Errate: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus.

The authors informed the journal that errors occurred in their manuscript, and were not noticed by the authors during the proofreading. Corrections: 1. Figure 1, top entry: "Predipocytes" should read "Preadipocytes". 2. Figure 3, chart "TIGAR": "-9" value on y axis should read "-8". 3. Figure 4, chart "let-7g-5p": the upper "-4" value on y axis should read "0". 4. Figure 5: the title of the bottom right chart should read "TIGAR". 5. Figure 6, chart "miR-26a-5p": the values on y axis should read from the top: 2, 1, 0, -1, -2. 6. Figure 6, chart "miR-374a-5p": the values on y axis should read from the top: 0, -1, -2, -3, -4. 7. Table 4., in the 6 rows from the bottom: in column "miRNAs", "hsa-miR-21-5" should read "hsa-miR-21-5p". 8. Supplementary Table1, 1st column on the left: "TG-HDL" should read "TG/HDL" Reference: Adam Wróblewski, Justyna Strycharz, Katarzyna Oszajca, Piotr Czarny, Ewa Swiderska, Tomasz Matyjas, Andrzej Zieleniak, Monika Rucinska, Lech Pomorski, Józef Drzewoski, Agnieszka Sliwinska, Janusz Szemraj: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus. Med Sci Monit, 2023; 29: e939299. DOI: 10.12659/MSM.939299.

Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus.

BACKGROUND Human visceral adipose tissue (VAT), now identified as an endocrine organ, plays a significant role in impaired fasting glucose and diabetes through the deregulated metabolism and adipogenesis of visceral adipocytes in obesity. Our study focuses on exploring the link between inflammation, oxidative stress, and glucose metabolism-associated genes with corresponding miRNAs in human visceral adipocytes and VAT from individuals with glucose metabolism disorders. MATERIAL AND METHODS We examined the expression of ATM, NFKB1, SOD2, INSR, and TIGAR, along with their related miRNAs using PCR, in two contexts:1 - During the three-stage visceral adipogenesis under normal glucose levels (5.5 millimoles), intermittent, and chronic hyperglycemia (30 millimoles).2 - In visceral adipose tissue from subjects (34 F, 18 M) with normal glucose metabolism, impaired fasting glucose, and type 2 diabetes mellitus. RESULTS Both chronic and intermittent hyperglycemia similarly influenced ATM, NFKB1, TIGAR, SOD2, INSR gene expression in visceral adipocytes, with corresponding changes in a few tested miRNAs (eg, let-7g-5p, miR-145-5p, miR-21-5p). Anthropometric and biochemical parameters led us to focus on female subjects. Our results showed transactivation of NFKB1, TIGAR, miR-10b-5p, miR-132-3p, miR-20a-5p, miR-21-5p, and miR-26a-5p exclusively in type 2 diabetes mellitus. Upregulated molecules (excluding miR-10b-5p and miR-20a-5p) positively correlated with glucose metabolism markers. CONCLUSIONS The genes studied may undergo miRNA interferences and hyperglycemic memory in visceral adipocytes under hyperglycemic conditions. VAT from women with type 2 diabetes mellitus, but not with impaired fasting glucose, showed transactivated miRNAs and a molecular dysregulation of TIGAR and NFKB1, possibly enhancing inflammation, oxidative stress, and disrupted glucose metabolism. These findings highlight the epigenetic and molecular disturbances in VAT related to glucose metabolism abnormalities. However, additional research is necessary to further understand their biological significance.

Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels).

Accumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which plays a key role in carcinogenesis, remains unclear. Therefore, the aim of our study was to evaluate the impact of metformin on histone acetyltransferases (HATs) (i.e., p300/CBP-associated factor (PCAF), p300, and CBP) and on histone deacetylases (HDACs) (i.e., SIRT-1 in human pancreatic cancer (PC) cell lines, 1.2B4, and PANC-1). The cells were exposed to metformin, an HAT inhibitor (HATi), or a combination of an HATi with metformin for 24, 48, or 72 h. Cell viability was determined using an MTT assay, and the percentage of early apoptotic cells was determined with an Annexin V-Cy3 Apoptosis Detection Assay Kit. Caspase-9 activity was also assessed. SIRT-1, PCAF, p300, and CBP expression were determined at the mRNA and protein levels using RT-PCR and Western blotting methods, respectively. Our results reveal an increase in caspase-9 in response to the metformin, indicating that it induced the apoptotic death of both 1.2B4 and PANC-1 cells. The number of cells in early apoptosis and the activity of caspase-9 decreased when treated with an HATi alone or a combination of an HATi with metformin, as compared to metformin alone. Moreover, metformin, an HATi, and a combination of an HATi with metformin also modified the mRNA expression of SIRT-1, PCAF, CBP, and p300. However, metformin did not change the expression of the studied genes in 1.2B4 cells. The results of the Western blot analysis showed that metformin diminished the protein expression of PCAF in both the 1.2B4 and PANC-1 cells. Hence, it appears possible that PCAF may be involved in the metformin-mediated apoptosis of PC cells.

MicroRNA profile and iron-related gene expression in hepatitis C-related hepatocellular carcinoma: a preliminary study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is very difficult to diagnose, especially in its early stages. Non-invasive diagnostic and prognostic factors for this cancer are urgently needed. The purpose of our study was to investigate whether the microRNAs (miRNAs) regulating genes involved in iron homeostasis, whose disruption is a hallmark of HCC, offer potential as diagnostic or prognostic factors of HCV-related hepatocellular carcinoma. MATERIAL AND METHODS: Serum and tumor samples, and adjacent liver specimens, were obtained from 65 HCC patients. Additionally, serum samples were obtained from 65 healthy controls. In total, 28 circulating and eight tissue microRNA expression profiles were estimated by TaqMan qPCR. RESULTS: The expression profiles of all tested miRNAs were altered in the hepatocellular carcinoma patients. Iron level was negatively related to serum miR-96 level in healthy controls. Although the expression of iron metabolism proteins correlated with the level of serum miRNA in the controls, this was not observed in cancer patients. In the group of cancer patients, Let-7a, miR-29b, and miR-133a were positively related to ferroportin, transferrin and ferritin levels, while miR-31, miR-221 and miR-532 were negatively related to ferroportin, transferrin receptor 1 and ferritin levels. According to ROC curve analyses, 15 miRNAs are able to discriminate with 100% sensitivity and specificity between hepatocellular carcinoma patients and healthy subjects, which is more efficient than α-fetoprotein. CONCLUSIONS: Circulating miRNAs that regulate the expression of iron metabolism proteins should be evaluated as promising candidates for HCV-related HCC diagnostic agents.

Chronic and Intermittent Hyperglycemia Modulates Expression of Key Molecules of PI3K/AKT Pathway in Differentiating Human Visceral Adipocytes.

BACKGROUND: Due to its prominence in the regulation of metabolism and inflammation, adipose tissue is a major target to investigate alterations in insulin action. This hormone activates PI3K/AKT pathway which is essential for glucose homeostasis, cell differentiation, and proliferation in insulin-sensitive tissues, like adipose tissue. The aim of this work was to evaluate the impact of chronic and intermittent high glucose on the expression of biomolecules of insulin signaling pathway during the differentiation and maturation of human visceral preadipocytes. METHODS: Human visceral preadipocytes (HPA-V) cells were treated with high glucose (30 mM)during the proliferation and/or differentiation and/or maturation stage. The level of mRNA (by Real-Time PCR) and protein (by Elisa tests) expression of IRS1, PI3K, PTEN, AKT2, and GLUT4 was examined after each culture stage. Furthermore, we investigated whether miR-29a-3p, miR-143-3p, miR-152-3p, miR-186-5p, miR-370-3p, and miR-374b-5p may affect the expression of biomolecules of the insulin signaling pathway. RESULTS: Both chronic and intermittent hyperglycemia affects insulin signaling in visceral pre/adipocytes by upregulation of analyzed PI3K/AKT pathway molecules. Both mRNA and protein expression level is more dependent on stage-specific events than the length of the period of high glucose exposure. What is more, miRs expression changes seem to be involved in PI3K/AKT expression regulation in response to hyperglycemic stimulation.

Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns of IL6 and ADIPOQ Genes and Their Associated Epigenetic Modifications in Differentiating Human Visceral Adipocytes.

Adipokines secreted by hypertrophic visceral adipose tissue (VAT) instigate low-grade inflammation, followed by hyperglycemia (HG)-related metabolic disorders. The latter may develop with the participation of epigenetic modifications. Our aim was to assess how HG influences selected epigenetic modifications and the expression of interleukin 6 (IL-6) and adiponectin (APN; gene symbol ADIPOQ) during the adipogenesis of human visceral preadipocytes (HPA-v). Adipocytes (Ads) were chronically or transiently HG-treated during three stages of adipogenesis (proliferation, differentiation, maturation). We measured adipokine mRNA, protein, proven or predicted microRNA expression (RT-qPCR and ELISA), and enrichment of H3K9/14ac, H3K4me3, and H3K9me3 at gene promoter regions (chromatin immunoprecipitation). In chronic HG, we detected different expression patterns of the studied adipokines at the mRNA and protein levels. Chronic and transient HG-induced changes in miRNA (miR-26a-5p, miR-26b-5p, let-7d-5p, let-7e-5p, miR-365a-3p, miR-146a-5p) were mostly convergent to altered IL-6 transcription. Alterations in histone marks at the IL6 promoter were also in agreement with IL-6 mRNA. The open chromatin marks at the ADIPOQ promoter mostly reflected the APN transcription during NG adipogenesis, while, in the differentiation stage, HG-induced changes in all studied marks were in line with APN mRNA levels. In summary, HG dysregulated adipokine expression, promoting inflammation. Epigenetic changes coexisted with altered expression of adipokines, especially for IL-6; therefore, epigenetic marks induced by transient HG may act as epi-memory in Ads. Such changes in the epigenome and expression of adipokines could be instrumental in the development of inflammation and metabolic deregulation of VAT.

The Importance of Epigenetics in Diagnostics and Treatment of Major Depressive Disorder.

Recent studies imply that there is a tight association between epigenetics and a molecular mechanism of major depressive disorder (MDD). Epigenetic modifications, i.e., DNA methylation, post-translational histone modification and interference of microRNA (miRNA) or long non-coding RNA (lncRNA), are able to influence the severity of the disease and the outcome of the therapy. This article summarizes the most recent literature data on this topic, i.e., usage of histone deacetylases as therapeutic agents with an antidepressant effect and miRNAs or lncRNAs as markers of depression. Due to the noteworthy potential of the role of epigenetics in MDD diagnostics and therapy, we have gathered the most relevant data in this area.

Visceral Adipose Tissue of Prediabetic and Diabetic Females Shares a Set of Similarly Upregulated microRNAs Functionally Annotated to Inflammation, Oxidative Stress and Insulin Signaling.

