles, particularly exosomes, as potential mediators of endogenous repair within the neurovascular unit (NVU). We hypothesized that these extracellular vesicles may play a role in achieving transient stroke neuroprotection. Using the established ischemic stroke model of middle cerebral artery occlusion in adult rats, we detected a surged in the extracellular vesicle marker CD63 in the peri-infarct area that either juxtaposed or co-localized with GFAP-positive glial cells, MAP2-labeled young neurons, and VEGF-marked angiogenic cells. This novel observation that CD63 exosomes spatially and temporally approximated glial activation, neurogenesis, and angiogenesis suggests that extracellular vesicles, especially exosomes, contribute to the endogenous repair of the NVU, warranting exploration of extracellular vesicle-based stroke therapeutics.

Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually. Primary injury following TBI is exacerbated by secondary brain injury; foremost is the deleterious inflammatory response. One therapeutic intervention being increasingly explored for TBI is hyperbaric oxygen therapy (HBOT), which is already approved clinically for treating open wounds. HBOT consists of 100% oxygen administration, usually between 1.5 and 3 atm and has been found to increase brain oxygenation levels after hypoxia in addition to decreasing levels of inflammation, apoptosis, intracranial pressure, and edema, reducing subsequent secondary injury. The following review examines recent preclinical and clinical studies on HBOT in the context of TBI with a focus on contributing mechanisms and clinical potential. Several preclinical studies have identified pathways, such as TLR4/NF-kB, that are affected by HBOT and contribute to its therapeutic effect. Thus far, the mechanisms mediating HBOT treatment have yet to be fully elucidated and are of interest to researchers. Nonetheless, multiple clinical studies presented in this review have examined the safety of HBOT and demonstrated the improved neurological function of TBI patients after HBOT, deeming it a promising avenue for treatment.

Androgen receptor (AR) stimulators, such as androgen and Tip60, play a pivotal role in prostatic carcinogenesis as androgen receptor signaling is critical for the growth and transformation of the prostate gland. Moreover, androgen and Tip60 promotes HIF-1α activation, involved in metabolic reprogramming by increasing glycolysis, a hallmark in cancer initiation and development. In this study we evaluated the effect of androgen and Tip60 stimulus in AR pathway activation and HIF-1α stabilization, in terms of proliferation and cell metabolism in androgen-sensitive LNCaP cells. The protective role of the bioactive compounds sulforaphane and capsaicin against the effect of these stimuli leading to pro-carcinogenic features was also addressed. Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells. These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1α stabilization induced by androgen and Tip60 in LNCaP cells. The protective role of sulforaphane and capsaicin on prostate cancer may rely on mechanisms involving the inhibition of Tip60, AR and HIF-1α effects.