Upregulation of Serum miR-132 and miR-152 in Vietnamese Patients with Heart Failure.

Background: MicroRNAs (miRs) are emerging targets for the diagnosis, prognosis and treatment of heart failure (HF). Accumulated evidence showed that microRNA-132 (miR-132) and microRNA-152 (miR-152) play critical roles in the development of multiple pathological processes of the heart. Although their upregulations have been detected in the failing hearts of humans and animal models, little is known about the circulating levels of miR-132 and miR-152 in patients with HF. Methods: Our study was conducted from January 2022 to August 2022 at the Cardiology Department of the University Medical Center in Ho Chi Minh City, Vietnam. During study period, 36 participants were consecutively enrolled, including 18 HF patients and 18 patients who age and sex matched the non-HF controls. Serum samples of study participants were collected on admission and the expression levels of miR-132 and miR-152 were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR). The comparative cycle threshold method (ΔCt) was applied to calculate the relative expression of miRs. Results: The miR concentration in HF group was significantly lower than that in the control group. In contrast, the serum levels of miR-132 and miR-152 were significantly higher in HF patients. Further analyses of receiver operating characteristic (ROC) curve showed that miR-132 and miR-152 individually had moderate diagnostic potential for HF (with area under curve [AUC] values of 0.713 and 0.698, respectively). A positive correlation between these miRs was also confirmed. Conclusion: Serum miR-132 and miR-152 were upregulated in Vietnamese patients with HF and may serve as candidate biomarkers for diagnostic purposes.

Vietnamese version of the Hypertension Knowledge-Level Scale (HK-LS): Translation and validation.

Introduction: In Vietnam, the prevalence of hypertension is increasing rapidly. Patients need to be conscious of the disease for timely prevention and treatment. The Hypertension Knowledge Level Scale (HK-LS) is commonly used to assess knowledge about hypertension. Methods: Data collection was took place in a hospital in Binh Thuan province, Vietnam in February 2020 with a total of 184 paticipants. Translation and adaptation of the HK-LS, validate the questionnaire through in-person interviews with outpatients diagnosed with hypertension. The translation process followed WHO guidelines. The appraisal process evaluates through reliability (Cronbach's alpha coefficient) and validity (meaningful relationship between the response results of the scale and the patient's characteristics). Results: The Vietnamese version of the HK-LS was translated and proven to be reliable (Cronbach's alpha=0.72) and valid (statistically significant difference between age groups (P=0.021) and educational background (P=0.007). Conclusion: The HK-LS was translated from English into Vietnamese; the questions are clear, intelligible, and suitable for surveying patients in Vietnam.

Awareness of having hypertension, diabetes and dyslipidaemia among US adults: The 2011-2018 NHANES data.

AIM: This study aimed to investigate awareness of having hypertension, diabetes and dyslipidaemia and their associated factors among US adults. METHODS: Data from the National Health and Nutrition Examination Survey, including 21,399 adults aged ⩾20 years (pregnant women excluded) collected between 2011 and 2018, were used. Blood pressure was measured using a Baumanometer calibrated mercury true gravity wall model sphygmomanometer. Serum total cholesterol levels were measured using enzymatic assays. The percentage of haemoglobin A1C (HbA1c), which reflects long-term blood glucose levels, was measured and used to identify diabetes. Participants self-reported whether they were told by a doctor that they have hypertension, dyslipidaemia and diabetes. Awareness was defined as alignment between objective and self-reported measures for having the conditions. Sampling weights and the Taylor series linearisation variance estimation method were used in the analyses. RESULTS: The findings showed that 64.06% of people with hypertension, 54.71% of those with dyslipidaemia and 78.40% of those with diabetes were aware of having the respective condition. Age, sex and health insurance were associated with awareness of having all three conditions, but marital status was not associated with any outcome. Weight status was associated with awareness of having hypertension and dyslipidaemia, whereas ethnicity was associated with awareness of having hypertension and diabetes. Relative family income was only associated with awareness of having hypertension. CONCLUSIONS: Large proportions of US adults with hypertension, dyslipidaemia and diabetes are not aware of having the conditions. Interventions targeting groups at higher risk of being unaware of these conditions are needed.

