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Background: Cardiorenal syndrome (CRS) type 4 is prevalent among the chronic kidney disease (CKD) population, with many patients dying from cardiovascular complications. However, limited data regarding cardiac transcriptional changes induced early by CKD is available. Methods: We used a murine unilateral ureteral obstruction (UUO) model to evaluate renal damage, cardiac remodeling, and transcriptional regulation at 21 days post-surgery through histological analysis, RT-qPCR, RNA-seq, and bioinformatics. Results: UUO leads to significant kidney injury, low uremia, and pathological cardiac remodeling, evidenced by increased collagen deposition and smooth muscle alpha-actin 2 expression. RNA-seq analysis identified 76 differentially expressed genes (DEGs) in UUO hearts. Upregulated DEGs were significantly enriched in cell cycle and cell division pathways, immune responses, cardiac repair, inflammation, proliferation, oxidative stress, and apoptosis. Gene Set Enrichment Analysis further revealed mitochondrial oxidative bioenergetic pathways, autophagy, and peroxisomal pathways are downregulated in UUO hearts. Vimentin was also identified as an UUO-upregulated transcript. Conclusions: Our results emphasize the relevance of extensive transcriptional changes, mitochondrial dysfunction, homeostasis deregulation, fatty-acid metabolism alterations, and vimentin upregulation in CRS type 4 development.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by alterations in motor capacity resulting from a decrease in the neurotransmitter dopamine due to the selective death of dopaminergic neurons of the nigrostriatal pathway. Unfortunately, conventional pharmacological treatments fail to halt disease progression; therefore, new therapeutic strategies are needed, and currently, some are being investigated. The endocannabinoid system (ECS), highly expressed in the basal ganglia (BG) circuit, undergoes alterations in response to dopaminergic depletion, potentially contributing to motor symptoms and the etiopathogenesis of PD. Substantial evidence supports the neuroprotective role of the ECS through various mechanisms, including anti-inflammatory, antioxidative, and antiapoptotic effects. Therefore, the ECS emerges as a promising target for PD treatment. This review provides a comprehensive summary of current clinical and preclinical evidence concerning ECS alterations in PD, along with potential pharmacological targets that may exert the protection of dopaminergic neurons.

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition with high morbidity and mortality. The therapeutic approach, even today, represents a major challenge. There is considerable interest in the understanding of the signaling pathways that regulate vasoconstriction and pulmonary vascular remodeling. Objective: We set out to identify the expression of genes S100A9 and solutes transporter, as well as their participation in the physiopathological events of PPHN. Design and methods: This is a cross-sectional study that focuses mainly on up- and down-regulated genes involved in endothelial metabolism, hypoxia transporters, ionic and nucleotides metabolism. The total RNA was obtained from blood samples of healthy full-term newborns (negative controls) and patients with PPHN. The preparation of samples for microarray analysis was as follows: control samples were stained with fluorescent nucleotides dUTP-Cy3 and pathological samples with dUTP-Cy5; samples were co-hybridized, a microarray analysis was performed using an Array Scanner Packard. Additionally, reverse transcriptase polymerase chain reaction (RT-PCR) for the genes S100A9 and solutes transporter was done. Comparative and descriptive analyses were done using t-test for independent variables, considering a p < 0.05 as significant. The elements with a z-score of more than 2 standard deviations are genes likely to be differentially expressed. Results: From the total (10,000) genes analyzed, 364 (3.64%) were differentially regulated in their expression; those that registered an up-regulation were 1.13%, while 2.51% were down-regulated. S100 proteins type A9 and A12 were the most over-expressed, as well as Rho family GTPase 3. Down-regulation in the hypoxia-inducible factor 1 (HIF-1) and HIF-1 alpha subunit inhibitor was found. S100A9 and RSC1A1 had increased mRNA expression under PPHN conditions compared to healthy newborn infants. Conclusions: The up-regulation from both genes could explain, in part, the vasoreactivity and vascular remodeling characteristic of PPHN. A deeper understanding of the pathophysiology of PPHN could have a positive impact on the development of specific therapies.

Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. Methods: The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). Results: The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. Conclusion: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.