Project description:While strongly implicated in Postural Tachycardia Syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) loss-of-function. POTS is characterized by the clinical symptoms of orthostatic intolerance, light-headedness, tachycardia and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with sequencing (RICh-Seq) we show let7i miRNA suppresses NET by MeCP2. Vorinostat restores epigenetic control and NET expression in POTS.
Project description:Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder leading to debilitating symptoms and the therapeutic alternatives are limited. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification on patients based on their protein background. We aimed to explore proteins that may be related with the putative etiology of POTS compared with healthy controls using a highly powerful targeted proteomic mass spectrometry technique. We aimed to explore proteins that may be related with the putative etiology of POTS compared with healthy controls using a highly powerful targeted proteomic mass spectrometry technique.
Project description:The gut microbiota plays an important role in host health. Microbiota dysbiosis has been implicated in the global epidemic of Metabolic Syndrome (MetS) and could impair host metabolism by noxious metabolites. It has been well established that the gut microbiota is shaped by host immune factors. However, the effect of T cells on the gut microbiota is yet unknown. Here, we performed a metagenomic whole-genome shotgun sequencing (mWGS) study of the microbiota of TCRb-/- mice, which lack alpha/beta T cells.
Project description:Postural orthostatic tachycardia syndrome (POTS) is a chronic neurological disorder of the autonomic nervous system (ANS) that is characterized by an excessive increase in heart rate upon orthostatic challenge. The symptoms of POTS are often debilitating, and it primarily affects young females. Even prior to coronavirus disease 2019 (COVID-19) pandemic, POTS was prevalent, affecting an estimated 0.5% to 1% of the entire population in the United States (US). Since the COVID-19 pandemic, the incidence of POTS has acutely risen, adding roughly 6-7 million POTS patients in the US alone. Despite its importance, there is currently no reliable serum biomarker for POTS. One of the major hurdles in identifying biomarkers of POTS is the heterogenous nature of the clinical syndrome. To address this challenge, we focused our analysis on patients from the recent increase in cases of post-COVID-19 onset POTS (PC-POTS). We hypothesized that PC-POTS represents a relatively homogeneous subgroup of POTS, likely triggered by the same pathogen, and presents with symptoms that are more pronounced compared to those in healthy controls. We identified 752 proteins from 18 serum proteome samples composed of 9 PC-POTS patients and 9 health control (HC) individuals, and 31 proteins showed a significant protein abundance difference in PC-POTS. Notably, the majority of the elevated proteins are associated with either actin filaments or immune functions/inflammation. The Weighted Gene Co-Expression Network Analysis (WGCNA) revealed that the module 7 (M7) most highly correlated with the diagnosis also exhibited strong correlations with various sample traits such as the Orthostatic Intolerance Score, Gastrointestinal Score, Pupillomotor Score, and the COMPASS-31 score. The proteins MTPN, TAGLN2, ADP-ribosylation factor 1, PDLIM1, PPIA, CNN2, LGALSL, TXN, TLN1, TUBA4A, IL4, TREML1, GP1BA, and GP6 were identified as common proteins overlapping in various sample traits. Cell-type enrichment analysis revealed that M7 is highly associated with immune and neuronal cells. The main pathways identified in this module include the integrin signaling pathway, blood coagulation, and glycolysis. This suggests that these proteins could potentially serve as biomarkers for PC-POTS. This study utilizes mass spectrometry-based proteomic analysis to identify serum biomarkers that differentiate patients with PC-POTS from HC individuals, thus establishing a foundation for further research and validation.
Project description:In this study we investigated whether gut microbiota profile of Italian healthy volunteers could differ based on their geaographical origin. To this purpose, fecal samples were collected from 31 healthy individuals living in 3 different italian regions (Lombardy, North; Lazio, Center; Apulia, South) and their respective microbiota profiles were analyzed employing 16S metagenomic sequencing method. This study identifies differences in the gut microbiota content and richness among individuals with the same ethnicity coming from three different Italian regions.
Project description:Polycystic ovary syndrome (PCOS) is a multifactorial disorder closely associated with metabolic dysfunction, yet the contribution of gut microbiota–derived metabolites remains incompletely understood.
Project description:Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis, characterized by altered gut function and frequent psychiatric co-morbidity. Although altered intestinal microbiome profiles have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role of the microbiota, we colonized germ-free mice with fecal microbiota from healthy controls or IBS patients with accompanying anxiety, and monitored gut function and behavior. Mouse microbiota profiles clustered according to their human donors. Despite having taxonomically similar composition as controls, mice with IBS microbiota had distinct serum metabolomic profiles related to neuro- and immunomodulation. Mice with IBS, but not control microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation and anxiety-like behavior. These results support the notion that the microbiota contributes to both intestinal and behavioral manifestations of IBS and rationalize the use of microbiota-directed therapies in ameliorating IBS.