Intelligent search system for resume and labor law.

Labor and employment are important issues in social life. The demand for online job searching and searching for labor regulations in legal documents, particularly regarding the policy for unemployment benefits, is essential. Nowadays, each function has some programs for its working. However, there is no program that combines both functions. In practice, when users seek a job, they may be unemployed or want to transfer to another work. Thus, they are required to search for regulations about unemployment insurance policies and related information, as well as regulations about workers working smoothly and following labor law. Ontology is a useful technique for representing areas of practical knowledge. This article proposes an ontology-based method for solving labor and employment-related problems. First, we construct an ontology of job skills to match curriculum vitae (CV) and job descriptions (JD). In addition, an ontology for representing labor law documents is proposed to aid users in their search for legal labor law regulations. These ontologies are combined to construct the knowledge base of a job-searching and labor law-searching system. In addition, this integrated ontology is used to study several issues involving the matching of CVs and JDs and the search for labor law issues. A system for intelligent resume searching in information technology is developed using the proposed method. This system also incorporates queries pertaining to Vietnamese labor law policies regarding unemployment and healthcare benefits. The experimental results demonstrate that the method designed to assist job seekers and users searching for legal labor documents is effective.

Genomic and vaccine preclinical studies reveal a novel mouse-adapted Helicobacter pylori model for the hpEastAsia genotype in Southeast Asia.

Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential.Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance.Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies.Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model.Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model.Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden.

Expanding Our Knowledge of DICER1 Gene Alterations and Their Role in Thyroid Diseases.

Mutations in DICER1, a gene involved in RNA interference, have been associated with a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically known for its association with pleuropulmonary blastoma, DICER1 syndrome has received more attention due to the association with newly discovered diseases and tumors. Recent studies evaluating DICER1 mutations and DICER1-driven thyroid disease in both pediatric and adult thyroid nodules revealed thyroid disease as the most common manifestation of DICER1 mutations. This study undertakes a comprehensive investigation into DICER1 mutations, focusing on their role in thyroid diseases. Specific attention was given to thyroid follicular nodular disease and differentiated thyroid carcinomas in infancy as highly indicative of germline DICER1 mutation or DICER1 syndrome. Additionally, poorly differentiated thyroid carcinoma and thyroblastoma were identified as potential indicators of somatic DICER1 mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify these patients as high risk for additional multi-organ malignancies. This study comprehensively synthesizes the current knowledge surrounding this genetically associated entity, providing intricate details on histologic findings to facilitate its diagnosis.

Promoting Pro-Environmental Behavior in Policymaking: A Text-Mining Approach for Literature Review.

The impact of pro-environmental behavior on policymaking has been an exciting area of research. While the relationship between pro-environmental behavior and policymaking has been explored in numerous studies, there needs to be more synthesis on this topic. This is the first text-mining study of pro-environmental effects in which policymaking is a significant factor. In response, this study, for the first time, takes a novel approach by using text mining in R programming to analyze 30 publications from the Scopus database on pro-environmental behavior in policymaking, highlighting major research themes and prospective research areas for future investigation. Results from text mining yielded 10 topic models, which are presented with a synopsis of the published research and a list of the primary authors, as well as a posterior probability via latent Dirichlet allocation (LDA). Additionally, the study conducts a trend analysis of the top 10 journals with the highest impact factor, considering the influence of each journal's mean citation. The study offers an overview of the impacts of pro-environmental behavior in policymaking, showing the most relevant and frequently discussed themes, introduces the scientific visualization of papers published in the Scopus database, and proposes future study directions. These findings can help researchers and environmental specialists better understand how pro-environmental behavior can be fostered more effectively through policymaking.

Insights into the epidemiology and clinical aspects of post-COVID-19 conditions in adult.

