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The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed. Enrichment analysis by pathfindR tool was carried-out, with p-adjusted ≤0.001 and fold-change ≥2.5. Nine main different network groups were significantly dysregulated in RLS: infections, inflammation, immunology, neurodegeneration, cancer, neurotransmission and biological, blood and metabolic mechanisms. Genetic predisposition plays a key role in RLS and evidence indicates its inflammatory nature; the high involvement of mainly neurotropic viruses and the TORCH complex might trigger inflammatory/immune reactions in genetically predisposed subjects and activate a series of biological pathways-especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer of activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, and ferroptosis-involved in neurotransmitter mechanisms, synaptic plasticity, axon guidance, neurodegeneration, carcinogenesis, and metabolism.

Conditions such as Alzheimers (AD) and Parkinsons diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health's Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel. [ABSTRACT FROM AUTHOR]

The triadic interplay between sleep, immunity, and cancer represents a growing area of biomedical research with significant clinical implications. This review synthesizes the current knowledge on how sleep influences immune function, the immune system's role in cancer dynamics, and the direct connections between sleep patterns and cancer risk. After a comprehensive overview of the interrelationships among these three domains, the mechanisms of sleep in immune function are described, detailing how sleep regulates the immune system, the effects of sleep duration and quality on immune responses, and the underlying molecular and cellular mechanisms. Also, the complex relationship between immunity and cancer is explored, highlighting the immune system's role in cancer prevention and progression, immune surveillance, tumor microenvironment, and the implications of immunodeficiency and immune modulation on cancer risk. The direct connections between sleep and cancer are then described, presenting epidemiological evidence linking sleep patterns to cancer risk, biological mechanisms that influence cancer development, and the role of sleep disorders in cancer prognosis. The mediating role of sleep between immunity and cancer is highlighted, proposing hypothesized pathways, summarizing evidence from experimental and clinical studies, and evaluating the impact of sleep interventions on immune function and cancer outcomes. This review concludes by discussing the clinical implications and future directions, emphasizing the potential for sleep-based interventions in cancer prevention and treatment, the integration of sleep management in oncology and immunotherapy, and outlining a future research agenda. This agenda includes understanding the mechanisms of the sleep–immunity–cancer interplay, conducting epidemiological studies on sleep and cancer risk, assessing the impact of sleep management in cancer treatment protocols, exploring sleep and tumor microenvironment interactions, and considering policy and public health implications. Through a detailed examination of these interconnected pathways, this review underscores the critical importance of sleep in modulating immune function and cancer outcomes, advocating for interdisciplinary research and clinical strategies to harness this knowledge for improved health outcomes. [ABSTRACT FROM AUTHOR]

Background/Aim: Bladder cancer (BC) is the most prevalent malignant tumor in the urinary tract, classified mainly into muscle-invasive BC (MIBC) and non-MIBC (NMIBC). Recent studies highlight the important role of changes in transcriptome activity in carcinogenesis, aiding in the identification of additional differentially regulated candidate genes, improving our understanding of the molecular basis of gene regulation in BC. This study aimed to evaluate the transcriptome of MIBC patients compared with normal subjects. Materials and Methods: mRNA sequencing was conducted using the Illumina NovaSeq 6000 Dx system in a case series comprising 11 subjects with MIBC and 19 healthy controls matched for age and sex. For functional analysis, the pathfindR package was utilized to comprehensively identify pathways enriched in omics data within active subnetworks. Results: Our results demonstrated the presence of differentiated pathways, including spliceosome activity, oxidative phosphorylation, and chemical carcinogenesis due to reactive oxygen species, in MIBC patients compared with controls. Conclusion: The identification of novel molecular pathways in MIBC patients could prove useful in defining cancer predisposition factors and exploring potential therapeutic options. [ABSTRACT FROM AUTHOR]

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds. A total of 733 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with ASD, namely the GO Biological Process term "Response to Oxygen-Containing Compound". Additionally, the GO Cellular Component pathway "Mitochondrion" stood out among other pathways, with differentially expressed genes predominantly affiliated with this specific pathway, implicating the involvement of different mitochondrial functions in ASD. Among the differentially expressed genes, FPR2 was particularly highlighted, belonging to three GO pathways. FPR2 can modulate pro-inflammatory responses, with its intracellular cascades triggering the activation of several kinases, thus suggesting its potential utility as a biomarker of pro-inflammatory processes in ASD. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a common adult-onset neurodegenerative disorder caused by a progressive loss of dopaminergic neurons due to the accumulation of α-synuclein in the substantia nigra. Mitochondria are known to play a key role in cell respiratory function and bioenergetics. Indeed, mitochondrial dysfunction causes insufficient energy production required to satisfy the needs of several organs, especially the nervous system. However, the profiling of messenger RNA (mRNA) expression of mitochondrial subunits in PD has not been systematically investigated yet. Material and methods: We explored the mRNA expression of mitochondrial DNA (mtDNA) encoded respiratory chain (RC) subunits in 43 PD patients and 43 normal controls (NC). Next generation sequencing analysis (NGS) was used and quantitative real-time polymerase chain reaction (qRT-PCR) assay was used for confirmation of the NGS results. Results: All tested mitochondrial RC subunits were significantly over-expressed in subjects with PD compared to NC. In qRT-PCR the mean expression of all mitochondrial subunits had an expression level of at least 7 times compared to NC. Conclusions: The over-expression of mitochondrial subunits in PD subjects with respect to NC might be secondary to a degeneration-related alteration of the mitochondrial structure and/or dynamics, or to the occurrence of a compensatory mechanism. The study of specific mRNA by peripheral blood mononuclear cells may provide a further diagnostic frame for early detection PD patients. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms.

Parkinson's disease (PD) is a neurodegenerative synucleinopathy that has a not yet fully understood molecular pathomechanism behind it. The role of risk genes regulated by small non-coding RNAs, or microRNAs (miRNAs), has also been highlighted in PD, where they may influence disease progression and comorbidities. In this case-control study, we analyzed miRNAs on peripheral blood mononuclear cells by means of RNA-seq in 30 participants, with the aim of identifying miRNAs differentially expressed in PD compared to age-matched healthy controls. Additionally, we investigated the pathways influenced by differentially expressed miRNAs and assessed whether a specific pathway could potentially be associated with PD susceptibility (enrichment analyses performed using the Ingenuity Pathway Analysis tools). Overall, considering that the upregulation of miRNAs might be related with the downregulation of their messenger RNA targets, and vice versa, we found several putative targets of dysregulated miRNAs (i.e., upregulated: hsa-miR-1275, hsa-miR-23a-5p, hsa-miR-432-5p, hsa-miR-4433b-3p, and hsa-miR-4443; downregulated: hsa-miR-142-5p, hsa-miR-143-3p, hsa-miR-374a-3p, hsa-miR-542-3p, and hsa-miR-99a-5p). An inverse connection between cancer and neurodegeneration, called "inverse comorbidity", has also been noted, showing that some genes or miRNAs may be expressed oppositely in neurodegenerative disorders and in some cancers. Therefore, it may be reasonable to consider these miRNAs as potential diagnostic markers and outcome measures. [ABSTRACT FROM AUTHOR]