Hypertrophic and hypoxic visceral adipose tissue (VAT) secretes proinflammatory cytokines promoting insulin resistance (IR), prediabetes and type 2 diabetes (T2DM) microRNAs (miRNAs) are markers of metabolic disorders regulating genes critical for e.g., inflammation, glucose metabolism, and antioxidant defense, with raising diagnostic value. The aim of the current study was to evaluate whether hyperglycemia is able to affect the expression of selected miRNAs in VAT of prediabetic (IFG) and diabetic (T2DM) patients vs. normoglycemic (NG) subjects using qPCR. Statistical analyses suggested that miRNAs expression could be sex-dependent. Thus, we determined 15 miRNAs as differentially expressed (DE) among NG, T2DM, IFG females (miR-10a-5p, let-7d-5p, miR-532-5p, miR-127-3p, miR-125b-5p, let-7a-5p, let-7e-5p, miR-199a-3p, miR-365a-3p, miR-99a-5p, miR-100-5p, miR-342-3p, miR-146b-5p, miR-204-5p, miR-409-3p). Majority of significantly changed miRNAs was similarly upregulated in VAT of female T2DM and IFG patients in comparison to NG subjects, positively correlated with FPG and HbA1c, yet, uncorrelated with WHR/BMI. Enrichment analyses indicated involvement of 11 top DE miRNAs in oxidative stress, inflammation and insulin signaling. Those miRNAs expression changes could be possibly associated with low-grade chronic inflammation and oxidative stress in VAT of hyperglycemic subjects.

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress.

Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

Mitochondrial DNA copy number, damage, repair and degradation in depressive disorder.

Objectives: We aimed to explore mitochondrial DNA (mtDNA) copy number, damage, repair and degradation in peripheral blood mononuclear cells (PBMCs) of patients with depression and to compare the results with healthy subjects.Methods: Total genomic DNA was isolated from PBMCs of 25 depressed and 60 healthy subjects before, immediately after, and 3 h after the exposure to H2O2. Evaluation of mtDNA copy number was performed using real-time PCR and 2-ΔCt methods. Semi-long run real-time PCR was used to estimate the number of mtDNA lesions.Results: Baseline mtDNA copy number did not differ in cells of healthy and depressed subjects; however, it was negatively correlated with the severity of the episode. After a 10-min challenge with hydrogen peroxide (H2O2), depressed patients' PBMCs exhibited slower changes of the copy number, indicating a lower efficiency of mtDNA degradation compared to controls. Moreover, a significantly higher number of mtDNA lesions was found in depressed patients at the baseline as well as at other experimental time points. mtDNA lesions were also elevated in depressed patient cells immediately after H2O2 exposure. Induction of oxidative stress had no significant influence on the cells of controls.Conclusions: We are the first to show that impairment in repair and degradation of mtDNA may be involved in the pathophysiology of depression.

DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives?

Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.

Hyperglycemia Changes Expression of Key Adipogenesis Markers (C/EBPα and PPARᵞ)and Morphology of Differentiating Human Visceral Adipocytes.

Disturbances in adipose tissue significantly contribute to the development of metabolic disorders, which are connected with hyperglycemia (HG) and underlain by epigenetics-based mechanisms. Therefore, we aimed to evaluate the effect of hyperglycemia on proliferating, differentiating and maturating human visceral pre/adipocytes (HPA-v). Three stages of cell culture were conducted under constant or variable glycemic conditions. Adipogenesis progress was assessed using BODIPY 505/515 staining. Lipid content typical for normal and hyperglycemic conditions of adipocytes was analyzed using Raman spectroscopy and imaging. Expression of adipogenic markers, PPARγ and C/EBPα, was determined at the mRNA and protein levels. We also examined expression of miRNAs proven to target PPARγ (miR-34a-5p) and C/EBPα (miR-137-3p), employing TaqMan Low-Density Arrays (TLDA) cards. Hyperglycemia altered morphology of differentiating HPA-v in relation to normoglycemia by accelerating the formation of lipid droplets and making their numbers and volume increase. Raman results confirmed that the qualitative and quantitative lipid composition under normal and hyperglycemic conditions were different, and that the number of lipid droplets increased in (HG)-treated cells. Expression profiles of both examined genes markedly changed either during adipogenesis under physiological and hyperglycemic conditions, orat particular stages of adipogenesis upon chronic and/or variable glycemia. Expression levels of PPARγ seemed to correspond to some expression changes of miR-34a-5p. miR-137-3p, whose expression was rather stable throughout the culture, did not seem to affect C/EBPα. Our observations revealed that chronic and intermittent hyperglycemia change the morphology of visceral pre/adipocytes during adipogenesis. Moreover, hyperglycemia may utilize miR-34a-5p to induce some expression changes in PPARγ.

Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders.

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.

Major depressive disorders accompanying autoimmune diseases - Response to treatment.

MDDs (major depressive disorders) belong to the most frequently diagnosed mental diseases and affect approximately 350 million people all over the world. A growing body of evidence suggests that inflammatory processes may play a significant role in the pathophysiology and progression of the disease. The comorbidity of MDDs with many other medical conditions, for example autoimmune diseases (ADs) caused by inflammation, has been observed on numerous occasions. In both cases, increased levels of pro-inflammatory cytokines, chemokines and other inflammatory agents are observed. Furthermore, higher rates of inflammatory markers are associated with a poorer response to antidepressant treatment. Additionally, the presence of any AD is associated with higher prevalence of depression and may reduce the chance of effective therapy. Interestingly, the administration of several anti-inflammatory agents used in AD treatment is positively correlated with a reduction of depressive symptoms. In conclusion, the factors contributing to the coexistence of depression as well as affecting antidepressant treatment effectiveness may lead to an alteration of the cytokine profiles in many autoimmune diseases.

Hyperglycemia Affects miRNAs Expression Pattern during Adipogenesis of Human Visceral Adipocytes-Is Memorization Involved?

microRNAs are increasingly analyzed in adipogenesis, whose deregulation, especially visceral, contributes to the development of diabetes. Hyperglycemia is known to affect cells while occurring acutely and chronically. Therefore, we aimed to evaluate the effect of hyperglycemia on human visceral pre/adipocytes from the perspective of microRNAs. The relative expression of 78 microRNAs was determined by TaqMan Low Density Arrays at three stages of HPA-v adipogenesis conducted under normoglycemia, chronic, and intermittent hyperglycemia (30 mM). Hierarchical clustering/Pearson correlation revealed the relationship between various microRNAs' expression profiles, while functional analysis identified the genes and signaling pathways regulated by differentially expressed microRNAs. Hyperglycemia affected microRNAs' expression patterns during adipogenesis, and at the stage of pre-adipocytes, differentiated and matured adipocytes compared to normoglycemia. Interestingly, the changes that were evoked upon hyperglycemic exposure during one adipogenesis stage resembled those observed upon chronic hyperglycemia. At least 15 microRNAs were modulated during normoglycemic and/or hyperglycemic adipogenesis and/or upon intermittent/chronic hyperglycemia. Bioinformatics analysis revealed the involvement of these microRNAs in cell cycles, lipid metabolism, ECM⁻receptor interaction, oxidative stress, signaling of insulin, MAPK, TGF-ß, p53, and more. The obtained data suggests that visceral pre/adipocytes exposed to chronic/intermittent hyperglycemia develop a microRNAs' expression pattern, which may contribute to further visceral dysfunction, the progression of diabetic phenotype, and diabetic complications possibly involving "epi"-memory.

Single-nucleotide polymorphisms of uracil-processing genes affect the occurrence and the onset of recurrent depressive disorder.

Depressive disorders (DD) are known to be associated with increased DNA damage, the impairment of DNA damage repair, and the presence of single-nucleotide polymorphisms (SNPs) in DNA damage repair genes. Some indirect evidence also suggests that uracil metabolism may be disrupted in depressed patients. Therefore, the current study genotypes three SNPs localized in genes encoding uracil-processing proteins: two glycosylases, i.e., UNG g.7245G>C (rs34259), SMUG1 c.-31A>G (rs3087404), and dUTPase, i.e., DUT g.48638795G>T (rs4775748). The polymorphisms were analyzed in 585 DNA samples (282 cases and 303 controls) using TaqMan probes. The G/G genotype and G allele of UNG polymorphism decreased the risk of depression, while the G/C genotype and C allele of the same SNP increased it. It was also found that G/G carriers had their first episode significantly later than the heterozygotes. Although there was no association between the occurrence of depression and the SMUG1 SNP, a significant difference was found between the homozygotes regarding the onset of DD. In conclusion, the SNPs localized in the uracil-processing genes may modulate the occurrence and the onset of depression, which further supports the hypothesis that impairment of DNA damage repair, especially base-excision repair, may play an important role in the pathogenesis of the disease.

