Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review.

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic ß-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.

Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2. METHODS: An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis. RESULTS: The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. CONCLUSIONS: Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.

Prevalence of Refractive Errors in Iranian University Students in Kazerun.

PURPOSE: To determine the prevalence of refractive errors and visual impairment and the correlation between personal characteristics, including age, sex, weight, and height, with different types of refractive errors in a population of university students in the south of Iran. METHODS: In this cross-sectional study, a number of university majors were selected as clusters using multi-stage sampling in all universities located in Kazerun (27 clusters of 133 clusters). Then, proportional to size, a number of students in each major were randomly selected to participate in the study. Uncorrected and corrected visual acuity, non-cycloplegic objective refraction and subjective refraction were measured in all participants. RESULTS: The prevalence and 95% confidence interval (CI) of presenting visual impairment and blindness was 2.19% (1.48-3.23) and 0.27% (0.12-0.62), respectively. Refractive errors comprised 75% of the causes of visual impairment. The prevalence (95% CI) of myopia [spherical equivalent (SE) ≤ -0.5 D], hyperopia (SE ≥ 0.5 D), and astigmatism (cylinder power < -0.5 D) was 42.71% (39.71-45.77), 3.75% (2.85-4.51), and 29.46% (27.50-31.50), respectively. Totally, 49.03% (46.39-51.68) of the participants had at least one type of refractive error. There was a positive association between weight and myopia (1.01; 95% CI: 1.01-1.02), anisometropia (1.03; 95% CI: 1.01-1.06), and refractive errors (1.01; 95% CI: 1.01-1.02). In comparison with the age group 18-19 years, the odds ratio (OR) of astigmatism in the age group 26-27 years was 1.64 (95% CI: 1.03-2.61), and the OR of anisometropia in the age group ≥ 30 years was 0.21 (95% CI: 0.04-0.98). CONCLUSIONS: The prevalence of refractive errors, especially myopia, is higher in university students than the general population. Since refractive errors constitute a major part of visual impairment, university students should receive special services for providing corrective lenses and glasses to reduce the burden of these disorders.

Therapeutic effects of hydro-alcoholic extract of Achillea wilhelmsii C. Koch on indomethacin-induced gastric ulcer in rats: a proteomic and metabolomic approach.

BACKGROUND: Gastric ulcer is one of the most prevalent diseases worldwide. In Iranian folk medicine, Achillea wilhelmsii (AW) is used as a treatment for gastric ulcer. Previous reports also mentioned Antiulcerogenic properties for this herbal plant. This study investigated the therapeutic effects of Achillea wilhelmsii C. Koch extract on indomethacin-induced gastric lesion in rats, from both proteomic and metabolomic perspectives. METHODS: The rats were divided into 4 groups. Gastric ulceration was induced by a single dose of indomethacin (45 mg/kg) by oral gavage. An amount of 800 mg/kg of AW extract was administered orally. Serum and tissue samples were collected for further investigations. The metabolomic study was performed by 1H-NMR CPMG spectrometry. Proteomic analysis was also executed by using two dimensional gel electrophoresis (2DE) followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS). Real time PCR was used to confirm some of the genes. RESULTS: The macroscopic and microscopic investigations confirmed the effectiveness of the AW extract. There was a panel of metabolites which showed alteration during gastric lesion development. The levels of some of these metabolite reversed nearly to their control values after the administration of AW extract. There were also changes in the levels of some proteins including Alb, Fabp5, Hspb1, Tagln, Lgals7, Csta and Myl9 which were reversed after AW administration. CONCLUSIONS: Our findings suggested that Achillea wilhelmsii C. Koch extract could be a potential therapy to be used for indomethacin-induced gastric lesion treatment in the future. However, further investigations are needed to confirm the results.

A Metabolomic Study to Identify Potential Tissue Biomarkers for Indomethacin-Induced Gastric Ulcer in Rats.

BACKGROUND: Gastric Ulcer (GU) is the most prevalent gastrointestinal disorder induced by various factors and Non-Steroid Anti-Inflammatory Drugs (NSAIDs) as one of the most common reasons. Due to the absence of appropriate molecular markers for GU, the aim of this study was to utilize a metabolomics approach in order to find potential metabolite markers for the disease. METHODS: Stomach tissue samples from indomethacin-treated rats and normal controls were used to perform a 1H-NMR metabolomics study. The altered metabolites were identified using random forest multivariate analysis. RESULTS: ROC curves showed that the random forest model had a good predictive performance with AUC of 1 for the test and 0.708 for the training sets. Seventeen differentially expressed metabolites were found between GU and normal tissue sample. These metabolites included trimethylamine, betaine, carnitine, methionine, acetylcho line, choline, N,N-Dimethylglycine, cis-aconitate, tryptophan, spermidine, acetylcarnitine, creatinine, pantothenate, taurine, isoleucine, glucose and kynurenine. CONCLUSION: The results of the study demonstrated that metabolomics approach could serve as a viable method to find potential markers for GU. Surely, further studies are needed for the validation of the results.

Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers.