OBJECTIVES: While most individuals infected with COVID-19 recover completely within a few weeks, some continue to experience lingering symptoms. This study was conducted to identify and describe the clinical and subclinical manifestations of adult patients from the long-term effects of COVID-19. METHODS: The study analyzed 205 medical records of inpatients (age ≥ 16 years, ≥ 4 weeks post-COVID-19 recovery, and a negative SARS-CoV-2 status at enrollment) at Thong Nhat Hospital, Vietnam, from 6 September 2021 to 26 August 2022, using R language software. RESULTS: The majority of patients hospitalized with long COVID-19 symptoms (92.68%) had normal consciousness. The most common symptoms on admission were fatigue (59.02%), dyspnea (52.68%), and cough (42.93%). In total, 80% of patients observed respiratory symptoms, primarily dyspnea, while 42.44% reported neurological symptoms, with sleep disturbance being the most common. Noticeably, 42.93% of patients experienced respiratory failure in the post-COVID-19 period, resembling acute respiratory distress syndrome. DISCUSSION: These findings provide crucial insights into the epidemiology, clinical, and subclinical aspects of post-COVID-19 conditions, shedding light on the prevalence of common symptoms and the demographic distribution of affected patients. Understanding these manifestations is vital for patient well-being, improved clinical practice, and targeted healthcare planning, potentially leading to better patient care, management, and future interventions.

A Simple, Rapid, and Cost-Effective PCR Procedure for Detection of NUDT15 Gene Variants in Vietnamese Patients with Acute Lymphoblastic Leukemia.

Objective The NUDT15 variants impact thiopurine dose selection in acute lymphoblastic leukemia patients. The ability to rapidly detect variants is important in clinical practice. This study aims to develop a simple polymerase chain reaction (PCR) procedure for detecting NUDT15 variants in Vietnamese patients. Materials and Methods Sanger sequencing was used to determine NUDT15 variants from 200 patients. We designed primers and optimized the PCR procedure for detection of wild-type and variant alleles and compared with Sanger sequencing results. Results The inserted variant c.55_56insGAGTCG was detected by differences in size through conventional PCR. The tetra-primer amplification refractory mutation system PCR was successful in detecting two variations, c.52G > A and c.415C > T. The sensitivity and specificity of PCR procedure achieved 100% when compared to 200 Sanger sequencing results. Conclusion Our PCR procedure is suitable for replacing Sanger sequencing to detect the NUDT15 variants in clinical setting.

Functionalization of an ionic honeycomb KF monolayer via doping.

Doping has been widely employed to functionalize two-dimensional (2D) materials because of its effectiveness and simplicity. In this work, the electronic and magnetic properties of pristine and doped KF monolayers are investigated using first-principles calculations based on density functional theory (DFT). Phonon dispersion curves and ab initio molecular dynamics (AIMD) snapshots indicate good stability of the pristine material. The band structure shows an insulating behavior of the KF monolayer, with indirect gaps of 4.80 (6.53) eV as determined using the PBE (HSE06) functional. Its ionic character is also confirmed by the valence charge distribution and Bader charge analysis, and is generated by charge transfer from the K-4s orbital to the F-2p orbital. Doping at both anion and cation sites is explored using N/O and Ca/Sr as dopants, respectively, due to their dissimilar valence electronic configuration in comparison with that of the host atoms. It is found that the KF monolayer is significantly magnetized, where total magnetic moments of 2.00 and 1.00 µB are obtained via N and O/Ca/Sr doping, respectively. Moreover, the appearance of new middle-gap energy states leads to the development of a magnetic semiconductor nature, which is regulated by N-2p, O-2p, Ca-3d, Ca-4s, Sr-4d, and Sr-5s orbitals. Further investigation of codoping indicates that a magnetic-semiconductor nature is preserved, where the synergistic effects of dopants play a key role in the electronic and magnetic properties of the codoped systems. The results presented herein introduce doping as an efficient approach to functionalize the ionic KF monolayer to obtain prospective d0 spintronic materials, a functionality that is not accounted for by the pristine monolayer.

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines.

BACKGROUND: Helicobacter pylori infection remains a major public health threat leading to gastrointestinal illness and increased risk of gastric cancer. Mostly affecting populations in developing countries no vaccines are yet available and the disease is controlled by antimicrobials which, in turn, are driving the emergence of AMR. MATERIALS AND METHODS: We have engineered spores of Bacillus subtilis to display putative H. pylori protective antigens, urease subunit A (UreA) and subunit B (UreB) on the spore surface. Following oral dosing of mice with these spores, we evaluated immunity and colonization in animals challenged with H. pylori. RESULTS: Oral immunization with spores expressing either UreA or UreB showed antigen-specific mucosal responses (fecal sIgA) including seroconversion and hyperimmunity. Following challenge, colonization by H. pylori was significantly reduced by up to 1-log. CONCLUSIONS: This study demonstrates the utility of bacterial spores for mucosal vaccination to H. pylori infection. The heat stability and robustness of Bacillus spores coupled with their existing use as probiotics make them an attractive solution for either protection against H. pylori infection or potentially for therapy and control of active infection.

