Anti-inflammatory and tissue repair effect of cinnamaldehyde and nano cinnamaldehyde on gingival fibroblasts and macrophages.

BACKGROUND: Recurrent aphthous stomatitis has a complex and inflammatory origin. Among the great variety of medications it is increasingly common to use herbal medicines due to the adverse side effects of chemical medications. Considering the anti-inflammatory properties of cinnamaldehyde and the lack of studies related to the effectiveness of its nano form; This study investigates the effect of cinnamaldehyde and nano cinnamaldehyde on the healing rate of recurrent aphthous stomatitis lesions. METHODS: In a laboratory experiment, cinnamaldehyde was converted into niosomal nanoparticles. The niosome vesicles diameter and polydispersity index were measured at 25°C using a dynamic light scattering (DLS) Mastersizer 2000 (Malvern Panalytical technologies: UK) and Zetasizer Nano ZS system (Malvern Instruments Worcestershire: UK). After characterizing these particles, the (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) [XTT] assay was used to assess the toxicity of cinnamaldehyde and nano cinnamaldehyde on gingival fibroblast (HGF) and macrophage (THP-1) cells. By determining the release of TNF-α, IL-6, and TGF-ß cytokines using ELISA kits, the level of tissue repair and anti-inflammatory capabilities of these two substances were evaluated. RESULTS: The size and loading rate of the cinnamaldehyde nanoparticles were established after its creation. The optimized nanovesicle exhibited the following characteristics: particle size of 228.75 ± 2.38 nm, PDI of 0.244 ± 0.01, the zeta potential of -10.87 ± 1.09 mV and the drug encapsulation percentage of 66.72 ± 3.93%. PDIs range was between 0.242-0.274. The zeta potential values at 25°C were from -2.67 to -12.9 mV. The results of the XTT test demonstrated that nano cinnamaldehyde exhibited dose-dependent toxicity effects. Moreover, nano cinnamaldehyde released more TGF-ß and had better reparative effects when taken at lower concentrations than cinnamaldehyde. CONCLUSION: Nano cinnamaldehyde and cinnamaldehyde are effective in repairing tissue when used in non-toxic amounts. After confirmation in animal models, it is envisaged that these substances can be utilized to treat recurrent aphthous stomatitis.

Efficacy of Oral Mucoadhesive N-Acetylcysteine Tablets in Treatment of Recurrent Aphthous Stomatitis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial.

Objectives: This study aimed to assess the efficacy of oral mucoadhesive N-acetylcysteine (NAC) tablets for treatment of recurrent aphthous stomatitis (RAS). Materials and Methods: Forty-nine patients with RAS were randomized to receive mucoadhesive NAC tablets (n=25) or placebo (n=24). Tablets were prescribed three times a day for 7 days in each group. Pain intensity was evaluated with visual analog scale (VAS) three times a day from day 1 to day 7. Also, patients were clinically examined on days 0 (before entering the study), 3, 5, and 7 using a metal caliper to measure the diameter of the lesions. The data were statistically analyzed and P<0.05 was considered statistically significant. Results: Regarding the VAS score, all participants in the treatment group showed complete recovery on day 7 (P<0.01). Also, the diameter of the lesions was significantly smaller in the treatment group than the placebo group at the end of the study (P<0.001). Conclusion: The results of this clinical trial showed for the first time that mucoadhesive NAC tablets can significantly decrease pain and the diameter of RAS lesions without any systemic complications.

Brain-derived extracellular vesicles as serologic markers of brain injury following cardiac arrest: A pilot feasibility study.

