Introducing Colorectal Cancer Screening in Romania - Preliminary Results from the Regional Pilot Programs (ROCCAS).

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 screening performance indicators. METHODS: People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. RESULTS: We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. CONCLUSIONS: According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024.

Gingival Manifestations in Oral Chronic Autoimmune Bullous Diseases: A Retrospective Study.

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 including 88 patients diagnosed between 1998 and 2019 with ABMD (intraepithelial and subepithelial autoimmune blistering diseases) was performed at the Oral Medicine Department, Faculty of Dentistry, "Carol Davila" University of Medicine and Pharmacy in Bucharest. For each patient, the sociodemographic and anamnestic data, as well as clinical features of oral lesions (location), histological evaluation, and direct immunofluorescence data were collected. Results: Most of the patients involved in the study were female (78.4%). In total, 34 patients (38.63%) were diagnosed with subepithelial autoimmune diseases (SAD) and 54 (61.36%) had intraepithelial autoimmune diseases (IAD). Differences in the anatomic distribution of oral involvement were found between SAD and IAD. The presence of DG was significantly more common in patients with SAD compared to those with a diagnosis of IAD. Conclusions: Specific anatomical locations of the oral lesions are significantly associated with different subtypes of ABMD, with gingiva and hard palate mucosa being more involved in SAD and the soft palate and buccal mucosa in IAD. Desquamative gingivitis is a clinical sign that raises diagnostic challenges for several conditions in oral medicine.

Non-Communicable Diseases and Associated Risk Factors in Burning Mouth Syndrome Patients.

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 Mouth Syndrome (BMS) and NCDs and their associated risk factors has not been deeply investigated. In this study, we aim to identify associations between BMS and NCDs in the Romanian population. Materials and Methods: Ninety-nine BMS patients and 88 age-matched controls (aged 50 and over) were clinically evaluated for the presence of eight noncommunicable diseases (NCDs) and their most common risk factors, including hypertension, dyslipidemia, smoking, and obesity. Results: The results of our study showed that the BMS in the Romanian population seems to be significantly associated with cardiovascular diseases (CVDs) (p < 0.001) and two of their risk factors, hypertension (p < 0.001) and dyslipidemia (p < 0.001). Moreover, evaluating the Framingham Risk Score (FRS) in the individuals not affected by CVDs (73 CTRL and 38 BMS), we found that 13.2% of BMS patients reported a moderate risk of developing CVDs in ten years, compared to the controls, all of whom presented a low risk (p = 0.002). Conclusions: Our findings suggest that a multidisciplinary clinical approach, which also includes a cardiovascular evaluation, is essential for the successful management of BMS. Moreover, these data highlighted the importance of introducing an integrated strategy for the prevention and care of NCDs in BMS patients.

Blood-Based MicroRNAs in Psychotic Disorders-A Systematic Review.

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 could assist in monitoring the disease evolution. This systematic review aims to highlight the dysregulated microRNAs (miRNAs) in the peripheral blood of patients with psychotic disorders. Using the PRISMA protocol, PubMed and Science Direct databases were investigated and 22 articles were included. Fifty-five different miRNAs were found differentially expressed in the blood of psychotic patients compared to controls. Seventeen miRNAs (miR-34a, miR-181b, miR-432, miR-30e, miR-21, miR-137, miR-134, miR-7, miR-92a, miR-1273d, miR-1303, miR-3064-5p, miR-3131, miR-3687, miR-4428, miR-4725-3p, and miR-5096) were dysregulated with the same trend (up- or down-regulation) in at least two studies. Of note, miR-34a and miR-181b were up-regulated in the blood of psychotic patients in seven and six studies, respectively. Moreover, the level of miR-181b in plasma was found to be positively correlated with the amelioration of negative symptoms. The panel of miRNAs identified in this review could be validated in future studies in large and well-characterized cohorts of psychotic patients.

Increased Levels of miR-15b-5p and miR-20b-5p in Pancreatic Ductal Adenocarcinoma with Hepatic Metastases.