SIRT1 as a Therapeutic Target in Diabetic Complications.

BACKGROUND: Sirtuin1 is an epigenetic enzyme involved in histone and nonhistone protein deacetylation. It acts primarily as a metabolic sensor, which responses to changing energy status by deacetylating crucial transcription factors and cofactors. In this way, Sirtuin1 regulates mitochondrial function and biogenesis, oxidative stress, inflammation, apoptosis and cellular senescence. Disturbance of all of these phenomena promotes the pathogenesis of diabetic complications. These disorders are inseparably connected with chronic hyperglycemia, which possesses a strong epigenetic determinant. OBJECTIVE: To summarize the contemporary knowledge regarding the role of Sirtuin1 in the development, progression and therapy of diabetic complications. METHODS: We extensively searched literature describing the importance of Sirtuin1 in pathophysiology and treatment of all kinds of diabetic complications till September 2017. We focused on the examples of synthetic and natural compounds-mediated Sirtuin1 upregulation along with Sirtuin1-associated epigenetics. RESULTS: Reduction of Sirtuin1 is implicated in endothelial dysfunction and metabolic memory, underlying the development of micro- and macrovascular complications. Declined Sirtuin1 also participates in diabetic testicular and erectile dysfunction. Sirtuin1 is elevated by naturally occurring anti-oxidant and anti-inflammatory compounds such as resveratrol, trans-δ-viniferin, vitamin D and more. Similarly, Sirtuin1 level increases after treatment with standard antihyperglycemic (metformin, exenatide, liraglutide), antihypertensive (sartans), lipid-lowering (fibrates, statins) and anticoagulant (fidarestat) drugs. Regarding epigenetics, a number of miRNAs trigger Sirtuin1 decrease, which further contributes to histone acetylation of Sirtuin1-regulated and relevant for diabetes genes. CONCLUSION: Evidence strongly suggest that Sirtuin1 upregulation may serve as a potent therapeutic approach against development and progression of diabetic complications.

Erratum to "Is p53 Involved in Tissue-Specific Insulin Resistance Formation?"

[This corrects the article DOI: 10.1155/2017/9270549.].

Is p53 Involved in Tissue-Specific Insulin Resistance Formation?

p53 constitutes an extremely versatile molecule, primarily involved in sensing the variety of cellular stresses. Functional p53 utilizes a plethora of mechanisms to protect cell from deleterious repercussions of genotoxic insults, where senescence deserves special attention. While the impressive amount of p53 roles has been perceived solely by the prism of antioncogenic effect, its presence seems to be vastly connected with metabolic abnormalities underlain by cellular aging, obesity, and inflammation. p53 has been found to regulate multiple biochemical processes such as glycolysis, oxidative phosphorylation, lipolysis, lipogenesis, ß-oxidation, gluconeogenesis, and glycogen synthesis. Notably, p53-mediated metabolic effects are totally up to results of insulin action. Accumulating amount of data identifies p53 to be a factor activated upon hyperglycemia or excessive calorie intake, thus contributing to low-grade chronic inflammation and systemic insulin resistance. Prominent signs of its actions have been observed in muscles, liver, pancreas, and adipose tissue being associated with attenuation of insulin signalling. p53 is of crucial importance for the regulation of white and brown adipogenesis simultaneously being a repressor for preadipocyte differentiation. This review provides a profound insight into p53-dependent metabolic actions directed towards promotion of insulin resistance as well as presenting experimental data regarding obesity-induced p53-mediated metabolic abnormalities.