AIM: Assessment of neurologic injury within the immediate hours following out-of-hospital cardiac arrest (OHCA) resuscitation remains a major clinical challenge. Extracellular vesicles (EVs), small bodies derived from cytosolic contents during injury, may provide the opportunity for "liquid biopsy" within hours following resuscitation, as they contain proteins and RNA linked to cell type of origin. We evaluated whether micro-RNA (miRNA) from serologic EVs were associated with post-arrest neurologic outcome. METHODS: We obtained serial blood samples in an OHCA cohort. Using novel microfluidic techniques to isolate EVs based on EV surface marker GluR2 (present on excitatory neuronal dendrites enriched in hippocampal tissue), we employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods to measure a panel of miRNAs and tested association with dichotomized modified Rankin Score (mRS) at discharge. RESULTS: EVs were assessed in 27 post-arrest patients between 7/3/2019 and 7/21/2022; 9 patients experienced good outcomes. Several miRNA species including miR-124 were statistically associated with mRS at discharge when measured within 6 hours of resuscitation (AUC = 0.84 for miR-124, p < 0.05). In a Kendall ranked correlation analysis, miRNA associations with outcome were not strongly correlated with standard serologic marker measurements, or amongst themselves, suggesting that miRNA provide distinct information from common protein biomarkers. CONCLUSIONS: This study explores the associations between miRNAs from neuron-derived EVs (NDEs) and circulating protein biomarkers within 6 hours with neurologic outcome, suggesting a panel of very early biomarker may be useful during clinical care. Future work will be required to test larger cohorts with a broader panel of miRNA species.

Endoscopic, laboratory, and clinical findings and outcomes of caustic ingestion in adults; a retrospective study.

Aim: Compared to the prevalence and complications, there is still limited evidence in this regard. Background: With an incidence rate of 200,000 cases annually and the induction of numerous complications, caustic ingestion imposes a significant burden on the healthcare system. Apart from being fatal in some cases, this injury affects its victims' quality of life as it is followed by many gastrointestinal problems. This injury mainly occurs accidentally among children, whereas in adults, it often occurs with suicidal intentions. Despite recent advances in internal medicine, gastroenterology, and toxicology, this type of injury remains a debilitating and, in some cases, fatal disorder for its victims. Methods: This study retrospectively evaluated the clinical, laboratory, and endoscopic findings of 150 patients admitted to a referral center of toxicology and forensic medicine and assessed factors associated with each type of injury. Results: The findings indicated a mortality rate as high as 7.3% in this population. Age, pH, and previous medical conditions were associated with more complications. Higher degrees of injury were also significantly associated with higher mortality. No significant difference was observed between types of corrosive substances. Conclusion: It seems that the most effective intervention for controlling caustic ingestion injuries would be psychiatric support, primary healthcare, and household education.

Improvement in use of best practice in the care of patients with oral mucositis in a comprehensive cancer center in Iran: a best practice implementation case study.

INTRODUCTION: Oral mucositis is a common debilitating complication of cancer treatments, particularly chemotherapy and radiation. OBJECTIVES: The purpose of this study was to improve oral mucositis prevention and control among cancer patients through the implementation of best practice guidelines in a tertiary referral center in Northern Iran. METHODS: A clinical audit design was utilized in this implementation project. A preimplementation audit was conducted against nine best practice criteria for the prevention and treatment of oral mucositis among new cases of cancer patients in November and December 2019. Fifty cancer patients and 20 nurses participated in this phase of the clinical audit. The next step included a facilitated multidisciplinary focus group identifying targeted strategies and implementing them, completed in late December 2019. A postimplementation audit was then conducted on another 50 cancer patients and the same 20 nurses in January and early February 2020. The project utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice software. RESULTS: The preimplementation audit revealed gaps between the current practice and best practice across eight of the nine criteria. After implementing the targeted strategies, the outcomes improved across most of the criteria in the follow-up audit: 80% increase was observed in compliance of staff education, 100% increase in providing standard oral hygiene protocol in place, 64% increase in carrying out a dental examination and conducting initial oral cavity examination, and also 34% increase in conducting of ongoing oral cavity examination by a dentist, and finally 100% increase in providing preventive and therapeutic oral care regimens in place and oral pain assessment using a validated tool. CONCLUSION: The results of this project indicate that clinical auditing is an effective approach to the assessment of evidence-based care practices for oral mucositis among new cancer patients. Evidence-based oral mucositis management among cancer patients can be achieved by educating the patients and nursing staff using the newest guidelines and dentists' comprehensive dental and oral hygiene examinations.