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, and some miRNAs have been reported to promote specific metastasis. In this study we aimed to identify the miRNAs dysregulated in PDAC tumoral tissues and a subset of miRNAs associated with tumoral characteristics, mainly metastasis presence and site. For this, the expression of 84 miRNAs was evaluated by qPCR in 30 tumoral tissues and 16 samples of non-tumoral pancreatic tissues. The comparison revealed 32 dysregulated miRNAs (19 upregulated and 13 downregulated) in the PDAC group. Reactome pathway over-representation analysis revealed that these miRNAs are involved in several biological pathways, including "ESR-mediated signaling", "PIP3 activates AKT signaling", and "Regulation of PTEN", among others. Moreover, our study identified an upregulation of miR-15b-5p and miR-20b-5p in the tumoral tissues of patients with hepatic metastasis, outlining these miRNAs as potential markers for hepatic metastasis. No significant difference in miRNA expression was observed in relation to anatomic location, lymphovascular invasion, lung metastasis, and the presence of diabetes.

Immunoglobulin genes expressed in lymphoblastoid cell lines discern and predict lithium response in bipolar disorder patients.

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 in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.

Impact of Altered Lipid Profile in Oral Lichen Planus.

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 was to investigate the correlations between lipid profile alterations and clinical features of oral lichen planus. Patients and methods:A total of 52 patients diagnosed with OLP were enrolled in this study. Data regarding the demography, symptoms, severity of lesions assesed by Thongprasom score and lipid profile status were collected from the medical charts. The study group was divided into two sub-cohorts: Group 1, which included OLP patients with lipid profile within the normal range, and Group 2 comprising OLP patients with alterations of the lipid status. Results:The comparative analysis between the two groups found a statistically significant association between the lipid profile and OLP symptoms. Thus, the most frequent symptom was pain, in OLP patients with normal lipid status (Group 1), and burning, in those with altered lipid status (Group 2) (p=0.050). Moreover, the presence of symptoms was reported by a higher percentage of patients from Group 2 (75%) than Group 1 (68.25%). Patients reporting burning symptomatology showed higher triglyceride levels than those who reported pain (p=0.032). Furthermore, we found that male OLP patients have higher levels of LDL compared with female subjects (p=0.021). Conclusion:Lipid profile changes are not associated with an increased severity of OLP lesions. A statistically significant association was found between burning sensation and higher lipid profile parameters.

Neuropsychological assessment of Romanian burning mouth syndrome patients: stress, depression, sleep disturbance, and verbal fluency impairments.

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 processing and psychologic function is occurring. In this work, we aimed to define the neuropsychological profile specific for BMS patients for a better management of this complex disease. We conducted a case-control study comparing 120 BMS patients and 110 non-BMS individuals (CTRL). Sociodemographic data and lifestyle habits, were collected, along with data regarding quality of life (SF-36 scale), stress (PSS), depression and anxiety (MADRS and HADS scales), sleep quality (PSQI scale), and cognitive functions (MoCA, SVF and PVF tests). The statistical analysis revealed a lower general quality of life (p < 0.001), worse sleep quality (p < 0.001) in BMS patients than CTRL. The BMS patients also displayed a higher prevalence of mild depressive symptoms than CTRL applying the MADRS (p < 0.001) and HADS-Depression scales (p = 0.001), whereas no differences in anxiety symptoms were found between the two groups (p = 0.174). Moreover, reduced scores semantic and phonemic verbal fluency tests (p < 0.05) were found, but no change in cognition was observed through MoCA (p = 0.551). Our results highlight that synergy between dentistry and neuropsychiatric assessment is essential for a successful management of BMS.

Lipid Handling Protein Gene Expression in Colorectal Cancer: CD36 and Targeting miRNAs.

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 SLC27A4 in 39 paired tumoral and peritumoral tissues from patients with CRC compared with 18 normal colonic mucosae. Moreover, the levels of seven miRNAs targeting CD36 and most of the analyzed genes were evaluated. We found a significant impairment of the expression of all the analyzed genes except GPC4 as well as the differential expression of miR-16-5p, miR-26b-5p, miR-107, miR-195-5p, and miR-27a-3p in the colonic mucosa of CRC patients. Interestingly, CD36 and miR-27a-3p were downregulated and upregulated, respectively, in tumoral tissues compared to peritumoral and control tissues, with a significant negative correlation in the group of patients developing lymph node metastasis. Our results sustain the relationship between CRC and fatty acid metabolism and emphasize the importance of related miRNAs in developing new therapeutic strategies.

Molecular profile of the NF-κB signalling pathway in human colorectal cancer.

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 assessed the expression levels of 84 NF-κB-related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case-control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR-182-5p was upregulated in T compared with PT, whereas miR-10b-5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF- κB pathway.

Does a Single Exposure to General Anesthesia Have a Cumulative Effect on the Developing Brain after Mild Perinatal Asphyxia?

