Elena Milanesi

• Researcher at Institutul National Victor Babes

Objective: Our understanding of the pathophysiology of pancreatic neuroendocrine tumors (PanNETs) remains incomplete, largely due to their historically underestimated incidence and the perception of these tumors as rare and slow-growing cancers. Additionally, conventional reliance on histological examination alone is gradually being supplemented by...

Background/Objectives: Oral leukoplakia (OLK) is an oral mucosal lesion classified in the oral potentially malignant disorder group and is associated with an increased risk of malignant transformation (MT). The aim of this study was to compare the clinical and histopathological features of two OLK groups, a group of smokers and a group of non-smoke...

Introduction Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer’s disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blo...

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11% in the United States. As for other types of tumors, such as colorectal cancer, aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC de...

Background Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer’s disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood...

Introduction Numerous studies have established a heightened prevalence of anxiety and depression (A&D) in individuals diagnosed with Inflammatory Bowel Diseases (IBD) when compared to the general population. Research indicates that patients with active IBD exhibit a higher frequency of anxiety symptoms and depression symptoms compared to those with...

Background and aims: Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screeni...

Background Vedolizumab (VDZ) is a safe, well tolerated and efficient biologic agent used for the treatment of inflammatory bowel disease (IBD), as confirmed by phase 3 randomised controlled trials. However, primary non-response and secondary loss-of-response to VDZ represent a clinically significant problem. The objectives of the present study are...

Background and Objectives: Desquamative gingivitis (DG) is a clinical term indicating “peeling gums” and is associated with different oral manifestations. In this study, we aimed to assess the association between DG and autoimmune blistering mucocutaneous diseases (ABMD) with oral manifestations. Materials and Methods: A retrospective study includi...

Background and Objectives: Noncommunicable diseases (NCDs) are a group of non-transmissible conditions that tend to be of long duration and are the result of a combination of genetic, physiological, environmental, and behavioral factors. Although an association between oral disorders and NCDs has been suggested, the relationship between Burning Mou...

Psychotic disorders are a heterogenous class of mental illness, with an intricate pathophysiology, involving genetics and environmental factors, and their interaction. The identification of accessible biomarkers in bodily systems such as blood may lead to more accurate diagnosis, and more effective treatments targeting dysfunctional pathways, and c...

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer. The symptoms appear in advanced stages, and diagnostic and prognostic tests for the early detection of PDAC and disease evolution are not available. The dysregulation of microRNAs (miRNAs) has been associated with cancer development and progression, an...

Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability...

Nowadays, hepatitis C-virus (HCV) represents a challenging liver condition for infected patients and health care systems worldwide. Thus, identifying new biomarkers for early diagnosis and therapy response prediction should be prioritized. Our study aims to identify new epigenetic markers in patients with HCV infection before and after successful d...

Burning Mouth Syndrome (BMS) is a chronic condition characterized by a burning sensation in the oral mucosa, lasting more than 2 hours daily for more than 3 months, without clinical and/or laboratory evidence. BMS is often comorbid with mood, and psychiatric disorders, and a complex pathophysiology and interaction between impairments in nociceptive...

Background:Oral lichen planus (OLP) is a chronic inflammatory disease that affects the oral mucosa. This disorder has been suggested to be related to an impairment of lipid metabolism and profile. A number of studies indicate a higher incidence of dyslipidemia in OLP patients compared to not-affected individuals. Objectives: The aim of this study w...

The reprogramming of lipid metabolism has been highlighted in colorectal cancer (CRC) studies, suggesting a critical role for the scavenger receptor CD36 and fatty acid synthase (FASN) in this malignancy. In this study, we analyzed the gene expression levels of CD36, FASN, the cell surface glypican 4 (GPC4), and the two transporters SLC27A3 and SLC...

The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF‐κB signalling pathway. The characterization of the NF‐κB expression profile in CRC is an important topic since the suppression of NF‐κB represents a potential therapeutic approach. In this study, we a...

Increased insulin-like growth factor (IGF) axis activity is associated with the development and progression of different types of malignancies, including colorectal cancer (CRC). MicroRNAs (miRNAs) belonging to the let-7 family have been reported to target genes involved in this axis and are known as tumor suppressors. In this study, in silico bioi...

Background: General anesthesia (GA) in pediatric patients represents a clinical routine. Factors such as increased birth age and maternal chronic conditions cause more infants to experience hypoxic-ischemic encephalopathy, an additional risk for anesthesia. Aim: This study evaluates the effect of one sevoflurane-induced GA episode on the immature b...

Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability...

Rheumatoid arthritis (RA) is an autoimmune disease with an important inflammatory component accompanied by deregulated redox-dependent signaling pathways that are feeding back into inflammation. In this context, we bring into focus the transcription factor NRF2, a master redox regulator that exerts exquisite antioxidant and anti-inflammatory effect...

Despite intensive research, the pathophysiology of Alzheimer’s disease (AD) is still not fully understood, and currently there are no effective treatments. Therefore, there is an unmet need for reliable biomarkers and animal models of AD to develop innovative therapeutic strategies addressing early pathologic events such as neuroinflammation and re...

Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox an...

Background Neuroinflammation plays a prominent role in Alzheimer’s disease (AD), both in pathogenesis and disease progression. It has been shown that TLR/MYD88 signaling is involved in the chronic low-grade sterile inflammation associated with AD. Several studies have evidenced high levels of MYD88 in the brain of patients and animal models of AD,...

Central nervous system (CNS) tumours have devastating effects and are recurrent, with dismal prognosis (gliomas) or life‐threatening by the compression effect (meningiomas). This disease's aetiology remains debatable. Over the last decade, the hypothesis that human viruses may be implicated in these tumours has been proposed. In this study, our aim...

Introduction : Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods : In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox...

Intestinal strictures are an important complication of Crohn's disease (CD), with ~40% of patients developing symptomatic obstruction within 10 years of diagnosis. However, there is a paucity of research examining the mechanisms driving the development of fibrotic strictures in CD. The present study aimed to identify the mucosal markers associated...

Background Although Alzheimer’s disease (AD) is associated with alterations of the central nervous system, this disease has an echo in blood that might represent a valuable source of biomarkers for improved diagnosis, prognosis and for monitoring drug response. Methods We performed a targeted transcriptomics study on 38 mild Alzheimer’s disease (A...

The effect of social lockdown during the COVID-19 outbreak on female aggressiveness is not well known. The strict measures of lockdown have resulted in millions of people, worldwide, confined to their homes during the pandemic. However, the consequence of lockdown strategies on females' psychological status including aggressiveness has not yet been...

Regulator of G protein signaling 2 (RGS2) is a gene involved in neuronal plasticity and synaptic signaling, whose expression in the brain is altered in neuropsychiatric and neurodegenerative disorders. Microarray data from large datasets suggested reduced RGS2 mRNA levels in the post-mortem brain tissue and blood of Alzheimer’s disease (AD) patient...

Background: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently avail...

Photodynamic therapy (PDT), a highly targeted therapy with acceptable side effects, has emerged as a promising therapeutic option in oncologic pathology. One of the issues that needs to be addressed is related to the complex network of cellular responses developed by tumor cells in response to PDT. In this context, this study aims to characterize i...

Colorectal cancer (CRC) is often characterized by mutations and aberrant DNA methylation within the promoters of tumor suppressor genes and proto-oncogenes. The most frequent somatic mutations occur within KRAS and BRAF genes. Mutations of the KRAS gene have been detected in approximately 40% of patients, while mutations in BRAF have been detected...

Purpose: Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case–control study for assessing in whole blood the expression p...

Purpose Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case–control study for assessing in whole blood the expression pr...

Background: Central nervous system (CNS) tumors have devastating effects. They are recurrent, with dismal prognosis (gliomas) or life-threatening by compression effect (meningiomas). The etiology is still debatable, and over the last decade the hypothesis that human viruses may be implicated in these tumors has been proposed. Our aim was to examine...

Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myeloid cells and extracellular matrix (ECM) remodelling. Currently, there are no specific biomarkers to diagnose the severity and prognosis of muscle lesions. In order to investigate the gene expression profile of extracellular matrix and adhesion molecules...

microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumora...

Background and aims: Therapeutic targets in ulcerative colitis (UC) have evolved over time from clinical remission to biological and endoscopic remission. Histologic remission remains a debatable outcome due to lack of data regarding its impact on long-term evolution. The development of histologic activity scores has brought standardization. We ai...

miR-146a is a microRNA involved in neuroinflammation and ageing; alterations in its expression were described in Alzheimer's disease (AD). However, most of the studies conducted so far on this miRNA included a limited number of participants and produced contradictory results. We compared miR-146a levels in plasma from 33 AD patients vs. 28 age-matc...

Background It is known that γ radiation is rapidly triggering in cells and in the surrounding medium a hydrogen peroxide burst through water radiolysis, which may have early and late consequence on the viability and functions of irradiated cells. Investigations on monocytes and macrophages are of utmost importance for assessing radiation risks, con...