Adenosine: The common target between cancer immunotherapy and glaucoma in the eye.

Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By acting upon particular, G-protein coupled adenosine receptors, i.e., A1, A2- a & b, and A3 receptors mediate a variety of intracellular and immunomodulatory actions. Several studies have elucidated Adenosine's effect and its up-and downstream molecules and enzymes on the anti-tumor response against several types of cancers. We have also targeted a couple of molecules to manipulate this pathway and get the immune system's desired response in our previous experiences. Besides, the outgrowth of the studies on ocular Adenosine in recent years has significantly enhanced the knowledge about Adenosine and its role in ocular immunology and the inflammatory response of the eye. Glaucoma is the second leading cause of blindness globally, and the recent application of Adenosine and its derivatives has shown the critical role of the adenosine pathway in its pathophysiology. However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma.

Natriuretic Peptide Levels and Clinical Outcomes Among Patients Hospitalized With Coronavirus Disease 2019 Infection.

OBJECTIVES: There is increasing evidence of cardiovascular morbidity associated with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). Pro-B-type natriuretic peptide is a biomarker of myocardial stress, associated with various respiratory and cardiac outcomes. We hypothesized that pro-B-type natriuretic peptide level would be associated with mortality and clinical outcomes in hospitalized coronavirus disease 2019 patients. DESIGN: We performed a retrospective analysis using adjusted logistic and linear regression to assess the association of admission pro-B-type natriuretic peptide (analyzed by both cutoff > 125 pg/mL and log transformed pro-B-type natriuretic peptide) with clinical outcomes. We additionally treated body mass index, a confounder of both pro-B-type natriuretic peptide levels and coronavirus disease 2019 outcomes, as an ordinal variable. SETTING: We reviewed hospitalized patients with coronavirus disease 2019 who had a pro-B-type natriuretic peptide level measured within 48 hours of admission between March 1, and August 31, 2020, from a multihospital U.S. health system. PATIENTS: Adult patients (≥ 18 yr old; n = 1232) with confirmed coronavirus disease 2019 admitted to the health system. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for demographics, comorbidities, and troponin I level, higher pro-B-type natriuretic peptide level was significantly associated with death and secondary outcomes of new heart failure, length of stay, ICU duration, and need for ventilation among hospitalized coronavirus disease 2019 patients. This significance persisted after adjustment for body mass index as an ordinal variable. The adjusted hazard ratio of death for log transformed pro-B-type natriuretic peptide was 1.56 (95% CI, 1.23-1.97; p < 0.0001). CONCLUSIONS: Further investigation is warranted on the utility of pro-B-type natriuretic peptide for clinical prognostication in coronavirus disease 2019 as well as implications of abnormal pro-B-type natriuretic peptide in the underlying pathophysiology of coronavirus disease 2019-related myocardial injury.

Angiotensin-converting enzyme as a new immunologic target for the new SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic has affected the daily lives of millions of people worldwide and had caused significant mortality; hence, the assessment of therapeutic options is of great interest. The leading cause of death among COVID-19 patients is acute respiratory distress syndrome caused by hyperinflammation secondary to cytokine release syndrome (CRS). Cytokines, such as tumor necrosis factor-α, interleukin-6, interferon-γ and interleukin-10, are the main mediators of CRS. Based on recent evidence, the angiotensin-converting enzyme (ACE) II is known to be the target of the COVID-19 spike protein, which enables the virus to penetrate human cells. ACE II also possesses an anti-inflammatory role in many pathologies such as cardiovascular disease, hypertension, diabetes mellitus and other conditions, which are the main risk factors of poor prognosis in COVID-19 infection. Changes in tissue ACE II levels are associated with many diseases and hyperinflammatory states, and it is assumed that elevated levels of ACE II could aggravate the course of COVID-19 infection. Therefore, the use of renin-angiotensin-aldosterone system inhibitors (RASis) in COVID-19 patients could be hypothetically considered, though sufficient evidence is not presented by the scientific community. In this work, based on the most recent pieces of evidence, the roles of RAS and RASi in immunologic interactions are addressed. Furthermore, the molecular and immunologic aspects of RASi and their potential significance in COVID-19 are discussed.

