👤 Angelica Pace

Schizophrenia Spectrum Disorders are complex mental health conditions that significantly impact cognitive function and quality of life. While pharmacological and psychotherapeutic interventions are available, their effectiveness remains limited, particularly for negative symptoms and cognitive impairments. These limitations, alongside drug side effects and adherence difficulties, highlight the need for new treatments. Cognitive remediation strategies like Neurofeedback show promise by harnessing neuroplasticity. This systematic review aims to evaluate the neurocognitive and humoral changes induced by Neurofeedback and its therapeutic effects in patients with schizophrenia spectrum disorders. Our review was conducted following PRISMA guidelines. Databases including EMBASE, ScienceDirect, Scopus, PsycINFO, and MEDLINE were searched for relevant studies: 14 studies, 10 RCTs, and 4 Clinical trials were selected. Inclusion criteria encompassed studies involving patients with schizophrenia spectrum disorders, Neurofeedback interventions, and outcomes related to neurocognitive and humoral changes. The Cochrane Risk-of-Bias Tool for randomized trials (RoB 2) was used to assess the quality of included studies. The reviewed studies suggest that Neurofeedback shows promise in addressing various aspects of schizophrenia spectrum disorders. Improvements were observed in processing speed, social functioning, working memory, and emotional regulation. Several studies reported successful modulation of brain activity in regions associated with auditory hallucinations. Neurofeedback training also led to increased functional connectivity between language networks and the default mode network. Some studies found improvements in brain-derived neurotrophic factor (BDNF) levels, self-efficacy, and clinical symptoms in schizophrenia patients. Future research should focus on personalizing Neurofeedback approaches and exploring their mechanisms of action in the context of schizophrenia pathophysiology. Show less

Overactive urinary bladder (OAB) negatively impacts quality of life, and stress is known to play a key role in its development. However, the mechanisms linking stress to OAB are not yet fully understood. This study examined how chronic activation of neuroendocrine stress pathways, independently of environmental or psychological stressors, affects bladder function and the control of micturition. Utilizing the central role of brain-derived-neurotrophic factor (BDNF) in orchestrating the neuroendocrine stress response within the paraventricular nucleus of the hypothalamus (PVN), our novel experimental model subjected 10-week-old male Sprague Dawley rats to bilateral PVN injections of AAV2 viral vectors expressing either BDNF or GFP (for control). Urine voiding behavior was assessed in UroVoid metabolic cages over 14 weeks post-injections. Bladder strip myography, assessment of bladder wall mechanics, and histology were also conducted to determine any BDNF-induced differences in bladder contractility, capacity and morphology. Prolonged activation of neuroendocrine stress mechanisms with BDNF overexpression in the PVN significantly reduced intermicturition intervals and voided volumes, lowered bladder capacity, and induced relative bladder wall hypertrophy but had no effect on bladder wall mechanics or detrusor contractility. These results indicate that chronic activation of neuroendocrine stress pathways, even without additional environmental or psychological influences of stress, lead to a significant OAB phenotype and reduced bladder capacity. Show less

The highly conserved long non-coding RNA (lncRNA) MIR505HG has been primarily recognized as a precursor for microRNAs (miR)-424 and miR-503. However, studies have since demonstrated that MIR503HG has distinct functions from its associated miRNAs, playing important roles in cell proliferation, invasion, apoptosis, and differentiation. While these miRNAs are known to influence cardiomyocyte differentiation, the specific role of MIR503HG in heart development remains unexplored. We seek to determine how MIR503HG deletion impacts ventricular chamber development and to identify underlying molecular mechanisms. To study the role of the lncRNA in vivo, we generated a functional MIR503HG knockout mouse model (MIR503HG-/-) using a synthetic polyadenylation signal to terminate MIR503HG transcription without affecting miR-424/503 expression. We performed morphological analyses on embryonic and adult hearts using microCT along with cardiac functional analysis via transthoracic echocardiography. We further apply single-nuclei RNA sequencing (snRNA-seq) on adult hearts to identify potential molecular mechanisms underlying the observed phenotypes. Functional deletion of MIR503HG alone was associated with reduced compact myocardium thickness and increased trabecular myocardium in the left ventricle (LV) at embryonic day 17.5 compared to wild-type mice, indicating a LV non-compaction (LVNC) phenotype. Moreover, adult MIR503HG-/- mutant hearts showed increased trabecular complexity, impaired LV relaxation, and mitral valve regurgitation. SnRNA-seq further revealed altered expression of several genes associated with cardiomyocyte function and LVNC, including Actc1, Mib1, Mybpc3, and Myh7. Lastly, Notch1 activity was also significantly increased in mutant hearts which has been previously associated with LVNC. MIR503HG plays a role in ventricular chamber development, and its deletion leads to an LVNC phenotype independent of the miRNA cluster within its locus, highlighting its importance in cardiac development and disease. We further suggest that abnormal Notch1 activity may underpin the LVNC phenotype presented. Show less

It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms. Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant ( SERPINA1 ; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD ( p = 1.1 × 10 -4 ). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 ( p = 8.05 × 10 -10 ) and FNBP1 ( p = 4.74 × 10 -9 ); suggestive, DUSP6 ( p = 1.51 × 10 -7 ) and ANKUB1 ( p = 4.69 × 10 -7 )] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [ CXCR1 ( p = 1.01 × 10 -6 ) , AAMP ( p = 1.07 × 10 -6 ), and TRBV24 ( p = 1.23 × 10 -5 )] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies. These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD. Show less

Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy. In this study, we analyzed the biological and molecular effects of pemigatinib on different cancer cell models (lung, bladder, and gastric), which are currently objective of clinical trial investigations. NCI-H1581 lung, KATO III gastric and RT-112 bladder cancer cell lines were evaluated for FGFR expression by qRT-PCR and Western blot. Cell lines were treated with Pem and then characterized for cell proliferation, apoptosis, production of intracellular reactive oxygen species (ROS), and induction of senescence. The expression of microRNAs with tumor suppressor functions was analyzed by qRT-PCR, while modulation of the proteins coded by their target genes was evaluated by Western blot and mRNA. Descriptive statistics was used to analyze the various data and student's t test to compare the analysis of two groups. Pemigatinib exposure triggered distinct signaling pathways and reduced the proliferative ability of all cancer cells, inducing G1 phase cell cycle arrest and strong intracellular stress resulting in ROS production, senescence and apoptosis. Pemigatinib treatment also caused the upregulation of microRNAs (miR-133b, miR-139, miR-186, miR-195) with tumor suppressor functions, along with the downregulation of validated protein targets with oncogenic roles (c-Myc, c-MET, CDK6, EGFR). These results contribute to clarifying the biological effects and molecular mechanisms mediated by the anti-FGFR TKI pemigatinib in distinct tumor settings and support its exploitation for combined therapies. Show less