Post-COVID-19 Pulmonary Fibrosis: Facts-Challenges and Futures: A Narrative Review.

Patients with coronavirus disease 2019 (COVID-19) usually suffer from post-acute sequelae of coronavirus disease 2019 (PASC). Pulmonary fibrosis (PF) has the most significant long-term impact on patients' respiratory health, called post-COVID-19 pulmonary fibrosis (PC19-PF). PC19- PF can be caused by acute respiratory distress syndrome (ARDS) or pneumonia due to COVID-19. The risk factors of PC19-PF, such as older age, chronic comorbidities, the use of mechanical ventilation during the acute phase, and female sex, should be considered. Individuals with COVID-19 pneumonia symptoms lasting at least 12 weeks following diagnosis, including cough, dyspnea, exertional dyspnea, and poor saturation, accounted for nearly all disease occurrences. PC19-PF is characterized by persistent fibrotic tomographic sequelae associated with functional impairment throughout follow-up. Thus, clinical examination, radiology, pulmonary function tests, and pathological findings should be done to diagnose PC19-PF patients. PFT indicated persistent limitations in diffusion capacity and restrictive physiology, despite the absence of previous testing and inconsistency in the timeliness of assessments following acute illness. It has been hypothesized that PC19-PF patients may benefit from idiopathic pulmonary fibrosis treatment to prevent continued infection-related disorders, enhance the healing phase, and manage fibroproliferative processes. Immunomodulatory agents might reduce inflammation and the length of mechanical ventilation during the acute phase of COVID-19 infection, and the risk of the PC19-PF stage. Pulmonary rehabilitation, incorporating exercise training, physical education, and behavioral modifications, can improve the physical and psychological conditions of patients with PC19-PF.

Shared Neural Activity But Distinct Neural Dynamics for Cognitive Control in Monkey Prefrontal and Parietal Cortex.

To better understand how prefrontal networks mediate forms of cognitive control disrupted in schizophrenia, we translated a variant of the AX continuous performance task that measures specific deficits in the human disease to 2 male monkeys and recorded neurons in PFC and parietal cortex during task performance. In the task, contextual information instructed by cue stimuli determines the response required to a subsequent probe stimulus. We found parietal neurons encoding the behavioral context instructed by cues that exhibited nearly identical activity to their prefrontal counterparts (Blackman et al., 2016). This neural population switched their preference for stimuli over the course of the trial depending on whether the stimuli signaled the need to engage cognitive control to override a prepotent response. Cues evoked visual responses that appeared in parietal neurons first, whereas population activity encoding contextual information instructed by cues was stronger and more persistent in PFC. Increasing cognitive control demand biased the representation of contextual information toward the PFC and augmented the temporal correlation of task-defined information encoded by neurons in the two areas. Oscillatory dynamics in local field potentials differed between cortical areas and carried as much information about task conditions as spike rates. We found that, at the single-neuron level, patterns of activity evoked by the task were nearly identical between the two cortical areas. Nonetheless, distinct population dynamics in PFC and parietal cortex were evident. suggesting differential contributions to cognitive control.SIGNIFICANCE STATEMENT We recorded neural activity in PFC and parietal cortex of monkeys performing a task that measures cognitive control deficits in schizophrenia. This allowed us to characterize computations performed by neurons in the two areas to support forms of cognitive control disrupted in the disease. Subpopulations of neurons in the two areas exhibited parallel modulations in firing rate; and as a result, all patterns of task-evoked activity were distributed between PFC and parietal cortex. This included the presence in both cortical areas of neurons reflecting proactive and reactive cognitive control dissociated from stimuli or responses in the task. However, differences in the timing, strength, synchrony, and correlation of information encoded by neural activity were evident, indicating differential contributions to cognitive control.