Inhibition of CD73 using folate targeted nanoparticles carrying anti-CD73 siRNA potentiates anticancer efficacy of Dinaciclib.

Conventional therapeutic methods against cancer, including chemotherapy, radiotherapy, surgery, and combination therapy, have exhibited different toxicity levels due to their unspecific mechanism of action. To overcome the challenges facing conventional cancer therapies, newly developed methods are being investigated. Significant levels of specificity, remarkable accumulation at the tumor site, limited side effects, and minimal off-target effects enable the newly synthesized nanoparticles (NPs) to become the preferred drug delivery method in anticancer therapeutic approaches. According to the literature, CD73 has a pivotal role in cancer progression and resistance to chemotherapy and radiotherapy. Therefore, CD73 has attracted considerable attention among scientists to target this molecule. Accordingly, FDA approved CDK inhibitors such as Dinaciclib that blocks CDK1, 2, 5, and 9, and exhibits significant anticancer activity. So in this study, we intended to simultaneously suppress CD73 and CDKs in cancer cells by using the folic acid (FA)-conjugated chitosan-lactate (CL) NPs loaded with anti-CD73 siRNA and Dinaciclib to control tumor progression and metastasis. The results showed that NPs could effectively transfect cancer cells in a FA receptor-dependent manner leading to suppression of proliferation, survival, migration, and metastatic potential. Moreover, the treatment of tumor-bearing mice with this combination strategy robustly inhibited tumor growth and enhanced survival time in mice. These findings imply the high potential of FA-CL NPs loaded with anti-CD73 siRNA and Dinaciclib for use in cancer treatment shortly.

Evaluation of zinc sulfate mucoadhesive formulation on recurrent aphthous stomatitis: a randomized double-blind, placebo-controlled clinical trial.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common lesion that affects the oral mucosa. There are several methods to treat RAS, including systemic and topical formulations. This study was conducted to evaluate the anti-inflammatory effect of topical zinc sulfate and its efficacy in the treatment of RAS. METHODS: A double-blind randomized clinical trial was conducted on 46 patients with RAS. They were randomly assigned into two groups to receive a zinc sulfate mucoadhesive tablet or placebo for 7 days. The pain severity was measured at baseline and daily while the diameter of the lesion was measured at baseline and on days 3, 5, and 7. The obtained data were analyzed in SPSS V.16. RESULTS: There was no significant difference in the mean diameter of lesions and pain at baseline between the two groups (P = 0.643 and P = 0.842, respectively). However, on the third, fifth, and seventh days of the study, the diameter of the lesion significantly reduced in the intervention group (P = 0.001) and the pain intensity became significantly different between groups from the fourth day of the study (P = 0.001). CONCLUSION: Zinc sulfate mucoadhesive tablet was effective in recovery and reducing the pain and diameter of the aphthous lesion and could be considered for the treatment of RAS. TRIAL REGISTRATION: Evaluation of the effectiveness of zinc sulfate mucoadhesive tablet in the improvement of recurrent aphthous stomatitis (RAS), IRCT20151109024975N9. Registered August 1, 2018, https://en.irct.ir/trial/32423 . This project was registered by the Iranian Registry of Clinical Trials ( http://www.irct.ir ). The IRCT ID was IRCT20151109024975N9.