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 brain previously exposed to perinatal asphyxia (PA). METHODS: Postnatal day 6 (PND6) Wistar rats were exposed to a 90-min episode of normoxia/PA and at PND15 to a 120-min episode of normoxia/GA. Four groups were analyzed: Control (C), PA, GA, and PA-GA. Post-exposures, fifteen pups/group were sacrificed and the hippocampi were isolated to assess S-100B and IL-1B protein levels, using ELISA. At maturity, the behavior was assessed by: forced swimming test (FST), and novel object recognition test. RESULTS: Hippocampal S-100B level was increased in PA, GA, and PA-GA groups, while IL-1B was increased in PA, but decreased in PA-GA. The immobility time was increased in PA and PA-GA, in FST. CONCLUSIONS: Both PA and GA contribute to glial activation, however with no cumulative effect. Moreover, PA reduces the rats' mobility, irrespective of GA exposure, while memory evaluated by the novel object recognition test was not influenced.

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis.

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 bioinformatic analysis was performed to assess miRNA-mRNA interactions between eight miRNAs belonging to the let-7 family and genes involved in the IGF signaling pathway, coding for receptors and substrates. miRNAs' expression analysis revealed that hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, hsa-let- 97 7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, and hsa-let-7g-5p were significantly down-regulated in 25 CRC tumoral tissues (T) compared to the corresponding adjacent peritumoral tissues (PT). Moreover, our results showed an upregulation of miR-let-7e-5p in CRC tissues with mutations in KRAS codon 12 or 13, and, for the first time, found a specific dysregulation of let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, and let-7i-5p in CRC with perineural invasion. Our results sustain the relationship between the IGF axis, let-7 miRNAs, and CRC and suggest an association between the expression of these miRNAs and perineural invasion.

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis.

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 effects. The review does not intend to be exhaustive, but to point out arguments sustaining the rationale for applying an NRF2-directed co-treatment in RA as well as its potential limitations. The involvement of NRF2 in RA is emphasized through an analysis of publicly available transcriptomic data on NRF2 target genes and the findings from NRF2-knockout mice. The impact of NRF2 on concurrent pathologic mechanisms in RA is explained by its crosstalk with major redox-sensitive inflammatory and cell death-related pathways, in the context of the increased survival of pathologic cells in RA. The proposed adjunctive therapy targeted to NRF2 is further sustained by the existence of promising NRF2 activators that are in various stages of drug development. The interference of NRF2 with conventional anti-rheumatic therapies is discussed, including the cytoprotective effects of NRF2 for alleviating drug toxicity. From another perspective, the review presents how NRF2 activation would be decreasing the efficacy of synthetic anti-rheumatic drugs by increasing drug efflux. Future perspectives regarding pharmacologic NRF2 activation in RA are finally proposed.

Altered Blood and Brain Expression of Inflammation and Redox Genes in Alzheimer's Disease, Common to APPV717I × TAUP301L Mice and Patients.

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 redox disturbances. The study aims to identify inflammatory and redox dysregulations in the context of AD-specific neuronal cell death and DNA damage, using the APPV717I× TAUP301L (AT) mouse model of AD. The expression of 84 inflammatory and 84 redox genes in the hippocampus and peripheral blood of double transgenic AT mice was evaluated against age-matched controls. A distinctive gene expression profile in the hippocampus and the blood of AT mice was identified, addressing DNA damage, apoptosis and thrombosis, complemented by inflammatory factors and receptors, along with ROS producers and antioxidants. Gene expression dysregulations that are common to AT mice and AD patients guided the final selection of candidate biomarkers. The identified inflammation and redox genes, common to AD patients and AT mice, might be valuable candidate biomarkers for preclinical drug development that could be readily translated to clinical trials.

Sulfiredoxin-1 blood mRNA expression levels negatively correlate with hippocampal atrophy and cognitive decline.

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 and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE<27 (n=14) and a normal cognition (NC) group with adjMMSE≥27 (n=20). A multiparametric approach, comprising structural magnetic resonance imaging measurement of different hippocampal segments and blood mRNA expression of redox and inflammatory genes was applied. Results: Our findings indicate that hippocampal segment volumes correlate positively with adjMMSE and negatively with the blood transcript levels of 19 genes, mostly redox genes correlating especially with the left subiculum and presubiculum. A strong negative correlation between hippocampal subfields atrophy and Sulfiredoxin-1 ( SRXN1) redox gene was emphasized. Conclusions: Concluding, these results suggest that SRXN1 might be a valuable candidate blood biomarker for non-invasively monitoring the evolution of hippocampal atrophy in CD patients.