Volatility spillovers from the Chinese stock market to the U.S. stock market: The role of the COVID-19 pandemic.

The COVID-19 pandemic, which originated in Wuhan, China, precipitated the stock market crash of March 2020. According to published global data, the U.S. has been most affected by the tragedy throughout this outbreak. Understanding the degree of integration between the financial systems of the world's two largest economies, particularly during the COVID-19 pandemic, necessitates thorough research of the risk transmission from China's stock market to the U.S. stock market. This study examines the volatility transmission from the Chinese to the U.S. stock market from January 2001 to October 2020. We employ a variant form of the EGARCH (1,1) model with long-term control over the excessive volatility breakpoints identified by the ICSS algorithm. Since 2004, empirical evidence indicates that the volatility shocks of the Chinese stock market have frequently and negatively affected the volatility of the U.S. stock market. Most importantly, we explore that the COVID-19 pandemic vigorously and positively promoted the volatility infection from the Chinese equity market to the U.S. equity market in March 2020. This precious evidence endorses the asymmetric volatility transmission from the Chinese to the U.S. stock market when COVID-19 broke out. These experimental results provide profound insight into the risk contagion between the U.S. and China stock markets. They are also essential for securities investors to minimize portfolio risk. Furthermore, this paper suggests that globalization has carefully driven the integration of China's stock market with the international equity markets.

T2 Hypointense Schwannoma Masquerading As A Vascular Lesion: A Case Report.

Spinal schwannomas are rare nerve root tumors that typically produce subtle symptoms from nerve root compression. These tumors are known to be heterogeneously hyperintense on T2-weighted MRI and avidly enhance with contrast. However, here we describe an L5 spinal schwannoma in a 66-year-old woman that was hypointense on T2-weighted imaging with other radiographic findings more closely aligning with a vascular lesion. The neuroradiologic characteristics on MRI, time resolved MR angiography, and catheter digital subtraction angiography are presented. The patient underwent a full workup for possible dural arteriovenous fistula and thrombosed venous varix before the nerve sheath tumor was discovered intraoperatively and confirmed as a schwannoma on histopathology.

Proteogenomic Markers of Chemotherapy Resistance and Response in Triple-Negative Breast Cancer.

Microscaled proteogenomics was deployed to probe the molecular basis for differential response to neoadjuvant carboplatin and docetaxel combination chemotherapy for triple-negative breast cancer (TNBC). Proteomic analyses of pretreatment patient biopsies uniquely revealed metabolic pathways, including oxidative phosphorylation, adipogenesis, and fatty acid metabolism, that were associated with resistance. Both proteomics and transcriptomics revealed that sensitivity was marked by elevation of DNA repair, E2F targets, G2-M checkpoint, interferon-gamma signaling, and immune-checkpoint components. Proteogenomic analyses of somatic copy-number aberrations identified a resistance-associated 19q13.31-33 deletion where LIG1, POLD1, and XRCC1 are located. In orthogonal datasets, LIG1 (DNA ligase I) gene deletion and/or low mRNA expression levels were associated with lack of pathologic complete response, higher chromosomal instability index (CIN), and poor prognosis in TNBC, as well as carboplatin-selective resistance in TNBC preclinical models. Hemizygous loss of LIG1 was also associated with higher CIN and poor prognosis in other cancer types, demonstrating broader clinical implications. SIGNIFICANCE: Proteogenomic analysis of triple-negative breast tumors revealed a complex landscape of chemotherapy response associations, including a 19q13.31-33 somatic deletion encoding genes serving lagging-strand DNA synthesis (LIG1, POLD1, and XRCC1), that correlate with lack of pathologic response, carboplatin-selective resistance, and, in pan-cancer studies, poor prognosis and CIN. This article is highlighted in the In This Issue feature, p. 2483.

Glutamine uptake and catabolism is required for myofibroblast formation and persistence.