Conjugated CAR T cell one step beyond conventional CAR T cell for a promising cancer immunotherapy.

Cancer immunotherapy aims to enhance the immune system reactivity against tumour cells. Chimeric Antigen Receptor (CAR), presented on the surface of the T cells, specifically redirects the cell and demonstrates significant promises in treating patients with different types of haematologic malignancies. Although several cases of improvement have been reported, clinical experiences, such as excessive activity, poor control, toxicity and limited life span of conventional CAR T cells have emerged as treatment challenges associated with this therapeutic strategy. Recently, multiple switchable CAR T platforms have been made to enable better control in a dose-dependent manner, which is correlated to distinct characteristics of different switch molecules. This review aimed at a brief represention of toxicities of the CAR T cells, the obstacles facing tumour treatments especially in solid tumours, and finally providing a framework for classification of the newly developed Conjugated/Split CAR-T cell technologies to overcome difficulties. Overall, Newly developed Conjugated CAR T cells using among with soluble switch molecules seems to be as responsive as the conventional CAR T cells, yet providing many new useful options to effectively overcome limitations and significantly improve patient safety.

Longitudinal Change in Galectin-3 and Incident Cardiovascular Outcomes.

BACKGROUND: Galectin-3 (Gal-3) has been associated with heart failure (HF) and poor cardiovascular outcomes. However, the effect of longitudinal changes in Gal-3 on clinical outcomes remains unclear. OBJECTIVES: The authors sought to study clinical determinants of change in Gal-3 among community-dwelling individuals. Further, they sought to examine the role of serial Gal-3 measurements in predicting risk of future HF, cardiovascular disease (CVD), and mortality. METHODS: A total of 2,477 participants in the Framingham Heart Study Offspring cohort underwent measurement of plasma Gal-3 levels at 2 examinations (1995 to 1998 and 2005 to 2008). Linear regression models were used to examine clinical correlates of change in Gal-3. Proportional hazards models were used to relate future clinical outcomes with change in Gal-3. RESULTS: The following clinical correlates were associated with greater longitudinal increases in Gal-3 levels: age, female sex, hypertension, diabetes, body mass index, interim development of chronic kidney disease, and HF (p < 0.0001 for all in multivariable model). Change in Gal-3 was associated with future HF (hazard ratio [HR]: 1.39 per 1-SD increase; 95% confidence interval [CI]: 1.13 to 1.71), CVD (HR: 1.29; 95% CI: 1.11 to 1.51), and all-cause mortality (HR: 1.30; 95% CI: 1.17 to 1.46). Change in Gal-3 was associated with both HF with preserved as well as reduced ejection fraction (p < 0.05 for both). CONCLUSIONS: Longitudinal changes in Gal-3 are associated with traditional cardiovascular risk factors and renal disease. In turn, change in Gal-3 predicts future HF, CVD, and mortality in the community. Future studies are needed to determine whether serial Gal-3 measures may be useful in disease prevention.

Efficacy of Camellia sinensis extract against Candida species in patients with denture stomatitis.

BACKGROUND AND PURPOSE: Denture stomatitis is a chronic inflammation disease of the oral mucosa, which is specified by erythematous lesions mainly in the upper palate. Nystatin as a polyene, a class of antifungal agents, is one of the effective drugs to treat denture stomatitis. Considering the expansion of utilizing herbal drugs to cure many kinds of diseases, the present study was conducted to investigate the effects of Camellia sinensis (green tea), which has the most chemical and influence similarity with nystatin, against denture stomatitis. MATERIALS AND METHODS: This study was conducted on 22 patients with a positive mycological evidence for denture stomatitis caused by Candida species. The study population was divided into two groups, namely green tea and nystatin, receiving green tea mouthwash 0.5% and nystatin suspension 100,000 U/ml, respectively. The lesion size and number of yeast colonies were measured before and after the treatment. RESULTS: According to the results, both groups showed reduced lesion size, clinical improvement, and significant reduction of Candida colony count in both group of patients were showedafter the therapeutic. Based on the results of polymerase chain reaction, Candida albicans was the most common species isolated from denture stomatitis. There was no significant difference between the two study groups in terms of Candida species distribution (P =0.700). CONCLUSION: Green tea demonstrated a comparable anti-Candida activity with regard to nystatin; therefore, it could be recommended as an alternative treatment.