Increased MYD88 blood transcript in a mouse model of Alzheimer's disease.

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, but no study has assessed so far its levels in blood. METHODS: In this study we evaluated the blood mRNA levels of MYD88 in a mouse model of AD, and also the putative effect of Rivastigmine treatment on MYD88 expression. Twenty-eight transgenic APP/TAU mice (AT) and twenty-two control C57/BL6j mice (WT) were included in this study, out of which five transgenic AT and five WT mice were treated with Rivastigmine. RESULTS: Increased MYD88 transcript in the whole blood from AT mice as compared to WT controls was found, which seems to increase in time due to disease progression and not to aging. This finding suggests that blood leukocytes are primed to develop TLR/MYD-mediated inflammatory processes. Moreover, results indicate that MYD88 blood levels were not modulated by the diseases-specific treatment with Rivastigmine. CONCLUSIONS: Our results suggest that MYD88 might be a promising blood biomarker to monitor AD progression.

Viral oncogenesis in tumours of the central nervous system: reality or random association? A retrospective study on archived material.

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 is to examine the presence of 11 viruses in the most frequent CNS primary tumours. Using polymerase chain reaction (PCR), we assessed the viral presence in archived, paraffin-embedded tumour tissues from 114 patients with glioma and meningioma and in the brain tissue from 40 controls lacking tumour pathology. We focused on candidate neuro-oncogenic types (herpesviridae and polyomaviruses) and on human papillomavirus (HPV). HPV presence, for which involvement in these tumours was hardly investigated, was found to be associated with both tumour categories compared with controls (glioma, p = 0.032; meningioma, p = 0.032), whereas the presence of the neuro-oncogenic viruses was found in a negligible number of both categories, suggesting a lack of association with the tumour presence. Moreover, our study reveals a positive correlation between HPV presence and glioma malignancy, and a negative correlation with meningioma grading. Our results suggest that the presence of HPV seems to be significantly associated with primary tumours of the CNS and its meninges.

Mucosal gene expression profile of stricturing Crohn's disease: A preliminary study.

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 with stricturing complications by examining the differences in the gene expression profiles of two patient cohorts: Patients diagnosed with inflammatory CD (n=12) and patients with stricturing CD (n=9). For each patient, a paired sample of inflamed and uninflamed mucosa was isolated and assessed by quantitative PCR using a large panel of genes associated with inflammatory bowel disease. The presents study revealed a significantly increased level of four genes in the mucosa of patients with strictures compared with the inflammatory pattern of the disease: Formyl-peptide receptor 1 [P=0.019; fold change (FC)=11.6], C-C chemokine receptor type 1 (P=0.035; FC=5.44), IFN-γ-inducible protein 10 (P=0.037; FC=3.8) and C-C chemokine ligand 25 (P=0.048; FC=3.56). The augmented expression of these four genes in the CD stricturing phenotype, if confirmed in larger cohorts of patients, could help elucidate the mechanisms leading to disease-associated complications.

Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer's Disease.

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 (AD) patients and 38 matched controls for evaluating the expression levels of 136 inflammation and 84 redox genes in whole blood. Patients were diagnosed as mild AD based on altered levels of total TAU, phospho-TAU and Abeta(1-42) in cerebrospinal fluid, and Abeta(1-40), Abeta(1-42) and total TAU levels in plasma. Whenever possible, blood and brain comparisons were made using public datasets. RESULTS: We found 48 inflammation and 34 redox genes differentially expressed in the blood of AD patients vs controls (FC >1.5, p < 0.01), out of which 22 pro-inflammatory and 12 redox genes exhibited FC >2 and p < 0.001. Receiver operating characteristic (ROC) analysis identified nine inflammation and seven redox genes that discriminated between AD patients and controls (area under the curve >0.9). Correlations of the dysregulated inflammation and redox transcripts indicated that RELA may regulate several redox genes including DUOX1 and GSR. Based on the gene expression profile, we have found that the master regulators of inflammation and redox homeostasis, NFκB and NRF2, were significantly disturbed in the blood of AD patients, as well as several zinc finger and helix-loop-helix transcription factors. CONCLUSION: The selected inflammation and redox genes might be useful biomarkers for monitoring anti-inflammatory therapy in mild AD.