BACKGROUND: Fibrosis and extracellular matrix remodeling are mediated by resident cardiac fibroblasts (CFs). In response to injury, fibroblasts activate, differentiating into specialized synthetic and contractile myofibroblasts producing copious extracellular matrix proteins (e.g., collagens). Myofibroblast persistence in chronic diseases, such as HF, leads to progressive cardiac dysfunction and maladaptive remodeling. We recently reported that an increase in αKG (alpha-ketoglutarate) bioavailability, which contributes to enhanced αKG-dependent lysine demethylase activity and chromatin remodeling, is required for myofibroblast formation. Therefore, we aimed to determine the substrates and metabolic pathways contributing to αKG biosynthesis and their requirement for myofibroblast formation. METHODS: Stable isotope metabolomics identified glutaminolysis as a key metabolic pathway required for αKG biosynthesis and myofibroblast formation, therefore we tested the effects of pharmacologic inhibition (CB-839) or genetic deletion of glutaminase (Gls1-/-) on myofibroblast formation in both murine and human cardiac fibroblasts. We employed immunofluorescence staining, functional gel contraction, western blotting, and bioenergetic assays to determine the myofibroblast phenotype. RESULTS: Carbon tracing indicated enhanced glutaminolysis mediating increased αKG abundance. Pharmacological and genetic inhibition of glutaminolysis prevented myofibroblast formation indicated by a reduction in αSMA+ cells, collagen gel contraction, collagen abundance, and the bioenergetic response. Inhibition of glutaminolysis also prevented TGFß-mediated histone demethylation and supplementation with cell-permeable αKG rescued the myofibroblast phenotype. Importantly, inhibition of glutaminolysis was sufficient to prevent myofibroblast formation in CFs isolated from the human failing heart. CONCLUSIONS: These results define glutaminolysis as necessary for myofibroblast formation and persistence, providing substantial rationale to evaluate several new therapeutic targets to treat cardiac fibrosis.

Renal denervation reduces atrial remodeling in hypertensive rats with metabolic syndrome.

Atrial fibrillation (AF) is highly prevalent in hypertensive patients with metabolic syndrome and is related to inflammation and activation of the sympathoadrenergic system. The multi-ligand Receptor-for-Advanced-Glycation-End-products (RAGE) activates inflammation-associated tissue remodeling and is regulated by the sympathetic nervous system. Its counterpart, soluble RAGE (sRAGE), serves as anti-inflammatory decoy receptor with protective properties. We investigated the effect of sympathetic modulation by renal denervation (RDN) on atrial remodeling, RAGE/sRAGE and RAGE ligands in metabolic syndrome. RDN was performed in spontaneously hypertensive obese rats (SHRob) with metabolic syndrome compared with lean spontaneously hypertensive rats (SHR) and with normotensive non-obese control rats. Blood pressure and heart rate were measured by telemetry. The animals were killed 12 weeks after RDN. Left atrial (LA) and right atrial (RA) remodeling was assessed by histological analysis and collagen types. Sympathetic innervation was measured by tyrosine hydroxylase staining of atrial nerve fibers, RAGE/sRAGE, RAGE ligands, cytokine expressions and inflammatory infiltrates were analyzed by Western blot and immunofluorescence staining. LA sympathetic nerve fiber density was higher in SHRob (+44%) versus controls and reduced after RDN (-64% versus SHRob). RAGE was increased (+718%) and sRAGE decreased (- 62%) in SHRob as compared with controls. RDN reduced RAGE expression (- 61% versus SHRob), significantly increased sRAGE levels (+162%) and induced a significant decrease in RAGE ligand levels in SHRob (- 57% CML and - 51% HMGB1) with reduced pro-inflammatory NFkB activation (- 96%), IL-6 production (- 55%) and reduced inflammatory infiltrates. This led to a reduction in atrial fibrosis (- 33%), collagen type I content (- 72%), accompanied by reduced LA myocyte hypertrophy (- 21%). Transfection experiments on H9C2 cardiomyoblasts demonstrated that RAGE is directly involved in fibrosis formation by influencing cellular production of collagen type I. In conclusion, suppression of renal sympathetic nerve activity by RDN prevents atrial remodeling in metabolic syndrome by reducing atrial sympathetic innervation and by modulating RAGE/sRAGE balance and reducing pro-inflammatory and pro-fibrotic RAGE ligands, which provides a potential therapeutic mechanism to reduce the development of AF.