Denture Stomatitis and Candida Albicans in Iranian Population: A Systematic Review and Meta-Analysis.

STATEMENT OF THE PROBLEM: Denture stomatitis is the common form of oral candidiasis, which is seen in the form of diffused inflammation in the areas covered by dentures. Many primary studies report the prevalence of denture stomatitis and candida albicans among patients in the Iranian population; therefore, using meta-analysis is valuable for health policy makers. PURPOSE: The purpose of the present study is to determine the prevalence of denture stomatitis and candida albicans in Iran. MATERIALS AND METHOD: Using relevant keywords, national and international databases were searched. After limiting the search strategy and deleting the duplicates, the remaining papers were screened by examining the title and abstract. In order to increase the sensitivity of search reference lists of papers were examined. Finally the index of heterogeneity between studies was defined using Cochran test (Q) and I-squared (I2). According to heterogeneity, the random effects model was used to estimate the prevalence of denture stomatitis and candida albicans in Iran. RESULT: The prevalence of denture stomatitis in 12 studies, and the prevalence of candida albicans in patients with denture stomatitis have been reported in 6 studies. The number of sample under investigated and its age range among primary studies included meta- analysis was 2271 individuals and 32.7 till 87.5 years respectively. The prevalence of denture stomatitis in preliminary studies imported to a meta-analysis varied from 1.9% to 54.6%, and its rate in Iran using the meta-analysis was estimated 28.9 % (CI 95%: 18.2-39.6). Also the overall prevalence of candida albicans in patients with denture stomatitis in Iran was estimated 60.6% (CI 95%:50.1-71.2). CONCLUSION: This study showed that the prevalence of denture stomatitis and candida albicans among patient infected denture stomatitis is relatively significant in Iran.

Dysplastic change rate in cases of oral lichen planus: A retrospective study of 112 cases in an Iranian population.

BACKGROUNDS: Lichen planus is a chronic systemic disease and oral mucosa is commonly involved. Oral lichen planus (OLP) most commonly affects middle-aged women. The prevalence of the disease ranges between 0.5% and 2.6% in the general population and the range of malignant transformation varies between 0% and 10%. OBJECTIVES: To assess the rate of malignant transformation of OLP samples. MATERIALS AND METHODS: This retrospective study was carried out on 112 medical records of patients with histological diagnosis of OLP who attended the Department of Pathology at the Educational Hospital from 2005 to 2012. H&E-stained slides were reviewed by two pathologists using strict clinical and histopathological diagnostic World Health Organization (WHO) criteria. Dysplastic changes were diagnosed and graded according to the latest WHO classification. RESULTS: Of the 112 cases diagnosed as OLP, there were 39 males and 73 females and the patients' ages ranged from 15 to 86 years (mean age 44.5 years). The erosive form with fifty cases was the most common clinical type and the papular type with one case was the least common clinical type. Regarding the site, the buccal mucosa was the most common site with 52 cases. Totally, dysplastic changes were found in 12 samples, among them five cases showed mild dysplasia and seven cases showed moderate dysplasia. One case developed oral squamous cell carcinoma after 3 years. CONCLUSION: OLP is considered as a premalignant condition by the WHO and several authors. Although the malignancy rate is not so high, to reduce morbidity and mortality from cancer arising on OLP lesions, a regular follow-up examination is recommended.

Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes.

BACKGROUND: Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling. METHODS AND RESULTS: We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to "modify" the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals. CONCLUSIONS: In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance, and dyslipidemia, but not with fasting glucose or blood pressure traits.