Chronic Kidney Disease (CKD) is a global health problem annually affecting millions of people around the world. It is a comprehensive syndrome, and various factors may contribute to its occurrence. In this study, it was attempted to provide an accurate definition of chronic kidney disease; followed by focusing and discussing on molecular pathogenesis, novel diagnosis approaches based on biomarkers, recent effective antigens and new therapeutic procedures related to high-risk chronic kidney disease such as membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy, which may lead to end-stage renal diseases. Additionally, a considerable number of metabolites and proteins that have previously been discovered and recommended as potential biomarkers of various CKDs using '-omics-' technologies, proteomics, and metabolomics were reviewed.

Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach.

OBJECTIVES: As the most prevalent endocrine system malignancy, papillary thyroid carcinoma had a very fast rising incidence in recent years for unknown reasons besides the fact that the current methods in thyroid cancer diagnosis still hold some limitations. Therefore, the aim of this study was to improve the potential molecular markers for diagnosis of benign and malignant thyroid nodules to prevent unnecessary surgeries for benign tumors. MATERIALS AND METHODS: In this study, 1H-NMR metabolomics platform was used to seek the discriminating serum metabolites in malignant papillary thyroid carcinoma (PTC) compared to benign multinodular goiter (MNG) and healthy subjects and also to better understand the disease mechanisms using bioinformatics analysis. Multivariate statistical analysis showed that PTC and MNG samples could be successfully discriminated in PCA and OPLS-DA score plots. RESULTS: Significant metabolites that differentiated malignant and benign thyroid lesions included citrate, acetylcarnitine, glutamine, homoserine, glutathione, kynurenine, nicotinic acid, hippurate, tyrosine, tryptophan, ß-alanine, and xanthine. The significant metabolites in the PTC group compared to healthy subjects also included scyllo- and myo-inositol, tryptophan, propionate, lactate, homocysteine, 3-methyl glutaric acid, asparagine, aspartate, choline, and acetamide. The metabolite sets enrichment analysis demonstrated that aspartate metabolism and urea cycle were the most important pathways in papillary thyroid cancer progression. CONCLUSION: The study results demonstrated that serum metabolic fingerprinting could serve as a viable method for differentiating various thyroid lesions and for proposing novel potential markers for thyroid cancers. Obviously, further studies are needed for the validation of the results.

Decreased apolipoprotein A4 and increased complement component 3 as potential markers for papillary thyroid carcinoma: A proteomic study.

BACKGROUND:: Thyroid carcinomas have comprised the fastest rising incidence of cancer in the past decade. Currently, the diagnosis of thyroid tumors is performed by the fine-needle aspiration biopsy (FNAB) method, which still holds some challenges and limitations, mostly in discriminating malignant and benign lesions. Therefore, the development of molecular markers to distinguish between these lesion types are in progress. METHODS:: A 2D-PAGE separation of proteins was performed followed by tandem mass spectrometry with the aim of discovering potential serum protein markers for papillary thyroid carcinoma and multinodular goiter. Protein-protein interaction network analysis revealed the most important pathways involved in the progression of papillary thyroid cancer. The enzyme-linked immunosorbent assay method was used to confirm a part of the results. RESULTS:: The significantly altered proteins included C3, C4A, GC, HP, TTR, APOA4, APOH, ORM2, KRT10, AHSG, IGKV3-20, and IGKC. We also confirmed that increased complement component 3 and decreased apolipoprotein A4 occurred in papillary thyroid cancer. Network investigations demonstrated that complement activation cascades and PPAR signaling might play a role in the pathogenesis of thyroid cancer. CONCLUSION:: The results demonstrated that serum proteomics could serve as a viable method for proposing novel potential markers for thyroid tumors. Surely, further research must be performed in larger cohorts to validate the results.

Lavandula angustifolia Effects on Rat Models of Alzheimer's Disease Through the Investigation of Serum Metabolic Features Using NMR Metabolomics.

BACKGROUND: Alzheimer's Disease (AD) is the most prevalent cause of memory impairment in the elderly population, but the diagnosis and treatment of the disease is still challenging. Lavender aqueous extract has recently been shown to have the potential in clearing Amyloid-beta plaques from AD rat hippocampus. To elucidate the therapeutic mechanisms of lavender, serum metabolic fingerprint of Aß-induced rat Alzheimer's models was investigated through nuclear magnetic resonance spectrometry. METHODS: For the establishment of rat Alzheimer's models, 10 µg of Amyloid beta 1-42 was injected to male Wistar rats. The lavender aqueous extract was injected 20 days after the establishment of the models, once daily for 20 days. Serum samples were collected and metabolite fingerprints were obtained using 500 MHz 1H-NMR spectrometry, following multivariate statistical analyses. The resulted metabolites were then subjected to pathway analysis tools to reveal metabolic pathways affected by the lavender extract treatment. RESULTS: Levels of 10 metabolite markers including alanine, glutamine, serine, isoleucine, valine, carnitine, isobutyrate, pantothenate, glucose and asparagine were reversed nearly to control values after treatment with lavender extract. The results revealed that the most significantly affected pathways during treatment with lavender extract belonged to carbohydrate and amino acid metabolism, including pantothenate and CoA metabolism, glyoxilate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism. CONCLUSION: As lavender extract reversed the direction of changes of some metabolites involved in AD pathogenesis, it was concluded that the extract might play a role in the disease improvement and serve as a potential therapeutic option for the treatment of AD. Moreover, the metabolites which were found in AD rats could serve as a potential marker panel for the disease; however, much further investigation and validation of the results is needed.