In the last two decades anti‐tumor necrosis factor (anti‐TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative...

The identification of mechanisms associated with Alzheimer's disease (AD) development in mild cognitive impairment (MCI) would be of great usefulness to clarify AD pathogenesis and to develop preventive and therapeutic strategies. In this study, blood levels of the candidate microRNAs (small noncoding RNAs that play a pivotal role in gene expressio...

Genetic research has shaped the inflammatory bowel disease (IBD) landscape identifying nearly two hundred risk loci. Nonetheless, the identified variants rendered only a partial success in providing criteria for the differential diagnosis between ulcerative colitis (UC) and Crohn’s disease (CD). Transcript levels from affected intestinal mucosa may...

Lithium is the first-line treatment for bipolar affective disorder (BPAD) but two-thirds of patients respond only partially or not at all. The reasons for this high variability in lithium response are not well understood. Transcriptome-wide profiling, which tests the interface between genes and the environment, represents a viable means of explorin...

Alzheimer's Disease (AD) is the most common cause of dementia in the elderly. Centenarians - reaching the age of >100 years while maintaining good cognitive skills - seemingly have unique biological features allowing healthy aging and protection from dementia. Here, we studied the expression of SIRT1 along with miR-132 and miR-212, two microRNAs kn...

In complex phenotypes (e.g., psychiatric diseases) single locus tests, commonly performed with Genome-Wide Association Studies, have proven to be limited in discovering strong gene associations. A growing body of evidence suggests that epistatic non-linear effects may be responsible for complex phenotypes arising from the interaction of different b...

In complex phenotypes (e.g., psychiatric diseases) single locus tests, commonly performed with Genome-Wide Association Studies, have proven to be limited in discovering strong gene associations. A growing body of evidence suggests that epistatic non-linear effects may be responsible for complex phenotypes arising from the interaction of different b...

OBJECTIVES: Lithium remains the oldest and most effective treatment for mood stabilization in bipolar disorder (BD) even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA-sequencing information derived from lymphobl...

Translational Psychiatry explores the more translational area between the research in neuroscience and conceptually novel treatments

OBJECTIVES: Insulin-like Growth Factor Binding Protein 2 (IGFBP2) is a member of the family of high-affinity binding proteins (IGFBP1-6) and appears to play a governing role in Insulin-like Growth Factor (IGF) regulation in the central nervous system. This study aimed to investigate the putative involvement of IGFBP2 in mood disorder pathogenesis b...

Background Lithium remains one of the oldest and most effective treatments for mood stabilization in bipolar disorder (BD), and is still the first-line BD treatment even that individual response is variable. Indeed, at least 30% of patients are only partially responsive, and more than 30% do not respond to lithium therapy. Biomarker predictors for...

Aim: A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a p...

Aim: Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in re...

Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by...

Preclinical Research Alterations in small non‐coding RNAs have been observed in many human disease states including cancer, cardiovascular, developmental, neurological, and psychiatric disorders. These molecules have recently raised the interest of the scientific community for novel therapeutic approaches. Nanotechnologies, including the developme...

Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative...

Several lines of evidence implicate abnormalities in glutamatergic neural transmission in major depressive disorder (MDD) and treatment response. A high percentage of MDD patients do not respond adequately to antidepressants and are classified as having treatment-resistant depression (TRD). In this study we investigated five GRIK4 variants, previou...

Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression h...

Whole-genome expression studies in the peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insight into the molecular basis of the disorder and innovative biomarkers that may be of great utility in clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful for in...

Grant Application Review: The Case of Transparency Public funding agencies should be more transparent in awarding research grants to allow researchers and the public better insight into decision making.

Objectives Evidence has supported a role for rare copy number variants in the etiology of attention-deficit hyperactivity disorder (ADHD), in particular, the region 15q13, which is also a hot spot for several neuropsychiatric disorders. This region spans several genes, but their role and the biological implications remain unclear.Methods We carried...

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Preclinical Research Frontotemporal lobar degeneration ( FTLD ) encompasses a spectrum of neurodegenerative disorders characterized by behavioral, executive and language impairment, with a common overlap with parkinsonism and motor‐neuron disease. Despite an increased understanding of its genetic background and molecular pathophysiology, FTLD is s...

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. We therefore investigated the molecular signaling pathways mediating the effects of cortisol on proliferation, neuronal differentiation and astrogliogenesis, in an immortalized human hippocampal progenitor cell li...